Long term toxicity and prognostic factors of radiation therapy for secreting and non-secreting pituitary adenomas

Abstract

BackgroundRadiotherapy is controversially discussed in the management of benign disorders for fear of late sequelae such as tumor induction. This study was initiated to investigate long-term toxicity, treatment outcome and prognostic factors after radiotherapy (RT) in patients with pituitary adenomas.Methods92 patients with pituitary adenomas were included in this analysis. RT was conducted using either 3D conformal (16%) or fractionated stereotactic techniques (83%) in a postoperative adjuvant setting (16%), as second-line treatment for recurring tumors (78%) or as primary treatment (6%). Postoperatively, RT was offered to patients with residual tumor tissue or in case of locally extensive adenomas, in whom early recurrence was deemed likely. Patients were followed for a median time of 152.5 months, and analysed for overall and local progression-free survival (OS and LPFS). Multiple factors were analysed for prognostic impact. Patients were contacted with an institutional questionnaire about qualiy of life (QOL). Statistical analysis was performed using the log-rank test and the Kaplan-Meier method using a software tool (SPSS 19.0).ResultsMedian follow-up was 152.5 months. Before treatment, 2% of all patients were diagnosed with adenoma-related hypopituitarism. Following surgery, 68% suffered from new pituitary deficits. RT was associated with mild toxicity, including visual deficits (5.4%) and hypopituitarism (10.9%). In particular, no radiation-induced brain necrosis or malignancy was observed. QOL was reported to be stable or improved in 92% of all patients, and RT was perceived to not compromise but increase QOL in the vast majority of patients (95%). OS after RT was 93.3% and 61.0% at 120 and 240 months. LPFS following RT was 90.4 and 75.5% at 120 and 240 months. Early initiation of RT after surgery instead of reserving it for recurring adenomas predisposed for improved outcome.ConclusionsRT for pituitary adenomas is safe and and self-reported QOL is stable or improved by almost all patients. Hypopituitarism rates are low. Local control appears improved in patients irradiated postoperatively over those undergoing RT for previously resected recurrent tumors.

The Efficacy of Early Postoperative Radiotherapy for Non-Functioning Pituitary Macro Adenomas, with Tumour Cells Expressing or not Expressing Pituitary Hormones

“…Early initiation of RT after surgery instead of reserving RT for recurring adenomas led to an improved outcome. Radiogenic hypopituitarism was detected more frequently in the patients who underwent irradiation for recurrent tumours than in those who were subjected to immediate postoperative RT (43).…”

A Phase I Study of Tomotherapy in Patients With Primary Benign and Low-grade Brain Tumors

“…40 In terms of study limitations, the questionnaires chosen (EORTC QOL 30, BN 20, MMSE, and KPS) have been fully validated mainly in brain metastases and purely benign brain tumors and are based completely on subjective patient opinion. Hence, they might not fully reflect the global picture of toxicity potentially present but not detected.…”

MANAGEMENT OF ENDOCRINE DISEASE: Neuroendocrine surveillance and management of neurosurgical patients

“…This theory is also supported by the common occurrence of hyperprolactinemia after irradiation, which is considered to result from a reduction in hypothalamic release of dopamine (95) although there is also evidence to suggest that cranial radiation causes direct pituitary damage (96). Direct pituitary damage is also suggested by the observation that stereotactic radiotherapy, which spares the hypothalamus, also causes hypopituitarism (97). The somatotroph axis is the most vulnerable to the effects of RT.…”