breast cancer radiotherapy

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  • 1.Whats New in Breast Cancer Radiotherapy? Roger M. Macklis, M.D. Cleveland Clinic Lerner College of Medicine Cleveland Clinic Healthcare System

2. RM 9/05 Whats New in Breast Cancer Radiotherapy?Recent Meta-Analysis fromLancet Partial Breast Irradiation Intensity ModulatedRadiation Therapy (IMRT) 3. RM 9/05 BREAST CANCER COMMANDS ATTENTION Few topics in medicine engender as much emotional response as the treatment of primary breast cancer.- Levene, Harris, Hellman Cancer (1977) 4. RM 9/05 Early Investigations Charles H. Moore, 1867 (surgeon to the Middlesex Hospital, London). Cancer of the breast requires the careful extirpation of the entire organ; that the situation in which this operation is most likely to be incomplete is at the edge of the mamma near the sternum 5. RM 9/05Early Investigations William Halsted, 1852-1922 (surgeon to the Johns Hopkins Hospital, Baltimore). Most of us have heard our teacher in surgery admit that they never cured a case of cancer of the breast Everyone knows how dreadful the end-results were before cleaning out the axilla became recognized as an essential part of the operation. 6. RM 9/05Early Investigations Sir Geoffrey Keynes, 1920s (St. Bartholomew Hospital, London). Interstitial radium implants of tumor bed andsurrounding regions of the breast. treatmentof choice for very advanced breast cancer. 7. RM 9/05Breast Cancer: Critical Benchmark StudiesNASBP (NEJM 2002: 347 1233-1241) 20 year F/U shows lumpectomy + XRT 14% LRR lumpectomy alone 39.2% LRRMilan (Ann Oncol 2001 12: 997-1003) Quadrantectomy + XRT 5.8% LRR Quadrantectomy alone 23.5% LRRNew Meta-Analysis from Lancet 12/05 8. New Meta-Analysis Data on Breast Radiotherapy strongly suggests that in addition to improving local control, radiotherapy ALSO improves survival 9. Meta-Analysis of Breast Cancer XRT Title: Effects of radiotherapy and of differencesin the extent of surgery for early breast canceron local recurrence and 15-year survival: anoverview of the randomised trials Early Breast Cancer Trialists Collaborative Group (EBCTCG) Lancet 366:2087-2106 (2005) Published Dec. 17, 2005 10. Meta-Analysis of Breast Cancer XRT Meta-Analysis of 78 randomized controlled trials beginning by 1995. These trials included approximately 42,000 women and roughly were involved in XRT vs no XRT trials for either conservation therapy (intact breast) or post-mastectomy therapy. Trials separated into groups showing > or < 10% difference in LR. 11. Data from Lancet Meta-Analysis (N=42,000) XRTNo XRT 5 year local recurrence: 7% 26% (conservation-intact breast)Post-Mastectomy (LN+)6% 23%15 year breast cancer mortality 30.5%35.9% (intact breast)15 year breast cancer mortality 54.7%60.1% (post-mastectomy LN+) Overall all-cause reduction in mortality approx 4.4%! Similar proportional reductions in all groups Major XRT-related toxicities included cardiac disease (RR 1.27) lung ca (RR 1.78) and contralateral breast ca (RR 1.18) 12. Interpretation of Meta-Analysis Data: Differences in local treatment that substantially affect local recurrence rates would, in the hypothetical absence of any other causes of death, avoid about one breast cancer death over the next 15 years for every four local recurrences avoided, and should reduce 15-year overall mortality. Lancet 366:2087 (2005)Will new treatment approaches further improve this data set? 13. RM 9/05 CRITICAL QUESTIONS ON PARTIAL BREAST IRRADIATIONCan less than the entire breast be treated? If so, for which types of cases? Which portion of the breast? How big a margin? External beam vs. brachytherapy? What about overall cosmesis? What about adjuvant systemic therapy? 14. RM 9/05General Approaches to Partial Breast RadiotherapyInterstitial implant brachytherapyIntra-Operative RadiotherapyExternal beam radiotherapyMammoSite brachytherapy 15. RM 9/05Interstitial Implant Breast Brachytherapy1. Ochsner Clinic Team (King et al, 2000)50 pts: Tis, T1, T2 up to 4 cm margins; 3 LN Target Tissue: tumor surgical bed plus 2-3 cm margin Either LDR or HDR technique Dose: 45 Gy LDR or 32 Gy (4 day BID) HDR With median f/u 75 months, 1 breast and 3 LN recurrences seen Cosmetic Outcomes: 75% good to excellent (less than 85-90% for external beam) 16. RM 9/05Interstitial Implant Breast Brachytherapy2. William Beaumont Team (Vicini et al, 2003)198 pts: Tis, T1, T2 3 cm margins; age >40; LN Target similar to Ochsner group Dose: LDR 50 Gy or LDR 3.4 Gy BID x 5 days Cosmetic Outcome good to excellent 99%!! Local recurrence rate 1% at 5 years Basis for subsequent RTOG trial which opened in 1997 17. RM 9/05Intra-Operative Breast IrradiationLondon study using Intrabeam device (Photo Electron, now owned by Zeiss) Spherical applicators of different sizes 50 kv orthovoltage beam producing 5 Gy at 1 cm from application surface Clinical trial by Tobias et al. now underway; each site chooses its own entrance criteria. Other intra-op programs at MSK, etc. CCF used for boost only. Veronesi (Milan) just published results of 590 pts treated with intra-op electron beam; 21 Gy single fraction. 3% breast fibrosis, 6/590 ipsilat. recurrence after 2-year median f/u. [Ann. Surg 242:101 (2005)] 18. RM 9/05External Beam Partial Breast IrradiationWilliam Beaumont group developed as non-invasive analog to implant studies 3D conformal XRT Target Tissue: tumor bed plus 2-3 cm (breathing margin) 34-38.5 Gy BID over 5-7 days RTOG 95-17 phase II protocol: 38.5 Gy BID over 5-7 days Excellent results led to current RTOG/ NSABP PBI trial 19. RM 9/05MammoSite Balloon Brachytherapy Catheter resembling Foley but with 2 channels: one for saline (expander) and a second for radioactive source (Ir-192) Placed directly in lumpectomy cavity either at time of original lumpectomy or in a second procedure (single scar) Dose: 34 Gy BID in 5-7 days With median F/U 29 months, local failure rate 0% and cosmesis good-to-excellent in 84%. FDA clearance granted 2002 Said to be the most rapidly growing breast cancer radiation procedure in the USA. 20. RM 9/05MammoSite: Coming to a Clinic Near You! 21. RM 9/05Current RTOG / NSABP Trial Phase III randomized comparison of whole breast vs. short-course partial breast XRT Stage 0, I, or II with T


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