• Jean Pinson, Julie Henriques, Ludivine Beaussire, Nasrin Sarafan-Vasseur, Sa CunhaAntonioADepartment of Hepato-Biliary and Pancreatic Surgery, and Liver Transplantation, Paul Brousse Hospital, AP-HP, Villejuif, France., Jean-Baptiste Bachet, Dewi Vernerey, Frederic Di Fiore, Lilian Schwarz, and PANACHE01-PRODIGE48 group.
• Department of Digestive Surgery, Rouen University Hospital, Rouen, France.
• Ann. Surg. 2024 Nov 1; 280 (5): 734744734-744.

ObjectiveTo investigate in patients treated for a resectable pancreatic ductal adenocarcinoma [pancreatic adenocarcinoma (PA)], the prognostic value of baseline carbohydrate antigen 19.9 (CA19-9) and circulating tumor DNA (ctDNA) for overall survival (OS), to improve death risk stratification, based on a planned ancillary study from PANACHE01-PRODIGE 48 trial.BackgroundBiological borderline situation that was first used by the MD Anderson, became a standard practice following the international consensus conference in 2016 to manage PA. Regarding the risk of systemic disease, especially in the setting of "markedly elevated" CA19-9, neoadjuvant therapy is advised to avoid unnecessary surgery, with a risk of early recurrence. To best define biological borderline situations, new biomarkers are needed.MethodsCharacteristics at diagnosis and OS were compared between patients with or without ctDNA status available. OS was estimated with the Kaplan-Meier method and compared with a log-rank test. The restricted cubic spline approach was used to identify the optimal threshold for biological parameters for death risk stratification. Univariate and multivariate Cox proportional hazard models were estimated to assess the association of ctDNA status and other parameters with OS.ResultsAmong the 132 patients from the primary population for analysis in the PANACHE01 -PRODIGE 48 trial, 92(71%) were available for ctDNA status at diagnosis. No selection bias was identified between patients with or without ctDNA status. Fourteen patients (15%) were ctDNA+ and exhibited a higher risk for death [ P = 0.0188; hazard ratio (95% CI): 2.28 (1.12-4.63)]. In the 92 patients with ctDNA status available among the other parameters analyzed, only CA19-9 was statically associated with OS in univariate analysis. Patients with a log of CA19-9 equal or superior to 4.4 that corresponds to a CA19-9 of 80 UI/mL were identified at higher risk for death [ P = 0.0143; hazard ratio (95% CI): 2.2 (1.15-4.19)]. In multivariate analysis, CA19-19 remained independently associated with OS ( P = 0.0323). When combining the 2 biomarkers, the median OS was 19.4 [IC 95%: 3.8-not reached (NR)] months, 30.2 (IC 95%: 17.1-NR) months and NR (IC 95%: 39.3-NR) for "CA19-9 high and ctDNA+ group," "CA19-9 high or ctDNA+ group," and "CA19-9 low and ctDNA- group," respectively (log-rank P = 0.0069).ConclusionsProgress in the management of potentially operable PA remains limited, relying solely on strategies to optimize the sequence of complete treatment, based on modern multidrug chemotherapy (FOLFIRINOX, GemNabPaclitaxel) and surgical resection. The identification of risk criteria, such as the existence of systemic disease, is an important issue, currently referred to as "biological borderline disease." Few data, particularly from prospective studies, allow us to identify biomarkers other than CA19-9. Combining ctDNA with CA19-9 could be of interest to best define biological borderline situations in PA.Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

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