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 R(2) 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 R(2) 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 R(2) 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 R(2) 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.