Thomas Michelle L, Hewett Peter J, Ruszkiewicz Andrew R, Moore James W E
Royal Adelaide Hospital, Department of Surgery, University of Adelaide, Adelaide, South Australia, Australia.
Department of Surgery, University of Adelaide, Adelaide, South Australia, Australia.
Asia Pac J Clin Oncol. 2015 Dec;11(4):343-51. doi: 10.1111/ajco.12411. Epub 2015 Oct 15.
In colorectal cancer (CRC), adjuvant therapy is offered on the basis of stage and attempts to identify factors to better target treatment have not been successful. Recent work suggested that mismatch repair deficient CRCs may not benefit from 5FU adjuvant chemotherapy but studies remain conflicting. We aimed to determine if gender, tumor site, tumor pathological characteristics and microsatellite instability (MSI) predict survival benefit from adjuvant chemotherapy in stage C CRC.
Data were collated on ACPS (Australian Clinico-pathological Staging System) stage C CRC cases that underwent curative resection over a 23-year period. Pathology was reevaluated, DNA was extracted from the formalin-fixed paraffin specimen, and MSI status was established by BAT26 instability. Multivariate analysis was performed using Cox proportional hazard model and effects modification interaction testing.
In total 814 unselected cases were included, of whom 37% received chemotherapy. Seventy-seven cases exhibited MSI. Overall, adjuvant chemotherapy produced a cancer-specific survival benefit (HR 0.52, 95% CI 0.39-0.70; P < 0.0001). On interaction testing, none of the examined parameters significantly influenced the magnitude of that survival benefit. Chemotherapy was beneficial in both the MSI (HR 0.08, 95% CI 0.02-0.27; P = < 0.0001) and the microsatellite stable cohort (HR 0.62, 95% CI 0.47-0.81; P = 0.001).
These results suggest that survival benefit from 5FU adjuvant chemotherapy for stage C CRC does not vary according to gender, site of tumor, pathological characteristics or MSI status. This study suggests that it would be unwise to exclude patients from being offered adjuvant chemotherapy on the basis of MSI.
在结直肠癌（CRC）中，辅助治疗是根据分期进行的，并且尚未成功确定能更好地靶向治疗的因素。近期研究表明，错配修复缺陷型结直肠癌可能无法从5-氟尿嘧啶辅助化疗中获益，但研究结果仍存在矛盾。我们旨在确定性别、肿瘤部位、肿瘤病理特征和微卫星不稳定性（MSI）是否能预测C期结直肠癌辅助化疗的生存获益。
收集了23年间接受根治性切除的澳大利亚临床病理分期系统（ACPS）C期结直肠癌病例的数据。重新评估病理，从福尔马林固定石蜡标本中提取DNA，并通过BAT26不稳定性确定MSI状态。使用Cox比例风险模型进行多变量分析和效应修饰相互作用检验。
共纳入814例未经选择的病例，其中37%接受了化疗。77例表现出MSI。总体而言，辅助化疗产生了癌症特异性生存获益（风险比0.52，95%置信区间0.39 - 0.70；P < 0.0001）。在相互作用检验中，所检查的参数均未显著影响该生存获益的程度。化疗在MSI组（风险比0.08，95%置信区间0.02 - 0.27；P < 0.0001）和微卫星稳定组（风险比0.62，95%置信区间0.47 - 0.81；P = 0.001）中均有益。
这些结果表明，C期结直肠癌5-氟尿嘧啶辅助化疗的生存获益不会因性别、肿瘤部位、病理特征或MSI状态而有所不同。本研究表明，基于MSI将患者排除在辅助化疗之外是不明智的。
