Purpose: The purpose of this study is to develop a normal tissue complication probability (NTCP) model based on the blood dose calculated by a computational tool (HEDOS) and clinical lymphopenia outcome data of hepatocellular carcinoma (HCC) patients.
Methods: Subjects are 27 patients with hepatocellular carcinoma (HCC) who have been treated with helical tomotherapy from 2015 to 2017 at Yonsei Cancer Center. The whole-body blood flow network implemented in HEDOS is used to calculate blood transition probability and to estimate the blood radiation dose. Input parameters are total 11 contoured organs (stomach, duodenum, liver, spleen, heart, vena cava, aorta, lung, kidney, and tumor), their dose volume histogram (DVH), tumor volume, beam on time, and fractionation. A normal tissue complication probability (NTCP) based on Lyman-Kutcher-Berman (LKB) model is derived using calculated blood mean dose and binary clinical endpoint: ≥ grade 3 lymphopenia. A negative log-likelihood loss is minimized to find the model fitting parameters TD₅₀(%) (the 50% tolerance dose) and m (the steepness of the curve). The bootstrap resampling is employed to evaluate the confidence interval of the model. In addition, the organ importance to the blood dose is quantitatively investigated by changing the irradiated dose to each organ.
Results: Based on the fitted parameters (TD₅₀(%): 5.39 Gy and m: 0.38), the developed NTCP model enables to predict the ≥ grade 3 radiation induced lymphopenia. The confidence interval bands for 95% and predicted model are obtained using bootstrap resampling. The Χ² of 0.1 shows excellent fitting performance of the model. The HEDOS also shows that delivering more radiation dose to larger veins in the abdomen can cause the most blood damage and should be avoided.
Conclusion: This study introduces the first NTCP model for severe lymphopenia. Our study demonstrates the feasibility of using the calculation tool in the clinic for lymphocyte-sparing radiotherapy.
Funding Support, Disclosures, and Conflict of Interest: This work was supported by grants from the National Research Foundation of Korea (NRF, No. 2021R1C1C1005930) funded by the Korea government (MSIT).
NTCP, Effective Dose, Radiation Therapy
IM/TH- Mathematical/Statistical Foundational Skills: Biostatistics- nonparametric and model validation