Preferences to receive unsolicited findings of germline genome sequencing in a large population of patients with cancer

• Published in: ESMO open 2020-04, Vol.5 (2), p.e000619, Article e000619
• Main Authors: Bijlsma, Rhode, Wouters, Roel, Wessels, Hester, Sleijfer, Stefan, Beerepoot, Laurens, ten Bokkel Huinink, Daan, Cruijsen, Hester, Heijns, Joan, Lolkema, Martijn P, Steeghs, Neeltje, van Voorthuizen, Theo, Vulink, Annelie, Witteveen, Els, Ausems, Margreet, Bredenoord, Annelien, May, Anne M, Voest, Emile
• Format: Article
• Language: English
• Subjects: cancer patients; ethics; genome sequencing; Original Research; preferences; unsolicited finding
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1136/esmoopen-2019-000619

BackgroundIn precision medicine, somatic and germline DNA sequencing are essential to make genome-guided treatment decisions in patients with cancer. However, it can also uncover unsolicited findings (UFs) in germline DNA that could have a substantial impact on the lives of patients and their relatives. It is therefore critical to understand the preferences of patients with cancer concerning UFs derived from whole-exome (WES) or whole-genome sequencing (WGS).MethodsIn a quantitative multicentre study, adult patients with cancer (any stage and origin of disease) were surveyed through a digital questionnaire based on previous semi-structured interviews. Background knowledge was provided by showing two videos, introducing basic concepts of genetics and general information about different categories of UFs (actionable, non-actionable, reproductive significance, unknown significance).ResultsIn total 1072 patients were included of whom 701 participants completed the whole questionnaire. Overall, 686 (85.1%) participants wanted to be informed about UFs in general. After introduction of four UFs categories, 113 participants (14.8%) changed their answer: 718 (94.2%) participants opted for actionable variants, 537 (72.4%) for non-actionable variants, 635 (87.0%) participants for UFs of reproductive significance and 521 (71.8%) for UFs of unknown significance. Men were more interested in receiving certain UFs than women: non-actionable: OR 3.32; 95% CI 2.05 to 5.37, reproductive significance: OR 1.97; 95% CI 1.05 to 3.67 and unknown significance: OR 2.00; 95% CI 1.25 to 3.21. In total, 244 (33%) participants conceded family members to have access to their UFs while still alive. 603 (82%) participants agreed to information being shared with relatives, after they would pass away.ConclusionOur study showed that the vast majority of patients with cancer desires to receive all UFs of genome testing, although a substantial minority does not wish to receive non-actionable findings. Incorporation of categories in informed consent procedures supports patients in making informed decisions on UFs.