Radiation Therapy Update: SABCS 2005

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Radiation Therapy Update: SABCS 2005

  1. 1. Radiation Therapy Update:Radiation Therapy Update: SABCS 2005SABCS 2005 Janice Ryu, M.D. UC Davis Radiation Oncology
  2. 2. SABCS Update 2005SABCS Update 2005 3 oral presentations Abstract 7: Bijker et al, EORTC DCIS Abstract 8: Gnant et al, ABCCSG low risk invasive breast CA Abstract 22: Gadd et al, MGH + sentinel LN dz: axillary RT w/o AND
  3. 3. Radiotherapy in breast-conserving treatmentRadiotherapy in breast-conserving treatment for ductal carcinoma in situ (DCIS): ten-yearfor ductal carcinoma in situ (DCIS): ten-year result of European Organization forresult of European Organization for Research and Treatment of CancerResearch and Treatment of Cancer (EORTC) randomized trial 10853(EORTC) randomized trial 10853 Bijker N, Meijnen PH, Bogaerts J, Peterse JL, on behalf of EORTC Breast Cancer Group & Radiotherapy Group. The Netherlands Cancer Institute, Amsterdam, Netherlands; EORTC, Brussels, Belgium
  4. 4. EORTC 10853: DCISEORTC 10853: DCIS Objective: To determine the role of breast RT post-WLE in DCIS Median f/u 10.2 yrs Sample size: 1010 women Clinically detected: 29% vs. mammographically detected: 71%
  5. 5. EORTC - 10853 DesignEORTC - 10853 Design Randomize Radiation 50 Gy Excise with Negative Margins* Observe < 5.0 cm *If repeat excision still has + margins mastectom
  6. 6. EORTC 10853EORTC 10853 4 Year Recurrence Rates4 Year Recurrence Rates No Further Treatment Radiation 503 pts. 507 pts. 83 (17%) 53 (10%) p.005 54 % of recurrences in each group were DCIS 46 % of recurrences in each group were Invasive Julien, J. P. et. al. Lancet;355;p528-532; 2000
  7. 7. EORTC 10853: 10-Yr ResultsEORTC 10853: 10-Yr Results Treatment Local Control p Group at 10 yrs (%) HR WLE 75 < 0.0001 WLE+RT 85 0.55
  8. 8. EORTC 10853: ResultsEORTC 10853: Results Risk of DCIS and invasive local recurrence both reduced by 42% (p=0.009 & p=0.006) Risk of contralateral breast cancer similar No difference in distant metastases and death 22 pts (2%) developed metastases due to invasive local recurrence
  9. 9. EORTC 10853: ResultsEORTC 10853: Results Multivariate analysis for factors predicting local recurrence Factors HR Age < 40 1.95 Clinical detection 1.53 Higher grades (2/3) 1.77 Solid/cribriform pattern 2.21 Doubtful margin status 1.82 WLE only 1.74
  10. 10. EORTC 10853: ConclusionEORTC 10853: Conclusion RT after WLE reduced the number of ipsilateral breast recurrences by 45% at 10 yrs. RT reduced the risk of local recurrence in all clinical and pathological subgroups. Women at high risk of local recurrence even after RT include young age < 40 yrs (27%) and close/involved margins (23%).
  11. 11. NSABP-17: 12-yr ResultsNSABP-17: 12-yr Results Lumpectomy Lumpectom + Radiatio atients 403 410 rrence 149 (31.7%) 101 (15. al Rate Breast cer events /100 pts. 4.8 2.8 Recurrences -Invasive 53% 47% 57% Relative Reduction In Recurrence For Pts. Receiving XRT Fisher, E. et.al. Sem. In Oncology August 2001
  12. 12. Breast Conservation without radiotherapyBreast Conservation without radiotherapy in low risk breast cancer patients – resultsin low risk breast cancer patients – results of 2 prospective clinical trials of theof 2 prospective clinical trials of the Austrian Breast and Colorectal CancerAustrian Breast and Colorectal Cancer Study Group involving 1,518Study Group involving 1,518 postmenopausal patients with endocrinepostmenopausal patients with endocrine responsive breast cancer.responsive breast cancer. Gnant MFX, Poetter R, Kwasny W, Tausch C, Handle-Zeller E, Pakesch B, Schmid M, Hausmaninger H, Stierer M, Kubista E, Sedlmayer F, Draxler W, Luschin-Ebengreuth G, Jakesz R, Austrian Breast and Colorectal Cancer Study Group. Medical Universities of Vienna, Graz, Salzburg, and Innsbruck, Vienna, Austria
  13. 13. Breast conservation without radiotherapyBreast conservation without radiotherapy  Eligible pts: 1. Older age 2. Significant co-morbid diseases 3. Hormone receptor positive 4. Early stage, small tumors 5. Candidates for systemic hormonal therapy
  14. 14. Breast conservation without radiotherapyBreast conservation without radiotherapy Is hormonal therapy as a local therapy option as effective as breast RT? Is hormonal therapy as safe as breast RT? Is hormonal therapy as cost-effective as breast RT?
  15. 15. Prospective study of axillary radiationProspective study of axillary radiation without axillary dissection for breastwithout axillary dissection for breast cancer patients with a positive sentinelcancer patients with a positive sentinel nodenode Gadd M, Harris J, Taghian A, Hughes K, O’Neill A, Powell S, Christian R, Lesnikoski B, Kaelin C, Rhei E, Iglehart J, Habin K, Oberg J, Younger J, Winer E, Smith B, Massachusettes General Hospital, Boston, MA; Brigham and Women’s Hospital, Boston, MA; Dana-Farbar Cancer Institute, Boston, MA
  16. 16. Axillary RT for SLN +:Axillary RT for SLN +: BackgroundBackground  Std of care for SLN+ pts: completion AD  50% have no additional LN disease on further ALND  Complications of ALND: 15-25% lymphedema or chronic pain  Axillary RT: equivalent axillary local control, less lymphedema  Systemic therapy decisions less dependent on the number of involved ALN’s
  17. 17. Axillary RT for SLN +: MethodsAxillary RT for SLN +: Methods 560 pts with CS T1/2 N0 treated by WLE/SLND from 1/00-2/04 73 pts with +SLN treated with axillary RT +SLN defined as any met. deposit on H&E RT: tangents and 3rd field (49 Gy / 27 fxs) F/U: q 6 months arm circumference & grip strength measurements, QOL questionnaires
  18. 18. Axillary RT for SLN +: ResultsAxillary RT for SLN +: Results Median F/U: 32 months All pts received systemic therapy Axillary recurrence: 1/73 pt at 17 months, currently NED after salvage AD Lymphedema: 1 pt with transient lymphedema at 6 months, but none at 4 yrs Minimal arm pain, numbness, better ROM, less time off work
  19. 19. Axillary RT for SLN +:Axillary RT for SLN +: DiscussionDiscussion Extremely low rates of axillary recurrence and arm symptoms after axillary RT for SLN + disease Can axillary RT replace completion dissection? Data may be premature: median f/u only 32 months, need longer follow-up
  20. 20. Poster Presentations:Poster Presentations: SABCS 2005SABCS 2005 1. Abstract 1003: lymphedema risk of ax RT after ax sampling 2. Abstracts 4035 & 4041: CVD risk with RT 3. Abstract 4037: IMRT for L breast 4. Abstract 4046: IMN recurrence without IMC RT 5. Abstracts 4038 & 4051: Mammosite brachytherapy
  21. 21. # 1003: Comparative study of lymphedema with axillary# 1003: Comparative study of lymphedema with axillary node dissection and axillary sampling with radiotherapynode dissection and axillary sampling with radiotherapy in women undergoing breast conservative surgery forin women undergoing breast conservative surgery for breast cancer. Mathew et al, Ysbyty Gwynedd, UKbreast cancer. Mathew et al, Ysbyty Gwynedd, UK  Retrospective review of pts undergoing breast conservation  Axillary sampling + AxRT if LN +(Group 1): 312 pts, 1994-98  Axillary clearance (Group 2): 194 pts 2000-02  Minimum f/u 2 yrs  Lymphedema defined as 2 cm difference in circumference of arms Groups 1 2 1 +LN 2 +LN Lymphedema rate 2.2% 12.3% 6.2% 15.4%
  22. 22. #4035: Long term risk of cardiovascular disease in 10-#4035: Long term risk of cardiovascular disease in 10- year survivors of breast cancer. Hooning et al,year survivors of breast cancer. Hooning et al, Netherlands Cancer InstituteNetherlands Cancer Institute  Retrospective review of CVD incidence in a group of 10-yr survivors (N=4,368) w/ early BC, 1970-1987  Med f/u 18 yrs  942 CV events (MI, angina, CHF): standardized excess risk (SIR) of 1.3, 63/10,000 person-yrs absolute excess risk Treatment period #pts RT/no RT HR <1980 1,882 80/20% 1.5 >1980 2,486 90/10% 1.3 Risk of CVD increased with IMC RT in period <1980 RT to left CW assoc’ed with increased CVD, but not to right CW RT to breast only not assoc’ed with increased CVD MI: RT+smoking: HR 3.0, RT-smoking: HR 1.3, smoking-RT: HR 1.4 After 1979, increased MI w/ RT to L CW, CHF w/ R & L IMC RT
  23. 23. #4041: Radiation therapy and cardiac toxicity in breast#4041: Radiation therapy and cardiac toxicity in breast cancer patients 65 years and older: a population-basedcancer patients 65 years and older: a population-based study. Doyle et al, Columbia University, New Yorkstudy. Doyle et al, Columbia University, New York  SEER-Medicare database, St. I-III breast CA pts of > 65 age (N=31,748), 1992-99  36% BCS, 63% MRM, 46% RT (73% of BCS)  L-sided RT assoc’ed w/ increased MI (HR=1.26), but not other cardiac outcome, compared to R-sided RT  Increased MI risk highest with L chest wall RT (HR=1.71)
  24. 24. #4037: Inverse-planned, dynamic, multi-beam, intensity#4037: Inverse-planned, dynamic, multi-beam, intensity modulated radiation therapy (IMRT) for left-sided breastmodulated radiation therapy (IMRT) for left-sided breast cancer: comparison to best standard of care. Olivotto,cancer: comparison to best standard of care. Olivotto, British Columbia, CanadaBritish Columbia, Canada  11-beam IMRT plan vs. best standard plans compared for 30 consecutive L-sided breast CA pts undergoing BCRT  Homogeneity of dose (H.I.), conformity(C.I.), and doses to heart, lungs, R breast, and “Healthy tissue” (CT dataset minus PTV)
  25. 25. L breast IMRT: Olivotto et alL breast IMRT: Olivotto et al  Benefits of IMRT Structure Parameter Best Std IMRT p value PTV H.I. 0.74 0.95 <0.001 C.I. 0.48 0.91 <0.001 Heart Mean V30 12.5% 1.7% <0.001 L Lung Mean V20 26.6% 17.1% <0.001  Costs of IMRT Healthy tissue Mean dose 6.9 Gy 6.0 Gy <0.001 V5(%) 23.6% 31.7% <0.001 R breast Mean dose 2.9 Gy 4.3 Gy <0.001 V5 (%) 7.9% 29.2% <0.001 R lung Mean dose 1.5 Gy 3.6 Gy <0.001 V5 (%) 2.0% 13.7% <0.001
  26. 26. #4046: Risk of internal mammary recurrence after#4046: Risk of internal mammary recurrence after mastectomy in absence of internal mammary chainmastectomy in absence of internal mammary chain radiation therapy. A retrospective study. Lerouge et al,radiation therapy. A retrospective study. Lerouge et al, Centre Francois Baclesse, Caen, FranceCentre Francois Baclesse, Caen, France  1,353 pts treated by mastectomy & postop RT 1985-96  RT: 50 Gy to the chest wall +/- SCF, no IMC RT for incomplete resection or extensive axillary LN involvement  T3-4 37%, pN0 37%, pN1 1-3 34%, N+>3 27%  RT 52%, CTX 42%, hormones 66%  5-yr rate of IMN recurrence 2%  IMN recurrence greatest in LN+ >9 group (8%)  No IMN recurrence in the historical control group of 1,226 pts treated with IMC RT 1973-84, but these pts had worse survival (probably due to less use of systemic therapy)

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