Early-Onset Pancreas Cancer: Clinical Descriptors, Genomics, and Outcomes
Menée aux Etats-Unis à partir des données d'un centre de cancérologie portant sur 450 patients atteints précocement d'un cancer du pancréas diagnostiqué entre 2008 et 2018, cette étude identifie les caractéristiques cliniques et génomiques des tumeurs et analyse la survie des patients
Background : Recent evidence suggests a rising incidence of cancer in younger individuals. Herein, we report the epidemiologic, pathologic, and molecular characteristics of a patient cohort with early-onset pancreas cancer (EOPC).
Methods : Institutional databases were queried for demographics, treatment history, genomic results and outcomes. Overall survival (OS) from date of diagnosis was estimated using Kaplan-Meier method.
Results : Four hundred and fifty patients with EOPC were identified at Memorial Sloan Kettering between 2008 and 2018. Median OS was 16.3 months (95% confidence interval [CI] = 14.6 to 17.7 months) in the entire cohort and 11.3 months (95% CI = 10.2 to 12.2 months) for patients with stage IV disease at diagnosis. One hundred and thirty-two (29.3% of the cohort) underwent somatic testing; 21 of 132 (15.9%) had RAS wild-type cancers with identification of several actionable alterations, including ETV6-NTRK3, TPR-NTRK1, SCLA5-NRG1 and ATP1B1-NRG1 fusions, IDH1 R132C mutation, and mismatch repair deficiency. One hundred and thirty-eight (30.7% of the cohort) underwent germline testing; 44 of 138 (31.9%) had a pathogenic germline variant (PGV) and 27.5% harbored alterations in cancer susceptibility genes. Of patients seen between 2015 and 2018, 30 of 193 (15.5%) had a pathogenic germline variant. Among 138 who underwent germline testing, those with a PGV had a reduced all-cause mortality compared to patients without a PGV controlling for stage and year of diagnosis (hazard ratio = 0.42, 95%CI = 0.26 to 0.69).
Conclusions : PGVs are present in a substantial minority of patients with EOPC. Actionable somatic alterations were identified frequently in EOPC, enriched in the RAS wild-type subgroup. These observations underpin the recent guidelines for universal germline testing and somatic profiling in pancreatic ductal adenocarcinoma.
Journal of the National Cancer Institute , résumé, 2020