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 , Chinedu I. Ukaegbu , C. Sloane Furniss , Barbara Kenner , Alison Klein , 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
Stand Up To Cancer-Lustgarten Foundation Pancreatic Cancer Interception Translational Cancer Research Grant (Grant Number: SU2C-AACR-DT25-17)

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 variant (cascade testing), thereby providing the opportunity for early detection and interception of PDAC and other associated cancers. 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 risk. Methods: 1000 individuals 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 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. All participants 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 self-reported genetic knowledge, cancer worry, distress, decisional preparedness, familial communication, and screening uptake, which will be measured via longitudinal surveys. Enrollment is underway nationwide as of May, 2019. Clinical trial information: NCT03762590

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Abstract Details

Meeting

2020 Gastrointestinal Cancers Symposium

Session Type

Trials in Progress Poster Session

Session Title

Trials in Progress Poster Session B: Hepatobiliary Cancer, Neuroendocrine/Carcinoid, Pancreatic Cancer, and Small Bowel Cancer

Track

Hepatobiliary Cancer,Neuroendocrine/Carcinoid,Pancreatic Cancer,Small Bowel Cancer

Sub Track

Prevention, Screening, and Hereditary Cancers

Clinical Trial Registration Number

NCT03762590

Citation

J Clin Oncol 38, 2020 (suppl 4; abstr TPS779)

Abstract #

TPS779

Poster Bd #

P22

Abstract Disclosures