Clinical exome sequencing vs. usual care for hereditary colorectal cancer diagnosis: A pilot comparative effectiveness study

• Published in: Contemporary clinical trials 2019-09, Vol.84, p.105820-105820, Article 105820
• Main Authors: Niu, Xin, Amendola, Laura M., Hart, Ragan, Bennette, Caroline S., Heagerty, Patrick, Horike-Pyne, Martha, Trinidad, Susan B., Rosenthal, Elisabeth A., Comstock, Bryan, Nefcy, Chris, Hisama, Fuki M., Bennett, Robin L., Grady, William M., Gallego, Carlos J., Tarczy-Hornoch, Peter, Fullerton, Stephanie M., Burke, Wylie, Regier, Dean A., Dorschner, Michael O., Shirts, Brian H., Robertson, Peggy D., Nickerson, Deborah A., Patrick, Donald L., Jarvik, Gail P., Veenstra, David L.
• Format: Article
• Language: English
• Subjects: Adenomatous Polyposis Coli - diagnosis; Adenomatous Polyposis Coli - genetics; Aged; Clinical exome sequencing; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - genetics; Communication; Comparative effectiveness; Comparative Effectiveness Research; Confidentiality; Cost-Benefit Analysis; Exome; Female; Genetic Predisposition to Disease - genetics; Health Resources - statistics & numerical data; Health Services - statistics & numerical data; Hereditary colorectal cancer/polyposis; Humans; Male; Middle Aged; Research Design; Sequence Analysis, DNA; Socioeconomic Factors
• ISSN: 1551-7144; 1559-2030; 1559-2030
• DOI: 10.1016/j.cct.2019.105820

Clinical exome sequencing (CES) provides the advantage of assessing genetic variation across the human exome compared to a traditional stepwise diagnostic approach or multi-gene panels. Comparative effectiveness research methods offer an approach to better understand the patient-centered and economic outcomes of CES. To evaluate CES compared to usual care (UC) in the diagnostic work-up of inherited colorectal cancer/polyposis (CRCP) in a randomized controlled trial (RCT). The primary outcome was clinical sensitivity for the diagnosis of inherited CRCP; secondary outcomes included psychosocial outcomes, family communication, and healthcare resource utilization. Participants were surveyed 2 and 4 weeks after results return and at 3-month intervals up to 1 year. Evolving outcome measures and standard of care presented critical challenges. The majority of participants in the UC arm received multi-gene panels [94.73%]. Rates of genetic findings supporting the diagnosis of hereditary CRCP were 7.5% [7/93] vs. 5.4% [5/93] in the CES and UC arms, respectively (P = 0.28). Differences in privacy concerns after receiving CRCP results were identified (0.88 in UC vs 0.38 in CES, P = 0.05); however, healthcare resource utilization, family communication and psychosocial outcomes were similar between the two arms. More participants with positive results (17.7%) intended to change their life insurance 1  month after the first return visit compared to participants returned a variant of uncertain significance (9.1%) or negative result (4.8%) (P = 0.09). Our results suggest that CES provides similar clinical benefits to multi-gene panels in the diagnosis of hereditary CRCP.