Correlation between biological effective dose and radiation-induced liver disease from hypofractionated radiotherapy

Background: The prevention of radiation-induced liver disease (RILD) is very significant in ensuring a safe radiation treatment and high quality of life. Aims and Objectives: The purpose of this study is to investigate the correlation of physical and biological effective dose (BED) metrics with liver toxicity from hypo-fractionated liver radiotherapy. Materials and Methods: 41 hypo-fractionated patients in 2 groups were evaluated for classic radiation-induced liver disease (RILD) and chronic RILD, respectively. Patients were graded for effective toxicity (post-treatment minus pre-treatment) using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Physical dose (PD) distributions were converted to BED. The V_10Gy, V_15Gy, V_20Gy, V_25Gy and V_30Gy physical dose-volume metrics were used in the analysis together with their respective BED-converted metrics of V_16.7Gy3, V_30Gy3, V_46.7Gy3, V_66.7Gy3 and V_90Gy3. All levels were normalized to their respective patient normal liver volumes (NLV) and evaluated for correlation to RILD. Results were measured quantitatively using R² regression analysis. Results: The classic RILD group had median follow-up time of 1.9 months and the average PD-NLV normalized V_10Gy, V_15Gy, V_20Gy, V_25Gy and V_30Gy metrics per grade were plotted against RILD yielding R² correlations of 0.84, 0.72, 0.73, 0.65 and 0.70, respectively while the BED-volume metrics of V_16.7Gy3, V_30Gy3, V_46.7Gy3, V_66.7Gy3 and V_90Gy3 resulted in correlation values of 0.84, 0.74, 0.66, 0.78 and 0.74, respectively. BED compared to PD showed a statistically significant (p=.03) increase in R² for the classic RILD group. Chronic RILD group had median follow-up time of 12.3 months and the average PD-NLV normalized V_10Gy, V_15Gy, V_20Gy, V_25Gy and V_30Gy metrics per grade were plotted against RILD grade yielding R² correlations of 0.48, 0.92, 0.88, 0.90 and 0.99 while the BED-volume metrics of V_16.7Gy3, V_30Gy3, V_46.7Gy3, V_66.7Gy3 and V_90Gy3 resulted in correlation values of 0.43, 0.94, 0.99, 0.21 and 0.00, respectively. Conclusion: The strong correlations of the V_10Gy and V_15Gy PD-volume metrics as well as the V_16.7Gy3(BED of V_10Gy) to both classic and chronic RILD imply the appropriateness of the current 15_Gy evaluation level for liver toxicity with hypo-fractionated treatments.