AUTHOR=Kim Nalee , Yu Jeong Il , Lim Do Hoon , Lee Jeeyun , Kim Seung Tae , Hong Jung Yong , Kang Won Ki , Jeong Woo Kyoung , Kim Kyoung-Mee 

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

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.701668

DOI=10.3389/fimmu.2021.701668

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>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).</p></sec><sec><title>Methods</title><p>Among 185 patients with AGC treated with ICB, we defined SAR as skeletal muscle index &lt;49 cm2/m2 for men and &lt;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.</p></sec><sec><title>Results</title><p>We frequently observed hNLR in patients with SAR (53% <italic>vs.</italic> 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] <italic>vs.</italic> 1 [N = 76] <italic>vs.</italic> 2 [N = 49]: 7.6 <italic>vs.</italic> 6.4 <italic>vs.</italic> 2.2 months, p &lt; 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 <italic>vs.</italic> 16.8 <italic>vs.</italic> 3.8 months, respectively). The benefit of RT was evident in patients with both SAR and hNLR (median OS, 3.1 <italic>vs.</italic> 1.3 months, p = 0.02) and MSS/EBV-negative tumor (median OS, 6.5 <italic>vs.</italic> 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 &lt; 0.05).</p></sec><sec><title>Conclusions</title><p>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.</p></sec>