Context: Craniopharyngiomas are rare, suprasellar tumours with excellent 5-year survival rates of 95%. Despite their benign histology, their tendency to invade vital nearby optic, hypothalamopituitary and vascular structures, complicates resection whilst potentially causing secondary life limiting morbidity, panhypopituitarism and premature mortality. Since 1997, conservative hypothalamic-sparing surgery and radiation to the residual tumour has replaced aggressive resection at our centre.
Objective: We aimed to differentiate treatment and tumour-dependent risk factors for neuroendocrinopathy across treatment decades.
Design: This study was a retrospective longitudinal case note review and Kaplan Meier analysis of treatment and tumour-dependent factors affecting neuroendocrine outcomes in 93 children treated for craniopharyngioma at our centre between 1987 and 2017.
Results: Patients were aged a median (range) 8.24 (0.6217.18) years at diagnosis and followed for 9.77 years (0.2526.92). Despite excellent 20-year overall survival (OS) of 96.77%, progression-free survival (PFS) was 63.4% and, endocrine-event-free survival (EEFS) was just 3.3%. Time to OS (P=0.660), PFS (P=0.667) and EEFS (P=0.401) showed no difference between the different treatment decades. Hypothalamic involvement (P=0.003) more than aggressive surgery (P=0.008) were both associated with relapse. Complete resection reduced the time to first endocrine deficit (P=0.044), with TSHd being most frequently diagnosed first (frequency=84.9%) followed by GnDd (76.1%, only M>14ys/F>13ys included), GHd (93.5%), ACTHd (75.0%), CDI (63.4%) and obesity (50.6%). GHd increased with later treatment decades (P=0.002) but prompt replacement did not reduce PFS. At last review, 63 patients (67.7%) had panhypopituitarism (33 with additional CDI) and 39 (42.0%) were obese. The BMI-SDS of the whole cohort increased by +0.96 (−2.83±4.17) from diagnosis and was worse overall in those undergoing gross total resection, increasing by +2.16 (+0.06±4.17) vs incomplete resection +0.87 (−0.62±2.36, P=0.03). There was a significant reduction in overall BMI-SDS increase across the different treatment eras (P=0.011). Radiotherapy was not predictive of cognitive outcome, with intelligence quotient (IQ) scores in a subset of 22 patients with available pre- and post- treatment data showing no difference (P=0.384).
Conclusions: This large, longitudinal, single-centre analysis of children undergoing changing treatment strategies for craniopharyngioma, confirms the evolutionary hierarchical loss of pituitary and hypothalamic deficits we previously described in a cohort of optic hypothalamo-chiasmatic gliomas (Gan et al JCEM 2015). Our data suggests that changing to a conservative surgical therapeutic approach, avoiding hypothalamic harm, coupled with adjuvant radiotherapy improves neuroendocrine morbidity without reducing survival, recurrence rate or cognitive ability.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology