Functional liver imaging and dosimetry for risk stratification in patients with hepatocellular carcinoma undergoing radiotherapy: validation study.

Abstract

Functional liver imaging has potential to personalize management of Hepatocellular Carcinoma (HCC) by mitigating hepatotoxicity risk. We validated functional liver imaging and dosimetric parameters for risk-stratification in an expanded cohort of patients with HCC. We reviewed 109 consecutive patients who underwent Sulfur Colloid (SC)-SPECT/CT scans for radiation therapy (RT) planning and extracted previously reported functional liver imaging metrics. We generated elastic net multivariable Cox models with event-stratified and nested cross-validation folds to predict Overall Survival (OS) and increase in Child-Pugh score ≥ 2 (CP+2). Test-fold patients were risk-stratified, and time-dependent model performance was characterized. ROC analysis generated prognostic cutoffs with confidence intervals to guide functional liver avoidance treatment planning. Cross-validated model concordance was 0.70 (95% CI: 0.67-0.73) for OS and 0.67 (95% CI: 0.63-0.71) for CP+2. Top-ranked OS predictors included tumor volume (HR=1.56, 1.54-1.58), CP-score (HR=1.36, 1.34-1.38), Liver-GTV V20 (HR=1.310, 1.306-1.314), prior liver-directed therapy (HR=0.83, 0.82-0.85), functional liver volume dosimetry (FLV V20) (HR=1.19, 1.14-1.23), and RT-year (HR=0.89, 0.88-0.91). Top-ranked CP+2 predictors were total liver function (TLF) (HR=0.64, 0.63-0.66), Liver-GTV mean dose (HR=1.40, 1.36-1.49), and CP-score (HR=1.19, 1.16-1.23). Test-fold risk groups were defined for each endpoint (log-rank P<0.001). OS model performance stabilized beyond 2 years; CP+2 model stability peaked within 1 year. Optimal strata for 2-yr OS were FLV V20 < 25.8% and Liver-GTV V20 < 25.4%; 1-yr CP+2 strata were TLF < 0.91 and Liver-GTV mean dose < 18.9 Gy. Functional liver metrics on SC-SPECT/CT were validated alongside clinical and dosimetric factors within robust outcome models. Testing of personalized RT planning for patients with HCC to preserve liver function is warranted in clinical trials.