ulice - cern documents/d_jra_5.2_public.pdf · although recommendation of target volume delineation...

D.JRA 5.2 - Results of robustness test with respect to inter-fraction variations Dissemination level [PU]

ULICE -GA n°228436 of 24

Project co-funded by the European Commission within the FP7 (2007–2013)

Grant agreement no.: 228436

ULICE Union of Light Centres in Europe

Project type: Combination of CP & CSA

Integrating Activities / e-Infrastructures / Preparatory phase

Start date of project: 1st February 2010 Duration: 36 months

Deliverable Report JRA5.2 – Results of robustness test with respect to inter-fraction variations Deliverable date: M18 2011/02/28

WP n° and title: WP 5 Adaptive treatment planning for ion radiotherapy

WP leader: Michael Krämer

Reporting period: 1

Name Partner

Author(s): Johannes Hopfgartner (MUW) MUW

Contributor(s): Filippo Ammazzalorso (UNIMAR) Urszula Jelen (UNIMAR) Dietmar Georg (MUW)

MUW, UNIMAR

Pillar coordinator: Richard Pötter MUW

Approved by TPB and CPO



Dissemination Level PU Public x PP Restricted to other programme participants (including the Commission Services) RE Restricted to a group specified by the consortium (including the Commission Services) CO Confidential, only for members of the consortium (including the Commission Services)

TABLE OF CONTENTS

LIST OF ABBREVIATIONS AND DEFINITIONS 3

PUBLISHABLE SUMMARY 4

CONTENTS AND SPECIFIC DOCUMENT STRUCTURE 5

CONCLUSION 21

REFERENCES 23



LIST OF ABBREVIATIONS AND DEFINITIONS

CBCT: Cone Beam Computed Tomography

CI: Conformity Index

CN: Conformity Number

CO: Coverage Index

CT: Computed Tomography

CTV: Clinical Target Volume

DVH: Dose Volume Histogram

HI: Homogeneity Index

HU: Hounsfield Unit

OAR: Organ At Risk

PTV: Planning Target Volume

ROI: Region of Interest

RT: Radiation Therapy

TPS: Treatment Planning System

WEPL: Water Equivalent Path Length

WP: Work Package



PUBLISHABLE SUMMARY

The aim of WP 5 in the ULICE project is to provide methods, protocols and software for adaptive ion

radiotherapy, i.e. taking into account treatment parameters which vary in time or location. They will be

designed as an enhancement of treatment planning systems and protocols used in current and upcoming ion

therapy facilities. A critical topic in ion radiation therapy is reduction of sources of error. Immobilization

devices as well as safety margins surrounding the clinical target volume must be carefully investigated taking

into account all their potential effects in the treatment planning and delivery process. Such sources of error

are above all intrafractional motion of the patient or its internal organs, interfractional alignment of patients

and anatomic as well as metabolic variations in the patient. WP 5 especially deals with the latter. The actual

report addresses robustness of ion beam treatment plans in the cranial region. The work is an attempt to

evaluate treatment plan robustness subject to heterogeneity displacement provoked by interfractional setup

uncertainties as well as different optimization techniques. Results are elaborated as a function of margin size

as well as beam arrangement. The latter virtually simulates a “gantry vs. no gantry” delivery approach and is

the first step to address treatment plan robustness from this point of view.



CONTENTS AND SPECIFIC DOCUMENT STRUCTURE

Introduction

The principal aim to be achieved in Radiation Therapy (RT), regardless of radiation quality, is that the target

is covered with the prescribed dose and healthy tissues receive as low dose as possible. Hence it is a crucial

step to ensure that delivered dose distributions show best conformance with the dose distribution intended at

the time of treatment planning. Many factors compromise the desired delivery of the dose that one cannot be

ensured that this assumption holds.

Arising sources of error in ion beam RT

Photons and charged particles have different physical as well as biological properties and that is the major

reason for some differences in the therapy planning approach. Charged particles, compared to photons, have

a finite and controllable penetration in depth. As range depends on traversed heterogeneities, the actual

delivered dose will be sensitive to the exact positioning of those heterogeneities in relation to the particle

beam (Lomax A. , 2008). Suspicious sources of error for planning charged particle therapy to be detected

and handled are:

• CT Hounsfield Units (HU) to Water Equivalent Path Length (WEPL) conversion

• Uncertainties in particle beam penetration due to non-homogeneous media (e.g. beam

pathways tangential to tissue – air surfaces)

• Interfractional patient setup errors

• Motion and/or anatomic and/or metabolic alterations of the patient’s internal organs and

time variation of the beam delivery (partly inter- as well as intra-fractional motion)

Immobilization methods and safety margins

In order to deal with the above mentioned potential uncertainties, precise patient positioning is an essential

aspect in RT, especially in charged particle therapy. The location of the distal edge of the particle beam at

fixed energy depends on the density and the amount of tissue traversed, and hence precise interfractional

patient positioning is vital (Shinohara 2009). The major goal of patient immobilization is to minimize

patient's motion during treatment as well as to facilitate rapid and consistent setup between fractions. The

immobilization devices should be easily customizable for the specific dimensions of the patient and easily

transportable from the imaging area to the treatment area. Moreover, immobilization devices must be

accounted for during the treatment planning process if they are within the beam path. That is because also

immobilization devices within the field can influence the lateral (thicker materials increase lateral penumbra)

and distal edge of the beam. To minimize both of these effects the thickness of the immobilization device

within the field should be kept to a minimum and the material should be as homogenous as possible.



Maximum rigidity as well as perfect compatibility with treatment devices such as high precision treatment

couches must be aspired. For detailed information concerning individual immobilization devices refer to

D.JRA 5.1.

Although recommendation of target volume delineation for charged particle therapy is similar as for photon

therapy, for charged particles great care must be taken in designing the Planning Target Volume (PTV).

Together with immobilization systems safety margins play the determining role in uncertainty management.

Not only lateral margins need to be carefully considered as in photon therapy but also the longitudinal

margin (in beam direction) due to the uncertainties related to range of particles (Yoon, 2008), (Langen,

2001).

WP 5.4 aims to address variation of anatomy and topography into treatment planning studies and hence

contribute to the overall knowledge and efficiency of (adaptive) ion beam RT. One task allocated to our

institutes is to tackle the simulation of setup uncertainties which represent the major potential source of

errors when dealing with intracranial tumor indications (see D.JRA5.1) and corresponding deviations in dose

distributions using treatment planning tools for particle therapy. Intracranial tumors represent a typical

indication for RT with charged particles and constituted e.g. the majority of the cases treated during the

German Carbon-ion Therapy Pilot Project (GSI ,2006). Therefore, in the framework of preparatory work for

upcoming ion beam facilities, investigations on the dosimetric robustness of intracranial proton and carbon

ion treatment plans against rigid mispositioning errors have been performed at the Medical University of

Vienna (MUW) and the University Hospital of Giessen and Marburg (UKGM). In particular, general

dosimetric stability against mispositioning as well as robustness of different beam arrangements should be

emphasized. Additionally the effect of different treatment plan optimization approaches is considered.



Proton treatment planning

A new mask system (see D.JRA 5.1) applying novel head immobilization approaches has recently been

implemented into clinical routine at the department of radiotherapy at the MUW. An extensive

reproducibility analysis has been carried out in order to derive realistic shifts for subsequent treatment

planning studies. By the application of the investigated translational and rotational shifts a “worst case”

scenario was simulated. It pretended the patients to be misaligned systematically by certain values. Planning

CT data sets which were used for the following treatment planning studies were shifted as well as rotated by

the deduced values and a full dose recalculation of initially generated proton plans has been performed.

Five patients suffering from skull base tumors who received conventional photon RT at the MUW were

gathered for proton treatment planning studies. Due to their medical indications those patients represented

potential candidates for justification of proton RT. All treatment plans were generated utilizing XiO® proton

Treatment Planning System (TPS) (CMS/Elekta, Crawley, UK) (Paganetti, 2008) in the active scanning

module. Standard protocols were followed in delineating Regions Of Interest (ROI). Tissues to be contoured

were: CTV, brainstem, eyes as well as optic nerves. In the actual treatment planning studies, a slightly

modified CTV to PTV safety margin definition as proposed by the ICRU and van Herk et al. (Herk 2000,

ICRU 2007) was adopted from the photon world, i.e. PTV provides reliability to cover 95% of the CTV with

95% prescribed dose over the entire RT treatment process. The evidently smaller and unusual fraction of

95% CTV coverage was chosen to diminish the above stated “worst case” scenario, which hardly reflects

reality. Firstly, CTV to PTV margin was set to 4 mm, decreasing in 1 mm steps to 2 mm in the planning

study progress. These values were chosen following former GSI routine for skull base cases (Karger 2001).

Plans were inversely validated acceptable if they fulfilled the CTV constraint defined above. Prescribed dose

to the PTV was 54 Gy. Normal tissue constraints were intended to be the maximum tolerable dose fraction

bothering the respective OAR, i.e. 55 Gy (optic nerves) and 56 Gy (brainstem).

Data preparation and recomputing methodology

The following planning and recomputing studies were performed

1. For a CTV to PTV safety margin of 4, 3, and 2 mm “original” proton treatment plans (Po) were

generated utilizing two lateral opposed as well as two frontal oblique beam ports, respectively. These

situations represented virtual “best case” scenario for respective margin sizes and served as reference

dose distributions.

2. For each individual “original” treatment plan (Po) two translationally shifted plans were created, in

positive and negative directions (P+(t) , P-(t)). Positive translational shift indicates simultaneous patient



movement in posterior, left lateral and cranial direction while negative shift means opposed

directions (anterior, right lateral and caudal direction) but application and full recalculation of the

“original” plans.

3. For each individual “original” treatment plan (Po) two rotationally shifted plans were generated, in

positive and negative directions (P+(r) , P-(r)). Positive rotational shift indicates simultaneous patient

movement around the longitudinal axis (roll angle) and around the vertical axis (yaw angle) in a

clockwise direction while negative rotational shift means in an anti-clockwise direction. Rotational

shifts were simulated by slightly changing the original incident port angle (roll angle) as well as the

original couch angle (yaw angle) but application and full recalculation of the “original” plans.

Rotation around the lateral axis (pitch angle) could not be simulated because the TPS did not provide

the feature to skip the treatment couch.

4. For each individual “original” treatment plan (Po) two recalculations of the dose distribution have

been performed, combining simultaneous translational and rotational shifts in positive and negative

directions (P+ , P-).

For all recomputed dose distributions “original” dose distributions (Po) served as reference dose distribution.

Dosimetric comparisons on CTV, PTV, brainstem, eyes, and optic nerves were evaluated. The following

evaluations were performed:

1. As a measure of Po proton treatment plan quality Conformity Index (CI) (Lomax 2003), Conformity

Number (CN) (Riet, 1997) as well as Homogeneity Index (HI) (Wu, 2002) were calculated for the

PTV and the CTV,

2. CI, CN, HI were calculated for P+(t), P-(t), P+(r) , P-(r), P+ and P- for the CTV and compared to their

reference values,

3. CI, CN, HI corresponding to respective beam arrangements (lateral opposed vs. oblique) were

compared.

The CI represents the fraction of the target volume receiving at least the reference dose and represents a

measure for target coverage. CI ranges from 0 (the entire target is situated outside the reference isodose) to 1

(the entire target is irradiated at the prescribed dose). The quality of irradiation of the target can be correctly

determined by the use of this index, but the volume of adjacent healthy tissue irradiated at the same dose is

not taken into account (Lomax, 2003).



Calculation of the CN simultaneously takes into account irradiation of the target volume as well as of healthy

tissue. It is composed of two terms whereby one is the CI and refers to target coverage and the other is

dedicated to healthy tissue surrounding the target and receiving a dose equal or higher the reference dose.

CN ranges between 0 and 1, while 1 indicates best case. Assessment of treatment plans based solely on CN is

rather difficult because for instance a CN of 0.6 can depict two situations: the target is partly irradiated with

complete protection of healthy tissue, or both target volume as well as healthy tissue are only partially

irradiated (Riet, 1997). By stating both, CN as well as CI, one can differentiate between the two scenarios.

Dose homogeneity in a volume of interest can be assessed as proposed by Wu et al. (Wu, 2002) with the

application of the HI. It correlates the difference between maximum and minimum Dose (D2% , D98%) with

prescribed dose. The ratio can be expressed in percentages, low percentage values indicating more

homogeneous target dose.

Results

Translational as well as rotational shift values were investigated for a novel mask system (HeadSTEPTM,

Elekta, Crawley, UK) (refer to D.JRA 5.1). For the application in the subsequent treatment planning study

they were derived by averaging the maximum shifts and rotations of the entire patient cohort participating in

the reproducibility study and adding or subtracting one standard deviation. Worst case shift values of 3 mm

were investigated in lateral and longitudinal while 2 mm in vertical patient direction. Concerning rotational

displacements 2° were deduced around respective axes.

Initial planning results

An example of a representative slice of an “original” proton treatment plan (P0) for one patient case is given

in Figure 1. In this treatment plan a CTV to PTV margin of 4 mm was chosen. Dosimetric data of P0 of all 5

patients are summarized in Table 1. All subsequent analyses refer to the values given in that table. The goal

of proton treatment planning was to deliver at least 95% of the prescription dose to 95% of the PTV, i.e. D95%

≥ 51.30 Gy. This objective was largely met for each patient, with small standard deviations. In fact, good

plan quality is also indicated by the other dose indexes with respective small standard deviations. Dose

indexes regarding OAR were within tolerance as well (Dmax (brainstem) < 56 Gy and Dmax (optic nerves) <

55 Gy) and are not listed in this context.



Figure 1: Representative slice of a P0 proton treatment plan for one patient case. Dose conformity depicted in axial, coronal as well as

sagittal view. Margin = 4 mm.

Table 1: Summary of characteristic dosimetric indexes of original proton treatment plans (P0) with different CTV to PTV safety

margin sizes (4 mm, 3 mm, and 2 mm). Lateral opposed vs. oblique beam arrangement. Abbreviations: Dx = Dose to x % of the

Volume, Vx = Volume getting at least x % of prescribed dose, cor. CTV = CTV correlating to the respective PTV specified above.



Post-shift recomputing results

Investigations revealed that there is barely difference of DVH parameters when comparing original plans P0

with rotated and recomputed plans (P±(r)) irradiated from a slightly different beam port and couch angles

differing ± 2° from the original ones. As a consequence we settle for analyzing differences in dose

distributions and consecutive deviations in plan quality exclusively between original plans P0 and

simultaneously shifted and rotated treatment plans P±. A representative slice of the post-shift isodose

distribution of the exemplary patient case is shown in Figure 2 representing proton treatment plans (lateral

opposed and oblique beam arrangements) being recalculated on the basis of a translationally as well as

rotationally shifted planning CT. Results of the recomputing investigations are shown in Table 2 and Table

3. In Figure 3 data are depicted graphically, where HI’ represents a transformation of the HI for better

visualization, that is (100-HU)/100.

Figure 2: Exemplary case: Upper row: Representative slice of proton treatment plan with lateral opposed beam arrangement a) P0 , b)

P+ and c) P- . Lower row: Representative slice of proton treatment plan with frontal oblique beam arrangement d) P0 , e) P+ and f) P-



Table 2: Summary of characteristic dosimetric indexes of positively shifted and rotated proton treatment plans (P+) with margin sizes

of 4, 3, and 2 mm. Lateral opposed vs. oblique beam arrangement. Abbreviations: Dx = Dose to x % of the Volume, Vx = Volume at

least x % of prescribed dose.

Table 3: Summary of characteristic dosimetric indexes of negatively shifted and rotated proton treatment plans (P-) with margin sizes

of 4, 3, and 2 mm. Lateral opposed vs. oblique beam arrangement. Abbreviations: Dx = Dose to x % of the Volume, Vx = Volume at

least x % of prescribed dose.



CI values derived from P+ were close to 1 and surrogate for adequate CTV dose coverage with lateral

opposed as well as with frontal oblique beam arrangement. When taking a closer look on P- CI values

systematically smaller values can be found. This is caused by a more direct and exclusive penetration of the

oral cavity region consisting of large inhomogeneous volumes and consequently degradation of the Bragg

peaks is much more pronounced at P-. This concludes in the fact that the average CI value of the treatment

plans P- does not fulfill the already loose dose coverage constraint specified above. While for oblique beam

arrangement each individual treatment plan P+ and P- passed the CTV constraint 2 out of 5 P- with lateral

opposed beam ports did not. The low mean value of the CI was caused by their tremendously low individual

CI values of around 0.80 and 0.90, respectively. Admittedly, such huge displacements of the patients within

the mask are rather infrequent and avoidable by the use of image guidance but still the worst case scenario is

not negligible. As expected CTV coverage is better at larger safety margins. Regarding the dependence of

the CI from beam arrangements it can be assumed that plans utilizing oblique beam arrangements were more

robust to heterogeneity misalignment than lateral opposed beam setups. This is surely caused by the

penetrated regions which are more homogeneous in case of oblique beams. Although there is no numerical

acceptance threshold HI’ values mirror the systematic behavior of CI, being worse for P- compared with P+.

The same holds if we compare lateral opposed with oblique beam setup. As expected the trend of healthy

tissue to be irradiated decreases with smaller margin size in P0.

The results reveal oblique beam arrangements to be slightly more robust to setup uncertainties of the patient

than their lateral opposed counterparts. The outcome of the studies showed that proton treatment plans

utilizing oblique beam ports fulfilled the CTV coverage constraint (95% coverage with 95% of the

prescribed dose) while treatment plans with lateral opposed beam directions did just partly. The work was

intended to show possible scenarios, which could happen at worst case.

In ion beam RT great care must be dedicated into designing the PTV. Not only do the lateral margins need to

be carefully considered, but also the distal margin due to the disastrous uncertainties related to the range of

ions. Therefore a margin on the CTV must be provided that can account for manifestation of additional

heterogeneities due to any kind of motion. While lateral margins to the CTV (accounting for beam penumbra

as well as lateral target miss) can theoretically be applied unchanged from photon RT, there is no accordance

to distal margins in this sense (Shinohara 2009). Ideally, there is the need of treatment field individual distal

margins which soon reaches software constraints (A. Lomax 2008, Zhang 2007). Here, margin sizes around

the CTV were chosen according to former GSI routine, starting with 4 mm and decreasing to 2 mm. The

smallest margin value (2 mm) in the actual studies is lower than the value of shifts in longitudinal and lateral

patient directions and consequently lateral misses of the CTV are obvious. Still it should be included in these

studies in order to reveal the hereby provoked range of coverage degradation keeping in mind that

exaggerated shifts are hardly realistic. Note that this comparison analysis has been performed on the CTV, as

the PTV in this case has been designed such as to try to deal with errors at the periphery of the CTV, as is the

case in conventional therapies.



Figure 3: Graphical representation of characteristic dosimetric indexes comparing different treatment planning strategies (i.e.

different margin sizes and beam arrangements). a) A CTV to PTV safety margin of 4 mm was chosen in P0 (PTV = 4 mm) for

compensation of setup uncertainties. b) and c): PTV = 3 mm and PTV = 2 mm, respectively. HI’ = (100-HU)/100). The first three

columns in respective plots represent lateral opposed beam arrangement while the last three columns describe oblique beam

arrangement.



Carbon ion treatment planning

Six patients, who received conventional photon RT at the Department of Radiotherapy and Radiation

Oncology of the UKGM, were selected for the carbon ion treatment planning studies. Five were originally

treated for intracranial tumors, with stereotactic RT. The remaining patient, affected by a head-and-neck

tumor, was treated with IMRT. For this patient case the boost volume, located in the oropharyngeal region,

was taken as target for carbon ion irradiation. For this study patients were explicitly selected, whose target

volumes were localized in a region characterized by elevated inhomogeneity and for which dosimetric

problems were expected. For all patients, the original contours, prepared for photon irradiation according to

internal planning protocols of the UKGM, were retained. A CTV to PTV safety margin of 2 mm was applied.

For all patients, biologically optimized treatment plans for carbon ion irradiation utilizing active scanning

were prepared using the TRiP98 TPS (Krämer 2000). The treatment plans for the cranial cases were all

composed of two beams. The five cranial patients all received at least one treatment plan with a lateral

opposed beam setup, typical for intracranial particle therapy treatments. All but one of these plans used a

purely horizontal (according to the CT reference system) lateral opposed beam arrangement while in the

remaining one a small inclination of one of the beams was introduced (to better encompass the target and

spare OAR in its vicinity). Two of the cranial patients were imaged with a slight rotation of the head around

the longitudinal patient axis, in order for their head to fit inside the stereotactic localization frame used for

their treatment. For them extra lateral opposed beam plans were created, introducing small rotations in the

beam setups (15 degrees in one case, 10 degrees in the other) to simulate the more realistic situation of

immobilization without head rotations (e.g. using a thermoplastic mask). Additionally, two of them received

a third plan using a more complex beam setup, representing a highly robust choice. All cranial plans were

optimized in single-field mode. Additionally two cranial plans were also re-optimized using multiple-field

optimization.

For the oropharyngeal patient two treatment plans were prepared, the first using two frontal beams (a vertical

one and a 45-degree-inclined one) and the second with an additional inclined beam, mirroring the one

already present. Because of stricter requirements on OAR sparing, multiple-field optimization was used for

both plans.

All plans were computed to deliver 3 GyE/fraction. For the biological modelling an alpha-beta ratio of 2 was

applied.

Data preparation and recomputing methodology

In order to test the dosimetric robustness of the prepared plans, treatment delivery in presence of translational

setup errors was extensively simulated. This was achieved by recomputing the plans in TRiP, introducing a

shift of the irradiation rasters with respect to the planning CT. For all patients, for all plans, a series of 52

translational setup errors was applied: all possible 3D displacement vectors having {0, 1mm} as single



components (e.g. (0,1,1), (-1,0,0), etc.) and all those having {0, 2mm} as single components (e.g. (2,-2,0),

(0,0,2), etc.). The magnitude of the applied shifts was based on the experience with immobilization

reproducibility of mask based systems collected at the Department of Radiotherapy and Radiation Oncology

of the UKGM (e.g. (Gross 2003)), from literature (e.g. (Karger 2001)) and summarized in D.JRA 5.1.

Figure 6: On the left two original cranial treatment plans, on the right the consequences of simulated setup errors, both of 2 mm in SI

direction: cold spots and high dose leakage are clearly visible in both cases

The resulting dose distributions (see e.g. Figure 6 and Figure 13) and their DVHs were scrutinized.

Moreover, in order to obtain an overview of the effects of all shifts on each plan and to quantitatively

characterize such effects and possibly compare different beam setups, three well-known dosimetric indexes

were extracted for the target volumes: the Homogeneity Index (HI), the Conformity Index (CI) and the

Coverage Index (CO). It should be emphasized that here CI as well as CO indexes are defined differently

compared to the proton studies. In this context CI is defined equal to the CN in the previous proton section

while CO assumes the role of the former CI.

The dose distributions generated and the dosimetric indexes extracted were used to investigate the following

issues:

• general dosimetric stability of carbon ion treatment plans (robustness) against mispositioning subject

to interfractional setup errors,

• compared stability of different beam setups (where applicable) in terms of target coverage,

• compared stability of the same beam setup optimized with/without multiple-field optimization

(where applicable) in terms of target coverage.



Results

General behaviour of the standard plans

Due to the presence of areas of high inhomogeneity in the vicinity of the tumor, as expected, all the carbon

ion plans suffered from dosimetric disturbance, in relation with the magnitude of the simulated positioning

errors (with the exclusion, of course, of the third plan of Pat1 and Pat2, explicitly chosen for their known

robustness).

Table 4: Population summary of dosimetric indexes

In Table 4 some of the results of the extensive dose computation with simulated setup errors are reported,

expressed as dosimetric quality indexes. For each shift the values of the indexes for all patients and for all

treatment plans (using standard clinical beam setups) have been put together. The table fully reports the

values for the 2-mm shifts in all directions and for the worst case scenario (average/std. deviation of the

individual worst cases).

Two full examples are given in Figure 7 and Figure 8, where the values of the three dosimetric quality

indexes (HI, CI and CO) are reported for the horizontal lateral opposed beam plans of Pat1 and Pat2 and for

all simulated setup errors. The datapoints (bars) are ordered by increasing magnitude of setup error. Position

translations with different single components, but having the same 3D magnitude, are grouped by colour. All

three indexes show a clear trend, with their values getting generally worse (i.e. lower for CI and CO and

higher for HI) for increasing length of the positioning error vector. Shifts below 1.5 mm had in general no

effect. Starting from 2 mm effects of the setup errors on CO95% become visible.



Figure 7: The three dosimetric quality indexes, for all the applied shifts, for cranial patient Pat1 (2 horizontal lateral opposed beams).

In CO empty bars represent CTV coverage, full bars represent PTV coverage.

Figure 8: The three dosimetric quality indexes, for all the applied shifts, for cranial patient Pat2 (2 horizontal lateral opposed beams).

In CO empty bars represent CTV coverage, full bars represent PTV coverage.



Such coverage loss appears in general not surprising, since it’s caused by setup errors greater than the

applied CTV to PTV margin. These effects are however worth of consideration, as it was observed for

analogous cases in the preceding proton study, because of their possible consequences in terms not only of

lateral coverage erosion, but also of “in-depth cold spots” (see e.g. Fig. 6 lower row or Fig. 13). An ideally

robust carbon ion or proton plan would exhibit almost constant (good) values of dosimetric indicators,

throughout the entire series of expected setup errors.

Comparison between different beam setups for the same patient

One of the most interesting applications of robustness tests against an extensive set of setup errors is the

direct comparison, in terms of dosimetric stability, of different plans for the same patient. In Figure 9 and

Figure 10 two examples of such comparison are reported. The charts show the CO95% level of three

different beam setups in two of the cranial cases (Pat1 and Pat2). For these patients, as described previously,

two different lateral opposed beam plans were prepared, differentiated by a slight rotation about the patient's

longitudinal axis (roll). In both figures they are indicated by “LR” (horizontal) and “roll/tilt” (rotated). PTV

coverage levels of two more plans, one for each patient, making use of more sophisticated beam setups, are

shown.

Figure 10: Comparison in terms of robustness of three beam setups for one patient.

Figure 9: Comparison in terms of robustness of three beam setups for one patient.



These extra plans were identified as optimal (hence the denomination “opt” in the figures) among a

predefined set through the RobuR software (Ammazzalorso 2010), implementing the Port Homogeneity

Index analysis ( Ammazzalorso 2009) developed at the Department of Radiotherapy and Radiation

Oncology of the UKGM.

Comparison of plan optimization modalities

Most of the plans for the cranial cases used in this study were optimized in single-field mode. For two

patients, however, additional multiple-field optimized plans were added. Comparisons of these two

approaches, for such two cases, in terms of robust target coverage, are shown in Figure 11 and Figure 12.

The multi-field-optimized plans appear to be sensibly weaker against mispositioning.

Qualitatively this result is consistent with the intrinsic properties of this optimization modality. In multiple-

field mode, in fact, beams are optimized to deliver different, inhomogeneous target coverage levels, which

add up to full coverage when all beams are delivered. Therefore, dosimetric issues affecting a single beam of

a multiple field optimized plan are likely to influence the optimality of the entire plan.



Figure 13: Consequences of a 2 mm shift in lateral patient direction on a multiple field optimized oropharyngeal case

Figure 12: Comparison, in terms of robustness, of plans optimized with the single-field and with the multiple-field optimization approaches.



CONCLUSION

Generally heterogeneities of the tissues through which the ions travel greatly affect their range. Hence, when

choosing incident beam angles it is important to try and minimize the amount of heterogeneous tissues

through which the projectiles must trespass. It is also desirable to avoid complex structures. Specific

examples include oral cavities which have numerous air cavities and a complex shape as well as the petrous

ridge. The effects of rigid patient mispositioning on the conformity of intracranial RT treatments with

protons as well as carbon ions were extensively simulated on patient cases with tumors located in areas

characterized by density inhomogeneities. For relatively large positioning errors, effects were evident for

both beam qualities. A trend between setup error magnitude and dosimetric problems could be observed, e.g.

for carbon ion treatment plans applying typical particle therapy beam setups (lateral opposed for base of the

skull, frontal inclined for oropharynx when a 45 degree line is available), starting at displacements above 2

mm (i.e. equal to the applied safety margin). Investigation of overly large setup errors (i.e. larger than the

CTV to PTV margin) was deemed worthy of attention in both studies, as they can produce “in-depth” cold

spots, due to changes in penetration range. These effects could be summarized in terms of dosimetric

indexes. Yet, it is not possible to make statements about the clinical relevance of such errors when they

interfere randomly with the correct treatment delivery. Definitely, if errors like those demonstrated in this

study were systematically present, they would affect the quality of the treatment. A relatively greater

sensitivity has been shown for multiple-field-optimized treatment plans. Multiple-field optimization

constitutes, nevertheless, an essential clinical tool to achieve e.g. better OAR sparing. Its use in combination

with robustness optimization approaches is suggested. Clinical relevance will have to be further investigated.

Nevertheless, to ensure the best and safest therapy possible, preventive countermeasures should be adopted,

like the use of accurate and reproducible immobilization (see D.JRA 5.1) and/or robust planning approaches,

based either on automatic tools or clinical experience.



REFERENCES

Ammazzalorso, F, Jelen U, Krämer M, Zink K,. “An integrated software tool for the selection of robust particle therapy irradiation setups GUNMA.” PTCOG49. 2010.

Ammazzalorso, F., Jelen, U., Krämer, M. et al. “Validation of a homogeneity index for the optimal selection of robust beam configurations in heavy ion radiotherapy planning.” ESTRO 10. Maastricht, 2009.

Gross. “Assessment of the accuracy of a conventional simulator for radiotherapy of head and skull base tumors.” Technol. Cancer Res. Treat. 2, 2003: 345-351.

GSI. Ion-Beam Radiotherapy in the Fight against Cancer. 2006. http://www.gsi.de/documents/DOC-2006-Aug-25-1.pdf.

Herk, van. “The probability of correct target dosage; dose population histograms for deriving treatment planning margins in radiation therapy.” Int. J. Radiation Oncology, Biol. Phys. Vol. 47; No. 4, 2000: 1121 - 1135.

ICRU. “ICRU Report 78, Prescribing, Recording, and Reporting Proton-Beam Therapy, Vol. 7 No 2.” Oxford, 2007.

Karger. “Three-dimensional accuracy and interfractional reproducibility of patient fixation and positioning using a stereotactic head mask system.” Int. J. Radiat. Oncol. Biol. Phys. 49, 2001: 1493-1504.

Krämer. “Treatment planning for heavy-ion radiotherapy: physical beam model and dose optimization.” Phys. Med. Biol. 45, 2000: 3299-3317.

Langen, Jones. “ Organ motion and its management.” Int. J. Radiation Oncology Biol. Phys.,Vol. 50, No.1, 2001: 265-278.

Lomax. “Quantifying the degree of conformity in radiosurgery treatment planning.” Int. J. Radiation Oncology Biol. Phys, 2003: 1409 –1419.

Lomax, A. “Intensity modulated proton therapy and its sensitivity to treatment uncertainties 1: the potential effects of calculational uncertainties.” Phys. Med. Biol. 53, 2008: 1027-1042.

Lomax, A.J. “Intensity modulated proton therapy and its sensitivity to treatment uncertainties 2: the potentioal effects of inter-fraction and inter-field motions.” Phys. Med. Biol. 53, 2008: 1043-1056.

Paganetti. “Clinical implementation of full Monte Carlo dose calculation in proton beam therapy.” Phys Med Biol.7 ;53(17), 2008: 4825-53.

Riet, van’t. “A conformation number to quantify the degree of conformality in brachytherapy: Application to the prostate.” Int J Radiat Oncol Biol Phys 37, 1997: 731–736.

Shinohara. “http://www.oncolink.org/treatment.” 2009.

Wu, Mohan. “Optimization of intensity-modulated radio-therapy plans based on the equivalent uniform dose.” Int J Radiat Oncol Biol Phys. ;52(1), 2002: 224-235.



Yoon, Kim ,, ,. “ Inter- and Infrafractional movement- induced dose reduction of prostate target volume in proton beam treatment.” Int. J. Radiation Oncology Biol. Phys., Vol. 71, No.4, 2008: 1091-1102.

Zhang, X. “Effect of anatomic motion on proton therapy dose distributions in prostate cancer treatment.” Int.J. Radiat. Oncol. Biol. Phys. 67, 2007: 620-629.

ulice - cern documents/d_jra_5.2_public.pdf · although recommendation of target volume delineation...

Documents