Dr. Andrew Blakely
By Dr. Andrew Blakely, Program Director, Surgical Oncology Research Fellowship, National Cancer Institute, National Institutes of Health
The vast majority of gastrointestinal stromal tumors (GISTs) contain mutations in the KIT or PDGFRA genes. These are sporadic tumors, without a genetic predisposition. GISTs with SDH mutations, with resultant SDH enzyme deficiency, are different from GISTs with KIT or PDGFRA mutations for several reasons. SDH mutations are inherited, predisposing patients to developing GISTs throughout their lives. SDH-deficient GISTs tend to be indolent yet unrelenting1. Such GISTs are more likely to also involve the liver and/or the lining of the abdominal cavity as opposed to remaining localized to the stomach or small intestine. Nowadays, patients diagnosed with SDH-deficient GISTs at a young age are much more likely to live well into adulthood than years ago. Increasingly, patients are diagnosed for the first time as adults2. Regardless of area of the first presentation, patients with SDH-deficient GISTs are likely to develop multiple areas of involvement requiring repeated treatment over their lifetimes.
Treatment for SDH-deficient GISTs is primarily surgical. Systemic treatment options are experimental and are often associated with either significant side effects and/or poor response rates2. Surgery is typically offered to patients with limited disease, patients with growing tumors, or patients with tumor-related symptoms such as pain or bleeding2. A recent study of the National Institutes of Health (NIH) experience in surgical treatment of SDH-deficient GISTs showed increased time to tumor progression among patients able to undergo surgery1. Of note, the use of systemic treatment was not associated with survival. Given the lifelong predisposition to developing GISTs among patients with SDH mutations, it is not uncommon for patients to require multiple surgeries to remove areas of disease.
Given the unique aspects of SDH-deficient GISTs, the Surgical Oncology Program at the NCI believes there is an unmet need for comprehensive assessment by a multidisciplinary surgical team able to care for tumors in the stomach, liver, and peritoneal surface. The surgical oncology program at the NIH is comprised of specialists in gastric (Dr. Jeremy Davis), liver (Dr. Jonathan Hernandez), peritoneal surface (Dr. Andrew Blakely), and endocrine (Dr. Naris Nilubol) diseases.
Together, this team provides comprehensive care of adult patients with SDH-deficient GISTs of any stage. This includes care of associated tumors such as paragangliomas, as in the case of Carney Triad and Carney Stratakis syndrome.
The need for better systemic therapy for SDH-deficient GISTs is clear. Tumors removed at the NIH are routinely sent for next generation genomic sequencing (TruSight Oncology 500, Illumina, Inc.) to identify mutations that available treatments may target. In addition, Dr. Hernandez’s lab is actively developing a platform for patient tumor tissue by which a broad range of treatments can be tested for potential response. On this platform, tissue perfusion is maintained for several days in order to keep the tissue alive and test the treatment effect of a panel of drugs. This platform is enhanced by NIH access to a bank of all FDA-approved and many investigational treatments. Using genomic sequencing and this platform, we aim to use tumor removed from patients to identify new, personalized treatments and to expand potential treatment options for all patients suffering from SDH-deficient GISTs.
This team’s goal is to expand the existing research in SDH-deficient GISTs. Combining basic science research, translational research, and clinical trial outcomes builds on the NIH’s history of robust, expert care of patients with SDH-deficient GISTs. The Surgical Oncology Program is proud to work with partners such as The Life Raft Group and investigators at the University of California, San Diego (Dr. Jason Sicklick), in order to better serve patients with GISTs. We are planning to develop a joint research venture that combines the basic science progress made by Dr. Sicklick’s laboratory and the facilities and resources available at the NIH. In this way, we will fully evaluate patients’ tumor tissue, and we hope to advance the care of patients with SDH-deficient GISTs.
Andrew M. Blakely, M.D.
Center for Cancer Research, National Cancer Institute
Building 10, Room 4-3760, Bethesda, MD 20892
Ph: 240-858-3610 firstname.lastname@example.org
1 Weldon CB et al. Surgical Management of Wild-Type Gastrointestinal Stromal Tumors: A Report From the National Institutes of Health Pediatric and Wildtype GIST Clinic. J Clin Oncol, 27 Dec 2016, 35(5):523-528. DOI: 10.1200/JCO.2016.68.6733
2 Neppala P et al. Current management of succinate dehydrogenase-deficient gastrointestinal stromal tumors Cancer Metastatsis Rev, 31 Aug 2019, 38(3):525-535 DOI: 10.1007/s10555-019-09818-0
Want to find a GIST specialist in your area?
See our GIST specialists database with doctors
in the U.S. and International
Need a checklist to take to your Doctor’s Visit?
A pdf is available to print out at: