Long-term safety of growth hormone replacement after CNS irradiation.
ABSTRACT Radiotherapy is a central component in the treatment of many brain tumors, but long-term sequelae include GH deficiency and increased risk of secondary neoplasms. It is unclear whether replacement therapy with GH (GHRT) further increases this risk.
The objective of the study was to assess the effect of GHRT on the incidence of secondary tumors and tumor recurrence after cranial irradiation.
We conducted a retrospective matched-pairs analysis of previously irradiated patients, with and without GHRT, attending a tertiary center between 1994 and 2009. Patients: We reviewed the records for all patients undergoing GHRT at our institution over the study period. Patients were included if they had received cranial irradiation, GHRT for at least 12 months, and records of serial magnetic resonance imaging data and data for dose and fractionation of irradiation were available. GH-naïve control patients were selected from a radiotherapy database of patients attending the same hospital. Patients were matched for date of radiotherapy, age, site of primary diagnosis, radiation dose, and fractionation.
The primary outcome measure was risk of tumor recurrence or secondary tumor.
Matched controls were identified for 110 GH-treated patients. Median follow-up was 14.5 yr. No significant differences were apparent in the number of tumor recurrences (six vs. eight, GHRT vs. control group) or secondary tumors (five vs. three, respectively) between groups.
Our study demonstrates no increased risk for recurrent or secondary neoplasms in patients receiving GHRT, thus supporting a high safety profile of GHRT after central nervous system irradiation.
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ABSTRACT: OBJECTIVE: CHILDHOOD CANCER SURVIVORS ARE COMMONLY TREATED WITH GROWTH HORMONE (GH) FOR GH DEFICIENCY THAT DEVELOPS EITHER AS A RESULT OF PRIMARY MALIGNANCY OR ITS TREATMENT. ONE STUDY - THE CHILDHOOD CANCER SURVIVOR STUDY (CCSS) - DEMONSTRATED INCREASED RISK OF SECOND NEOPLASM (SN) IN GH-TREATED CHILDHOOD CANCER SURVIVORS COMPARED TO NON-GH-TREATED, AFTER ADJUSTING FOR KEY RISK FACTORS. WE ASSESSED THE INCIDENCE OF SN IN GH-TREATED CHILDHOOD CANCER SURVIVORS IN OUTPATIENT OBSERVATIONAL STUDIES OF GH REPLACEMENT.DESIGN: RETROSPECTIVE ANALYSIS OF TWO PROSPECTIVE COHORT STUDIES THAT COLLECTED DATA ON SAFETY OF GH REPLACEMENT AS PRESCRIBED IN CLINICAL PRACTICE.METHODS: CHILDHOOD CANCER SURVIVORS ENROLLED IN ELI LILLY AND COMPANY'S PEDIATRIC (GENESIS: Genetics and Neuroendocrinology of Short Stature International Study) and adult (HypoCCS: Hypopituitary Control and Complications Study) observational studies of GH treatment were assessed for incidence of SN.Results: The percentage of childhood cancer survivors treated with GH who developed a SN was 3.8% in pediatric GeNeSIS participants and 6.0% in adult HypoCCS participants. The estimated cumulative incidence of SN at 5 years of follow-up in these studies was 6.2% and 4.8%, respectively.Conclusions: The incidence of SN in GeNeSIS and HypoCCS GH-treated participants is similar to the published literature, and thus is consistent with increased risk of SN in childhood cancer survivors treated with GH. As follow-up times were relatively short (< 3 years), longer observation is recommended. Nevertheless, clinicians should be alerted to the possibility of increased risk of SN in childhood cancer survivors treated with GH and continue chronic surveillance.European Journal of Endocrinology 01/2013; · 3.14 Impact Factor
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ABSTRACT: Balancing bone resorption and formation is the quintessential component for the prevention of osteoporosis. Signals that determine the recruitment, replication, differentiation, function, and apoptosis of osteoblasts and osteoclasts direct bone remodeling and determine whether bone tissue is gained, lost, or balanced. Therefore, understanding the signaling pathways involved in the coupling process will help develop further targets for osteoporosis therapy, by blocking bone resorption or enhancing bone formation in a space- and time-dependent manner. Insulin-like growth factor type 1 (IGF-1) has long been known to play a role in bone strength. It is one of the most abundant substances in the bone matrix, circulates systemically and is secreted locally, and has a direct relationship with bone mineral density. Recent data has helped further our understanding of the direct role of IGF-1 signaling in coupling bone remodeling which will be discussed in this review. The bone marrow microenvironment plays a critical role in the fate of mesenchymal stem cells and hematopoietic stem cells and thus how IGF-1 interacts with other factors in the microenvironment are equally important. While previous clinical trials with IGF-1 administration have been unsuccessful at enhancing bone formation, advances in basic science studies have provided insight into further mechanisms that should be considered for future trials. Additional basic science studies dissecting the regulation and the function of matrix IGF-1 in modeling and remodeling will continue to provide further insight for future directions for anabolic therapies for osteoporosis.Journal of Molecular Medicine 09/2013; · 4.77 Impact Factor