HOPE - Practice for Oncology, Hamburg, Germany.
Division of Hematology, Oncology and Palliative Care, Medical Department, St Josef-Hospital, Ruhr University, Bochum, Germany.
Eur J Cancer. 2018 Sep;101:105-113. doi: 10.1016/j.ejca.2018.06.015. Epub 2018 Jul 20.
The major prognostic relevance of primary tumour location (LPT) in advanced colorectal cancer was shown in large retrospective studies, but quantitative estimates are highly heterogeneous, and there is still limited information about its impact within the framework of biomarker-guided treatment strategies. Therefore, we analysed LPT in relation to other clinical and molecular parameters, based on mature survival data from the recent randomised AIO KRK0207 trial.
Patients uniformly received first-line induction treatment with a combination of bevacizumab, oxaliplatin and fluoropyrimidine. LPT was retrospectively determined using surgical reports, pathology reports and endoscopy reports. The prognostic analyses were performed using Kaplan-Meier estimations and log-rank tests, while hazard ratios (HRs) and multivariable results were derived from Cox models.
Among 754 patients with unequivocal information on LPT, patients with left-sided tumours showed a median overall survival of 24.8 months compared with the right-sided cohort with 18.4 months (HR: 1.54, 95% confidence interval: 1.30-1.81, P < 0.0001). In a multivariable model, LPT proved to be the strongest prognosticator (HR 1.60), with performance status, number of metastatic sites, baseline carcinoembryonic antigen (CEA) and platelets independently retaining prognostic significance. In the subgroup of patients with known RAS/BRAF status (n = 567, 75%), a BRAF mutation showed the greatest unfavourable impact (HR 3.16). Although BRAF is strongly correlated to LPT, the latter remained a significant prognosticator in the BRAF wild-type subgroup. In contrast, no major impact of LPT was seen on tumours carrying RAS mutations.
Within the framework of a uniform treatment strategy according to the current standards, LPT proved to have an important, although not solely dominating, relevance for survival prognosis. Its impact seems to be low in tumours with a RAS mutation.
ClinicalTrials.govNCT00973609.
在大型回顾性研究中已经证明了原发肿瘤部位（LPT）在晚期结直肠癌中的主要预后相关性，但定量估计结果高度异质，并且在基于生物标志物指导的治疗策略的框架内，关于其影响的信息仍然有限。因此，我们基于最近的随机 AIO KRK0207 试验的成熟生存数据，分析了 LPT 与其他临床和分子参数的关系。
患者统一接受贝伐单抗、奥沙利铂和氟嘧啶联合一线诱导治疗。LPT 通过手术报告、病理报告和内窥镜报告回顾性确定。使用 Kaplan-Meier 估计和对数秩检验进行预后分析，而风险比（HR）和多变量结果则来自 Cox 模型。
在 754 名明确有 LPT 信息的患者中，左肿瘤患者的中位总生存期为 24.8 个月，而右肿瘤患者为 18.4 个月（HR：1.54，95%置信区间：1.30-1.81，P<0.0001）。在多变量模型中，LPT 被证明是最强的预后因素（HR 1.60），表现状态、转移部位数量、基线癌胚抗原（CEA）和血小板独立保留预后意义。在已知 RAS/BRAF 状态的患者亚组（n=567，75%）中，BRAF 突变显示出最大的不利影响（HR 3.16）。尽管 BRAF 与 LPT 强烈相关，但在 BRAF 野生型亚组中，LPT 仍然是一个重要的预后因素。相比之下，LPT 对携带 RAS 突变的肿瘤没有重大影响。
在根据当前标准进行的统一治疗策略框架内，LPT 被证明对生存预后具有重要但并非唯一主导的相关性。在携带 RAS 突变的肿瘤中，其影响似乎较低。
ClinicalTrials.govNCT00973609。
