Normal Tissue Complication Probability Modeling of Severe Radiation-Induced Lymphopenia Using Blood Dose for Patients With Hepatocellular Carcinoma.

Abstract

This study aimed to develop a normal tissue complication probability (NTCP) model to estimate the risk of severe radiation-induced lymphopenia (SRIL; absolute lymphocyte count [ALC] < 500/μL) by using the blood dose of patients with hepatocellular carcinoma (HCC). We retrospectively collected data from 75 patients with HCC who received radiation therapy (RT) between 2015 and 2018. The hematological dose framework calculated blood dose-volume histograms (DVHs) using a predefined blood flow model, organ DVHs, the number of treatment fractions, and beam delivery time. A Lyman-Kutcher-Burman model with a generalized equivalent dose was used to establish the NTCP model, reflecting the whole-blood DVHs. Optimization of the Lyman-Kutcher-Burman parameters was conducted by minimizing a negative log-likelihood function. There were 6, 4, 18, 33, and 14 patients in the groups with radiation-induced lymphopenia grades 0, 1, 2, 3, and 4, respectively. The median pre- and post-RT ALC values were 1410/μL (range, 520-3710/μL) and 470/μL (range, 60-1760/μL), respectively. There was a correlation between mean blood dose and ALC depletion (Pearson r = -0.664; P < .001). The average mean blood doses in each radiation-induced lymphopenia group were 2.90 Gy (95% CI, 1.96-3.85 Gy) for grade 0 to 1, 5.29 Gy (95% CI, 4.12-6.45 Gy) for grade 2, 8.81 Gy (95% CI, 7.55-10.07 Gy) for grade 3, and 11.69 Gy (95% CI, 9.82-17.57 Gy) for grade 4. When applying the developed NTCP model to predict SRIL, the area under the receiver operating characteristic curve and Brier score values were 0.89 and 0.12, respectively. We developed the first NTCP model based on whole-blood DVHs for estimating SRIL after abdominal RT in patients with HCC. Our results showed a strong correlation between blood dose and ALC depletion, suggesting the potential to predict the risk of SRIL occurrence using blood dose.