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Objectives: To develop a mutation-based radiomics signature to predict response to imatinib in Gastrointestinal Stromal Tumors (GISTs). Methods: Eighty-two patients with GIST were enrolled in this retrospective study, including 52 patients from one center that were used to develop the model, and 30 patients from a second center to validate it. Reference standard was the mutational status of tyrosine-protein kinase (KIT) and platelet-derived growth factor α (PDGFRA). Patients were dichotomized in imatinib sensitive (group 0 - mutation in KIT or PDGFRA, different from exon 18-D842V), and imatinib non-responsive (group 1 - PDGFRA exon 18-D842V mutation or absence of mutation in KIT/PDGFRA). Initially, 107 texture features were extracted from the tumor masks of baseline computed tomography scans. Different machine learning methods were then implemented to select the best combination of features for the development of the radiomics signature. Results: The best performance was obtained with the 5 features selected by the ANOVA model and the Bayes classifier, using a threshold of 0.36. With this setting the radiomics signature had an accuracy and precision for sensitive patients of 82 % (95 % CI:60-95) and 90 % (95 % CI:73-97), respectively. Conversely, a precision of 80 % (95 % CI:34-97) was obtained in non-responsive patients using a threshold of 0.9. Indeed, with the latter setting 4 patients out of 5 were correctly predicted as non-responders. Conclusions: The results are a first step towards using radiomics to improve the management of patients with GIST, especially when tumor tissue is unavailable for molecular analysis or when molecular profiling is inconclusive.
RESUMO
OBJECTIVES: To investigate the correlation between CT imaging features and risk stratification of gastrointestinal stromal tumors (GISTs), prediction of mutation status, and prognosis. METHODS: This retrospective dual-institution study included patients with pathologically proven GISTs meeting the following criteria: (i) preoperative contrast-enhanced CT performed between 2008 and 2019; (ii) no treatments before imaging; (iii) available pathological analysis. Tumor risk stratification was determined according to the National Institutes of Health (NIH) 2008 criteria. Two readers evaluated the CT features, including enhancement patterns and tumor characteristics in a blinded fashion. The differences in distribution of CT features were assessed using univariate and multivariate analyses. Survival analyses were performed by using the Cox proportional hazard model, Kaplan-Meier method, and log-rank test. RESULTS: The final population included 88 patients (59 men and 29 women, mean age 60.5 ± 11.1 years) with 45 high-risk and 43 low-to-intermediate-risk GISTs (median size 6.3 cm). At multivariate analysis, lesion size ≥ 5 cm (OR: 10.52, p = 0.009) and enlarged feeding vessels (OR: 12.08, p = 0.040) were independently associated with the high-risk GISTs. Hyperenhancement was significantly more frequent in PDGFRα-mutated/wild-type GISTs compared to GISTs with KIT mutations (59.3% vs 23.0%, p = 0.004). Ill-defined margins were associated with shorter progression-free survival (HR 9.66) at multivariate analysis, while ill-defined margins and hemorrhage remained independently associated with shorter overall survival (HR 44.41 and HR 30.22). Inter-reader agreement ranged from fair to almost perfect (k: 0.32-0.93). CONCLUSIONS: Morphologic contrast-enhanced CT features are significantly different depending on the risk status or mutations and may help to predict prognosis. KEY POINTS: ⢠Lesions size ≥ 5 cm (OR: 10.52, p = 0.009) and enlarged feeding vessels (OR: 12.08, p = 0.040) are independent predictors of high-risk GISTs. ⢠PDGFRα-mutated/wild-type GISTs demonstrate more frequently hyperenhancement compared to GISTs with KIT mutations (59.3% vs 23.0%, p = 0.004). ⢠Ill-defined margins (hazard ratio 9.66) were associated with shorter progression-free survival at multivariate analysis, while ill-defined margins (hazard ratio 44.41) and intralesional hemorrhage (hazard ratio 30.22) were independently associated with shorter overall survival.
