Primary Tumor Location as a Prognostic Factor in Metastatic Colorectal Cancer
Primary Tumor Location as a Prognostic Factor in Metastatic Colorectal Cancer
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DOI：
10.1093/jnci/dju427
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发表时间：
2015-03-01
影响因子：
10.3
通讯作者：
Lenz, Heinz-Josef
中科院分区：
文献类型：
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作者：
Loupakis, Fotios;Yang, Dongyun;Lenz, Heinz-Josef
背景：我们试图阐明原发肿瘤位置对转移性结直肠癌 (mCRC) 的预后影响。方法：我们在三个独立队列中评估了先前未经治疗的 mCRC 患者接受一线化疗+/-贝伐珠单抗的肿瘤位置与生存参数之间的关联：一项前瞻性药物遗传学研究 (PROVETTA) 和两项随机 III 期试验 AVF2107g 和 NO16966。脾曲近端或远端的癌症分别分为右侧或左侧。主要终点是总生存期（OS）。使用 Cox 比例风险和逻辑回归模型对数据进行分析。所有统计检验均为两侧。 结果：在 PROVETTA (n = 200)、AVF2107g (n = 559) 和 NO16966 (n = 1268) 研究中的可评估患者中，分别有 72.0%、63.1% 和 73.7% 患有左侧肿瘤。在 PROVETTA 中，左侧肿瘤患者具有优异的 OS（左侧与右侧：风险比 [HR] = 0.44，95% 置信区间 [CI] = 0.28 至 0.70，P < 0.001）和无进展生存期（HR = 0.52，95% CI = 0.36 至 0.75，P < 0.001）结果。多变量分析证实右侧位置是一个阴性预后变量，与粘液组织学和 BRAF 突变状态无关。 AVF2107g（OS 的 HR = 0.55，95% CI = 0.43 至 70）和 NO16966 试验（OS 的 HR = 0.71，95% CI = 0.62 至 0.82，均 P < 0.001）的数据也显示出左侧肿瘤患者的良好结局。在这两项随机研究中，贝伐珠单抗的疗效与肿瘤位置无关。结论：这些数据表明，原发肿瘤位置是先前未经治疗的 mCRC 的重要预后因素。鉴于探索性研究和两项验证性 III 期研究的一致性，随机试验中应考虑肿瘤起源侧进行分层。
Background: We sought to clarify the prognostic impact of primary tumor location in metastatic colorectal cancer (mCRC).Methods: We evaluated the association between tumor location and survival parameters in patients with previously untreated mCRC receiving first-line chemotherapy +/- bevacizumab in three independent cohorts: a prospective pharmacogenetic study (PROVETTA) and two randomized phase III trials, AVF2107g and NO16966. Cancers proximal or distal of the splenic flexure were classified as right-sided or left-sided, respectively. The primary end point was overall survival (OS). Data were analyzed with Cox proportional hazards and logistic regression models. All statistical tests were two-sided.Results: Among evaluable patients in the PROVETTA (n = 200), AVF2107g (n = 559), and NO16966 (n = 1268) studies, 72.0%, 63.1%, and 73.7% had left-sided tumors, respectively. In PROVETTA, patients with left-sided tumors had superior OS (left-sided vs right-sided: hazard ratio [HR] = .44, 95% confidence interval [CI] = .28 to .70, P < .001) and progression-free survival (HR = .52, 95% CI = .36 to .75, P < .001) outcomes. Multivariable analyses confirmed right-sided location as a negative prognostic variable, independent of mucinous histology and BRAF mutational status. Data from the AVF2107g (HR for OS = .55, 95% CI = .43 to.70) and NO16966 trials (HR for OS = .71, 95% CI = .62 to .82 both P < .001) also showed favorable outcomes in patients with left-sided tumors. In both randomized studies, the efficacy of bevacizumab was independent of tumor location.Conclusions: These data demonstrate that primary tumor location is an important prognostic factor in previously untreated mCRC. Given the consistency across an exploratory set and two confirmatory phase III studies, side of tumor origin should be considered for stratification in randomized trials.