Abstract 1308: Policy guiding secondary findings from genome sequencing pertinent to cancer: Results from a systematic review
Authors: Majeed Safa , Johnston Christine , Saeedi Saumeh , Mighton Chloe , Rokoszak Vanessa , Abbasi Ilham , Grewal Sonya , Aguda Vernie , Malkin David , Bombard Yvonne 
Published: March 2024

Background: While genomic sequencing has personalized patient care across disciplines like oncology, secondary findings (SFs) unrelated to the primary indication are a common complicating factor. SFs relevant for oncology are categorized as cancer-related potentially leading to a cancer diagnosis (CA-SFs) or non-cancer findings revealing important medical conditions, predispositions, or carrier status in cancer patients (NC-SFs). These SFs can inform disease prevention, early detection, or management decisions, but may cause distress, overdiagnosis, and overuse of resources if actionability is limited. There is a lack of consensus for identifying, analyzing, and interpreting the clinical relevance of SFs. This significantly impacts cancer care, where paired tumor-normal sequencing is standard practice. Widespread practice variation can lead to detrimental impacts on patient outcomes and overall health. We synthesized policy guiding the clinical investigation of SFs for cancer to help providers navigate decisions regarding SFs.

Methods: We carried out a systematic review of international guidance directing the identification, analysis, and management of SFs from genomic sequencing, and analyzed the subset of policies specifically relating to oncology. We searched the grey literature (IFHGS members) and academic databases including MEDLINE, Embase and Cochrane. Two reviewers independently assessed policy documents for screening, data extraction and quality assessment (using AGREE-II).

Results: We identified 7 policies guiding the investigation of SFs relating to cancer across the general population (n=4), adults (n=1), pediatrics (n=1) and research (n=2) contexts. Most policies included guidelines for SF variant selection (identification; n=5) and management (n=4), with a minority detailing analysis processes (n=2). Recommended CA-SFs included medically actionable cancer predisposition variants, while suggested NC-SFs were variants important for drug therapies (identification). Laboratories were advised to ensure adequate coverage and read depth during SF analysis (analysis), while policies recommended that a medical genetics healthcare provider return results, specifically discussing their clinical utility (management).

Conclusions: To our knowledge, our review is the most comprehensive synthesis of policy guiding SFs for cancer. Policies outline the types of SFs to investigate from genome sequencing in cancer and non-cancer patients, and related strategies for disclosure. However, best practices for SF analyses and patient follow-up including SF surveillance, treatment, etc. remain poorly described. This synthesis will help cancer care providers navigate critical decision points based on current evidence and direct policymakers on gaps to fill in the future.

Citation Format: Safa Majeed, Christine Johnston, Saumeh Saeedi, Chloe Mighton, Vanessa Rokoszak, Ilham Abbasi, Sonya Grewal, Vernie Aguda, David Malkin, Yvonne Bombard. Policy guiding secondary findings from genome sequencing pertinent to cancer: Results from a systematic review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1308.