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

TL;DR

This study develops a model to predict kidney damage in children undergoing stem cell transplants with total body irradiation, emphasizing the role of dose rate and fraction timing.

Contribution

A novel two-component repair model is introduced to predict late renal toxicity in pediatric stem cell transplant patients.

Findings

A two-component sublethal repair EQD2 model showed a statistically significant relationship with renal toxicity (p = 0.03).

Predicted probabilities of renal toxicity correlate with EQD2 values of 10.4, 11.1, and 13.2 Gy for 5%, 10%, and 50% toxicity rates.

Dose rate and time between fractions are identified as important factors in predicting renal toxicity.

Abstract

•Efforts have been made recently to reduce toxicities in myeloablative TBI.•We utilize a linear quadratic schema with two component dose rate repair mechanism.•We compare this kidney dose response model to others in the literature.•Dose rate is an important factor, along with total dose and dose per fraction.

Efforts have been made recently to reduce toxicities in myeloablative TBI.

We utilize a linear quadratic schema with two component dose rate repair mechanism.

We compare this kidney dose response model to others in the literature.

Dose rate is an important factor, along with total dose and dose per fraction.

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.

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.

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.

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.

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