IMRT RTOG Definitive IMRT for Low Risk Prostate Cancer. All about dose and dose matters, probably Although hormones may matter

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1 Definitive for Low Risk Prostate Cancer Howard Sandler, MD, MS Bloom Family Chair in Cancer Therapeutics Cedar-Sinai Medical Center All about dose and dose matters, probably Although hormones may matter more PTV TCP OAR NTCP IGRT RTOG 9406 Tucker IJROBP 78:1253, 2010 Tucker IJROBP 78:1253,

2 Observed toxicity vs. NTCP Comparisons between modalities Without randomization, there are concerns about bias and selection factors Challenges with endpoints (PSA, DM, OS, PRO) Changes over time Learning curves Tucker IJROBP 78:1253, 2010 Final Four AS SBRT Sanda NEJM 358:1250,

3 vs. SBRT Final Four SBRT dose is highly model dependent SBRT is less forgiving Limited follow-up and data Until phase III data emerges: AS Winner is SBRT AS vs. Final Four Low risk prostate cancer Hard to determine a priori A matter of numbers (NNT) Emerging data from Swedish randomized trial suggests survival advantage is broad based AS Winner SBRT 3

4 vs. Comparison of NNT Cure rates? Have to be the same or close What about morbidity? Sanda et al. Less with Winner:! Study SWOG-RTOG Post-op adjuvant trial Swedish Surg vs Observation (SPCG-4) SPCG-7: Widmark NCIC: Reported at ASTRO NNT for overall survival endpoint 9 (13 yrs) 19 (12 yrs) 11 (10 yrs)* 13 (7 yrs)* *NNT calculations courtesy of Andre Rogatko and Ning Li, -Sinai Thompson J Urol 181:956, 2009, Bill-Axelson JNCI 100:1144, 2008 vs. Final Four Cure rates? Have to be the same or close What about morbidity? Sanda et al. Less with AS Winner:! SBRT 4

5 How is done? Rectal Definition Whole, RTOG 0126 Rectal wall, SI joint to IT Whole, RTOG 0126 Whole, 1 cm sup/inf PTV Whole, RTOG 0126 Whole, RTOG 0126 Whole, RTOG 0126 Whole, RTOG sup, anus inf Whole, RTOG 0126 Wall, 1 cm sup/inf PTV RECTAL CONTOUR EXAMPLE RECTAL CONTOUR EXAMPLE Bottom of the Sacro-iliac Joint Sigmoid Flexure 1cm above PTV Bottom of Anus Bottom of the Ishial Tuberosities 1 cm below PTV 5

6 Rectal Constraint <20% over 70, <50% over 50 <40% over 70, <30% over 75.6 <17% over 65, <35% over 40 <25% over 70, <30% over 60, <50% over 50 <10% over 75, <17% over 65, <40% over 40 <20% over 65, <50% over 45 <20% over 65, <45% over 40 <15% over 70, <45% over 50 < 5% over 75, <20% over 70, <25% over 65, <35% over 60, <50% over 50 <53% over 47, max dose Gy RECTAL DVH EXAMPLE 40 Gy < 35% < 40% < 45% 45 Gy < 50% Lower Dose Constraint 50 Gy < 45% < 50% 65 Gy < 17% < 20% < 25% 70 Gy < 15% < 20% High Dose Constraint 75 Gy < 5% < 10% < 20% Sim Filling Instructions PTV Constraints Rectal/Full Bladder Instructions Empty Rectum/Full Bladder Empty Rectum/Full Bladder Empty Rectum/Full Bladder Rectal/Full Bladder Empty Rectum/ Bladder Empty Rectum/Full Bladder Rectal/Full Bladder Empty Rectum/Empty Bladder 100% to 99.55% PTV (except post) 100% to 98% PTV 100% to 98% PTV 99% to 95% PTV 100% to 95% PTV 98% to 95% PTV 100% to 98% PTV 100% to 95% PTV 100% to 98% PTV 90% to 95% PTV 6

7 Dose for T1c, GS 3+4 (1/12 cores), PSA 5 ng/ml 77.7 Gy in 42 fractions 79.2 Gy in 44 fractions 77.4 Gy in 43 fractions 78 Gy in 39 fractions 76 Gy in 38 fractions 77.7 Gy in 42 fractions 77.4 Gy in 43 fractions 75.6 Gy in 42 fractions 75.6 Gy in 42 fractions 86.4 Gy in 48 fractions IGRT? kv and fiducials, Calypso Adaptive MV with fiducials, Calypso kv and fiducials CBCT and fiducials, Calypso CBCT, kv and fiducials, Calypso CBCT and fiducials, Calypso CBCT without fiducials kv and fiducials kv and fiducials, Calypso CTV-PTV Margin (mm) 5 everywhere Adaptive based on wk 1 CBCT 5 everywhere 7 post, 10 elsewhere 3 post, 5 elsewhere 5 everywhere 4 posteriorly, 6 inf, 5 elsewhere 3 post, 5 elsewhere 4-5 post, 5-7 laterally, 5 elsewhere 6 everywhere VMAT Yes (prefer ) 100% 90% 10% 7

8 VMAT Regional Lymph des in High Risk Regional Lymph des CTV to PTV margin 10 mm N/A 7-9 mm sup/inf, 5 mm elsewhere N/A N/A 10 mm 5 mm 5-7 mm 7-12 mm 6-10 mm for prostate Hard to prove that it is superior to 3DCRT (or SBRT, brachy, protons,, AS.) But intermodality comparisons are challenging Heterogeneity between centers t taking full advantage of DVH information ASTRO/ROI developing registry 8