Testicular Function Continues to Improve Many Years After Treatment for Some Childhood Cancers

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(ChemotherapyAdvisor) – Recovery of testicular function can continue to improve more than 15 years after treatment for some childhood cancers, according to a retrospective cross-sectional study published online in the European Journal of Cancer.

“This study suggests that in the male after initial impairment of function, gonads can recover over time in subsets of CCS (childhood cancer survivors) even after a very long follow-up time,” reported lead author Wendy van Dorp of the Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital in The Netherlands, and coauthors. “We showed that in general, inhibin B levels are stable or increase over time, suggesting that recovery from gonadal damage may occur long after cessation of treatment for childhood cancer. However, this increase does not occur in survivors with critically low serum inhibin B levels more than 15 years after treatments, such as survivors treated with high-dose alkylating agents or total body irradiation.”

With improved survival rates for childhood cancers, long-term treatment toxicities have become apparent, including gonad dysfunction associated with chemotherapy and radiotherapy—particularly treatment with alkylating agents and cytosine arabinoside, or whole body or local radiotherapy that included irradiation of the testicles, the authors noted. But to date, no large studies of the recovery of gonadal function in this patient population have been conducted with a follow-up of longer than 15 years. Therefore, little is known about the recovery of gonadal function in long-term male survivors of childhood cancers.

To assess recovery of testicular function long after treatment for childhood cancer, the authors conducted a single-institution study measuring inhibin B levels as a surrogate for gonad function in 201 adult male long-term childhood cancer survivors who had been diagnosed between 1964 and 2005. Inhibin B is a hormone produced by the testis; its levels are hypothesized to reflect recovery of spermatogenesis over time, the authors noted.

The median age at diagnosis was 6.0  years (range 0.0 – 17.5 years) and discontinuation of treatment was reached at a median age of 8.3 years (range 0.0-20.8 years), the authors noted. “Inhibin B levels were first measured after a median follow-up time of 15.7 years (range 3.0-37.0 years).”  The median interval between first (T1) and second measurement (T2) of inhibin B was 3.3 years (range, 0.7-11.3 years), the authors reported.

The median inhibin B level was 127 ng/L (range 5-366 ng/L) at T1, and 155 ng/L (range 10-507) at T2.

“Survivors of rhabdomyosarcoma (median 38 ng/L; range 10-342 ng/L) and Hodgkin lymphoma (median 41 ng/L; range 10-269 ng/L) still had dramatically low serum median inhibin B levels at T2, whereas acute lymphoblastic leukemia survivors (median 193 ng/L; range 10-411 ng/L) and renal tumor survivors (median 220 ng/L; range 10-371 ng/L) had the highest serum inhibin B levels,” the authors reported.

Except for patients who had been treated for childhood Hodgkin lymphoma or rhabdomyosarcoma, all childhood cancer survivors participating in the study exhibited a significant increase of inhibin B levels between T1 and T2, they noted.

Merck-Serono, Serono, Organon, Schering Plough have supported one coauthor's research, according to a conflict-of-interest disclosure published with the study.


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