【评论】原发肿瘤位于横结肠作为转移性结直肠癌的生物标志物:CCTG/AGITG CO.17和CO.20随机临床试验的汇总分析

[Comment]Transverse colon primary tumor location as a biomarker in metastatic colorectal cancer:a pooled analysis of CCTG/AGITG CO.17 and CO.20 randomized clinical trials

目的原发肿瘤部位是转移性结直肠癌抗EGFR疗效的预后影响因素和预测因素。在既往几项关于原发肿瘤部位的分析研究中,横结肠均被排除。左、右半结肠癌的最佳划分方式尚无定论。本文旨在探讨原发肿瘤位于横结肠作为转移性结直肠癌生物标志物的可能性。方法这是关于西妥昔单抗治疗化疗难治性转移性结直肠癌的CCTG/AGITG CO.17和CO.20试验的汇总分析。根据原发肿瘤部位,分析来自CO.17试验的RAS/BRAF野生型转移性结直肠癌和来自CO.20试验的KRAS野生型转移性结直肠癌患者的研究结果。结果共纳入553例患者,包括32例(5.8%)横结肠癌患者、101例(18.3%)右半结肠癌患者和420例(75.9%)左半结肠癌患者。与最佳支持治疗相比,采用西妥昔单抗治疗转移性横结肠癌患者在总生存期(中位数,5.9个月vs.2.1个月;HR=0.63,95%CI为0.28~1.42,P=0.26)和无进展生存期(中位数,1.8个月vs.1.3个月;HR=0.57,95%CI为0.26~1.28,P=0.16)方面均无明显获益。仅分析随机接受西妥昔单抗治疗的患者的结果显示,转移性右半结肠癌和转移性横结肠癌的总生存期(中位数,5.6个月vs.5.9个月;HR=0.82,95%CI为0.50~1.34,P=0.43)和无进展生存期(中位数,1.9个月vs.1.8个月;HR=0.78,95%CI为0.49~1.26,P=0.31)相近。而与转移性横结肠癌患者相比,转移性左半结肠癌患者采用西妥昔单抗治疗在总生存期(中位数,9.7个月vs.5.9个月;HR=0.42,95%CI为0.27~0.67,P=0.0002)和无进展生存期(中位数,3.8个月vs.1.8个月;HR=0.49,95%CI为0.31~0.76,P=0.001)均有明显获益。对于单独接受最佳支持治疗的患者而言,原发肿瘤部位不是预后的影响因素。结论转移性横结肠癌具有与转移性右半结肠癌相近的预后及其预测特征。

Purpose Sidedness is prognostic and predictive of anti-EGFR efficacy in metastatic colorectal cancer(mCRC).Transverse colon has been historically excluded from several analyses of sidedness and the optimal division between leftand right-sided colorectal cancer is unclear.We investigated transverse colon primary tumor location as a biomarker in mCRC.Experimental design Pooled analysis of CCTG/AGITG CO.17 and CO.20 trials of cetuximab in chemotherapyrefractory mCRC.Outcomes of patients with RAS/BRAF wild-type(WT)mCRC from CO.17 and KRAS WT mCRC from CO.20 were analyzed according to location.Results A total of 553 patients were analyzed,32(5.8%)with cancers from the transverse,101(18.3%)from right,and 420 from(75.9%)left colon.Transverse mCRC failed to reach significant benefit from cetuximab versus best supportive care(BSC)for overall survival[OS;median,5.9 vs.2.1 months;HR,0.63;95%confidence interval(CI),0.28-1.42;P=0.26]and progression-free survival(PFS;median,1.8 vs.1.3 months;HR,0.57;95%CI,0.26-1.28;P=0.16).Analyzing exclusively patients randomized to cetuximab,right-sided and transverse had comparable outcomes for OS(median,5.6 vs.5.9 months;HR,0.82;95%CI,0.50-1.34;P=0.43)and PFS(median,1.9 vs.1.8 months;HR,0.78;95%CI,0.49-1.26;P=0.31).Patients with left-sided mCRC had superior outcomes with cetuximab compared with transverse for OS(median,9.7 vs.5.9 months;HR,0.42;95%CI,0.27-0.67;P=0.0002)and PFS(median,3.8 vs.1.8 months;HR,0,49;95%CI,0.31-0.76;P=0.001).Location was not prognostic in patients treated with BSC alone.Conclusions Transverse mCRC has comparable prognostic and predictive features with right-sided mCRC.