Anna M Varghese1,2,3, Isha Singh1, Rituraj Singh4, Siddharth Kunte5, Joanne F Chou6, Marinela Capanu6, Winston Wong7, Maeve A Lowery8, Zsofia K Stadler1,3, Erin Salo-Mullen1, Lily V Saadat9, Alice C Wei9, Marsha Reyngold10, Olca Basturk11, Ryma Benayed11, Diana Mandelker11, Christine A Iacobuzio-Donahue2,11, David P Kelsen1,2,3, Wungki Park1,2,3, Kenneth H Yu1,2,3, Eileen M O'Reilly1,2,3. 1. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 2. David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 3. Department of Medicine, Weill Cornell Medical College, New York, NY, USA. 4. Department of Medicine, Indiana University School of Medicine, Fort Wayne, IN, USA. 5. Department of Medicine, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA. 6. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 7. Department of Medicine, Columbia University Herbert Irving Comprehensive Cancer Center, New York, NY, USA. 8. School of Medicine, Trinity College Dublin, Dublin, Ireland. 9. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 10. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 11. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Abstract
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 from date of diagnosis was estimated using Kaplan-Meier method. RESULTS: Between 2008 and 2018, 450 patients with EOPC were identified at Memorial Sloan Kettering. Median overall survival was 16.3 (95% confidence interval [CI] = 14.6 to 17.7) months in the entire cohort and 11.3 (95% CI = 10.2 to 12.2) months for patients with stage IV disease at diagnosis. Of the patients, 132 (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. A total of 138 patients (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 PGV. Among 138 who underwent germline testing, those with a PGV had a reduced all-cause mortality compared with 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.
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 from date of diagnosis was estimated using Kaplan-Meier method. RESULTS: Between 2008 and 2018, 450 patients with EOPC were identified at Memorial Sloan Kettering. Median overall survival was 16.3 (95% confidence interval [CI] = 14.6 to 17.7) months in the entire cohort and 11.3 (95% CI = 10.2 to 12.2) months for patients with stage IV disease at diagnosis. Of the patients, 132 (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. A total of 138 patients (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 PGV. Among 138 who underwent germline testing, those with a PGV had a reduced all-cause mortality compared with 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.
Authors: Maria Grazia Tibiletti; Ileana Carnevali; Valeria Pensotti; Anna Maria Chiaravalli; Sofia Facchi; Sara Volorio; Frederique Mariette; Paolo Mariani; Stefano Fortuzzi; Marco Alessandro Pierotti; Fausto Sessa Journal: Biomedicines Date: 2022-05-23