The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada.
The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada; NCIC Clinical Trials Group, Kingston, Canada.
Eur J Cancer. 2015 Jul;51(11):1405-14. doi: 10.1016/j.ejca.2015.03.015. Epub 2015 May 12.
Right- and left-sided colon cancers (RC, LC) differ with respect to biology, pathology and epidemiology. Previous data suggest a mortality difference between RC and LC. We examined if primary tumour side also predicts for outcome in chemotherapy refractory, metastatic colon cancer (MCC). We also compared RC versus LC as a predictor of efficacy of epidermal growth factor receptor (EGFR) inhibition with cetuximab.
Reanalyzing NCIC CO.17 trial (cetuximab versus best supportive care [BSC]), we coded the primary tumour side as RC (caecum to transverse colon) or LC (splenic flexure to rectosigmoid). The association between tumour side and baseline characteristics was assessed. Cox regression models determined factors affecting overall survival (OS) and progression free survival (PFS).
Patients with RC (150/399) had more poorly differentiated, mutant KRAS, mutated PIK3CA and wild-type BRAF tumours, fewer liver and lung metastases, and shorter interval between diagnosis and study entry. Among BSC patients, tumour side was not prognostic for PFS (hazard ratios (HR) 1.07 [0.79-1.44], p = 0.67) or OS (HR 0.96 [0.70-1.31], p = 0.78). Among wild-type KRAS patients, those with LC had significantly improved PFS when treated with cetuximab compared to BSC (median 5.4 versus 1.8 months, HR 0.28 [0.18-0.45], p < 0.0001), whereas those with RC did not (median 1.9 versus 1.9 months, HR 0.73 [0.42-1.27], p = 0.26), [interaction p = 0.002].
In refractory MCC, tumour location within the colon is not prognostic, but is strongly predictive of PFS benefit from cetuximab therapy. Additional research is needed to understand the molecular differences between RC and LC and their interaction with EGFR inhibition.
右半结肠癌（RC）和左半结肠癌（LC）在生物学、病理学和流行病学方面存在差异。先前的数据表明 RC 和 LC 之间存在死亡率差异。我们研究了原发性肿瘤侧是否也能预测化疗耐药性转移性结直肠癌（MCC）的结局。我们还比较了 RC 和 LC 作为表皮生长因子受体（EGFR）抑制剂西妥昔单抗疗效的预测指标。
重新分析 NCIC CO.17 试验（西妥昔单抗对比最佳支持治疗[BSC]），我们将原发肿瘤侧编码为 RC（盲肠至横结肠）或 LC（脾曲至直肠乙状结肠）。评估肿瘤侧与基线特征之间的关联。Cox 回归模型确定影响总生存（OS）和无进展生存（PFS）的因素。
RC 患者（150/399）的肿瘤分化程度较差、KRAS 突变、PIK3CA 突变和 BRAF 野生型更多，肝转移和肺转移较少，诊断与研究入组之间的间隔更短。在 BSC 患者中，肿瘤侧对 PFS（风险比[HR]1.07[0.79-1.44]，p=0.67）或 OS（HR 0.96[0.70-1.31]，p=0.78）无预后意义。在野生型 KRAS 患者中，与 BSC 相比，LC 患者接受西妥昔单抗治疗的 PFS 显著改善（中位 5.4 个月对比 1.8 个月，HR 0.28[0.18-0.45]，p<0.0001），而 RC 患者则没有（中位 1.9 个月对比 1.9 个月，HR 0.73[0.42-1.27]，p=0.26），[交互作用 p=0.002]。
在难治性 MCC 中，肿瘤在结肠内的位置与预后无关，但强烈预测西妥昔单抗治疗的 PFS 获益。需要进一步研究以了解 RC 和 LC 之间的分子差异及其与 EGFR 抑制的相互作用。
