Spatial Dose-Response Pattern Associated With Severe Radiation-Induced Lymphopenia in the Liver: A Voxel-Based Analysis

Abstract

Purpose: This study aimed to investigate the dose-response pattern of severe radiation-induced lymphopenia (SRIL) in patients with hepatocellular carcinoma (HCC) undergoing radiation therapy (RT). We focused on identifying specific liver regions associated with SRIL development. Methods and Materials: We analyzed data from 75 patients with HCC treated with RT. Segment-wise and voxel-based analyses (VBAs) were conducted to investigate the spatial relationship between delivered dose and SRIL occurrence (absolute lymphocyte count [ALC] < 500/mL). Logistic regression was performed for segment-wise analysis, whereas generalized linear models and Mann-Whitney U tests were employed for VBAs. The liver was divided into Couinaud segments, and dose distributions were analyzed at both the segment and voxel levels. Results: Segment-wise logistic regression revealed that pre-RT ALC (odds ratio [OR], 0.006; P = .002), liver segments 1 (OR, 1.228; P = .048), and 7 (OR, 1.314; P = .016) were statistically associated with SRIL occurrence. VBAs demonstrated heterogeneous dose-response patterns across the liver, with segment 1 consistently showing the strongest association with SRIL across different statistical methods. Segment 1 contained the highest proportion of statistically significant voxels (94%) in relation to SRIL occurrence among all liver segments. Conclusions: This study revealed an inhomogeneous dose-response pattern regarding SRIL manifestation in the liver. Our results suggest that certain regions within a single organ may require rigorous dosimetric constraints to mitigate SRIL. (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.