novel rt techniques for treating lung cancer 1403
DESCRIPTION
Novel RT techques for treating lung cancerTRANSCRIPT
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Novel RT Techniques
For Lung Cancer Treatment
Yong Chan Ahn, MD, PhD
Dept. of Radiation Oncology
Samsung Medical Center
Sungkyunkwan University School of Medicine
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Fundamental of RT
• To deliver high dose to tumor
• To limit dose to normal tissues
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From Classic to Conformal
• Better local control
• Enhanced quality of life and reduced morbidity
• Improve accuracy of every step!
• Patient-specific:
– Individualized
– Customized
– Adaptive
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RT Process
Steps in RT that can be represented by links in a chain.
Tx accuracy will be limited by the weakest link in the chain
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Preparation for Radiation Therapy
• Acquisition of CT (MR, PET-CT)
• Contouring
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Novel Technology in RT
Image guided RT (IGRT)
Stereotactic Ablative RT (SABR, SBRT)
Intensity Modulated RT (IMRT)
Particle Beam Therapy (Proton; Carbon)
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Image guided RT (IGRT)
Stereotactic Ablative RT (SABR, SBRT)
Intensity Modulated RT (IMRT)
Particle Beam Therapy (Proton; Carbon)
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Image Guided RT (IGRT)
If you can’t see it, you can’t hit it.
If you can’t hit it, you can’t cure it.
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To identify and correct problems
arising from inter- and intra-
fractional variations in patient setup
and anatomy
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Electronic Portal Image (EPI)
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KV Cone-beam CT (CBCT)
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In-Room CT
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MV CT (Tomotherapy)
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Fluoroscopy-based IGRT
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CyberKnife (Synchrony)
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Image guided RT (IGRT)
Stereotactic Ablative RT (SABR, SBRT)
Intensity Modulated RT (IMRT)
Particle Beam Therapy (Proton; Carbon)
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Ablative RT (by conventional technique)
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Stereotactic Ablative (Body) RT
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SABR
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Conventional RT SABR
Dose/fraction 1.8~3.0 Gy 10~20 Gy
Fraction number 10~30 fractions 1~5 fractions
Target delineation GTV, CTV, (ITV), PTV GTV, CTV, ITV, PTV
(GTV CTV)
Margins cm range mm range
Need for mechanical
accuracy Low to medium Very high
Need for respiratory
motion control Moderate High
Radiobiology Well understood Still poorly understood
Interaction with
systemic therapy Currently active Will become active
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Rationale of SABR in Stage I NSCLC
• RT is better than doing nothing.
• (+) dose-response relationship in local control.
• The smaller the tumor, the higher the local control
and survival by RT.
• LN metastasis incidence is very low.
• Shorter RT is better than protracted RT in survival.
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Importance of tumor size Importance of RT duration
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SABR Indications at SMC
• cT1-2,N0
• Single metastasis or recurrence
• ≤ 5 cm in size (preferably ≤ 3 cm)
• Location (peripheral > central, upper > lower)
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Respiratory Training (Respiratory Signal Analysis Program)
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Characteristics # Pt (%)
Age Median 69 (39~88) years
Sex Male 98 (84.5%)
Female 18 (15.5%)
Tumor nature Primary 38 (32.8%)
Metastatic 78 (67.2%)
Lung 32 (41.0 %)
GI Track 24 (30.8 %)
Head & Neck 9 (11.5 %)
Others 13 (16.7 %)
Patients’ Characteristics I (116 Patients: ’01/Feb~’10/Nov)
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Characteristics # Pt (%)
Tumor size ≤ 2.0 cm 58 (50.0%)
> 2.0 cm 58 (50.0%)
RT dose 50 Gy/5 Fx’s (’01/Jun~’02/May) 8 ( 6.9%)
60 Gy/5 Fx’s (’02/June~’09/Dec) 72 (62.1%)
60 Gy/4 Fx’s (’10/Jan~’10/Dec) 36 (31.0%)
Patients’ Characteristics II (116 Patients: ’01/Feb~’10/Nov)
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Survival
Months
Pro
bab
ilit
y
p = 0.036
66.4%
53.8%
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Summary
• SBRT to lung cancer at SMC:
– High local control (90%)
– Favorable 5 year survival (primary/metastatic –
66.4%/53.8%)
– Very low risk of complication (Grade 2/3 –
3.4%/1.7%)
– Highly effective and curative modality to patients
who are unfit for surgery.
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Acta Oncologica, 2012
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Summary
• SBRT for single or oligo-metastasis seems
quite effective and safe.
• Tumor size, disease-free interval, and presence
of extrathoracic disease are prognosticators for
survival.
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Image guided RT (IGRT)
Stereotactic Ablative RT (SABR, SBRT)
Intensity Modulated RT (IMRT)
Particle Beam Therapy (Proton; Carbon)
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Multi-leaf Collimator
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LINAC-based IMRT
• Static MLC (“step-and-shoot”)
• Dynamic MLC (“sliding window”)
• Volumetric modulated arc (VMAT)
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Tomotherapy
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Example Case: Sq, cT2N3
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SMC Experience of IMRT
• May 2010~November 2012
• 77 patients with N3 (+) stage IIIB NSCLC
• Definitive CCRT by 3DCRT or LINAC- IMRT
– 66 Gy/33 Fx’s to CTV
– 3DCRT (48); IMRT (29)
– Weekly pacli-/docetaxel + cis-/carboplatin (67)
– 3 weekly pemetrexed/etoposide + cisplatin (10)
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Characteristics 3D-CRT (48) IMRT (29) p-value
Median age (range) 62 (44-72) yrs 59 (40-80) yrs 0.7441
Gender Male
Female
35 (72.9%)
13 (27.1%)
18 (62.1%)
11 (37.9%) 0.3904
Smoking history Yes
No 34 (70.8%) 17 (58.6%) 0.2722
Median FEV1 (range) 2.49 (1.17-3.90) L 2.50 (1.46-3.71) L 0.7909
ECOG performance 0
1
10 (20.8%)
38 (79.2%)
6 (20.7%)
23 (79.3%) 0.9880
Primary site lobe Upper/middle
Lower
39 (81.3%)
9 (18.7%)
13 (44.8%)
16 (55.2%) 0.0009
Histology Adenoca
Sq cell ca
Others
31 (64.6%)
15 (31.2%)
2 (4.2%)
22 (75.9%)
3 (10.3%)
4 (13.8%)
0.0533
Median tumor size (range) 3.8 (1.3-12.2) cm 3.7 (1.0-9.2) cm 0.7852
cT stage cT1-2
cT3-4
34 (70.8%)
14 (29.2%)
23 (79.3%)
6 (20.7%) 0.4111
Involved N3 region Contralateral mediastinum
Supraclavicular
29 (60.4%)
26 (54.2%)
7 (24.1%)
24 (82.8%)
0.0020
0.0108
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Dosimetric Parameters Variable 3D-CRT (48) IMRT (29) p-value
CTV
Median
<300 cm3
≥300 cm3
279.3 (89-1,543) cm3
28 (59.3%)
20 (41.7%)
357.5 (89-763) cm3
10 (34.5%)
19 (65.5%)
0.7064
0.0425
Dose to lung
Mean
V5
V10
V15
V20
18.4 (9.3-28.0) Gy
57.2 (29.8-72.9)%
48.6 (24.5-63.5)%
40.6 (18.1-54.5)%
32.8 (14.3-50.0)%
19.6 (14.6-25.2) Gy
65.1 (48.4-90.0) %
51.8 (41.8-62.9) %
42.3 (34.7-53.6) %
35.6 (28.2-45.9) %
0.0306
0.0002
0.1072
0.0519
0.0612
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Clinical Outcomes 3D-CRT (48) IMRT (29) Total (77)
Disease progression 24 (50.0%) 21 (72.4%) 45 (58.4%)
Failure pattern LR
Distant
Both
4 (8.3%)
17 (35.4%)
3 (6.3%)
2 (6.9%)
15 (51.7%)
4 (13.8%)
6 (7.8%)
32 (41.6%)
7 (9.1%)
Median time to progression 9.1 months 6.0 months 8.2 months
Esophagitis Grade ≤2
Grade 3
41 (85.4%)
7 (14.6%)
21 (72.4%)
8 (27.6%)
62 (80.5%)
15 (19.5%)
Pneumonitis Grade 1
Grade ≥2
32 (66.7%)
16 (33.3%)
22 (75.9%)
7 (24.1%)
54 (70.1%)
23 (29.9%)
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Summary
• Limitations:
– Small number of patients
– Heterogeneous patient population
– Retrospective nature
• IMRT group:
– More extensive disease and larger CTV
– More frequent early distant metastasis
• Careful case selection and intensified systemic Tx
maybe considered
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Image guided RT (IGRT)
Stereotactic Ablative RT (SABR, SBRT)
Intensity Modulated RT (IMRT)
Particle Beam Therapy (Proton)
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Why Proton Beam Therapy?
• Bragg peak (1946, Wilson et al. first proposed PBT)
• RBE=1.1
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History of PBT
• 1950: 1st clinical application
to suppress pituitary
function and to reduce
metastases from breast ca
• 1950’s: Uppsala Group
(Sweden) pioneered proton
RT for cancer
• Early 1960’s: Harvard
Cyclotron Group (US)
developed most current
techniques
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50
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PBT for Stage I NSCLC
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PBT for Stage III NSCLC
• Need for dose escalation:
– RTOG trials (X-rays): 8311 (+) and 0617 (-)
• Few dosimetric comparison studies:
– Advantage of PBT over X-rays seems more
significant in stage III than stage I
• Recent on-going trials of high-dose PBT with
concurrent chemotherapy
– Safe and effective
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Dose (Gy)
No
rmal
ized
vo
lum
e (%
)
Dose-volume Histogram (DVH)
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70 80
Proton PTV
Proton Spinal Cord
Proton Both Lungs
IMRT PTV
IMRT Spinal Cord
IMRT Both Lungs
3DCRT PTV
3DCRT Spinal Cord
3DCRT Both Lungs
Tomo PTV
Tomo Spinal Cord
Tomo Both Lungs
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Normal Tissue DVH
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No
rmal
ized
vo
lum
e (%
)
CTV DVH
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CTV DVH
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PBT for III NSCLC
• Need for dose escalation:
– RTOG trials (X-rays): 8311 (+) and 0617 (-)
• Few dosimetric comparison studies:
– Advantage of PBT over X-rays seems more
significant in stage III than stage I
• Recent on-going trials of high-dose PBT with
concurrent chemotherapy
– Safe and effective
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Summary
• PBT can give excellent dose distribution using less ports (Bragg peak)
• PBT maybe more widely applicable than SABR even with pulmonary comorbidity and difficult tumor location in stage I
• PBT may save more normal tissue in stage III than in stage I
• Pencil beam scanning seems promising
• Dose-escalated PBT with concurrent CTx may be safe and effective
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Proton Therapy Center
Samsung Medical Center
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Multidisciplinary
approach
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Importance of Target Delineation
• Target contouring errors generate systematic errors
which no level of image guidance will eliminate.
• Target delineation accuracy cannot be overemphasized!
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