[Efficacy of conversion therapy and prognostic factors in patients with synchronous gastric cancer liver metastasis].

Objective: To investigate the efficacy of conversion therapy and prognostic factors in patients with synchronous gastric cancer liver metastasis (GCLM), and to evaluate the clinical value of the Chinese Classification of GCLM (C-GCLM) and Tumor Regression Grade (TRG). Methods: This was a retrospective cohort study. Clinical data of patients with synchronous GCLM who received conversion therapy at Tianjin Medical University Cancer Institute & Hospital between January 2019 and December 2024 were retrospectively analyzed. Inclusion criteria: (1) pathologically confirmed gastric adenocarcinoma by gastroscopic biopsy, with synchronous liver metastasis verified by imaging or postoperative pathology; (2) age ≥18 years; (3) Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2; (4) received conversion therapy based on systemic chemotherapy; (5) complete clinical and follow-up data. Exclusion criteria: (1) concurrent malignant tumors at other sites; (2) history of other malignancies; (3) metachronous liver metastasis (liver metastasis occurring after gastrectomy). A total of 86 patients were enrolled, including 65 males and 21 females, with a median age of 63.0 (53.0-68.0) years. There were 54 cases of C-GCLM type I, 21 type II, and 11 type III. Conversion therapy was based on fluoropyrimidine- and platinum-containing systemic chemotherapy, among which 58 patients (67.4%) received combined immune checkpoint inhibitors, and 46 patients (53.5%) received combined targeted therapy, of whom 14 (16.3%) with human epidermal growth factor receptor 2 (HER2)-positive status received anti-HER2 targeted therapy. The median number of treatment cycles was 5 (3.0, 7.8). Patients were divided into the conversion therapy with surgery group (39 cases) and conversion therapy without surgery group (47 cases) according to whether surgery was performed after conversion therapy. Treatment efficacy was evaluated using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1): (1) objective response rate (ORR) = complete response (CR) + partial response (PR); (2) disease control rate (DCR) = CR + PR + stable disease (SD); (3) progressive disease (PD). Successful conversion was defined as achievement of R0 resection after conversion therapy. Survival curves were plotted and survival rates calculated using the Kaplan-Meier method, and differences in overall survival (OS) between groups were compared using the Log-rank test. Univariate and multivariate Logistic regression models were used to identify independent predictive factors for successful conversion. Results: The ORR of this cohort was 26.7% (23/86), DCR was 62.8% (54/86), and conversion success rate was 43.0% (37/86). Median OS was 36.9 months in the surgery group and 13.8 months in the non-surgery group, with a statistically significant difference (P<0.001). The 1-year and 3-year OS rates in the surgery group were 89.0% and 54.0% respectively, with an R0 resection rate of 94.9% (37/39). C-GCLM showed a significant gradient correlation with both OS and conversion success rate: median OS for C-GCLM type I, II and III was 30.0, 15.9 and 13.8 months respectively, with type I superior to type II (P=0.016) and type III (P<0.001). The conversion success rate decreased in a gradient by C-GCLM subtype: 63.0% (34/54) for type I, 14.3% (3/21) for type II, and 0 (0/11) for type III (P<0.001). The 3-year OS rate in the TRG 0+1 group was 85.7%, which was superior to 44.7% in the TRG 2+3 group (P=0.005). Multivariate Logistic regression revealed that C-GCLM type I was an independent predictor of successful conversion (OR=44.21, P=0.004). Among patients who underwent R0 resection in the surgery group, there was no significant difference in OS among three management strategies for liver metastases: observation after complete radiological response, surgical resection, or radiofrequency ablation (P=0.819). Median OS was similar between the combined immunotherapy group and the non-immunotherapy group (18.1 vs. 17.6 months, χ²=0.056, P=0.813). Conclusions: R0 resection following conversion therapy significantly improves prognosis in patients with synchronous gastric cancer liver metastasis. C-GCLM is valuable for both prognostic stratification and prediction of conversion feasibility, with type I serving as an independent predictor of successful conversion. TRG can provide a basis for prognostic stratification in patients after conversion surgery.