Radiation (RT)-Associated Kidney Injury in Pediatric Cancer Patients: Results from the Pediatric Normal Tissue Effects in the Clinical (PENTEC) Genitourinary (GU) Task Force

Abstract

<h3>Purpose/Objective(s)</h3> RT-Associated kidney injury is a complication in children treated for cancer. Reported injury includes mildly elevated serum markers, decreased glomerular filtration rate, hypertension, abnormal renal imaging and rarely, renal failure. Through systematic review of available studies, The PENTEC GU task force aims to model the relationships between RT dose and chronic kidney disease (CKD). <h3>Materials/Methods</h3> We conducted a PubMed search of peer-reviewed reports from 1990-2017 evaluating pediatric CKD and RT. 2048 articles were retrieved with 98 fully reviewed. 19 contained whole kidney data for modeling but no article met criteria for partial kidney modeling. However, a 2021 investigation contained usable partial kidney data by Green et al. (JASN 2021). We used the National Kidney Foundation's (NKF) stages for CKD toxicity. Partial kidney dose was modeled from the odds radios (OR) reported in a St. Jude Lifetime Cohort Study (SJLCS) with coefficients in a logistic regression model calculated. The intercepts of the logistic regression models were obtained directly from the investigators. As only V5 and V10 were statistically significant in the SJLCS, we limited our partial kidney model to these doses. <h3>Results</h3> Normal Tissue Complication Rates ≥ 5%, expressed as EQD2 (equivalent doses, 2 Gy/fx) for whole kidney exposures occurred at 8.5, 10.2 and 14.5 Gy for NKF grades ³ 1, ³ 2, and ³ 3, respectively. Conventional Wilms whole abdominal RT (WAI) of 10.5 Gy in 6 fractions had risks of ³ grade 2 toxicity ∼ 4%, and ³ grade 3 toxicity ∼ 1%. For fractionated 12 Gy total body RT (TBI) those risks were 8%, and < 3%, respectively. Data did not support modeling with chemotherapy. Partial kidney modeling from 439 survivors of the SJLCS who received RT (median age 7.3 yrs) showed that 5 or 10 Gy RT to 100% kidney gave a <5% risk of grades 3-5 (severe) toxicity with 1500 mg/m2 carboplatin or no chemo. With 480 mg/m2 cisplatin, a 3% risk of severe toxicity occurred without RT, and a 5% risk when 26% kidney received ≥ 10 Gy. With 63 gm/m2 of ifosfamide, a 5% risk of severe toxicity occurred with no RT, and a 10% toxicity risk occurred when 42% kidney received ≥ 10 Gy. <h3>Conclusion</h3> In patients with Wilms, the risk of toxicity from 10.5 Gy of WAI is low. For 11-12 Gy fractionated TBI with various chemotherapies, the risk of severe toxicity is low but low-grade toxicity is not uncommon. In our partial kidney modeling of RT in the absence of chemo, or with only carboplatin, 10 Gy RT can be delivered to the entire kidney with a low risk of severe CKD. Cisplatin and ifosfamide, however, significantly increase the risk of CKD and decrease the tolerable RT dose. A better understanding of chemo effects, and dose-response-curves for regional renal injury will facilitate optimal use of tools such as IMRT and protons.