Metastatic and multiply relapsed SDH deficient GIST and paraganglioma
displays clinical response to combined Poly ADP-Ribose Polymerase
inhibition and Temozolomide
Abstract
Pediatric GIST (gastrointestinal stromal tumors) are mostly KIT/
PDGFRA-WT and harbor mutations in SDH (succinate dehydrogenase), making
them TKI (tyrosine kinase inhibitor) resistant due to the absence of
gain-of-function tyrosine kinase mutations. Due to rarity of GIST in
children, there have been few clinical trials available for patients
with advanced disease, resulting in limited treatment options and a lack
of pediatric-specific consensus guidelines. Here, we report the case of
a patient with progressive, metastatic SDHB-mutant GIST that displayed a
significant clinical response with a combination of Olaparib and TMZ
(temozolomide).