Aarnink Anne, Richard Corentin, Truntzer Caroline, Vincent Julie, Bengrine Leila, Vienot Angélique, Borg Christophe, Ghiringhelli Francois
Department of Medical Oncology, Center Georges Francois Leclerc, Dijon, France.
Platform of Transfer in Oncology, Besançon University Hospital, Besançon, France.
Oncotarget. 2018 May 22;9(39):25617-25629. doi: 10.18632/oncotarget.25424.
The FOLFIRINOX regimen is the standard first-line treatment for advanced pancreatic adenocarcinoma (aPDAC). However, because of its potential toxicity, predictive biomarkers could help clinical decision-making.
A cohort of 97 aPDAC patients treated with first-line FOLFIRINOX were studied. The association between splenic volume and progression-free survival (PFS) and overall survival (OS) was evaluated using univariate and multivariable Cox analyses. The external validation cohort was composed of 117 patients treated with Gemcitabine and 52 patients treated with FOLFIRINOX.
In the training cohort, the splenic volume of 97 patients was measured at baseline and at the end of therapy. The spleen size increased in 81% of patients, with at least a 50% increase in 27% of patients. Baseline splenomegaly predicted PFS (HR 1.812, 95% CI = [1.036-3.169]; = 0.03) and OS (HR 1.983, 95% CI = [1.085-3.624]; = 0.02) in the training cohort. These results were then validated in an external cohort of patients who were treated with FOLFIRINOX excluding those in the control cohort who were treated with gemcitabine. In a multivariate model based on the CoxBoost method, the following were selected as predictive markers of FOLFIRINOX efficacy (AUC = 0.81): performance status, liver metastasis, baseline Ca199 and CEA levels and baseline splenomegaly. The predictive ability of the model was validated in the external cohort that was also treated with FOLFIRINOX.
Baseline splenomegaly is a predictive marker of a poor response to FOLFIRINOX in aPDAC and remained predictive when associated with other clinical variables.
FOLFIRINOX方案是晚期胰腺腺癌（aPDAC）的标准一线治疗方案。然而，由于其潜在毒性，预测性生物标志物有助于临床决策。
对97例接受一线FOLFIRINOX治疗的aPDAC患者进行队列研究。采用单因素和多因素Cox分析评估脾体积与无进展生存期（PFS）和总生存期（OS）之间的关联。外部验证队列由117例接受吉西他滨治疗的患者和52例接受FOLFIRINOX治疗的患者组成。
在训练队列中，对97例患者在基线和治疗结束时测量脾体积。81%的患者脾脏大小增加，27%的患者至少增加50%。基线脾肿大预测训练队列中的PFS（HR 1.812，95%CI = [1.036 - 3.169]；P = 0.03）和OS（HR 1.983，95%CI = [1.085 - 3.624]；P = 0.02）。然后在接受FOLFIRINOX治疗的患者外部队列中验证这些结果，不包括接受吉西他滨治疗的对照队列中的患者。在基于CoxBoost方法的多变量模型中，选择以下因素作为FOLFIRINOX疗效的预测标志物（AUC = 0.81）：体能状态、肝转移、基线Ca199和CEA水平以及基线脾肿大。该模型的预测能力在同样接受FOLFIRINOX治疗的外部队列中得到验证。
基线脾肿大是aPDAC患者对FOLFIRINOX反应不佳的预测标志物，与其他临床变量相关时仍具有预测性。
