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Incorporating sarcopenia and inflammation with radiation therapy in patients with hepatocellular carcinoma treated with nivolumab

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Abstract

Background

We investigated the combined effects of sarcopenia and inflammation on outcomes in patients with HCC treated with nivolumab.

Materials and Methods

We reviewed 102 patients treated with nivolumab between 2017 and 2018. Sarcopenia was diagnosed when the L3 skeletal muscle indices were < 42 cm2/m2 and < 38 cm2/m2 in men and women, respectively. Baseline neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count were used as surrogate markers of inflammation and immune cell reservoir. High NLR (hNLR) was defined as NLR ≥ 3, and severe lymphopenia (sLP) was defined as lymphocyte < 800/μL. The overall survival (OS) and progression-free survival (PFS) were analyzed.

Results

With a median follow-up of 21.9 (interquartile range, 8.3–58.3) months, patients with sarcopenia showed shorter OS than those without sarcopenia (median, 2.9 vs. 7.5 months, respectively). Patients with either hNLR or sLP exhibited inferior survival than those without risk factor (median OS, 2.8 vs. 14.5 months; median PFS, 1.3 vs. 3.7 months, respectively). Among 70 patients treated with RT, benefit of RT was observed in patients with sarcopenia or those without hNLR/sLP (all p < 0.05). After multivariable analysis, RT, hNLR/sLP, albumin–bilirubin (ALBI) grade, and alpha-fetoprotein were significantly associated with OS (all p < 0.05), and hNLR/sLP was also associated with decreased PFS together with ALBI grade, alpha-fetoprotein, and RT (all p < 0.05).

Conclusion

The current study hypothetically demonstrated that the risk group stratified by hNLR/sLP outweighs the significance of sarcopenia in predicting outcomes after nivolumab. Furthermore, patients with sarcopenia might benefit from RT, especially those without risk factors of hNLR/sLP.

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Data availability

Data availability is limited due to institutional data protection law and confidentiality of patient data.

Abbreviations

ALBI:

Albumin–bilirubin

HCC:

Hepatocellular carcinoma

hNLR:

High neutrophil-to-lymphocyte ratio

HR:

Hazard ratio

ICB:

Immune checkpoint blockade

IQR:

Interquartile range

NLR:

Neutrophil-to-lymphocyte ratio

OS:

Overall survival

PFS:

Progression-free survival

RT:

Radiation therapy

sLP:

Severe lymphopenia

SMI:

Skeletal muscle index

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Funding

This study was partly supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2017R1D1A1B03031275).

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Authors and Affiliations

  1. Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea

    Nalee Kim, Jeong Il Yu, Hee Chul Park, Gyu Sang Yoo & Changhoon Choi

  2. Department of Medical Device Management and Research, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea

    Hee Chul Park

  3. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea

    Jung Yong Hong, Ho Yeong Lim, Jeeyun Lee, Moon Seok Choi & Jung Eun Lee

  4. Statistics and Data Center, Samsung Medical Center, Research Institute for Future Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea

    Kyunga Kim

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  1. Nalee Kim
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Contributions

Conception, design, data collection, interpretation, and drafting of the manuscript were performed by NK and JIY. Data collection and interpretation were performed by HCP, GSY, CC, JYH, HYL, JL, and MSC. Statistical analysis and editing of the manuscript were performed by JEL and KK. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jeong Il Yu.

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Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethical approval

This study was approved by the Health Institutional Review Boards of Samsung Medical Center (No. 2020–03-012).

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The requirement for informed consent was waived because of the retrospective nature of this study.

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The requirement for informed consent was waived because of the retrospective nature of this study.

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Kim, N., Yu, J.I., Park, H.C. et al. Incorporating sarcopenia and inflammation with radiation therapy in patients with hepatocellular carcinoma treated with nivolumab. Cancer Immunol Immunother 70, 1593–1603 (2021). https://doi.org/10.1007/s00262-020-02794-3

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