Adherence to genetic testing guidelines in pancreatic cancer and impact on treatment.

Abstract

e16238 Background: NCCN June 2019 Guidelines recommend that clinicians consider germline (GL) testing for patients(pts) diagnosed with pancreatic cancer (PDAC) and consider molecular analysis of tumors in pts with metastatic disease. Up to 25% of advanced PDAC pts have GL or somatic mutations in the DNA damage repair (DDR) pathway which are predictive of response to platinum chemotherapy (plat) and maintenance therapy with olaparib. Referral for genetic testing (GT) at our institution is currently made at provider discretion. We aimed to determine rates of GT, factors associated with GT, and outcomes of those tested. Methods: Frequency of GT testing was examined in pts with non-endocrine PDAC and >2 visits between 6/2019 and 6/2021 at Mount Sinai Health System. Clinicopathological variables and treatment outcomes were also recorded. Results: 149 pts were included. 71 pts (48%) were male. 25 pts (17%) had a personal history of cancer and 8 (5.3%) with history of DDR related cancer (prostate, breast, ovarian). 66 pts (44%) had GL testing: 42 (28%) at diagnosis with the remainder later in treatment. The rate of GL testing increased every year: 33% (2019), 44% (2020), 61% (2021). There was no statistically significant association between decision to do GL testing and age, ECOG, race, personal or family history (FH) of cancer. A FH of DDR related cancer was positively associated with GL testing (47% vs 27% p=0.039). 8 pts (12% of pts tested) had pathological gMut: BRCA1 (1), BRCA2 (1), ATM (2), PALB2 (2) , NTHL1 (1), both CHEK2 and APC (1). 6 pts (75%) had GL testing at diagnosis. One g BRCA2 pt had a plat response. Neither g BRCA pt received a PARP inhibitor. 24 pts in total had a response to plat, 16 (67%) of whom had GL testing. 94 pts (63%) had molecular tumor testing (including 65% of pts with metastases). Pathogenic mut in DDR genes were identified in 9 pts: ARID1A (2), BRCA2 (3), ATM (2), PALB2 (2), CHEK2 (1). Four of these pts had corresponding gMuts. One pt with somatic ATM mut had g BRCA1 mut. Two pts with BRCA2 somatic mut did not have GL testing. Conclusions: GT based on provider discretion resulted in suboptimal rates of GL testing. However, since inception of national guidelines, testing rates nearly doubled. Rates of GL DDR mutations were lower than previously reported, with varying response to plat in this cohort. Future studies are needed to understand barriers to GT and improve implementation.[Table: see text]