Radiosurgery for brain tumours.
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Brain Neoplasms↗
Biomedical subjects
M Brada
Publications and source records attributed to M Brada.
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-Hodgkin's 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.
Adolescent↗
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.
Adolescent↗
Somnolence syndrome in adults following cranial irradiation for primary brain tumours.
The purpose of this study was to assess the incidence, pattern and severity of somnolence and fatigue in patients treated with cranial irradiation for primary brain tumours and to identify factors that may influence or mediate symptoms. A detailed prospective study was carried out of 19 patients who received high-dose (45-55 Gy) cranial irradiation as treatment for primary brain tumours. Data were collected for each patient over a 3 month period using a prospective diary utilizing visual analogue scales of common somnolence symptoms and fatigue, and detailed interviews at 2, 6 and 12 weeks following the completion of treatment. Sixteen patients developed somnolence syndrome following treatment. Time series analysis identified a cyclical pattern to the symptoms, with a period of drowsiness and fatigue occurring from day 11 to day 21 and from day 31 to day 35 after radiotherapy. The principal symptoms were those of excessive drowsiness, feeling clumsy, an inability to concentrate, lethargy, being mentally slow and fatigue. Patients treated with accelerated (n = 11) compared with more conventional (n = 8) fractionation experienced more severe drowsiness and fatigue (P < 0.01), although there was no difference in the pattern or the incidence of symptoms. Interview data suggested that patients frequently attributed their symptoms of somnolence to 'flu or other ailments. The unexplained and overwhelming nature of the symptoms was a cause of anxiety. The prospective assessment of symptoms following radiotherapy highlighted a more detailed definition of the symptom complex and pattern of occurrence. Somnolence syndrome is a collection of symptoms consisting of drowsiness, lethargy and fatigue. Forewarning patients and planning supportive management around times of drowsiness and fatigue can help to reduce the anxiety that these symptoms cause.
Adult↗
Whole body doses from linear accelerator-based stereotactic radiotherapy.
PURPOSE: The objective of this work was to measure whole body radiation doses in a humanoid phantom from linear accelerator-based cranial stereotactic radiosurgery/therapy (SRS/T), using different beam arrangements. METHODS AND MATERIALS: A standard noncoplanar five-arc beam arrangement and a four-arc technique without a sagittal arc were used to deliver 20 Gy in a single fraction to a midline spherical target volume in the corpus callosum region of an Alderson-Rando anthropomorphic phantom using (i) a 20-mm and (ii) a 40-mm circular collimator. Whole body dose measurements were made using lithium fluoride thermoluminescent dosimetry. Whole body isodose plots in the sagittal and coronal planes and organ doses were compared for the two arcing beam arrangements. An ionization chamber was used to record the exit dose at intervals along the length of the phantom at midline and 4.5 cm off-axis for (i) a single fixed field and (ii) a solitary 90 degrees sagittal arc using a 40-mm circular collimator. RESULTS: The sagittal arc was the major contributor to neck and trunk doses when the five- and four-arc arrangements were compared, with fourfold greater thyroid dose. The gonad dose was increased by the sagittal arc, but was largely due to leakage radiation. The dose from a fixed field exiting down the long axis of the phantom was tenfold greater than that from a solitary 90 degrees sagittal arc. When the fixed field or arc traversed the lung or exited through the pharynx and major upper airways, the dose measurements below the diaphragm were 30-40% higher than those along the exit path of maximum soft tissue density. CONCLUSION: When SRS/T is used in nonmalignant conditions such as cranial arteriovenous malformations or benign tumors the exit paths of arcing beams or fixed fields should be taken into account when deciding upon the final treatment plan. Such consideration should minimize the risk of radiation-induced malignancy, notably in the thyroid gland of younger patients.
Particle Accelerators↗
Malignant cerebral glioma. Modern radiotherapy can give good quality survival for six months.
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Brain Neoplasms↗
Malignant cerebral glioma. Patients should be treated in specialist units.
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Brain Neoplasms↗
Craniopharyngioma: improving outcome by early recognition and treatment of acute complications.
PURPOSE: To assess the frequency, mode of presentation, treatment, and outcome of acute complications in patients with craniopharyngioma around the time of radiotherapy. METHODS AND MATERIALS: A review was made of 188 patients with craniopharyngioma treated with conservative surgery and external beam radiotherapy at the Royal Marsden Hospital between 1950 and 1992. RESULTS: Twenty six (14%) (95% confidence interval: 9-19%) patients with craniopharyngioma developed acute deterioration immediately before, during and 2 months after radiotherapy with visual deterioration (19 patients), hydrocephalus (7 patients), and global deficit (7 patients). Cystic enlargement with or without hydrocephalus was the most common cause of deterioration. No patient or disease characteristics were predictive of deterioration on univariate or multivariate analysis. Eighteen patients had surgical intervention at the time of deterioration and survived the immediate period. Six of seven patients who did not have surgical intervention died. All patients who survived the postcomplication period completed the full course of external beam radiotherapy. The 10-year progression-free survival of 162 patients without deterioration was 86%, and of 18 patients with acute deterioration who recovered after surgery, 77%. CONCLUSION: Patients with craniopharyngioma develop acute deterioration around the time of radiotherapy owing to cystic enlargement and/or hydrocephalus which does not represent tumor progression. Early recognition and appropriate surgical treatment followed by conventional full-dose radiotherapy are associated with good long-term outcome.
Adolescent↗
Hypofractionated stereotactic radiotherapy in the management of recurrent glioma.
PURPOSE: This study aimed to assess the efficacy and toxicity of hypofractionated stereotactic radiotherapy (SRT) in the management of patients with recurrent glioma. METHODS AND MATERIALS: From January 1989 to July 1994, 36 patients with glioma were treated at the time of recurrence. Twenty-nine had recurrent high-grade astrocytoma, 3 high-grade oligodendroglioma, 1 high-grade ependymoma, and 3 pilocytic astrocytoma. Hypofractionated stereotactic radiotherapy was given using either three noncoplanar arcs or four to six noncoplanar fixed beams at 5 Gy/fraction, to doses ranging from 20 to 50 Gy initially on a dose escalation program. Two patients received 20 Gy, 8 received 30 Gy, 10 received 35 Gy, 10 received 40 Gy, 5 received 45 Gy, and 1 received 50 Gy, treating 5 days/week. RESULTS: The median survival of 29 patients with recurrent high-grade astrocytoma was 11 months from the time of SRT. This compared to a median survival of 7 months for a cohort matched for age, performance status, and initial histologic grade who received nitrosourea-based chemotherapy at recurrence (p < 0.05). Initial low-grade astrocytoma histology was the only favorable prognostic factor for survival on univariate analysis. Three patients with recurrent oligodendroglioma remain alive 11, 23, and 34 months after SRT. Three children treated for recurrent pilocytic astrocytoma remain alive 14, 41, and 55 months following SRT. Presumed radiation damage, defined as reversible steroid-dependent toxicity, was observed in 13 patients (36%) and required reoperation in 2 (6%). A total dose of >40 Gy was a major predictor of radiation damage (p < 0.005). CONCLUSION: Hypofractionated SRT is a noninvasive, well-tolerated, outpatient-based method of delivering palliative, high-dose, focal irradiation.
Adult↗
Multicentre CRC phase II trial of temozolomide in recurrent or progressive high-grade glioma.
PURPOSE: Patients with progressive or recurrent supratentorial high-grade gliomas were entered into a multicentre phase II trial to evaluate the efficacy and toxicity of temozolomide. METHODS: The treatment schedule was 150-200 mg/m2 per day orally for 5 days repeated every 28 days. Response evaluation was by a combination of neurological status evaluation (MRC scale) and imaging. RESULTS: Of 103 eligible patients enrolled, 11 (11%) achieved an objective response and a further 48 (47%) had stable disease. The median response duration was 4.6 months. Response rates were similar for anaplastic astrocytomas (grade III) and glioblastoma multiforme (grade IV) tumours. Predictable myelosuppression was the major toxicity. CONCLUSIONS: The observation of objective responses and tolerable side effects in this heterogeneous population of patients supports the further investigation of this agent in high-grade gliomas.
Adult↗
The content and efficacy of conventional methods of follow-up in neuro-oncology: the need for new strategies.
In a combined retrospective and prospective analysis, we examined the content and outcome of conventional follow-up of patients with malignant brain tumours. Most consultations consisted of discussion and advice from the clinic doctor or nurse in certain well defined areas. Clinical examination, including neurological examination, was ineffective at detecting tumour recurrence. All recurrences presented with clinical features noted by the patient or by carers prior to the clinic attendance. The analysis of content and outcome of conventional outpatient consultation suggests that patients with high grade gliomas might be better served by methods of follow-up other than routine hospital attendance. There is a need to develop new follow-up strategies which are patient orientated and which address issues specific to the disease type other than tumour recurrence alone.
Brain Neoplasms↗
Verbally administered Barthel Index as functional assessment in brain tumour patients.
OBJECTIVE: To investigate verbally administered Barthel Index as a measure of functional status in patients with high grade gliomas. BACKGROUND: Barthel Index (BI) is a performance score of activities of daily living which has been validated in patients with neurological disability. While any assessment of quality of life in brain tumour patients should include all the aspects of CNS function we concentrated on measurement of physical performance status and evaluated the role of BI as a measure of palliative effect of treatment in patients with high grade glioma undergoing radiotherapy. METHODS: BI was verbally administered on 504 occasions in 107 patients with high grade glioma. The BI scores were correlated with Karnofsky performance score (KPS), and neurological performance score (NPS) as a measure of inter-index reliability. The BI's prognostic value was assessed using actuarial survival data. RESULTS: BI was sensitive to change and reflected the degree of functional impairment. In patients with high grade glioma BI correlated with KPS, and NPS (R2 = 0.872 and 0.658 respectively). BI score was also of prognostic value in terms of survival. The median survival of patients with functional independence was 9 months with moderate disability 5 months and with severe disability 4 months. CONCLUSION: Verbally administered Barthel Index is easy to use, reliable and sensitive to change and is of prognostic value. It is a useful tool in the management of patients with gliomas, as an objective evaluation of palliative effectiveness of treatment in patients with functional disability.
Activities of Daily Living↗
Effect of neurological dysfunction on health-related quality of life in patients with high-grade glioma.
The purpose of the study was to assess health-related quality of life (HQL) in patients with high-grade malignant glioma of the brain. The EORTC core Quality of Life Questionnaire (QLQ-C30) and a Brain Cancer Module (BCM20) were administered at baseline and several weeks later (follow-up) to 105 patients with either recently-diagnosed (n = 41) or recurrent (n = 64) malignant glioma. In addition, the attending neurologists completed a standard neurological examination, a modified Barthel Activities of Daily Living Index (BADLI) and the Karnofsky Performance Scale (KPS). In a preliminary step, the QLQ-C30 was found to have acceptable reliability (internal consistency and test-retest reliability). Newly-diagnosed patients and those with a KPS of 80-100 had significantly better physical, role and cognitive functioning and global quality of life with less fatigue, visual disorder, motor dysfunction, communication deficit, weakness of both legs and trouble controlling the bladder than did those with recurrent disease and those with a KPS of 50-70. Similarly, those capable of independent activities of daily living, as reported on the BADLI, had higher functioning scores and less fatigue than did those who were not independent. Patients with dysphasia, mental confusion or motor deficit on neurological examination reported significantly lower levels of physical, role, cognitive, emotional and social functioning and global quality of life than did patients not having these difficulties. They also had significantly more symptoms. In patients with deteriorating neurological status between baseline and follow-up, there was a marked decline in cognitive, physical, role, emotional and social functioning and global quality of life and an increase in fatigue. Thus, there are significant differences in HQL between patients with newly-diagnosed and recurrent brain cancer and between patients with differing KPS and BADLI scores. In addition, the HQL scores provide details not provided by the KPS and the BADLI. Deterioration in neurological function is accompanied by significant deterioration in a range of HQL domains and in global quality of life.
Adolescent↗
The use of significant others as proxy raters of the quality of life of patients with brain cancer.
OBJECTIVES: The use of self-report questionnaires for the assessment of health-related quality of life (HRQOL) is increasingly common in clinical research. This method of data collection may be less suitable for patient groups who suffer from cognitive impairment, however, such as patients with brain cancer. In such cases, one can consider employing the patients' significant others as proxy raters of the patients' health-related quality of life. The authors examined the response agreement between patients with brain cancer and their significant others on a health-related quality of life instrument commonly used in cancer clinical trials, the EORTC QLQ-C30, and on a brain cancer-specific questionnaire module, the QLQ-BCM. METHODS: The study sample consisted of 103 pairs of patients, with either recently diagnosed or recurrent brain cancer, and their significant others (75% spouses, 22% relatives, and 3% friends). Patients and proxies independently completed the EORTC QLQ-C30 and the QLQ-BCM at three different times. RESULTS: Approximately 60% of the patient and proxy scores were in exact agreement, with more than 90% of scores being within one response category of each other. For most HRQOL dimensions assessed, moderate to good agreement was found. Statistically significant differences in mean scores were noted for several dimensions, with proxies tending to rate the patients as having a lower quality of life than the patients themselves. With the exception of fatigue ratings, this response bias was of a limited magnitude. Less agreement and a more pronounced response bias was observed for the more impaired patients, and particularly for patients exhibiting mental confusion. This finding was confirmed by longitudinal analyses, which indicated lower levels of patient-proxy agreement at follow-up for those patients whose physical or neurologic condition had deteriorated over time. CONCLUSIONS: In general, patients and their significant others provide similar ratings of the patients' quality of life. Lower levels of agreement and more biased ratings can be expected among those patients for whom the need for proxies is most salient. It is argued, however, that discrepancies between patient-proxy ratings should not be interpreted, a priori, as evidence of the inaccuracy or biased nature of proxy-generated data. Future studies are needed to examine the relative validity and reliability of patient-versus proxy-generated health-related quality of life scores.
Adolescent↗
Enteropathy associated T cell lymphoma presenting as an isolated CNS lymphoma three years after diagnosis of coeliac disease: T cell receptor polymerase chain reaction studies failed to show the original enteropathy to be a clonal disorder.
A case of enteropathy associated T cell lymphoma is reported in a 45 year old woman, presenting with isolated disease in the CNS, three years after diagnosis of coeliac disease. Initial staging showed no evidence of gastrointestinal tract lymphoma. A presumptive diagnosis of T cell primary cerebral lymphoma was made and the patient was treated with combination chemotherapy and craniospinal radiotherapy. The patient relapsed, seven months after treatment, with small bowel lymphoma. The immunophenotype and T cell receptor polymerase chain reaction analysis confirmed the same tumour as in the CNS. Retrospective polymerase chain reaction analysis of intraepithelial lymphocytes in the duodenal biopsy sample, taken at the time of diagnosis of coeliac disease, failed to show evidence of a clonal T cell proliferation.
Brain Neoplasms↗
The development and psychometric validation of a brain cancer quality-of-life questionnaire for use in combination with general cancer-specific questionnaires.
A self-report questionnaire module consisting of 24 items, comprising 5 scales and 7 single items, has been developed for measuring health-related quality of life in patients with brain cancer. Module development proceeded through several stages, including a listing of patient, family and health care professional concerns, the writing of items, field testing in 105 patients with brain cancer and subsequent item reduction and scale construction after multitrait scaling analysis and assessment of internal consistency (Cronbach's coefficient alpha). The final version of the module exhibits reasonable test-retest stability over a period of one week. Differences in the responses between patients with recently-diagnosed and recurrent cancer and between patients with a Karnofsky Performance Score (KPS) of 50-70 and 80-100 were in the expected direction, indicating that the module of questions is responsive to differing conditions. Patients with either mental confusion, motor deficit or dysphasia indicated problems in several domains and single items as compared to patients without these neurological deficits. Thus, differences in the responses to the items in the brain cancer module appear to reflect differences in neurological status. In addition, deteriorating neurological status was accompanied by a marked increase in emotional distress, future uncertainty and motor dysfunction. A comparison of the responses in the module with the KPS and with a modified Barthel Activities of Daily Living Index (BADLI) shows moderate correlations, primarily with scales and items that pertain to motor dysfunction, while other scales (such as emotional distress, visual disorder and communication deficit) and most single items are not associated with the KPS or BADLI. Since the emotional distress scale of the module was found to be highly correlated with the emotional function scale of the EORTC QLQ-C30, it could be omitted when the module is used in combination with the QLQ-C30. This would reduce the module to a total of 20 items with four scales and seven single items. The intention is to combine this module of questions with other core or general quality-of-life questionnaires when studying patients with brain cancer in clinical trials.
Adult↗
Controversies in the management of metastatic spinal cord compression.
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Germinoma↗
Final results of the Royal College of Radiologists' trial comparing two different radiotherapy schedules in the treatment of cerebral metastases.
Between February 1990 and February 1993, 25 centres in the UK recruited 544 patients into a prospective randomized trial comparing two whole-brain radiotherapy regimens (30 Gy in ten fractions over 2 weeks versus 12 Gy in two fractions on consecutive days) for the treatment of patients with symptomatic cerebral metastases. Of these patients 533 were eligible for analysis: 270 assigned to the two-fraction arm and 263 to the ten-fraction arm. The two groups were well balanced with respect to patient characteristics. Median survival was 77 days with two fractions (95% CI 68-89) and 84 days for the longer schedule (95% CI 67-102). Analysis of the survival curves showed a marginal advantage for ten fractions (P = 0.04). Performance status (P = 0.0001), site of primary tumour (P = 0.006), dose of dexamethasone (P = 0.004), age (P = 0.04) and randomization treatment (P = 0.03) were independant factors associated with survival. The classification of patients into good or poor risk groups based on these factors, excluding treatment, showed highly significant differences in survival (P < 0.0001). Predictive models suggested that any benefit attributable to the longer radiotherapy schedule was confined to those in a good prognostic group (these patients formed 22% of the study population). Radiation related side effects, other than alopecia, were seen in 12% of patients receiving two fractions and 8% of those given ten fractions. The short survival of many patients hampered the assessment of response, but overall responses were seen in 39% of those given two fractions and 44% of patients receiving ten fractions. These results suggest that any increase in survival due to longer radiotherapy treatment is confined to good prognosis patients, but, for the majority, there is no advantage and the value of radiotherapy for these patients relates purely to the possibility of control or relief of distressing symptoms.
Brain Neoplasms↗