Gastrointestinal Stromal Tumor

In light of the lack of metastatic dissemination and the patient's advanced age, targeted therapy with imatinib was commenced, leading to the elimination of hypoglycemia episodes. This case underscores the necessity of incorporating NICTH into the differential diagnosis of hypoglycemia in non-diabetic individuals, particularly when a tumor is present. Timely identification and focused intervention of the underlying neoplasm can result in positive outcomes.

The identification of patients with NF1 and their interittent follow-up are important for the early detection of potential complications, especially tumorigenesis. This review aimed to summarize NF1-associated tumors in pediatric patients and recently developed targeted therapies for treating these tumors.

Using a 73-gene panel, we characterized the molecular characteristics of GISTs and revealed a correlation with their clinical features. Moreover, KIT/PDGFRA-dependent and KIT/PDGFRA-independent mechanisms underlying resistance to imatinib were explored. Overall, our 73-gene panel is sufficient for clinical application in cases of GISTs.

P3, N=442, Active, not recruiting, Cogent Biosciences, Inc. | Trial primary completion date: Jul 2025 --> Sep 2025

In addition, NGS identified MDM2 and MYC amplification. This is the first report describing an NF1-mutant GIST harboring coamplification of MDM2 and MYC and associated with a higher-grade tumor progression.

In patients with locally advanced GIST, preoperative imatinib therapy for 7-12 months yielded the most favorable prognosis, with significantly improved RFS and OS compared to ≤6 months of treatment. Extending preoperative therapy beyond 12 months did not provide additional survival benefit.

Instead of neoadjuvant therapeutic options for wild-type (WT) NF1-related GIST, surgical resection remains the most advantageous treatment. The efficacy of tyrosine kinase inhibition and other chemotherapies tailored for WT GIST is currently untenable and warrants increased clinical trials and exploration of WT pathogenesis concerning NF1 to support Imatinib-sensitive patients.

Our findings provided preliminary evidence that novel FGFR2 fusions might act as primary oncogenic drivers in a rare subset of KIT/PDGFRA wild-type GISTs. These cases highlight the importance for comprehensive genomic profiling and suggest that fibroblast growth factor receptor-targeted inhibitors could be a potential therapeutic strategy for advanced or imatinib-resistant diseases, warranting further investigation in larger cohorts.

SDH deficient GIST is a unique subtype of gastrointestinal stromal tumor with distinct clinic-pathological features, diagnostic modalities, therapeutic strategies, and genetic implications as compared to C-kit/PDGFR-alpha mutated GIST.

Second- and third-line TKIs, such as sunitinib and regorafenib, provide limited benefits, highlighting the urgent need to address resistance mechanisms. These findings uncover a TGF-β1/CCN2/Rack1/PGK1 mechanism linking CAF-mediated metabolic reprogramming to imatinib resistance in GISTs. Targeting CAF-GIST interactions and key metabolic pathways presents a promising therapeutic strategy.

CGP revealed actionable alterations in most patients with advanced GISTs; however, its impact on treatment decisions remains limited under current practice. Early CGP implementation may facilitate access to matched therapies or clinical trials, enabling prognostic stratification in patients with advanced GISTs.

This analysis suggests that most ADRs associated with pimitespib are manageable and reversible, thus supporting its use in patients with advanced GIST.