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San Antonio Breast Cancer Symposium 2007 Highlights – Radiotherapy

San Antonio Breast Cancer Symposium 2007 Highlights – Radiotherapy. Kathleen C. Horst, M.D. Assistant Professor Department of Radiation Oncology Stanford University. Post-lumpectomy XRT Technique Fractionation Partial Breast Irradiation Post-mastectomy XRT Nodal XRT.

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San Antonio Breast Cancer Symposium 2007 Highlights – Radiotherapy

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  1. San Antonio Breast Cancer Symposium 2007 Highlights – Radiotherapy Kathleen C. Horst, M.D. Assistant Professor Department of Radiation Oncology Stanford University

  2. Post-lumpectomy XRT Technique Fractionation Partial Breast Irradiation Post-mastectomy XRT Nodal XRT

  3. The Cambridge Breast Intensity Modulated Radiotherapy (IMRT) Trial: Dosimetry Results Abstract # 4086 Coles, et al. 1089 patients with breast cancer treated with BCT Standard treatment plan < 2 cm3 of breast tissue > 107% > 2 cm3 of breast tissue > 107% Non-randomized Randomized Standard RT IMRT

  4. The Cambridge Breast Intensity Modulated Radiotherapy (IMRT) Trial: Dosimetry Results Abstract # 4086 Coles, et al. 317/1089 (29%) had acceptable homogeneity with standard 2D radiotherapy. IMRT significantly reduced both “hot spots” and “cold spots”.

  5. Prospective trial of individual optimal positioning (prone vs supine) for whole breast radiotherapy: results of 224 patients Abstract # 4082 Formenti, et al.

  6. Prospective trial of individual optimal positioning (prone vs supine) for whole breast radiotherapy: results of 224 patients Abstract # 4082 Formenti, et al. CONCLUSIONS: Prone enables best sparing of heart and lung in most patients (204/224) Most patients best treated supine (17/20) had left-sided lesions When prone, heart is displaced anteriorly 5-19 mm (Duke) May limit utility of prone technique

  7. R Radiotherapy Fractionation Schedules Abstract #21 Whelan, et al. Long-term results of a randomized trial of accelerated hypofractionated whole breast irradiation following breast conserving surgery in women with node negative breast cancer Standard Whole Breast Irradiation (SWBI) 50 Gy/25 fractions 612 patients Node-Negative Post BCS 1234 patients Accelerated Hypofractionated Whole Breast Irradiation (AHWBI) 42.5 Gy/16 fractions 622 patients Stratification: Age Size Systemic tx Center Recruitment April ’93- Sept ’96

  8. BASELINE CHARACTERISTICS SWBI AHWBI n=612n=622 n (%) n (%) Age < 50 yrs 148 (24)157 (25) Tumor size ≥ 2 cm 203 (33)190 (31) ER negative 157 (26)165 (26) Tumor grade high 116 (21)117 (20) Tamoxifen 266 (41)265 (41) Chemotherapy 72 (11)75 (11)

  9. Radiotherapy Fractionation Schedules Abstract #21 Whelan, et al. LOCAL RECURRENCE SWBI AHWBI 5 years 3.2% 2.8% 10 years 6.7%6.2% No difference in Overall Survival Whelan T, et al. J Natl Cancer Inst. 94(15):1143-50, 2002. Whelan T, et al. Abstract #21. SABCS 2007.

  10. Local Recurrence Rates at 10 years SWBIAHWBI Age (y) < 50 10.77.5 ≥ 50 5.45.8 Tumor < 2 cm 6.1 5.4 Size (cm)≥ 2 cm 7.8 8.0 Systemic yes 5.96.5 Therapy no 7.45.8

  11. Cosmetic Outcome by Time and Treatment Baseline 3 yr 5 yr 10 yr SWBI 83% (604) 77% (496) 79% (423) 71% (216) AHWBI 84% (616) 77% (518) 78% (448) 70% (235) % excellent or good (# evaluable)

  12. RTOG/EORTC Late Radiation Morbidity by Time and Treatment 3 yr 5 yr 10 yr Skin SWBI 2% 3% 8% AHWBI 2% 3% 9% Subcutaneous tissue SWBI 5% 6% 11% AHWBI 4% 5% 12% % Grades 2-3

  13. Cause of Death SWBI AHWBI (n=612) (n=622) Cancer related 13.2% (81) 13.7% (85) Non-cancer related 7.4% (45)5.9% (37) Total 20.6% (126)19.6% (122)

  14. CONCLUSIONS • Accelerated Hypofractionated Whole Breast Irradiation: • Demonstrated excellent local control • Was not associated with long-term morbidity • Skin and soft tissue toxicity • Breast Cosmesis • Non-cancer deaths

  15. 50 Gy/25 fractions/5 weeks START A 2236 patients 41.6 Gy/13 fractions/5 weeks 39 Gy/13 fractions/5 weeks 50 Gy/25 fractions/5 weeks START B 2215 patients 40 Gy/15 fractions/3 weeks Radiotherapy Fractionation Schedules ASCO 2007 Dewar, et al. Hypofractionation for early breast cancer: First results of the UK standardisation of breast radiotherapy (START) trials T1-3, N0-1 Post BCS Recruitment 1999-2002 JCO. 25:18S (June 20 Supplement), 2007: LBA518

  16. Radiotherapy Fractionation Schedules RATIONALE Tumor response (i.e., local control) thought to be as sensitive to fraction size as late adverse effects Radiation fraction sizes > 2.0 Gy may have advantages in breast cancer treatment1 Goals: test the benefit of fraction sizes > 2.0 Gy in terms of locoregional control late normal tissue responses 1Owen R et al. Lancet Oncol 7:467-71, 2006.

  17. Radiotherapy Fractionation Schedules ASCO 2007 Dewar, et al. Hypofractionation for early breast cancer: First results of the UK standardisation of breast radiotherapy (START) trials Median follow up = 5.1 yrs Median follow up = 6.0 yrs

  18. Radiotherapy Fractionation Schedules ASCO 2007 Dewar, et al. Hypofractionation for early breast cancer: First results of the UK standardisation of breast radiotherapy (START) trials

  19. Are patients with T1-2 breast cancer with 1-3 +LN suitable candidates for partial breast radiotherapy trial enrollment? Abstract # 4089 Truong, et al.

  20. Are patients with T1-2 breast cancer with 1-3 +LN suitable candidates for partial breast radiotherapy trial enrollment? Abstract # 4089 Truong, et al. 5688 women pT1-2, 0-3 N+ breast ca Treated with BCT (1989-1999) N0 (n=4433) vs 1-3 N+ (n=1255) Median follow up = 8.6 yrs

  21. Are patients with T1-2 breast cancer with 1-3 +LN suitable candidates for partial breast radiotherapy trial enrollment? Abstract # 4089 Truong, et al.

  22. Are patients with T1-2 breast cancer with 1-3 +LN suitable candidates for partial breast radiotherapy trial enrollment? Abstract # 4089 Truong, et al. CONCLUSIONS: Patients with 1-3 N+ have high risks of regional nodal relapse ~10-15% despite standard whole breast XRT and systemic therapy, particularly young age grade III histology ER- disease >20% positive nodes Such patients should receive standard whole breast XRT and are not ideal candidates for PBI trial enrollment

  23. Update of the Phase II MammoSite Brachytherapy Trial for DCIS Abstract # 4079 Streeter, et al.

  24. Ongoing Trials in Partial Breast Irradiation Other Intraoperative techniques Stanford University of North Carolina MSKCC (Intraoperative HAM applicator) Protons MGH Permanent radioactive seed University of Toronto, Canada Other Intracavitary applicators Cianna Medical SenoRx North American Scientific Xoft NSABP B39/RTOG 0413 Interstitial/intracavitary brachytherapy, 3DCRT European Institute of Oncology Intraoperative electrons TARGIT Intrabeam – photoelectron 50 kV photons RAPID Canadian External Beam

  25. Identification of Patients for Post-Mastectomy Radiotherapy using the Cambridge Index Abstract # 4093 Wilson, et al. Index designed to help identify intermediate and low risk patients who might be at higher risk of local recurrence after mastectomy. Applied since 1999. Retrospective review of patients from 2000-2003

  26. Identification of Patients for Post-Mastectomy Radiotherapy using the Cambridge Index Abstract # 4093 Wilson, et al. High risk (n=125) Intermediate risk Score > 3 (n=63) Low risk Score > 3 (n=17) Chest Wall XRT n=198 (55%) Intermediate risk Score < 3 (n=21) Low risk Score < 3 (n=131) No XRT n=159 (45%) Low level of LR in both the Low and Intermediate risk groups confirms that appropriate patients in the Intermediate risk group are receiving PMRT

  27. Increased use of regional radiotherapy is associated with improved outcome in a population based cohort of women with breast cancer and 1-3 positive nodes Abstract # 4076 Wai, et al.

  28. Ongoing Trials in Regional Nodal RT in Breast Conservation Therapy EORTC 10925 LN+ or any medial/central lesion Breast Only vs Breast + Upper IM/Medial SCV NCIC MA.20 LN+ and high risk LN- Breast Only vs Breast + Upper IM, high axilla, SCV

  29. Post-operative radiotherapy does not adversely affect the outcome of autologous free abdominal flap breast reconstruction Abstract # 4084 Chatterjee, et al. • No significant difference by objective mammometry in the volume of reconstructed breast compared with contralateral breast • No significant difference in fibrosis and thickening in the reconstructed breast • Postoperative XRT does not adversely affect the outcome of immediate DIEP reconstruction following mastectomy

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