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Long-term safety of growth hormone replacement therapy after childhood medulloblastoma and PNET: it is time to set aside old concerns

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Abstract

To assess the long-term safety of administering growth hormone (GH) in patients with GH deficiency due to treatment for childhood medulloblastoma and primitive neuroectodermal tumor (PNET). Data were retrospectively retrieved on children receiving GH supplementation, assessing their disease-free and overall survival outcomes and risk of secondary malignancies using Kaplan–Meier and Cox models. Overall 65 children were consecutively collected from May 1981 to April 2013. All patients had undergone craniospinal irradiation (total dose 18–39 Gy), and subsequently received GH for a median (interquartile range, IQR) of 81 (50.6–114.9) months. At a median (IQR) of 122.4 months (74.4–149.5) after the end of their adjuvant cancer treatment, two patients (3 %) experienced recurrent disease and 8 (12.3 %) developed secondary malignancies, all but one of them (an osteosarcoma) related to radiation exposure and occurring within the radiation fields. There was no apparent correlation between the administration of GH replacement therapy (or its duration) and primary tumor relapse or the onset of secondary malignancies [HR: 1.01 (95 % CI: 0.98, 1.03) for every additional 12 months of GH supplementation; p = 0.36). At univariate analysis, the large cell or anaplastic medulloblastoma subtype, metastases and myeloablative chemotherapy correlated with a higher risk of secondary malignancies (p < 0.1), but multivariate analysis failed to identify any factors independently associated with this risk. Our data supports once more the safety of long-term GH replacement therapy in children treated for medulloblastoma/PNET, previously reported in larger data sets. The neurooncology community now need to warrant large-scale meta-analyses or international prospective trials in order to consolidate our knowledge of factors other than GH, such as genetic predisposition, high-grade/metastatic disease, high-dose chemotherapy and era of treatment, in promoting the occurrence of secondary malignancies.

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Authors and Affiliations

  1. Pediatric Oncology Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy

    Alice Indini, Elisabetta Schiavello, Veronica Biassoni, Luca Bergamaschi, Maria Chiara Magni, Nadia Puma, Stefano Chiaravalli & Maura Massimino

  2. Nuclear Medicine Units, Fondazione IRCCS, Istituto Nazionale Tumori, Milan, Italy

    Federica Pallotti & Ettore Seregni

  3. Radiotherapy Units, Fondazione IRCCS, Istituto Nazionale Tumori, Milan, Italy

    Barbara Diletto, Emilia Pecori & Lorenza Gandola

  4. Acquired Brain Injury Unit, Scientific Institute, IRCCS Eugenio Medea, Milan, Italy

    Geraldina Poggi

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  1. Alice Indini
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Correspondence to Alice Indini.

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11060_2016_2306_MOESM1_ESM.docx

Supplemental Figure 1: Diagram showing the flow of patients across the time of the study. Abbreviation: Y, yes; N, no; CSI, craniospinal irradiation; GHRT, Growth hormone replacement therapy; PNET, primitive neuroectodermal tumor. (DOCX 33 KB)

11060_2016_2306_MOESM2_ESM.docx

Supplemental Figure 2: Risk of secondary malignancies by treatment protocol and decade of primary diagnosis. Number of children treated on different time period (1980-1989: n=3; 1990-1999: n=9; 2000-2009: n=48; 2010-2013: n=5). (DOCX 2942 KB)

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Indini, A., Schiavello, E., Biassoni, V. et al. Long-term safety of growth hormone replacement therapy after childhood medulloblastoma and PNET: it is time to set aside old concerns. J Neurooncol 131, 349–357 (2017). https://doi.org/10.1007/s11060-016-2306-7

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  • DOI: https://doi.org/10.1007/s11060-016-2306-7

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