Abstract
BackgroundThe clinical impact of addressing potential germline alterations from tumor-only next-generation sequencing (NGS) is not well characterized. Current guidelines for cancer genetic testing may miss clinically actionable germline changes, which may have important implications for cancer screening, treatment, and prevention. We examined whether increasing involvement of the clinical genetics service during somatic tumor-only NGS review at Molecular Tumor Board (MTB) increases the detection of germline findings.MethodsIn a retrospective evaluation of patients who underwent tumor-only NGS and were reviewed at MTB, we quantified genetic counseling (GC) referrals as well as germline testing uptake and results across three cohorts: before (C1) and after (C2) the addition of tumor-only NGS review and after (C3) instituting a formal process to coordinate NGS-based genetics referrals to preexisting oncology appointments. All statistical tests were two-sided.ResultsFrom 2013 to 2017, 907 tumor-only NGS reports were reviewed at MTB (nC1 = 281, nC2 = 493, nC3 = 133); gastrointestinal (22.5%), lung (19.7%), genitourinary (14.8%), and breast (14.1%) were the most common index cancers. GC visits due to MTB increased with each successive cohort (C1 = 1.1%, C2 = 6.9%, C3 = 13.5%; P for trend [Ptrend] < .001), as did germline testing (C1 = 0.7%, C2 = 3.2%, C3 = 11.3%; Ptrend < .001). Diagnosis of germline pathogenic variants increased with each successive cohort (C1 = 1.4%, C2 = 2.0%, C3 = 7.5%; Ptrend = .003) and with germline pathogenic variants found by MTB review (C1 = 0.4%, C2 = 0.4%, C3 = 2.3%; Ptrend = .12).ConclusionsBoth review of tumor-only NGS by genetics and the institution of a process coordinating GC with oncology appointments increased the discovery of germline pathogenic variants from tumor-only NGS testing. Furthermore, this process identified germline pathogenic variant carriers who would not have otherwise met standard criteria for germline testing.
Highlights
The clinical impact of addressing potential germline alterations from tumor-only next-generation sequencing (NGS) is not well characterized
We examined whether increasing involvement of the clinical genetics service during somatic tumor-only NGS review at Molecular Tumor Board (MTB) increases the detection of germline findings
When these trends were evaluated for those cases where MTB directly influenced germline followup, we found that genetic counseling (GC) visits increased from C1 to C2 to C3 (1.1% to 6.9% to 13.5%, P for trend (Ptrend) < .001); germline testing increased from C1 to C2 to C3 (0.7% to 3.2% to 11.3%, Ptrend < .001); and the discovery of germline pathogenic variants increased in C3, without the trend reaching statistical significance (C1 to C2 to C3, 0.4% to 0.4% to 2.3%, Ptrend 1⁄4 .12). (Table 2)
Summary
The clinical impact of addressing potential germline alterations from tumor-only next-generation sequencing (NGS) is not well characterized. Methods: In a retrospective evaluation of patients who underwent tumor-only NGS and were reviewed at MTB, we quantified genetic counseling (GC) referrals as well as germline testing uptake and results across three cohorts: before (C1) and after (C2) the addition of tumor-only NGS review and after (C3) instituting a formal process to coordinate NGS-based genetics referrals to preexisting oncology appointments. Conclusions: Both review of tumor-only NGS by genetics and the institution of a process coordinating GC with oncology appointments increased the discovery of germline pathogenic variants from tumor-only NGS testing. This process identified germline pathogenic variant carriers who would not have otherwise met standard criteria for germline testing
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