Growth hormone replacement therapy does not predict relapse across medulloblastoma subgroups

Abstract Background Treatment for medulloblastoma can lead to significant long-term endocrine sequelae, including growth hormone (GH) deficiency. There has been some concern that GH replacement can increase the risk of tumor relapse. Our goal was to assess the risk of recurrence after GH therapy in medulloblastoma (MB) patients treated with ­modern, molecularly informed protocols. Methods We conducted a retrospective observational cohort study at a tertiary pediatric hospital from January 1999 to December 2022. Patients < 18 years old with MB who received craniospinal irradiation (CSI) were included, treated according to contemporary risk-adapted protocols. Epidemiological, molecular, and clinical data were collected. Results A total of 148 patients with MB were treated with CSI, with a median age of 8.3 years (IQR 5.9-10.8). The molecular subgroups included Group 4 (n = 69, 46.6%), Group 3 (n = 27, 18.2%), WNT (n = 21, 14.2%), and SHH (n = 20, 13.5%). During follow-up, 79 patients (53.4%) were diagnosed with GH deficiency, and 73 of them initiated GH therapy. We found no association between sex (P = 1), presence of metastases (P = .14), or molecular subgroup (P = .71) and the use of GH therapy. Thirty-four patients (22.9%) relapsed during follow-up, with 10 of them receiving GH therapy (13.7% of all patients on GH). Progression-free survival (PFS) was higher among those who received GH replacement therapy, even within each subgroup independently. In a multivariate analysis of patients who had not relapsed at least 2 years post-diagnosis, GH replacement was associated with significantly improved overall survival (OS) and a trend toward improved PFS (PFS: HR 0.35, 95% CI, 0.12-1.08, P = .068; OS: HR 0.34, 95% CI, 0.12-0.99, P = .049). Conclusions The use of GH is not associated with an increased risk of recurrence or death in children with medulloblastoma treated with CSI according to current protocols. Our results provide further reassurance that all children with requiring treatment for growth hormone deficiency after medulloblastoma therapy should be offered physiological growth hormone replacement.