Succinate dehydrogenase-deficient gastrointestinal stromal tumor: from diagnostic dilemma to novel personalised therapy in 2 case reports

Abstract

Succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) is a unique and distinctive subtype of gastric GIST. The literature on this subtype from developing countries is exceedingly sparse. Patients with SDH-deficient GIST often experience a lack or delay in genomic profiling, despite stereotypical clinicopathologic features, potentially resulting in sub-optimal management. SDH-deficient GISTs are highly syndromic, typically have more indolent behavior, a prognosis not predicted by size and mitotic rate, a tendency to lymph node metastases, and are insensitive to standard tyrosine kinase inhibitors (TKIs). We report two women with SDH-deficient GIST. In the first case, SDH deficiency was identified late due to lack of awareness and poor access to diagnostic facilities. The patient progressed through TKI therapy, but responded to temozolomide, which is under investigation in clinical trials. In the second case, SDH deficiency was identified at diagnosis, and the patient responded well to 177 Lutetium peptide radionuclide receptor therapy (PRRT) after progressing through two lines of TKIs. We aim to highlight the need for more awareness and access to genomic diagnostic facilities for GIST patients, temozolomide as a novel therapy for SDH-deficient GIST, and the potential value of DOTATATE positron emission tomography (PET) and PRRT as a novel imaging modality and therapy for TKI insensitive GIST patients.

Insights into the medical management of gastrointestinal stromal tumours: lessons learnt from a dedicated gastrointestinal stromal tumour clinic in North India

“…Wild-type and SDH-deficient GISTs were seen in 16.4% and 10.9%, respectively. There has been only one case report of SDH-deficient GIST described from India to this date, which had been reported from our GIST clinic [28]. The associated genetic syndromes (Carney triad and NF1) have also been identified and elaborated earlier.…”

Uncommon Association Between Gastrointestinal Stromal Tumors (GIST) and Pheochromocytoma With Abdominal Wall Relapse: Case Report and Literature Review

“…Surgical treatment remained a key intervention for the management of early GIST, with a success rate of 60% in the pre-imatinib era [ 13 ]. The introduction of tyrosine kinase inhibitors revolutionized the treatment of GIST tumors due to their impressive and effective control of the disease.…”

SDHA Germline Mutations in SDH-Deficient GISTs: A Current Update

“…Moreover, the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation markedly prevalent in SDH-deficient GISTs has represented some proof of concept about the potential role of alkylating agents in this subset of GISTs [ 50 ], whereas a phase II trial on temozolomide in advanced SDH-GISTs is still ongoing (NCT03556384); a prolonged disease stability after 18 consecutive cycles of temozolomide has been recently reported in a female metastatic and progressive SDH-deficient GIST 45. The same authors presented another anecdotal case with avid disease on DOTATATE PET, experiencing a durable partial response to 177lutetium-DOTA-octreotate PRRT after failing two lines of TKI therapy [ 51 ].…”