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

Purpose This study aims 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 hepatocellular carcinoma (HCC) patients. Methods and Materials We retrospectively collected data from 75 HCC patients who received radiotherapy (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 (LKB) model with a generalized equivalent dose was used to establish the NTCP model, reflecting the whole blood DVHs. The optimization of the LKB parameters was conducted by minimizing a negative log-likelihood function. Results 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/post-RT ALC were 1410/μL (range, 520–3710/μL) and 470/μL (range, 60–1760/μL), respectively. There was a correlation between blood mean dose and ALC depletion (Pearson r = -0.664; p < 0.001). The average blood mean doses in each radiation-induced lymphopenia group were 2.90 Gy (95% CI, 1.96–3.85 Gy) for grade 0–1, 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 developed an NTCP model to predict SRIL, the area under the receiver operating characteristic curve and Brier score were 0.89 and 0.12, respectively. Conclusion We developed the first NTCP model based on whole blood DVHs for estimating SRIL after abdominal RT in HCC patients. Our results showed a strong correlation between blood dose and ALC depletion, suggesting the potential to predict the risk of SRIL occurrence for using blood dose.