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. 2025 Jun 18:17:1169-1183.
doi: 10.2147/CMAR.S539527. eCollection 2025.

Risk Factors of Non-Classic Radiation-Induced Liver Disease (ncRILD) After Intensity-Modulated Radiotherapy in Hepatocellular Carcinoma

You-Qin Du  1   2 , Su-Ping Tao  3 , Jian-Xu Li  1 , Yin-Nong Zhao  2
Affiliations

Risk Factors of Non-Classic Radiation-Induced Liver Disease (ncRILD) After Intensity-Modulated Radiotherapy in Hepatocellular Carcinoma

You-Qin Du et al. Cancer Manag Res. .

Abstract

Purpose: This study aimed to identify independent risk factors for non-classic radiation-induced liver disease (ncRILD) in hepatocellular carcinoma (HCC) patients treated with intensity-modulated radiation therapy (IMRT) and to construct a predictive nomogram.

Patients and methods: We retrospectively analyzed 177 primary HCC patients treated with IMRT between 2013 and 2021. Univariate and multivariate analyses were conducted to identify risk factors for ncRILD. A nomogram was developed based on significant variables. Dosimetric parameters were also assessed across different fractionation doses.

Results: Multivariate analysis identified tumor number ≥ 2, mean liver dose ≥ 1371.4 cGy, and normal liver volume < 700 mL as independent risk factors for ncRILD. A nomogram was established using logistic regression. In patients receiving ≥ 4 Gy per fraction, ncRILD was significantly associated with Vs5-Vs40 (p < 0.05), but not with V5-V40. No such associations were found for 2 Gy and 3 Gy groups.

Conclusion: Patients with multifocal tumor, lower normal liver volume and higher mean liver dose are at increased risk of developing radiation-induced liver injury. These findings suggest that dosimetric parameters, especially at higher fraction doses, may play a critical role in the occurrence of ncRILD.

Keywords: IMRT; child-Pugh score; hepatocellular carcinoma; liver toxicity; ncRILD.

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Conflict of interest statement

The authors declare no competing interests in this work.

Figures

Figure 1
Figure 1
Study flowchart.
Figure 2
Figure 2
Survival Outcomes in Patients with and Without Non-Classic Radiation-Induced Liver Disease Post-Radiotherapy.
Figure 3
Figure 3
ROC curves. (A) ROC curve of major tumor diameter when ncRILD as the end point. (B) ROC curve of GTV volume when ncRILD as the end point. (C) ROC curve of normal liver mean dose when ncRILD as the end point.
Figure 4
Figure 4
Nomogram based on mean liver dose, normal liver volume, and tumor numbers for ncRILD prediction.
Figure 5
Figure 5
Comparison of Predictive Performance: Nomogram vs NLV and MLD.
See this image and copyright information in PMC

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