Effect of childhood cancer treatment on fertility markers in adult male long‐term survivors

Abstract

BackgroundAlthough it is accepted that pediatric cancer treatment harbors a risk of gonadal damage, large cohort studies using up‐to‐date fertility markers are lacking.ProcedureThe aim of our study was to evaluate the gonadal toxicity of childhood cancer treatment using fertility markers. We included 248 adult male long‐term survivors of childhood cancer. Median age at diagnosis: 5 years, median age at follow‐up: 24 years, median follow‐up time 18 years. We evaluated patient characteristics, treatment modalities, testicular size, and endocrinological parameters including Inhibin B, luteinizing hormone (LH), follicle‐stimulating hormone (FSH), and testosterone.ResultsThe median value of Inhibin B in the cancer survivor group was 126 ng/L versus 177 ng/L in the control group (P < 0.001). In the survivors, 67% had Inhibin B levels below the normal reference value of 150 ng/L compared with 26% in the control group (P < 0.05). Inhibin B was the most sensitive discriminator between survivors and controls. Significantly decreased Inhibin B levels and increased FSH levels were found in men treated for Hodgkin and non‐Hodgkin lymphoma, acute‐myeloid leukemia, neuroblastoma, and sarcoma as compared to other malignancies. Cumulative dosages of procarbazine and cyclophosphamide were the only independent chemotherapy‐related predictors for decrease of Inhibin B levels and increase of FSH. Age at time of treatment did not influence post‐treatment Inhibin B or FSH levels.ConclusionsSevere gonadal impairment is a risk in a considerable subgroup of childhood cancer survivors based on current fertility markers like Inhibin B. Males receiving gonadotoxic treatment before puberty are not protected from post treatment gonadal dysfunction. Pediatr Blood Cancer 2009;52:108–112. © 2008 Wiley‐Liss, Inc.

Hypogonadism After Childhood Cancer Treatment

“…This observation is consistent with reports of other authors (Byrne et al1987, Casteren et al 2009). In the group of 61 male patients who didn't receive ChT with AA, all 6 patients with GEI had pelvic or testicular RT (Fig.8).…”

Gonadal function and parenthood 20 years after treatment for childhood lymphoma: A cross‐sectional study

“…Eleven % of our male CLSs were considered to be infertile. In other studies among survivors treated for several types of childhood cancer, azospermia was found in about 30% of the survivors, and elevated FSH levels were observed in approximately every third survivor [20,21]. Elevated FSH is generally viewed to reflect reduced spermatogenesis, and may on a group level together with a single sperm count be useful to screen for possibility of future parenthood.…”

“…Previous studies have been inconclusive as to this issue [20,21], although Green et al [23] demonstrated a higher chance of parenthood in male childhood cancer survivors treated at age 0-4 years compared to age 15-20 years. Neither could we demonstrate any significant difference in levels of FSH when comparing patients treated before or after 1985.…”

Rationale for the treatment of children with CCSK in the UMBRELLA SIOP–RTSG 2016 protocol

“…Moreover, the benefit of including alkylating agents in the treatment of patients diagnosed with CCSK is incorporated in the UMBRELLA protocol 2 , to reduce the risk of serious renal toxicity caused by ifosfamide [39][40][41][42] as well as the occurrence of second tumours or fertility problems caused by cyclophosphamide [43][44][45] . Combining the alkylating agents ifosfamide and cyclophosphamide in an alternating setting to reduce the total cumulative dose of either drug was decided by consensus (TABLE 2).…”