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Objective: To assess cerebrovascular mortality in a UK cohort of patients with pituitary adenoma known to have increased incidence of cerebrovascular accidents (CVA)., Methods: A total of 334 patients treated at the Royal Marsden Hospital (RMH) between 1962 and 1986 with surgery and postoperative radiotherapy were followed up via the NHS Central Register (NHSCR) to identify deaths and emigrations. The causes of death were assessed by NHSCR-based death certificates and coded according to the 9th revision of ICD. Follow-up was censored at age 85, on emigration or cancellation of NHSCR. Thirteen patients could not be traced. A total of 4982 person-years was accumulated in the cohort. Expected numbers of deaths were computed from the national age-, sex- and period-specific mortality rates for England and Wales., Results: In the pituitary adenoma cohort, 128 deaths were observed compared to 80.9 expected [relative risk (RR) of death 1.58 (95% CI: 1.32-1.90)]. There were 33 cerebrovascular deaths compared with 8.04 expected (RR 4.11, 95% CI 2.84-5.75). Three deaths were from subarachnoid haemorrhage compared to 0.54 expected (RR 5.51, 95% CI 1.14-16.09). There was an increased cerebrovascular mortality in women (RR 6.93, 95% CI 4.29-10.60) compared to men (RR 2.4, 95% CI 1.24-4.20; P = 0.002) and in patients having debulking surgery (RR 5.19, 95% CI 3.50-7.42) compared to biopsy/no surgery (RR 1.33, 95% CI 0.27-3.88; P = 0.02). The RR in patients with nonsecretory tumours was 3.65 (95% CI 2.26-5.58), compared with 5.23 (95% CI 2.25-10.30) in secretory tumours (P = 0.4). The effect of age at radiotherapy was not significant (P = 0.4)., Conclusion: Patients with pituitary adenoma treated with surgery and radiotherapy have an increased risk of cerebrovascular mortality compared to the general population, which mirrors the increased incidence of CVA. The possible risk factors include hypopituitarism, radiotherapy and extent of surgery but none are at present proven causes. The evaluation of new treatment strategies should not only assess intermediate end-points of tumour and endocrine control but should concentrate on long-term survival with particular emphasis on CVA incidence and mortality.

Objective: Stereotactic conformal radiotherapy (SCRT) is a high precision technique of fractionated radiotherapy which ensures accurate delivery of radiation with reduction in the volume of normal tissue irradiated as compared to conventional external beam radiotherapy. We describe the technique and preliminary experience of SCRT in patients with residual and recurrent pituitary adenomas., Patients and Methods: Between February 1995 and March 1999, 22 patients (mean age: 45.3, range: 20-67 years) with residual or recurrent pituitary adenomas (13 nonfunctioning, nine secretory) were treated with SCRT. All were immobilized in a relocatable Gill-Thomas-Cosman (GTC) frame and tumour was localized on a postcontrast planning computerized tomography (CT) and MRI scan. The gross tumour volume (GTV) and the critical structures were outlined on contiguous 2-3 mm separated slices. A margin of 5 mm (12 patients) to 10 mm (10 patients) was grown around GTV in three-dimensions (3-D) to generate the planning target volume (PTV). The treatment was delivered by three (five patients) and four (17 patients) maximally separated conformal fixed fields with each field conformed to the shape of the tumour using customized lead alloy blocks (19 patients) or multileaf collimator (three patients). The patients were treated on a 6-MV linear accelerator to a dose of 45 Gy in 25 fractions (18 patients) and 50 Gy in 30 fractions (four patients)., Results: The technique of SCRT has become a part of the routine work of the radiotherapy department. The treatment was well tolerated with minimal acute toxicity. One patient developed transient quadrantanopia 2 weeks after treatment with full recovery after a short course of corticosteroids. One patient had a transient visual deterioration 7 months after treatment due to cystic degeneration of the tumour which fully recovered following surgical decompression. Nine of the 15 patients presenting with visual impairment had improvement after treatment and the visual status remained stable in all others. One patient with acromegaly and one with a prolactinoma achieved normalization of elevated hormonal abnormality four and 10 months after SCRT, respectively. The remaining seven patients with a secretory adenoma had declining hormone levels at last follow-up. Newly initiated hormone replacement therapy was required in five patients. At a median follow-up of 9 months (range 1-44 months), the 1 and 2 year actuarial progression free and overall survival were 100%., Conclusion: Stereotactic conformal radiotherapy is a high precision technique suitable for the treatment of pituitary adenomas requiring radiotherapy. Preliminary results suggest effective tumour control and low toxicity within the range expected for conventional external beam radiotherapy. While the technique is of potential benefit in reducing the volume of normal brain irradiated, the advantages in terms of sustained tumour control and reduced toxicity over conventional radiotherapy need to be demonstrated in long-term prospective studies.

Background and Purpose: Patients with pituitary adenomas are effectively treated with a combination of surgery, radiotherapy, and medical therapy. Nevertheless, long-term studies suggest increased mortality that is independent of tumor control, with cerebrovascular accidents (CVA) as the major contributing cause. The purpose of this study was to define the frequency of CVAs in a cohort of patients with pituitary adenoma and identify potential predisposing factors., Patients and Methods: A cohort of 331 United Kingdom (UK) residents with pituitary adenoma treated at the Royal Marsden Hospital (RMH) between 1962 and 1986 was studied. The frequency of CVA was assessed from RMH and referring hospital records and clinicians, by postal questionnaire of referring hospitals and general practitioners, and by examination of all death certificates. The data were analyzed by actuarial methods, and risk factors were assessed by multivariate analysis. The data were compared to the incidence of CVA in the general population using a published UK population cohort., Results: Sixty-four of 331 patients developed CVA after primary treatment of pituitary adenoma. The actuarial incidence of CVA was 4% (95% CI: 2-7%) at 5 years, 11% (95% CI: 8-14%) at 10 years, and 21% (95% CI: 16-28%) at 20 years measured from the date of radiotherapy. The relative risk of CVA compared to the general population in the UK was 4.1. Age was an independent predictive factor for CVA. However, the relative risk in comparison to the general population was independent of age. The relative risk of developing CVA was higher in women compared to men, in patients undergoing debulking surgery compared to less radical procedures, and in patients diagnosed and treated in the 1980s compared to previous decades. The dose of radiotherapy was an additional independent prognostic factor on multivariate analysis., Conclusion: Patients with pituitary adenoma treated with surgery and radiotherapy have a significantly increased risk of CVA compared to the general population. The factors which may contribute to the increased risk include the presence of pituitary adenoma and consequent endocrine disturbances and the treatment, particularly the extent of surgery and the dose of radiotherapy. When assessing the value of treatment strategies, it is therefore important to include not only intermediate endpoints of tumor and hormonal control, but also late toxicity, including the incidence of CVA and overall survival as the primary endpoint. The potential predisposing factors for CVA need further elucidation to develop treatment strategies with lower risk and consequently, reduced mortality.