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Background  We explored the combined effects of sarcopenia (SAR) and radiotherapy (RT) on outcomes in patients with advanced gastric cancer (AGC) treated with immune-checkpoint blockade (ICB).    Methods  Among 185 patients with AGC treated with ICB, we defined SAR as skeletal muscle index <49 cm2/m2 for men and <31 cm2/m2 for women; 93 patients met criteria. We defined high neutrophil-to-lymphocyte ratio (hNLR) as NLR≥3. Palliative RT was performed in 37 patients (20%) before ICB.    Results  We frequently observed hNLR in patients with SAR (53%  vs.  35%, p = 0.02). The median overall survival (OS) for the entire cohort was 5 months. Stratification by risk factors of SAR or hNLR revealed a significant difference in median OS (0 [N = 60]  vs.  1 [N = 76]  vs.  2 [N = 49]: 7.6  vs.  6.4  vs.  2.2 months, p < 0.001). Patients with microsatellite instability-high (MSI-H, N = 19) or Epstein-Barr virus (EBV)-positive tumors (N = 13) showed favorable outcomes compared to those with microsatellite stable (MSS, N = 142) tumors (median OS, not reached  vs.  16.8  vs.  3.8 months, respectively). The benefit of RT was evident in patients with both SAR and hNLR (median OS, 3.1  vs.  1.3 months, p = 0.02) and MSS/EBV-negative tumor (median OS, 6.5  vs.  3.5 months, p = 0.03), but outcomes after RT in MSI-H tumor were not significantly different. In multivariable analysis, SAR/hNLR, molecular subtypes, and a history of RT were associated with OS (all p < 0.05).    Conclusions  We demonstrated the negative predictive value of SAR/hNLR on outcomes after ICB for AGC, and the history of RT could overcome the negative impact of SAR/hNLR and the MSS/EBV-negative subtype.

Prognostic Impact of Sarcopenia and Radiotherapy in Patients With Advanced Gastric Cancer Treated With Anti-PD-1 Antibody