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Abstract
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.

Affiliations

Nalee Kim  1 , Jeong Il Yu  1 , Do Hoon Lim  1 , Jeeyun Lee  2 , Seung Tae Kim  2 , Jung Yong Hong  2 , Won Ki Kang  2 , Woo Kyoung Jeong  3 , Kyoung-Mee Kim  4
1 Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
2 Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
3 Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
4 Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.