Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Br J Cancer. 2018 Feb 6;118(3):331-337. doi: 10.1038/bjc.2017.423. Epub 2017 Dec 12.
A randomised phase 2 trial of trimodality with or without induction chemotherapy (IC) in oesophageal cancer (EC) patients showed no advantage in overall survival (OS) or pathologic complete response rate. To identify subsets that might benefit from IC, a secondary analysis was done.
The trial had accrued 126 patients (NCT 00525915). Recursive partitioning and proportional hazards regression with interactions were performed.
The median follow-up of surviving patients was 6.7 years and the median OS duration was 3.8 years (95% confidence interval (CI), 2.6-5.8 years). OS was associated with tumour length (P=0.03), cT (P=0.02), cN (P=0.04), clinical stage (P=0.01), and tumour grade (P<0.001). The effect of IC differed according to tumour grade. Among patients with well or moderately differentiated (WMD) ECs (n=59), the 5-year survival rate was 74% with IC and 50% without IC, P=0.001. IC had no effect on OS of patients with poorly differentiated (PD) ECs (31% and 28%, respectively; interaction, P=0.04; IC, P=0.03). In the multivariate reduced model, WMD with IC was an independent prognosticator for better OS (HR=0.41, 95% CI, 0.25-0.67; P=<0.001). The following four EC phenotypes emerged for OS: (1) very high risk (PD, cN2/N3), (2) high risk (PD, cN0/N1, stage cIII), (3) moderate risk (PD, cN0/N1, stage cI/II or WMD without IC), and (4) low risk (WMD with IC). The 5-year survival rates were 11%, 27%, 48%, and 74%, respectively (P<0.001).
Our data show that IC significantly prolonged OS of WMD EC patients who undergo trimodality; prospective evaluation is needed.
一项针对食管鳞癌患者的三联疗法（放化疗）加或不加诱导化疗的随机 2 期试验显示，总生存期（OS）或病理完全缓解率均无优势。为了确定可能从 IC 中获益的亚组，进行了二次分析。
该试验共纳入 126 例患者（NCT 00525915）。采用递归分区和带有交互作用的比例风险回归进行分析。
存活患者的中位随访时间为 6.7 年，中位 OS 时间为 3.8 年（95%置信区间，2.6-5.8 年）。OS 与肿瘤长度（P=0.03）、cT（P=0.02）、cN（P=0.04）、临床分期（P=0.01）和肿瘤分级（P<0.001）有关。IC 的效果因肿瘤分级而异。在肿瘤分化良好或中等（WMD）的 EC 患者（n=59）中，IC 组的 5 年生存率为 74%，无 IC 组为 50%，P=0.001。IC 对肿瘤分化不良（PD）EC 患者的 OS 无影响（分别为 31%和 28%，交互作用，P=0.04；IC，P=0.03）。在多变量简化模型中，IC 联合 WMD 是 OS 更好的独立预后因素（HR=0.41，95%CI，0.25-0.67；P<0.001）。OS 出现以下四种 EC 表型：（1）极高风险（PD，cN2/N3），（2）高风险（PD，cN0/N1，cIII 期），（3）中危（PD，cN0/N1，cI/II 期或无 IC 的 WMD），（4）低危（有 IC 的 WMD）。5 年生存率分别为 11%、27%、48%和 74%（P<0.001）。
我们的数据表明，IC 显著延长了接受三联疗法的 WMD EC 患者的 OS；需要进行前瞻性评估。
