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Updates in Radiotherapy for Breast Cancer

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Updates in Radiotherapy for Breast Cancer. By Prasert Lertsanguansinchai

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Updates in Radiotherapy for Breast Cancer

  1. 1. The 5th Annual Update in Breakthrough in Hematology and Oncology (AUBHO 2015) 28-29th August 2015 At the Nai Lert Park Swissotel Bangkok ,Thailand
  2. 2.  Updates in Radiotherapy for Breast Cancer Prasert Lertsanguansinchai,M.D. Radiation Oncologist Wattanosoth Hospital
  3. 3. 50 Years of Advances in Radiotherapy for Breast cancer Radiation Therapy (RT) : What have we Learned ? Where are we Now ? Where are we Going ?
  4. 4. What have we learned ? Breast Cancer Radiation Therapy (RT) 50 years ag0
  5. 5. The overview of eight unconfounded randomized trials of radiotherapy initiated before 1975 (total 7,941 women) Surgery = radical mastectomy or simple mastectomy None of the patients received chemotherapy Surgery alone VS Surgery + Radiation J. Cuzick JCO 12: 447-453,1994
  6. 6. JCO 12 : 447-453,1994 The overall mortality rate was similar in the first 10 years . A divergence in favor of patients not given radiotherapy is apparent after approximately 15 years in the radical mastectomy trials . For the simple mastectomy trials, the overall survival curves remain similar after 10 and 20 years.
  7. 7. Where are we now ? Breast Cancer Radiation Therapy (RT)
  8. 8. Tumor Biology Breast cancer is a systemic disease needs 1.Locoregional control. 2.Prevent and get rid of microdistant metastasis.
  9. 9. Local Radiation Treatment The additional of radiotherapy to surgery resulted in an improvement rate of local recurrence by ⅔ to ¾ (70%) as compare to surgery alone. Radiation contribute to improve overall survival when combined with systemic therapy. NEJM 1995 ; 333 : 1444-1455 Lancet 2000 ; 355 ; 1757-1770
  10. 10. Radiotherapy after Mastectomy and axillary clearance 5-Y Isolated LRR No PMRT PMRT Node-negative 6.3% 2.3% (p=0.0002) No significant reduction in 15 year breast cancer mortality Node-positive 22.8% 5.8% 15-Y breast cancer mortality 60.1% 54.7% (reduction 5.4%) (p=0.0002) 15-y overall mortality reduction 4.4 % (p=0.0009) EBCTCG PMRT
  11. 11. BCS alone BCS + RT 5-Y LRR 26% 7% (reduction 19%) 15-Y breast cancer mortality 35.9% 30.5% (reduction 5.4%) (p=0.0002) Radiotherapy after BCS (7311 women in 10 trials), most had node-negative disease 15-y overall mortality reduction 5.3% p=0.005 EBCTCG BCT
  12. 12. 50 Years of Progress :  Integration of RT with surgery and systemic treatment has made RT more effective.  Postmastectomy Radiation in high risk disease improve locoregional control.  Combining BCS and Breast RT (BCT) as an alternative to mastectomy.
  13. 13. Where are we going ? Breast Cancer Radiation Therapy (RT)
  14. 14.  Postmastectomy Radiation :- 45-50.4 Gy /25-28F in 5-51/2 weeks.  Conserving Breast Surgery followed by whole breast irradiation 45- 50.4Gy/25-28F in 5-51/2 wks with/without tumor bed boost 10-16Gy/5-8F in 1-1 1/2 weeks (total 5-6 ½ wks).  However, for convinence and cost, hypofractionated RT for breast has been explored.  Lancet 2005; 366:2087-2106 Radiation Schedules
  15. 15. CANADA START A START B  Energy Co-60, 4-6 MV 6 MV 6MV  2D + Wedge Yes Yes Yes  Planning 2D 2D/3DCRT 2D/3DCRT  Central Axis Dose +/- 7% +/- 5% +/- 5%  Tumor bed boost 0% 61 % 39 %  Boost dose - 10 Gy/5 F 10 Gy/5F  Energy of boost - Electron Electron  Regional nodal RT 0 % 14.2% 7.3 % The Breast 19 ( 2010) : 163-167 Hypofractionation WBI VS CONVENTIONAL WBI
  16. 16.   Median FU IBTR LRR DFS OS  CANADA 12 yrs 50Gy/25F 7.5% 84.4% 42.5Gy/16F 7.4% 84.6%  START A 5.1 yrs 50Gy/25F 3.2% 3.6% 86% 89 % 41.6Gy/13F 3.2% 3.5% 88% 89%  START B 6.0 yrs 50Gy/25F 3.3% 3.3% 86% 89% 40Gy/15F 2.0% 2.2% 89% 92% Results
  17. 17.  Trial Median FU TD/F Cosmesis (good+excellence)  CANADA 5 / 10 y 50/25 79.2 / 71.3 % 42.5/16 77.9 / 69.8 %  START A 5 y 50/25 59.0 % 41.6/ 13 58.1 %  START B 5y 50/25 58.8% 40/15 64.5 % The Breast 19 (2010) : 163-167 Result :- Cosmesis
  18. 18. HF –WBRT is an acceptable treatment option for patient with  pT1-2 tumor  p N0 disease  Age > 50 years  Especially for patient who do not receive chemotherapy or do not require tumor bed boost  Patient who do not have plan for breast reconstruction  World Journal of Clinical Oncology 2014 Aug 10;5(3):425-439 ASTRO Guideline
  19. 19.  acute skin toxicity :- moist desquamation in 30%-50% of patients  erythema and edema of the irradiated breast  telangiectasia and fibrosis of the skin  effect cosmetic result and QOL Clin Oncol 2004 ; 16 :12-16 Eur J Cancer 2008 ; 44 : 2587-2599 Radiother Oncol 1994 ;33: 106-112 IJROBP 2007 ; 68 : 1375-1380 With Conventional 2D-RT :-cause
  20. 20. Modern Radiotherapy Techniques  Imaging  Treatment Planning System  New Radiation Machine Results  Improved efficacy  Decreased toxicity  Faster and convenient treatment
  21. 21. Modern RT techniques (3D-CRT/IMRT)  Advances of computed tomography can now demonstrate three dimensional tissues/organs  Advances in radiation treatment planning system  Advance in radiation machine We can now give high radiation doses to the tumor while sparing the normal surrounding tissue
  22. 22. LINAC with MLC
  23. 23. We are moving from 2D-RT to 1. Three-dimension RT (3D-CRT) 2. Intensity Modulated RT (IMRT) IMRT has been shown to improve homogeneity and reduce acute toxicity with improve QOL CO 2008 ,May 1 : 28 (13):2085; 2085-2072 New RT techniques
  24. 24. 2D-Tangential beams 3D-CRT/IMRT High exposure dose to lung and heart and also hot spot at periphery area More precise beam to target with dose homogeneity
  25. 25. LUNG: V20 = 22% (wedge) = 19% (IMRT) HEART: V5 = 0% (wedge) = 10% (IMRT) V25 = 0% (wedge) = 0% (IMRT) VOLUME : 2288.09 cc Breast Separation : 29.5 cm Pt.1
  26. 26.  Showed no statistically significant difference in 5- year  Locoregional recurrence 2.56% VS 1.35 % Overall survival 92.5 % VS 91.7 % JCO 2013 ;31 : 4488-4495 IJROBP 2008 ;72 :1031-1040 Standard Wedge-based tangential fields VS IMRT
  27. 27. Acute reaction Conventional Wedge IMRT Dermatitis grade >/= 2 85% 41% Breast edema 28% 1% Hyperpigmentation 50% 5% Change in breast appearance 58% 40% Late toxicity :- no difference in the reported occurrence of reaction pneumonitis, fat necrosis , or second malignancy IJROBP 2008 ;72 :1031-1040 IJROBP 2007; 68 : 1375-1380 IJROBP 2012 ; 84 : 888-893 Side effects
  28. 28.  70%-90% of IBTRs occurred at or in close proximity to the lumpectomy cavity.  APBI may offer equivalent local control to WBRT NEJM 2002 ; 347 : 1233-1241 NEJM 2002 ; 347 : 1227-1232 Accelerated Partial Breast Irradiation (APBI)
  29. 29. Include  short treatment time :- from 5-6 weeks to 1-2 weeks  decreased breast , heart and lung RT volume  Possible improved cosmesis  reduce cost and waiting time Potential Disadvantage :- the possibility that occult foci of cancer exist elsewhere in the breast and will not be treated. Ann Surg Oncol 2012 ;19 : 3275-3281 Potential advantages of APBI
  30. 30. Brachytherapy : - Interstitial brachytherapy - Intracavitary brachytherapy - Intraoperative radiation External beam RT : - 3DCRT - IMRT/VMAT Ongoing trial : - NSABP B-39 RTOG 0413 - WBRT VS APBI Modalities for APBI
  31. 31. Partial Breast Irradiation (PBI) Implantation Mammosite (3D-CRT / IMRT) Intrabeam
  32. 32. Patients : - Quadrantectomy , age >/= 48 years - IDC , T </= 2.5 cm Lancet Oncol 2013;14:1269-1277 - Node negative BreastCancer Res treat 2010;124:141-151 Treatment : ARM I :- WBRT 50Gy/25F , +/- 10 Gy boost ARM II :- IORT 21 Gy x 1 F ( electron up to 9 MeV) Results : - median FU 5.8 y WBRT IORT -IBTR 4 pts 35 pts p=0.0001 - 5-y OS 96.95% 96.8% p=0.59 ELIOT trial 1,305 patients
  33. 33. Patients : - Lumpectomy , age >/= 45 years - IDC , node negative Treatment :- ARM I :- WBRT 40-56 Gy +/- Boost 10-16 Gy VS ARM II :- IORT single dose 20 Gy ( low –energy X-ray 50 KV) TARGIT – A trial 3,451 pts
  34. 34. Results : TARGIT –A results WBRT IORT  4-y LR 0.95% 1.2 % p=0.4  5-y LR 1.3 % 3.3 % p=0.042  Breast cancer death 1.9 % 2.6 % p= 0.56  Non-breast cancer death 3.5% 1.41%  The overall mortality was similar  Major toxicity 3.3% 3.9 % P = 0.44  14% of patient received WBRT in addition to IORT according to the final pathological report. Lancet 2010 ; 376 ; 91-102 Lancet 2014 ; 383 ; 603-613
  35. 35.  Currently, standard of care after conserving breast surgery is still whole breast irradiation.  APBI :- awaiting the prospective setting (RTOG 0413/NSABP B-39) Summary
  36. 36. B-39/0413 Protocol Design Eligible patient treated with lumpectomy Stratification Disease stage-DCIS, invasive N0, invasive N1(1-3) Age ≤ 49, ≥ 50 Hormone receptor status (ER-,ER+) Randomization WBI 50-50.4 Gy in 1.8-2.0 Gy fractions to whole breast, followed by electron boost to surgical bed with margin for total dose of 60- 66.6 Gy APBI 34 Gy in 3.4 Gy bid x 5-7 days Interstitial Brachytherapy Or 34 Gy in 3.4 Gy bid x 5-7 days Mammosite Balloon Catheter Or 38.5 Gy in 3.85 Gy bid x 5-6 days 3D Conformal External Beam VS
  37. 37.  WBRT 50 Gy/ 25 F  VS  HF 6 Gy x 5 F once weekly  HF 5.7 Gy x 5 F once weekly  The preliminary results showed inferior outcome for HF regimen Radiother Oncol 2011 ; 93- 100 Semin Radiat Oncol 2008;18:257-264 Semin Radiat Oncol 2008 ;18:215-222 Ongoing Trial-UK FAST trial
  38. 38.  Proton Beam Therapy VS IMRT for Breast Radiation MDACC

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