Predicting late renal toxicity using a two-component repair model among pediatric patients receiving total body irradiation for stem cell transplant

Abstract

Purpose/Objectives

Late renal toxicity can be impactful for stem cell transplant (SCT) patients with total body irradiation (TBI) as part of the conditioning regimen. This work describes a two component repair model to predict renal toxicity among pediatric patients.

Materials/Methods

Systematic literature searches described in two other reports were used to identify articles describing late renal toxicity in children treated with TBI as part of SCT. Six studies were included with a combined sample size of 172 patients. Data pertaining to TBI and renal toxicity endpoints were extracted. Probability of renal toxicity was analyzed in relation to TBI dose, fractionation, and dose rate. A logistic regression model was developed using studies with sufficient TBI and pediatric outcome data. The toxicity was calculated from reported rates from each study and were primarily based on abnormal laboratory values.

Results

Physical dose and a traditional method of calculating EQD2 were tested for a significant dose response relationship although none were found. Instead, a statistically significant relationship was found with a two component sublethal repair EQD2 calculation model using logistic regression (p = 0.03). The model predicted the odds ratio for renal toxicity to be 2.9 Gy⁻¹. Predicted probabilities of 5 %, 10 %, and 50 % clinically significant renal toxicities are associated with EQD2 values of 10.4, 11.1, and 13.2 Gy, respectively.

Conclusions

A model to predict the risk of renal toxicity was determined. This model indicates that dose rate and the time interval between fractions are important factors in renal toxicity for pediatric patients receiving SCT with TBI as part of the conditioning regimen.