Radiosurgery for brain tumours.
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Brain Neoplasms↗
Biomedical subjects
M Brada
Publications and source records attributed to M Brada.
Modifying radical radiotherapy in high grade gliomas; shortening the treatment time through acceleration.
PURPOSE: To evaluate the efficacy and toxicity of accelerated radiotherapy in patients with primary high grade glioma, where acceleration is used as a means of delivering a shortened course of radical radiotherapy. PATIENTS AND METHODS: Two-hundred and eleven patients with primary high grade glioma were treated at the Royal Marsden NHS Trust between 1987 and 1997 with accelerated radiotherapy (55 Gy in 34 fractions twice daily), to planning target volume (PTV) defined as enhancing tumour and a 3 cm margin. All had histologically confirmed high grade glioma (53 anaplastic astrocytoma, 137 glioblastoma multiforme, 4 gliosarcoma, 5 gemistocytic astrocytoma, 12 high grade astrocytoma not otherwise specified). The mean Karnofsky performance status (KPS) was 90 and median age was 54 years (range 19-77). RESULTS: Of 211 patients entered, 201 were able to complete radiotherapy; 39 patients (19%) had deterioration in KPS during radiotherapy and this was transient in 11. Median survival of 211 patients was 10 months with 1 year, 2 year, and 3 year survival probabilities of 38%, 14%, and 8% respectively. Age and extent of excision were independent prognostic factors for survival. Previous comparison to matched cohort receiving 60 Gy in 30 daily fractions did not demonstrate significant survival difference. CONCLUSION: Accelerated radiotherapy is a feasible treatment approach for patients with high grade glioma. The survival and functional outcome are comparable to conventional radiotherapy and the treatment is without serious acute toxicity. While acceleration of conventional dose irradiation could be tested in randomised studies, it is unlikely this approach would result in a clinically meaningful survival benefit. Accelerated radiotherapy therefore remains one of the ways of delivering radical irradiation in patients with high grade glioma. However, it adds complexity to what is a palliative treatment regimen and the rationale and advisability should be re-examined, particularly in terms of impact on quality of life, true patient preference, and health economic considerations.
Adult↗
Effect of gastric pH on the relative oral bioavailability and pharmacokinetics of temozolomide.
PURPOSE: Temozolomide is an imidazotetrazine alkylating agent which undergoes chemical conversion at physiological pH to the active species 5-(3-methyltriazene-1-yl)imidazole-4-carboxamide (MTIC) but is stable at acid pH. This study evaluated the effect of an increase in gastric pH, through the use of ranitidine, on the oral bioavailability and plasma pharmacokinetics of temozolomide and MTIC. METHODS: Fifteen patients with advanced cancer were enrolled of which 12 were evaluable, all of whom had pharmacokinetic blood sampling. Each patient received temozolomide 150 mg m(-2) day(-1) for 5 days in cycle 1 and also received ranitidine 150 mg every 12 h either on days 1 and 2 or days 4 and 5. Gastric pH was monitored by the use of the Heidelberg capsule system. RESULTS: Following the administration of ranitidine there was a rise in gastric pH by 1-2 pH units over the duration of the study period (pH range 2.2-5.2 without ranitidine and 3.5-6.0 with ranitidine). There was no difference in the pharmacokinetic parameters of temozolomide or MTIC with or without the concomitant administration of ranitidine. There was however, a lower C(max) for temozolomide and MTIC for patients receiving ranitidine on day 1 and 2 versus day 4 and 5. Temozolomide was rapidly absorbed [time to maximum plasma concentration (t(max)) 1.8 h] and eliminated [elimination half-life (t(1/2)) 1.8 h] and MTIC followed a similar pattern with a t(max) of 1.9 h and a t(1/2) of 1.9 h. Overall, the AUC of the MTIC represented about 2-4% of the AUC for temozolomide.
Administration, Oral↗
Stereotactically guided conformal radiotherapy for meningiomas.
PURPOSE: Stereotactically guided conformal radiotherapy, (SCRT) is a high precision technique of conformal radiotherapy (RT) which reduces the volume of normal tissue irradiated compared to conventional RT and may lead to a reduction in long-term toxicity We describe the technique and the preliminary results in patients with inoperable, residual or recurrent meningiomas. MATERIAL AND METHODS: From July 1993 to November 1997, 24 patients (median age: 56 years, range: 28-72) with base of skull (n = 21). falx or upper skull (n = 3) meningiomas were treated with SCRT. The technique employed immobilization in a Gill-Thomas-Cosman (GTC) frame and CT localization with a Brown-Roberts-Wells (BRW) fiducial system for stereotactic space definition. The planning target volume (PTV) was defined as gross tumour volume (GTV) and a 0.5-1 cm margin. Treatment was delivered with three (12 patients) or four non-coplanar conformal fixed fields (12 patients) Conformal blocking was achieved either with lead alloy blocks (n = 11) or with a multi-leaf collimator (MLC) (n = 13). Patients were treated on a 6 MV linear accelerator to doses of 50-55 Gy, in 30-33 daily fractions. The treatments were carried out as part of a routine work of a busy radiotherapy department. RESULTS: Median GTV for 24 meningiomas was 21.7 cm3 (range: 4.4-183 cm3). SCRT was well tolerated with minimal toxicity Three months after the end of radiotherapy, seven of 15 patients with neurological deficit had an improvement and eight remained unchanged. Two patients experienced early side effects (one VII nerve palsy, one Addisonian state). At a median follow-up of 13-months (range: 3-43) the 1 year progression free survival and overall survival are 100%. which is within the range expected for conventional fractionated radiotherapy for meningiomas. CONCLUSIONS: SCRT is a feasible technique of high precision conformal RT for patients with meningiomas. Potential advantages in tumour control, survival and toxicity over conventional RT, require evaluation in long-term prospective studies.
Adult↗
Patient position reproducibility in fractionated stereotactic radiotherapy: an update after changing dental impression material.
The reproducibility of patient positioning within the Gill-Thomas-Cosman relocatable stereotactic frame was re-evaluated following the substitution of a new, softer, dental impression material for the original hard acrylic compound. The average total displacement for a series of 10 patients was 1.1 mm (+/- 0.6 mm). Rotational discrepancies were small. This technique cannot deliver accurate repositioning in the absence of patient co-operation.
Acrylic Resins↗
Comparison of a multi-leaf collimator with conformal blocks for the delivery of stereotactically guided conformal radiotherapy.
Stereotactically-guided conformal radiotherapy is a practical technique for irradiating irregular lesions in the brain. The shaping of the conformal fields may be achieved using lead alloy blocks, a conventional multi-leaf collimator (MLC) or a mini/micro-MLC. Although the former gives more precise shaping, it is labour intensive. The latter methods are more practical as both mould room and treatment room times are reduced, but the shaping is limited by the finite leaf-width. This study compares treatment plans, in terms of normal tissue doses and tumour coverage, for fields shaped using conformal blocks and a conventional MLC in two series of geometrical shapes and nine patient tumours. For the range of tumour sizes considered (volumes 14-264 cm3, minimum dimension 30 mm, maximum 102 mm), the MLC treats, on average, 14% (range 3-34%) and 17% (range 0-36%) more normal brain tissue than conformal blocks to >50% and >80% of the prescription dose, respectively. The large variability is due to strong dependence on tumour shape and the presence of partial leaf-widths in the MLC fit. It is therefore important to consider both of these effects when deciding whether the MLC is appropriate for a particular target volume.
Brain Neoplasms↗
Phase I dose-escalation and pharmacokinetic study of temozolomide (SCH 52365) for refractory or relapsing malignancies.
Temozolomide, an oral cytotoxic agent with approximately 100% bioavailability after one administration, has demonstrated schedule-dependent clinical activity against highly resistant cancers. Thirty patients with minimal prior chemotherapy were enrolled in this phase I trial to characterize the drug's safety, pharmacokinetics and anti-tumour activity, as well as to assess how food affects oral bioavailability. To determine dose-limiting toxicities (DLT) and the maximum tolerated dose (MTD), temozolomide 100-250 mg m(-2) was administered once daily for 5 days every 28 days. The DLT was thrombocytopenia, and the MTD was 200 mg m(-2) day(-1). Subsequently, patients received the MTD to study how food affects the oral bioavailability of temozolomide. When given orally once daily for 5 days, temozolomide was well tolerated and produced a non-cumulative, transient myelosuppression. The most common non-haematological toxicities were mild to moderate nausea and vomiting. Clinical activity was observed against several advanced cancers, including malignant glioma and metastatic melanoma. Temozolomide demonstrated linear and reproducible pharmacokinetics and was rapidly absorbed (mean Tmax approximately 1 h) and eliminated (mean t1/2 = 1.8 h). Food produced a slight reduction (9%) in absorption of temozolomide. Temozolomide 200 mg m(-2) day(-1) for 5 days, every 28 days, is recommended for phase II studies.
Administration, Oral↗
Current approaches to radiation therapy for malignant gliomas.
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Boron Neutron Capture Therapy↗
Focal fractionated conformal stereotactic boost following conventional radiotherapy of high-grade gliomas: a randomized phase III study. A joint study of the EORTC (22972) and the MRC (BR10).
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Brachytherapy↗
Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group.
PURPOSE: To determine the antitumor efficacy and safety profile of temozolomide in patients with malignant astrocytoma at first relapse. PATIENTS AND METHODS: This open-label, multicenter, phase II trial enrolled 162 patients (intent-to-treat [ITT] population). After central histologic review, 111 patients were confirmed to have had an anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma. Chemotherapy-naive patients were treated with temozolomide 200 mg/m(2)/d. Patients previously treated with chemotherapy received temozolomide 150 mg/m(2)/d; the dose could be increased to 200 mg/m(2)/d in the absence of grade 3/4 toxicity. Therapy was administered orally on the first 5 days of a 28-day cycle. RESULTS: Progression-free survival (PFS) at 6 months, the primary protocol end point, was 46% (95% confidence interval, 38% to 54%). The median PFS was 5.4 months, and PFS at 12 months was 24%. The median overall survival was 13.6 months, and the 6- and 12-month survival rates were 75% and 56%, respectively. The objective response rate determined by independent central review of gadolinium-enhanced magnetic resonance imaging scans of the ITT population was 35% (8% complete response [CR], 27% partial response [PR]), with an additional 26% of patients with stable disease (SD). The median PFS for patients with SD was 4.4 months, with 33% progression-free at 6 months. Maintenance of progression-free status and objectively assessed response (CR/PR/SD) were both associated with health-related quality-of-life (HQL) benefits. Adverse events were mild to moderate, with hematologic side effects occurring in less than 10% of patients. CONCLUSION: Temozolomide demonstrated good single-agent activity, an acceptable safety profile, and documented HQL benefits in patients with recurrent AA.
Adult↗
Radiotherapy in the treatment of benign meningioma of the skull base.
OBJECT: This study was undertaken to assess the long-term efficacy and toxicity of conventional fractionated external-beam radiation in the treatment of benign skull base meningioma. METHODS: This is a retrospective study of 82 patients with histologically verified benign skull base meningioma treated by surgery followed by fractionated external-beam radiation at the Royal Marsden Hospital between 1962 and 1992. The 5- and 10-year progression-free survival (PFS) rates were 92% and 83%, respectively, with the site of disease being the only independent prognostic factor for tumor control according to multivariate analysis. The 10-year PFS rate for patients with sphenoid ridge meningiomas was 69% compared with 90% for those with tumors in the parasellar region. The overall 10-year survival rate was 71%, with performance status and patient age found to be significant independent prognostic factors. Six patients had worsening vision, which was due to cataract in five cases and retinopathy in one. There were no recorded cases of cranial nerve neuropathy. CONCLUSIONS: The excellent long-term tumor control and length of survival with minimal toxicity associated with conventional external-beam radiation should serve as a baseline for evaluation of new treatment strategies such as radiosurgery and skull base surgery.
Adolescent↗
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↗