Background: PanEuropean(SIOP) trials of treatment for childhood brain cancers (medulloblastomas/PNET) showed a 5% survival advantage with sandwich gonadotoxic chemotherapy (CT) over surgical excision, neuraxial radiation and tumour boost (RT) alone. But this was tempered by a reduced quality of survival at 7 years.
Objective: To assess the long term prevalence of subfertility after CT with/without neuraxial radiation.
Methods: Retrospective longitudinal case note review of all patients diagnosed with intracranial PNETs between 1.1.1980 and 31.12.2013 and follow-up >1year. Data on treatment, relapse, gonadotrophin levels, puberty and (in girls) estrogen/HRT replacement were collected from diagnosis. Time to, and cross-sectional rates of, subfertility (FSH>15 IU/l and/or HRT use) at last follow-up were compared between patients groups with (A) and without (B) CT.
Results: 158/284 with available fertility data were 6.5±2.7 (2.69.9) years at diagnosis and 16.3 (2.329.7) years after 9.5±4.6 (1.322.1) years follow-up; 64(40%) were female and 22(20%) were infants (12 female). At last assessment, 95(60%) had CT (88(56%) of whom additional RT) and 62(40%) had RT alone (2 with CT only are not further discussed). 36/158(23%), being girls 25(69%)(P<0.0001), had evidence of subfertility at 12.1±4.7(1.7216.54) years, whilst a further 26/158 (16.5%) were still under 10 y at last visit. Patients given CT had greater subfertility rates than those with radiation alone (30/9531.6% vs 6/629.7%, P=0.001) and those on infant protocols (5.21±4.41 y vs 13.41±3.70 y, P<0.0001 demonstrated this earlier. None had gonadotropin deficiency.
Conclusion: CT in the intracranial PNET treatment protocol significantly increased the prevalence of subfertility in children, which is especially evident in females and in infant protocols. This is likely to increase with time. By contrast, gonadotropin deficiency is not a radiation consequence despite even at a long 9.5 y follow-up. Pretreatment fertility preservation should be considered in adolescent boys, families should be warned of likely subfertility and need for routine endocrine referral for pubertal assessment.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology