Efficacy and safety of radiofrequency hyperthermia combined with immune checkpoint inhibitors and chemotherapy as first-line treatment for HER2-negative advanced gastric/gastroesophageal junction adenocarcinoma: A propensity score–matched study

Radiofrequency hyperthermia (RFH) increases local tumor temperature and may enhance sensitivity to systemic therapies. We evaluated the association between adding RFH to first-line immune checkpoint inhibitor (ICI) plus chemotherapy and outcomes in patients with HER2-negative advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. This study adopted a single-center, retrospective, observational design. Patients treated between January 2021 and January 2024 were retrospectively enrolled and grouped by receipt of RFH (hyperthermia vs. non-hyperthermia). The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. A 1:1 propensity score matching (PSM) analysis was performed. A total of 212 patients were included: 119 in the hyperthermia group and 93 in the non-hyperthermia group. In the overall cohort, RFH was associated with longer median PFS (10.17 vs. 7.06 months; HR = 0.70; p = .011) and median OS (19.31 vs. 14.98 months; HR = 0.71; p = .018). ORR did not differ significantly between groups (21.0% vs. 21.5%; p = .930), whereas DCR was higher with RFH (96.6% vs. 86.0%; p = .005). After PSM, 168 patients were matched; balance improved, but residual imbalance remained. Matched-cohort estimates remained directionally similar for PFS (9.72 vs. 7.09 months; HR = 0.67; p = .013) and OS (19.02 vs. 15.12 months; HR = 0.67; p = .015). Recorded grade ≥3 immune-related adverse events occurred in 5.0% and 4.3% of patients, respectively. RFH-related events were mainly transient local skin erythema and induration, and no RFH-related serious adverse events were recorded. RFH added to ICIs and chemotherapy was associated with longer PFS and OS, requiring confirmation in prospective randomized studies.