Clinical features of GIST in real-world setting

Abstract

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal cancers, most often arising in the stomach or small intestine. Their development is typically driven by KIT or PDGFRA mutations, while a minority are linked to SDH deficiency, NF1, NTRK, or BRAF mutations. Surgery remains the treatment of choice for localized disease, whereas tyrosine kinase inhibitors (TKIs) have transformed outcomes in advanced GIST. Imatinib, the first-line standard, has significantly improved survival compared to early clinical trials.

This thesis analyzes real-world data primarily derived from the Dutch GIST Registry (DGR), complemented by data from multiple European sarcoma centers for rare rectal and esophageal GISTs. Findings show that Dutch patients treated with first-line imatinib achieve longer progression-free and overall survival than reported in historic trials. In second-line settings, sunitinib and imatinib dose escalation demonstrate comparable efficacy, suggesting dose escalation as a viable alternative in non-KIT exon 9 mutated GIST. Neoadjuvant response is strongly influenced by mutation profile, with KIT exon 11 mutations showing the best outcomes.

Rare GISTs present unique challenges, with specialist centers achieving superior results through multimodal approaches. Large registry analyses reveal significant treatment variation across Europe, underscoring the need for standardized data collection to optimize patient care and guide future therapies.