11. Breath adapted radiotherapy D eep inspiration breath hold Free breathing Irradiated heart volume 8% Irradiated heart volume 1%
12. 4D radiotherapy ‘ .. is the explicit inclusion of temporal changes in anatomy during imaging, planning and delivery of radiotherapy [Keall ’03] 4D imaging 4D planning 4D delivery 4D CT scans Tumour mobility Normal organ avoidance Respiratory gating
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14. T owards optimization of r adiotherapy Treatment and patient tailoring Better imaging Better beam delivery
15. T owards optimization of r adiotherapy Treatment tailoring Better imaging Better beam delivery Integration with targeted therapy Optimal integration with medical therapy
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20. Van Nuys Prognostic Index Scores of 3-4 - 98% local control without RT Scores of 5-7 - 32% failed without RT, 16% with RT Scores of 8-9 - 100% failure without RT, 60% with RT
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22. Distant Failure Jatoi et el. JCO 2005. Trial Pt Time pt. Mast. BCT WHO 1972-79 179 22 yrs 24% 23% Milan I 1973-80 701 20 51% 54% NSABP06 1976-84 1406 20 33% 40% US NCI 1979-89 279 20 34% 39% EORTC 10801 1980-86 903 10 34% 30% Denmark 82TM 1983-89 859 6 32% 34%
23. Local Failure Jatoi et el. JCO 2005. Trial Pt Time pt. Mast. BCT WHO 1972-79 179 22 yrs 14 % 9 % Milan I 1973-80 701 20 2 % 9 % NSABP06 1976-84 1406 20 10 % 14 % US NCI 1979-89 279 20 6 % 22 % EORTC 10801 1980-86 903 10 12 % 2 0% Denmark 82TM 1983-89 859 6 4 % 3%
24. Overall Survival Trial Pt Time pt. Mast. BCT WHO 1972-79 179 22 yrs 41% 42% Milan I 1973-80 701 20 47% 46% NSABP06 1976-84 1406 20 58% 53% US NCI 1979-89 279 20 66% 65% EORTC 10801 1980-86 903 10 79% 82% Denmark 82TM 1983-89 859 6 67% 67%
30. Randomized Clinical Trials No significant differences are seen in toxicity or LRR Canadian Start A Start B RMH/GOC Necker Pts 1234 2236 2215 1410 230 Med FU 12 yrs 5.1 yrs 6.0 yrs 9.7 yrs 4 yr Min Arms (Gy x Fx) 2 x 25 2.67 x 16 2 x 25 3 x 13 3.2 x 13 2 x 25 2.67 x 15 2 x 25 3 Gy x 13 3.3 x 13 1.8 x 25 5.75 x 4
31. RANDOMI ZED adjuvant radiotherapy – 16 x 2.67 Gy – no boost adjuvant radi therapy – 25 x 2 Gy – no boost 1234 patients T1 and T2, N0 patients, BCS and ALND Primary endpoint: Local recurrence (LR) Other endpoints: Toxicity, cosmetic results, overall survival (OS) Long-Term Results of Hypofractionated Radiation Therapy for Breast Cancer Whelan et al.NEJM 2010.
34. 10- Yr Toxicity Whelan TJ et al. N Engl J Med 2010;362:513-520 P = NS Standard HypoFx Skin 0 71% 67% 1 22% 24% 2-3 7% 9% Subcut Tissue 0 45% 48% 1 44% 40% 2-3 11% 12%
35. 10-Yr Cosmetic Results Whelan TJ et al. N Engl J Med 2010;362:513-520 P = NS Standard HypoFx Excellent 28% 31% Good 44% 39% Fair 26% 25% Poor 3% 5%
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38. Patients in the RCT’s Patients older, favorable cancers, chemo/boost not routine Canadian Start A Start B RMH/GOC Necker ER- 27% 21% 12% - - Gr 3 19% 28% 23% - 10% Age < 50 25% 23% 21% 30% - Boost 0% 61% 43% 75% 0% Nodal RT 0% 14% 7% 21% - Chemo 11% 36% 22% 14% 21%
39. ASTRO Guidelines (2010) Smith B et al . IJROBP In Press Age/Stage > 50 yrs, T1,2 N- Surgery BCS Chemotherapy None Fractionation 266 cGy x 16 Heart in Field 0 Boost No Agreement Dose Homogeneity < +/- 7%
40. Clinical Trials in Progress FAST IMPORT High IMPORT Low SHARE RTOG # Pts 915 840 2100 2796 2150 Sites UK UK UK France US Arms (Gy x # Fx) 2 x 25 5.7 x 5 6 x 5 All in 5 weeks 2.4 x 15 integrated boost 2.67 x 15 -> boost 2.67 x 15 2.4 x 15 integrated boost APBI 2.67 x 15 2 x 25 + 2 x 8 2.67 x 15 APBI 4 x 10 2.0 x 25 -> boost 2.67 x 15 integrated boost
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45. 10 trials of post BCS RT Effect on LR and breast cancer mortality in N- pts BC S BCS + RT BCS BCS + RT
46. 10 trials of post BCS RT Effect on LR and breast cancer mortality in N+ pts BCS BCS + RT BCS + RT BCS
47. The 18-y probability of any DM was significantly higher in No RT vs RT group No RT median time RT median time
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49. Incidence of 2nd cancers and mortality from causes other than breast cancer
50. Breast cancer and overall mortality after BCS/RT BCS + RT BCS BCS + RT BCS
51. Main findings II RT can increase mortality for heart disease and lung cancer and incidence of contr a lateral breast cance r which reduce its net beneficial effect on 15-y breast cancer mortality. Nevertheless, RT produced reductions not only in 15-y breast cancer mortality but also in 15-y overall mortality.
Figure 1. Outcomes in Patients with Breast Cancer Who Received a Hypofractionated Regimen of Radiation Therapy as Compared with Patients Who Received the Standard Regimen. Panel A shows Kaplan-Meier estimates for local recurrence (P<0.001 for noninferiority), and Panel B shows Kaplan-Meier estimates for overall survival (P=0.79).
Figure 2. Hazard Ratios for Ipsilateral Recurrence of Breast Cancer in Subgroups of Patients.
Table 1. Late Toxic Effects of Radiation, Assessed According to the RTOG-EORTC Late Radiation Morbidity Scoring Scheme.
Table 2. Global Cosmetic Outcome, Assessed According to the EORTC Scale.
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