A 5-Metabolite Plasma Panel Predicts Progression-Free Survival and Adds Prognostic Value in Imatinib-Treated Gastrointestinal Stromal Tumors.

Among patients with gastrointestinal stromal tumor receiving first-line imatinib, outcomes vary substantially, and traditional stratification based on KIT/PDGFRA genotype and tumor burden does not fully explain individual prognostic differences. Baseline plasma metabolomics may noninvasively reflect the tumor-host systemic state and provide additional prognostic information. This single-center prospective cohort study aimed to develop and internally validate a baseline plasma-based metabolomic risk score and to assess its incremental discrimination, calibration, and clinical net benefit over a clinical benchmark model. Patients with gastrointestinal stromal tumor receiving first-line imatinib were enrolled from 2019 to 2023 and followed until June 30, 2025. Baseline plasma samples were collected before the first dose of imatinib, and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-derived metabolomic features were processed using quality-control procedures and normalization. An elastic-net penalized Cox model was used to select metabolites and construct the risk score, with 0.632+ bootstrap resampling used for optimism correction, time-dependent receiver operating characteristic analysis for discrimination, calibration analysis, and decision curve analysis for exploratory net-benefit assessment. A total of 200 patients were included, with 5178.64 person-months of follow-up and 104 progression-free survival events. A five-metabolite panel was identified, and in the development cohort, the fitted continuous metabolomic risk score showed an apparent association with progression-free survival. Compared with the clinical benchmark model, the combined model improved the C-index by 0.06 and showed overall higher time-dependent area under the curve (AUC) values over 0-36 months. Calibration at 1 and 2 years was close to the ideal line, and decision curve analysis showed higher model-based net benefit across the evaluated threshold ranges. The baseline five-metabolite plasma panel, therefore, provides incremental prognostic information beyond conventional clinical factors. External validation and prospective impact studies are required before the score can be used to guide clinical management.