Blood dose estimates in radiotherapy and correlations with adverse clinical outcomes in hepatocellular carcinoma

This study aims to investigate the potential correlation between the hematological dose (HEDOS), representing the dynamic blood dose, and severe radiation-induced lymphopenia (SRIL). The study examines whether SRIL mediates the relationship between HEDOS and oncologic outcomes in patients with hepatocellular carcinoma (HCC). A total of 41 patients with HCC who received radiation therapy to the liver and/or perihepatic metastatic lesions were retrospectively analyzed. Blood-related organs (spleen, heart, veins, aortas, lungs, and liver) were manually delineated. HEDOS was calculated using a Markov chain model. The effective dose to immune cells (EDIC), representing the static blood dose, was calculated for comparison with HEDOS. We examined whether these two blood dose metrics correlated with SRIL, defined as an absolute lymphocyte count below 500/μL one month after radiotherapy. The association between blood dose metrics and clinical outcomes, local and distant recurrence-free survival (LFS and DFS) was also evaluated. The mean HEDOS was significantly associated with SRIL, with an odds ratio of 1.61 (95% confidence interval [CI]: 1.10-2.54, P = 0.02). The mean HEDOS was associated with worse LFS and DFS, with hazard ratios of 1.35 (95% CI: 1.06-1.71, P = 0.01) for LFS and 1.28 (95% CI: 1.01-1.63, P = 0.04) for DFS. No association was observed between EDIC and any of the outcomes. A higher mean HEDOS showed a statistically significant correlation with SRIL and clinical outcomes, whereas the EDIC did not. The HEDOS, which incorporates temporal delivery characteristics such as dose rate and beam-on-time, may have an advantage for predicting SRIL and clinical outcomes of patients with HCC.