Table 1.

The questions and key summary statements from the consensus workshop on safety of growth hormone treatment in survivors of cancer and intracranial tumours.

What is the role of GH-IGF-I in tumour genesis? In vitro and in vivo models Preclinical data suggest that GH and IGF-I are involved in cancer development. It is not clear how to reconcile the convincing and concerning in vitro/in vivo data with the reassuring clinical data related to GH replacement and development of cancers. What is the role of GH-IGFI in tumour genesis? Epidemiology Epidemiological studies have shown an association between serum IGF-I levels in the higher normal reference range and an increased risk of certain cancer types, but it is not clear that markedly excessive GH levels in acromegaly are independently associated with increased cancer occurrence. Is GH replacement associated with a higher risk of recurrence of the primary cancer/tumour? Current evidence does not support an association between GH replacement therapy and primary tumour or cancer recurrence in GHD survivors. Is GH replacement associated with a higher risk of a secondary neoplasm? The specific effect of GH replacement on secondary neoplasia risk is minor in comparison to host and tumour treatment-related factors. Is GH replacement associated with a higher risk of death from cancer? Current evidence does not support an association between treatment with GH and increased mortality from cancer among GHD childhood cancer survivors. Should GH replacement be considered in an adult patient previously treated for cancer? GH replacement might be considered in GHD adult cancer survivors (either with childhood- or adult-onset cancer) in remission after careful individual risk/benefit analysis. Should GH replacement therapy be avoided in patients who are in remission from certain malignancies? A decision to prescribe GH replacement therapy in GHD patients with breast, colon, prostate, or liver cancer in remission should be made on a case-by-case basis after detailed counseling about possible risks and benefits and in close conjunction with the treating oncologist. Are there specific considerations related to diagnosing GHD in cancer and intracranial tumour survivors? Specific considerations include the limited reliability of IGF-I levels as a marker for GHD, avoiding the use of GHRH for dynamic testing in patients who have received cranial irradiation, and the need to take into account the presence of other endocrine deficiencies for the interpretation of clinical and laboratory data. Should GH replacement (dosing, serum IGF-I target, monitoring, and transition) be different in patients surviving cancer? GH replacement dosing and monitoring in cancer survivors follow the general recommendations, but closer vigilance is required to avoid over-treatment. How long should providers wait between completion of therapy for cancer or intracranial tumour and the initiation of GH therapy? The timing of initiation of GH therapy following completion of cancer therapy or treatment of an intracranial tumour depends on many factors and should be individualized as a joint decision between treating physicians, patient, and caregivers. This period may be as early as 3 months in children with radiologically proven stable craniopharyngiomas who have significant growth failure and metabolic disturbance and up to at least 5 years in adults with a history of solid tumour such as breast cancer. Are there any specific side effects that may occur after short- and long-term GH replacement? Some side effects related to GH replacement in children occur more frequently among cancer survivors, such as increased intracranial pressure, slipped capital femoral epiphysis, and worsening of scoliosis. In adults, there are no data to suggest a different side-effect profile. Should GH replacement therapy be modified in patients with pituitary tumour or craniopharyngioma after primary surgery? Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH replacement. Are there special considerations for GH replacement in patients who are on long-term therapy with a tyrosine kinase inhibitor/other chronic therapies for tumour control? For patients with a stable low grade glioma or those on long-term therapy with a tyrosine kinase inhibitor/other chronic therapy, there should be shared decision-making between oncologist, endocrinologist, and the patient/family when considering GH therapy. If cancer occurs in the context of a cancer predisposing genetic condition or strong family history of cancers, should there be additional considerations in starting GH therapy? In children with cancer predisposition syndromes, GH treatment is usually contraindicated but it may be cautiously considered in particular cases with proven GHD. There are no data justifying an absolute contraindication for GH replacement in GH-deficient patients with a strong family history of cancer, so each case needs to be considered individually. Is there a role for long-acting GH (LAGH) preparations in cancer survivors? At this time, there are no data to support LAGH use in cancer survivors.

The key statements in the table should be interpreted in the context of their associated text in the core consensus document.