Cancer Res Treat.  2025 Apr;57(2):422-433. 10.4143/crt.2024.493.

Unraveling the Impact of Sarcopenia-Induced Lymphopenia on Treatment Response and Prognosis in Patients with Stage III Non–Small Cell Lung Cancer: Insights for Optimizing Chemoradiation and Immune Checkpoint Inhibitor

• Lee J
• Kim KH
• Kim J
• Lee CG
• Cho J
• Yoon HI
• Cho Y

• KMID: 2566861
• DOI: http://doi.org/10.4143/crt.2024.493

Abstract

Purpose
Sarcopenia is a poor prognostic factor in non–small cell lung cancer (NSCLC). However, its prognostic significance in patients with NSCLC receiving immune checkpoint inhibitors (ICIs) and its relationship with lymphopenia remain unclear. We aimed to investigate the prognostic role of sarcopenia and its effect on lymphocyte recovery in patients with stage III NSCLC treated with concurrent chemoradiotherapy (CCRT) followed by ICI.
Materials and Methods
We retrospectively evaluated 151 patients with stage III NSCLC who received definitive CCRT followed by maintenance ICI between January 2016 and June 2022. Sarcopenia was evaluated by measuring the skeletal muscle area at the L3 vertebra level using computed tomography scans. Lymphocyte level changes were assessed based on measurements taken before and during CCRT and at 1, 2, 3, 6, and 12 months post-CCRT completion.
Results
Even after adjusting for baseline absolute lymphocyte count through propensity score-matching, patients with pre-radiotherapy (RT) sarcopenia (n=86) exhibited poor lymphocyte recovery and a significantly high incidence of grade ≥ 3 lymphopenia during CCRT. Pre-RT sarcopenia and grade ≥ 3 lymphopenia during CCRT emerged as prognostic factors for overall survival and progression-free survival, respectively. Concurrent chemotherapy dose adjustments, objective response after CCRT, and discontinuation of maintenance ICI were also analyzed as independent prognostic factors.
Conclusion
Our results demonstrated an association between pre-RT sarcopenia and poor survival, concurrent chemotherapy dose adjustments, and impaired lymphocyte recovery after definitive CCRT. Moreover, CCRT-induced lymphopenia not only contributed to poor prognosis but may have also impaired the therapeutic efficacy of subsequent maintenance ICI, ultimately worsening treatment outcomes.

Keyword

Non-small-cell lung carcinoma; Immune checkpoint inhibitors; Radiotherapy; Sarcopenia; Lymphopenia

Figure

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  Fig. 1. Scatter plot illustrating the relationship between L3 skeletal muscle index and baseline absolute lymphocyte count; a)Pearson’s correlation coefficient, b)Partial correlation coefficient after adjusting for sex.

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  Fig. 2. Changes in absolute lymphocyte counts based on pre-radiotherapy (RT) sarcopenia before (A) and after (B) propensity score-matching. *p < 0.05 and ***p < 0.001; data are represented as mean±standard error.

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  Fig. 3. Changes in absolute lymphocyte counts based on grade 3 or higher lymphopenia during concurrent chemo radiotherapy (CCRT). *p < 0.05 and ***p < 0.001; data are represented as mean±standard error.

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  Fig. 4. Kaplan-Meier curves depicting overall survival (OS) and progression-free survival (PFS). OS (A) and PFS (B) in patients with or without pre-radiotherapy (RT) sarcopenia. OS (C) and PFS (D) in patients with or without grade 3 or higher lymphopenia during chemoradiotherapy.

Reference

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