原发性肿瘤位置作为转移性结直肠癌的一个预后因素
Primary tumor location as a prognostic factor in metastatic colorectal cancer.
作者信息
Loupakis Fotios, Yang Dongyun, Yau Linda, Feng Shibao, Cremolini Chiara, Zhang Wu, Maus Martin K H, Antoniotti Carlotta, Langer Christiane, Scherer Stefan J, Müller Thomas, Hurwitz Herbert I, Saltz Leonard, Falcone Alfredo, Lenz Heinz-Josef
机构信息
University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA (FL, DY, WZ, HJL); U.O. Oncologia Medica, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy (FL, CC, CA, AF); Genentech, Inc., South San Francisco, CA (LY, SF, CL, SJS, TM); Department of General, Visceral, and Tumor Surgery, University of Cologne, Cologne, Germany (MKHM); Response Genetics, Inc., Los Angeles, CA (MKHM); Department of Medical Oncology and Transplantation, Duke University, Durham, NC (HIH); Memorial Sloan-Kettering Cancer Center, New York, NY (LS) Current Affiliations: Onyx Pharmaceuticals, Inc. South San Francisco, CA (SF); Biocenter, Physiological Chemistry 1, University of Wuerzburg, Wuerzburg, Germany (SJS); Biomarker, Translational and Predictive Medicine Consulting, San Francisco, CA (TM).
出版信息
J Natl Cancer Inst. 2015 Feb 24;107(3). doi: 10.1093/jnci/dju427. Print 2015 Mar.
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.
背景
我们试图阐明原发性肿瘤位置对转移性结直肠癌（mCRC）预后的影响。
方法
我们在三个独立队列中评估了肿瘤位置与接受一线化疗±贝伐单抗的既往未治疗的mCRC患者生存参数之间的关联：一项前瞻性药物遗传学研究（PROVETTA）以及两项随机III期试验，AVF2107g和NO16966。脾曲近端或远端的癌症分别分类为右侧或左侧。主要终点为总生存期（OS）。使用Cox比例风险模型和逻辑回归模型分析数据。所有统计检验均为双侧检验。
结果
在PROVETTA研究（n = 200）、AVF2107g研究（n = 559）和NO16966研究（n = 1268）中可评估的患者中，分别有72.0%、63.1%和73.7%的患者患有左侧肿瘤。在PROVETTA研究中，左侧肿瘤患者的总生存期（左侧vs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）结局更佳。多变量分析证实右侧位置是一个负面预后变量, 独立于黏液组织学和BRAF突变状态。AVF2107g研究（OS的HR =0.55, 95% CI =0.43至0.70）和NO16966试验（OS 的HR =0.71,95% CI =0.62至0.82, 两者P<0.001）的数据也显示左侧肿瘤患者预后良好。在两项随机研究中，贝伐单抗的疗效均与肿瘤位置无关。
结论
这些数据表明，原发性肿瘤位置是既往未治疗的mCRC的一个重要预后因素。鉴于探索性数据集和两项验证性III期研究结果一致, 在随机试验中应考虑根据肿瘤起源部位进行分层。
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