Germline evaluation of patients undergoing tumor genomic profiling: An academic cancer center’s experience with implementing a germline review protocol

Abstract

Tumor genomic profiling (TGP) has the potential to identify germline variants in addition to its primary use of informing cancer treatment based on genetic alterations within the tumor. However, there are no formal consensus guidelines to identify patients who would be eligible for genetic counseling (GC) and germline testing (GT) testing in patients undergoing TGP. The purpose of this study is to describe an institutionally developed Germline Review Protocol (GRP) to evaluate adult cancer patient cases already undergoing TGP to determine GC referral eligibility. We report on our retrospective experience implementing this protocol into practice wherein 172 patients out of 638 patients reviewed (27%) were recommended for a GC referral over a 17-month time period. Of those 172 patients recommended for a GC referral, only 34 patients (20%) completed GC and GT. Among patients who received GT, 15 (44%) were positive for at least one pathogenic or likely pathogenic (P/LP) variant, seven patients (21%) were negative and 12 patients (35%) had at least 1 variant of uncertain significance (VUS). The primary reason GC and GT was not completed was because the patient moved to hospice care or was deceased. This is one of the first studies outlining the process and results of a formalized institutional protocol to facilitate patient referrals for GC and GT based on TGP results.

Genetic Testing Utilization: Discrepancies Between Somatic and Germline Results in Patients With Cancer Reviewed at the UW Health Precision Medicine Molecular Tumor Board

“…Current literature primarily focuses on streamlining referrals for germline testing on the basis of results of somatic testing. 20,21 Although identifying hereditary cancer predisposition is not the primary goal of molecular tumor boards, they are uniquely positioned to facilitate recommendations for germline genetic evaluation in patients who have not yet had it. In this cohort, germline genetic testing after a recommendation from the PMMTB helped to identify germline pathogenic variants in 12 patients, all of which have clinical implications for patients and their families.…”

“…19 With the increasing and earlier use of somatic analysis on tumors, the likelihood that patients will only receive somatic testing may rise. [19][20][21][22][23] Without an understanding of the nuanced differences in methodology, variant classification, and reporting criteria between germline and somatic testing strategies, it is easy to assume, incorrectly, that all germline variants would appear on somatic testing. 11 Differences in testing design and purpose mean that not all genes included on germline testing are analyzed on somatic testing.…”