TY - JOUR
T1 - Long-term safety of growth hormone replacement therapy after childhood medulloblastoma and PNET
T2 - it is time to set aside old concerns
AU - Indini, Alice
AU - Schiavello, Elisabetta
AU - Biassoni, Veronica
AU - Bergamaschi, Luca
AU - Magni, Maria Chiara
AU - Puma, Nadia
AU - Chiaravalli, Stefano
AU - Pallotti, Federica
AU - Seregni, Ettore
AU - Diletto, Barbara
AU - Pecori, Emilia
AU - Gandola, Lorenza
AU - Poggi, Geraldina
AU - Massimino, Maura
PY - 2017/10/21
Y1 - 2017/10/21
N2 - 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.
AB - 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.
KW - Brain tumors
KW - Childhood medulloblastoma
KW - GH
KW - Late-effect
UR - http://www.scopus.com/inward/record.url?scp=84992151544&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84992151544&partnerID=8YFLogxK
U2 - 10.1007/s11060-016-2306-7
DO - 10.1007/s11060-016-2306-7
M3 - Article
AN - SCOPUS:84992151544
VL - 131
SP - 349
EP - 357
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
SN - 0167-594X
IS - 2
ER -