development of a technique using vmat and robust
TRANSCRIPT
Development of a technique using VMAT and robust optimisation to replace the use of surface bolus during radiotherapy for patients post-
mastectomy.
A thesis submitted to The University of Manchester for the degree of Doctor of Clinical Science in the Faculty of Biology, Medicine and Health
2021
Helen P. Howard
School of Medical Sciences Division of Cancer Sciences
2
Contents
1 Introduction ............................................................................................................ 21
1.1 Cancer ............................................................................................................... 21
1.2 Breast Anatomy ................................................................................................ 22
1.3 Breast Cancer.................................................................................................... 22
1.3.1 Breast Cancer Diagnosis ............................................................................ 23
1.3.2 Breast Cancer Treatment .......................................................................... 25
1.4 Radiotherapy Treatment .................................................................................. 26
1.5 Radiotherapy Treatment Planning ................................................................... 27
1.6 Radiotherapy Volume Definitions .................................................................... 29
1.7 Breast Planning Volumes .................................................................................. 30
1.8 Radiotherapy Planning Techniques .................................................................. 31
1.8.1 Radiotherapy Planning Techniques for Breast Treatments ...................... 32
1.9 Radiotherapy Treatment Delivery .................................................................... 34
1.10 Radiotherapy Treatment Planning for Mastectomy Patients ...................... 34
1.11 Use of IMRT and VMAT Treatment Planning for Mastectomy Patients ....... 37
1.12 Robust Optimisation ..................................................................................... 39
1.13 Specifying Superficial Doses for Post-Mastectomy Radiotherapy ............... 41
1.14 Definition of the Skin Structure in Mastectomy Patients ............................. 42
1.15 Measurement of Superficial Doses ............................................................... 43
1.16 Scope of Project ............................................................................................ 46
2 Evaluation of current treatment method ............................................................... 48
2.1 Current technique for the treatment of post-mastectomy patients ............... 48
2.2 Dosimetric effect of bolus in post-mastectomy patients ................................. 52
2.2.1 Patient selection........................................................................................ 52
3
2.3 Method ............................................................................................................. 54
2.4 Results .............................................................................................................. 56
2.4.1 Plan comparison – Dose Distribution (single patient example) ................ 56
2.4.2 Plan comparison – PTVtoSurface (single patient example) ...................... 57
2.4.3 Plan comparison – Skin Structures (single patient example).................... 58
2.4.4 Plan comparison – Organs at Risk (single patient example) ..................... 60
2.4.5 Plan comparison – PTVtoSurface (8 patient study set) ............................ 62
2.4.6 Plan comparison – Skin Structures (8 patient study set) .......................... 64
2.4.7 Plan comparison – Organs at Risk (8 patient study set) ........................... 65
2.5 Discussion ......................................................................................................... 67
2.6 Summary ........................................................................................................... 68
3 Comparison of VMAT plans to Clinical plans .......................................................... 69
3.1 Method ............................................................................................................. 69
3.2 Results .............................................................................................................. 70
3.2.1 Plan comparison – Dose Distribution (single patient example) ................ 70
3.2.2 Plan comparison – PTVtoSurface (single patient example) ...................... 71
3.2.3 Plan comparison – Skin Structures (single patient example).................... 73
3.2.4 Plan comparison – Organs at Risk (single patient example) ..................... 75
3.2.5 Plan comparison – PTVtoSurface (8 patient study set) ............................ 77
3.2.6 Plan comparison – Skin Structures (8 patient study set) .......................... 78
3.2.7 Plan comparison – Organs at Risk (8 patient study set) ........................... 80
3.3 Discussion ......................................................................................................... 83
3.4 Summary ........................................................................................................... 84
4 Surface Dose Measurements .................................................................................. 85
4.1 Method ............................................................................................................. 86
4.2 Results .............................................................................................................. 90
4.3 Discussion ......................................................................................................... 94
4
4.4 Summary ........................................................................................................... 95
5 Effect of Perturbation ............................................................................................. 96
5.1 Method ............................................................................................................. 96
5.2 Results .............................................................................................................. 98
5.2.1 Perturbation Effect – Dose Distribution (single patient example) ........... 98
5.2.2 Perturbation Effect – PTVtoSurface (single patient example) ................ 100
5.2.3 Perturbation Effect – Skin Structures (single patient example) ............. 103
5.2.4 Perturbation Effect – Organs at Risk (single patient example) ............... 105
5.2.5 Perturbation Effect – PTVtoSurface (8 patient study set) ...................... 107
5.2.6 Perturbation Effect – Skin Structures (8 patient study set) .................... 112
5.2.7 Perturbation Effect – Organs at Risk (8 patient study set) ..................... 115
5.3 Discussion ....................................................................................................... 118
5.4 Summary ......................................................................................................... 122
6 Robust Optimisation ............................................................................................. 123
6.1 Method ........................................................................................................... 123
6.2 Results ............................................................................................................ 124
6.2.1 Plan comparison – Dose Distribution (single patient example) .............. 125
6.2.2 Plan comparison – PTVtoSurface (single patient example) .................... 125
6.2.3 Plan comparison – Organs at Risk (single patient example) ................... 125
6.2.4 Plan comparison – PTVtoSurface (8 patient study set) .......................... 128
6.2.5 Plan comparison – Organs at Risk (8 patient study set) ......................... 130
6.2.6 Plan comparison – Skin Structures (8 patient study set) ........................ 132
6.2.7 Perturbation Effect - PTVtoSurface ......................................................... 134
6.2.8 Perturbation Effect – Organs at Risk ....................................................... 139
6.2.9 Perturbation Effect – Skin Structures ..................................................... 142
6.3 Discussion ....................................................................................................... 145
6.4 Summary ......................................................................................................... 146
5
7 Summary ............................................................................................................... 148
7.1 Overview of Results ........................................................................................ 148
7.2 Limitations ...................................................................................................... 150
7.3 Further work ................................................................................................... 151
8 References ............................................................................................................. 153
Appendix 1 .................................................................................................................... 164
Appendix 2 .................................................................................................................... 167
Appendix 3 .................................................................................................................... 170
Appendix 4 .................................................................................................................... 173
Appendix 5 .................................................................................................................... 178
Word Count: 24,900
6
Figures
Figure 1.1: Cross section of the mammary gland. (Source: Cancer Research UK) ...................... 22
Figure 1.2: Diagram showing a) lobular carcinoma in situ and invasive carcinoma and b) ductal
carcinoma in situ and invasive carcinoma (Source: Cancer Research UK) .................................. 23
Figure 1.3: a) Virtual 3D representation of linear accelerator (Prosoma v4.2, MedCom,
Germany) b) MLCs defining beam shape c) Intersecting radiation beams over region of
treatment .................................................................................................................................... 28
Figure 1.4: Radiotherapy target volumes as defined in ICRU 50, ICRU 62 and ICRU 83 reports. 29
Figure 1.5: Field-based approach for PTV creation in breast treatments a) field edges defined to
cover in sup/inf and ant/post directions b) treated volume (shaded pink structure) defined by
intersection of tangential beams with breast tissue c) PTV (shaded purple structure) – treated
volume clipped from beam edges, surface and lung. ................................................................. 31
Figure 1.6: a) Beam arrangement and dose distribution for radiotherapy breast treatment b)
Beam segments for medial beam ............................................................................................... 33
Figure 1.7: Measured Depth Dose curve for a 6MV photon beam, 10x10cm field size. ............. 35
Figure 2.1: a) water equivalent bolus slab 40x40cm b) 3D rendered image from CT scan
showing bolus placement in treatment position......................................................................... 49
Figure 2.2: a) 3D rendered image from CT scan with wires defining area for treatment b)
Transverse CT image with opposing tangential beams applied ................................................. 50
Figure 2.3: Blue contour on transverse CT slice indicates position of computer- generated bolus
.................................................................................................................................................... 51
Figure 2.4: PTVtoSurface (red shaded structure) ........................................................................ 54
Figure 2.5: Skin5mm (shaded green structure) with PTVtoSurface (red contour) ...................... 56
Figure 2.6: Example 38Gy dose distribution for a) No Bolus plan b) Clinical Plan ...................... 57
Figure 2.7: Example of DVH for structure PTVtoSurface. (Dashed line = Clinical Plan, Dotted line
= No Bolus Plan) .......................................................................................................................... 58
Figure 2.8: Example DVHs for a) Skin1mm b) Skin3mm c) Skin5mm (Dashed line = Clinical Plan,
Dotted line = No Bolus Plan) ....................................................................................................... 59
Figure 2.9: Example DVHs for Heart (red line) and Ipsilateral Lung (Orange line) (Dashed line =
Clinical Plan, Dotted line = No Bolus Plan) .................................................................................. 61
Figure 2.10: Box and Whisker plots showing the a)V95% b) average dose c) V105% d) V107%
and e) D1% parameters for the PTVtoSurface structure for No Bolus Plans (Blue) and Clinical
Plans (Red) in 8 patients. ............................................................................................................ 63
7
Figure 2.11: Box and Whisker plots showing the doses for a) Skin1mm – D99% b) Skin3mm –
D99% c)skin5mm D99% d)Skin1mm – average e)Skin3mm – average f) Skin5mm – average g)
Skin1mm – D1% h) Skin3mm – D1% i) Skin5mm – D1% for No Bolus Plans (Blue) and Clinical
Plans (Red) for the 8 patients. ..................................................................................................... 65
Figure 2.12: Dosimetric parameters for organs at risk a) Box and Whisker plot for Ipsilateral
Lung V30% b) Bar Chart for Heart V5% c) Bar Chart for Heart V25% for No Bolus Plans (Blue)
and Clinical Plans (Red) for the 8 patients. ................................................................................. 66
Figure 3.1: Example Dose Distribution for a) No Bolus plan b) Clinical plan c) VMAT plan ........ 71
Figure 3.2: Example of DVH for structure PTVtoSurface. (Dashed line= Clinical Plan, Dotted line
= No Bolus Plan and Solid line = VMAT plan) .............................................................................. 72
Figure 3.3: Example DVHs for a) Skin1mm b)Skin3mm c)Skin5mm (Dashed line=Clinical plan,
Dotted line = No Bolus plan, Solid line=VMAT plan) ................................................................... 74
Figure 3.4: Example DVHS for Heart (red line), Ipsilateral Lung (Orange line) and Contralateral
Breast (Blue line). (Dashed line = Clinical plan, Dotted line = No Bolus Plan and Solid line=VMAT
plan) ............................................................................................................................................ 75
Figure 3.5: Box and Whisker plots showing the a) V95% b) average dose c) V105% d)107% and
e) D1% parameters for the PTVtoSurface structures for No Bolus Plans (Blue), Clinical Plans
(Red) and VMAT Plans (Green) in the 8 patients. ....................................................................... 77
Figure 3.6: Box and Whisker plots showing the doses for a) Skin1mm – D99% b) Skin3mm –
D99% c)skin5mm D99% d)Skin1mm – average e)Skin3mm – average f) Skin5mm – average g)
Skin1mm – D1% h) Skin3mm – D1% i) Skin5mm – D1% for No Bolus plans (Blue), Clinical plans
(Red) and VMAT plans (Green) for the 8 patients. ...................................................................... 79
Figure 3.7: Dosimetric parameters for organs at risk a) Box and Whisker plot for Ipsilateral Lung
V30% b) Bar Chart for Heart V5% (mandatory constraint shown in dashed line) c) Bar Chart for
Heart V25% d) Box and Whisker plot for Contralateral Breast for No Bolus Plans (Blue), Clinical
Plans (Red) and VMAT Plans (Green) for the 8 patients. ............................................................ 82
Figure 4.1: Dose distribution for a) No Bolus b) Bolus and c) VMAT partial arc plan on the CIRS
anthropomorphic thorax phantom ............................................................................................. 87
Figure 4.2: Points showing the TLD position on central axis of CT Scan of CIRS phantom. Each
TLD point is positioned to intersect with the body contour (green), ........................................... 88
Figure 4.3: a) anthropomorphic phantom position for treatment delivery b) packets position
with TLD either side of central axis ............................................................................................. 89
Figure 4.4: 1cm water equivalent material placed over phantom prior to delivery of bolus plan.
.................................................................................................................................................... 89
Figure 4.5: TLD results for No Bolus plan compared to treatment plan dose - 1 fraction delivery.
(Plan delivered 4 times) ............................................................................................................... 91
8
Figure 4.6: TLD results for Bolus plan compared to treatment plan dose - 1 fraction delivery
(Plan delivered 3 times) ............................................................................................................... 92
Figure 4.7: TLD results for VMAT plan compared to treatment plan dose - 1 fraction delivery.
(Plan delivered once) ................................................................................................................... 93
Figure 5.1: Example of perturbed plans a) Clinical plan -non perturbed b) Clinical plan –
perturbed 0.5cm TS direction c) Clinical plan – perturbed 0.5cm AS direction d) VMAT plan –
non perturbed e) VMAT plan – perturbed 0.5cm TS direction f) VMAT plan – perturbed 0.5cm AS
direction ...................................................................................................................................... 99
Figure 5.2: Example of DVHs for PTVtoSurface a)Clinical plan non-perturbed v Clinical plan
perturbed 0.5 in TS direction b) Clinical plan non-perturbed v Clinical plan perturbed 0.5cm in
AS direction c)VMAT plan non-perturbed v VMAT plan perturbed 0.5cm in TS direction d) VMAT
plan non-perturbed v VMAT plan perturbed 0.5cm in AS direction. (Dotted line = original plan,
dashed line = perturbed plan) ................................................................................................... 101
Figure 5.3: Example of DVHs for Skin3mm a)Clinical plan non-perturbed v Clinical plan
perturbed 0.5 in TS direction b) Clinical plan non-perturbed v Clinical plan perturbed 0.5cm in
AS direction c)VMAT plan non-perturbed v VMAT plan perturbed 0.5cm in TS direction d) VMAT
plan non-perturbed v VMAT plan perturbed 0.5cm in AS direction. (Dotted line = original plan,
dashed line = perturbed plan) ................................................................................................... 104
Figure 5.4 : Bar chart showing the perturbation effect on the parameters D99%, average dose
and D1%, for the Skin3mm. The graph shows the impact for both Clinical and VMAT plans.
(Non-perturbed = blue, perturbation 0.5cm TS = red and perturbation 0.5cm AS= green). ..... 105
Figure 5.5: DVH for Heart (Red) Ipsilateral Lung (Orange) and Contralateral Breast (Blue)
a)Clinical plan non-perturbed v Clinical plan perturbed 0.5 in TI direction b) Clinical plan non-
perturbed v Clinical plan perturbed 0.5cm in AI direction c)VMAT plan non-perturbed v VMAT
plan perturbed 0.5cm in TI direction d) VMAT plan non-perturbed v VMAT plan perturbed
0.5cm in AI direction. (Dotted line = original plan, dashed line = perturbed plan) ................... 106
Figure 5.6: Bar chart showing perturbation effect on the parameters V95% (blue), V105% (red)
and V107% (green), displayed as volume difference from non-perturbed plan, for PTVtoSurface,
averaged for 8 patient cases. The graph shows the impact for both Clinical and VMAT plans.109
Figure 5.7: Bar chart showing perturbation effect on the parameters average dose (blue) and
D1% (green), displayed as dose difference from non-perturbed plan, for PTVtoSurface,
averaged for 8 patient cases. The graph shows the impact for both Clinical and VMAT plans.109
Figure 5.8: Bar chart showing V95% for PTVtoSurface, averaged over 8 patients, under the
indicated perturbation conditions. Clinical Plans (blue) and VMAT plans (red). (Dotted line =
mandatory constraint, dashed line = optimal constraint) ........................................................ 110
9
Figure 5.9: Bar chart showing V105 values% for PTVtoSurface, averaged over 8 patients, under
the indicated perturbation conditions. Clinical Plans (blue) and VMAT plans (red). (Dotted line =
mandatory constraint, dashed line = optimal constraint) ........................................................ 110
Figure 5.10: Bar chart showing V107% values for PTVtoSurface, averaged over 8 patients,
under the indicated perturbation conditions. Clinical Plans (blue) and VMAT plans (red). (Dotted
line = mandatory constraint)..................................................................................................... 111
Figure 5.11: Bar chart showing D1% values for PTVtoSurface, averaged over 8 patients, under
the indicated perturbation conditions. Clinical Plans (blue) and VMAT plans (red). (Dotted line =
mandatory constraint) .............................................................................................................. 111
Figure 5.12: Bar chart showing perturbation effect on the parameters D99% (blue), average
dose (orange) and D1% (green) for Skin3mm, displayed as dose difference from non-perturbed
plan, averaged for 8 patient cases. The graph shows the impact for both Clinical and VMAT
plans. ......................................................................................................................................... 113
Figure 5.13: Bar chart showing D1% values for Skin3mm, averaged over 8 patients, under the
indicated perturbation conditions. Clinical Plans (blue) and VMAT plans (red). ...................... 114
Figure 5.14: Bar chart showing perturbation effect on the V25% for the heart, displayed as
volume difference from non-perturbed plan, averaged over left-sided cases (n=5). The graph
shows the impact for both Clinical and VMAT plans. ............................................................... 116
Figure 5.15: Bar chart showing V5% (2Gy) for heart for plans perturbed in the 0.5cm AI
direction. The graph shows the impact for both Clinical and VMAT plans (Dotted
line=mandatory constraint). ..................................................................................................... 116
Figure 5.16: Bar chart showing perturbation effect on V30% for the ipsilateral lung, displayed
as volume difference from non-perturbed plan, averaged over the 8 patient cases. The graph
shows the impact for both Clinical and VMAT plans (Dotted line = mandatory constraint
permitted, based on volume irradiated in non-perturbed plan) ............................................... 117
Figure 5.17: Bar chart showing perturbation effect on contralateral breast, displayed as dose
difference from non-perturbed plan, averaged over the 8 patient cases. The graph shows the
impact for both Clinical and VMAT plans. ................................................................................. 118
Figure 5.18: DRRs displaying treatment field segment for a)non-perturbed Clinical plan b)
Perturbed plan 0.5cm in TS direction showing PTVtoSurface (green contour) no longer fully
covered. ..................................................................................................................................... 119
Figure 5.19: Typical MLC segments for VMAT plan a) Non-perturbed b) Perturbed plan 0.5cm in
TS direction showing segment now outside PTVtoSurface (green contour). ............................ 120
Figure 6.1: Dose distribution a)VMATRO plan b)VMAT plan c) dose difference between
VMATRO and VMAT .................................................................................................................. 126
10
Figure 6.2: DVH for PTVtoSurface for example patient. The dashed line represents the Clinical
Plan, the dotted line the VMAT plan and the solid line is the VMATRO plan ........................... 126
Figure 6.3: Box and Whisker plots showing the a) V95% b) average dose c) V105% d)107% and
e) D1% parameters for the PTVtoSurface structures for No Bolus Plans (Blue), Clinical Plans
(Red), VMAT Plans (Green) and VMATRO Plans (Purple) in the 8 patients. .............................. 129
Figure 6.4: Dosimetric parameters for organs at risk a) Box and Whisker plot for Ipsilateral Lung
V30% b) Bar Chart for Heart V5% (mandatory constraint shown in dashed line) c) Bar Chart for
Heart V25% d) Box and Whisker plot for Contralateral Breast for No Bolus Plans (Blue), Clinical
Plans (Red),VMAT Plans (Green) and VMATRO Plans (Purple) for the 8 patients. ................... 131
Figure 6.5: Box and Whisker plot showing the doses for the D99% parameter for the Skin3mm
structure for the 8 patients for the No Bolus plans (Blue), Clinical plans (Red), VMAT plans
(Green) and VMATRO plans (Purple) ........................................................................................ 132
Figure 6.6: Box and Whisker plot showing the doses for the D1% parameter for the Skin3mm
structure for the 8 patients for the No Bolus plans (Blue), Clinical plans (Red), VMAT plans
(Green) and VMATRO plans (Purple) ........................................................................................ 133
Figure 6.7: Box and Whisker plot showing the doses for the average dose parameter for the a)
Skin1mm b) Skin3mm and C) Skin5mm structures for the 8 patients for the No Bolus plans
(Blue), Clinical plans (Red), VMAT plans (Green) and VMATRO plans (Purple). ....................... 134
Figure 6.8: Bar chart showing perturbation effect on the parameters V95% (blue), V105% (red)
and V107% (green), displayed as volume difference from non-perturbed plan, for PTVtoSurface,
averaged for 8 patient cases. The graph shows the impact for Clinical, VMAT and VMATRO
plans.) ........................................................................................................................................ 136
Figure 6.9: Bar chart showing V105 values% for PTVtoSurface, averaged over 8 patients, under
different perturbation conditions. Clinical Plans (blue), VMAT plans (red) and VMATRO (green).
(Dotted line = mandatory constraint, dashed line = optimal constraint) .................................. 137
Figure 6.10: Bar chart showing V107% values for PTVtoSurface, averaged over 8 patients,
under different perturbation conditions. Clinical Plans (blue) and VMAT plans (red (Dotted line =
mandatory constraint) .............................................................................................................. 137
Figure 6.11: Bar chart showing V95% for PTVtoSurface, averaged over 8 patients, under
different perturbation conditions. Clinical Plans (blue), VMAT plans (red) and VMATRO (green).
(Dotted line = mandatory constraint, dashed line = optimal constraint) .................................. 138
Figure 6.12: Bar chart showing perturbation effect on the parameters average dose (blue) and
D1% (green), displayed as dose difference from non-perturbed plan, for PTVtoSurface,
averaged for 8 patient cases. The graph shows the impact for Clinical, VMAT and VMATRO
plans. ......................................................................................................................................... 138
11
Figure 6.13: Bar chart showing perturbation effect on V30% for the ipsilateral lung, displayed
as volume difference from non-perturbed plan, averaged over the 8 patient cases. The graph
shows the impact for Clinical, VMAT and VMATRO plans. (Dotted line=mandatory constraint
permitted, based on volume irradiated in non- perturbed plan. For the Clinical plan the average
non-perturbed volume = 11.7%, for the VMAT plan the average non-perturbed volume = 8.4%
and for the VMATRO the average non-perturbed volume = 10.1%. The constraint for V30% <
17%, therefore permitted constraint for perturbation is 5.3%, 8.6% and 6.9% for Clinical, VMAT
and VMATRO plans, respectively). ............................................................................................ 140
Figure 6.14: Bar chart showing V5% (2Gy) for heart for plans perturbed in the 0.5cm AI
direction. The graph shows the impact for Clinical, VMAT and VMATRO plans (Blue bars= non-
perturbed, red bars=perturbed, dotted line=mandatory constraint)........................................ 141
Figure 6.15: Bar chart showing perturbation effect on contralateral breast, displayed as dose
difference from non-perturbed plan, averaged over the 8 patient cases. The graph shows the
impact for Clinical, VMAT and VMATRO plans. ........................................................................ 141
Figure 6.16: Bar chart showing perturbation effect on the parameters D99% (blue), average
dose (orange) and D1% (green) for Skin3mm, displayed as dose difference from non-perturbed
plan, averaged for 8 patient cases. The graph shows the impact for Clinical, VMAT and
VMATRO plans. ......................................................................................................................... 143
Figure 6.17: Bar chart showing D1% values for Skin3mm, averaged over 8 patients, under
different perturbation conditions. Clinical Plans (blue), VMAT plans (red) and VMATRO plans
(green). ...................................................................................................................................... 143
Figure 6.18: Bar chart showing average values for Skin3mm, for the 8 patients, under different
perturbation conditions. Clinical Plans (blue), VMAT plans (red) and VMATRO plans (green) . 144
Figure 6.19: Bar chart showing D99% values for Skin3mm, averaged over 8 patients, under
different perturbation conditions. Clinical Plans (blue), VMAT plans (red) and VMATRO plans
(green) ....................................................................................................................................... 144
12
Tables
Table 2.1: Departmental objectives and constraints used for breast planning based on those
used in FAST-Forward Trial (ISRCTN19906132) .......................................................................... 50
Table 2.2: Summary of patient information including treatment site (CW=chest wall), machine
and beam energy ........................................................................................................................ 53
Table 2.3: Summary of dosimetric parameters recorded for each patient ................................. 56
Table 2.4: Example of dosimetric parameters obtained for the structure PTVtoSurface for the
Clinical and No Bolus Plans for one patient. ............................................................................... 58
Table 2.5: Example of dosimetric parameters obtained for the Skin Structures for the Clinical
and No Bolus Plans. (Values is brackets represent the dose received as a percentage of the
prescription dose, 40Gy). ............................................................................................................ 60
Table 2.6: Example of dosimetric parameters obtained for the heart and ipsilateral lung OARS,
for the Clinical and No Bolus Plans. ............................................................................................ 61
Table 3.1: Typical starting values for planning objectives used for the VMAT plans. ................. 70
Table 3.2: Example of dosimetric parameters obtained for the structure PTVtoSurface for the
Clinical, No Bolus and VMAT plans ............................................................................................. 72
Table 3.3: Example of dosimetric parameters obtained for the skin structures for the Clinical, No
Bolus and VMAT plans (Values in brackets represent the dose received as a percentage of the
prescription dose, 40Gy) ............................................................................................................. 73
Table 3.4: Example of dosimetric parameters obtained for the heart, lung and contralateral
breast, for the Clinical, No Bolus and VMAT plans...................................................................... 76
Table 4.1: Results of TLD measurements for No Bolus plan as percentage of prescribed dose
compared to planned dose, absolute dose in brackets. .............................................................. 91
Table 4.2: Results of TLD measurement for Bolus plan as percentage of prescribed dose
compared to planned dose absolute dose in brackets. (Measurement 2 at TLD position 3
disregarded in these results) ....................................................................................................... 92
Table 4.3: Results of TLD measurements for VMAT plan as percentage of prescribed dose
compared to planned dose absolute dose in brackets. ............................................................... 93
Table 5.1: Summary of shifts for perturbed plans. Abbreviation for perturbation direction are
included. ...................................................................................................................................... 97
Table 5.2: Example of dosimetric parameters for the non-perturbed Clinical plan and with a
perturbation of 0.5cm in the TS and AS directions. Values underlined show where constraints
were not met. ............................................................................................................................ 102
13
Table 5.3: Example of dosimetric parameters for the non-perturbed VMAT plan and with a
perturbation of 0.5cm in the TS and AS directions. Values underlined show where constraints
were not met ............................................................................................................................. 102
Table 5.4: Example of dosimetric parameters for the non-perturbed Clinical plan and with a
perturbation of 0.5cm in the TI and AI directions. Values underlined show where constraints
were not met. ............................................................................................................................ 107
Table 5.5: Example of dosimetric parameters for the non-perturbed VMAT plan and with a
perturbation of 0.5cm in the TI and AI directions. Values underlined show where constraints
were not met. ............................................................................................................................ 107
Table 6.1: Dosimetric parameters achieved for PTVtoSurface single patient example. The
mandatory and optimal constraints are defined. ..................................................................... 127
Table 6.2: Dosimetric parameters achieved for organs at risk single patient example. The
mandatory and optimal constraints are defined. ..................................................................... 127
Table A1.1: Comparison of dosimetric parameters for planning structures, with VMAT plan re-
calculated using dose grids 0.2cm and 0.3cm......................................................................... 1643
Table A1.2: Comparison of dosimetric parameters for planning structures, with VMAT plan re-
calculated using dose grids 0.2cm and 0.3cm and perturbed in the 0.5cm AS direction ........ 1654
Table A1.3: Comparison of dosimetric parameters for planning structures, with VMAT plan re-
optimised using dose grids 0.2cm and 0.3cm ......................................................................... 1654
Table A1.4: Comparison of dosimetric parameters for planning structures, with VMAT plan re-
optimised using dose grids 0.2cm and 0.3cm and perturbed 0.5cm in the AS direction ........ 1665
Table A2.1 -Comparison of dose parameters for structures in VMATRO plans optimised in all
directions and limited directions, including the perturbation in AS direction…………………………168
Table A3.1: V105% parameter for PTVtoSurface for every patient. VMAT RO plans perturbed in
the AS direction to different extents……………………………………………………………………………………..170
Table A3.2: V107% parameter for PTVtoSurface for every patient. VMAT RO plans perturbed in
the AS direction to different extents……………………………………………………………………………………..170
Table A4.1: Additional information on the range of perturbation effect on the planning
parameters V95%, V105%, V107%, average dose and D1%, for the PTVtoSurface structure, for
the 8 patient cases. Data is included for the Clinical, VMAT and VMATRO plans, the data shows
the average volume difference or dose difference from the non-perturbed plan and the
min/max difference over the 8 patients. The averaged data for the planning parameters shown
in Figures 5.6, 5.7, 6.8 and 6.12. …………………………………………………………………………………………..172
Table A4.2: Additional information on the range of perturbation effect on the planning
parameters V95%, V105%, V107%, average dose and D1%, for the PTVtoSurface structure, for
the 8 patient cases. Data is included for the Clinical, VMAT and VMATRO plans, the data shows
14
the average volume or dose and the min/max values across the 8 patients. The averaged data
for the planning parameters shown in Figures 5.8-5.11 and 6.9-6.11……………………………………173
Table A4.3: Additional information on the range of perturbation effect on the planning
parameters D99%, Average and D1% for the Skin3mm structure, over the 8 patient cases. Data
is included for the Clinical, VMAT and VMATRO plans, the data shows the dose difference from
the non-perturbed plan and the min/max difference over the 8 patients. The averaged data for
the planning parameters shown in Figures 5.12, 6.16…………………………………………….…….………174
Table A4.4: Additional information on the range of perturbation effect on the planning
parameters D99%, D1% and Average dose for the Skin3mm structure, for the 8 patient cases.
Data is included for the Clinical, VMAT and VMATRO plans, the data shows the average doses
and the min/max difference over the 8 patients. The averaged data for the planning
parameters shown in Figures 5.13, 6.17-6.19……………………………………………………………………….175
Table A4.5: Additional information on the range of perturbation effect on the planning
parameters for heart and lungs structures, heart. Data is included for the Clinical, VMAT and
VMATRO plans, the data shows the average doses and the min/max difference over the 8
patients for the lung parameter and the 5 left chest wall patients for the heart parameters. The
averaged data for the planning parameters shown in Figures 5.14-5.16 and 6.13-6.14……..…176
15
Acronyms 3D-CRT Three-dimensional conformal radiotherapy
ASCO American Society of Clinical Oncology
CBCT Cone beam computed tomography
CT Computer tomography
CTV Clinical target volume
DIBH Deep inspiration breath hold
DNA Deoxyribonucleic acid
DVH Dose volume histogram
GTV Gross tumour volume
ICRP International commission on Radiological Protection
ICRU International Commission on Radiological Units &
Measurements
IMRT Intensity-modulated radiotherapy
ITV Internal target volume
MLC Multi-leaf collimator
MOSFET Metal oxide semiconductor field effect transistor
MU Monitor units
NICE National Institute for Health and Care Excellence
NTCP Normal tissue complication probability
OAR Organ at risk
OSLD Optically stimulated luminescence
PMRT Post-mastectomy radiotherapy
PRV Planning organ at risk volume
PTV Planning target volume
SMLC Segmented multileaf collimation
QEHB Queen Elizabeth Hospitals Birmingham
TCP Tumour control probability
TLD Thermoluminescent dosimeter
TNM Tumour, nodes, metastases
VMAT Volumetric modulated arc therapy
WED Water equivalent depth
16
Abstract
Radiotherapy following surgery is routine practice for patients that have had a
mastectomy and are at high risk of the cancer recurring. To ensure that the chest-wall
receives an adequate radiation dose a tissue equivalent material, or bolus, 1cm thick is
placed on the patient surface. At the Queen Elizabeth Hospitals Birmingham (QEHB)
this is applied for 7 of the 15 fractions of treatment. This technique however requires
the creation of two treatment plans, increasing planning time in the patient pathway.
In addition, the lack of flexibility of the bolus can cause air gaps between the skin and
material affecting the surface dose and since the bolus is only required for a number of
the fractions, treatment errors can occur if it is omitted by mistake. The aim of the
research was to investigate a single, no bolus planning solution for these patients to
reduce these issues.
For a sample of 8 patients it was shown that bolus increased the target volume
receiving 95% of the prescription dose by 7.7% compared to using no bolus at all. The
use of VMAT could replicate these dose distributions, including superficial doses,
without the need for bolus. Although the VMAT plans did produce a low dose bath
which in some cases increased the doses to organs at risk, the plans still met all the
required dose constraints.
However, fluence loading in the surface region (to overcome the build-up effect)
means that VMAT plans show unacceptable changes in dose distribution with changes
in patient position or contour.
Combining VMAT with robust optimisation significantly reduced dose differences
caused by perturbation. These plans however still resulted in distributions that did not
meet accepted dose constraints within the target structure, potentially causing
undesired side effects for the patients. The use of robust optimisation also
compromised the non-perturbed plans, reducing the dose enhancement effect to the
patient surface.
A single plan solution using the VMAT technique and combined with robust
optimisation produced plans that mimic the clinical plans, without the use of bolus.
Although the robust optimisation significantly reduced the variation in dose due to
perturbation, these plans are still susceptible to patient movement and can result in
tolerance doses being exceeded.
The combination of VMAT and robust optimisation shows promise in producing a
single, no bolus plan solution for chest-wall irradiation, but further work is required to
quantify patient motion if the technique is to be applied clinically.
17
Declaration
I declare that no portion of the work referred to in the thesis has been submitted in
support of an application for another degree or qualification of this or any other
university or other institute of learning.
Copyright
i. The author of this thesis (including any appendices and/or schedules to this
thesis) owns certain copyright or related rights to it (the “Copyright”) and
he has given The University of Manchester certain rights to use such
Copyright, including for administrative purposes.
ii. Copies of the thesis, either in full or in extracts and whether in hard or
electronic copy, may be made only in accordance with the Copyright,
Designs and Patents Act 1988 (as amended) and regulations issued under it
or, where appropriate, in accordance with licensing agreements which the
University has from time to time. This page must form part of any such
copies made.
iii. The ownership of certain Copyright, patents, designs, trademarks and other
intellectual property (the “Intellectual Property”) and any reproductions of
copyright works in the thesis, for example graphs and tables
(“Reproductions”), which may be described in the thesis, may not be owned
by the author and may be owned by third parties. Such Intellectual Property
and Reproductions cannot and must not be made available for use without
18
the prior written permission of the owner(s) of the relevant Intellectual
Property and/or Reproductions.
iv. Further information on the conditions under which disclosure, publication
and commercialisation of this thesis, the Copyright and any Intellectual
Property and/or Reproductions described in it may take place is available in
the University IP Policy (see
http://documents.manchester.ac.uk/DocuInfo.aspx?DocID=24420 ), in any
relevant Thesis restriction declarations deposited in the University Library,
The University Library’s regulations (see
http://www.library.manchester.ac.uk/about/regulations/ ) and in The
University’s policy on Presentation of Theses.
19
Acknowledgements
The completion of this thesis and additional aspects of this professional doctorate as
part of the Higher Specialist Scientist Training, would not have been possible without
the support and assistance I have received from many people.
I would like to thank my thesis supervisors Jason Cashmore and Helen Mayles for their
guidance and encouragement with this project. Their experience and advice has been
invaluable.
I am very grateful to my colleagues in the radiotherapy team at the Queen Elizabeth
Hospitals Birmingham for enabling me to take part in the HSST program and for their
continued support and reassurance throughout the process.
I would also like to thank the staff involved with the DClinSci for the organisation and
delivery of the course. Being one of the first cohort to go through the scheme has been
particularly challenging at times and I am grateful to have met and overcome these
issues with a wonderful group of people. In particular I would like to thank Peter
McGookin and Pedrum Kamali for their friendship and support especially in the last
few months.
To my friends and family, thank you for your endless encouragement and finally to my
partner, Jonathan Trinder, thank you for always being there.
20
Statement for Examiners
This research project forms part of the Doctor of Clinical Science (DClinSci). In addition
to the research project the DClinSci includes taught components and an innovation
project. Specialist scientific units in Medical Physics, have been delivered by the
University of Liverpool and the University of Manchester, and the teaching and
assessment for the Post Graduate Diploma in Healthcare Science Leadership has been
provided by Alliance Manchester Business School. The generic scientific units and the
innovation project were undertaken through the University of Manchester. A summary
of units and associated assessments is provided in Appendix 5. The Alliance
Manchester Business School (A units) account for 120 credits. The specialist and
generic scientific (B units) account for 150 credits, the innovation project (C1), 70
credits, and the Research Project accounts for 200 credits.
21
Chapter 1
1 Introduction
This chapter provides a brief overview of cancer biology, particularly focussing on
breast cancer, and the role of external beam radiotherapy in the treatment of patients
who have had undergone a mastectomy. The current techniques used in radiotherapy
treatment of breast cancer will be discussed and the rationale for the introduction of a
new approach to the technique will be presented.
1.1 Cancer
Cancer is a term used to describe a disease where a group of cells within the body
divide uncontrollably. Cell division, replication and multiplication are fundamental
processes within the human body to enable growth, maintenance and repair.
However, mutations to the DNA can cause disruptions to the normal cell cycle, making
cells divide more quickly or avoid cell death, resulting in abnormal growth of tissue, a
tumour. Tumours can be defined as malignant or benign. Those that divide too much,
but that do not have the potential to invade other tissues or spread around the body,
are described as benign. Tumours that can invade other tissues and spread to other
organs within the body (metastasize) are known as malignant.
Cancer Research UK report that one in two people born in the UK after 1960 will be
diagnosed with cancer at some time during their lifetime (excluding non-melanoma
skin cancer) with 367, 000 new cases reported each year in the period 2015-2017
(Cancer Research UK, 2021c). In the UK the most prevalent cancers, accounting for
more than half of all new cases, male and female combined, are breast (15%), prostate
(13%), lung (13%) and bowel (11%). In females, breast cancer accounts for 30% of all
new cases, with 1 in 7 women in the UK predicted to develop it at some point their
lifetime. The incidence rate of breast cancer in the UK has increased by 4% in the last
decade with mortality rates decreasing by 21%. The doubling of breast cancer survival
22
in the past 40 years is thought to be a result of a combination of improvements in
treatment and care, and in early detection through screening and faster diagnosis.
1.2 Breast Anatomy
The breast is defined as the tissue that overlies the pectoral muscles in the chest and
consists of glandular tissues called lobules which produce milk during lactation. The
lobules consist of a series of lobes surrounded by fat cells and connective tissue and
are supported with ligaments. Blood vessels circulate blood around the breast tissue
and nerves running through the tissue are responsible for sensation. The breast tissue
also contains lymphatic vessels which connect to lymph nodes in the axilla and behind
the sternum which maintain the fluid balance within the breast tissue and remove
unwanted toxins from the tissue. Figure 1.1 shows the key structures within the breast
(Cancer Research UK, 2021g).
Figure 1.1: Cross section of the mammary gland. (Source: Cancer Research UK)
1.3 Breast Cancer
Breast cancer most commonly occurs in the epithelial cells that line the ducts of the
breast and the breast lobules. If the tumour has started to invade other tissue within
the breast and grown out of the lining of the duct or lobule, the carcinoma is described
23
as invasive, Figure 1.2. When the cells remain contained within the basal membrane
they are referred to as, in situ. In the case of lobular carcinoma in situ, this is not
considered cancerous, though may be indicative of a higher risk of developing cancer
in the future, so treatment is usually limited to regular monitoring. Ductal carcinoma in
situ, may eventually spread to surrounding tissues if not treated and is usually graded
to establish the course of treatment required. In the UK around 70 % of invasive breast
cancers arise from the ducts, whilst around 15% start in the breast lobules (Cancer
Research UK, 2021e, 2021d). Other, rarer, types of breast cancer include inflammatory
breast cancer, which effects the lymph ducts and angiosarcomas, which effect the soft
tissue in the breast. Breast cancer can also spread via the lymphatic system to nodes in
the armpit (axillary), near the breastbone (internal mammary) or to nodes above the
collar bone (supraclavicular).
a)
b)
Figure 1.2: Diagram showing a) lobular carcinoma in situ and invasive carcinoma and b) ductal carcinoma in situ and invasive carcinoma (Source: Cancer Research UK)
1.3.1 Breast Cancer Diagnosis
The most common route for the diagnosis of breast cancer is via the ‘two-week wait’
pathway when patients who meet a particular criteria for age and symptoms, are
referred to specialists by their General Practitioner. 51% of female invasive breast
24
cancers are diagnosed via the ‘two-week wait’ referral route and 31% are detected via
mammography screening, which detects the highest proportion of cases diagnosed at
an early stage (Cancer Research UK, 2021a)
Tests for diagnosing breast cancer are often performed as part of a triple assessment,
consisting of physical examination, imaging and a biopsy. The imaging normally
consists of an ultrasound, which can distinguish whether a lump is solid or fluid. Fluid-
filled lumps may be drained, and solid lumps may be biopsied, followed by further
imaging using mammography.
To establish the prognosis of a patient with breast cancer and recommend the most
suitable treatment plan, information about the stage and grade of the tumour is
required along with the tumour type or its response to hormones.
Tumour staging takes into account the physical properties of the tumour, its size and
whether it has spread. The TNM staging system gives the complete stage of the cancer.
T describes the tumour size, N the nodal involvement and M whether the cancer has
metastasised. Similarly, breast cancer can be divided into 4 stages, with further sub-
categories for Stage 1 and 2 (A and B) and 3 for Stage 3 (A, B and C). Each category and
sub-category have a solid tumour size, and indication of nodal involvement associated
with it. Macmillan Cancer Support describe the stages as follows (Macmillan Cancer
Support, 2021). Stage 1A breast cancer is when the cancer is <2cm and has not spread
outside the breast. Stage 1B indicates small areas of breast cancer cells are found in
the lymph nodes and that no tumour is found in the breast or it is <2cm. Stage 2A
means that there is no tumour in the breast or it is <2cm, and there is 1-3 lymph nodes
involved. Stage 2B can mean that the tumour 2-5cm in size, with some cancer cells
identified in the nodes or 1-3 lymph nodes are involved. Stage 2B can also mean that
the tumour >5cm but not involving any lymph nodes. Stage 3 is referred to as locally
advanced and means that the cancer has spread to lymph nodes or to the skin of the
breast or chest wall. Stage 3A includes cases where the tumour is any size in the breast
tissues (including no tumour) but 4-9 lymph nodes are involved or is >5cm with small
clusters of cancer cells in the lymph nodes or up to 3 lymph nodes in the armpit or
near the breast bone. Stage 3B indicates the tumour has spread to the skin or into the
chest wall and Stage 3C indicates there is cancer in the skin and the breast cancer cells
have spread to 10 or more lymph nodes in the arm pits, lymph nodes above or below
25
the collar bone, or lymph nodes in the armpit and near the breastbone. The stage 3C
cancers may be considered operable or inoperable. Stage 4 breast cancer is used to
described secondary or metastatic breast cancer, when the tumour has spread to
other parts of the body. Tumour grading describes the abnormality of the cells
examined microscopically and is indicative of how aggressive the cancer is likely to be.
For invasive breast cancer there are three grades, Grade 1 to Grade 3. Grade 1 (low
grade) cancer cells look most like normal breast cells, well differentiated, usually slow-
growing and less likely to spread. Grade 2 (intermediate grade) the cells look more
abnormal and slightly faster growing that Grade 1. Grade 3 (high grade) look very
difference from normal breast tissue cells and are more likely to grow quickly and
spread to other sites.
Tumour biomarkers are also used in breast cancer to help define the prognosis and
stratify patient treatment. Tumours that are oestrogen or progesterone receptor
positive will respond well to hormone therapies that will stop the hormone stimulating
cancer cells to grow and divide. Similarly, breast cancers with high levels of the protein
HER2 are likely to respond to drugs that will attach to the protein and supress the cell
growth and division.
Survival for breast cancer is related to the stage of disease at diagnosis. Data published
by the Office for National Statistics is summarised by Cancer Research UK (2021e)
indicating that for female patients diagnosed with Stage 1 breast cancer, survival at 1
year was 100% reducing to 97.9% at 5 years. For Stage 2 breast cancer at diagnosis,
survival went from 98.9% at year one to 89.6% at year 5, and Stage 3 and 4, were
95.5% to 72% and 66% to 26.2%, respectively, at the same time points.
1.3.2 Breast Cancer Treatment
Treatment for breast cancer is primarily surgery, with 81.2% of patients diagnosed
with breast cancer in England (2013-2014) having it as part of their primary treatment
(Cancer Research UK, 2021b).The proportion of patients having surgery is dependent
on the stage at diagnosis with 92.8% of Stage 1 patients having surgery compared with
25.1% of Stage 4 patients. This may either be a breast-conserving procedure, surgery
removing part of the breast containing the cancer or mastectomy, removal of all the
26
breast tissue. Both surgeries may also involve the removal of lymph nodes, dependent
on involvement. Additional treatment such as radiotherapy, chemotherapy, endocrine
or biological therapies, will be dependent on several factors. These include the staging,
grading and presence of tumour biomarkers, the risk of local recurrence, which may be
age related, and any patient comorbidities.
For patients with invasive breast cancer the National Institute for Clinical Excellence
guidelines NG101 (NICE, 2018) recommend offering whole-breast radiotherapy
following breast-conserving surgery with clear margins, unless the patient is at very
low risk of local recurrence and are willing to take adjuvant endocrine therapy for at
least 5 years. For patients having undergone a mastectomy it is recommended that
adjuvant radiotherapy is offered to those with node-positive (macrometastases)
invasive breast cancer or those with involved margins. Radiotherapy should also be
considered for people with node-negative T3 or T4 breast cancer but not be offered to
those with invasive breast cancer at a low risk of local recurrence, where risks
associated with radiotherapy outweigh the benefits.
In 2013-2014 63.2% of all patients diagnosed with breast cancer received radiotherapy
as part of their treatment. The proportion of patients receiving radiotherapy was
dependent on the stage of cancer at diagnosis. For patients with stage 1, 2 and 3 at
diagnosis the percentage receiving radiotherapy was 70.2%, 65.1% and 80.4%
respectively. For those with Stage 4 cancer at diagnosis 39.2% received radiotherapy
(Cancer Research UK, 2021b).
1.4 Radiotherapy Treatment
Radiotherapy is the use of high energy radiation to treat cancer cells. It works by
delivering ionising radiation which damages the DNA (deoxyribonucleic acid) of the
tumour cells. As radiation can also damage normal tissue it is important that the
treatment is designed so that the tumour volume receives enough damaging radiation
to kill the tumour cells, high ‘tumour control probability’ (TCP) whilst minimising the
dose to the healthy tissues, low ‘normal tissue complication probability’ (NTCP). As
normal tissue cells are usually better at repairing from the damage from radiation than
the tumour cells, the radiation is delivered in daily fractions, allowing the healthy
27
tissue to undergo some repair, before another treatment is delivered. For breast
cancer treatments the radiotherapy is delivered using a linear accelerator with a
technique known as external beam radiotherapy. The radiation beam enters the
patient from an external source, in the head of the linear accelerator, and deposits
energy that damages the cells, when it intersects with the patient. The gantry design of
the linear accelerator allows radiation beams to enter the patient from a range of
different coplanar directions, Figure 1.3a. Overlapping the radiation beam at the site of
the tumour intensifies the dose in this area whilst minimising dose to the surrounding
area, Figure 1.3c. The beam can also be modified to conform to the shape of the
tumour. This is done in the head of the linear accelerator with the use of multi-leaf
collimators, individual tungsten leaves which can be adjusted to create the required
beam shape, Figure 1.3b.
1.5 Radiotherapy Treatment Planning
When a patient has been referred for breast radiotherapy a computer tomography
(CT) scan is performed. The scan provides detailed cross-sectional anatomical
information that is used to define the area to be treated, determine the optimal
direction that radiation beams need to enter the patient and to calculate the dose the
linear accelerator needs to deliver. To ensure that the patient is in the same position
for every fraction of treatment an immobilisation device is used. Patients receiving
radiotherapy for breast cancer are positioned on a breast board which keeps the arms
above the head. To help with daily set up the patient may also be tattooed, providing
an external reference to aid in locating the treatment area. The CT scans are
transferred to computer software where virtual simulation packages reconstruct the
data into a 3D model of the patient. The system is then used by the clinician to define
the area that needs to be treated and any organs at risk or areas of normal tissue
where dose should be kept to a minimum. Treatment planning is performed using
specialised software that is able to accurately calculate the dose deposited in the
patient. The software uses complex algorithms to model how the radiation will interact
with the patient based on electron density information acquired from the CT scan.
28
a)
b)
c)
Figure 1.3: a) Virtual 3D representation of linear accelerator (Prosoma v4.2, MedCom, Germany) b) MLCs defining beam shape c) Intersecting radiation beams over region of treatment
29
1.6 Radiotherapy Volume Definitions
To ensure that the tumour is treated adequately the international commissioning on
radiation units and measurements (ICRU) published recommendations, ICRU report 50
(International Commission on Radiation Units and Measurements, 1993), ICRU report
62 (ICRU, 1999) and ICRU report 83 (ICRU, 2010) on the use of margins to account for a
variety of uncertainties. The GTV is the Gross Tumour Volume and defined as the
extent of the malignant tumour growth. The CTV (Clinical Target Volume) is the GTV
plus a margin to encompass sub-clinical microscopic malignant disease. An ITV
(Internal Target Volume) may be created around the CTV to account for internal
movement and the PTV (Planning Target Volume) is a margin added that accounts for
geometrical variations in the CTV and inaccuracies in treatment delivery. The treated
volume is then defined as the volume receiving the prescribed dose and the irradiated
volume, the volume receiving a dose that is considered significant in relation to normal
tissue tolerance. Figure 1.4 summarises these target volumes.
Figure 1.4: Radiotherapy target volumes as defined in ICRU 50, ICRU 62 and ICRU 83 reports.
30
Other planning volumes that are defined in the reports include the Organs At Risk
(OAR), healthy tissue whose radiation sensitivity may influence treatment planning
decisions and the planning organ at risk volume (PRV). As with the PTV, the PRV
includes a margin around the OAR to account for geometric variation and inaccuracies
in delivery.
The PTV is the structure to which a treatment plan is optimised to, with the treatment
planner aiming to deliver the prescribed dose to this structure within -5% and +7%
(ICRU, 1993; ICRU, 1999), and keep the dose to the surrounding tissue as low as
possible.
1.7 Breast Planning Volumes
For breast radiotherapy treatments the approach for defining planning target volumes
can be different to that described in the previous section. For breast treatment
planning, a field- based approach is often used, although not a true PTV it is useful for
the purpose of reporting. In this situation the extent of the PTV is determined by edges
of a tangential pair of beams that have been selected to cover the treatment area. The
superior/inferior field lengths cover the breast tissue, the posterior edge, to cover the
tissue but not exposing more than 1.5cm lung, and the anterior edge to cover the
extent of the soft tissue plus a flash margin, typically 1-2cm, to ensure coverage due to
inaccuracies in treatment delivery or patient movement. A ‘treated volume’ is then
created which is the intersection of the fields with the patient tissue. The PTV is then
created by clipping 5mm from the patient surface, lung and posterior beam edge, and
10mm from the superior and inferior beam edges. Figure 1.5 outlines the field-based
approach for PTV in the case of breast treatments.
Alternatively, the CTV can be manually outlined to include soft tissues of the whole
breast from 5mm below the skin surface down to the deep fascia, excluding muscle
and underlying rib cage. A PTV is then created from the CTV by adding an appropriate
margin to take account of set-up error, breast swelling and breathing.
31
a)
b)
c)
Figure 1.5: Field-based approach for PTV creation in breast treatments a) field edges defined to cover in sup/inf and ant/post directions b) treated volume (shaded pink structure) defined by intersection of tangential beams with breast tissue c) PTV (shaded purple structure) – treated volume clipped from beam edges, surface and lung.
1.8 Radiotherapy Planning Techniques
The aim of radiotherapy is to deliver adequate dose to the tumour whilst minimising
dose to normal tissues. As mentioned previously, ICRU reports 50 and 62 (ICRU, 1993;
ICRU, 1999) recommend that the homogeneity over the PTV is between -5% to +7% of
the prescribed dose. Three key techniques in external beam radiotherapy that can be
used to achieve these objectives are three-dimensional conformal radiotherapy (3D-
CRT), intensity modulated radiotherapy (IMRT) and volumetric arc therapy (VMAT).
32
3D-CRT is a term used to describe a planning technique that uses coplanar static
beams which conform to the shape of the PTV in all 3 dimensions. To achieve the
conformity, multi-leaf collimators (MLCs) are used to shape the radiation beams which
can be delivered from multiple directions. To ensure the distribution is homogeneous
wedges, high-density material in the head of the linear accelerator, can be used to
attenuate parts of the beam. This homogeneity can also be achieved with the use of
additional beam segments to modulate the radiation, also referred to as field -in-field
treatment, this can replicate the effect of the wedge. 3D-CRT typically requires input
from the treatment planner in decisions regarding beam direction, beam weighting
and segment shaping. The field -in field method is a step towards IMRT, a technique
which uses multiple beam segments with the intensity of the beam modulated to
produce a homogeneous dose across the tumour. With the IMRT technique an inverse
approach to treatment planning is more often used. In this situation the number of
beams and beam direction may be selected by the treatment planner along with
objectives for PTV coverage and OAR sparing. The treatment planning software then
optimises the beam segments, MLC positions and segment weightings to optimise the
dose distribution to meet the planning objectives. VMAT is a type of IMRT treatment
that is delivered whilst dynamically rotating around the patient. The dose rate is
changing, and the MLCs are constantly moving to modulate the beam in order to
achieve a conformal and uniform distribution.
1.8.1 Radiotherapy Planning Techniques for Breast Treatments
For patients with breast cancer the widely used approach to treatment planning is the
use of opposing tangential fields. The fields are typically set up with a non-divergent
posterior edge to minimise lung dose. Megavoltage photon beams are used to achieve
the required depth penetration and the homogeneity of dose distribution is controlled
with wedges or a field-in-field technique. In the field-in-field technique tangents
typically consist of an open field that cover the treatment area and 4-5 segments that
control the homogeneity. A 40Gy in 15# dose schedule is the UK standard
recommended by NICE in their guidelines for the diagnosis and management of early
and locally advanced breast cancer (NICE, 2018). Figure 1.6 shows a typical beam
33
arrangement and dose distribution for a breast treatment, with the beam segments for
the medial beam also displayed.
a)
b)
Figure 1.6: a) Beam arrangement and dose distribution for radiotherapy breast treatment b) Beam segments for medial beam
34
1.9 Radiotherapy Treatment Delivery
A completed treatment plan is checked and approved by a clinician, before being
transferred electronically to the linear accelerator. When the patient comes for
treatment they will be set-up in the same position as they were imaged for their
planning CT scan and the tattoos are used to move the patient to the required position
for delivery of the radiation. Before each treatment is delivered, image verification
takes place to ensure that the patient is in the same position and assess if there has
been any anatomical changes. Typically 2D transmission (portal) or 3D cone-beam
(CBCT) images are acquired. The difference is assessed and where appropriate the
patient is shifted to ensure that the treatment plan will be accurately delivered. If the
difference exceeds pre-determined limits and the patient position cannot be adjusted
to match the planned treatment the CT scan and planning process may need to be
repeated.
More recently, as an alternative to tattoos, there has been an increased use of surface
guided radiotherapy for patient treatments. This technology uses wall mounted,
optical surface imaging to help with patient set-up and enables motion management
to be carried out during the delivery of the radiation beam, rather than just prior to
treatment. The system works by disabling the radiation beam when the surface
position exceeds a defined tolerance. When used in conjunction with Deep Inspiration
Breath Hold (DIBH) for left-sided breast treatments it can be particularly beneficial in
minimising dose to the heart.
1.10 Radiotherapy Treatment Planning for Mastectomy Patients
As previously discussed, radiotherapy is recommended by NICE (NICE, 2018) for
patients who have undergone a mastectomy and that are at risk of local recurrence.
Radiotherapy post-mastectomy can be delivered using the same technique as
previously described using opposing tangential fields. However the technique can pose
some challenges for this treatment technique which are discussed as follows.
High energy photon beams are required in radiotherapy treatments to ensure
significant penetration of the radiation beam at depth within the patient. The use of
high energy photons also results in a skin sparing at the patient surface. This is as a
35
result of the photon interactions within the tissue and is also known as the build-up
effect. When high energy photons are incident on the tissue surface secondary
electrons are produced. These electrons travel primarily in a forward direction, into
the tissue and deposit their energy at depth in the patient. Since there are minimal
interactions upstream from, or outside, the patient surface, the dose to the surface is
relatively low. The effect can be seen in Figure 1.7 which shows the variation in dose at
depth within water. The dose builds up to a maximum value at a depth of
approximately 1.4cm, and then decreases at the depth increases. This can normally be
advantageous in external beam treatments where tumours are at depth, as reduced
dose at the surface can minimise radiation induced skin reactions such as erythema.
However in the case of mastectomy patients local recurrences have been shown to
occur on the skin and in subcutaneous tissues suggesting the importance of treating
this superficial area (Andry et al., 1989). Similarly, Thoms et al. (1989) found that in a
retrospective study of 61 patients with inflammatory breast cancer, the most common
site of failure was in the chest wall and more common in patients who did not suffer
from skin toxicities such as erythema or moist desquamation.
Figure 1.7: Measured Depth Dose curve for a 6MV photon beam, 10x10cm field size.
A common method to overcome the build-up effect is the use of a tissue equivalent
material in the form of a 0.5 – 1cm thick, gel slab that covers the entire chest-wall and
is placed directly on to the skin during treatment. The bolus then provides a material
36
for photon interactions to occur outside the patient and allows dose to be deposited at
the surface.
The clinical use of bolus between centres varies widely. In 2004 an international survey
of radiation oncologists was carried out by Vu et al., (2007) which focused on the
technical details regarding the use of bolus in post-mastectomy radiotherapy (PMRT).
1035 responses were received from oncologists practising in the USA, Canada, Europe
and Australasia. The results showed that 68% of responders always used a bolus, 6%
never used one and 26% used bolus if there were specific indications (for example, skin
involvement or inflammatory disease). Respondents from the Americas were
significantly more likely to always use bolus (82%) compared to the Europeans (31%).
There was also variation in frequency of use, with 33% or respondents using bolus
throughout treatment and 46% using it on alternate days. Furthermore the thickness
of bolus varied, with 35% using <1cm and 48% ≥ 1cm. The variation in practice is
reported in other studies, Blitzblau and Horton (2013) and Mayadev et al. (2015)
similarly identifying a range in use of bolus with regards to frequency and thickness.
Mayadev et al. (2015) also recognising that a range of materials were also being
including brass bolus mesh and customised wax bolus.
As in the UK with the NICE guidelines, The American Society of Clinical Oncology
(ASCO), recommend the use of radiotherapy post-mastectomy, but similarly offer no
specific advice on how bolus should be used (Recht et al., 2016). Recent clinical trials
recruiting post-mastectomy patients SUPREMO (ISRCTN61145589) and FAST-Forward
(ISRCTN19906132) also fail to define a consistent approach to the use of bolus in their
protocols.
There is also evidence that suggests bolus is not required at all. A number of studies
have reported that retrospective data analysis showed no significant differences in
chest-wall recurrence between patients that were treated with bolus and those who
were not (Tieu et al., 2011; Turner et al., 2016; Abel et al., 2017; Nakamura et al.,
2017). The use of bolus has also been associated with increased skin toxicity (Pignol et
al., 2015) which has further been associated with treatment interruptions (Abel et al.,
2017).
37
The use of bolus also has practical challenges associated with it. Bolus materials can
increase the attenuation of dose at depth within the patient depending on the
thickness of material. When bolus is only used for a proportion of the fractions this
means that two treatment plans are required for every patient. There can also be
issues with the malleability of the bolus material, resulting in a lack of conformity of
the bolus to the chest wall during treatment delivery. It has been demonstrated that
air gaps between the bolus and chest wall can reduce the surface dose (Butson et al.,
2000; Boman et al., 2018). Since treatment planning software often assumes the bolus
is in constant contact with the skin, air gaps at treatment will result in a discrepancy
between planned and delivered superficial doses. A solution to these problems include
the use of thinner bolus material for use at all treatment fractions, being thinner the
sheets may conform better to the patient surface and if used in every treatment only
one treatment plan is required (Das et al., 2017). Alternatively, the use of a brass mesh
bolus is becoming more common, overcoming both these issues (Healy et al., 2013;
Ordonez-Sanz et al., 2014; Richmond et al., 2016). However, the use of any additional
bolus material as part of the treatment will also incur cost to purchase, requires
infection control considerations and runs the risk of potential clinical error if it there is
failure to use it during the patient’s treatment or it is incorrectly positioned.
1.11 Use of IMRT and VMAT Treatment Planning for Mastectomy Patients
As IMRT has become more common place in radiotherapy centres, the use of IMRT
(forward and inverse) and VMAT has increasingly been investigated as an alternative
treatment to 3DCRT for breast and chest-wall patients. Whilst most of this literature
focuses on radiotherapy treatment for breast patients after breast conserving surgery
(Donovan et al., 2007; Badakhshi et al., 2013; Jin et al., 2013; Haciislamoglu et al.,
2015; Virén et al., 2015; De Rose et al., 2016; Jo et al., 2017; Jensen et al., 2018)
increasingly the use of the technique is being investigated for post-mastectomy
patients too (Cavey et al., 2005; Rudat et al., 2011; Zhang et al., 2015; Xu and Hatcher,
2016). There is no consistently applied treatment approach, with the specific
techniques for IMRT and VMAT varying widely in the literature. IMRT breast plans can
range from a tangential two field beam arrangement as used by Rudat et al. (2011) to
a 7 or 9 field beam arrangement with the beams at evenly spaced angles to cover the
38
breast as used in studies by Ekambaram et al. (2015) and Popescu et al. (2010).
Similarly, VMAT plans may constitute two partial tangential arcs, or be a solid arc
around the chest-wall (Karpf et al., 2019). The optimisation methods also vary across
studies. For example Cavey et al. (2005) investigated use of the IMRT with a forward-
planned technique, requiring input from treatment planners to optimise the plans
whilst others use the inverse planning technique, allowing the treatment planning
software to optimise the distribution (Popescu et al., 2010; Virén et al., 2015).
The use of IMRT and VMAT has in general been shown to be favourable, for the
treatment of breast cancer, with conservative surgery, with more homogeneous dose
distributions, better conformity, ability to achieve similar dose to organs at risk and
increased skin sparing (Freedman et al., 2009; Johansen, Cozzi and Olsen, 2009;
Almberg, Lindmo and Frengen, 2011; Haciislamoglu et al., 2015; Jo, Kim and Son,
2017). In a randomised trial of standard 2D radiotherapy versus IMRT, it was shown
that the minimisation of in-homogeneities reduced late effects and reduced the
incidence of change in breast appearance (Donovan et al., 2007). A phase II trial of
hypo-fractionated VMAT-based treatment of early stage breast cancer also
demonstrated that the technique was well tolerated, with no pulmonary or
cardiological toxicities reported (De Rose et al., 2016). In papers that compared IMRT
and VMAT for whole breast treatment, a number reported that VMAT was less
favourable than IMRT due to higher contralateral breast doses and some organs at risk
receiving higher volumes of low dose (Badakhshi et al., 2013; Jin et al., 2013; Virén et
al., 2015).
Similarly for post-mastectomy patients the advantages of VMAT and IMRT were
reported by a number of authors comparing plans dosimetrically with standard
techniques (Ma et al., 2015; Zhang et al., 2015; Lai et al., 2016). However, the issue of
low dose bath was highlighted again, with Xu and Hatcher (2016) suggesting that this
limited the benefit of VMAT as there was not significant improvement in PTV coverage,
they did however propose that in cases where the standard technique could not
achieve the required planning constraints VMAT should be considered.
Previous studies have shown that IMRT and VMAT is a radiotherapy technique that can
be used to treat post-mastectomy patients. The definition and exact technique used
for these plans varies including the use of forward planned or inverse planned
39
approaches. However, inverse-planned IMRT can potentially pose some problems for
superficial lesions. Lee et al. (2002) reported severe skin reactions with the use of IMRT
for treatment of head and neck cancers. Similarly, a study by Higgins et al. (2007)
comparing the use of IMRT to a bilateral field arrangement for head and neck
treatments showed that IMRT increased the maximum surface dose from 69% of the
prescription dose to 82%. The effect was discussed in a study by Thomas and Hoole
(2004) which concluded that the issue was due to the PTV, created to account for
uncertainties in set-up, extending outside the patient surface. To meet the objectives
related to PTV coverage, defined in the treatment planning software, beam segments
near the patient surface require a high photon fluence. The high fluence is required to
overcome the build-up effect due to low electron density outside the patient surface,
and lack of material to induce scatter of the incident photons. If the patient position or
contour changes, the tissue intersecting the high fluence will change, potentially
resulting in a skin dose greater than originally predicted by the treatment planning
system.
1.12 Robust Optimisation
Radiotherapy treatment planning systems simulate the dose deposited within the
patient based on modelling the interactions of the radiation from the linear
accelerator as it enters the patient. For inverse planned treatments using IMRT and
VMAT, the intensity and variation of the radiation beam is determined by specifying
the ideal dose to structures defined on the patient’s CT scan. This would include the
dose needed to control the tumour and the dose to organs at risk which would
minimise any side effects. Since radiation travels through and interacts with both
tumour and normal tissue, optimising the dose distribution is a complex mathematical
problem. Within the planning system software objective functions are used on the
targets and organs at risk, which reflect the optimal clinical goals and can be expressed
as a dose to volume. The beam intensities are then modified in an iterative process to
minimise the difference between the required objective functions and the deposited
dose. Additional weightings can be put on the objective functions to increase the
probability of meeting the clinical goal.
40
The robustness of a treatment plan is its ability to maintain its clinical goals despite
differences between the patient at CT and at treatment. The differences could include
changes in patient contour or set-up position.
The typical approach to dealing with uncertainty has been described previously and is
the use of a margin around the tumour volume referred to as a PTV. Similarly margins
around organs at risk can be generated, Planning Risk Volumes (PRV). The PTV and
PRVs are then used as the structures in the treatment planning software to which
objective functions are applied.
There are however several limitations to the PTV concept, as described by Unkelbach
et al. (2018) including the assumption of a static cloud dose distribution where the
dose distribution is considered invariant. In the case of breast and chest-wall
treatments, where the target structure is in close proximity to a large density
difference (air outside the patient) this approximation is likely to be challenged. Two
alternative approaches described in literature that have been used for radiotherapy
treatment planning include probabilistic planning (Chan et al., 2006; Ramlov et al.,
2017; Tilly et al., 2019) and minimax optimisation (Fredriksson et al,. 2011; Byrne et
al.,2016; Archibald-Heeren et al., 2017; Miura et al., 2017; Wagenaar et al., 2019). In
both methods robust optimisation dose distributions are optimised in different
scenarios, for example, geometric position. The probabilistic approach optimises the
objectives on the likelihood of a particular scenario. The minimax optimisation
approach optimises the objective value in the worst-case scenario based on
positioning accuracy in different directions. The advantage of the minimax method is
that only knowledge of the different geometric scenario is needed, rather than the
probability distribution, however the minimax may over optimise in scenarios of where
likelihood of a geometric position is lower, potentially compromising treatment plan
quality.
In the context of breast radiotherapy, the combination of robust optimisation with
IMRT and VMAT has previously been established as a clinically acceptable approach
(Byrne et al., 2016, Liang et al. 2020 and Dunlop et al. 2019). As mentioned in the
previous section the challenge with treating superficial lesions with IMRT is trying to
ensure coverage with setup variations without creating high photon fluence segments,
which can result from using PTVs extending into air. Techniques such as the use of
41
virtual bolus can help overcome this, where the plan is initially optimised with a bolus
material at the surface, and then removed for the final calculation, resulting in
segments with suitable flash but not with a high fluence. However the dose differences
between the optimised and final dose, can lead to multiple re-optimisations required
to achieve an acceptable plan. Byrne et al. (2016) therefore evaluated the use of
robust optimisation with IMRT as an alternative approach to virtual bolus, showing
that it was a comparable technique to ensure coverage of breast CTV with setup
variations. Liang et al. (2020) compared the robust optimisation method to IMRT plans
where the flash margin was manually created by editing MLC positions. They
concluded that the robustly optimised plans were the only ones that met acceptable
criteria for PTV coverage under geometric error scenarios. Dunlop et al. (2019) also
demonstrated that the robust optimisation with VMAT could be used for patients
requiring breast radiotherapy that included the treatment of the internal mammary
chain. In addition to showing that compared to non-robust plans there was no
compromise in dose to organs at risk, the target coverage was improved using the
robust optimisation feature, when robustness was assessed over a typical treatment
course.
1.13 Specifying Superficial Doses for Post-Mastectomy Radiotherapy
In radiotherapy, treatment plans are usually assessed on particular, well-defined
criteria. Typically, the PTV is considered sufficiently covered if 95% of the volume is
covered by 95% of the prescription dose and 2% of the volume does not exceed 107%.
In addition to the ICRU guidelines on PTV homogeneity, clinical trials are often a good
source for PTV objectives and OAR constraints. However assessing dose distributions in
the case of post-mastectomy patients can be challenging. The variation in the use of
bolus, discussed previously, suggests that there is no consensus in the skin dose
required to ensure successful treatment and reduce recurrence. Thoms et al. (1989)
suggested that the measure of skin reaction is a good indication that sufficient dose
had been received, with reactions such as erythema and moist desquamation being
linked to an improvement in local control, though the absolute dose to skin was not
discussed. However, with it known that skin toxicity is also affected by patient habits
such as smoking (Pignol et al., 2015) the use of erythema may not be a good measure
of dose received. In the international survey on post-mastectomy radiotherapy
42
practise, Vu et al. (2007) found that responders generally defined an ‘adequate’ dose
to the skin was 85-90% of the prescription dose. This is in line with 75%-90% of the
prescribed dose that is suggested as the required dose to skin and the mastectomy
scar, in a chapter of ‘Radiation Oncology Management Decisions’ (Chao et al., 2011)
describing the management of breast cancer. Ordonez-Sanz et al. (2014) investigating
a single-plan solution for a cohort of post-mastectomy patients, measured superficial
doses which were on average 85.1% of prescription dose. Another approach to skin
dose assessment, taken by Xu and Hatcher (2016), was to create a skin volume of 3mm
below the patient and aim to ensure that 5% of the structure received 100% of the
dose and 85-95% should receive 80% of the dose.
The lack of consistency in defining the required dose and where the dose should be
delivered, means comparing techniques and patient outcomes between studies is
particularly challenging.
1.14 Definition of the Skin Structure in Mastectomy Patients
The use of skin volumes for plan assessment and patient outcome analysis could be
considered a valid approach in radiotherapy treatment, where reporting on dose to
structures is routine. The skin is composed of two distinct regions, the epidermis and
the dermis. The epidermis being the most superficial layer, made up of closely packed
epithelial cells. The dermis lies below the epidermis and is made up of connective
tissues, nerve endings, oil glands, blood vessels and lymphatic vessels. The ICRP
(International Commission on Radiological Protection and ICRU (International
Commission on Radiation Units) recommend that skin depth for practical dose
assessment is defined at 0.07mm deep, the basal layer, the deepest epidermal layer
and interface with the dermis (ICRU, 1985; ICRP, 1991). However, from a radiotherapy
treatment perspective, it is suggested by Butson et al. (2000) and Javedan et al. (2009),
that the dermal layer containing the dermal lymphatics, should be targeted as a site of
recurrence, which is thought to be >1mm deep. The actual values for epidermis and
dermis layers will also vary between patient and body region. A study by Oltulu et al.
(2018) using a histometric technique, reported the mean dermal layer in the female
breast to be 4.7mm deep. With the development of new imaging techniques, breast CT
43
studies by Huang et al. (2008) and Shi et al. (2013) found the average breast skin
thicknesses (including epidermis and dermis layers) were approximately 1.45 mm and
ranged from 0.8mm to 2.5mm.
The suggested range of breast skin thickness and ambiguity over the layers required to
be treated during radiotherapy further complicates comparisons with other planning
studies and conclusions regarding recurrences.
1.15 Measurement of Superficial Doses
In Figure 1.7 a steep dose gradient is observed when photon beams intersect an air-
tissue interface. Measurements by Devic et al. (2006) using Gafchromic film, showed
that for a 6MV photon beam and field size 10x10 cm2 the dose increases from 14% at a
depth of 4µm to 43% at 1mm. The superficial dose in this region is attributed to
contaminant electrons, from the treatment head and secondary electrons from the
irradiated material. The magnitude of these effects will depend on beam
characteristics including field size, distance from source (Bjärngard et al., 1995; Kim et
al., 1998) and beam incident angle (Gerbi et al., 1987). For correct superficial doses to
be reported by the treatment planning system it is important that the algorithm
models this correctly. However as reported by Panettieri et al. (2009), Cao et al. (2017)
and Dias et al. (2019) the measured dose difference can be up to 20% depending on
the sophistication of the algorithm. Furthermore, the accepted tolerance in this region
recommended by the American Association of Physicists in Medicine (AAPM) is ±20%
(Fraass et al., 1998). The discrepancies between planning system and measurements in
the build-up region can be attributed to type of treatment planning algorithm Cao et
al. (2017), accuracy of data measurements input into the planning system Chetty et al.
(2007) and the size of dose calculation grid (Kan et al., 2012). The size of dose grid used
may not be clinically appropriate for reporting skin dose, if larger than the defined skin
thickness.
With these limitations in mind it is appropriate to measure the skin dose directly. The
types of detectors used by research groups to assess superficial breast and chest-wall
doses include detectors thermoluminescent (TLDs), optical luminescent detectors
(OSLDs), metal-oxide semiconductor field effects transistors (MOSFETs) and
44
radiochromic film. There are no papers that directly compare all of these techniques at
once, but a few have compared a combination of the detectors. Quach et al. (2000)
measured superficial doses on a chest-wall phantom using radiochromic film, TLDs and
MOSFETs. With a single tangential field applied to a hemicylindrical phantom it was
shown that on the central axis, with an obliquity of 0⁰, the surface dose measurements
from each detector differed significantly: 28% (of Dmax) for the radiochromic film, 30%
for the TLDs (extra thin type) and 43% for the MOSFETs. This was attributed to the
effective depth of measurement of each detector. The group also identified
advantages and disadvantages of each detector from a practical view. They found that
the radiochromic film was potentially useful as a skin dosimeter due to its effective
depth of 0.17mm and ability to simultaneously measure the dose profile. However, the
sensitivity of the material meant it could only be used in the dose range of 10-100Gy.
The TLDs used (an extra thin type with an effective depth of 0.14mm) were felt to have
a more appropriate dose range for measuring a single fraction but had the
disadvantage of only being able to take point measurements. With an effective depth
of 0.5mm the MOSFETS, had the advantage of instant read outs and good spatial
resolution but also had some directional sensitivity. It was concluded that TLDs
provided good clinical skin dose measurements despite the work required in annealing
and calibrating.
Jong et al. (2016) investigated the use of the MOSkin detectors, MOSFETs designed to
provide a WED (water equivalent depth) of 0.07mm, making them suitable for
measuring skin dose. Comparing MOSkin measurements with Gafchromic (EBT2) film
and the treatment planning system (pencil beam convolution algorithm) they observed
no significant difference in skin doses when measurements were made under the
bolus. However, when measurements were made with no bolus the mean skin doses
measured using EBT2 were 11.4% higher than the MOSkin, with the planning system
reporting 14.2% higher. The dose difference between the detectors and planning
system were explained as the limitations in the planning system algorithms, grid size,
and the WED difference between detectors. Similar results using MOSkin and
Gafchromic (EBT3) film were described by another research group that used the
detectors to assess the effect of brass bolus for chest wall irradiation. EBT3 Gafchromic
film has the same composition and thickness of sensitive layer as EBT2 but has a
45
symmetric layer configuration allowing both sides of the film to be used.
Measurements were also made with an Advanced Markus ionisation chamber.
Measurements of entrance dose, attenuation and PDD were measured in a solid water
phantom, and surface beam profile on a curved phantom. In the no-bolus situation
they reported that the Markus chamber measured the surface dose for a 6MV beam as
16.5%, EBT3 22.8±3.8% and MOSkin detectors 19.2±1.0%. This difference was also
considered to be a function of the WED, with effective depth of the Markus chamber
reported as 0.023mm, EBT3 as 0.153mm and MOSkin 0.07mm.
Yusof et al. (2015) investigating dosimeters for assessing surface dose compared OSLDs
with Gafchromic EBT3 and Markus ionisation chamber measurements. The primary
objective of this study was to investigate whether OSLDs could provide accurate in-vivo
measurements for patients within a reasonable time frame and were easy to process.
They acknowledged that the advantage of Gafchromic film was with its ability to
provide a two-dimensional distribution but highlighted that waiting for 24 hours post
irradiation to ensure the film was stable could be a problem. TLDs they described as
tissue equivalent but the process for reading them was tedious and time consuming,
and MOSFETs although provided useful real-time read out had a WED of 0.8-1.8mm,
deeper than the recommended skin measurement depth. They describe OSLDs as
having good reproducibility and linearity, that reach stability 16 minutes post
irradiation and are easier and less time consuming to readout compared to TLDs and
film. The group determined the WED of the OSLDs to be 0.4mm. Surface dose
measurements in a solid water phantom with a 6MV photon beam were reported as
15.95±0.08% for the Markus chamber, 23.79±0.68% for the Gafchromic EBT3 and
37.77±2.0% for the OSLD, with the dose difference explained by the high dose gradient
and differing WEDs of the detectors.
TLDs were used to measure superficial doses by (Ordonez-Sanz et al. (2014) to assess
the use of different bolus materials for chest-wall irradiation. As part of their
investigation they found that in the build-up region TLD measurements were
consistent with diode measurements to within 3% giving them confidence that TLDs
could be calibrated and used effectively for measurements in steep dose gradients. In
comparison to the treatment planning system which used an anisotropic analytical
algorithm (AAA) it was shown that the TLDs measured slightly lower than predicted. It
46
was suggested that this was an overestimation of the dose by the treatment planning
system and due to the electron contamination source used in the AAA model.
The literature demonstrates that a range of dosimeters can be used for measuring
superficial doses. Factors to be considered in deciding which dosimeter to use include;
the requirement for discrete or 2D distributions, the need for immediate read-out of
results and the actual depth of measurement required, as discussed previously the
definition of skin depth can vary.
1.16 Scope of Project
The use of radiotherapy for treating patients following mastectomy is a well evidenced
and globally accepted technique. Evidence suggests that these patients also benefit
from increased surface dose, however there is little consensus as to the actual dose
required. A common approach to increasing surface dose is the use of bolus materials
for part of the patients’ treatment. The addition of this bolus material can present
problems including; the requirement to create two treatment plans, increasing
planning time in the patient pathway, air gaps between the patient and bolus affecting
surface dosimetry and the risk of treatment errors due to bolus placement being
missed. It has been shown that IMRT techniques can deliver higher surface doses
compared with 3DCRT by loading the build-up region with beam segments from
glancing angles. This is often unintentional but could be beneficial for patients with
lesions close to the skin surface, potentially negating the need for bolus. However,
fluence loading in the surface regions means that IMRT plans could show unacceptable
changes in dose distribution when positioning errors are examined. The use of robust
optimisation could be a means to minimise this effect as part of the treatment
planning process.
The overall aim of this thesis therefore, is to investigate whether a combination of
inverse planning with robust optimisation could provide an alternative, one plan
solution, to the current approach to radiotherapy treatments for patients requiring
post-mastectomy radiotherapy.
The thesis firstly establishes the effect of bolus on surface dose using the current
clinical technique, and then demonstrates that clinically acceptable VMAT plans can be
47
created with comparable skin doses. To confirm superficial doses predicted by the
treatment planning system, results of physical measurements with TLDs are also
presented. With limitations expected of VMAT plans due to patient positioning, the
impact of perturbation on these plans is investigated and shown to be clinically
unacceptable. Treatment plans using VMAT and robust optimisation are then
presented, demonstrating the impact that including robust optimisation has on
reducing the effect of perturbation. Finally, limitations to the results and further work
that would be required in order to use the technique clinically is discussed.
48
Chapter 2
2 Evaluation of current treatment method
The objective of this study is to assess whether a novel radiotherapy technique can be
used to plan radiotherapy treatments for post-mastectomy patients. The particular
challenge with this site of treatment is the skin surface, which is normally spared with
high energy photon beams, but that evidence suggests requires treatment to some
extent. Although the acceptable dose to this area is not well defined either in dose
required or the definition of its volume, the primary objective of this study is to see
whether similar distributions can be achieved compared to the current method using
bolus, particularly within the first 5mm of the skin surface.
As the literature does not specify in detail what radiation dose is required to reduce
local recurrence at the skin surface, dose delivered to the skin structures using the new
technique will be compared directly to the current technique used within this clinic.
However, the current level of recurrences within the department is deemed to be
acceptable, and the constraints and objectives for target coverage and organ at risk
dose used within our clinic have been implemented based on those defined in the
control arm of the breast trial, FAST-Forward (ISRCTN19906132).
2.1 Current technique for the treatment of post-mastectomy patients
At the University Hospitals Birmingham radiotherapy is prescribed following
mastectomy when there is:
Node positive disease
Incomplete or close margin (<1mm) on microscopy
Muscle invasion at deep margin and further surgery not possible
Tumours >5cm
49
Vascular/Lymphatic invasion with other risk factors e.g. high grade
High grade tumours with additional risk factors e.g. tumour >30mm
Multifocality with additional risk factors.
The prescription dose for these post-mastectomy patients is 40Gy in 15#. This is
delivered on a daily basis, over a 3-week period (not including weekends). Bolus is used
when requested by the clinicians and is typically used in cases of high-risk patients with
documented skin involvement. A large square of bolus slab of 1cm thick water
equivalent material, is used which covers the entire treatment areas and is applied for
the last 7 fractions of the patients’ treatment (Figure 2.1).
a)
b)
Figure 2.1: a) water equivalent bolus slab 40x40cm b) 3D rendered image from CT scan showing bolus placement in treatment position
As mentioned in the introduction the bolus is used to increase the surface dose by
counteracting the build-up effect when using high energy photons.
Patients are scanned on a Philips Brilliance Big Bore CT Scanner (Philips Medical
Systems, Eindhoven, Netherlands) with a slice thickness of 3mm. The patients are set-
up in a supine position with arms above their head, immobilised using a MT-350 CIVCO
(CIVCO Radiotherapy, Orange City IA, USA) breast board. Radio-opaque wires are
placed on the surface of the patient’s chest during the scan to delineate the area for
treatment and the CT images are exported to the radiotherapy simulation software
ProSoma (MedCom, Darmstadt, Germany). The patient is not routinely scanned with
50
bolus in situ, this is applied virtually by the treatment planning software during plan
optimisation. In the simulation software tangential beams, with a non-divergent back
edge are applied to the patients CT scan to cover the area of treatment, this is
reviewed and approved by the clinician (Figure 2.2).
a)
b)
Figure 2.2: a) 3D rendered image from CT scan with wires defining area for treatment b) Transverse CT image with opposing tangential beams applied
Patient CT scans are transferred to the treatment planning software, RayStation
version 6.0.0.24 (RaySearch, Stockholm, Sweden). The software uses atlas-based
segmentation to automatically generate the required OARs:- heart, left lung and right
lung, patient surface and a PTV structure. As described previously a field based PTV is
created from the intersection of the tangential fields with the patient tissue.
Treatment plans are created to meet the objectives and constraints defined in the
FAST-Forward Trial summarised in Table 2.1. The plans are calculated using a 3mm
dose grid with the RayStation collapsed cone treatment planning algorithm.
Structure Mandatory Optimal
PTV V95% ≥ 90% V95% ≥ 95% V105% ≤ 7% V105% ≤ 5% V107% ≤ 2% - D1% ≤ 110% (Dmax) -
Ipsilateral Lung V30% ≤ 17% V30% ≤ 15% Heart V25% ≤ 5% -
V5% ≤ 30% -
Table 2.1: Departmental objectives and constraints used for breast planning based on those used in FAST-Forward Trial (ISRCTN19906132)
51
For post-mastectomy patients two treatment plans are created, one with and one
without bolus. The bolus is assigned virtually to the dataset in the treatment planning
system, with the creation of a 1cm rind over the surface of the chest-wall with a
density set to 1g/cm3(water equivalence). Figure 2.3 shows an example of the bolus
structure created in the treatment planning system.
Figure 2.3: Blue contour on transverse CT slice indicates position of computer- generated bolus
The no-bolus plans are optimised to deliver 21.33Gy in 8# and the bolus plans 18.66Gy
in 7#. Plans are created using 6MV, 10MV or a mixture of both energies, dependent on
the size of the patient and the separation between the medial and lateral beams.
Treatment plans are generated using a SMLC technique for delivery on Elekta Precise
or Elekta VersaHD (Elekta, Crawley, UK) linear accelerators with 1cm and 5mm MLCs
respectively.
52
2.2 Dosimetric effect of bolus in post-mastectomy patients
2.2.1 Patient selection
To assess whether a new technique using no bolus is a suitable alternative the current
technique, the impact of bolus in the current setting was first evaluated. The dose to
the skin was of particular importance in comparison of techniques but the impact of
dose to organs at risk also needed to be considered. The treatment plans of 25
previously treated post-mastectomy patients were collated and reviewed. At
University Hospitals Birmingham the patient consent process allows the use of data for
audit and service development purposes provided these are anonymised. No further
ethics approval was sought for this planning study. All patients within the study were
receiving treatment of the chest wall only and did not include the treatment of
supraclavicular nodes, axilla or internal mammary nodes. The initial cohort of patients
were a group of consecutively planned treatments and included 12 right sided
treatments and 13 left sided treatments. Table 2.2 summarises the treatment machine
and beams energies used for these patients.
After reviewing the treatment plans of the 25 consecutively treated post-mastectomy
patients, the variation of treatment machines parameters used for each case was
analysed. It was noticed that 7 of these patients had no bolus requested at all, and a
range of energy combinations and different treatment machines had been used. The
current radiotherapy treatment technique does not aim to ensure a particular skin
dose and as discussed previously there is no consensus on what this should be and the
use of bolus is left to the discretion of the clinician. It was decided therefore, that the 7
cases without bolus originally, would be removed from the analysis as enhancement to
skin dose had not been required. As previously discussed, build-up effect, and
therefore skin dose is directly related to beam energy, this means that patients treated
with 6MV for both the bolus and no bolus plans will have different relative skin doses
to a patient treated with 10MV for both the bolus and no bolus plans. Therefore to
ensure that any conclusions drawn from this work were a result of the new technique
rather than variation in original skin dose, it was decided to rationalise the data set to
those with the same original beam energy characteristics. The largest proportions of
cases with the same characteristics were treated with 6MV for the no bolus plan and
53
10MV for the bolus plan, these 8 patients went on for further analysis. In this group of
8 patients 5 were left sides cases and 3 were right sided.
Patient Site Treatment machine
No Bolus Energy, MV
Bolus Energy, MV
1 Right CW Elekta Precise 6 NA
2 Right CW Elekta Precise 6 10
3 Left CW Elekta Precise 6 10
4 Right CW Elekta Precise 6 & 10(segments) 10
5 Right CW Elekta Precise 6 6 medial & 10 lateral
6 Left CW Elekta Precise 6 NA
7 Right CW Elekta Precise 6 NA
8 Right CW Elekta Precise 6 NA 9 Left CW Elekta Precise 6 NA
10 Left CW Elekta Precise 6 10
11 Right CW Elekta Precise 10 10
12 Right CW Elekta Precise 6 10
13 Left CW Elekta Precise 6 & 10(segments) 10
14 Left CW Elekta Precise 6 & 10(segments) 10 15 Left CW Elekta Precise 6 10
16 Right CW Elekta VersaHD
6 & 10(segments) 10
17 Left CW Elekta Precise 6 10
18 Right CW Elekta Precise 6 10
19 Left CW Elekta Precise 6 & 10(segments) 10
20 Right CW Elekta Precise 10 10
21 Left CW Elekta VersaHD
6FFF 6FFF
22 Left CW Elekta Precise 6 NA
23 Left CW Elekta Precise 6 10
24 Right CW Elekta Precise 10 & 6 (segments) NA 25 Left CW Elekta Precise 10 & 6 (segments) 10 & 6 (segments)
Table 2.2: Summary of patient information including treatment site (CW=chest wall), machine and beam energy
54
2.3 Method
To assess the impact of bolus a retrospective study was conducted in this group of 8
patients, all receiving 40Gy in 15#. The dose to clinically relevant structures were
compared for two different treatment plans. The first treatment plan being that of the
clinically delivered plan, 8# no bolus and 7# bolus, subsequently referred to as ‘Clinical’
plan. The second plan received all 15# with no bolus, subsequently referred to as ‘No
Bolus’ plan.
Structures created for the dose comparison were selected due to their clinical
relevance in the plan analysis and to assess whether the plan was clinically acceptable,
based on the dose constraints and objectives in Table 2.1.
Since dose to the skin was of particular interest in this study it was therefore decided
to include this in the PTV structure and was created using the field-based technique
described previously, without clipping 5mm from the patient surface. This structure
was named PTVtoSurface, an example is shown in Figure 2.4. It should be noted that
the chest-wall shown in Figure 2.4, and used as an example later in the text is an
outlier with regards to chest wall thickness. The average chest wall thickness for the 8
cases analysed was 2.1cm ranging from 1.1cm to 3.9cm.
Figure 2.4: PTVtoSurface (red shaded structure)
55
Due to the particular interest in the superficial area of the chest-wall tissue, 3 skin
structures were created to report on. These structures were 1mm, 3mm and 5mm skin
rinds directly below the patient’s external surface, which was defined by the treatment
planning software. The skin rinds extended laterally to the same extent as the
PTVtoSurface. These structures were named Skin1mm, Skin3mm and Skin5mm. An
example of Skin5mm is shown in Figure 2.5. The organs at risk heart and ipsilateral
lung were also used for the plan comparison. Dose volume histograms (DVH) were
generated in the treatment planning system for each patient, structure and technique.
To analyse the plan techniques quantitatively particular dosimetric parameters were
also extracted. For the PTVtoSurface structure, in addition to the parameters described
in Table 2.1 the average dose to the structure was also recorded. For the skin
structures D99% (dose covering 99% of the volume, minimum dose), D1% (near
maximum dose) and average dose were recorded. For the organs at risk, V25% and
V5% were recorded for heart and V30% for the ipsilateral lung. A summary of the
dosimetric data that was collated for each structure and is summarised in Table 2.3,
with the absolute dose values stated where appropriate based on the prescription
40Gy/15#.
56
Figure 2.5: Skin5mm (shaded green structure) with PTVtoSurface (red contour)
Structure Dosimetric Parameter (%)
Dosimetric Parameter (Gy)
PTVtoSurface V95% V105% V107% Average D1%
V38Gy V42Gy V42.8Gy Average D1%
Skin1mm, Skin3mm, Skin5mm D99% D1% Average
D99% D1% Average
Heart V25% V5%
V10Gy V2Gy
Ipsilateral Lung V30% V12Gy
Table 2.3: Summary of dosimetric parameters recorded for each patient
2.4 Results
2.4.1 Plan comparison – Dose Distribution (single patient example)
Figure 2.6 shows an example of the 38Gy coverage achieved with the No Bolus and
Clinical plans through a transverse plane for one of the patients in the group. It can be
57
observed that the dose in the Clinical Plan extends closer to the surface than for the
No Bolus plan.
a)
b)
Figure 2.6: Example 38Gy dose distribution for a) No Bolus plan b) Clinical Plan
2.4.2 Plan comparison – PTVtoSurface (single patient example)
Figure 2.7 shows an example of the DVH for the PTVtoSurface, for one of the patients.
Specific dose parameters were extracted from the DVHs for each plan technique. The
values achieved for the specified dose parameters for the PTVtoSurface, along with the
mandatory and optimal constraints, where appropriate, are shown in Table 2.4.
In the DVHs for the No Bolus and Clinical plans, for the PTVtoSurface structure (Figure
2.7), a difference in the shape at the shoulder of the curves at around 35-39Gy is
observed, with the rest of the DVH matching closely. As expected, it is the No Bolus
plan that reports lower volumes in this dose region. This effect is also seen in the
analysis of the dosimetric parameters. The volume reported for the No Bolus plan for
the V95% parameter, is 3.5% lower than the Clinical plan and the volume difference for
the V105% and V107% parameters is +0.5% and +0.1%, respectively. The maximum
dose difference to the PTVtoSurface structure between the plans is 0.5% and the
average dose is 0.2Gy lower in the case of the No Bolus plan.
58
Figure 2.7: Example of DVH for structure PTVtoSurface. (Dashed line = Clinical Plan, Dotted line = No Bolus Plan)
Structure Dosimetric Parameter
Mandatory Constraint
Optimal Constraint
Clinical Plan
No Bolus Plan
PTVtoSurface V95% V105% V107% D1 % Average
≥ 90% ≤ 7% ≤ 2% ≤ 110%
≥ 95% ≤ 5%
96.0% 1.1% 0.0% 104.9% 40.0Gy
92.4% 1.7% 0.1% 105.4% 39.8Gy
Table 2.4: Example of dosimetric parameters obtained for the structure PTVtoSurface for the Clinical and No Bolus Plans for one patient.
2.4.3 Plan comparison – Skin Structures (single patient example)
Figure 2.8 shows the dose volume histograms for the skin structures for the same
patient. The specific dose parameters as described in Table 2.3 were extracted from
the DVHs for the skin structure and each plan technique. Table 2.5 shows the doses
recorded in the case of the Clinical and No Bolus plan for the example case.
59
a)
b)
c)
Figure 2.8: Example DVHs for a) Skin1mm b) Skin3mm c) Skin5mm (Dashed line = Clinical Plan, Dotted line = No Bolus Plan)
60
Structure Dosimetric Parameter, Gy Clinical Plan No Bolus Plan
Skin1mm D99% Average D1%
34.1Gy (85.3%) 38.0Gy (95.0%) 40.7Gy (101.7%)
29.2Gy (73.0%) 36.2Gy (90.5%) 40.8Gy (102.0%)
Skin3mm D99% Average D1%
35.0Gy (87.5%) 38.7Gy (96.8%) 41.1Gy (102.8%)
30.9Gy (77.3%) 37.5Gy (93.8%) 41.5Gy (103.8%)
Skin5mm D99% Average D1%
35.4Gy (88.5%) 39.2Gy (98.0%) 41.5Gy (103.8%)
31.7Gy (79.3%) 38.3Gy (95.8%) 41.9Gy (104.8%)
Table 2.5: Example of dosimetric parameters obtained for the Skin Structures for the Clinical and No Bolus Plans. (Values is brackets represent the dose received as a percentage of the prescription dose, 40Gy).
The greatest dose difference is seen for the most superficial structure (Skin1mm),
gradually reducing for the 3mm and 5mm rinds. A difference in DVH curves is observed
for all skin structures in comparing the Clinical and No Bolus plan, with the largest
effect seen with the Skin1mm structure, the rind closest to the surface and the
smallest effect seen on the Skin5mm structure. The general trend seen in all the skin
structure DVHs is that in the No Bolus plan the volume receiving dose in the range of
30-40Gy is less than in the case of the Clinical plan. Furthermore, the maximum dose
the DVHs indicated is slightly greater using the No Bolus technique. The detail of this is
highlighted in the comparison of the dosimetric parameters in Table 2.5. The use of
bolus in the Clinical plan increases the minimum dose (D99%) to the Skin1mm,
Skin3mm and Skin5mm by 4.9Gy, 4.1Gy and 3.7Gy respectively. Similarly, the average
dose was also enhanced but to not the same extent, Skin1mm increased by 1.8Gy,
Skin3mm by 1.3Gy and Skin 5mm by 0.9Gy. In the case of the maximum dose (D1%)
the dose was lower in the Clinical cases however these differences were small, 0.1Gy
for the Skin1mm structure and 0.4Gy for the Skin3mm and Skin5mm structures.
2.4.4 Plan comparison – Organs at Risk (single patient example)
Figure 2.9 shows the DVH for the for the heart and lung OARs for the same patient
example, and Table 2.6 shows the extracted dosimetric parameters.
61
Figure 2.9: Example DVHs for Heart (red line) and Ipsilateral Lung (Orange line) (Dashed line = Clinical Plan, Dotted line = No Bolus Plan)
Structure Dosimetric Parameter
Mandatory Constraint
Optimal Constraint
Clinical Plan
No Bolus Plan
Heart
Ipsilateral Lung
V25% (10Gy) V5% (2Gy) V30%(12Gy)
≤5% ≤30% ≤17%
≤15%
0% 6.4% 13.6%
0% 6.5% 13.4%
Table 2.6: Example of dosimetric parameters obtained for the heart and ipsilateral lung OARS, for the Clinical and No Bolus Plans.
The DVH curves for heart and ipsilateral lung are almost identical in both the Clinical
and No Bolus cases. The DVH for the ipsilateral lung in the Clinical case suggests
slightly larger volumes receive dose in the range 3-15Gy but the difference is very
small. From the values reported for the dosimetric parameters shown in Table 2.6, this
is the case, with the ipsilateral lung volume that receives 12Gy being only 0.2% higher
than the Clinical plan. Table 2.6 also shows a 0.1% volume difference between the
Clinical plan and No Bolus plan for the heart parameter V5%. The shapes of the DVHs
and values reported for the dose parameters suggest that the use of bolus has very
little effect on the organs at risk.
62
2.4.5 Plan comparison – PTVtoSurface (8 patient study set)
Figure 2.10 shows each of the dosimetric parameters for the PTVtoSurface structure,
for the 8 patient cohort and for both the No Bolus and Clinical plans.
Similar trends are observed across all 8 patients. It can be seen that the volume of
PTVtoSurface receiving 95% of the prescription dose is greater in the case of the
Clinical plan compared to the No Bolus plan, on average the difference is 7.7%. The
average dose to the structure is slightly higher in the Clinical cases with the mean
difference being 0.4Gy. Over the 8 datasets the maximum dose to the PTVtoSurface
structure is on average slightly less in the Clinical case by a small value of 0.2Gy.
Similarly, the average volume of the structures receiving 105% and 107% of the
prescription dose, are slightly more in the No Bolus case, with differences of 0.6% and
0.1%, respectively. The effect observed, in using the bolus, is that it increases the
volume of the target structure receiving 95% of the prescription dose, it increases the
average dose to the target and reduces hotspots.
63
a)
b)
c)
d)
e)
Figure 2.10: Box and Whisker plots showing the a)V95% b) average dose c) V105% d) V107% and e) D1% parameters for the PTVtoSurface structure for No Bolus Plans (Blue) and Clinical Plans (Red) in 8 patients.
64
2.4.6 Plan comparison – Skin Structures (8 patient study set)
Figure 2.11 shows the results for the dosimetric parameters associated with the skin
structures for the No Bolus and Clinical plans
From the data presented in Figure 2.11a, 11b and 11c it can be seen that the minimum
dose to all three skin structures is greater in the case of the Clinical plan. The increase
on average, for the minimum dose parameter for Skin1mm, Skin3mm and Skin5mm is
5.3Gy, 4.6Gy and 4.2Gy, respectively.
A similar trend can be seen in the average dose to the skin structures (Figure
2.11d,11e, 11f). With the mean difference in the Clinical Plan being greater in all cases,
with a dose difference of 2.2Gy, 1.5Gy and 1.1Gy for Skin1mm, Skin3mm and
Skin5mm, respectively. In the case of the maximum dose to each of the skin structures
it can be seen in Figure 2.11i, 11g and 11j that there is a lot of overlap in the range of
values for each technique. This suggests that the different techniques do not have a
significant impact on this dose parameter. A similar trend for all three volumes is
observed with the addition of bolus increasing the minimum dose to the surface. The
effect is largest for the 1mm volume which is in the region of the greatest dose
gradient. Likewise, the average dose to the structures is increased with the use of
bolus, with the greatest impact observed for the 1mm skin structure. The maximum
dose in the skin structure does not appear to be affected by bolus, unlike the decrease
in hotspots that was observed for the PTVtoSurface structure. This indicates that the
hotspots lie within the main PTV rather than superficially.
65
a)
b)
c)
d)
e)
f)
g)
h)
i)
Figure 2.11: Box and Whisker plots showing the doses for a) Skin1mm – D99% b) Skin3mm – D99% c)skin5mm D99% d)Skin1mm – average e)Skin3mm – average f) Skin5mm – average g) Skin1mm – D1% h) Skin3mm – D1% i) Skin5mm – D1% for No Bolus Plans (Blue) and Clinical Plans (Red) for the 8 patients.
2.4.7 Plan comparison – Organs at Risk (8 patient study set)
The dosimetric parameters for the organs at risk are displayed in Figure 2.12 for the 8
patients. For the ipsilateral lung parameter, V30% (volume receiving 30% of the
prescription dose, 12Gy), the two techniques show a similar range in volumes and
66
median value that received that dose, suggesting that the difference between the
techniques is not significant.
a)
b)
c)
Figure 2.12: Dosimetric parameters for organs at risk a) Box and Whisker plot for Ipsilateral Lung V30% b) Bar Chart for Heart V5% c) Bar Chart for Heart V25% for No Bolus Plans (Blue) and Clinical Plans (Red) for the 8 patients.
In both techniques the optimal constraint (volume receiving 12Gy ≤15%) is achieved.
For the heart dosimetric parameters it should be noted that the patient cases cw2,
cw12 and cw18 are right sided treatments and therefore due to the position of the
67
heart the dose is significantly less. For the V5% parameter, volume of heart receiving
2Gy, the volume is on average 0.6% higher in the Clinical plan. In only 3 of the cases
the heart volume receives 10Gy (V25%) and the dose differences between the
techniques are ≤0.02%. As with the lung, the heart constraints (V5% ≤ 30% and V25% ≤
5%) are met in both treatment technique cases. The use of bolus has minimal impact
on the organs at risk.
2.5 Discussion
In this section the clinical technique which consists of a treatment plan where 8# are
delivered without any bolus and 7# are delivered with 1cm bolus, has been compared
to a treatment of 15# with no bolus used. This was done to establish the effect of
bolus in the clinical setting which we will attempt to emulate with the new treatment
technique. Dosimetric parameters for PTVtoSurface, Skin1mm, Skin3mm, Skin5mm
and the organs at risk, heart and lung, were used to analyse the effect.
For the target structure, PTVtoSurface, the results showed that the use of bolus in the
Clinical plan increased the volume that received 95% of the prescription dose (38Gy).
This was observed in the DVH of the example case, where the shoulder of the DVH
curve was shallower in the case of the No Bolus plan and the analysis of the 8 patients
which showed on average a 7.7% increase in volume receiving 38Gy when bolus was
used. With reference to the mandatory constraints for the target coverage (≥90%
volume should receive 95% prescription dose) the use of bolus meant that on average
this constraint was achieved (V95%=93.0%), where this was not the case with the No
Bolus plans (V95%=85.3%), Figure 2.10a. For the maximum dose (D1%), V105% and
V107% parameters the Clinical plans on average reported slightly lower values,
however both plans were within the required dose constraints. The difference in the
average dose to the PTVtoSurface structure was slightly higher in the Clinical cases
with a mean difference on 0.4Gy.
The use of bolus was shown to have an effect on the minimum and average dose
parameters for all the skin structures with minimal impact on the maximum dose. The
effect of bolus was seen most on the D99% and average parameters for the Skin1mm
68
structure, the most superficial, with the effect decreasing as the skin thickness
increased.
For the organs at risk, heart and lung, the comparison of the dosimetric parameters
between the Clinical and No Bolus plans showed that the two techniques were very
similar and, in both cases, met the defined constraints.
2.6 Summary
The use of bolus increases the PTVtoSurface volume receiving 95% of the
prescription dose.
The use of bolus reduces hotspots in the PTVtoSurface structure.
The use of bolus increases the minimum and average dose to the skin
structures, with most effect on 1mm. Bolus has little effect on the maximum
dose to these structures.
The use of bolus has minimal effect on dose to organs at risk.
69
Chapter 3
3 Comparison of VMAT plans to Clinical plans
This section aims to assess whether VMAT plans can be created that reproduce the
distributions of the Clinical plans without the use of bolus. The advantage of this would
be in reducing the number of treatment plans created for each patient, removing the
requirement to ensure bolus has been positioned before the treatment and reducing
any inaccuracies in dosimetry due to ill-fitting bolus.
3.1 Method
VMAT plans were created for the 8 patients analysed in the previous section. The
VMAT plans were optimised using RayStation with an Elekta VersaHD machine model
(5mm MLCs). The VMAT plans consisted of two 360⁰ arc deliveries (clockwise and anti-
clockwise), with a collimator of 10⁰ and using a beam energy of 6 MV FFF (flattening
filter free).
The plans were calculated using a 3mm dose grid with a collapsed-cone convolution
algorithm, the same conditions as for the Clinical plans (supplementary information is
provided in Appendix 1 showing impact of dose grid selection). Each plan was
normalised to 40Gy.
The same structures and dose constraints that were used to evaluate the Clinical and
No Bolus plans were used for this comparison with the addition of a structure,
Contralateral Breast. A constraint of mean contralateral breast dose <3.5Gy was used,
based on the Royal College of Radiologists recommendations for internal mammary
chain radiotherapy (RCR, 2016). This additional constraint was used due to the known,
dose bath effect when using VMAT and IMRT techniques.
The beam optimisation parameters in the treatment planning system were set as
follows; Gantry Spacing= 2⁰, Max Delivery Time = 200 seconds. Table 3.1 shows the
typical starting values used for the plan optimisation process for a left sided treatment.
70
Volume Objective/Function Starting weight
PTVtoSurface Max Dose 40.0 50 PTVtoSurface Min Dose 40.0 100
Heart Max DVH 2.0Gy to 27% volume
20
Left Lung Max Dose 38.3Gy 2 Left Lung Max DVH 5.0Gy to 15%
volume 15
Contralateral Breast Max Dose 4Gy 10 External Dose Fall-Off [H] 40.00Gy
[L] 5.0Gy, Low dose distance 3.0cm
100
External Max Dose 44.0Gy 50
Table 3.1: Typical starting values for planning objectives used for the VMAT plans.
3.2 Results
3.2.1 Plan comparison – Dose Distribution (single patient example)
Figure 3.1 shows the dose distribution for the No Bolus, Clinical and VMAT plan for the
same example patient discussed in Section 2. The difference between the No Bolus
and Clinical plans highlights visually the conclusions from the previous section, that
bolus reduces the hotspots within the treated volume, increases the dose to the
patient surface and has minimal impact on the dose to organs at risk plus normal
tissue. The main difference between the VMAT plan and both the Clinical and No Bolus
plans is the low dose distribution, where doses <20Gy, spill out of the treated area; as
typical of VMAT plans. Visually the distribution across the treated area also appears
more homogeneous for the VMAT technique. The plans are analysed quantitatively in
the following sections.
a) b)
71
c)
Figure 3.1: Example Dose Distribution for a) No Bolus plan b) Clinical plan c) VMAT plan
3.2.2 Plan comparison – PTVtoSurface (single patient example)
Figure 3.2 shows the DVH for the PTVtoSurface structure in the example patient case,
for each of the treatment techniques.
Dose values were extracted from the PTVtoSurface DVHs for the specified dose
parameters. Table 3.2 shows the values achieved for each treatment technique.
72
Figure 3.2: Example of DVH for structure PTVtoSurface. (Dashed line= Clinical Plan, Dotted line = No Bolus Plan and Solid line = VMAT plan)
Structure Dosimetric Parameter
Mandatory Constraint
Optimal Constraint
Clinical Plan
No Bolus Plan
VMAT Plan
PTVtoSurface V95% V105% V107% D1 % Average
≥ 90% ≤ 7% ≤ 2% ≤ 110%
≥ 95% ≤ 5%
96.0% 1.1% 0.0% 104.9% 40.0Gy
92.4% 1.7% 0.1% 105.4% 39.8Gy
96.6% 0.2% 0.0% 103.6% 40.0Gy
Table 3.2: Example of dosimetric parameters obtained for the structure PTVtoSurface for the Clinical, No Bolus and VMAT plans
In Figure 3.2 it is observed that the DVH for the VMAT plan displays a steeper gradient
centred on 40Gy prescription dose point than either the Clinical or No Bolus
techniques. This indicates that the VMAT technique is more homogeneous than the
other two over this target structure. The VMAT DVH falls slightly below the Clinical
plan between 35-38Gy, which suggests the minimum dose to the PTVtoSurface volume
is slightly higher in the Clinical plan. The improved homogeneity can also be observed
in the analysis of dose parameters in Table 3.2. The value for V95% is slightly higher in
73
the case of the VMAT plan compared to the Clinical plan, V105% slightly less and the
average dose remaining the same.
3.2.3 Plan comparison – Skin Structures (single patient example)
Figure 3.3 shows the DVHs for the skin structures in the same example patient. Specific
dose parameters were extracted from the DVHs for each skin structure and plan
technique. Table 3.3 reports the dose values obtained.
Structure Dosimetric
Parameter,
Gy
Clinical Plan No Bolus Plan VMAT Plan
Skin1mm D99%
Average
D1%
34.1Gy (85.3%)
38.0Gy (95.0%)
40.7Gy (101.7%)
29.2Gy (73.0%)
36.2Gy (90.5%)
40.8Gy (102.0%)
31.6Gy (79.0%)
37.9Gy (94.8%)
41.2Gy (103.0%)
Skin3mm D99%
Average
D1%
35.0Gy (87.5%)
38.7Gy (96.8%)
41.1Gy (102.8%)
30.9Gy (77.3%)
37.5Gy (93.8%)
41.5Gy (103.8%)
32.9Gy (82.3%)
39.1Gy (97.8%)
41.5Gy (103.8%)
Skin5mm D99%
Average
D1%
35.4Gy (88.5%)
39.2Gy (98.0%)
41.5Gy (103.8%)
31.7Gy (79.3%)
38.3Gy (95.8%)
41.9Gy (104.8%)
33.6Gy (84.0%)
39.6Gy (99.0%)
41.6Gy (104.0%)
Table 3.3: Example of dosimetric parameters obtained for the skin structures for the Clinical, No Bolus and VMAT plans (Values in brackets represent the dose received as a percentage of the prescription dose, 40Gy)
The DVHs in Figure 3.3 and the data in Table 3.3, show that for the example case, the
average dose for the Skin3mm and Skin5mm structures, is greater with the VMAT
technique compared to the Clinical plan and for the Skin1mm structure the average
dose is slightly lower for the VMAT technique compared to the one used clinically. For
all the skin structures the maximum dose is slightly higher in the VMAT cases than the
clinical situation, 0.5Gy, 0.4Gy and 0.1Gy for Skin1mm, Skin 3mm and Skin5mm,
respectively. The minimum dose to the skin structures is also lower with the VMAT
technique. For the Skin1mm volume, the minimum dose is 2.5Gy less with the VMAT
technique compared with the Clinical, and 2.1Gy and 1.8Gy less, for the Skin3mm and
Skin 5mm volumes.
74
Figure 3.3: Example DVHs for a) Skin1mm b)Skin3mm c)Skin5mm (Dashed line=Clinical plan, Dotted line = No Bolus plan, Solid line=VMAT plan)
a)
b)
c)
75
Comparing the VMAT technique to the Clinical plan there is a greater difference
between the minimum and maximum doses in each of the skin structures, indicating
the dose is not as homogenous, in this superficial area. Although compared to the
Clinical plans the minimum dose is not as great with the VMAT plans, the VMAT
technique still enhances the minimum dose compared to that achieved in the No Bolus
situation. Compared with the No Bolus plan the minimum dose to Skin1mm, Skin3mm
and Skin 5mm is increased by 2.4Gy, 2.0Gy and 1.9Gy, respectively. As was seen with
the comparison of the Clinical plan to the No Bolus plan, the VMAT technique has most
impact on the most superficial structure, Skin1mm.
3.2.4 Plan comparison – Organs at Risk (single patient example)
Figure 3.4 shows the DVH for the heart and lung OARs and the structure, Contralateral
Breast, for the example patient. Table 3.4 shows the extracted dosimetric parameters.
Figure 3.4: Example DVHS for Heart (red line), Ipsilateral Lung (Orange line) and Contralateral Breast (Blue line). (Dashed line = Clinical plan, Dotted line = No Bolus Plan and Solid line=VMAT plan)
Structure Dosimetric Mandatory Optimal Clinical No VMAT
76
Parameter Constraint Constraint Plan Bolus Plan
Plan
Heart
Ipsilateral Lung
Contralateral
Breast
V25% (10Gy) V5% (2Gy) V30%(12Gy) Mean Dose
≤5% ≤30% ≤17%
≤15% <3.5Gy
0% 6.4% 13.6% 0.3Gy
0% 6.5% 13.4% 0.2Gy
0% 29.9% 7.1% 2.0Gy
Table 3.4: Example of dosimetric parameters obtained for the heart, lung and contralateral breast, for the Clinical, No Bolus and VMAT plans.
It has been previously discussed that the use of bolus had minimal impact on the
organs at risk, heart and ipsilateral lung, and from Figure 3.4 and Table 3.4 we can also
observe, as expected, that it has minimal impact on the dose to the contralateral
breast. In Figure 3.4 we can observe that for the VMAT plan there is significant shift in
the DVH curve for the heart structure, towards the higher doses, and the value
reported for the V5% shows that for the VMAT plan this heart dose is just within the
mandatory constraint. For the lung structure it can be seen in the DVH, that when
using the VMAT technique more of the lung volume receives doses less than 5Gy
compared to the Clinical and No Bolus techniques however the volume of lung
receiving doses above 5Gy is greater for the Clinical or No Bolus technique. This is
supported by the V30% parameter for the lung volume, where only 7.1% of the lung
receives 12Gy using the VMAT technique compared to 13.6% for the Clinical plan. All
techniques however do produce dose distributions that meet the required constraints
for heart and lung. It can also be observed that the dose to the contralateral breast is
significantly higher using the VMAT technique, however this is still less than the
recommended constraint of <3.5Gy. The increased lung volume receiving lower doses
and the contralateral breast receiving higher dose are the effects of the low dose bath
expected with VMAT.
77
3.2.5 Plan comparison – PTVtoSurface (8 patient study set)
Figure 3.5 shows the dosimetric parameters for the PTVtoSurface structure for the 8
patient cohort, for each of the treatment techniques, with similar trends observed
across all the patients.
a)
b)
c)
d)
e)
Figure 3.5: Box and Whisker plots showing the a) V95% b) average dose c) V105% d)107% and e) D1% parameters for the PTVtoSurface structures for No Bolus Plans (Blue), Clinical Plans (Red) and VMAT Plans (Green) in the 8 patients.
78
From Figure 3.5a it can be observed that the use of the VMAT technique can increase
the volume of 38Gy (95% of the prescription dose) that the target structure receives.
The average value for the V95% objective increases from 93%, for the Clinical plan to
95.6% for the VMAT plan, resulting in the VMAT plans, on average, meeting the
optimal constraint for target coverage (V95% >95%). For this set of patients, it can also
be seen that in the VMAT plans the mandatory constraint is consistently achieved
(V95%>90%) compared with the Clinical case and the variation of this value is reduced
between patients. The average dose to the target structure is also slightly increased
with the VMAT technique compared to the Clinical case with the mean dose to the
PTVtoSurface structure increasing by 0.6Gy. For the parameters reflecting the hotter
dose distribution (areas receiving a dose greater than the prescription dose) within the
structure, D1%, V105% and V107%, it is observed that the VMAT technique results in
plans that produce slightly higher hotspots than the Clinical Plan but lower than the No
Bolus plan. However, all the volumes still meet the mandatory requirements. The
VMAT technique can produce plans with better V95% coverage than the Clinical plans,
with slightly larger hotspots, but which are clinically acceptable
3.2.6 Plan comparison – Skin Structures (8 patient study set)
In Figure 3.6 the results for the dosimetric parameters obtained for the skin structures
are summarised for the 8 patients, for each technique.
From Figure 3.6 a similar trend is seen for all the skin structures, for each of the
parameters used to compare the three techniques. It can be observed in Figure 3.6a,
Figure 3.6b and Figure 3.6c that the VMAT technique does not have the same impact
as using bolus on the minimum dose to the skin structures. Where the bolus increased
the minimum dose on average by 5.3Gy, 4.6Gy and 4.2Gy to the Skin1mm, Skin3mm
and Skin5mm, the VMAT technique increased the dose by 3.5Gy, 3.3Gy and3.3Gy,
respectively, compared with the No Bolus plan. As with the Clinical plan the VMAT
technique had the most impact on the most superficial structure, Skin1mm.
79
a)
b)
c)
d)
e)
f)
g)
h)
i)
Figure 3.6: Box and Whisker plots showing the doses for a) Skin1mm – D99% b) Skin3mm – D99% c)skin5mm D99% d)Skin1mm – average e)Skin3mm – average f) Skin5mm – average g) Skin1mm – D1% h) Skin3mm – D1% i) Skin5mm – D1% for No Bolus plans (Blue), Clinical plans (Red) and VMAT plans (Green) for the 8 patients.
With reference to the average dose parameter the VMAT technique enhances the dose
to all the skin structures more than with the use of bolus. With the VMAT technique
80
the Skin 1mm, Skin3mm and Skin 5mm receive an additional 0.7Gy, 0.9Gy and 0.8Gy,
respectively compared to the Clinical plan.
In the case of the maximum dose to the skin structures the VMAT technique results in
slightly higher hotspots than the other two techniques, particularly in the most
superficial skin layer, Skin1mm. The increase in hotpots using the VMAT technique was
also observed within the PTVtoSurface structure, however not to the same extent,
suggesting that the hotspots are within the superficial area. It should be noted that the
maximum doses are still within the accepted tolerance of <110% (44Gy).
Although the VMAT technique can increase the V95% for the PTVtoSurface structure
compared to the Clinical plan, the minimum dose to the skin structures was not
increased as much as when bolus is used. The average dose to the skin structures can
be increased with the VMAT technique, as is the maximum dose, however the
hotspots are still clinically acceptable.
3.2.7 Plan comparison – Organs at Risk (8 patient study set)
The dosimetric parameters for heart, ipsilateral lung and contralateral breast for each
of the treatment techniques are summarised for the 8 patients in Figure 3.7.
In Figure 3.7a it can be seen that on average the VMAT technique results in a smaller
volume of lung receiving 30% of the prescription dose (12Gy) than the Clinical and No
Bolus plans. On average the volume difference between the Clinical and VMAT plan is
2.8%. For this set of patients, the mean ipsilateral lung volume is 1392cm3 so with the
VMAT technique the volume receiving 12Gy is on average 38.9 cm3 less compared to
the Clinical treatment.
81
a)
b)
c)
82
d)
Figure 3.7: Dosimetric parameters for organs at risk a) Box and Whisker plot for Ipsilateral Lung V30% b) Bar Chart for Heart V5% (mandatory constraint shown in dashed line) c) Bar Chart for Heart V25% d) Box and Whisker plot for Contralateral Breast for No Bolus Plans (Blue), Clinical Plans (Red) and VMAT Plans (Green) for the 8 patients.
Figure 3.7b shows that, for the heart dosimetric parameter V5% (volume of the heart
receiving 5% of the prescription dose) all the plans are within the mandatory
constraint. However, it is clear that the VMAT technique results in larger volumes
receiving a dose of 2Gy. One reason for the higher doses in the VMAT plans is that
although the heart was used in the optimisation process for the plans, if the heart
constraint was met the plan was deemed acceptable and no further optimisation took
place. Therefore, there may be scope for further reducing these doses further. In
particular, for the three right-sided cases cw2, cw12 and cw18, the 2Gy dose received
by the heart is a likely result of the low dose bath produced by the VMAT technique
with beams entry from multiple directions, however there may be scope to reducing
this too, if additional constraints are added to the optimisation process.
Three of the eight plans showed dose in the heart over 10Gy, with the VMAT
technique resulting in a smaller volume receiving this dose. The difference in volume
compared to the Clinical technique however is relatively small, on average 0.2%, with
83
the average heart volume for these three cases being 779cm3, this is to an average
volume difference of 1.6cm3.
The effect of the VMAT dose bath is also seen for the contralateral breast structure,
with the average mean dose in the case of the VMAT technique being 1.5Gy higher.
The VMAT technique still however meets the recommended requirement than the
mean dose <3.5Gy.
Unlike the use of bolus, the use of the VMAT technique does impact the organs at risk.
However the mandatory constraints for the organs at risk can still be achieved.
3.3 Discussion
In this chapter the VMAT technique using two 360⁰ arcs was analysed to establish
whether similar dose distributions to the Clinical technique, using bolus, could be
produced. Results from the No Bolus plans were also included to compare the impact
of the two skin enhancing techniques.
For the target structure PTVtoSurface the results showed that the VMAT plan could
increase the volume that received the prescription dose more than with bolus. On
average the VMAT plans met the optimal constraint (V95%>95%) for this target
structure whereas the Clinical technique on average only met the mandatory
constraint (V95%>90%). The average dose to the PTVtoSurface structure was also
0.6Gy greater using the VMAT technique compared to the Clinical one. The maximum
dose, V105% and V107% were on average greater for the VMAT technique compared
to the Clinical plans, but still within the mandatory constraints.
The DVH for the PTVtoSurface structure in the example patient suggested that the
minimum dose was slightly lower using the VMAT technique than the Clinical case. This
was also observed in the DVH for the skin structures and seen in the average data
across the 8 patients for the minimum dose parameter. However, the results for the
average and maximum dose parameters for the skin structures showed that the VMAT
technique could enhance the dose more than the Clinical plans, compared to using no
bolus. Although the maximum dose to the skin structures was higher, using the VMAT
technique, the dose was still within the specified constraint.
84
However, unlike with the Clinical plan where the use of bolus had minimal impact on
the dose to the heart, lung and contralateral breast, the dose distribution from the
VMAT plans did affect these parameters. The VMAT technique had a positive effect on
the ipsilateral lung volume parameter V30%, where on average this volume was
smaller (2.8%), and there also a slight decrease in heart volumes receiving 10Gy (0.2%),
for the three cases where this parameter was reported. In contrast, a larger volume of
the heart received 2Gy and the mean dose to the contralateral breast on average
increased by 1.5Gy, this was expected and due to the low dose bath as consequence of
using the VMAT technique However the recommended constraints were met in all the
patients and further optimisation in the treatment planning software could have
potentially reduced these values.
3.4 Summary
VMAT plans can be produced that meet the required dose objectives for target
structure.
With the VMAT technique the volume of the target structure receiving 95% of
the prescription dose can be greater than in the Clinical case using bolus.
The mean dose to the target volume is increased using the VMAT technique
compared to the Clinical case.
The VMAT technique enhances the minimum dose to the patient surface but
not to the same extent as the Clinical plans, however average and maximum
doses to the skin structures are greater in the VMAT plans.
A consequence of using VMAT plans is a low dose bath to tissues outside the
target however dose constraints to organs at risk can still be achieved.
85
Chapter 4
4 Surface Dose Measurements
Chapter 2 quantified the effect of using bolus as part of the department’s current
technique of opposed tangential fields and in Chapter 3 it has been shown that an
alternative technique using VMAT can produce similar dose distributions, including
skin doses. The impact of dose and comparison of techniques have so far been limited
to evaluating the distributions calculated in the treatment planning system.
The limitations of treatment planning systems to accurately calculate dose at the
surface of air-tissue interfaces has been discussed in the introduction and included the
ability of the treatment planning algorithm to account for electron contamination that
originates in the treatment head and the effect of obliquity of incident beams.
In this chapter superficial doses have been measured to investigate the accuracy of the
dose calculation. The aim to determine whether the calculations for both the Clinical
and VMAT techniques are reliable and match physical measurements.
Two phases of measurements had originally been planned, measurements on an
anthropomorphic phantom followed by measurements on patients. Measurement of
superficial doses using the current technique would have taken place with the consent
of the patients, as part of a departmental audit. However, this aspect of the
investigation was unable to be completed due to the Covid-19 pandemic, which limited
unnecessary access to patients, treatment rooms and also brought about a change in
dose and fractionation for these patients. The measurements presented were carried
out on the anthropomorphic phantom as part of developing a method to be used in
patient cases. These were made just prior to Covid-19 restrictions being put into place
and therefore some repeats of experiments were unable to be completed.
86
4.1 Method
Three treatment plans were generated in RayStation using the CIRS anthropomorphic
thorax phantom (CIRS Inc., Norfolk, VA, USA). The CIRS phantom was CT scanned on a
Philips Brilliance Big Bore CT Scanner (Philips Medical Systems, Eindhoven,
Netherlands) at 3mm slice thickness. The 3 plans created were:
1. A tangential plan with no bolus
2. A tangential plan with 1cm bolus (virtually applied in the treatment planning
system)
3. A VMAT partial arc plan
The bolus and no bolus plans consisted of two opposed open fields with no segments
using a 6MV cFF (conventional flattening filter) for delivery on an Elekta VersaHD linac.
The VMAT plan was created using a 6MV FFF beam for delivery on the same machine.
All plans were prescribed to deliver 40Gy in 15#, calculated with the on a dose grid of
0.3cm. The dose distributions for the three plans are shown in Figure 4.1.
Dose measurements were performed using lithium fluoride thermoluminescent
dosimeters (TLDs), TLD-100H (ThermoFisher Scientific, Waltham, MA, USA) with a
dimension of 3mmx3mm and 0.8mm thick. The TLDs were readout using a Harshaw
3500 TLD reader (ThermoFisher Scientific, Waltham, MA, USA). Absolute dose was
obtained by irradiating a small batch of TLDs under standard calibration conditions
(6MV, 10x10 cm field, 90SSD, 10cm depth) with reference to the same measurement
using a Farmer chamber (NE2571), in accordance to our standard departmental
protocol. The TLD measurements were also corrected for dose response by irradiating
at different MU (50MU, 100MU, 200MU) and individual TLD calibration factors.
87
a)
b)
c)
Figure 4.1: Dose distribution for a) No Bolus b) Bolus and c) VMAT partial arc plan on the CIRS anthropomorphic thorax phantom
88
Five reference points, approximately 5cm apart, were created on the central slice of
the phantom, from medial to lateral, representing the positions that TLD
measurements would be made. The points were placed on the external contour, as
created by the treatment planning system (Figure 4.2).
Figure 4.2: Points showing the TLD position on central axis of CT Scan of CIRS phantom. Each TLD point is positioned to intersect with the body contour (green),
Treatment plans were delivered on the Elekta VersaHDs, using the treatment machine
laser system to align and set-up the CIRS phantom for irradiation at the planned
isocentre position. Two TLDS were placed at each measurement position, for each plan
delivered, one TLD either side of the central axis in the sup/inf direction (Figure 4.3).
For the bolus plans a slab of 1cm thick of tissue equivalent material is placed over the
whole phantom prior to plan delivery (Figure 4.4).
89
a)
b)
Figure 4.3: a) anthropomorphic phantom position for treatment delivery b) packets position with TLD either side of central axis
Figure 4.4: 1cm water equivalent material placed over phantom prior to delivery of bolus plan.
90
To establish the consistency of the TLD measurements the aim was to deliver each
treatment plan 5 times, however due to availability of treatment machines during the
Covid-19 pandemic, the no bolus treatment plan was repeated 4 times, the bolus plan
3 times and the VMAT plan was delivered once.
4.2 Results
Figure 4.5 shows the TLD dose measurements for the no bolus plan compared with the
predicted treatment planning system for one fraction. The TLD measurements at each
point, except position 3, are within 5% of each other. The variation in measurement
dose at position 3 is 6.4%. Table 4.1 summarises the average TLD measurement at
each point as a percentage of the prescribed dose compared with the treatment plan.
Figure 4.5 and Table 4.1 show that the TLD measurements are consistently lower than
the calculated doses but that the size of the difference is dependent on position. On
average the TLD measurement is 8.2% lower than planning system predicted dose.
Figure 4.6 shows the TLD measurements for the bolus plan compared with the
calculated doses in the treatment planning system. At positions 1,2, 5 and 3 (if outlier
value is ignored) the TLD measurements are within 5% of each other. At position 4 the
variation in measurement is 6.9%. From Table 4.2 it is observed that the average TLD
measurement at each position, excluding the outlier at position 3, are a higher dose
than predicted. On average the dose difference between measured doses is 2.0%
higher than predicted.
Figure 4.7 shows the measurements for the VMAT plan compared with the calculated
doses, only one set of measurements was performed. From Figure 4.7 and Table 4.3 it
can be seen that at all positions the TLDs measured a lower dose than was predicted
by the planning system. The dose difference is on average 6.4% lower with the
greatest dose difference seen at position 1, 8.0%.
91
Figure 4.5: TLD results for No Bolus plan compared to treatment plan dose - 1 fraction delivery. (Plan delivered 4 times)
Position Dose Measured, % of prescribed dose (absolute dose, Gy)
Dose Predicted, % of prescribed dose (absolute dose, Gy)
Dose Difference (%)
1 61.0 (1.63) 66.8 (1.78) -8.7 2 66.3 (1.77) 75.2 (2.0) -11.7 3 82.8 (2.21) 83.3 (2.22) -0.6 4 64.6 (1.72) 73.1 (1.95) -11.6 5 56.7 (1.51) 62.8 (1.67) -9.8
Average Difference -8.5
Table 4.1: Results of TLD measurements for No Bolus plan as percentage of prescribed dose compared to planned dose, absolute dose in brackets.
92
Figure 4.6: TLD results for Bolus plan compared to treatment plan dose - 1 fraction delivery (Plan delivered 3 times)
Position Dose Measured, % of prescribed dose (absolute dose, Gy)
Dose Predicted, % of prescribed dose (absolute dose, Gy)
Dose Difference (%)
1 104.6 (2.79) 101.9 (2.72) 2.7 2 101.9 (2.72) 100.6 (2.68) 1.3 3 101.0 (2.83) 104.1 (2.77) 2.2 4 104.0 (2.77) 102.1 (2.72) 1.9 5 101.3 (2.70) 100.0 (2.67) 1.3
Average Difference 1.9
Table 4.2: Results of TLD measurement for Bolus plan as percentage of prescribed dose compared to planned dose absolute dose in brackets. (Measurement 2 at TLD position 3 disregarded in these results)
93
Figure 4.7: TLD results for VMAT plan compared to treatment plan dose - 1 fraction delivery. (Plan delivered once)
Position Dose Measured, % of prescribed dose (absolute dose, Gy)
Dose Predicted, % of prescribed dose (absolute dose, Gy)
Dose Difference (%)
1 66.8 (1.78) 72.8 (1.94) -8.2 2 72.6 (1.94) 78.9 (2.10) -8.0 3 72.3 (1.93) 76.2 (2.03) -5.1 4 60.3 (1.61) 62.7 (1.67) -3.7 5 44.0 (1.17) 46.9 (1.25) -6.1
Average Difference -6.2
Table 4.3: Results of TLD measurements for VMAT plan as percentage of prescribed dose compared to planned dose absolute dose in brackets.
94
4.3 Discussion
The results, with the no bolus case using tangents, showed that the measured surface
dose ranged from 56.7% - 82.8% of the prescription dose. The highest dose was at the
apex of the phantom, position 3, where the incident beams are at their shallowest.
This variation in dose distribution and range of doses reflects those measured by
Quach et al. (2000) where TLDs were used on a hemicylindrical phantom and surface
doses from 49%-75% were obtained from the steepest to shallowest beam incidence.
Manger et al. (2016) also reported superficial dose distributions of the same
magnitude and profile, 40%-70% of the prescription dose, using Gafchromic EBT3 film,
with a no-bolus plan using 6MV tangential fields. Both of these groups also showed
that with the use of 1cm of tissue equivalent bolus the surface-dose profile become
shallower, with Manger et al. (2016) reporting Gafchromic film measurements
increasing to 85%-109% of the prescription dose. Although similar results are not
available to compare the VMAT plans directly the implication that beam incidence
angle influences the superficial dose provides some explanation for the dose variation
in the plan investigated in this chapter.
With the plans calculated on a dose grid of 3mm, the TLD measurements in the bolus
plan were consistent with the RayStation planning system to within 3%, however the
no bolus and VMAT plans, showed lower measurement doses compared to the
planning system of 8.5% and 6.2% respectively. This discrepancy is not unexpected as
the TLD position defined in the treatment planning system for the VMAT and No Bolus
plans lie at the intersection between tissue and air, where the treatment planning
system accuracy is most limited as discussed previously. However, the results
presented here are consistent with a study conducted by Chung et al. (2005) where it
was shown that the treatment planning systems, Pinnacle3 and Corvus overestimated
surface dose by ~15% and ~18% respectively. Similarly, Cao et al. (2017) suggested that
the collapsed cone algorithm used in RayStation performed well in the calculation of
superficial dose despite overestimation of skin dose at the reference depth of 70µm of
14.11%. Other sources of inaccuracy include the dose grid that the plans were
calculated at, 0.3cm, and calculation at a smaller dose grid could improve the dose
difference.
95
There are limitations to the accuracy of this data due to the inability to repeat some of
the measurements, particularly for the VMAT cases as access to the treatment
machines was limited due to the Covid restrictions. However, the results presented are
consistent with published data and suggest that TLDs are sensitive enough to measure
the superficial doses for comparison of the treatment techniques in addition to
comparing technique through treatment planning systems. In reporting dose to skin, it
has been previously been discussed that there is lack of consensus as to how skin is
defined. Therefore TLDs with a thickness of 0.8mm may be suitable for reporting skin
dose if this thickness is considered appropriate for skin, however for skin doses at the
ICRU recommended depth of 0.07mm, alternative dosimeters would be required.
4.4 Summary
TLD measurements on an anthropomorphic phantom were shown to be within
3% of the dose predicted by the treatment planning system when
measurement position at 1cm depth (under bolus).
Surface dose measurements with TLDs demonstrated that the treatment
planning system over-estimated the dose by 8.5% for the no bolus, tangential
plans and 6.2% for VMAT plans. This over-estimation is expected due to the
challenges in accurately modelling the build-up effect in the treatment planning
system.
96
Chapter 5
5 Effect of Perturbation
In the previous chapters it was shown that VMAT plans could be optimised that
produced similar dose distributions to the Clinical plans. The VMAT plans met the
required dose objectives for the target volume and with the exception of the D99%
value, dose parameters were comparable for the skin structures. Constraints were also
met for the heart, lung and contralateral breast.
To achieve the increase in dose to the surface region, without using bolus, IMRT
techniques need to overcome the skin-sparing effect by adding more dose into the
build-up region. This is achieved using small, narrow segments, targeting the surface
from a glancing angle. However, patient motion may result in this dose being delivered
outside the build-up region generating hotspots in the patient tissue. VMAT plans may
therefore be more susceptible to movement than the current clinical technique.
This section therefore attempts to determine the impact of changes in patient set-up
by assessing the effect on dose distribution for the Clinical and VMAT plans.
5.1 Method
To simulate the effect of setup uncertainties and patient changes the Clinical and
VMAT plans created for the cohort of 8 patients were recalculated on perturbed CT
datasets. This was performed using the ‘compute perturbed dose’ in the RayStation
software, which recalculates the original plan on the CT dataset with the isocentre
shifted by a defined value, no further optimisation of the plan is made. It is
acknowledged that this does not represent the random set-up error in the clinical
situation but instead assumes the same patient shift for all 15 fractions of treatment.
In addition, the perturbation shifts were applied to a rigid body, so non-uniform
patient changes were not taken into account. In the case of the Clinical plans, the
97
perturbation was applied to the individual no bolus and bolus parts of the plan, prior
to summation. The results in this study should be considered a worse-case scenario for
the patient treatment and should give an indication of how the dose distribution
changes with patient set-up in different directions.
Perturbed dose calculations were carried out on both the Clinical and VMAT plans for
the 8 patients. Perturbation values of 0.5cm and 0.3cm were used to establish whether
there was an acceptable limit of set-up error. The perturbation was applied in each of
the left-right, superior-inferior and anterior-posterior directions, moving the isocentre
towards and away from the patient surface, and in the superior and inferior direction.
Figure 5.1 summarises the shifts applied to the isocentres.
DVHs were obtained for each perturbed plan and the dosimetric metrics for
PTVtoSurface, skin structures and organs at risks as in previous chapters, were used for
the quantitative analysis.
Direction of Perturbation
Left Sided Treatment Shift Direction
Left Sided Perturbation Values
Right Sided Treatment Shift Direction
Right Sided Perturbation values
Towards patient surface
and superior (TS)
Left, Sup, Ant 0.5, 0.5, 0.5 0.3, 0.3, 0.3
Right, Sup, Ant -0.5, 0.5, 0.5 -0.3, 0.3, 0.3
Away from patient surface
and superior (AS)
Right, Sup, Post -0.5, 0.5, -0.5 -0.3, 0.3, -0.3
Left, Sup, Post 0.5, 0.5, -0.5 0.3, 0.3, -0.3
Towards patient surface
and inferior (TI)
Left, Inf, Ant 0.5, -0.5, 0.5 0.3, -0.3, 0.3
Right, Inf, Ant -0.5, -0.5, 0.5 -0.3, -0.3, 0.3
Away from patient surface
and inferior (AI)
Right, Inf, Post -0.5, -0.5, -0.5 -0.3, -0.3, -0.3
Left, Inf, Post 0.5, -0.5, -0.5 0.3, -0.3, -0.3
Table 5.1: Summary of shifts for perturbed plans. Abbreviation for perturbation direction are included.
98
5.2 Results
5.2.1 Perturbation Effect – Dose Distribution (single patient example)
In Figure 5.1 the impact of perturbation on the dose distribution for the Clinical and
VMAT plans perturbed by 0.5cm in the TS and AS directions (TS and AS have been
shown as they demonstrated the worse-case scenario perturbed calculations).
Figure 5.1b and Figure 5.1e show the impact of perturbation towards the patient
surface with a shift of 0.5cm. The posterior edge of the treatment volume loses
coverage of the 95% isodose line in both the plans. In the Clinical plan there is an
increased dose to the superficial region of the target volume and the opposite is
observed for the VMAT plan.
Figure 5.1c and Figure 5.1f show the impact of perturbation with a shift 0.5cm away
from the patient surface. As the isocentre is moved closer to the lung the 95% isodose
spills over the posterior edge of the target volume in both cases. In the Clinical plan a
lower dose is observed in the superficial region of the target and an increase is dose is
seen in the case of the VMAT plan.
99
a)
b)
c)
d)
e)
f)
Figure 5.1: Example of perturbed plans a) Clinical plan -non perturbed b) Clinical plan – perturbed 0.5cm TS direction c) Clinical plan – perturbed 0.5cm AS direction d) VMAT plan – non perturbed e) VMAT plan – perturbed 0.5cm TS direction f) VMAT plan – perturbed 0.5cm AS direction
100
5.2.2 Perturbation Effect – PTVtoSurface (single patient example)
The DVHs in Figure 5.2a and Figure 5.2c show the effect of a 0.5cm shift towards the
patient surface for the Clinical and VMAT plans. The coverage of the PTVtoSurface
reduces, as was observed with the dose distributions. It is clear however, from the
DVHs that the impact is greater for the VMAT case.
The DVHs in Figure 5.2b and Figure 5.2d shows the perturbation effect with a shift
away from the patient surface. For the Clinical plan the shift appears to reduce the
dose over most of the volume and slightly increase the maximum dose. For the VMAT
plan a slightly higher minimum dose is seen, however the maximum dose to the
PTVtoSurface is notably greater.
Specific dose parameters were extracted from the DVHs for each of the perturbed
plans. The values achieved, along with the mandatory and optimal constraints are
shown in Table 5.2 and Table 5.3, the values not meeting the mandatory constraints
are highlighted.
101
a)
b)
c)
d)
Figure 5.2: Example of DVHs for PTVtoSurface a)Clinical plan non-perturbed v Clinical plan perturbed 0.5 in TS direction b) Clinical plan non-perturbed v Clinical plan perturbed 0.5cm in AS direction c)VMAT plan non-perturbed v VMAT plan perturbed 0.5cm in TS direction d) VMAT plan non-perturbed v VMAT plan perturbed 0.5cm in AS direction. (Dotted line = original plan, dashed line = perturbed plan)
102
Structure Dosimetric Parameter
Mandatory Constraint
Optimal Constraint
Non – Perturbed (Clinical)
0.5cm TS Shift
0.5cm AS Shift
PTVtoSurface V95% V105% V107% D1 % Average
≥ 90% ≤ 7% ≤ 2% ≤ 110%
≥ 95% ≤ 5%
96.0% 1.1% 0.0% 104.9% 40.0Gy
81.1% 4.8% 0.2% 106.0% 38.5Gy
90.5% 3.4% 0.9% 106.7% 39.5Gy
Table 5.2: Example of dosimetric parameters for the non-perturbed Clinical plan and with a perturbation of 0.5cm in the TS and AS directions. Values underlined show where constraints were not met.
Structure Dosimetric Parameter
Mandatory Constraint
Optimal Constraint
Non – Perturbed (VMAT)
0.5cm TS Shift
0.5cm AS Shift
PTVtoSurface V95% V105% V107% D1 % Average
≥ 90% ≤ 7% ≤ 2% ≤ 110%
≥ 95% ≤ 5%
96.6% 0.2% 0.0% 103.6% 40.0Gy
74% 1.3% 0.1% 105.3% 37.7Gy
98% 22.3% 16.8% 119% 40.8Gy
Table 5.3: Example of dosimetric parameters for the non-perturbed VMAT plan and with a perturbation of 0.5cm in the TS and AS directions. Values underlined show where constraints were not met
Table 5.2 and Table 5.3 show quantitatively the impact of patient movement on the
dose distribution. A perturbation in the 0.5cm TS direction results in failure to meet
the V95% mandatory constraint in both the Clinical and VMAT cases, with a greater
reduction in volume for the VMAT case. Similarly, average dose decreases for both
plans and both plans get hotter. For shifts in the 0.5cm AS direction, the V95% for the
Clinical plan again decreases compared to its non-perturbed plan, however for the
VMAT plan the value increases. Following the same trend as V95% the average dose
decreases in the perturbed Clinical plan and increases for the VMAT plan. In both cases
a shift away from the surface increases the hotspots, and in the case of the VMAT plan
the constraints are significantly exceeded.
For perturbation towards the surface with both the Clinical and VMAT techniques a
reduction in coverage of the PTVtoSurface is seen. For shifts away from the surface a
103
slight reduction is observed for the Clinical plans and a significant increase in hotspots
is seen for the VMAT plan.
5.2.3 Perturbation Effect – Skin Structures (single patient example)
The DVHs shown in Figure 5.3a and Figure 5.3c demonstrate the impact of shifts 0.5cm
towards the patient surface for the Clinical and VMAT plans on the Skin3mm structure.
For the Clinical plan on average the dose over the structure increases though the
minimum dose decreases. In contrast for the VMAT plan a significant decrease in the
dose is observed over the whole skin structure, as was visualised in the dose
distribution (Figure 5.1e).
For perturbation in the AS direction Figure 5.3b shows that for the Clinical plan a
decrease in dose is observed for the skin structure and for the VMAT plan the opposite
is seen(Figure 5.3d), with doses increasing to more than 125% of the prescription dose.
The Skin3mm structure was chosen to demonstrate the effect, a similar trend is seen
with the Skin1mm and Skin5mm.
The bar chart in Figure 5.4 shows quantitatively the impact perturbations have on the
parameters D99%, average dose and D1% for the Skin3mm structure. In this example,
a shift towards the surface by 0.5cm (red bars), reduces the minimum dose (D99%) in
both the Clinical and VMAT cases, with more effect seen for the Clinical case, 12.6Gy
compared to 7.7Gy. The average dose is slightly increased for the Clinical plan but
reduced for the VMAT plan, as in seen for the D1% parameter. For shifts away from
the surface (green bars) the minimum dose is also reduced for both techniques,
however not to the same extent as shifts towards the surface. The impact on the
average dose for the Clinical plan is a slight reduction in dose compared to the non-
perturbed case, in contrast to the VMAT plans which see an increase in average dose.
For the D1% parameter, there is no change in dose in the perturbation of the Clinical
plan, but a significant increase in dose for the VMAT technique is observed.
For the skin structures, shifts towards the surface result in a reduction in dose for the
VMAT plan, but only reduces the minimum dose parameter for the Clinical plan. For
shifts away from the surface there is a modest decrease in minimum and average skin
dose parameters for the Clinical plan, and for the VMAT plan, as was seen in the
PTVtoSurface structure, a significant increase in maximum dose.
104
a)
b)
c)
d)
Figure 5.3: Example of DVHs for Skin3mm a)Clinical plan non-perturbed v Clinical plan perturbed 0.5 in TS direction b) Clinical plan non-perturbed v Clinical plan perturbed 0.5cm in AS direction c)VMAT plan non-perturbed v VMAT plan perturbed 0.5cm in TS direction d) VMAT plan non-perturbed v VMAT plan perturbed 0.5cm in AS direction. (Dotted line = original plan, dashed line = perturbed plan)
105
Figure 5.4 : Bar chart showing the perturbation effect on the parameters D99%, average dose and D1%, for the Skin3mm. The graph shows the impact for both Clinical and VMAT plans. (Non-perturbed = blue, perturbation 0.5cm TS = red and perturbation 0.5cm AS= green).
5.2.4 Perturbation Effect – Organs at Risk (single patient example)
The DVHs shown in Figure 5.5 and dose parameters in Table 5.4 and Table 5.5
demonstrate the impact of a 0.5cm perturbation on the heart, lung and contralateral
breast. The effect of perturbation in the TI and AI directions are shown as they
represent the worse-case scenario in the superior/inferior direction. The same impact
on dose is observed for the Clinical and VMAT plans. Perturbation towards the patient
surface (TI) reduces the dose to the heart and lung, and shifts away from the surface
(AI) increases the dose. A 0.5cm shift away from the patient surface results in both the
Clinical and VMAT plans exceeding the required dose constraint for lung, and for the
VMAT plan the heart V5% parameter is also exceeded.
There is minimal impact on the contralateral breast dose with perturbation of both the
Clinical and VMAT plans.
106
a)
b)
c)
d)
Figure 5.5: DVH for Heart (Red) Ipsilateral Lung (Orange) and Contralateral Breast (Blue) a)Clinical plan non-perturbed v Clinical plan perturbed 0.5 in TI direction b) Clinical plan non-perturbed v Clinical plan perturbed 0.5cm in AI direction c)VMAT plan non-perturbed v VMAT plan perturbed 0.5cm in TI direction d) VMAT plan non-perturbed v VMAT plan perturbed 0.5cm in AI direction. (Dotted line = original plan, dashed line = perturbed plan)
107
Structure Dosimetric Parameter
Mandatory Constraint
Optimal Constraint
Non-Perturbed (Clinical)
0.5cm TI Shift
0.5cm AI Shift
Heart
Ipsilateral Lung
Contralateral
Breast
V25% (10Gy) V5% (2Gy) V30%(12Gy) Mean Dose
≤5% ≤30% ≤17%
≤15% <3.5Gy
0% 6.4% 13.6% 0.3Gy
0% 2.9% 6.5% 0.2Gy
0.8% 13.7% 23.9% 0.3Gy
Table 5.4: Example of dosimetric parameters for the non-perturbed Clinical plan and with a perturbation of 0.5cm in the TI and AI directions. Values underlined show where constraints were not met.
Structure Dosimetric Parameter
Mandatory Constraint
Optimal Constraint
Non-perturbed (VMAT)
0.5cm TI Shift
0.5cm AI Shift
Heart
Ipsilateral Lung
Contralateral
Breast
V25% (10Gy) V5% (2Gy) V30%(12Gy) Mean Dose
≤5% ≤30% ≤17%
≤15% <3.5Gy
0% 29.9% 7.1% 2.0Gy
0% 22.3% 1.6% 2.0Gy
0% 42.3% 18.7% 2.2Gy
Table 5.5: Example of dosimetric parameters for the non-perturbed VMAT plan and with a perturbation of 0.5cm in the TI and AI directions. Values underlined show where constraints were not met.
With both the Clinical and VMAT plans, perturbation can result in dose constraints
being exceeded.
5.2.5 Perturbation Effect – PTVtoSurface (8 patient study set)
Figure 5.6 shows the difference in volume of the perturbed plans compared to the
non-perturbed plan, for the PTVtoSurface dosimetric parameters V95%, V105% and
V107%. The difference in volume is the average of the 8 patient cases, data is shown
for the Clinical and VMAT techniques and perturbations of 0.5cm and 0.3cm (Appendix
4, Table A4.1 includes the range of values for each of these parameters over the 8
patients). Similarly Figure 5.7 shows the dose difference averaged over the 8 cases, for
the mean dose to the PTVtoSurface and D1%. From these graphs it can be seen that
108
perturbation of the VMAT plan has a greater effect than perturbation of clinical plans.
As expected the magnitude of the effect is reduced with smaller shifts.
For both the Clinical and VMAT plans shifts towards the patient surface result in a
decrease in the V95% value, with the greatest impact seen for the VMAT plans. For a
0.5cmTS shift the decrease in V95%, for VMAT plans, compared to the non-perturbed
plan was on average 43.5%, ranging from 22.6%-68.1% over the 8 patients (see
Appendix 4, Table A4.1). For the Clinical plans with the same shift the decrease in
V95% was on average 23.4% (ranging from 14.9% to 29.9% over the 8 patients). A
smaller decrease in V95% is also seen for the Clinical plans with shifts away from the
patient surface. For the VMAT plans shifts away from the surface result in small
changes and in all but the 0.5cm AI direction, a slight increase in dose can be observed.
For the V105% and V107% parameters perturbation in any direction result in an
increase in PTVtoSurface volume receiving this dose. For the Clinical plans the greatest
difference between non-perturbed and perturbed, is with a shift of 0.5cm towards the
surface, which results on average with a volume difference <5%. For the VMAT plans
shifts away from the surface results in the greatest differences, with dose differences
of 52% on average for the V105% parameter for a 0.5cmAS shift, with this value
ranging from 22.1% to 73.4% across the 8 patients (Appendix 4, Table A4.1).
In Figure 5.7 it can also be observed that the impact of perturbation is in general more
signficiant for the VMAT plans. For the Clinical plans perturbation in any direction
reduces the average dose to the PTVtoSurface and increases the maximum dose, the
plans become less homogeneous. For the VMAT plans the average dose and maximum
dose, increase with shifts away from the surface. The maximum dose also increases
slightly with shifts towards the surface but average dose decreases. The average D1%
dose difference is 9.9Gy, for a shift in the 0.5cm AS direction, ranging from 6.2Gy to
15.3Gy, over the 8 patients (Appendix 4, Table A4.1).
109
Figure 5.6: Bar chart showing perturbation effect on the parameters V95% (blue), V105% (red) and V107% (green), displayed as volume difference from non-perturbed plan, for PTVtoSurface, averaged for 8 patient cases. The graph shows the impact for both Clinical and VMAT plans.
Figure 5.7: Bar chart showing perturbation effect on the parameters average dose (blue) and D1% (green), displayed as dose difference from non-perturbed plan, for PTVtoSurface, averaged for 8 patient cases. The graph shows the impact for both Clinical and VMAT plans.
110
Figure 5.8: Bar chart showing V95% for PTVtoSurface, averaged over 8 patients, under the indicated perturbation conditions. Clinical Plans (blue) and VMAT plans (red). (Dotted line = mandatory constraint, dashed line = optimal constraint)
Figure 5.9: Bar chart showing V105 values% for PTVtoSurface, averaged over 8 patients, under the indicated perturbation conditions. Clinical Plans (blue) and VMAT plans (red). (Dotted line = mandatory constraint, dashed line = optimal constraint)
111
Figure 5.10: Bar chart showing V107% values for PTVtoSurface, averaged over 8 patients, under the indicated perturbation conditions. Clinical Plans (blue) and VMAT plans (red). (Dotted line = mandatory constraint)
Figure 5.11: Bar chart showing D1% values for PTVtoSurface, averaged over 8 patients, under the indicated perturbation conditions. Clinical Plans (blue) and VMAT plans (red). (Dotted line = mandatory constraint)
112
Figure 5.8-Figure 5.11 shows the impact that the perturbation has on achieving the
required plan objectives and constraints. The data in the bar charts is the average
parameter value over the 8 patients, Appendix 4, Table A 4.2, includes additional
information on the range of these values. Figure 5.8 shows that on average the Clinical
plans only maintain the mandatory objective for V95% if the shift is <0.3cm away from
the patient surface. The range for perturbation in the 0.3cmAS perturbation direction
over the 8 patients was 84.9% to 95.2%, therefore in some cases the mandatory
objective was not achieved (Appendix 4, Table A4.2). In the other perturbation
situations the mandatory objective is, on average no longer achieved. For the VMAT
plans this objective is not achieved if perturbation is towards the patient surface.
However, for shifts up to 0.5cm away from the surface, the mandatory objective it is
maintained and this was seen across all the 8 patients (Appendix 4, Table A4.2). Figure
5.9 and Figure 5.10 show that the mandatory constraints for the parameters V105%
and V107%, are met, on average, for the Clinical plans, for perturbations of up to
0.5cm in any direction. For the VMAT plans shifts away from the surface significantly
exceed the mandatory constraints. The same is observed for the D1% parameter
(Figure 5.11).
Perturbation of the VMAT plans has a greater impact on the PTVtoSurface plan
evaluation parameters than the Clinical plans. Perturbation of both techniques can
result in mandatory objective for V95% not being achieved however the perturbation
of VMAT plans can result in dose volumes and doses that significantly exceed
mandatory planning constraints.
5.2.6 Perturbation Effect – Skin Structures (8 patient study set)
Figure 5.12 shows the difference in dose of the perturbed plans compared to the non-
perturbed plan, for the Skin3mm structure, for the dosimetric parameters D99%,
average dose and D1%. Dose differences are averaged across the 8 patients, for the
Clinical and VMAT techniques, and perturbations of 0.5cm and 0.3cm 3cm (Appendix 4,
Table A4.3 includes the range of values for each of these parameters over the 8
patients). Data for Skin3mm is shown, but the same trends were observed for the
Skin1mm and Skin5mm structures.
As was observed with the PTVtoSurface structure, in Figure 5.12 it can be seen that the
dose to the skin is impacted more by perturbation in the case of the VMAT plans
113
compared to the Clinical plans. For the Clinical plans, the maximum dose is not
significantly impacted by perturbation in any direction. For the VMAT plans,
perturbation away from the skin surface results in an increase in maximum skin dose
and shift towards the surface reduces the dose. The size of the dose difference is
proportional to the size of the perturbation. A 0.5cm TS shift on average results in a
10.5Gy dose increase, ranging from a 6.2 to 16.2Gy increase over the 8 patients
(Appendix 4, Table A4.3).
Figure 5.13 shows the impact of perturbation on the absolute dose values for the D1%
parameter for Skin3mm, it can be seen that the D1% parameter is >44Gy for the VMAT
plans with shifts away from the surface and indicates that the maximum dose
parameter is more robust to perturbations in the case of the Clinical plan (Appendix 4,
Table A4.4 shows that this is consistent over all 8 patients).
Figure 5.12: Bar chart showing perturbation effect on the parameters D99% (blue), average dose (orange) and D1% (green) for Skin3mm, displayed as dose difference from non-perturbed plan, averaged for 8 patient cases. The graph shows the impact for both Clinical and VMAT plans.
114
In Figure 5.12 as was seen for the D1% parameter, perturbation in any direction have
minimal effect on the average dose to the skin structures in the Clinical plans. The
effect on the average dose parameter in the case of the VMAT plans is consistent with
the effect observed for the PTVtoSurface structure, shifts towards the surface
reducing the average dose and shifts away increasing it. As with the maximum dose
parameter, the larger the perturbation, the larger the dose difference from non-
perturbed plan.
Figure 5.13: Bar chart showing D1% values for Skin3mm, averaged over 8 patients, under the indicated perturbation conditions. Clinical Plans (blue) and VMAT plans (red).
For the minimum dose parameter, D99%, perturbation in any direction results in a
decrease in dose for the Clinical plan. For shifts away from the surface, the average
dose differences, in the case of Clinical plans are small <0.6Gy. For Clinical plans
perturbed towards the surface, the larger the perturbation the larger the dose
difference. For Clinical plans perturbed in the 0.5cmTS direction on average this dose
difference is 11.9Gy, ranging from 8.5Gy-17.3Gy over the 8 patients (Appendix 4, Table
A4.3). Similarly, for the VMAT plans a decrease in minimum dose is also observed for
perturbations towards the surface, for the same perturbation the average dose
difference is 10.6Gy, ranging from 7.8Gy-15.4Gy. However, for the VMAT plans
115
perturbations 0.3cm away from the surface slight increase in minimum dose is
observed.
Dose to the skin structures is more robust to perturbations of the Clinical plan than the
VMAT plan.
5.2.7 Perturbation Effect – Organs at Risk (8 patient study set)
Figure 5.14 and Figure 5.15 show the average impact of perturbation on the heart
parameters for the left chest-wall cases, Appendix 4 Table 4.5 includes the range of
these values. The right sided cases have been excluded from this data as the location
of the heart results in significantly smaller doses that skew the results. As expected,
the general trend is that if the plan is perturbed away from the patient surface the
volume of the heart that receives dose increases and moving towards the surface the
volume irradiated decreases. The size of this volume correlates with the size of shift. In
addition, a perturbation in the inferior direction also impacts the volume differences
due to the location of the heart.
In Figure 5.14 it can be seen that slightly greater volume differences are observed, for
the V25% heart parameter, in the Clinical plans. The greatest difference in volume is
observed with shifts in the 0.5cmAI direction, for both techniques. However, since the
non-perturbed volumes for the Clinical and VMAT plans are 0.3% and 0.2%,
respectively, the effect of perturbation would need to increase the irradiated heart
volume by 4.7% before the dose constraint was exceeded (V25% <5%). Appendix 4,
Table 4.5 indicates that this was not exceeded in any of the patient cases.
A 0.5cm perturbation away from the patient surface also has the greatest impact on
the V5% heart parameter. In Figure 5.15 the V5% is shown for the left chest-wall
patients with the plans perturbed in this worse-case scenario. It can be seen that for
the Clinical plans the heart constraint is still met with a shift in this direction, however
in some cases the VMAT plans exceed this.
116
Figure 5.14: Bar chart showing perturbation effect on the V25% for the heart, displayed as volume difference from non-perturbed plan, averaged over left-sided cases (n=5). The graph shows the impact for both Clinical and VMAT plans.
Figure 5.15: Bar chart showing V5% (2Gy) for heart for plans perturbed in the 0.5cm AI direction. The graph shows the impact for both Clinical and VMAT plans (Dotted line=mandatory constraint).
117
Figure 5.16: Bar chart showing perturbation effect on V30% for the ipsilateral lung, displayed as volume difference from non-perturbed plan, averaged over the 8 patient cases. The graph shows the impact for both Clinical and VMAT plans (Dotted line = mandatory constraint permitted, based on volume irradiated in non-perturbed plan)
Figure 5.16 shows the impact of perturbing the plans on the ipsilateral lung volume, as
with the heart volumes a shift away from the patient surface increases the ipsilateral
lung volume irradiated and shifts towards the surface reduce this. The mandatory
constraint for the lung volume receiving 30% (12Gy) is ≤17%. The average non-
perturbed volume for the VMAT plan is 8.4% and for the Clinical plan 11.7%, therefore
for the perturbation effect to not exceed the mandatory constraint, a volume
difference of <8.6% and <5.3%, respectively is required. Figure 5.16 shows that with
the Clinical technique the 0.5cm shifts away from the surface are both > 5.3%, so
exceed the mandatory constraint (Appendix 4, Table 4.5 shows this range was from
2.2% to 12.4ki%), but the smaller 0.3cm perturbations and perturbation on the VMAT
plans are still, on average, within the required tolerance.
In Figure 5.17 the effect of plan perturbation is shown for the contralateral breast
dose. The perturbation of VMAT plans show slightly greater dose differences than the
Clinical ones, the size of the dose difference is proportional to the shift and shifts away
from the patient surface increase the dose with a decrease in dose with shifts towards
118
the surface. However, it should be noted that these dose differences are very small <
0.1Gy, so unlikely to be clinically significant. In addition, the average contralateral
breast dose for the non-perturbed Clinical plan was 0.3Gy and for the VMAT plan,
1.7Gy, therefore an increase of 0.1Gy would not exceed the tolerance of 2.5Gy.
The direction of plan perturbation had the expected effect on organ at risk dose, with
shifts towards the patient surface (away from heart and lung) reducing the volume
irradiated, and shifts away from the patient surface, increasing the volumes irradiated,
with the size of volume difference was proportional to the size of the shift.
Perturbation resulted in organ at risk dose constraints being exceeded for both Clinical
and VMAT plans.
Figure 5.17: Bar chart showing perturbation effect on contralateral breast, displayed as dose difference from non-perturbed plan, averaged over the 8 patient cases. The graph shows the impact for both Clinical and VMAT plans.
5.3 Discussion
In Chapter 3 it was concluded that VMAT plans could be created that produced dose
distributions resulting in near equivalent target and skin doses compared with Clinical
119
plans using bolus, and that met the dosimetric requirements for organs at risk, heart
and lung.
In this section the effect of set-up errors and patient contour changes on the Clinical
and VMAT plans have been investigated by applying shifts to the treatment plans and
analysing the impact on the plan evaluation parameters for target structure, skin doses
and organs at risk.
For both the Clinical and VMAT plans it was observed that shifts towards the patient
surface resulted in a decrease in PTVtoSurface volume receiving 95% of the
prescription dose, this resulted in mandatory planning objectives failing to be
achieved. The reduction in V95% is a result of the posterior edge of the target no
longer being covered by the beams, this effect is demonstrated in Figure 5.18.
a)
b)
Figure 5.18: DRRs displaying treatment field segment for a)non-perturbed Clinical plan b) Perturbed plan 0.5cm in TS direction showing PTVtoSurface (green contour) no longer fully covered.
It was seen in the DVHs, Figure 5.2a and Figure 5.2c, that the reduction in V95%, was
more significant for the VMAT plan compared to the Clinical plan, for shifts towards
the surface, suggesting that for the VMAT plans, this is not just an effect of reduced
posterior edge coverage. The reduction in skin dose also observed for VMAT plans
120
perturbed in this direction (Figure 5.3c), suggests that lack of dose coverage over the
anterior aspect of the target volume is causing this difference. In Figure 5.19 a typical
segment produced for VMAT plans is shown, non-perturbed and perturbed. It can be
seen that in the original plan the segment exposes the superficial edge of the
PTVtoSurface structure, however with the shift, most of the segment is treating air. It
is this effect that causes the V95% PTVtoSurface to be impacted more by shifts
towards the surface for VMAT plans.
The reduction in V95% for the Clinical and VMAT plans caused by under-coverage at
the posterior edge could be considered not clinically significant. This is because the
PTVtoSurface already contains a margin to take into account the effect of set-up
errors. In retrospect analysis of a CTVtoSurface structure would have been more
appropriate.
a)
b)
Figure 5.19: Typical MLC segments for VMAT plan a) Non-perturbed b) Perturbed plan 0.5cm in TS direction showing segment now outside PTVtoSurface (green contour).
121
A slight reduction in the PTVtoSurface V95% was also observed for the Clinical plans,
when the shifts were away from the patient surface. This is most likely due to the
segmented MLCS shielding a slightly larger proportion of the target area. For the VMAT
plans the V95% is largely unaffected by shifts in this direction. However unlike for the
Clinical cases, perturbation away from the surface for the VMAT plans result in the
PTVtoSurface V105%, V107% and D1% values increasing significantly. The increase
exceeds mandatory planning constraints, even with the smaller perturbation of 0.3cm.
A similar trend is observed with the maximum dose to the skin structures. This is as a
result of segments in the non-perturbed plan requiring high fluences to over-come the
build-up effect at the skin surface to deliver the required dose to the superficial
aspects of the PTVtoSurface structure. When the plan is shifted the high fluence
segments then intersect the patient where overcoming the build-up effect is not
required, resulting in significant dose to that tissue.
For the PTVtoSurface and skin structures a greater perturbation effect was seen for the
VMAT plans compared to the Clinical plans, however the same trend was not observed
for the organ at risk dose evaluation parameters with the size of the effect similar for
both techniques. The direction of perturbation effected the dose parameters as
expected, in both cases, with a shift towards the patient surface (away from heart and
lung) decreasing the organ at risk values and shifts away from the surface, increasing
them. With shifts away from the patient surface, mandatory planning constraints for
heart were shown to be exceeded with the VMAT plans, but similarly the ipsilateral
lung constraint was exceeded with the Clinical plans.
The consequences of the perturbation effect causing an underdose the target and skin
surface, is that this could affect the local control of the tumour. Perturbation resulting
in excess dose to target, skin or organs at risk could also be detrimental, resulting in
side-effects such as erythema, moist desquamation, pneumonitis or cardiomyopathy.
Although the effect of perturbation demonstrates the impact of set-up uncertainties
associated with radiotherapy deliveries, it also indicates the impact changes in the
patient contour could have, as a result of increase/decrease in swelling or weight gain
or loss.
122
5.4 Summary
VMAT plans can be created that produce similar dose distributions to the
Clinical technique using bolus however perturbation can result in under-dose or
over-dose of targets and organs at risk.
VMAT plans are not as robust as the Clinical plans with regards to target and
skin dose.
123
Chapter 6
6 Robust Optimisation
In the previous chapters it was demonstrated that VMAT plans can be created that
achieve similar target coverage and skin doses to plans produced clinically with the use
of bolus, whilst meeting organ at risk dose requirements. However, investigations
showed that VMAT plans failed to maintain target coverage when perturbations were
applied, resulting in large, high dose volumes that would unacceptable clinically. This
section investigates whether the addition of robust optimisation can resolve this issue.
The concept of plan robustness can be defined by its ability to maintain its dosimetric
qualities, which define its tumour control rate and normal tissue toxicities, despite,
changes in set-up position and variations in patient anatomy. Variations in patient
anatomy can be caused by a number of factors including change in breast shape due to
weight gain or loss, or reduction/decrease in swelling post-surgery. Limitations to the
traditional approach to maintain target coverage and organ at risk constraints, with
the use of margins around the structures, has been discussed in the introduction.
Alternative techniques to the margin approach include the optimisation of dose
distributions in different scenarios such as geometric position, using the minimax
method, as is available in RayStation. The minimax approach aims to minimise the
objective function in the worse-case scenario (e.g. the geometric position that
produces the worst result).
This chapter therefore investigates whether the addition of this optimisation feature
can produce VMAT plans that are more robust to the impact of patient movement.
6.1 Method
RayStation uses the minimax robust optimisation method whereby the objective
function is minimised in the worse-case scenario. In this study the maximum errors in
patient position were set as 0.5cm in the anterior-posterior, left-right and superior-
124
inferior directions, generating 7 scenarios to compute. For simplicity all beams were
assumed to move together (i.e. an overall isocentre shift) rather than moving
independently to each other.
As in Chapter 3, VMAT plans were created for the 8 patient cohort and consisted of
two 360⁰ arcs, collimator set to 10⁰, using a 6MV FFF beam energy. The same beam
optimisation parameters and the same starting objectives were used. The patient
position uncertainty (robustness objective) was assigned to the PTVtoSurface
minimum and maximum dose objective functions, and in cases where the heart was in
close proximity to the PTVtoSurface structure, the robustness objective was also
applied. These plans are referred to as VMATRO. As previously a dose grid of 3mm was
used (supplementary information is provided in Appendix 1 showing impact of dose
grid selection).
The robust optimisation procedure is likely to produce plans that are compromised in
some quality compared to standard optimisation as additional objectives increase the
complexity of the mathematical problem and concessions to the dose distribution will
be needed somewhere. These VMATRO were therefore assessed against the dose
evaluation metrics previously used to test for any degradation in plan quality.
The VMATRO plans were then perturbed as in the previous section by 0.5cm and
0.3cm in the TS, TS, AS and AI directions Figure 5.1 to assess to what extent the robust
optimisation function maintains plan quality when patient movement is applied.
6.2 Results
Previously it was concluded that VMAT plans could be created with dose distributions
that were equivalent to the current Clinical technique in reference to target coverage
and resulted in similar skin dose parameters. However, perturbation of the VMAT
plans in one direction resulted in greater under-dosage of the target compared with
the Clinical plan, and significant over dosage in the other.
In this section the results presented include evaluation of the VMATRO technique
against the other treatment plans using the previously described evaluation metrics,
and a comparison of the perturbation effect on VMATRO with the other treatment
125
techniques, to assess whether the use of robust optimisation on VMAT plans resolves
the issue of under and over-dosage.
6.2.1 Plan comparison – Dose Distribution (single patient example)
Figure 6.1 shows the difference in dose distribution between the VMAT and VMATRO
plans. From the dose difference map (Figure 6.1b) it is observed that the area of tissue
posterior to the target structure is receiving more dose, this is to ensure that with
perturbation away from the patient surface the target is still covered. The dose
difference map also indicates that the dose to the surface is lower.
6.2.2 Plan comparison – PTVtoSurface (single patient example)
From the DVH for the PTVtoSurface structure in Figure 6.2, the gradients of the curves
indicate that the VMATRO plan is not quite as homogeneous as the VMAT plan though
more homogeneous that the Clinical plan.
Table 6.1 shows that there is some slight degradation in the VMATRO plan compared
to VMAT and Clinical plans with regards to V95% parameter, however these
differences are small, and it still meets the optimal constraint. Hotspots are still
reduced, and homogeneity remains increased relative to the Clinical plan.
6.2.3 Plan comparison – Organs at Risk (single patient example)
Table 6.2 shows that the VMATRO meets the mandatory and optimal heart, ipsilateral
lung and contralateral breast constraints. In the case of the VMATRO plan, as with the
VMAT plan, for the low dose parameter to the heart, V5%, the volume is significantly
greater than the Clinical and No Bolus plans, this is due to the low dose bath using the
VMAT techniques. The volume however is lower for the VMATRO plan than the VMAT
plan and this will be due to the robustness objective added to the heart in the plan
optimisation. For the ipsilateral lung the V30% parameter for the VMATRO plan is 1.3%
more than the VMAT plan, this is as a result of the additional dose beyond the back
edge of target structure, observed in Figure 6.1 and the robustness objective not
added to the lung as part of the plan optimisation.
126
a)
b)
c)
Figure 6.1: Dose distribution a)VMATRO plan b)VMAT plan c) dose difference between VMATRO and VMAT
Figure 6.2: DVH for PTVtoSurface for example patient. The dashed line represents the Clinical Plan, the dotted line the VMAT plan and the solid line is the VMATRO plan
127
Structure Dosimetric Parameter
Mandatory Constraint
Optimal Constraint
Clinical Plan
No Bolus Plan
VMAT Plan
VMATRO Plan
PTVtoSurface V95% V105% V107% D1 % Average
≥ 90% ≤ 7% ≤ 2% ≤ 110%
≥ 95% ≤ 5%
96.0% 1.1% 0.0% 104.9% 40.0Gy
92.4% 1.7% 0.1% 105.4% 39.8Gy
96.6% 0.2% 0.0% 103.6% 40.0Gy
95.8% 0.3% 0% 104% 39.9Gy
Table 6.1: Dosimetric parameters achieved for PTVtoSurface single patient example. The mandatory and optimal constraints are defined.
Structure Dosimetric Parameter
Mandatory Constraint
Optimal Constraint
Clinical Plan
No Bolus Plan
VMAT Plan
VMATRO Plan
Heart
Ipsilateral Lung
Contralateral Breast
V25% (10Gy) V5% (2Gy) V30%(12Gy) Mean Dose
≤5% ≤30% ≤17%
≤15% <3.5Gy
0% 6.4% 13.6% 0.3Gy
0% 6.5% 13.4% 0.2Gy
0% 29.9% 7.1% 2.0Gy
0% 23.9% 8.4% 2.0Gy
Table 6.2: Dosimetric parameters achieved for organs at risk single patient example. The mandatory and optimal constraints are defined.
128
6.2.4 Plan comparison – PTVtoSurface (8 patient study set)
Figure 6.3 shows the grouped average results for the 8 patient cases, for each of the
dose evaluations parameters assessed for the PTVtoSurface structure. For the V95%
parameter, as was observed in the single patient example, the volumes for the
VMATRO plans suggest a slight degradation in plan quality compared to the VMAT
plans, however they are still comparable to the Clinical plans. For the average dose to
the PTVtoSurface the dose is slightly inferior compared to the VMAT plans but still
higher than the Clinical technique. For the V105% metric the VMATRO technique
creates plans with larger 105% hotspots than the VMAT and Clinical techniques, with
one patient exceeding the mandatory tolerance, V105% ≤7%, by 0.4%. A similar trend
is seen with the V107% and D1% parameters, but in these cases the VMATRO plans still
meet the plan objectives.
129
Figure 6.3: Box and Whisker plots showing the a) V95% b) average dose c) V105% d)107% and e) D1% parameters for the PTVtoSurface structures for No Bolus Plans (Blue), Clinical Plans (Red), VMAT Plans (Green) and VMATRO Plans (Purple) in the 8 patients.
a)
b)
c)
d)
e)
130
6.2.5 Plan comparison – Organs at Risk (8 patient study set)
The results in Figure 6.4 indicate that for the VMATRO plans all the organ at risk
dosimetric parameters used to define plan acceptability are met. For all the patients
the V30% lung parameter ≤17%, the heart V5%≤30%, the heart V25% ≤5% and the
contralateral breast mean dose <3.5Gy.
a)
b)
131
c)
d)
Figure 6.4: Dosimetric parameters for organs at risk a) Box and Whisker plot for Ipsilateral Lung V30% b) Bar Chart for Heart V5% (mandatory constraint shown in dashed line) c) Bar Chart for Heart V25% d) Box and Whisker plot for Contralateral Breast for No Bolus Plans (Blue), Clinical Plans (Red),VMAT Plans (Green) and VMATRO Plans (Purple) for the 8 patients.
These results show that the plans using robust optimisation remain clinically
acceptable with reference to the plan evaluation parameters for PTVtoSurface and
organs at risk. Where there is some compromise in V95% coverage compared to the
original VMAT technique, the coverage is still comparable to the Clinical technique and
132
hotter areas observed with the VMATRO plans, are still on average, within the planning
constraints.
6.2.6 Plan comparison – Skin Structures (8 patient study set)
Although the PTVtoSurface volume remains clinically acceptable it was also important
to determine the effect on skin doses and establish whether they are still equivalent to
technique using bolus. Figure 6.5 shows the D99% parameter for Skin3mm and shows
that the VMATRO plans result in a lower dose than the VMAT and Clinical plans, but
higher than without the use of bolus. The same trend was observed for the other skin
structures.
Figure 6.5: Box and Whisker plot showing the doses for the D99% parameter for the Skin3mm structure for the 8 patients for the No Bolus plans (Blue), Clinical plans (Red), VMAT plans (Green) and VMATRO plans (Purple)
For the D1% parameter, the dose variation between the techniques for all three skin
structures was <1.4Gy and all maximum dose parameters were <43.1Gy. Figure 6.6
shows the variation in maximum dose for the Skin3mm structure.
133
Figure 6.6: Box and Whisker plot showing the doses for the D1% parameter for the Skin3mm structure for the 8 patients for the No Bolus plans (Blue), Clinical plans (Red), VMAT plans (Green) and VMATRO plans (Purple)
Figure 6.7 shows a similar trend in effect for the average dose to all the skin structures
between the techniques, with the VMATRO plans resulting in a lower average dose
than the VMAT technique. For the structures, Skin3mm and Skin5mm, the VMATRO
plans demonstrate an equivalence in dose to the Clinical plans. However, in the
Skin1mm structure, the VMATRO plans result in a lower average dose than the Clinical
technique but compared to the No Bolus plans the median dose difference is 1.5Gy
greater.
As expected, the VMAT plans created using robust optimisation produce plans that
are slightly compromised compared with the original plans, but on the whole remain
clinically acceptable. The main differences are in the minimum dose to the skin
structures and average dose to the Skin1mm structure.
a) b)
134
c)
Figure 6.7: Box and Whisker plot showing the doses for the average dose parameter for the a) Skin1mm b) Skin3mm and C) Skin5mm structures for the 8 patients for the No Bolus plans (Blue), Clinical plans (Red), VMAT plans (Green) and VMATRO plans (Purple).
6.2.7 Perturbation Effect - PTVtoSurface
In the previous chapter it was concluded that whilst the VMAT plans, without bolus
were of similar quality to the Clinical plans, the impact of perturbations means these
should not be used clinically.
In this section the effect of perturbation is investigated for the VMATRO technique to
assess whether the robust optimisation removed this limitation.
Figure 6.8 shows the average change in volume seen for each of the parameters when
perturbations are applied over the 8 patients. Figure 6.8 demonstrates that the same
trend in perturbation effect is seen for the VMATRO plans as is seen in the VMAT
plans, but the magnitude of these effects is reduced.
For perturbation in the 0.5cm AS direction there is a reduction in V105% volume of
35.1% (52.1% to 17.0%), and for the V107% parameter a reduction of 38.4% (46.1% to
7.7%) between the VMAT and VMATRO techniques, with similar effects seen in the AI
135
direction. For a smaller perturbation of 0.3cm, in the AS direction the V105%
decreases from 38.7% to 8.2% and for V107%, a decrease from 30.9% to 2.7% can be
observed. However, as with the VMAT plans, on average the dose constraints for
V105% and V107% are exceeded, though not to the same extent, Figure 6.9 and Figure
6.10. It should be noted that for perturbations in the 0.3cm AS direction the volumes
for the V105% and V107% parameters, in the VMATRO plans, range from 4.9% to
20.2% and 0.4% to 9.5% respectively, so although on average across all patients the
constraint is exceeded, in some patient cases the constraints are met (Appendix 4,
Table A4.1).
For perturbations towards the surface, the volume difference for the V95% parameter
is less for the VMATRO plans compared with the VMAT plans (Figure 6.8). The average
volume difference for VMATRO plans perturbed in a 0.5cm TS direction is 16.5% less
than the VMAT plans, with a similar magnitude difference seen in the 0.5 TI direction.
A similar trend is observed for 0.3cm perturbations towards the surface resulting in
the impact of perturbation on V95% for the VMATRO plans, being equivalent to that of
the Clinical plan. Figure 6.11 shows the impact that the perturbation has on achieving
the mandatory and optimal constrains for V95% parameter. It can be seen that with
perturbations away from the surface the VMATRO plans maintain the V95% value
better than the VMAT plans, however this is well below the mandatory value. For shifts
away from the surface the V95% mandatory objectives are achieved for the VMATRO
plans for all shifts except in the 0.5cmAI direction.
136
Figure 6.8: Bar chart showing perturbation effect on the parameters V95% (blue), V105% (red) and V107% (green), displayed as volume difference from non-perturbed plan, for PTVtoSurface, averaged for 8 patient cases. The graph shows the impact for Clinical, VMAT and VMATRO plans.)
137
Figure 6.9: Bar chart showing V105% values for PTVtoSurface, averaged over 8 patients, under different perturbation conditions. Clinical Plans (blue), VMAT plans (red) and VMATRO (green). (Dotted line = mandatory constraint, dashed line = optimal constraint)
Figure 6.10: Bar chart showing V107% values for PTVtoSurface, averaged over 8 patients, under different perturbation conditions. Clinical Plans (blue) and VMAT plans (red (Dotted line = mandatory constraint)
138
Figure 6.11: Bar chart showing V95% for PTVtoSurface, averaged over 8 patients, under different perturbation conditions. Clinical Plans (blue), VMAT plans (red) and VMATRO (green). (Dotted line = mandatory constraint, dashed line = optimal constraint)
Figure 6.12: Bar chart showing perturbation effect on the parameters average dose (blue) and D1% (green), displayed as dose difference from non-perturbed plan, for PTVtoSurface, averaged for 8 patient cases. The graph shows the impact for Clinical, VMAT and VMATRO plans.
139
Figure 6.12 demonstrates that the average dose parameter for perturbed VMATRO
plans show less dose difference than perturbed VMAT plans. The same trend is
observed for VMATRO and VMAT plans, that perturbed plans shifted by a greater
distance result in a larger dose difference. VMATRO and Clinical plans perturbed
towards the surface result in similar dose differences. The dose difference for the
maximum dose parameter is also reduced with the VMATRO technique. The average
value for D1% for the non-perturbed VMATRO plan was 42.4Gy, therefore all
perturbations except 0.5cm AS (1.8Gy) meet the required dose constraint, 44Gy.
The PTVtoSurface structure is more robust for the VMATRO plans than the VMAT
plans, however still not as robust as Clinical plans. Although the maximum dose
volumes for the VMATRO are reduced compared to the VMAT plans, the dose
objectives associated with hotspots are still exceeded.
6.2.8 Perturbation Effect – Organs at Risk
Figure 6.13, Figure 6.14 and Figure 6.15 show the effect of perturbing the treatment
plans on; the ipsilateral lung receiving 30% of the prescription dose, the heart volume
receiving 5% of the prescription dose, and the mean dose to the contralateral breast.
Unlike the trend observed in the dose evaluation parameters for the PTVtoSurface,
where it was clear that the robust optimisation reduced the effect of perturbation, the
same is not true for the organs at risk. However, this is as expected as apart from in
the cases where the heart was in very close proximity to the target structure, the
robustness objective was only applied to the PTVtoSurface structure and therefore no
worse-case scenario optimisation occurred. In the case of the VMATRO plans the
effect of non-robustness and the additional dose spillage covering the posterior edge,
as shown in Figure 6.1, results in the dose constraint being exceeded for the ipsilateral
lung V30% parameter when perturbed 0.5cm in the AI direction. For the heart V5%
parameter the effect of applying the robustness objective can be seen in the cases
cw17 and cw23, where the volume receiving 5% of the prescription dose is lower for
the non-perturbed VMATRO plan than the non-perturbed VMAT plan. However, it is
140
suggested that the objective weighting was not sufficient as the heart constraint is still
exceeded in several cases.
In Figure 6.15, it can be seen that the perturbed doses to the contralateral breast are
greater for the VMATRO plans than the VMAT plans and this could be due to a trade-
off for maintaining the robustness of the PTVtoSurface structure. However, the dose
differences are very small, with the largest difference in dose =0.26Gy, for
perturbation in the 0.5cm AI direction. With a non-perturbed mean contralateral
breast dose of 1.8Gy, the perturbed VMATRO plans would still be within the tolerance
of 3.5Gy.
Figure 6.13: Bar chart showing perturbation effect on V30% for the ipsilateral lung, displayed as volume difference from non-perturbed plan, averaged over the 8 patient cases. The graph shows the impact for Clinical, VMAT and VMATRO plans. (Dotted line=mandatory constraint permitted, based on volume irradiated in non- perturbed plan. For the Clinical plan the average non-perturbed volume = 11.7%, for the VMAT plan the average non-perturbed volume = 8.4% and for the VMATRO the average non-perturbed volume = 10.1%. The constraint for V30% < 17%, therefore permitted constraint for perturbation is 5.3%, 8.6% and 6.9% for Clinical, VMAT and VMATRO plans, respectively).
141
Figure 6.14: Bar chart showing V5% (2Gy) for heart for plans perturbed in the 0.5cm AI direction. The graph shows the impact for Clinical, VMAT and VMATRO plans (Blue bars= non-perturbed, red bars=perturbed, dotted line=mandatory constraint)
Figure 6.15: Bar chart showing perturbation effect on contralateral breast, displayed as dose difference from non-perturbed plan, averaged over the 8 patient cases. The graph shows the impact for Clinical, VMAT and VMATRO plans.
142
For the organs at risk, as expected, the VMATRO plans were no more robust that the
VMAT or Clinical plans as the robustness objective was not routinely added to these
structures.
6.2.9 Perturbation Effect – Skin Structures
Figure 6.16 demonstrates for Skin3mm, the impact robust optimisation has on the
perturbation effect for the dosimetric parameters D1%, Average dose and D99%. Both
the Skin1mm and Skin5mm structures followed the same trend. In Figure 6.17 it can be
seen that for the VMATRO, the absolute doses for D1% are reduced to a value <44Gy
for the Skin3mm structure, even when perturbed, this was also observed for the 1mm
and 5mm volumes. A similar consistency in dose is observed in Figure 6.18,
demonstrating the perturbation effect for the average dose parameter.
With regard to the D99% parameter, perturbation towards the patient surface for
VMATRO plans result in a smaller dose difference compared to VMAT or Clinical plans
and perturbation away from the surface for the VMATRO plans the dose difference is
greater (the same effect was observed in the 1mm and 5mm structures). In Figure 6.19
the effect of perturbation can be seen on the D99% parameter, for the 3mm skin
structure, in direct comparison with the non-perturbed doses. It is observed that the
non-perturbed, D99% value, for the Clinical and VMAT plans, the doses are greater
than in the VMATRO cases. However, in some situations under perturbation, for
example 0.5cmTS, the VMATRO plans maintain a higher dose.
143
Figure 6.16: Bar chart showing perturbation effect on the parameters D99% (blue), average dose (orange) and D1% (green) for Skin3mm, displayed as dose difference from non-perturbed plan, averaged for 8 patient cases. The graph shows the impact for Clinical, VMAT and VMATRO plans.
Figure 6.17: Bar chart showing D1% values for Skin3mm, averaged over 8 patients, under different perturbation conditions. Clinical Plans (blue), VMAT plans (red) and VMATRO plans (green).
144
Figure 6.18: Bar chart showing average dose values for Skin3mm, averaged over the 8 patients, under different perturbation conditions. Clinical Plans (blue), VMAT plans (red) and VMATRO plans (green).
Figure 6.19: Bar chart showing D99% values for Skin3mm, averaged over 8 patients, under different perturbation conditions. Clinical Plans (blue), VMAT plans (red) and VMATRO plans (green)
Dose to the skin structures is more robust to perturbations for the VMATRO plans
compared to the VMAT plans. The maximum dose to the skin is controlled with the
VMATRO plans and the variation in minimum and average dose to the skin is reduced.
145
However, the values for the average and minimum dose parameters for the non-
perturbed VMATRO plans are slightly compromised compared to the VMAT and
Clinical plans.
6.3 Discussion
In this chapter the VMAT plans using robust optimisation were investigated as an
alternative, single plan solution to the current technique for treating post-mastectomy
patients. Unperturbed VMATRO plans were shown to be clinically acceptable when
analysing the evaluation parameters for PTVtoSurface and OAR structures. There were
slight compromises to the D99% parameter for all the skin structures, and a
compromise to the average dose parameter to the Skin1mm structure, as compared to
the Clinical technique.
Robust optimisation increased the resilience of the VMAT plans to perturbations. For
the PTVtoSurface structure, robust optimisation reduced the V105% and V107%
parameters by 35.1% and 38.7% respectively, for perturbations in the 0.5cm AS
direction. However, despite this significant reduction the volumes still exceeded the
plan objectives. The coverage of the PTVtoSurface was also shown to be better
maintained in the VMATRO plans than the VMAT plans, when perturbations were
towards the patient surface, however the V95% parameter still appeared to fall below
the mandatory required value. This may however be clinically inconsequential as the
use of robust optimisation should negate the need for a posterior margin that is
included in this PTV, and a more appropriate evaluation structure, CTVtoSurface, could
have been used.
No change in doses to the organs at risk; heart, ipsilateral lung and contralateral breast
were observed as the robust optimisation objective was not assigned to these organs
in most cases. The impact the objective does have if used on the heart constraint can
be seen in the patient example, with the V5% reduced from 29.9% to 23.9%, with the
VMATRO technique compared to the VMAT plan. For the ipsilateral lung V30%
parameter it can be seen that without using the robust optimisation objective on the
structure, the mandatory constraint is exceeded with shifts away from the patient
146
surface. This will in part be due to the spillage dose the VMATRO plans create at the
back edge of the target structure to ensure that the PTVtoSurface is robust to these
perturbations. However, including the robust optimisation function in more
optimisation objectives, will increase the calculation time. In addition, since
PTVtoSurface already contains a margin for this posterior edge, it may be more
appropriate to optimise the VMATRO plans to CTVtoSurface, which would potentially
reduce dose to heart and lung.
As was observed in the PTVtoSurface structure the robust optimisation has the desired
effect reducing maximum dose to the skin structures in the perturbed plans. The dose
reduction is to a more acceptable dose, <110% of the prescription dose, however
these are still greater than doses observed in the Clinical plans. It can also be seen that
with the VMATRO plans, perturbations towards the surface result in the D99%
parameter for the skin structures being closer to their non-perturbed values. However,
compared to the Clinical and VMAT techniques the non-perturbed value is not as
great.
Despite results showing that the VMATRO technique can produce clinically acceptable
plans, based on the dose evaluation parameters and that for skin structures of 3mm
and 5mm, the average and max dose parameters, are comparable to plans with bolus,
there are drawbacks to the technique. The most concerning issue is the high doses in
the PTVtoSurface structure. Side effects from excess dose to chest-wall tissue can
include erythema, fibrosis, chronic pain, telangiectasia and cosmetic changes, all of
which can impact quality of life for the patient.
6.4 Summary
VMAT Plans using the robust optimisation feature remain clinically acceptable
with reference to the plan evaluation parameters for PTVtoSurface and organs
at risk.
The maximum dose to the skin parameters for the VMATRO plans is
comparable to the other techniques, as is the average dose for the Skin3mm
and Skin5mm.
147
The minimum dose to the skin structures is lower for the VMATRO plans than
the Clinical or VMAT plans but higher than without the use of bolus. This also
applies to the Skin1mm structure.
The use of robust optimisation on the target structure in VMAT plans can
impact the effect of perturbation, reducing hotspots and minimising under-
dose. However perturbed plans can still exceed dose constraints.
148
Chapter 7
7 Summary
This chapter summarises the main results of the thesis, discusses the limitations to the
work undertaken and suggests further investigations that could be carried out.
7.1 Overview of Results
Radiotherapy following surgery is routine practice for patients that have had a
mastectomy and are at a high risk of recurrence. The routine approach to treating
these patients is the use of high energy, tangential photons fields which are wide
enough to encompass any change in patient contour or inaccuracies due to patient set-
up. For patients requiring radiotherapy post-mastectomy it is also common practice to
use bolus for a proportion of the treatment fractions to ensure the dose to the surface
is sufficient, though there is little consensus on the exact dose that is required and the
use of bolus can vary between clinics. The requirement for two plans adds additional
time in the patient pathway, and the use of bolus can cause inaccuracies in skin dose
due to air gaps or errors due to failure to use it. The aim of the thesis was therefore to
investigate whether a single plan solution, without the use of bolus, was achievable.
Due to the lack of consensus in the radiotherapy community in defining the required
skin dose for this group of patients, and no consistency on how skin should be defined,
the new technique was compared to the current approach used within the clinic.
The impact of bolus was initially investigated. For a sample of 8 patients it was shown
that bolus used for 7 out of 15 fractions of treatment increased the target volume
receiving 95% of the prescription dose by 7.7% compared to using no bolus at all. The
minimum dose to the 3mm thickness skin structure was enhanced by 4.6Gy, the mean
dose increased by 1.5Gy and the use of bolus had no impact on organ at risk doses.
149
Similar dose enhancements were seen for the 1mm and 5mm skin structures, with the
greatest impact observed for the 1mm structure.
It was demonstrated that VMAT plans could be created and optimised that produced
dose distributions that met required dose objectives and enhanced target coverage
compared to the clinical technique. The average dose to the skin structures could be
enhanced more than with bolus, however the minimum dose could not be increased to
the same extent but was better than no bolus treatments. The VMAT plans were also
shown to produce a low dose bath which in some cases increased the doses to organs
at risk, however still met required dose constraints.
Due to known limitations in treatment planning systems, particularly in the superficial
regions at air-tissue interfaces, physical measurements with TLDs were carried out on
an anthropomorphic phantom. The results showed measurements of dose in the build-
up region were lower than the treatment planning system predictions by, on average
8.5% for tangential treatments and 6.2% for VMAT treatments. This was consistent
with published data and sources of inaccuracy.
For VMAT plans to achieve skin doses comparable to clinical plans the optimisation
process results in high fluence segments at the surface of the patient to overcome the
build-up effect. Change in shape or movement of the patient could therefore result in
different dose deposition and was therefore investigated. For the target and skin
structures, perturbation of VMAT plans resulted in greater differences for the
evaluation parameters than with the Clinical plans, suggesting the clinical plans are
more robust. The perturbation of VMAT plans, particularly with shifts away from the
patient surface resulted in significant increases in dose which were clinically
unacceptable. Whilst the difference in dose measurements compared to the treatment
planning system suggested that the superficial dose could be 6% lower than predicted,
these increases generated by perturbation, were less superficial than where the
measurements were acquired.
Finally, the use of the mini-max robust optimisation feature in RayStation was
investigated to see whether the use of robust optimisation combined with VMAT could
overcome the limitations seen using the VMAT method alone. The robust optimisation
150
objective was applied to the target structure. The results showed a significant
reduction in dose parameter difference in the target structure, for the perturbed
VMAT plans that had been robustly optimised, compared with the original VMAT
plans. This suggested that the robust optimisation had made some impact. A reduction
in the maximum dose to skin structures was also observed when the VMATRO plans
were perturbed. The perturbed VMATRO plans however still exceeded the target
structure maximum dose constraints. Organs at risk dose constraints were also
exceeded with perturbed VMATRO plans however robust optimisation constraints
were not always applied to these structures. The use of robust optimisation also
compromised the non-perturbed VMATRO plan, reducing the enhancement to the
superficial dose. The average dose to the 3mm and 5mm skin structures remained
comparable to the clinical technique but the average dose to the 1mm structure and
minimum doses to all the skin structures were not.
Although robustly optimised VMAT plans could be created to give similar dose
distributions to the clinical technique, there was some compromise to the skin
structure doses and perturbation of these plans still resulted in distributions that did
not meet accepted dose constraints within the target structure.
7.2 Limitations
There are limitations to the data presented. The patient cohort that was used was
small, n=8, and restricted to the criteria that the Clinical plan had been created using
6MV beams for the no-bolus proportion of the plan and 10MV for the bolus part. The
small number of patients restricts confidence in the conclusions and as the choice of
energy impacts the skin dose, the findings using skin structures for comparison, are
only applicable to this group. The group of patients was also made up of both left and
right sided chest-wall sites, the position of the heart towards the left of mid-line,
meant that conclusions presented for heart doses were further impacted by the effect
of small patient numbers.
151
The data in this study represents the worst-case scenario situation, with perturbations
assumed to be in the same direction for all 15 treatments and also assumes motion in
of a rigid body. In addition, only perturbations up to 0.5cm have been examined. If the
trend is consistent with observations seen, greater perturbations will cause an increase
in the dose difference, particularly with parameters defining the hotter dose
distribution.
As previously discussed, the robust optimisation within the treatment planning
software is based on the minimax solution where the aim is to minimise the treatment
planning objective functions for the worst geometrical position. As no probability
dependence is included in this optimisation, the minimax method could over optimise
in situations which are of low probability, resulting in compromised plan quality.
Although not currently available within this treatment planning software the use of the
VMAT technique in conjunction with probabilistic optimisation functions could
produce more favourable results.
It should be noted that conclusions presented for the use of VMAT and VMATRO plans
are based on the comparison between plans within the treatment planning system and
limited TLD measurements. No further assessment or measurements were carried out
on the treatment machine’s capability of delivering the dose accurately. Similarly, the
time taken to create the VMAT plans was not compared with the creation of two plans
for the clinical technique, therefore no specific conclusions regarding reducing time in
patient pathway could be made.
7.3 Further work
Investigating the use of different methods of robust optimisation algorithms within the
planning system would require input from software manufacturer. However, there are
some aspects to the VMATRO technique where further investigation can be carried out
as an extension to this project. One aspect to this would be to evaluate the target
volume used for optimisation. In this study the structure PTVtoSurface was used, it has
been discussed that when using robust optimisation this is likely to exceed the
clinically required margin to the posterior of the treatment area, therefore
152
CTVtoSurface would be a more appropriate target optimisation structure. The target
contour is also limited at the patient surface, using a structure that extends beyond the
patient surface may enhance the surface dose but could result in more excessive
hotspots during perturbation. Alternatively, a non-uniform uncertainty of the patient
position could be used within the robustness setting, this would also reduce the
number of scenarios required to computer, reducing planning optimisation time.
Additional plans were produced to investigate whether limiting the direction of
optimisation would improve the robustness of the plans to hotspots generated within
the PTVtoSurface, by minimising the complexity of the optimisation. This however this
did not appear to have the effect required, Appendix 2.
Within this study it was observed that with a maximum error of uncertainty of 0.5cm,
used uniformly in the robustness setting, the 0.3cm perturbation dose differences for
V105% and V107%, were reduced to values that just exceeded the dose objectives.
Additional investigations into smaller perturbations, Appendix 3, showed that if the
patient was on average, perturbed in the AS direction by 0.2cm, or had an increase in
contour of 0.2cm, then in 5 out of the 8 cases, mandatory constraints would have been
met. However, it is difficult to ensure this level of accuracy.
For all the VMATRO plans used for in this planning study, two 360⁰ arcs have been
used. Other studies have shown that reduced or partial arc angles can minimise dose
to organs at risk but the compromise this may have on skin doses is not discussed in
those papers.
153
8 References
Abel, S. et al. (2017). ‘Local failure and acute radiodermatological toxicity in patients
undergoing radiation therapy with and without postmastectomy chest wall bolus: Is
bolus ever necessary?’, Practical Radiation Oncology, 7(3), pp. 167–172. doi:
10.1016/j.prro.2016.10.018.
Almberg, S. S., Lindmo, T. and Frengen, J. (2011). ‘Superficial doses in breast cancer
radiotherapy using conventional and IMRT techniques: A film-based phantom study’,
Radiotherapy and Oncology. Elsevier, 100(2), pp. 259–264. doi:
10.1016/j.radonc.2011.05.021.
Andry, G. et al. (1989). ‘Locoregional recurrences after 649 modified radical
mastectomies: incidence and significance’, European journal of surgical oncology : the
journal of the European Society of Surgical Oncology and the British Association of
Surgical Oncology. Department of Surgical Oncology, Institut Jules Bordet, Brussels,
Belgium., 15(6), pp. 476–485. Available at:
http://europepmc.org/abstract/MED/2557247.
Archibald-Heeren, B. R. et al. (2017). ‘Robust optimization of VMAT for lung cancer:
Dosimetric implications of motion compensation techniques’, Journal of Applied
Clinical Medical Physics, 18(5), pp. 104–116. doi: 10.1002/acm2.12142.
Badakhshi, H. et al. (2013). ‘Image-guided volumetric modulated arc therapy for breast
cancer: a feasibility study and plan comparison with three-dimensional conformal and
intensity-modulated radiotherapy’, The British Journal of Radiology, 86(1032). doi:
10.1259/bjr.20130515.
Bjärngard, B. E., Vadash, P. and Zhu, T. (1995). ‘Doses near the surface in high-energy
x-ray beams’, Medical Physics. John Wiley & Sons, Ltd, 22(4), pp. 465–468. doi:
10.1118/1.597477.
Blitzblau, R. C. and Horton, J. K. (2013). ‘Treatment planning technique in patients
receiving postmastectomy radiation therapy’, Practical Radiation Oncology. Elsevier,
3(4), pp. 241–248. doi: 10.1016/J.PRRO.2012.09.004.
154
Boman, E., Ojala, J., Rossi, M., & Kapanen, M. (2018). ‘Monte Carlo investigation on
the effect of air gap under bolus in post-mastectomy radiotherapy’, Physica Medica.
Elsevier, 55, pp. 82–87. doi: 10.1016/J.EJMP.2018.10.023.
Butson, M. J., Cheung, T., Yu, P., & Metcalfe, P. (2000). ‘Effects on skin dose from
unwanted air gaps under bolus in photon beam radiotherapy’, Radiation
Measurements, 32(3), pp. 201–204. doi: 10.1016/S1350-4487(99)00276-0.
Byrne, M., Hu, Y. and Archibald-Heeren, B. (2016). ‘Evaluation of RayStation robust
optimisation for superficial target coverage with setup variation in breast IMRT’,
Australasian Physical and Engineering Sciences in Medicine. Springer Netherlands,
39(3), pp. 705–716. doi: 10.1007/s13246-016-0466-6.
Cancer Research UK (2021a). Breast cancer screening and diagnosis statistics | Cancer
Research UK. Available at: https://www.cancerresearchuk.org/health-
professional/breast-cancer-screening-and-diagnosis-
statistics?_ga=2.184417830.1414124571.1609771846-
2017946323.1609771846#heading-Zero (Accessed: 4 January 2021).
Cancer Research UK (2021b). Breast cancer treatment statistics | Cancer Research UK.
Available at: https://www.cancerresearchuk.org/health-professional/cancer-
statistics/statistics-by-cancer-type/breast-cancer/diagnosis-and-treatment (Accessed:
4 January 2021).
Cancer Research UK (2021c). Cancer Statistics for the UK. Available at:
https://www.cancerresearchuk.org/health-professional/cancer-statistics-for-the-uk
(Accessed: 4 January 2021).
Cancer Research UK (2021d). Ductal carcinoma in situ (DCIS) | Breast Cancer | Cancer
Research UK. Available at: https://www.cancerresearchuk.org/about-cancer/breast-
cancer/stages-types-grades/types/ductal-carcinoma-in-situ-dcis (Accessed: 4 January
2021).
Cancer Research UK (2021e). Lobular carcinoma in situ (LCIS) | Breast conditions |
Cancer Research UK. Available at: https://www.cancerresearchuk.org/about-
155
cancer/breast-cancer/stages-types-grades/types/lobular-carcinoma-in-situ-lcis
(Accessed: 4 January 2021).
Cancer Research UK (2021f). Survival for breast cancer | Breast Cancer | Cancer
Research UK. Available at: https://www.cancerresearchuk.org/about-cancer/breast-
cancer/survival (Accessed: 4 January 2021).
Cancer Research UK (2021g). What is breast cancer? | Cancer Research UK. Available
at: https://www.cancerresearchuk.org/about-cancer/breast-cancer/about (Accessed: 4
January 2021).
Cao, Y. et al. (2017). ‘Superficial dose evaluation of four dose calculation algorithms’,
Radiation Physics and Chemistry. Pergamon, 137, pp. 23–28. doi:
10.1016/J.RADPHYSCHEM.2016.02.032.
Cavey, M. L. et al. (2005). ‘Dosimetric comparison of conventional and forward-
planned intensity-modulated techniques for comprehensive locoregional irradiation of
post-mastectomy left breast cancers’, Medical Dosimetry. Pergamon, 30(2), pp. 107–
116. doi: 10.1016/J.MEDDOS.2005.02.002.
Chan, T. C. Y., Bortfeld, T. and Tsitsiklis, J. N. (2006). ‘A robust approach to IMRT
optimization’, Physics in Medicine and Biology, 51(10), pp. 2567–2583. doi:
10.1088/0031-9155/51/10/014.
Chao, K. S. C., Perez, C. A., Wang, T. J. C., & Brady, L. W. (2011). Radiation Oncology :
Management Decisions 3rd Edition. 3rd Editio. Philadelphia: Wolters Kluwer
Health/Lippincott Williams & Wilkins. Available at:
http://ovid.com/site/catalog/books/1755.jsp (Accessed: 29 March 2019).
Chetty, I. J. et al. (2007). ‘Report of the AAPM Task Group No. 105: Issues associated
with clinical implementation of Monte Carlo-based photon and electron external beam
treatment planning’, Medical Physics, 34(12), pp. 4818–4853. doi: 10.1118/1.2795842.
Chung, H. et al. (2005). ‘Evaluation of surface and build-up region dose for intensity-
modulated radiation therapy in head and neck cancer’, Medical Physics, 32(8), pp.
2682–2689. doi: 10.1118/1.1992067.
156
Das, L. C. et al. (2017). ‘A feasibility study of 2-mm bolus for postmastectomy radiation
therapy’, Practical Radiation Oncology. Elsevier, 7(3), pp. 161–166. Available at:
https://www.sciencedirect.com/science/article/pii/S1879850016302429 (Accessed: 8
March 2018).
Devic, S. et al. (2006). ‘Accurate skin dose measurements using radiochromic film in
clinical applications; Accurate skin dose measurements using radiochromic film in
clinical applications’, Medical Physics. John Wiley & Sons, Ltd, 33(4), pp. 1116–1124.
doi: 10.1118/1.2179169.
Dias, A. G. et al. (2019). ‘Optimization of skin dose using in-vivo MOSFET dose
measurements in bolus/non-bolus fraction ratio: A VMAT and a 3DCRT study.’, Journal
of applied clinical medical physics. Wiley-Blackwell, 20(2), pp. 63–70. doi:
10.1002/acm2.12525.
Donovan, E. et al. (2007). ‘Randomised trial of standard 2D radiotherapy (RT) versus
intensity modulated radiotherapy (IMRT) in patients prescribed breast radiotherapy’,
Radiotherapy and Oncology, 82(3), pp. 254–264. doi: 10.1016/j.radonc.2006.12.008.
Dunlop, A. et al..(2019).' Evaluation of organ motion-based robust optimisation for
VMAT planning for breast and internal mammary chain radiotherapy.' Clinical and
Translational Radiation Oncology, 16, pp.60-66.
Ekambaram, V. et al. (2015). ‘Planning Aspects of Volumetric Modulated Arc Therapy
and Intensity Modulated Radio therapy in Carcinoma Left Breast - A Comparative
Study’, Asian Pacific Journal of Cancer Prevention, 16(4), pp. 1633–1636. doi:
10.7314/APJCP.2015.16.4.1633.
Fraass, B. et al. (1998). ‘American Association of Physicists in Medicine Radiation
Therapy Committee Task Group 53: Quality assurance for clinical radiotherapy
treatment planning’, Medical Physics. John Wiley and Sons Ltd, 25(10), pp. 1773–1829.
doi: 10.1118/1.598373.
Fredriksson, A., Forsgren, A. and Hårdemark, B. (2011) ‘Minimax optimization for
handling range and setup uncertainties in proton therapy’, Medical Physics, 38(3), pp.
1672–1684. doi: 10.1118/1.3556559.
157
Freedman, G. M. et al. (2009). ‘Breast intensity-modulated radiation therapy reduces
time spent with acute dermatitis for women of all breast sizes during radiation.’,
International journal of radiation oncology, biology, physics. NIH Public Access, 74(3),
pp. 689–694. doi: 10.1016/j.ijrobp.2008.08.071.
Gerbi, B. J., Meigooni, A. S. and Khan, F. M. (1987) ‘Dose buildup for obliquely incident
photon beams’, Medical Physics. John Wiley & Sons, Ltd, 14(3), pp. 393–399. doi:
10.1118/1.596055.
Haciislamoglu, E. et al. (2015). ‘Dosimetric comparison of left-sided whole-breast
irradiation with 3DCRT, forward-planned IMRT, inverse-planned IMRT, helical
tomotherapy, and volumetric arc therapy’, Physica medica : PM : an international
journal devoted to the applications of physics to medicine and biology : official journal
of the Italian Association of Biomedical Physics (AIFB). Elsevier, 31(4), pp. 360–7. doi:
10.1016/j.ejmp.2015.02.005.
Healy, E. et al. (2013). ‘Skin dose effects of postmastectomy chest wall radiation
therapy using brass mesh as an alternative to tissue equivalent bolus.’, Practical
radiation oncology. Elsevier, 3(2), pp. e45-53. doi: 10.1016/j.prro.2012.05.009.
Higgins, P. D. et al. (2007). ‘Evaluation of surface and superficial dose for head and
neck treatments using conventional or intensity-modulated techniques’, Physics in
Medicine and Biology. IOP Publishing, 52(4), pp. 1135–1146. doi: 10.1088/0031-
9155/52/4/018.
Huang, S. Y. et al. (2008). ‘The effect of skin thickness determined using breast CT on
mammographic dosimetry’, Medical Physics. John Wiley and Sons Ltd, 35(4), pp. 1199–
1206. doi: 10.1118/1.2841938.
ICRP (1991). The Biological Basis for Dose Limitation in the Skin. ICRP Skin Task Group
Report,ICRP Publication 59. Annals of the ICRP 22(2).
ICRU (1985). Determination of Dose Equivalents Resulting from External Radiation
Sources (Report 39), Journal of the International Commission on Radiation Units and
Measurements. Washington, DC: Internation Commission on Radiation Units and
Measurements. doi: 10.1093/jicru/os20.2.report39.
158
International Commission of Radiation Units and Measurements (1999). ICRU Report
62: prescribing, recording and reporting photon beam therapy (supplement to ICRU
report 50), Journal of the International Commission on Radiation Units and
Measurements. Bethesda, MD.
International Commission on Radiation Units and Measurements (1993). ICRU report
50: prescribing, recording and reporting photon beam therapy. Bethesda, MD.
International Commission on Radiation Units and Measurements (2010). ‘ICRU report
83: prescribing, recording and reporting photon beam intensity-modulated therapy
(IMRT)’.
ISRCTN Registry, ISRCTN19906132: A clinical trial testing a one week schedule of whole
breast radiotherapy against a three week schedule 2011. London. Available at:
http://www.isrctn.com/ISRCTN19906132 (Accessed: 11 April 2019).
ISRCTN Registry, ISRCTN61145589: SUPREMO, an MRC Phase III randomised trial to
assess the role of adjuvant chest wall irradiation in ‘intermediate risk’ operable breast
cancer following mastectomy 2005. London. Available at:
http://www.isrctn.com/ISRCTN61145589 (Accessed: 11 April 2019).
Javedan, K. et al. (2009). ‘Skin dose study of chest wall treatment with tomotherapy’,
Jpn J Radiol, 27, pp. 355–362. doi: 10.1007/s11604-009-0357-9.
Jensen, C. A. et al. (2018). ‘Robustness of VMAT and 3DCRT plans toward setup errors
in radiation therapy of locally advanced left-sided breast cancer with DIBH’, Physica
Medica: European Journal of Medical Physics, 45, pp. 12–18. doi:
10.1016/j.ejmp.2017.11.019.
Jin, G.-H. et al. (2013). ‘A comparative dosimetric study for treating left-sided breast
cancer for small breast size using five different radiotherapy techniques: conventional
tangential field, field-in-field, Tangential-IMRT, Multi-beam IMRT and VMAT’,
Radiation Oncology, 8(1), pp. 89–96. doi: 10.1186/1748-717X-8-89.
Jo, I. Y., Kim, S.-W. and Son, S. H. (2017). ‘Dosimetric evaluation of the skin-sparing
effects of 3-dimensional conformal radiotherapy and intensity-modulated
159
radiotherapy for left breast cancer’, Oncotarget, 8(2), pp. 3059–3063. Available at:
www.impactjournals.com/oncotarget (Accessed: 8 March 2018).
Johansen, S., Cozzi, L. and Olsen, D. R. (2009). ‘A planning comparison of dose patterns
in organs at risk and predicted risk for radiation induced malignancy in the
contralateral breast following radiation therapy of primary breast using conventional,
IMRT and Volumetric modulated arc treatment techniqu’, Acta Oncologica, 48(4), pp.
495–503. doi: 10.1080/02841860802657227.
Jong, W. L. et al. (2016). ‘In vivo skin dose measurement using MOSkin detectors in
tangential breast radiotherapy’, Physica Medica. Elsevier, 32(11), pp. 1466–1474. doi:
10.1016/J.EJMP.2016.10.022.
Kan, M. W. K., Leung, L. H. T. and Yu, P. K. N. (2012). ‘Verification and dosimetric
impact of Acuros XB algorithm on intensity modulated stereotactic radiotherapy for
locally persistent nasopharyngeal carcinoma’, Medical Physics. John Wiley and Sons
Ltd, 39(8), pp. 4705–4714. doi: 10.1118/1.4736819.
Karpf, D., Sakka, M., Metzger, M., & Grabenbauer, G. G. (2019). ‘Left breast irradiation
with tangential intensity modulated radiotherapy (t-IMRT) versus tangential volumetric
modulated arc therapy (t-VMAT): Trade-offs between secondary cancer induction risk
and optimal target coverage’, Radiation Oncology. Radiation Oncology, 14(1), pp. 1–11.
doi: 10.1186/s13014-019-1363-4.
Kim, S., Liu, C. R., Zhu, T. C., & Palta, J. R. (1998). ‘Photon beam skin dose analyses for
different clinical setups’, Medical Physics, 25(6), pp. 860–866. doi: 10.1118/1.598261.
Lai, Y. et al. (2016). ‘Modified Volumetric Modulated Arc Therapy in Left Sided Breast
Cancer After Radical Mastectomy With Flattening Filter Free Versus Flattened Beams’,
Medicine, 95(14), p. e3295. doi: 10.1097/MD.0000000000003295.
Liang, X. er al. 2020).' Using Robust Optimization for Skin Flashing in Intensity
Modulated Radiation Therapy for Breast Cancer Treatment: A Feasibility
Study.' Practical Radiation Oncology, 10(1), pp.59-69.
160
Lee, N. et al. (2002). ‘Skin toxicity due to intensity-modulated radiotherapy for head-
and-neck carcinoma’, International Journal of Radiation Oncology • Biology • Physics.
Elsevier, 53(3), pp. 630–637. doi: 10.1016/S0360-3016(02)02756-6.
Ma, C. et al. (2015). ‘Dosimetric Comparison and Evaluation of Three Radiotherapy
Techniques for Use after Modified Radical Mastectomy for Locally Advanced Left-sided
Breast Cancer’, Scientific Reports, 5(1), p. 12274. doi: 10.1038/srep12274.
Macmillan Cancer Support (2021). Staging and grading of breast cancer - Macmillan
Cancer Support. Available at: https://www.macmillan.org.uk/cancer-information-and-
support/breast-cancer/staging-and-grading-of-breast-cancer (Accessed: 4 January
2021).
Manger, R., Paxton, A. and Cerviño, L. (2016). ‘Dosimetric assessment of brass mesh
bolus for postmastectomy photon radiotherapy’, Journal of Applied Clinical Medical
Physics. Wiley-Blackwell, 17(6), pp. 86–96. doi: 10.1120/jacmp.v17i6.6221.
Mayadev, J. et al. (2015). ‘Practice Patterns in the Delivery of Radiation Therapy After
Mastectomy Among the University of California Athena Breast Health Network’,
Clinical Breast Cancer, 15(1), pp. 43–47. doi: 10.1016/j.clbc.2014.07.005.
Miura, H., Ozawa, S. and Nagata, Y. (2017). ‘Efficacy of robust optimization plan with
partial-arc VMAT for photon volumetric-modulated arc therapy: A phantom study’,
Journal of Applied Clinical Medical Physics, 18(5), pp. 97–103. doi:
10.1002/acm2.12131.
Nakamura, N. et al. (2017). ‘Post-mastectomy radiation therapy without usage of a
bolus may be a reasonable option.’, Journal of radiation research. Oxford University
Press, 58(1), pp. 66–70. doi: 10.1093/jrr/rrw055.
NICE (2018). Early and locally advanced breast cancer: Early and locally advanced
breast cancer: diagnosis and management diagnosis and management NICE guideline.
Available at: https://www.nice.org.uk/guidance/ng101/resources/early-and-locally-
advanced-breast-cancer-diagnosis-and-management-pdf-66141532913605 (Accessed:
25 March 2019).
161
Oltulu, P. et al. (2018). ‘Measurement of epidermis, dermis, and total skin thicknesses
from six different body regions with a new ethical histometric technique’, Turkish
Journal of Plastic Surgery. Medknow Publications and Media Pvt. Ltd., 26(2), p. 56. doi:
10.4103/tjps.TJPS_2_17.
Ordonez-Sanz, C., Bowles, S., Hirst, A., MacDougall, N. D. (2014). ‘A single plan solution
to chest wall radiotherapy with bolus?’, The British Journal of Radiology. British
Institute of Radiology, 87(1037), p. 20140035. doi: 10.1259/bjr.20140035.
Panettieri, V. et al. (2009). ‘AAA and PBC calculation accuracy in the surface build-up
region in tangential beam treatments. Phantom and breast case study with the Monte
Carlo code penelope’, Radiotherapy and Oncology. Elsevier, 93(1), pp. 94–101. doi:
10.1016/J.RADONC.2009.05.010.
Pignol, J.-P. et al. (2015). ‘Prospective Evaluation of Severe Skin Toxicity and Pain
During Postmastectomy Radiation Therapy’, Radiation Oncology Biology, 91(1), pp.
157–164. doi: 10.1016/j.ijrobp.2014.09.022.
Popescu, C. C. et al. (2010). ‘Volumetric Modulated Arc Therapy Improves Dosimetry
and reduces treatment time compared to conventional intensity-modulated
radiotherapy for locoregional radiotherapy of left-sided breast cancer and internal
mammary nodes.’, Radiation Oncology Biology. Elsevier, 76(1), pp. 287–295. doi:
10.1016/j.ijrobp.2009.05.038.
Quach, K. Y. et al. (2000). ‘Measurement of radiotherapy x-ray skin dose on a chest
wall phantom’, Medical Physics. John Wiley & Sons, Ltd, 27(7), pp. 1676–1680. doi:
10.1118/1.599035.
Ramlov, A. et al. (2017). ‘Clinical implementation of coverage probability planning for
nodal boosting in locally advanced cervical cancer’, Radiotherapy and Oncology.
Elsevier B.V., 123(1), pp. 158–163. doi: 10.1016/j.radonc.2017.01.015.
Recht, A. et al. (2016). ‘Postmastectomy radiotherapy: An American Society of clinical
oncology, American society for radiation oncology, and society of surgical oncology
focused guideline update’, Journal of Clinical Oncology, 34(36), pp. 4431–4442. doi:
10.1200/JCO.2016.69.1188.
162
Richmond, N. D., Daniel, J. M., Whitbourn, J. R., & Greenhalgh, A. D. (2016).
‘Dosimetric characteristics of brass mesh as bolus under megavoltage photon
irradiation’, The British Journal of Radiology. The British Institute of Radiology.,
89(1059), p. 20150796. doi: 10.1259/bjr.20150796.
De Rose, F. et al. (2016). ‘Phase II trial of hypofractionated VMAT-based treatment for
early stage breast cancer: 2-year toxicity and clinical results’, Radiation Oncology, 11,
pp. 120–128. doi: 10.1186/s13014-016-0701-z.
Rudat, V. et al. (2011). ‘Tangential beam IMRT versus tangential beam 3D-CRT of the
chest wall in postmastectomy breast cancer patients: A dosimetric comparison’,
Radiation Oncology. BioMed Central, 6(1), p. 26. doi: 10.1186/1748-717X-6-26.
Shi, L., Vedantham, S., Karellas, A., & O’Connell, A. M. (2013). ‘Technical note: Skin
thickness measurements using high-resolution flat-panel cone-beam dedicated breast
CT’, Medical Physics. John Wiley and Sons Ltd, 40(3), p. 031913. doi:
10.1118/1.4793257.
The Royal College of Radiologists (2016). Postoperative radiotherapy for breast cancer:
UK consensus statements. Available at: www.rcr.ac.uk (Accessed: 5 January 2021).
Thomas, S. J. and Hoole, A. C. F. (2004). ‘The effect of optimization on surface dose in
intensity modulated radiotherapy (IMRT).’, Physics in medicine and biology, 49(21), pp.
4919–4928. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15584527 (Accessed:
5 March 2018).
Thoms, W. W. et al. (1989). ‘Multimodal Treatment For Inflammatory Breast Cancer’,
International Journal of Radiation Oncology • Biology • Physics. Elsevier, 17(4), pp.
739–745. doi: 10.1016/0360-3016(89)90060-6.
Tieu, M. T., Graham, P., Browne, L., & Chin, Y. S. (2011). ‘The Effect of Adjuvant
Postmastectomy Radiotherapy Bolus Technique on Local Recurrence’, Radiation
Oncology Biology. Elsevier, 81(3), pp. e165–e171. doi: 10.1016/j.ijrobp.2011.01.002.
Tilly, D., Holm, Å., Grusell, E., & Ahnesjö, A. (2019). ‘Probabilistic optimization of dose
coverage in radiotherapy’, Physics and Imaging in Radiation Oncology, 10(March), pp.
1–6. doi: 10.1016/j.phro.2019.03.005.
163
Turner, J. Y. et al. (2016). ‘Technique and outcome of post-mastectomy adjuvant chest
wall radiotherapy-the role of tissue-equivalent bolus in reducing risk of local
recurrence.’, The British journal of radiology. British Institute of Radiology, 89(1064), p.
20160060. doi: 10.1259/bjr.20160060.
Unkelbach, J. et al. (2018). ‘Robust radiotherapy planning’, Physics in Medicine and
Biology. IOP Publishing, 63(22). doi: 10.1088/1361-6560/aae659.
Virén, T. et al. (2015). ‘Tangential volumetric modulated arc therapy technique for left-
sided breast cancer radiotherapy’, Radiation Oncology, 10(1), pp. 79–86. doi:
10.1186/s13014-015-0392-x.
Vu, T. T. T. et al. (2007). ‘Variability in Radiation Oncologists’ Opinion on the Indication
of a Bolus in Post-mastectomy Radiotherapy: an International Survey’, Clinical
Oncology. Elsevier, 19(2), pp. 115–119. doi: 10.1016/j.clon.2006.10.004.
Wagenaar, D. et al. (2019). ‘Composite minimax robust optimization of VMAT
improves target coverage and reduces non-target dose in head and neck cancer
patients’, Radiotherapy and Oncology. Elsevier B.V., 136, pp. 71–77. doi:
10.1016/j.radonc.2019.03.019.
Xu, H. and Hatcher, G. (2016). ‘Treatment planning study of Volumetric Modulated Arc
Therapy and three dimensional field-in-field techniques for left chest-wall cancers with
regional lymph nodes’, Reports of Practical Oncology & Radiotherapy, 21(6), pp. 517–
524. doi: /10.1016/j.rpor.2016.07.005.
Yusof, F. H. et al. (2015). ‘On the Use of Optically Stimulated Luminescent Dosimeter
for Surface Dose Measurement during Radiotherapy.’, PloS one. Public Library of
Science, 10(6), p. e0128544. doi: 10.1371/journal.pone.0128544.
Zhang, Q. et al. (2015). ‘Dosimetric comparison for volumetric modulated arc therapy
and intensity-modulated radiotherapy on the left-sided chest wall and internal
mammary nodes irradiation in treating post-mastectomy breast cancer.’, Radiology
and oncology. De Gruyter Open, 49(1), pp. 91–98. doi: 10.2478/raon-2014-0033.
164
Appendix 1
Supplementary Information Dose Grids.
For all the treatment plans analysed in this work, optimisation and final dose calculation
have been carried out using a dose grid of 0.3cm. To assure the conclusions from the thesis
were not dependent on the choice of dose grid resolution, the VMAT plans, in one case,
were re-calculated with dose grids of 0.2cm and 0.1cm and a robustly optimised VMAT plan
was re-optimised with a dose grid of 0.2cm (re-optimisation at 0.1cm was deemed to take
too long). Selected structures and dosimetric parameters were then compared. Perturbation
in one direction was also analysed to check there was no significant impact on the
conclusions.
Results:
Re-calculation of VMAT plan at 0.2cm and 0.1cm:
Dosimetric Parameter
Structure Dose Grid D99% (Gy) Average (Gy) D1% (Gy)
Skin3mm 0.3cm 32.9 39.1 41.5 0.2cm 32.7 38.8 41.4 0.1cm 31.6 38.4 41.3
V95 (%) V105 (%) V107 (%)
PTVtoSurface 0.3cm 96.6 0.2 0.0 0.2cm 96.4 0.3 0.0 0.1cm 96.0 0.4 0.0
Table A1.1: Comparison of dosimetric parameters for planning structures, with VMAT plan re-calculated using dose grids 0.2cm and 0.3cm
165
Perturbation of recalculated plans in 0.5cm AS direction:
Dosimetric Parameter
Structure Dose Grid D99% (Gy) Average (Gy) D1% (Gy)
Skin 3mm 0.3cm 32.6 41.6 48.8 0.2cm 32.7 41.6 48.7 0.1cm 32.1 41.0 48.5
V95 (%) V105 (%) V107 (%)
PTVtoSurface 0.3cm 98.0 22.3 16.8 0.2cm 97.9 22.1 16.8 0.1cm 97.5 21.6 16.3
Table A1.2: Comparison of dosimetric parameters for planning structures, with VMAT plan re-calculated using dose grids 0.2cm and 0.3cm and perturbed in the 0.5cm AS direction
Re – optimisations of robustly optimised plan at 0.2cm:
Dosimetric Parameter
Structure Dose Grid D99% (Gy)
Average (Gy) D1% (Gy)
Skin3mm 0.3cm 31.6 34.0 41.3 0.2cm 30.9 33.3 42.0
V95 (%) V105 (%) V107 (%)
PTVtoSurface 0.3cm 95.8 0.3 0.0 0.2cm 95.6 3.2 0.5
Table A1.3: Comparison of dosimetric parameters for planning structures, with VMAT plan re-optimised using dose grids 0.2cm and 0.3cm
166
Perturbation of re-optimised plan in 0.5cm AS direction:
Dosimetric Parameter
Structure Dose Grid D99% (Gy) Average (Gy) D1 %(Gy)
Skin 3mm 0.3cm 28.0 37.8 43.9 0.2cm 29.5 37.4 44.4
V95 (%) V105 (%) V107 (%)
PTVtoSurface 0.3cm 93.7 14.1 5.6 0.2cm 93.6 13.2 6.4
Table A1.4: Comparison of dosimetric parameters for planning structures, with VMAT plan re-optimised using dose grids 0.2cm and 0.3cm and perturbed 0.5cm in the AS direction
Summary:
In the case of re-calculation, small differences in absolute doses are observed, D99% for the
Skin3mm structure ranging the most by 1.3Gy (31.6Gy to 32.9Gy calculated at 0.1mm and
0.3mm, respectively). Similarly a 0.6% difference is noted in the V95% parameter for
PTVtoSurface. However, the magnitude of the effect, due to perturbation, for the D1% Skin
3mm, and V105%/V107% PTVtoSurface, indicate that using recalculated plans at a smaller
dose grid would have minimal impact on the conclusions.
This is also true in the cases of the re-optimised plans with a dose grid of 0.2cm. Although
small differences in dose and volumes are observed, Skin 3mm D99% differing by 0.7Gy,in
the non-perturbed plan and PTVtoSurface V105% differing by 2.9%, the magnitude of the
parameters when plans are perturbed suggest that re-optimisation with a smaller dose grid
does not significantly change or improve the problem.
167
Appendix 2
Supplementary information: Robust Optimisation Direction.
Within this study the robust optimisation was applied to the structure PTVtoSurface for the
VMATRO plans. In the discussion it was noted that robust optimisation may not have been
necessary in all directions as the PTV defining the back edge of the treatment volume
already accounted for set-up errors in this direction. Since robust optimisation is a
challenging process for the treatment planning system, re-optimisation in limited directions,
to account for changes in position of the patient surface only, was carried out to assess
whether the effect of perturbation could be controlled better.
Two left sided patients had the VMATRO plans re-optimised, with robust optimisation
applied in the anterior and left directions only. As with the previous plans a 0.5cm
uncertainty was applied. Selected structures and dosimetric parameters were then
compared, and the effect of perturbation in one direction analysed (AS- away from surface)
at 0.5cm and 0.3cm,
Results:
Table A2.1 shows the dosimetric parameters for Skin3mm and PTVtoSurface for robustly
optimised plans 0.5cm in all directions (VMATRO all dir) and VMAT plans optimised in the
anterior and left lateral directions only (VMAT RO limited). The dosimetric parameters are
included for the non – perturbed, perturbed 0.5cm AS and 0.3cm AS plans.
Summary:
In both cases it can be seen there are slight differences in the non-perturbed plans robustly
optimised in all directions and those robustly optimised in limited directions. For the
Skin3mm structure for the D99% parameter, in Case 2 a dose difference of 0.9Gy is seen,
and for the PTVtoSurface structure volume differences up to 2.3% are observed for the
168
V105% parameter. For the perturbed plans it can be seen that the dosimetric parameters
are of a similar magnitude for both the robustly optimised plans in limited directions and
robustly optimised plans in all directions. For PTVtoSurface the V107% parameter in case 1,
is 13.7% for the plan optimised in all directions compared to 15.6% for that optimised in
limited directions, when perturbed by 0.5cm. A similar trend can be observed with the D1%
parameter for Skin 3mm, and for perturbations at 0.3cm. In case 2, it appears that the use
of limited direction robust optimisation results in plans that are worse when perturbed than
those robustly optimised in all directions.
The conclusions from the re-optimisation of only a small number of the patient plans are
limited. However, it is clear from these two cases that, despite minimising the complexity of
the calculation, the robustly optimised plans in limited directions still result in perturbed
plans with dose parameters of similar magnitudes to the plans optimised in all directions.
The conclusions from the main body of work suggested that whilst using robust optimisation
can reduce the hotpots observed in perturbed plans, these hotspots can still be of a size that
would be clinically unacceptable. These additional results show that even if optimisation
complexity is reduced, the hotspots seen on perturbed plans are of a similar magnitude and
therefore would also be clinically unacceptable.
169
Structure Plan Non-perturbed 0.5cm AS Perturbation 0.3cm AS Perturbation
Case 1
D99% (Gy)
Average (Gy)
D1% (Gy)
D99% (Gy)
Average (Gy)
D1% (Gy)
D99% (Gy)
Average (Gy)
D1% (Gy)
Skin 3mm VMATRO all dir 31.6 38.2 41.3
29.8 38.3 43.7
31.4 38.7 42.8 VMAT RO limited 32.3 38.6 40.6
32 40.1 44.7
32.9 39.7 43.2
V95 (%) V105 (%)
V107 (%)
V95 (%) V105 (%) V107 (%)
V95 (%) V105 (%) V107 (%)
PTVtoSurface VMAT RO all dir 95.8 0.3 0.0
94.5 5.6 13.7
96.1 7 1.3 VMAT RO limited 95.2 0.1 0.0 97.5 8.8 15.6 97.8 5.2 1
Case 2
D99% (Gy)
Average (Gy)
D1% (Gy)
D99% (Gy)
Average (Gy)
D1% (Gy)
D99% (Gy)
Average (Gy)
D1% (Gy)
Skin 3mm VMATRO all dir 32.1 38.8 42.1
29.1 39 45.6
31.9 39.7 44.5
VMAT RO limited 33.0 39.1 42
32.6 41.3 46.6
34.0 40.9 44.9
V95 (%) V105 (%)
V107 (%)
V95 (%) V105 (%) V107 (%)
V95 (%) V105 (%) V107 (%)
PTVtoSurface VMAT RO all dir 95.4 2.0 0.2
93.5 29.3 17.5
95.8 20.2 9.5
VMAT RO limited 95.3 4.3 1.5 97.5 38.2 26.5 98.0 23.3 11.6
Table A2.1 -Comparison of dose parameters for structures in VMATRO plans optimised in all directions and limited directions, including the perturbation in AS direction.
170
Appendix 3
Supplementary Information – Perturbation Effect
The VMATRO plans used in this study were optimised to a maximum uncertainty of 0.5cm in
all directions on the PTVtoSurface structure. The results of perturbing these plans by
displacing the isocentre by 0.5cm and 0.3cm showed that one of the most significant issues
was that the dose volume parameters V105%, V107% were exceeded for PTV if the shifts
were away from the surface, with the mandatory constraint for V105%<7% (less than 7%
volume should receive 42Gy) and V107% (less than 2% volume should receive 42.8Gy).
Alternatively, this could be a considered as a change in patient contour, as an increase in
surface by 0.3cm or 0.5cm. The conclusions assumed that the perturbation or change in
contour was the same for the entire treatment, so if on average the patient position
resulted in a perturbation by 0.5cm in the AS direction across the whole treatment or the
surface increased by 0.5cm on average throughout the whole treatment, the PTVtoSurface
volume receiving 105% of the dose, averaged over the 8 patients, was 19.6% ranging from
9.3% to 29.3%, with none of the plans meeting the mandatory constraint. With a shift of
0.3cm in the AS direction, on average PTVtoSurface V105% was 10.8% ranging from 4.9% to
20.2%, therefore some patients would meet the mandatory constraint, but some still
received a significant volume. To try to establish whether there was an acceptable average
perturbation with a shift away from the surface or average increase in contour that would
meet the mandatory criteria for V105% and V107%, 3 of the patient plans were further
investigated with perturbations calculated on their VMATRO plans which included 0.1cm,
0.2cm and 0.4cm.
171
Results:
V105% values for PTVtoSurface for perturbed VMATRO plans (red boxes indicate value fails
mandatory constraint, green boxes indicate value passes mandatory constraint):
Perturbation (cm)
Patient 0.5 0.4 0.3 0.2 0.1 0.0
cw 17 13.7 10.7 7.0 3.4 1.0 0.3 cw 10 29.3 25.6 20.2 13.6 7.4 2.0 cw3 19.2 10.5 4.5 2.8 2.1 1.1 cw2 25.8 17.5 10.5 5.3 2.9 1.2 cw12 28.7 20.9 13.3 7.8 4.0 2.1 cw15 14.1 11.5 8.4 5.6 4.0 3.1 cw18 10.3 9.7 7.8 5.9 3.6 1.4 cw23 15.9 15.7 14.7 12.2 9.3 7.4
Average 19.6 15.3 10.8 7.1 4.3 2.3
Table A3.1: V105% parameter for PTVtoSurface for every patient. VMAT RO plans perturbed in the AS direction to different extents.
V107% values for PTVtoSurface for perturbed VMATRO plans (red boxes indicate value fails
mandatory constraint, green boxes indicate value passes mandatory constraint):
Perturbation (cm)
Patient 0.5 0.4 0.3 0.2 0.1 0.0
cw 17 5.6 3.3 1.3 0.3 0.0 0.0 cw 10 17.5 14.0 9.5 4.8 2.1 0.2 cw3 4.5 1.0 0.4 0.3 0.2 0.0 cw2 10.6 5.3 1.8 0.8 0.3 0.0 cw12 12.0 6.8 3.2 1.3 0.6 0.2 cw15 5.6 4.0 2.4 1.3 0.8 0.6 cw18 2.9 2.6 2.0 1.1 0.4 0.1 cw23 7.0 6.0 4.8 3.6 2.4 1.5
Average 8.2 5.4 3.2 1.7 0.8 0.3
Table A3.2: V107% parameter for PTVtoSurface for every patient. VMAT RO plans perturbed in the AS direction to different extents.
172
Summary:
For two of the key dosimetric parameters, V105% and V107%, which resulted in the
conclusion that the VMATRO was not a viable technique, were investigated further to see if
there was an ‘average’ perturbation over a whole treatment, that would be acceptable.
From the results we can see that for this set of patients, the V105% objective is met in 5/8
cases, when perturbed by 0.2cm in the AS direction and for the same perturbation the
V107% objective is met in 6/8 cases. The results indicate that the impact of perturbation is
patient specific however, in most cases if the patient set-up and contour difference over the
entire patient treatment is within 0.2cm of the planned treatment, these parameters could
be achievable.
173
Appendix 4
Perturbation V95% (%) V105% (%) V107% (%) D1% (Gy) Ave. (Gy)
Direction Average Min Max Average Min Max Average Min Max Average Min Max Average Min Max
Clinical 0.5cm TS -23.4 -14.9 -29.9
4.9 8.8 0.6
0.7 2.7 0.0
0.8 1.6 0.2
-2.4 -2.4 -3.0
0.5cm TI -18.3 -10.2 -24.4
4.3 9.6 0.7
0.7 4.3 0.0
0.8 1.4 0.3
-1.5 -1.5 -2.8
0.5cm AS -7.7 -1.0 -19.9
2.2 4.9 1.0
0.4 0.9 0.0
0.7 0.9 0.2
-0.5 -0.5 -0.8
0.5cm AI -9.6 -1.5 -18.3
3.4 6.2 2.0
0.8 1.6 0.0
0.9 1.2 0.5
-0.5 -0.5 -0.8
0.3cm TS -11.2 -8.0 -14.2
0.8 3.8 -0.2
0.0 0.2 0.0
0.3 0.9 -0.1
-0.6 -0.6 -1.1
0.3cm TI -8.3 -5.0 -12.3
0.7 2.3 -0.1
0.0 0.4 0.0
0.2 0.6 -0.1
-0.4 -0.4 -1.0
0.3cm AS -2.2 0.5 -6.9
1.3 2.9 0.4
0.1 0.5 0.0
0.4 0.7 0.1
-0.2 -0.2 -0.5
0.3cm AI -2.7 -0.2 -6.5
2.0 3.1 1.0
0.3 0.9 0.0
0.6 0.8 0.3
-0.2 -0.2 -0.5
VMAT 0.5cm TS -43.5 -22.6 -68.1
2.1 4.8 -0.5
0.6 1.7 0.0
0.6 1.2 -0.1
-3.9 -3.9 -6.2
0.5cm TI -39.6 -18.6 -64.9
2.1 6.2 -0.2
0.6 1.9 -0.1
0.5 1.2 -0.4
-3.1 -3.1 -5.4
0.5cm AS 1.4 4.4 -1.8
52.1 72.4 22.1
46.1 66.7 16.8
9.9 15.3 6.2
3.0 3.0 0.8
0.5cm AI -1.4 0.7 -5.6
51.8 72.8 23.1
46.1 67.4 18.5
9.6 14.9 6.5
2.8 2.8 0.8
0.3cm TS -28.9 -13.8 -49.9
0.3 1.9 -1.0
0.1 0.2 -0.1
0.1 0.5 -0.4
-1.8 -1.8 -3.1
0.3cm TI -26.2 -10.8 -47.4
0.2 1.8 -0.9
0.0 0.2 -0.1
0.0 0.5 -0.5
-1.6 -1.6 -2.8
0.3cm AS 2.5 5.2 0.8
38.8 58.2 13.8
30.9 48.5 8.3
6.2 9.6 3.8
1.8 1.8 0.5
0.3cm AI 1.3 2.8 -0.4
39.5 59.7 15.4
31.6 49.8 10.0
6.2 9.4 4.1
1.7 1.7 0.5
VMATRO 0.5cm TS -27.0 -16.4 -40.7
-0.5 2.7 -3.6
-0.1 0.6 -1.2
-0.3 0.4 -1.3
-2.2 -2.2 -2.8
0.5cm TI -22.6 -12.2 -33.9
-0.3 3.2 -2.7
0.0 0.7 -0.8
-0.2 0.5 -1.0
-1.7 -1.7 -2.2
0.5cm AS -2.1 2.8 -9.2
17.0 26.6 8.5
7.7 15.9 2.9
1.9 2.6 1.1
0.4 0.4 -0.4
0.5cm AI -3.8 1.0 -10.8
17.5 36.1 7.9
7.6 17.0 2.4
1.6 2.5 1.0
0.3 0.3 -0.5
0.3cm TS -10.7 -5.9 -13.6
-1.2 0.0 -3.5
-0.3 0.0 -0.9
-0.5 0.0 -1.1
-0.8 -0.8 -1.0
0.3cm TI -8.7 -4.4 -10.9
-1.0 0.2 -2.8
-0.2 0.0 -0.6
-0.3 0.0 -0.8
-0.7 -0.7 -0.9
0.3cm AS 0.3 2.5 -2.6
8.2 15.9 3.8
2.7 8.0 0.4
1.0 1.2 0.5
0.3 0.3 0.0
0.3cm AI -0.2 1.7 -3.6 8.4 15.5 4.2 2.2 4.5 0.6 0.8 1.3 0.5 0.3 0.3 0.0
Table A4.1: Additional information on the range of perturbation effect on the planning parameters V95%, V105%, V107%, average dose and D1%, for the PTVtoSurface structure, for the 8 patient cases. Data is included for the Clinical, VMAT and VMATRO plans, the data shows the average volume difference or dose difference from the non-perturbed plan and the min/max difference over the 8 patients. The averaged data for the planning parameters shown in Figures 5.6, 5.7, 6.8 and 6.12.
174
Perturbation V95% (%) V105% (%) V107% (%) D1% (Gy) Ave. (Gy) Direction Average Min Max Average Min Max Average Min Max Average Min Max Average Min Max
Clinical non-perturbed 93.0 88.4 96.1
0.6 0.0 1.8
0.0 0.0 0.0
39.8 39.5 40.0
41.8 41.3 42.2 0.5cm TS 69.6 62.3 81.1
5.5 0.8 8.8
0.7 0.0 2.7
37.4 36.5 38.5
42.6 41.9 43.1
0.5cm TI 74.7 64.1 85.8
4.8 0.9 11.4
0.7 0.0 4.3
38.3 36.7 39.4
42.5 42.0 43.6 0.5cm AS 85.3 72.9 93.7
2.8 1.7 5.0
0.4 0.0 0.9
39.3 38.9 39.6
42.4 42.2 42.7
0.5cm AI 83.4 71.5 93.1
3.9 2.4 6.4
0.8 0.0 1.6
39.3 38.7 39.7
42.7 42.3 43.1 0.3cm TS 81.8 75.6 88.0
1.4 0.2 3.9
0.0 0.0 0.2
39.1 38.4 39.6
42.0 41.6 42.5
0.3cm TI 84.7 76.1 91.0
1.2 0.1 4.1
0.0 0.0 0.4
39.4 38.5 39.9
42.0 41.6 42.5 0.3cm AS 90.8 84.9 95.2
1.8 0.7 3.0
0.1 0.0 0.5
39.6 39.2 39.8
42.2 41.9 42.6
0.3cm AI 90.3 82.5 95.1
2.5 1.4 3.7
0.3 0.0 0.9
39.5 39.1 39.8
42.4 42.1 42.8
0.0 0.0 0.0
0.0 0.0 0.0
VMAT non-perturbed 95.6 92.9 97.3
0.7 0.2 1.5
0.1 0.0 0.1
40.0 39.8 40.1
41.9 41.4 42.1 0.5cm TS 52.1 24.9 74.0
2.9 0.3 5.5
0.6 0.0 1.7
36.1 33.6 37.7
42.4 41.7 43.0
0.5cm TI 56.0 28.1 78.0
2.9 0.0 6.9
0.7 0.0 1.9
36.9 34.4 38.5
42.3 41.2 43.1 0.5cm AS 97.0 94.5 98.6
52.8 22.3 72.6
46.2 16.8 66.7
43.0 40.8 44.5
51.7 47.6 57.2
0.5cm AI 94.3 90.8 97.9
52.5 23.3 72.9
46.2 18.5 67.4
42.8 40.7 45.1
51.5 48.4 56.8 0.3cm TS 66.8 43.0 82.8
1.0 0.0 2.6
0.1 0.0 0.3
38.2 36.7 38.9
41.9 41.3 42.4
0.3cm TI 69.4 45.5 85.9
1.0 0.0 2.5
0.1 0.0 0.2
38.4 37.0 39.3
41.9 41.0 42.4 0.3cm AS 98.2 97.2 99.1
39.5 14.0 58.4
31.0 8.3 48.5
41.8 40.5 42.6
48.0 45.3 51.5
0.3cm AI 96.9 95.7 99.0
40.2 15.6 59.9
31.7 10.0 49.8
41.7 40.5 42.8
48.0 45.9 51.3
0.0 0.0 0.0
0.0 0.0 0.0
VMATRO non-perturbed 92.8 90.9 95.8
2.6 0.3 7.4
0.5 0.0 1.5
40.0 39.8 40.3
42.4 41.6 43.4 0.5cm TS 65.8 50.5 79.4
2.1 0.0 4.8
0.4 0.0 1.1
37.8 37.1 38.8
42.1 41.2 42.8
0.5cm TI 70.2 57.3 83.6
2.3 0.0 5.3
0.5 0.0 1.2
38.3 37.7 39.3
42.2 41.0 42.9 0.5cm AS 90.8 82.9 95.9
19.6 10.3 29.3
8.2 2.9 17.5
40.4 39.7 41.2
44.2 43.3 46.0
0.5cm AI 89.0 81.5 95.4
20.1 9.3 38.2
8.1 2.5 17.1
40.3 39.6 41.4
44.0 43.3 45.0 0.3cm TS 82.1 77.6 88.5
1.5 0.0 3.9
0.2 0.0 0.7
39.2 38.9 39.8
41.9 40.9 42.6
0.3cm TI 84.1 80.0 90.1
1.7 0.0 4.6
0.3 0.0 1.1
39.3 38.9 39.9
42.0 41.2 42.8 0.3cm AS 93.1 89.1 96.1
10.8 4.9 20.2
3.2 0.4 9.5
40.3 40.0 40.8
43.3 42.5 44.5
0.3cm AI 92.6 88.8 95.9 11.0 6.2 17.6 2.7 0.7 6.0 40.3 40.0 40.9 43.2 42.7 44.0
Table A4.2: Additional information on the range of perturbation effect on the planning parameters V95%, V105%, V107%, average dose and D1%, for the PTVtoSurface structure, for the 8 patient cases. Data is included for the Clinical, VMAT and VMATRO plans, the data shows the average volume or dose and the min/max values across the 8 patients. The averaged data for the planning parameters shown in Figures 5.8-5.11 and 6.9-6.11
175
Perturbation D99% (Gy) Average (Gy) D1% (Gy) Direction Average Min Max Average Min Max Average Min Max
Clinical 0.5cm TS -11.9 -8.5 -17.3
-0.4 0.2 -1.3
0.9 1.7 0.3 0.5cm TI -6.8 -3.2 -15.6
-0.1 0.5 -1.1
0.8 1.4 0.1
0.5cm AS -0.6 -0.1 -1.3
-0.5 -0.2 -0.9
0.0 0.3 -0.3 0.5cm AI -0.5 -0.1 -0.9
-0.5 -0.1 -0.9
0.1 0.4 -0.2
0.3cm TS -2.0 -0.9 -4.7
0.1 0.3 -0.3
0.4 0.9 0.0 0.3cm TI -1.1 -0.3 -4.1
0.2 0.4 -0.3
0.3 0.7 -0.1
0.3cm AS -0.3 0.1 -0.7
-0.3 -0.1 -0.6
0.0 0.3 -0.3 0.3cm AI -0.2 0.1 -0.5
-0.3 -0.1 -0.6
0.1 0.3 -0.1
VMAT 0.5cm TS -10.6 -7.8 -15.4
-4.1 -3.3 -5.9
-1.3 0.2 -1.9 0.5cm TI -8.1 -4.9 -11.5
-3.8 -3.0 -5.3
-1.4 0.0 -2.1
0.5cm AS -1.0 1.9 -4.7
4.2 7.2 1.8
10.5 16.2 6.2 0.5cm AI -3.4 -0.9 -5.6
3.9 7.5 1.3
10.0 15.9 6.0
0.3cm TS -4.5 -3.2 -6.8
-3.0 -2.4 -3.7
-1.7 -1.1 -2.1 0.3cm TI -3.8 -2.3 -5.2
-2.9 -2.1 -3.5
-1.7 -1.1 -2.1
0.3cm AS 1.0 2.5 -0.1
3.4 4.9 2.1
7.1 11.3 4.6 0.3cm AI 0.4 2.3 -0.9
3.3 5.4 2.2
7.0 10.9 4.5
VMATRO 0.5cm TS -4.3 -2.6 -6.6
-1.6 -1.0 -2.1
-0.6 0.4 -1.5 0.5cm TI -2.6 -1.9 -3.7
-1.4 -0.8 -1.9
-0.7 0.4 -1.4
0.5cm AS -2.0 0.3 -5.2
-0.1 1.1 -2.3
2.0 3.5 0.2 0.5cm AI -2.8 -0.1 -5.9
-0.3 1.2 -2.6
1.8 2.8 0.1
0.3cm TS -1.1 -0.8 -1.5
-0.8 -0.6 -1.1
-0.6 -0.1 -1.0 0.3cm TI -0.9 -0.5 -1.4
-0.8 -0.5 -1.2
-0.7 0.0 -1.1
0.3cm AS -0.2 0.5 -1.3
0.3 0.9 -0.7
1.1 2.4 0.3 0.3cm AI -0.4 0.4 -1.5 0.2 0.9 -0.7 1.0 1.7 0.3
Table A4.3: Additional information on the range of perturbation effect on the planning parameters D99%, Average and D1% for the Skin3mm structure, over the 8 patient cases. Data is included for the Clinical, VMAT and VMATRO plans, the data shows the dose difference from the non-perturbed plan and the min/max difference over the 8 patients. The averaged data for the planning parameters shown in Figures 5.12, 6.16.
176
Perturbation D1% (Gy) D99% (Gy) Ave, (Gy) Direction Average min max Average Min Max Average Min Max
Clinical non-perturbed 41.3 40.8 41.8 34.6 33.9 35.0 38.6 38.4 38.9 0.5cm TS 42.2 41.9 42.7 22.7 17.2 26.4 38.2 37.1 38.9 0.5cm TI 42.0 41.7 42.6 27.9 18.9 31.5 38.6 37.4 39.2 0.5cm AS 41.3 40.9 41.8 34.0 33.7 34.4 38.1 37.7 38.7 0.5cm AI 41.4 40.9 41.8 34.2 33.8 34.6 38.2 37.7 38.7 0.3cm TS 41.7 41.3 41.9 32.6 29.8 34.0 38.7 38.1 39.0 0.3cm TI 41.6 41.4 41.8 33.5 30.4 34.6 38.8 38.2 39.1 0.3cm AS 41.3 40.8 41.8 34.4 34.0 34.7 38.3 38.0 38.8 0.3cm AI 41.3 40.9 41.8 34.4 34.0 34.7 38.3 38.0 38.8
VMAT non-perturbed 42.0 41.5 42.4 33.4 32.2 35.1 39.5 39.1 40.0 0.5cm TS 40.8 39.8 42.3 22.8 17.8 25.1 35.4 33.5 36.4 0.5cm TI 40.6 39.6 42.1 25.2 21.6 28.0 35.7 34.1 36.5 0.5cm AS 52.5 48.5 58.3 32.3 28.2 36.5 43.7 41.4 47.2 0.5cm AI 52.0 48.2 58.0 29.9 27.3 34.2 43.4 40.9 47.5 0.3cm TS 40.3 39.8 41.0 28.8 26.3 30.3 36.5 35.7 37.1 0.3cm TI 40.3 39.7 41.0 29.6 28.3 30.6 36.7 35.9 37.0 0.3cm AS 49.1 46.5 53.4 34.4 32.8 37.6 42.9 41.1 44.9 0.3cm AI 49.0 46.9 53.0 33.8 32.0 37.4 42.9 41.3 45.4
VMATRO non-perturbed 41.7 41.3 42.4 31.6 29.8 33.0 38.5 37.9 39.0 0.5cm TS 41.1 40.1 42.1 27.2 25.7 30.4 36.9 36.5 38.0 0.5cm TI 41.0 40.1 42.2 28.9 27.6 31.1 37.0 36.7 38.2 0.5cm AS 43.7 41.9 45.6 29.5 24.6 33.3 38.3 35.8 40.1 0.5cm AI 43.5 42.0 44.9 28.8 23.9 32.9 38.1 35.5 40.3 0.3cm TS 41.2 40.4 42.2 30.4 28.9 32.0 37.6 37.1 38.4 0.3cm TI 41.1 40.2 41.9 30.6 29.2 32.2 37.7 37.2 38.5 0.3cm AS 42.9 42.1 44.5 31.3 28.5 33.5 38.8 37.4 39.7 0.3cm AI 42.7 42.1 43.8 31.2 28.2 33.4 38.7 37.4 39.9
Table A4.4: Additional information on the range of perturbation effect on the planning parameters D99%, D1% and Average dose for the Skin3mm structure, for the 8 patient cases. Data is included for the Clinical, VMAT and VMATRO plans, the data shows the average doses and the min/max difference over the 8 patients. The averaged data for the planning parameters shown in Figures 5.13, 6.17-6.19.
177
Heart (Left CWs) Heart (Left CWs) Ipsilateral Lung (all patients)
V5 (%)
V25 (%)
V30 (%)
Perturbation Direction Average Min Max Average Min Max Average Min Max
Clinical 0.5cm TS -5.1 -6.5 -2.6 -0.3 -0.7 0.0 -5.6 -9.8 0.7 0.5cm TI -4.1 -5.1 -2.4
-0.3 -0.7 0.0
-3.3 -7.1 11.7
0.5cm AS 5.5 3.7 6.9
1.4 0.2 2.9
6.7 3.4 12.4 0.5cm AI 7.7 5.4 9.2
2.1 0.8 3.7
6.2 2.2 10.4
0.3cm TS -3.4 -4.3 -1.9
-0.2 -0.6 0.0
-3.2 -6.2 2.7 0.3cm TI -2.7 -3.3 -1.6
-0.2 -0.6 0.0
-1.8 -4.4 9.2
0.3cm AS 3.2 2.1 3.9
0.6 0.1 1.5
4.3 2.0 9.7 0.3cm AI 4.3 2.9 5.2
0.9 0.2 1.9
3.1 -3.5 6.2
VMAT 0.5cm TS -9.7 -11.1 -7.8
-0.2 -0.5 0.0
-5.9 -6.7 -4.0 0.5cm TI -7.2 -9.2 -3.9
-0.2 -0.5 0.0
-5.2 -5.9 -3.5
0.5cm AS 9.1 4.7 12.4
1.1 0.0 2.5
6.3 3.9 7.8 0.5cm AI 12.9 11.7 14.2
1.5 0.0 2.8
7.4 4.4 11.6
0.3cm TS -6.2 -6.9 -5.2
-0.2 -0.5 0.0
-3.9 -5.1 -2.6 0.3cm TI -4.6 -5.7 -2.4
-0.2 -0.5 0.0
-3.3 -3.8 -2.2
0.3cm AS 5.4 2.9 7.2
0.5 0.0 1.3
3.7 2.4 4.7 0.3cm AI 7.5 6.7 8.1
0.7 0.0 1.5
4.4 2.7 6.9
VMAT RO 0.5cm TS -10.0 -10.9 -8.5
-0.4 -1.1 0.0
-6.7 -7.9 -4.6 0.5cm TI -8.0 -10.8 -5.8
-0.4 -1.2 0.0
-5.8 -6.7 -3.9
0.5cm AS 9.2 6.3 12.5
1.5 0.0 3.1
6.5 4.0 7.8 0.5cm AI 12.7 11.1 14.4
1.8 0.1 3.4
7.7 4.5 11.7
0.3cm TS -6.4 -7.0 -5.4
-0.3 -1.0 0.0
-4.3 -5.9 -2.9 0.3cm TI -5.0 -6.9 -3.5
-0.3 -1.0 0.0
-3.6 -4.3 -2.4
0.3cm AS 5.4 3.8 7.4
0.7 0.0 1.7
3.9 2.5 4.7 0.3cm AI 7.3 6.4 8.1 0.9 0.0 1.8 4.6 2.8 7.0
Table A4.5: Additional information on the range of perturbation effect on the planning parameters for heart and lungs structures, heart. Data is included for the Clinical, VMAT and VMATRO plans, the data shows the average doses and the min/max difference over the 8 patients for the lung parameter and the 5 left chest wall patients for the heart parameters. The averaged data for the planning parameters shown in Figures 5.14-5.16 and 6.13-6.14.
178
Appendix 5
List of Alliance Manchester Business School - A units, and Specialist Medical Physics -B
units, together with credit value and assignment word count.
Unit title Credits Assignment wordcount
AMBS – A Units
A1: Professionalism and professional development in the healthcare environment
30 Practice paper – 2000 words A1 – assignment 1 – 1500 words A1 – assignment 2 – 4000 words
A2: Theoretical foundations of leadership 20 A2 – assignment 1 – 3000 words A2 – assignment 2 – 3000 words
A3: Personal and professional development to enhance performance
30 A3 – assignment 1 – 1500 words A3 – assignment 2 – 4000 words
A4: Leadership and quality improvement in the clinical and scientific environment
20 A4 – assignment 1 – 3000 words A4 – assignment 2 – 3000 words
A5: Research and innovation in health and social care
20 A5 – assignment 1 – 3000 words A5 – assignment 2 – 3000 words
Medical Physics – B Units
B1: Medical Equipment Management 10 2000 word assignment
B2: Clinical and Scientific Computing 10 2000 word assignment
B3: Dosimetry 10 Group presentation + 1500 word assignment
B4: Optimisation in Radiotherapy and Imaging
10 Group presentation + 1500 word assignment
B6: Medical statistics in medical physics 10 2000 word assignment (study design) 2000 word assignment (statistical analysis)
B8: Health technology assessment 10 3000 word assignment
B9: Clinical applications of medical imaging technologies in radiotherapy physics
20 Group presentation 2000 word assignment
B10a: Advanced Radiobiology 10 Virtual experiment + 1500 word report
B10c: Novel and specialised external beam radiotherapy
10 2000 word assignment
B10f: Radiation Protection Advice 10 1500 word report/pieces of evidence for portfolio
Generic - B Units
B5: Contemporary issues in healthcare science
20 1500 word assignment + creative project
B7: Teaching Learning Assessment 20 20 minute group presentation
Section C
C1: Innovation Project 70 4000-5000 word Literature Review Lay Presentation