Baseline splenic volume as a surrogate marker of FOLFIRINOX efficacy in advanced pancreatic carcinoma
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Anne Aarnink1, Corentin Richard2, Caroline Truntzer2, Julie Vincent1, Leila Bengrine1, Angélique Vienot3, Christophe Borg3,5 and Francois Ghiringhelli1,2,4,5
1Department of Medical Oncology, Center Georges Francois Leclerc, Dijon, France
2Platform of Transfer in Oncology, Besançon University Hospital, Besançon, France
3Department of Medical Oncology, Besançon University Hospital, Besançon, France
4INSERM, Unit 1231, Besançon, France
5University of Bourgogne-Franche-Comté, Besançon, France
Francois Ghiringhelli, email: [email protected]
Keywords: advanced pancreatic carcinoma; splenic volume; biomarker; FOLFIRINOX
Received: December 17, 2017 Accepted: April 27, 2018 Published: May 22, 2018
Background: 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.
Methods: 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.
Results: 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]; p = 0.03) and OS (HR 1.983, 95% CI = [1.085–3.624]; p = 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.
Conclusions: Baseline splenomegaly is a predictive marker of a poor response to FOLFIRINOX in aPDAC and remained predictive when associated with other clinical variables.
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