Pancreatic cancer germline mutation report: An in-depth analysis of demographics, mutation profile, and patient survival.

Journal of Clinical Oncology(2022)

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摘要
e16233 Background: Germline genetic testing is now recommended for patients with pancreatic ductal adenocarcinoma (PDAC). We explored whether attributes of testing, such as uptake fraction and rate, were associated with various clinical features. Here we examined germline mutations found in our database, identified barriers to germline testing, and explored a relationship between mutations and survival in our cohort of patients from New York’s largest healthcare system. Methods: Patients with PDAC were identified using billing records across our institution with an IRB-approved protocol. Germline mutation data were assessed through chart review. Median income was annotated using zip codes and www.census.gov. Date of diagnosis (DOD) was recorded as the date of biopsy or, if no biopsy was performed, the date of earliest lesion-found CT scan. Lag of testing was calculated as the difference between DOD and the date of germline sample collection. Overall survival (OS) was calculated by mutational status. Results: Between Mar 2016 and Feb 2022, 305 patients with PDAC were identified, with 103 (36.3%) having reports found (F), and 202 (63.7%) not having reports found (NF). Availability of germline testing did not vary by median income (F: 95954 dollars vs NF: 94368 dollars, t = 0.414, p = 0.68). The geographic distribution of patients among F and NF is listed below in Table. Pearson analysis between median income and lag of testing showed a negative correlation (y = -0.0027x+315.6, R = -0.241, p = 0.014). Level of income (cutoff: 100k) also affected the mean days in lag of testing (below: 111.8d, above: -44.0d, t = 2.190, p = 0.031). There was no difference in the median survival between F and NF (median: F: 573d, NF: 717d, HR 0.459-1.155, p = 0.17). For mutational analysis, 103 patients with PDAC were identified: 59 without germline mutations (GMs) (12 deaths), and 44 with GMs (16 deaths). We identified 7 patients with pathogenic GMs (APC, ATM, BRCA2, CHEK2, CDKN2A, and PALB2) and 41 patients with variants of unknown significance (VUS), including ATM (6), BRCA2 (4), MSH6 (3) and CHEK2 (2). OS was not statistically different between GM and no GM (Median OS: no GM 1520d; GM 573d, HR 0.394-1.871, p = 0.702). Conclusions: Analysis of germline and clinical data from our 305-patient cohort identified a striking and concerning negative correlation between patient median income and lag between DOD and germline testing. These results compel further investigation into the operational processes that prompt germline testing at our institution. [Table: see text]
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关键词
pancreatic cancer,mutation profile,patient survival,in-depth
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