Rachael Lowney, MD (she/her/hers)
Surgical Oncology Research Fellow
Surgical Oncology Program/ National Cancer Institute/ National Institute of Health
Bethesda, Maryland, United States
Shadin Gabra, MD
Medstar
Columbia, Maryland, United States
Urania Dagalakis, MD
Pediatric Oncology Branch/ National Cancer Institute/ National Institute of Health
Bethesda, Maryland, United States
Erika Kaschak, BA
Pediatric Oncology Branch/ National Cancer Institute/ National Institute of Health
Bethesda, Maryland, United States
Barbara Thomas, RN
Pediatric Oncology Branch/ National Cancer Institute/ National Institute of Health
Bethesda, Maryland, United States
J. Keith Killian, MD
Foundation Medicine
Cambridge, Massachusetts, United States
Paul Meltzer, MD, PhD
Genetics Branch/ National Cancer Institute/ National Institute of Health
Bethesda, Maryland, United States
Brigitte Widemann, MD
Pediatric Oncology Branch/ National Cancer Institute/ National Institute of Health
Bethesda, Maryland, United States
Mary Frances Wedekind Malone, DO
Associate Research Physician, Staff Clinician
Pediatric Oncology Branch/ National Cancer Institute/ National Institute of Health
Besthesda, Maryland, United States
John Glod, MD, PhD
Oncology Attending
Pediatric Oncology Branch/ National Cancer Institute/ National Institute of Health
Bethesda, Maryland, United States
Andrew M. Blakely, MD
Surgical Oncologist
Surgical Oncology Branch / National Cancer Institute / National Institute of Health
Bethesda, Maryland, United States
This is a retrospective chart review of patients diagnosed with SDH-def GIST by immunohistochemistry and/or molecular testing from the Wild-Type (WT) GIST clinic database from 01/2008 to 10/2025. Medical records, clinical notes, operative and histopathology reports, imaging studies, germline testing, and results of next generation sequencing of tumor tissue were reviewed. Time from diagnosis to date of last known follow-up was used as a surrogate for survival. Kaplan-Meier curves and cumulative distribution graphs were used to model overall survival.
Results:
Among 117 patients with confirmed SDH-def GIST, all mutational subtypes were represented. Mean follow-up with our institution was 3.6 years (SD 4.4, 95% CI [2.8-4.4]). 40 patients (34.2%) had metastases at diagnosis via imaging or discovered at index surgery, with the liver being the most common site (50%). 71 patients (64%) experienced recurrence or progression after their first surgery, with multiple sites involved (liver, intra-abdominal/peritoneal, and/or lymph nodes) in 47.9% of all recurrences. 14 patients (12%) died during the course of this study. Mean survival was calculated to be 8.4 years (SD 8.4, 95% CI [0.69-38.9]). Kaplan-Meier curves showed a mean overall survival of 10.8 years for patients who underwent 1 surgery, 10.2 years for patients who underwent 2 surgeries, and 19.8 years for patients who underwent ≥3 surgeries.
Conclusions:
SDH def GISTs exhibit an indolent course, with most patients living more than 5 years after diagnosis. Many patients will experience recurrence and/or progression during their disease courses but lack proven effective systemic therapies. Until such therapies exist, our data supports the close monitoring and intermittent debulking of these recurrences for symptomatic management and prolonging survival.