YO4 - Succinate Dehydrogenase deficient GISTs is a diagnostic and therapeutic dilemma? : A case report.

Case summary

Gastrointestinal stromal tumours (GISTs) are a rare disease compared to other cancers of the gastrointestinal tract. In most cases (80-90%), GISTs harbour activating c-KIT and PDGFRA mutations. The remainder are termed wild type GISTs. Succinate dehydrogenase complex subunit B protein (SDHB) identifies a unique subgroup of wild type GISTs, now known succinate dehydrogenase deficient GISTs (SDH deficient GISTs). These tumours are female predominant, occur at a younger age, exclusively affect the stomach and have a wide spectrum of behaviour from indolent to progressive.Most importantly these tumours do not respond to standard targeted therapy. SDH deficient GISTs have a unique clinical presentation and pathological features which may be misinterpreted as standard GISTs.
A case of a 55-year-old man initially presented with upper gastrointestinal (GI) bleeding in April 2020. Gastric endoscopy found a mass in the antrum of the stomach which was confirmed to be GIST on histopathological examination. Immunohistochemistry showed that the tumour cells have membranous staining for DOG-1 in areas but negative for CD117. PET CT staging revealed a hypermetabolic region at the gastro hepatic region with liver metastases. He had progressed on standard treatment with Imatinib within 6 months and second line Sunitinib within 5 months before a next generation sequencing (NGS) test showed SDHA loss. To date there is no standard treatment available for SDHA loss. There is an ongoing phase 2 trial for this population with Temozolomide 85mg/m2, 21 days on and 7 days off.The patient received Temozolomide 55mg/m2 for about a year. Unfortunately, in June 2022 PET CT showed disease progression. His combined positive score (CPS) was more than 30. However due to financial constraints he was started on Regorafenib.
SDH deficient GISTs comprise a subgroup of rare disease, hence the difficulty in diagnosing and to ascertain treatment as infrequency of cases seen has been a challenge up till date. At the moment there are no guidelines available and novel treatment is still yet to be discovered. Temozolomide may be an option in this population as it has the longest progression free survival outcome compared to standard treatment, as seen in this case.

Clinical trial identification

Editorial acknowledgement

Reference
1. Adam Burgoyne, An Open-Label, Phase 2 Efficacy Study of Temozolomide (TMZ) In Advanced Succinate Dehydrogenase (SDH)-Mutant/Deficient Gastrointestinal Stromal Tumour (GIST), NCT03556384