Decision-making for multimodal treatment of gastrointestinal stromal tumors based on molecular profiling

Background: Gastrointestinal stromal tumors (GIST) comprise a broad spectrum of different molecular subtypes. Due to improved accessibility to molecular pathology, genotyping has become an integral part of interdisciplinary case discussions.Aim: To provide an overview on existing literature on the relevance of genotyping for treatment decisions in GIST.Results and conclusions: Most patients with KIT exon 11 mutations and high risk of relapse benefit from adjuvant imatinib treatment. The evidence for this benefit is weak for less frequent KIT genotypes (e.g., exon 9, 13, and 17 mutations). Neoadjuvant treatment is particularly relevant in imatinib-sensitive subtypes when significant surgery-related morbidity is expected. For patients in the metastatic setting, multimodal treatment can be considered in responding patients when macroscopically complete resection seems feasible. Next generation inhibitors such as ripretinib in pretreated GIST and particularly avapritinib in GIST with PDGFRA (platelet-derived growth factor receptor A) mutations are associated with relevant tumor regression. The role for multimodal approaches in the respective treatment settings remains to be determined.

Automated summary

Summary: Gastrointestinal stromal tumors (GIST) consist of various molecular subtypes with different treatment implications. Genotyping plays a crucial role in treatment decision-making. Adjuvant imatinib treatment is beneficial for patients with KIT exon 11 mutations and high risk of relapse. Evidence for this benefit is weaker for less frequent KIT genotypes, such as exon 9, 13, and 17 mutations. Neoadjuvant treatment is important in imatinib-sensitive subtypes with significant surgery-related morbidity. Multimodal treatment may be considered for metastatic patients with potential complete resection. Next generation inhibitors like ripretinib and avapritinib show promising results in pretreated GIST and GIST with PDGFRA mutations, but the role of multimodal approaches in these settings is yet to be determined.