D. Traish

Risk of second brain tumour after conservative surgery and radiotherapy for pituitary adenoma.

OBJECTIVE--To assess the risk of second brain tumour in patients with pituitary adenoma treated with conservative surgery and external beam radiotherapy. DESIGN--Long term follow up of a cohort of patients with pituitary adenoma and comparison of tumour occurrence with population incidence rates. SETTING--The Royal Marsden Hospital. SUBJECTS--334 patients with pituitary adenoma treated with conservative surgery and radiotherapy (median dose 45 Gy) and followed up for 3760 person years. MAIN OUTCOME MEASURES--Second intracranial tumour and systemic malignancy. RESULTS--Five patients developed a second brain tumour: two had astrocytoma, two meningioma, and one meningeal sarcoma. The cumulative risk of developing a second brain tumour over the first 10 years after treatment was 1.3% (95% confidence interval 0.4% to 3.9%) and over 20 years 1.9% (0.7% to 5.0%). The relative risk of a second brain tumour compared with the incidence in the normal population was 9.38 (3.05 to 21.89). There was no excess risk of any other type of second primary malignancy. CONCLUSIONS--There is an increased risk of second intracranial tumour in patients with pituitary adenoma treated with surgery and radiotherapy. Although radiation is likely to be the most important factor contributing to the excess risk, further study is required in a cohort of similar patients not receiving radiation.

The long-term efficacy of conservative surgery and radiotherapy in the control of pituitary adenomas

OBJECTIVES We assessed the long‐term efficacy and toxicity of conservative surgery and radiotherapy in the control of pituitary adenomas.

The incidence of cerebrovascular accidents in patients with pituitary adenoma

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.

Cerebrovascular mortality in patients with pituitary adenoma

Objective To assess cerebrovascular mortality in a UK cohort of patients with pituitary adenoma known to have increased incidence of cerebrovascular accidents (CVA).

Fractionated stereotactic conformal radiotherapy for secreting and nonsecreting pituitary adenomas

Objective  To assess the medium‐term outcome in a cohort of patients with residual or recurrent pituitary adenoma treated with fractionated stereotactic conformal radiotherapy (SCRT).

Short Intensive Primary Chemotherapy and Radiotherapy in Sporadic Primary CNS Lymphoma (PCL)

PURPOSE To assess the efficacy and toxicity of combined modality therapy with short intensive primary chemotherapy in the treatment of primary CNS lymphoma (PCL). METHODS AND MATERIALS Prospective study of 31 nonimmunodeficient patients with PCL treated with initial chemotherapy (13 shortened MACOP-B; and 18 modified MACOP with high dose methotrexate) followed by radiotherapy (whole brain and a boost). Patients were aged 18-72 years (median 51 years). Eight patients had positive CSF cytology of which one had spinal meningeal disease; one patient had vitreous involvement. RESULTS The overall complete response (CR) rate after chemotherapy and radiotherapy was 69% (95% Confidence Interval: 49-84%). At a median follow-up of 24 months (4 months to 10 years) median survival was 23 months and 5-year survival 34%. Age, sex, performance status, number of lesions, CSF cytology, and extent of surgery were not of prognostic significance for survival on univariate analysis. Eleven patients developed mucositis (Grade 3+) and 21 hematological toxicity (Grade 3+) with 22 septicemic episodes in 15 patients. Three patients developed dementia, one assumed to be treatment related, and two due to recurrent disease. CONCLUSION The survival results of short intensive primary chemotherapy followed by radiotherapy are similar to the results of chemotherapy in Stage IV aggressive systemic non-Hodgkins lymphoma, although the treatment was associated with high morbidity. The apparently favorable results when compared to radiotherapy alone may at least in part be due to selection of patients with good prognostic factors. To confirm the benefit of combined chemotherapy and radiotherapy over either of the two modalities alone requires evaluation in large prospective and ideally randomized studies.

Management of spinal astrocytoma with conservative surgery and radiotherapy.

Twenty-seven patients with histologically verified spinal astrocytoma were treated at the Royal Marsden Hospital with postoperative radiotherapy. All patients had previous surgery; 10 had partial resection and 17 biopsy alone. All patients received involved field radiotherapy to a median dose of 50 Gy in 33 fractions. Overall 5- and 10-year survival was 59 and 52%, and progression free survival was 38 and 26% at 5 and 10 years, respectively, at a median follow-up of 6.5 years. Following radiotherapy, eight patients showed functional improvement, 15 were unchanged and two deteriorated. Sixteen patients relapsed, eleven at the primary site and five elsewhere in the CNS. Low grade histology, female gender and the presence of intramedullary cysts were favourable prognostic factors for survival on univariate analysis. The extent of surgery was not a significant predictor of survival. It is not possible to define the precise role of radiotherapy. However, all patients had residual tumour prior to irradiation, and 53% of low grade and 33% of high grade gliomas remained controlled locally at 3 years with stabilization or improvement in neurological function in all but two patients. This suggests that radiotherapy may result in temporary disease control analogous to cerebral gliomas.

Temozolomide as second-line chemotherapy for relapsed gliomas.

AbstractBackground: Temozolomide, an imidazotetrazine prodrug has shown activity in phase II studies in patients with high-grade glioma at first recurrence. We assessed the efficacy of Temozolomide as second-line therapy following failure of PCV chemotherapy in patients with recurrent/progressive gliomas. Patients and methods: Between September 1994 and November 2000, 32 patients with high-grade gliomas at second recurrence/progression received Temozolomide as salvage therapy and results were received retrospectively. Results: Of 32 assessable patients 7 had clinical improvement; there were no imaging responses. Median survival of the cohort was 4 months, with 28% alive at 6 months. Age, performance status, histology and previous response to PCV chemotherapy did not predict for clinical response to Temozolomide. Conclusion: In the small cohort of patients with recurrent malignant glioma who failed PCV chemotherapy Temozolomide demonstrated limited activity as second-line treatment although this remains within the confidence intervals of response seen in patients with glioblastoma.

Haematological toxicity of cranio-spinal irradiation.

BACKGROUND To assess the frequency and severity of myelosuppression due to cranio-spinal irradiation either alone or in combination with chemotherapy and to identify patients at high risk of haematological toxicity who may require supportive therapy. MATERIALS AND METHODS Between 1965 and 1994, 210 patients received cranio-spinal axis (CSA) radiotherapy as a component of treatment for primary CNS tumours at the Royal Marsden Hospital. Full blood counts (FBC) were obtained before, during and after radiotherapy in 200 patients. Haematological toxicity was graded according to the WHO criteria and duration was measured from the onset of grades 3 and 4 toxicity until recovery to grade 2. RESULTS Sixty-six (33%) patients developed grades 3 and 4 haematological toxicity. Nadir occurred during radiotherapy and was most frequent during the second week of spinal radiotherapy. Low haemoglobin and white cell counts prior to radiotherapy increased the likelihood of myelosuppression. Nine patients had febrile episodes requiring antibiotic therapy. Treatment was interrupted in 49 patients but treatment time was extended beyond 12 weeks in only 17 (8%) patients of which nine were due to haematological toxicity. Chemotherapy (vincristine) during radiotherapy did not impact on haematological toxicity. Age and prior chemotherapy were independent predictive factors for haematological toxicity. The relative risk of leukopaenia in children compared to adults was 7.9 (95% CI 3.4-18.6%). Patients who received prior chemotherapy had a relative risk of toxicity of 6.1 (95% CI 2.9-12.8%). CONCLUSION One-third of patients undergoing CSA radiotherapy develop grades 3 and 4 haematological toxicity. The risk is higher in children and in patients who receive chemotherapy prior to radiation. There was no treatment-related mortality and only nine of 200 patients (9/60 of those with toxicity) required supportive treatment for neutropaenic sepsis. The low incidence severe haematological toxicity does not warrant routine use of haemopoietic growth factors during CSA irradiation and future studies should target high risk subgroups.

Somnolence syndrome in patients receiving radical radiotherapy for primary brain tumours: a prospective study.

BACKGROUND AND PURPOSE To characterise the incidence, pattern and severity of post cranial radiotherapy somnolence and to identify factors predictive of frequency and severity. MATERIALS AND METHODS Seventy consecutive patients receiving radical cranial irradiation were prospectively assessed for somnolence at baseline, during and up to 10weeks following radiotherapy using five variables scored on a visual analogue scale (VAS) and the Littman scale. Fatigue was measured using the FACT-G score and quality of life using the EORTC QLQC30+3 with the brain tumour module questionnaire. RESULTS Ninety percent of patients experienced ⩾grade 1 somnolence (Littman score) and this correlated with VAS scores (r=0.456, p<0.001). The score increased from 3 to 12weeks (p<0.001) with a peak at the end of treatment and improvement 6weeks later. None of the patient, disease or treatment characteristics analysed were predictive for the development or the severity of somnolence. CONCLUSIONS The majority of patients experience some degree of somnolence following radical radiotherapy for primary brain tumour and this follows a clear pattern during and after treatment. While there are no clear predictors of severity, the pattern described allows for provision of information for patients and carers to minimise the distress the syndrome may cause.