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Peer-reviewedCC BY 4.0Frontiers in Oncology

Muscle strength and muscle mass phenotypes and survival in unresectable hepatocellular carcinoma receiving hepatic arterial infusion chemotherapy-based combination therapy

  • Chan Su1
  • Guibao Ji1
  • Xinze Wang2
  • Qiuxia Guo3
  • Xing Lv4
  • Xin Jin1
  • Ding Xiao1
4 affiliations
  1. 1Department of Hepatobiliary-Pancreatic and Hernia Surgery, Wuhan Fourth Hospital
  2. 2Department of Trauma and Orthopedics, Wuhan Fourth Hospital
  3. 3Department of Gastroenterology, Wuhan Fourth Hospital
  4. 4Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
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Abstract

Background: Muscle strength and muscle mass may decline discordantly in hepatocellular carcinoma (HCC), but the prognostic relevance of combined strength–mass phenotypes during hepatic arterial infusion chemotherapy (HAIC)-based combination therapy is unclear. We evaluated survival and incremental prognostic value according to handgrip strength (HGS) and skeletal muscle index (SMI) phenotypes in patients with unresectable HCC.

Methods: We performed a secondary analysis of 154 patients from the 1:1 propensity score-matched subset of a previously reported 265-patient cohort receiving HAIC with targeted therapy and immunotherapy. Patients were classified as Normal, SMI-low, HGS-low, or Both-low. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan–Meier and multivariable Cox analyses. Incremental prognostic value for OS was evaluated using Harrell’s concordance index (C-index) and likelihood-ratio tests, with internal validation using bootstrap optimism correction.

Results: Median follow-up was 22.1 months, as estimated using the reverse Kaplan–Meier method. PFS and OS differed across phenotypes (both log-rank P < 0.001). After multivariable adjustment, HGS-low was associated with shorter PFS (hazard ratio [HR], 2.81; 95% confidence interval [CI], 1.71–4.60) and OS (HR, 3.09; 95% CI, 1.87–5.11), and Both-low showed similar associations (PFS: HR, 2.53; 95% CI, 1.40–4.56; OS: HR, 3.72; 95% CI, 2.00–6.92). The 10-patient SMI-low estimates were imprecise for PFS (HR, 0.79; 95% CI, 0.29–2.16) and OS (HR, 0.81; 95% CI, 0.28–2.31). After bootstrap optimism correction, adding low HGS increased the C-index from 0.625 to 0.705, whereas the four-phenotype model yielded 0.701 and did not improve model fit beyond low HGS ( P = 0.798).

Conclusion: Low HGS, with or without low SMI, was associated with poorer survival. HGS may provide a simple and practical measure for baseline prognostic assessment in unresectable HCC treated with HAIC-based combination therapy.

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Cite

BibTeXRIS
BibTeX
@article{su2026muscle,
  title = {{Muscle strength and muscle mass phenotypes and survival in unresectable hepatocellular carcinoma receiving hepatic arterial infusion chemotherapy-based combination therapy}},
  author = {Chan Su and Guibao Ji and Xinze Wang and Qiuxia Guo and Xing Lv and Xin Jin and Ding Xiao},
  journal = {Frontiers in Oncology},
  year = {2026},
  month = oct,
  doi = {10.3389/fonc.2026.1974237},
  url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1974237/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Muscle strength and muscle mass phenotypes and survival in unresectable hepatocellular carcinoma receiving hepatic arterial infusion chemotherapy-based combination therapy
AU  - Chan Su
AU  - Guibao Ji
AU  - Xinze Wang
AU  - Qiuxia Guo
AU  - Xing Lv
AU  - Xin Jin
AU  - Ding Xiao
PY  - 2026
DA  - 2026/10/21
JO  - Frontiers in Oncology
DO  - 10.3389/fonc.2026.1974237
UR  - https://www.frontiersin.org/articles/10.3389/fonc.2026.1974237/full
AB  - Background: Muscle strength and muscle mass may decline discordantly in hepatocellular carcinoma (HCC), but the prognostic relevance of combined strength–mass phenotypes during hepatic arterial infusion chemotherapy (HAIC)-based combination therapy is unclear. We evaluated survival and incremental prognostic value according to handgrip strength (HGS) and skeletal muscle index (SMI) phenotypes in patients with unresectable HCC.  Methods: We performed a secondary analysis of 154 patients from the 1:1 propensity score-matched subset of a previously reported 265-patient cohort receiving HAIC with targeted therapy and immunotherapy. Patients were classified as Normal, SMI-low, HGS-low, or Both-low. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan–Meier and multivariable Cox analyses. Incremental prognostic value for OS was evaluated using Harrell’s concordance index (C-index) and likelihood-ratio tests, with internal validation using bootstrap optimism correction.  Results: Median follow-up was 22.1 months, as estimated using the reverse Kaplan–Meier method. PFS and OS differed across phenotypes (both log-rank P < 0.001). After multivariable adjustment, HGS-low was associated with shorter PFS (hazard ratio [HR], 2.81; 95% confidence interval [CI], 1.71–4.60) and OS (HR, 3.09; 95% CI, 1.87–5.11), and Both-low showed similar associations (PFS: HR, 2.53; 95% CI, 1.40–4.56; OS: HR, 3.72; 95% CI, 2.00–6.92). The 10-patient SMI-low estimates were imprecise for PFS (HR, 0.79; 95% CI, 0.29–2.16) and OS (HR, 0.81; 95% CI, 0.28–2.31). After bootstrap optimism correction, adding low HGS increased the C-index from 0.625 to 0.705, whereas the four-phenotype model yielded 0.701 and did not improve model fit beyond low HGS ( P = 0.798).  Conclusion: Low HGS, with or without low SMI, was associated with poorer survival. HGS may provide a simple and practical measure for baseline prognostic assessment in unresectable HCC treated with HAIC-based combination therapy.
SN  - 2234-943X
ER  -