Department of Gastroenterology, Methodological and Quality of Life in Oncology Unit, EA 3181, Department of Digestive Surgery and Liver Transplantation, and Department of Medical Oncology, Besançon University Hospital, Besançon, France; Department of Medical Oncology, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Est Créteil University (UPEC), Créteil, France; Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France; Department of Hepato-Gastroenterology, Reims University Hospital, Reims, France; INSERM, Unit 1098, and Clinical Investigation Center 1431, University of Bourgogne-Franche-Comté, Besançon, France; Department of Gastroenterology, Vesoul Hospital, Vesoul, France.
J Natl Cancer Inst. 2017 Oct 1;109(10). doi: 10.1093/jnci/djx037.
In advanced pancreatic ductal adenocarcinoma (aPDAC), there is no consensual strategy for second-line chemotherapy (L2). Better discrimination of overall survival (OS) may help clinical decision-making. We aimed to predict OS from the beginning of L2 and to assess the benefit from chemotherapy among the identified risk groups.
Analyses were derived from all consecutive aPDAC patients treated at Besancon University Hospital, Besancon, France, between January 2003 and December 2013 (n = 462). The association of 50 parameters with OS was evaluated using univariate and multivariable Cox analyses. Based on the final model, a prognostic nomogram and score were developed and externally validated. Patients in the external validation cohort who received L2 (n = 163) were treated at three French institutions between January 2010 and April 2016. All statistical tests were two-sided.
In the development cohort, 395 patients (85.5%) were eligible for L2, of which 261 (66.1%) were treated. Age, smoking status, liver metastases, performance status, pain, jaundice, ascites, duration of first-line, and type of L2 regimen were identified as independent prognostic factors for OS in L2. The score determined three groups with median OS of 11.3 months (95% confidence interval [CI] = 9.1 to 12.9 months), 3.6 months (95% CI = 2.6 to 4.7 months), and 1.4 months (95% CI = 1.2 to 1.7 months), for low-, intermediate-, and high-risk groups, respectively ( P < .001). By applying the score in the population eligible for L2 but untreated, the chemotherapy benefit was statistically significant across all groups, but with a magnitude of the effect decreased statistically significantly from low- to high-risk groups ( P = .001 for treatment and risk groups interaction term). The ability of the score to discriminate OS was confirmed in the external validation cohort.
This prognostic nomogram and score in patients with aPDAC can accurately predict OS before administration of L2 and may help clinicians in their therapeutic decisions.
在晚期胰腺导管腺癌（aPDAC）中，二线化疗（L2）尚无共识策略。更好地区分总生存期（OS）可能有助于临床决策。我们旨在预测从 L2 开始的 OS，并评估在确定的风险组中化疗的获益。
分析来自法国贝桑松大学医院 2003 年 1 月至 2013 年 12 月连续治疗的所有 aPDAC 患者（n=462）。使用单变量和多变量 Cox 分析评估 50 个参数与 OS 的关系。基于最终模型，开发并外部验证了一个预后列线图和评分。在外部验证队列中，接受 L2 治疗的 163 例患者于 2010 年 1 月至 2016 年 4 月在法国的三个机构接受治疗。所有统计检验均为双侧。
在发展队列中，395 例患者（85.5%）有资格接受 L2 治疗，其中 261 例（66.1%）接受了治疗。年龄、吸烟状况、肝转移、体能状态、疼痛、黄疸、腹水、一线治疗持续时间和 L2 方案类型被确定为 L2 中 OS 的独立预后因素。该评分确定了三组，中值 OS 分别为 11.3 个月（95%置信区间[CI]：9.1 至 12.9 个月）、3.6 个月（95%CI=2.6 至 4.7 个月）和 1.4 个月（95%CI=1.2 至 1.7 个月），低、中、高危组，分别为（P<0.001）。在有资格接受 L2 但未接受治疗的患者中应用评分，化疗获益在所有组中均具有统计学意义，但从低危组到高危组的效应幅度统计学上显著降低（P=0.001 用于治疗和风险组交互项）。该评分在外部验证队列中区分 OS 的能力得到了证实。
在 aPDAC 患者中，该预后列线图和评分可准确预测 L2 治疗前的 OS，并可能有助于临床医生做出治疗决策。
