Abstract PO-052: A multisystem approach doubles the number of patients referred for genetic testing and diagnosed with Lynch syndrome with equally success among ethnic/racial groups
Authors: Singh Vinit , Ganzak Amanda , Gershkovich Peter , Gibson Joanna , Xicola Rosa M. , Llor Xavier 
Published: January 2022

Abstract
Background: Lynch syndrome (LS) affects 1/279 individuals and accounts for 3-5% of all colorectal cancers (CRC). LS is due to germline mutations in mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2. Tumors exhibit MMR deficiency, expressed as loss of MMR protein expression on immunohistochemistry (IHC). A subset of sporadic tumors also has MMR deficiency due to inactivation of MLH1 via promoter methylation and about 2/3 have BRAFV600E mutations. Increased surveillance and chemoprevention reduce cancer incidence and mortality in LS. LS is largely underdiagnosed, particularly among minorities. Universal screening of CRC tumors through IHC is recommended in order to help identify patients for LS genetic testing. Nevertheless, even in programs that have implemented this, minority patients with MMR deficient tumors were found to be consistently under-referred mostly due to referral bias. We set up a strategy to increase LS and tackle disparities in cancer genetics (CG). Methods: This study reports on the analysis of universal CRC IHC testing for MMR expression, initially followed by BRAF V600E and later by MLH1 testing for loss of MLH1/PMS2 expression, from implementation (1/1012) until 1/1021. In 6/2015, a system was established where a designated Pathologist reviewed all results and a list of identified candidates for germline LS testing (abnormal MMR expression/wild type BRAF or methylation of MLH1) was sent to the CG program. After a two-week period, if no referral had been placed, a genetic counselor (GC) messaged the provider requesting a referral. The pathology side was fully automated in 9/2018 through the monitoring engine Repetitive Tasks Scheduling Engine (RTSE) that pulls data stored in the underlying relational database-Adaptive Server Enterprise, which is accessible to RTSE via a Java Database Connectivity API. This process automatically generates weekly emails that report all cases with suspicion criteria for LS to CG. Results: Since 1-2012, 1,433 patients with CRC underwent tumor testing and were included in this study: 78.5% non-Hispanic white (NHW); 12.2% African American (AA); 6.77% Hispanic (H). Prior to the interventions 25% of eligible patients were referred to CG and none among AA. Once the interventions were established, appropriate referrals prior to messaging the provider were 39.5% for NHW, 35.7% for AA, and 42.8% for H. As a result of the messages, referral rates increased to 80.5% (p=0.00) in NHW, 85.7% in AA (p=0.05), and 71.5% in H (ns). The total number of patients diagnosed with LS since universal testing started was 19: 2 prior to the interventions (0.8% of all CRC); 17 during the interventions (1.5% of all CRC). Conclusion: A systematic, automated, multi-system approach, that includes a targeted message to providers can double the number of appropriate referrals for genetic testing to rule out Lynch syndrome and resulted in almost twice the percentage of LS diagnosis with equal success among AA, H, and NHW.
Citation Format: Vinit Singh, Amanda Ganzak, Peter Gershkovich, Joanna Gibson, Rosa M. Xicola, Xavier Llor. A multisystem approach doubles the number of patients referred for genetic testing and diagnosed with Lynch syndrome with equally success among ethnic/racial groups [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-052.