CT-based assessment of sarcopenia for differentiating wild-type from mutant-type gastrointestinal stromal tumor

Non-invasive prediction for KIT/PDGFRA status in GIST is a challenging problem. This study aims to evaluate whether CT based sarcopenia could differentiate KIT/PDGFRA wild-type gastrointestinal stromal tumor (wt-GIST) from the mutant-type GIST (mu-GIST), and to evaluate genetic features of GIST. A total of 174 patients with GIST (wt-GIST = 52) were retrospectively identified between January 2011 to October 2019. A sarcopenia nomogram was constructed by multivariate logistic regression. The performance of the nomogram was evaluated by discrimination, calibration curve, and decision curve. Genomic data was obtained from our own specimens and also from the open databases cBioPortal. Data was analyzed by R version 3.6.1 and clusterProfiler (http:// cbiop ortal. org/ mskimpact). There were significantly higher incidence (75.0% vs. 48.4%) and more severe sarcopenia in patients with wt-GIST than in patients with mu-GIST. Multivariate logistic regression analysis showed that sarcopenia score (fitted based on age, gender and skeletal muscle index), and muscle fat index were independent predictors for higher risk of wt-GIST (P < 0.05 for both the training and validation cohorts). Our sarcopenia nomogram achieved a promising efficiency with an AUC of 0.879 for the training cohort, and 0.9099 for the validation cohort with a satisfying consistency in the calibration curve. Favorable clinical usefulness was observed using decision curve analysis. The additional gene sequencing analysis based on both our data and the external data demonstrated aberrant signal pathways being closely associated with sarcopenia in the wt-GIST. Our study supported the use of CT-based assessment of sarcopenia in differentiating the wt-GIST from the mu-GIST preoperatively.

Automated summary

This study aimed to evaluate whether CT-based sarcopenia could differentiate between KIT/PDGFRA wild-type gastrointestinal stromal tumors (wt-GIST) and mutant-type GIST (mu-GIST), and to evaluate the genetic features of GIST. The results showed a significantly higher incidence and more severe sarcopenia in patients with wt-GIST compared to those with mu-GIST. Multivariate logistic regression analysis identified sarcopenia score and muscle fat index as independent predictors for higher risk of wt-GIST. The study supported the use of CT-based assessment of sarcopenia in preoperatively differentiating wt-GIST from mu-GIST.