A population-based virtual solution to reduce gaps in genetic risk evaluation and management in families at high risk for hereditary cancer syndromes: The Georgia-California GeneLINK Trial

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Project Abstract: There is growing evidence that targeting genetic risk evaluation (GRE) in families where a cancer susceptibility gene pathogenic variant (PV) has been identified may be the most cost-effective approach to reduce the population burden of cancer through prevention. However, there are enormous challenges to implementing successful cascade genetic risk evaluation in families with hereditary cancer syndromes. The clinical context of GRE after cancer diagnosis is increasingly complex: As MGP testing has become the norm, guideline organizations have converged on a list of >40 cancer susceptibility genes in which PVs are clinically actionable, with wide variability in cancer threat and a myriad of strategies for prevention and early detection. A daunting challenge is that the cancer patient is responsible for communication and engagement of relatives for GRE. Despite the shared health threat among at risk relatives (ARRs), the social and contextual factors that affect family communication are complex. Furthermore, ARRs are dispersed world- wide and receive care in disparate health care practices. Importantly, there is little incentive and limited resources for clinicians to engage cancer patients’ relatives and genetic counseling services are increasingly strained. Given the lack of guidance for families, it is not surprising that most ARRs of cancer patients with PVs do not undergo GRE. We are uniquely positioned to develop and optimize a direct-to-family virtual genetic risk evaluation and testing solution offered to all at risk relatives of a population-based sample of adults recently diagnosed with cancer in Georgia and California who tested positive for a clinically relevant PV. We will use a unique data infrastructure we pioneered to identify and invite a diverse cohort of cancer patients with clinically relevant PVs and their families to participate in our study. We propose a 2 x 3 factorial randomized trial of 900 patients diagnosed in 2018-2019 in the two states who had a clinically significant PV detected by genetic testing that will offer genetic risk evaluation and testing to all 1st and 2nd degree relatives. We will evaluate the effects of two intervention design features on patient- and relative-centered outcomes: 1) the level of personalized family genetic risk support (a technology assisted personally tailored patient and family member education and communication tool called the Family Genetic Health Program, FGHP) vs. the FGHP plus direct assistance from a human FGHP Navigator); and 2) the price offered to the relatives for the genetic test (standard $200 vs. $100 vs. $50 per test). We will determine the independent effects of the two design features on 1) the cancer patient’s appraisal of communication and their engagement with relatives about hereditary cancer and GRE; 2) the invited relative’s appraisal of decision-making and receipt of genetic testing; and 3) on the enrolled relative’s completion of formal GRE. We will also explore the effect of the features on the outcomes across patient SES subgroups. The findings of this study have enormous potential to improve cancer prevention and early detection in families at high risk of hereditary cancer syndromes in the US.