GAME-SCORE predicts pathological and radiological response to chemotherapy in patients with colorectal liver metastases.

Background: Genetic And Morphological Evaluation (GAME) score is the newest prognostic model for patient with colorectal liver metastases (CRLMs). Pathological and radiological responses to neoadjuvant chemotherapy (NAC) are key factors for prognostic stratification of these patients. The present study aims to evaluate the GAME-score's ability to predict pathological and radiologic responses to NAC.

Methods: CRLM patients who underwent liver resection after NAC from January 2010 to December 2021 were categorized by GAME scores: low risk (LR, 0-1), moderate risk (MR, 2-3), and high risk (HR, ≥4). Correlations between groups and radiological/pathological features were analyzed. Poor pathological response was defined as Tumor Regression Grade 4-5.

Results: Of 1054 liver resections for CRLMs, 448 were included. GAME scores were LR: 80 (18 %), MR: 228 (51 %), and HR: 140 (31 %). In this cohort, HR-GAME scores were associated with lower pathological response (LR: 67.1 %, MR: 74.9 %, HR: 82.6 %; p = 0.010). Radiologic progression occurred in 10 % of HR patients, significantly more than in LR (3.8 %) and MR (3.5 %) groups (p = 0.011). Multivariable analysis for independent predictors of pathological response confirmed HR-GAME (RR 1.843, p=0.025) along with age higher than 70 years (RR 2.111, p=0.022) and irinotecan-based NAC (RR 3.066, p < 0.001). For radiological progression disease after NAC, the HR-GAME score (RR 2.77, p=0.016) was the only independent predictor. HR-GAME scores were also associated with higher rates of mucinous differentiation (p = 0.021), satellitosis (p = 0.001), vascular invasion (p = 0.011), and perineural invasion (p = 0.010).

Conclusions: GAME score category should be considered into planning of therapeutic strategy of patients with CRLMs.