17.6% of patients in a German cohort with exocrine pancreatic cancer were diagnosed with a genetic tumor syndrome-a case for universal genetic testing?
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
William D, Bermúdez M, Kübler A, Kahlert C, Distler M, Weitz J, Uhrig S, Fröhlich M, Hutter B, Aust D, Baretton G, Wimberger P, Kast K, Meisel C, Gieldon L, Porrmann J, Wagner J, Arlt M, Franke M, Fischer J, Hackmann K, Kreutzfeldt S, Mock A, Heilig C E, Lipka D B, Teleanu M-V, Schlenk R F, Brors B, Hübschmann D, Paramasivam N, Richter D, Beck K, Pfütze K, Buchhalter I, Weichert W, Herold T, Spiekermann K, Jost P J, Keilholz U, Klauschen F, Bauer S, Siveke J T, Kindler T, Boerries M, Illert A L, Bitzer M, Schulze-Osthoff K, Schirmacher P, Stenzinger A, Horak P, Heining C, Folprecht G, Fröhling S, Glimm H, Schröck E, Jahn A
Аннотация
PATIENTS AND METHODS: We retrospectively evaluated prospective cancer predisposition testing in 125 patients with exocrine PCA from a single-center clinical genetics clinic (n = 41) and a multicenter precision oncology program (n = 84) within 64 genes, including 14 established PCA risk genes. Associations with clinical and somatic molecular parameters, as well as therapy recommendations, were assessed.
RESULTS: PGVs were identified in 21.6% of patients (n = 27/125) across 14 CPGs. A genetic tumor syndrome was diagnosed in 17.6% of patients (n = 22/125). Existing inclusion criteria for germline testing [European Society for Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO), National Comprehensive Cancer Network (NCCN)] would have missed up to 23.8% of PGV carriers (n = 5/21). Age of onset was not associated with PGV yield. A meta-analysis of 10 other PCA cohorts showed a median PGV yield of 14.1%.In a precision oncology program, 10.7% (n = 9/84) of PCA patients received treatment recommendations supported by PGVs. Genetic testing was carried out on relatives of 73.3% of PGV-positive patients (n = 11/15), with one family demonstrating PGV confirmation in 7 of 13 tested relatives.
CONCLUSIONS: These findings support ASCO and NCCN recommendations for germline testing in all PCA patients. We suggest offering large-panel genetic diagnostics early in clinical management, regardless of clinical parameters, with ongoing evaluation and adjustment of the gene panel.