CT radiomics-based intratumoral and intertumoral heterogeneity indicators for prognosis prediction in gastric cancer patients receiving neoadjuvant chemotherapy.

[OBJECTIVES] CT-based intratumoral and intertumoral heterogeneity indicators were integrated to develop a prognostic model for locally advanced gastric cancer (LAGC) patients undergoing neoadjuvant chemotherapy (NACT).

[METHODS] This retrospective study included 568 LAGC patients treated with NACT from two hospitals. The intratumor heterogeneity score (ITHscore) was developed to quantify the intratumoral heterogeneity of LAGCs on CT; intertumoral heterogeneity was characterized by combining the primary tumor (PT) and lymph node (LN) sizes on CT. CT indicators were measured on baseline and posttreatment CT scans; the reduction rates (%Δ) were calculated. The overall survival (OS) of all patients was recorded. Cox regression analysis was used to construct a preoperative survival prediction model (Pre-SPM) based on the baseline indicators and %Δ indicators. The predictive performance of Pre-SPM for OS was assessed. The clinicopathological data, including the ypTNM stage, were also collected to evaluate their impact on OS.

[RESULTS] Patients with lower baseline ITHscore had better prognoses (p < 0.001). Approximately 13.01% of patients exhibited contradictory changes in PT and LN sizes. Cox regression analysis selected the baseline ITHscore, baseline PT area, %ΔPT, and %ΔLN to establish the Pre-SPM. In the external validation cohort, the c-index of Pre-SPM for predicting OS was 0.72, while the AUC for predicting 5-year OS was 0.73. After adjusting for the influence of clinicopathological features, including the ypTNM stage, Pre-SPM remained an independent prognostic factor.

[CONCLUSION] The Pre-SPM model, combining intratumoral heterogeneity and intertumoral heterogeneity, has the potential to predict the OS of LAGC patients receiving NACT.

[KEY POINTS] Question Increased tumor heterogeneity in LAGC affects prognosis, but effective non-invasive CT methods for assessing intratumoral and intertumoral heterogeneity are lacking. Findings ITHscore indicates intratumoral heterogeneity, while changes in PT and LN sizes reflect intertumoral heterogeneity. The Pre-SPM model, integrating both, independently predicts patient outcomes. Clinical relevance Pre-SPM enhances prognosis prediction by quantifying intratumoral and intertumoral heterogeneity, potentially guiding more personalized and effective treatment strategies for patients with LAGC.