Post-treatment neuroendocrine outcomes among pediatric brain tumor patients: Is there a difference between proton and photon therapy?

Anthony T Yip,Justin D Yu,Minh-Phuong Huynh-Le,Mia Salans,Soumya Unnikrishnan,Alexander S Qian,Ronghui Xu,Ryan Kaner,Iain Macewan,John R Crawford,Jona A Hattangadi-Gluth

doi:10.1016/j.ctro.2022.02.010

Abstract

PurposePediatric brain tumor patients are vulnerable to radiotherapy (RT) sequelae including endocrinopathies. We compared post-RT neuroendocrine outcomes between pediatric brain tumor patients receiving photons (XRT) versus protons (PRT). MethodsUsing a prospectively maintained single-institution database, we analyzed 112 pediatric primary brain tumor patients (80 XRT, 32 PRT) from 1996 to 2019. Patient/treatment characteristics and endocrinopathy diagnoses (growth hormone deficiency [GHD], sex hormone deficiency [SHD], hypothyroidism, and requirement of hormone replacement [HRT]) were obtained via chart review. Univariable/multivariable logistic regression identified neuroendocrine outcome predictors. Time-adjusted propensity score models accounted for treatment type. Craniospinal irradiation (CSI) patients were evaluated as a sub-cohort. ResultsMedian follow-up was 6.3 and 4.4 years for XRT and PRT patients respectively. Medulloblastoma was the most common histology (38%). Half of patients (44% in XRT, 60% in PRT) received CSI. Common endocrinopathies were GHD (26% XRT, 38% PRT) and hypothyroidism (29% XRT, 19% PRT). CSI cohort PRT patients had lower odds of hypothyroidism (OR 0.16, 95% CI[0.02–0.87], p = 0.045) on multivariable regression and propensity score analyses. There were no significant differences in endocrinopathies in the overall cohort and in the odds of GHD or HRT within the CSI cohort. SHD developed in 17.1% of the XRT CSI group but did not occur in the PRT CSI group. ConclusionEndocrinopathies were common among pediatric brain tumor survivors. Among CSI patients, PRT was associated with lower risk of hypothyroidism, and potentially associated with lower incidence of SHD. Future studies should involve collaborative registries to explore the survivorship benefits of PRT.

Highlights

While brain radiotherapy (RT) plays a critical role in the management of pediatric brain tumors, it is associated with neuroendocrine sequalae such as growth, thyroid, and sex hormone deficiencies, via radiation effects on the hypothalamic-pituitary axis
We examined neuroendocrine outcomes following PRT and XRT in a cohort of pediatric primary brain tumor patients including medulloblastoma patients and other brain tumor types
Photon (n=80) and proton (n=32) patients mainly differed in age and follow-up time

Summary

Introduction

While brain radiotherapy (RT) plays a critical role in the management of pediatric brain tumors, it is associated with neuroendocrine sequalae such as growth, thyroid, and sex hormone deficiencies, via radiation effects on the hypothalamic-pituitary axis. Patients who develop endocrinopathies at younger ages have shown poorer quality of life in areas including emotional stability and social functionality[6,7]. These effects are maintained even throughout adulthood and are associated with increased lifetime medical costs[6,8]. The extent of post-radiation endocrinopathy appears to be a dose-dependentphenomenon, with growth hormone deficiency being the most common[2,9] This differential sensitivity suggests potential benefits from radiation techniques that offer increased sparing of the hypothalamic-pituitary axis. Another study 17, found no significant differences by modality

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Conclusion