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

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/m...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298191/
https://www.ncbi.nlm.nih.gov/pubmed/34305941
http://dx.doi.org/10.3389/fimmu.2021.701668
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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
author_facet 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
author_sort Kim, Nalee
collection PubMed
description 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.
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spelling pubmed-82981912021-07-24 Prognostic Impact of Sarcopenia and Radiotherapy in Patients With Advanced Gastric Cancer Treated With Anti-PD-1 Antibody 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 Front Immunol Immunology 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. Frontiers Media S.A. 2021-07-08 /pmc/articles/PMC8298191/ /pubmed/34305941 http://dx.doi.org/10.3389/fimmu.2021.701668 Text en Copyright © 2021 Kim, Yu, Lim, Lee, Kim, Hong, Kang, Jeong and Kim https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
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
Prognostic Impact of Sarcopenia and Radiotherapy in Patients With Advanced Gastric Cancer Treated With Anti-PD-1 Antibody
title Prognostic Impact of Sarcopenia and Radiotherapy in Patients With Advanced Gastric Cancer Treated With Anti-PD-1 Antibody
title_full Prognostic Impact of Sarcopenia and Radiotherapy in Patients With Advanced Gastric Cancer Treated With Anti-PD-1 Antibody
title_fullStr Prognostic Impact of Sarcopenia and Radiotherapy in Patients With Advanced Gastric Cancer Treated With Anti-PD-1 Antibody
title_full_unstemmed Prognostic Impact of Sarcopenia and Radiotherapy in Patients With Advanced Gastric Cancer Treated With Anti-PD-1 Antibody
title_short Prognostic Impact of Sarcopenia and Radiotherapy in Patients With Advanced Gastric Cancer Treated With Anti-PD-1 Antibody
title_sort prognostic impact of sarcopenia and radiotherapy in patients with advanced gastric cancer treated with anti-pd-1 antibody
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298191/
https://www.ncbi.nlm.nih.gov/pubmed/34305941
http://dx.doi.org/10.3389/fimmu.2021.701668
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