City of Hope Precision Oncology Tumor Board Identifies Hereditary CRC Risk

A premier multidisciplinary precision oncology tumor board (POTB) at City of Hope National Medical Center identified colorectal cancer patients with possible hereditary predisposition who might not have been recommended for cancer genetics evaluation otherwise, according to findings presented at the 2020 Collaborative Group of the Americas on Inherited Gastrointestinal Cancer (CGA-IGC) meeting.¹

POTBs can inform targeted therapy options and clinical trial eligibility for cancer patients who undergo tumor next-generation sequencing (NGS). City of Hope is one of few institutions in the U.S. that not only conducts somatic sequencing (analyzing cell mutations developed over an individual’s lifetime) but also does germline sequencing, which screens for hereditary cancer risk.

“The City of Hope precision oncology tumor board has a special focus on inherited susceptibility that brings the lifesaving power of genetics not only to patients but also to their families, and that’s quite unique,” Kevin McDonnell, MD, PhD, a medical oncologist specializing in clinical cancer genetics at City of Hope and co-lead author of the poster presentation, said in a press release.²

The new findings are the result of a multidisciplinary POTB aiming to identify patients with potential hereditary colorectal cancer risk based on their tumor somatic NGS. The research included 1129 patients who underwent paired tumor-normal whole exome NGS with Ashion’s GEM ExTra clinical assay at City of Hope from 2019-2020. Of that population, 112 (9.9%) were colorectal cancer patients.

The cases were reviewed by a multidisciplinary POTB including medical oncologists, genetic counselors, computational biologists, epidemiologists, cancer geneticists, and others. They used National Comprehensive Cancer Network (NCCN) criteria to identify possible germline cancer predisposition in patients with colorectal cancer. Those criteria were cancer diagnosis at less than 50 years of age; microsatellite instability (MSI-H) and/or high tumor mutational burden (BRAF-mutated cases excluded); and BRCA1 or BRCA2 alterations with allelic frequencies greater than 35%.

Once reviewed by the POTB, 26 (23.2%) of the colorectal cancer cases were recommended for cancer genetics evaluation. Just 21 of those patients had been referred prior to the POTB review, meaning the POTB identified 5 colorectal cancer cases that would have been missed and increased the rate of appropriate referrals by 24%.

Researchers concluded that the POTB’s systematic review of colorectal tumor somatic NGS significantly increased the identification and referral for cancer genetics evaluation of patients with possible germline colorectal cancer susceptibility. This could impact the genetic clinical management of both patients and their families.

“Multidisciplinary review of the DNA found in the tumors of colorectal cancer patients provides an unexpected benefit – it helps doctors identify patients who inherited a predisposition for colorectal cancer,” Stephen Gruber, MD, PhD, MPH, director of the Center for Precision Medicine at City of Hope and senior author of the poster presentation, said in a release. “These patients can then be referred for a genetics evaluation and, if needed, receive heightened preventive screening or targeted treatment for colorectal cancer.”

References

1. McDonnell KJ, Hong CA, Solomon IB, et al. Somatic Sequencing and Multidisciplinary Tumor Board Review Improves Identification of Patients at Risk for Inherited Colorectal Cancer. Presented at CGA Annual Meeting; November 14-15, 2020.

2. City of Hope’s precision oncology tumor board able to identify patients who may have inherited increased risk for colorectal cancer. City of Hope. November 16, 2020. Accessed November 19, 2020. https://www.cityofhope.org/news/precision-oncology-tumor-board-can-id-inherited-increased-risk