Oncologists’ and cancer patients’ views on whole-exome sequencing and incidental findings: results from the CanSeq study

Abstract

Purpose While targeted sequencing improves outcomes for many cancer patients, how somatic and germline whole-exome sequencing (WES) will integrate into care remains uncertain. Methods We conducted surveys and interviews, within a study of WES integration at an academic center, to determine oncologists' attitudes about WES and to identify lung and colorectal cancer patients' preferences for learning WES findings. Results 167 patients (85% white, 58% female, mean age 60) and 27 oncologists (22% female) participated. Although oncologists had extensive experience ordering somatic tests (median 100/year), they had little experience ordering germline tests. Oncologists intended to disclose most WES results to patients but anticipated numerous challenges in using WES. Patients had moderately low levels of genetic knowledge (mean 4 correct of 7). Most patients chose to learn results that could help select a clinical trial, pharmacogenetic and positive prognostic results, and results suggesting inherited predisposition to cancer and treatable non-cancer conditions (all ≥95%). Fewer chose to receive negative prognostic results (84%) and results suggesting predisposition to untreatable non-cancer conditions (85%). Conclusion The majority of patients want most cancer-related and incidental WES results. Patients' low levels of genetic knowledge and oncologists' inexperience with large-scale sequencing presage challenges to implementing paired WES in practice.

Patient preferences regarding incidental genomic findings discovered during tumor profiling

“…For example, Miller et al 19 surveyed 29 patients with metastatic solid tumors and found that the majority found the risk of incidental findings as part of tumor profiling to be acceptable, whereas a small minority believed that such findings would come as an additional burden to them. Gray et al 20 reported that nearly all of the 105 patients enrolled in the CanSeq tumor sequencing research project desired information regarding incidental findings, as did Master et al 21 in a survey of 100 patients with leukemia, among whom 98% expressed a desire to learn about incidental health findings found in research samples. Although these studies certainly support the recommendations of ASCO for the disclosure of incidental findings to patients with cancer, the reported surveys were small and were limited to patients with advanced or metastatic disease who were specifically enrolled in tumor profiling or biobanking research studies.…”

“…1 Although growing data have suggested that patients in both general and oncology settings favor the disclosure of incidental germline variants, ASCO acknowledges that further research is needed to determine best practices. 1,[17][18][19][20][21] Toward this end, the goal of the current study was to survey a broad cohort of patients with cancer presenting in a clinical oncology setting regarding their attitudes toward incidental germline variants discovered during tumor profiling that could affect their personal health or that of their families.…”

The Right to Know: A Revised Standard for Reporting Incidental Findings

“…One 2006 survey found that, among 105 neuroimaging study participants, 97 percent wished to have incidental findings of incurable malignancies disclosed, and 91 percent wanted even benign abnormalities reported 18. Other more recent studies have found similar support for reporting genetic incidental findings 19. Even when individuals are reluctant to hear results, they want to be given control over whether results will be disclosed 20.…”

Ethical considerations for modern molecular pathology

“…Generally, they are very focused on obtaining a proper diagnosis and treatment and are not so concerned or familiar with the (e.g. hereditary) side effects of their molecular tumor workup [27][28][29][30][31]. Third, the analysis and input material are different.…”