Toledano A, Garaud P, Serin D, Fourquet A, Bosset J-F, Miny-Buffet J, Favre A, Azria D, Body G, Le Floch O, Calais G
Service d'Oncologie-Radiothérapie, Hôpital Tenon, APHP, Paris, France.
Cancer Radiother. 2006 Jun;10(4):158-67. doi: 10.1016/j.canrad.2006.03.001. Epub 2006 Apr 24.
In 1996, a multicenter randomized study comparing after breast-conservative surgery, sequential vs concurrent adjuvant chemotherapy (CT) with radiation therapy (RT) was initiated (ARCOSEIN study). Seven hundred sixteen patients were included in this trial. After a median follow-up of 6.7 (4.3-9) years, we decided to prospectively evaluate the late effects of these two strategies.
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/m(2)), 5-FU (500 mg/m(2)), and cyclophosphamide (500 mg/m(2)), 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 tumour 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).
Among the 214 evaluated patients, 107 were treated in each arm. The two populations were homogeneous for patients', tumors' and treatment characteristics. Subcutaneous fibrosis (SF), telengectasia (T), skin pigmentation (SP), and breast atrophy (BA) were significantly increased in arm B. Twenty patients experienced grade superior or equal to 2 (SF) in arm B vs five in arm A (P=0.003). Twenty-five and seven patients showed grade superior or equal to 2 (T) in arm B and A, respectively (P=0.001). Forty-four and twenty patients showed grade superior or equal to 2 (BA) in arm B and A, respectively (P=0.0006). Thirty patients experienced grade superior or equal to 3 (SP) in arm B vs fifteen in arm A (P=0.02). No statistical difference was observed between the two arms concerning grade superior or equal to 2 pain, breast oedema, and lymphoedema. No deaths were caused by late toxicity.
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.
1996年启动了一项多中心随机研究（ARCOSEIN研究），比较保乳手术后序贯与同步辅助化疗（CT）联合放射治疗（RT）的效果。该试验纳入了716例患者。在中位随访6.7（4.3 - 9）年后，我们决定前瞻性评估这两种治疗策略的晚期效应。
从五家较大的参与机构邀请了总共297例患者进行随访。72%（214例患者）符合晚期毒性评估条件。在保乳手术加腋窝清扫术后，患者接受序贯治疗（先CT后RT，A组）或同步CT与RT治疗（B组）。所有患者的CT方案均为米托蒽醌（12 mg/m²）、5-氟尿嘧啶（500 mg/m²）和环磷酰胺（500 mg/m²），共6个周期（第1天至第21天）。在B组中，患者同步接受前3个周期的CT与RT。在A组中，RT在CT第6个周期后3至5周开始。采用2 Gy分次方案对全乳进行常规RT，总剂量为50 Gy（±对原发肿瘤床进行加量照射）。毒性评估对治疗方案设盲，由放射肿瘤学家根据LENT-SOMA量表进行分级。皮肤色素沉着也使用个人5分评分系统（优秀、良好、中等、差、非常差）进行评估。
在214例接受评估的患者中，每组各有107例接受治疗。两组患者在患者、肿瘤及治疗特征方面具有同质性。B组的皮下纤维化（SF）、毛细血管扩张（T）、皮肤色素沉着（SP）和乳腺萎缩（BA）显著增加。B组有20例患者出现2级及以上SF，而A组为5例（P = 0.003）。B组和A组分别有25例和7例患者出现2级及以上T（P = 0.001）。B组和A组分别有44例和20例患者出现2级及以上BA（P = 0.0006）。B组有30例患者出现3级及以上SP，A组为15例（P = 0.02）。两组在2级及以上疼痛、乳腺水肿和淋巴水肿方面未观察到统计学差异。晚期毒性未导致死亡。
保乳手术后，同步使用CT与RT与2级及以上晚期副作用发生率增加显著相关。
