Impact of Testicular Boost on Oncologic Outcomes and Late Effects in Pediatric Patients With Leukemia Receiving Fractionated Total Body Irradiation (TBI): A Single-Institution Experience

Abstract

Late toxicity of treatment remains a major consideration among survivors of childhood leukemia. Pediatric patients with leukemia who receive fractionated total body irradiation (fTBI) as conditioning prior to stem cell transplantation (SCT) are frequently treated with a 4 Gy testicular boost in addition to fTBI to 12-13.2 Gy to reduce the risk of testicular relapse in this "sanctuary site." However, total body irradiation can be associated with risk of impaired hormonal function; it is unclear if the 4 Gy testicular boost is needed to reduce risk of testicular relapse, and whether it contributes to the toxicity beyond that imparted by fTBI. This study investigated patients both with and without a boost for risk of recurrence, hormonal function, and fertility.We retrospectively reviewed records of boys treated for leukemia with fTBI as part of conditioning for SCT at our institution from 1989-present. We included patients with both AML and ALL in our analysis. We excluded patients who died in the peri-transplant period. Cumulative incidence was tested using Gray's Test for Equality of Cumulative Incidence Functions. Endocrine outcomes were tested using chi square test.We identified 91 boys (age range 9 months - 22 years), 62 with ALL and 29 with AML. Median follow up was 43.4 months. In addition to fTBI to 12-13.2 Gy, 52 patients received a midplane testicular dose of 4 Gy (49 with ALL, 3 with AML), while 39 patients did not receive the testicular boost (13 with ALL, 26 with AML). There was no difference in time to first relapse or cumulative incidence of relapse between the boost and no-boost groups. There were 2 testicular relapses, one ALL patient who received boost and one AML patient who did not receive boost. The risk of abnormal luteinizing hormone (LH) was 65% in the boost group vs 26% in the non-boost group, P = 0.0063. Serum follicle-stimulating hormone, total testosterone, free testosterone, abnormal sperm studies did not differ between groups, nor did the percentage of patients who required endocrine or fertility treatments. We further investigated the subset of patients with ALL and similarly found no difference in risk of relapse between patients who had received a testicular boost and those who had not boost.Omission of boost was associated with comparable risk of recurrence and improved endocrine outcomes, specifically LH levels. Our data suggest that omission of testicular boost in the fTBI program is oncologically safe and results in improved hormonal function.