Locoregional treatment Session Oral Abstract Presentation Saulo Brito Silva

Locoregional treatment Session Oral Abstract Presentation Saulo Brito Silva

Background Post-operative radiotherapy (PORT) improves disease free and overall suvivallin selected patients with breast cancer (BC) who underwent neoadjuvant chemotherapy (1). Due to financial restrictions and/or overloaded oncology services, timely initiation of cancer treatments has been a concern worldwide, particularly in developing economies (2). The impact of delayed PORT remains unclear, as data have been inconclusive (3). No studies evaluated the neoadjuvant scenario, in which patients have high-risk disease. 1- Huang EH et al. J Clin Oncol 2004;22(23):4691-9. 2- Barton MB et al. Lancet Oncol 2006;7(7):584-95. 3-Huang Jet al. J Clin Oncol 2003;21(3):555

Methods Retrospective analysis Eligibilitycriteria: allpatientswithbc whoreceivednac, curativesurgeryandport between2008 and2014 atour institution(icesp). Electronic charts were reviewed for NAC schedule, HER-2 and hormonal therapy; type of surgery and axillary dissection; time of PORT start since surgery. Extracted data on relevant prognostic factors commonly associated with cancer recurrence (age, clinical stage, histological grade, hormonal receptors and HER-2 status, pcr)

Study endpoints Primary endpoint:disease-free survival (DFS) among 3 groups defined by the time for initiation of PORT (<8 weeks, 8-16 weeks, >16 weeks). Secondary endpoints: Overall survival (OS) Subgroup analyses of DFS and OS, stratifying results according to molecular profile, clinical stage and pcr.

Statistical Methods All time-to-event endpoints were measured from the date of surgery OS and DFS curves were estimated with the Kaplan-Meier method and compared them with the log-rank test adjusted for pcr. Cox proportional hazard regression models and multivariate analysis adjusted for the following covariates: age, pcr, molecular profile, clinical stage and histological grade A two-sided p value of <0.05 was considered statistically significant.

Results 581 patients Median follow-up of 32 months (range: 2-82) 96 patients had died, 66 had experienced a loco-regional recurrence event and 153 a distant recurrence event (51 patients had both loco-regional and distant recurrence).

Table 1. Patient and Clinical characteristics Characteristic Age at diagnosis, years Mean Range < 8 weeks (N=43) --------------------- N % 50.79-25 - 78-8-16 weeks (N=354) --------------------- N % 50.96-24 - 84 - > 16 weeks (N=184) --------------------- N % 49.51-23 - 76 - p 0.36 Clinical stage I II III 0 0 11 25.6 32 74.4 0 0 89 25.2 264 74.8 1 0.5 46 25.1 136 74.4 0.79 Histological grade 1 2 3 4 9.3 16 37.2 23 53.5 21 6.0 146 41.7 183 52.3 13 7.2 83 45.8 85 47 0.69 Hormonal and HER-2 status HR posandher-2 neg HRposandHER-2 pos HRnegandHER-2 pos HR negandher-2 neg 21 48.8 6 14 3 7.0 13 30.2 149 42.1 52 14.7 41 11.6 112 31.6 89 48.4 27 14.7 28 15.2 40 21.7 0.25

Table 1. Patient and Clinical characteristics Characteristic < 8 weeks (N=43) --------------------- N % 8-16 weeks (N=354) --------------------- N % > 16 weeks (N=184) --------------------- N % p NAC Anthracycline-taxane Others Trastuzumab in HER-2 pos Yes No Hormone therapy in HR pos Yes No Surgery Mastectomy BCS Axillary dissection Yes No pcr Yes No 42 97.7 1 2.3 8 88.9 1 11.1 27 100 0 0 27 60.5 17 39.5 40 93.0 3 7.0 10 23.3 33 76.7 335 94.6 19 5.4 97 99.0 1 1.0 193 100 0 0 265 75.1 88 24.9 319 90.4 34 9.6 76 21.5 277 78.5 174 94.6 10 5.4 52 92.9 4 7.1 115 100 0 0 147 79.9 37 20.1 173 94.0 11 6.0 32 17.4 152 82.6 0.74 0.053 1.00 0.03 0.34 0.47

Subgroup analyses -multivariable Cox Proportional Hazards Model according to stage, pcrand BC subtypes. Time to Radiotherapy DFS ------------------------------------- HR 95%CI p OS ------------------------------------- HR 95%CI p All <8w vs. > 8w 0.34 0.14-0.84 0.02 0.24 0.06 0.97 0.045 Stage II <8w vs. > 8w 0.44 0.06 3.29 0.42 1.00 0.13 7.94 0.99 Stage III <8w vs. > 8w 0.30 0.11 0.82 0.02 0.12 0.02 0.86 0.04 Hormone receptor positive <8w vs. > 8w 0.22 0.05-0.89 0.03 0.22 0.03 1.65 0.14 HER2 positive <8w vs. > 8w 0.32 0.04-2.36 0.26 * * * Triple Negative <8w vs. > 8w 0.56 0.14 2.33 0.43 0.36 0.05 2.70 0.32 Without pcr <8w vs. > 8w 0.39 0.16 0.94 0.04 0.29 0.07-1.21 0.09

Conclusion PORT within 8 weeks was statistically significant both in terms of DFS (HR 0.34; 95% CI 0.14-0.84; p=0.02) and OS (HR 0.24; 95% CI 0.06-0.97; p=0.045) in patients who underwent NAC. Statistically significant improved DFS to the subgroup of patients with clinical stage III; to patients without pcrand to those with HR-positive.

Discussion Largest study addressing the clinical impact of delaying PORT in patients treated with NAC followed by surgery. Limited by its retrospective analysis and not long enough follow up. However, a clear difference is already evident at this early point. The large number of patients who delayed the start of PORT in our study is troubling, and could be a consequence of limited resources that many countries deploy to cancer care. Optimizing radiotherapy referrals might achieve disproportionally great returns in terms of improving in cancer outcomes.

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