GENETIC TESTING TO GUIDE MRI SCREENING FOR PANCREATIC ADENOCARCINOMA: RESULTS OF A MICROSIMULATION MODEL

   Purpose:   First-degree relatives (FDRs) of patients with pancreatic adenocarcinoma (PAC) have elevated PAC risk, in part due to known genetic mutations.  While MRI screening is effective for early PAC detection in some high-risk populations, false-positive results – and associated, downstream mortality risks – attenuate its benefits.  Our goal was to evaluate the potential of genetic testing to improve screening decisions and life expectancy (LE) in the population of FDRs.

   Methods:   We developed a microsimulation model of PAC, calibrated to Surveillance, Epidemiology, and End Results program data.  We compared two strategies for FDRs: 1) test all FDRs with a panel of genetic mutations (e.g. BRCA2, CDKN2A), and screen with MRI for test+ FDRs if LE gains were achievable; 2) test no FDRs, and screen with MRI (all or none) if LE gains were achievable.  For test+ individuals, our model accounted for mutation-specific relative risks of PAC.  For test+, test-, and no-test scenarios, we simulated multiple screening approaches, defined by starting age and frequency, to determine if any resulted in an increase in LE.  Primary outcomes were LE gains by test outcome, and LE differences for the test vs. no-test decisions.     

Results: For test+ women, MRI screening yielded LE gains for 81% of mutation carriers.  Among those mutation carriers for whom screening could increase LE, maximum LE gains ranged from 1.2 days (BRCA2+ women screened once at age 55) to 156 days (STK11+ women screened annually from age 35). For test- women, MRI screening did not yield LE gains.  For no-test women, the LE gain from screening was minimal (0.18 days or less) regardless of the screening approach.  For test+ men, MRI screening also yielded LE gains for 81% of mutation carriers.  For test+ men, maximum LE gains ranged from 1.50 days (BRCA2+ men screened once at age 55) to 178 days (STK11+ men screened annually from age 35)  For men in the no-test and test- groups,  LE gains from screening were minimal (0.73 days and 0.44 days, respectively). 

   Conclusions:   Genetic testing of FDRs can target MRI screening for PAC to higher risk populations.  Timing and frequency of screening can be optimized by genetic test result, sparing morbidity and adding life expectancy.