Improving cascade genetic testing for families with inherited pancreatic cancer (PDAC) risk: The genetic education, risk assessment and testing (GENERATE) study.

Authors

Matthew Yurgelun

Matthew B. Yurgelun

Dana-Farber Cancer Institute, Boston, MA

Matthew B. Yurgelun , C. Sloane Furniss , Barbara Kenner , Alison Klein , Catherine C. Lafferty , Andrew M. Lowy , Florencia McAllister , Maureen E Mork , Scott H. Nelson , Alison Robertson , Jill E. Stopfer , Meghan Underhill , Allyson J. Ocean , Lisa Madlensky , Gloria M. Petersen , Judy Ellen Garber , Scott Michael Lippman , Michael Goggins , Anirban Maitra , Sapna Syngal

Organizations

Dana-Farber Cancer Institute, Boston, MA, Kenner Family Research Fund, New York, NY, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, UCSD Moores Cancer Center, La Jolla, CA, The University of Texas MD Anderson Cancer Center, Houston, TX, Mayo Clinic, Rochester, MN, Center for Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA, Weill Cornell Medical College, New York, NY, University of California, San Diego, La Jolla, CA, Johns Hopkins University, Baltimore, MD, University of Texas MD Anderson Cancer Center, Houston, TX

Research Funding

Other Foundation

Background: 4-10% of PDAC patients harbor pathogenic germline variants in cancer susceptibility genes, including APC, ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, and TP53. For families with such pathogenic variants, the greatest potential impact of germline testing is to identify relatives with the same pathogenic variant (cascade testing), thereby providing the opportunity for early detection and cancer interception of PDAC and other associated malignancies. Numerous factors limit cascade testing in real-world practice, including family dynamics, widespread geographic distribution of relatives, access to genetic services, and misconceptions about the importance of germline testing, such that the preventive benefits of cascade testing are often not fully realized. The primary aim of this study is to analyze two alternative strategies for cascade testing in families with inherited PDAC susceptibility. Methods: 1000 individuals (from approximately 200 families) with a confirmed pathogenic germline variant in any of the above genes in a 1st/2nd degree relative and a 1st/2nd degree relative with PDAC will be remotely enrolled through the study website (www.generatestudy.org) and randomized between two different methods of cascade testing (individuals with prior genetic testing will be ineligible): Arm 1 will undergo pre-test genetic education with a pre-recorded video and live interactive session with a genetic counselor via a web-based telemedicine platform (Doxy.me), followed by germline testing through Color Genomics; Arm 2 will undergo germline testing through Color Genomics without dedicated pre-test genetic education. Color Genomics will disclose results to study personnel and directly to participants in both arms. Participants in both arms will have the option of pursuing additional telephone-based genetic counseling through Color Genomics. The primary outcome will be uptake of cascade testing. Secondary outcomes will include participant self-reported genetic knowledge, cancer worry, distress, decisional preparedness, familial communication, and screening uptake, which will be measured via longitudinal surveys. Enrollment will begin February, 2019. Clinical trial information: NCT03762590

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Abstract Details

Meeting

2019 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Gastrointestinal (Noncolorectal) Cancer

Track

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Sub Track

Pancreatic Cancer

Clinical Trial Registration Number

NCT03762590

Citation

J Clin Oncol 37, 2019 (suppl; abstr TPS4162)

DOI

10.1200/JCO.2019.37.15_suppl.TPS4162

Abstract #

TPS4162

Poster Bd #

256b

Abstract Disclosures

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