Concurrent Administration of Adjuvant Chemotherapy and Radiotherapy After Breast-Conservative Surgery Enhances Late Toxicities: Long Term Results of the ARCOSEIN Multicenter Randomized Study

Abstract

Purpose/Objective: In 1996, a multicenter randomized study comparing after breast-conservative surgery, sequential versus concurrent adjuvant chemotherapy (CT) with radiation therapy (RT) was initiated (ARCOSEIN study). 716 patients were included in this trial. Long term results will be presented during this meeting. After a median follow-up of 6.7 (4.3–9) years, we decided to prospectively evaluate the late effects of these two strategies. Materials/Methods: A total of 297 patients were asked to follow-up from the five larger including institutions. Seventy-two percent (214 patients) were eligible for late toxicity. After breast-conserving surgery with axillary dissection, patients were treated either with sequential treatment with CT first followed by RT (arm A) or CT administered concurrently with RT (arm B). In all patients, CT regimen combined mitoxantrone (12 mg/m2), 5-FU (500 mg/m2), and cyclophosphamide (500 mg/m2), 6 cycles (day 1-day 21). In arm B, patients received concurrently the first 3 cycles of CT with RT. In arm A, RT started 3 to 5 weeks after the 6th cycle of CT. Conventional RT was delivered to the whole breast using a 2 Gy-fraction protocol to a total dose of 50 Gy (± boost to the primary tumor bed). The assessment of toxicity was blinded to treatment and was graded by the radiation oncologist according to the LENT/SOMA scale. Skin pigmentation was also evaluated using a personal 5-points scoring system (excellent, good, moderate, poor, very poor). Results: Among the 214 evaluable patients, 107 were treated in each arm. Subcutaneous fibrosis (SF), telengectasia (T), skin pigmentation (SP), and breast atrophy (BA) were significantly increased in arm B. Twenty patients experienced grade ≥ 2 (SF) in arm B vs five in arm A (p=0.003). Twenty five and seven patients showed grade ≥ 2 (T) in arm B and A, respectively (p=0.001). Forty four and twenty patients showed grade ≥ 2 (BA) in arm B and A, respectively (p=0.0006). Thirty patients experienced grade ≥ 3 (SP) in arm B vs fifteen in arm A (p=0.02). No statistical difference was observed between the two arms concerning grade ≥ 2 pain, breast oedema, lymphoedema. No deaths were caused by late toxicity. Correlation between late toxicities and radiation parameters, concurrent hormonal treatment, and type of initial surgery will be presented during the meeting. Conclusions: Following breast conserving surgery, the concurrent use of CT with RT is significantly associated with an increase incidence of grade 2 or greater late side effects.