Prognostic value of pretreatment sarcopenia in unresectable hepatocellular carcinoma treated with yttrium-90 radioembolization

Technical Summary: Prognostic Value of Pretreatment Sarcopenia in Unresectable HCC Treated with Yttrium-90 Radioembolization

Problem Statement
While sarcopenia is established as a prognostic biomarker in hepatocellular carcinoma (HCC), its specific impact on outcomes following transarterial radioembolization (TARE) with yttrium-90 ($^{90}$Y) microspheres remains unclear. Furthermore, the relationship between sarcopenia and tumor absorbed dose in this context has not been fully elucidated. This study addresses the need to assess the prognostic value of pretreatment sarcopenia regarding local progression-free survival (LPFS), progression-free survival (PFS), and overall survival (OS) in patients with unresectable HCC undergoing TARE.

Methodology
The study employed a retrospective analysis of 75 patients with HCC treated with $^{90}$Y glass or resin microspheres between June 2022 and December 2024.

• Sarcopenia Assessment: Skeletal muscle index (SMI) was calculated from the CT component of [$^{18}$F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) scans at the L3 vertebral level. Sarcopenia was defined using sex- and BMI-specific SMI cut-offs.
• Dose Stratification: Tumor absorbed dose was dichotomized at a threshold of 485 Gy.
• Statistical Analysis: Survival outcomes were evaluated using Kaplan–Meier analysis. Prognostic factors were assessed via Cox regression models to determine independent predictors of LPFS, PFS, and OS.

Key Results

• Prevalence: Sarcopenia was identified in 32 patients (42.7% of the cohort).
• Treatment Response: Sarcopenic patients demonstrated significantly lower objective response rates (34.4% vs. 97.7%; $p < 0.001$) and disease control rates (62.5% vs. 100%; $p < 0.001$) compared to non-sarcopenic patients.
• Survival Outcomes:
  • Sarcopenic Group: Median LPFS was 6 months, median PFS was 6 months, and median OS was 10 months.
  • Non-Sarcopenic Group: Median LPFS was 21 months, median PFS was 19 months, and median OS was not reached.
  • All differences were statistically significant ($p < 0.001$).
• Multivariable Analysis:
  • Sarcopenia: Independently predicted shorter LPFS (HR 4.0; 95% CI 2.1–7.7), PFS (HR 2.8; 95% CI 1.6–5.2), and OS (HR 5.5; 95% CI 2.5–12.0).
  • Tumor Absorbed Dose: A dose < 485 Gy independently predicted shorter LPFS (HR 1.9; 95% CI 1.1–3.6; $p = 0.034$). However, it did not significantly predict PFS ($p = 0.078$) or OS ($p = 0.161$).

Significance and Claims
The paper concludes that pretreatment sarcopenia is a robust, independent predictor of inferior LPFS, PFS, and OS following TARE for HCC. While tumor absorbed dose remains associated with local tumor control, the study explicitly states that an adequate dose does not overcome the adverse prognosis associated with sarcopenia.

The authors assert that the routine assessment of skeletal muscle mass can improve risk stratification for patients undergoing TARE. This assessment may help identify individuals who require closer surveillance and earlier initiation of systemic therapy, addressing the limitations of relying solely on dosimetric parameters for prognosis.