Long-term neurocognitive and other side effects of radiotherapy, with or without chemotherapy, for glioma.
Topic: Radiation/Chemotherapy

Gliomas are brain tumours arising from glial cells with an annual incidence of 4 to 11 people per 100,000. In this review we focus on gliomas with low aggressive potential in the short term, i.e. low-grade gliomas. Most people with low-grade gliomas are treated with surgery and may receive radiotherapy thereafter. However, there is concern about the possible long-term effects of radiotherapy, especially on neurocognitive functioning.

PICO
Population: Patients with low-grade gliomas
Intervention: Radiotherapy, with or without chemotherapy
Comparison: No radiotherapy or alternative treatment
Outcomes: Long-term neurocognitive and other side effects

Included studies:
title: Phase II study of donepezil in irradiated brain tumor patients: effect on cognitive function, mood, and quality of life.
abstract: A prospective, open-label phase II study was conducted to determine whether donepezil, a US Food and Drug Administration-approved reversible acetylcholinesterase inhibitor used to treat mild to moderate Alzheimer's type dementia, improved cognitive functioning, mood, and quality of life (QOL) in irradiated brain tumor patients.
title: NRG oncology RTOG 9006: a phase III randomized trial of hyperfractionated radiotherapy (RT) and BCNU versus standard RT and BCNU for malignant glioma patients.
abstract: From 1990 to 1994, patients with newly diagnosed malignant gliomas were enrolled and randomized between hyperfractionated radiation (HFX) of 72.0 Gy in 60 fractions given twice daily and 60.0 Gy in 30 fractions given once daily. All patients received 80 mg/m
title: Heterochromatin in cells derived from Aedes albopictus (Skuse) mosquito tissue culture.
title: Accidental poisoning in children in Jamaica and Belfast: a comparative study.
title: Health-related quality of life in patients with high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study.
abstract: Temozolomide chemotherapy versus radiotherapy in patients with a high-risk low-grade glioma has been shown to have no significant effect on progression-free survival. If these treatments have a different effect on health-related quality of life (HRQOL), it might affect the choice of therapy. We postulated that temozolomide compromises HRQOL and global cognitive functioning to a lesser extent than does radiotherapy.
title: Bevacizumab plus hypofractionated radiotherapy versus radiotherapy alone in elderly patients with glioblastoma: the randomized, open-label, phase II ARTE trial.
abstract: The addition of bevacizumab to temozolomide-based chemoradiotherapy (TMZ/RT → TMZ) did not prolong overall survival (OS) in patients with newly diagnosed glioblastoma in phase III trials. Elderly and frail patients are underrepresented in clinical trials, but early reports suggested preferential benefit in this population.
title: A randomized trial on dose-response in radiation therapy of low-grade cerebral glioma: European Organization for Research and Treatment of Cancer (EORTC) Study 22844.
abstract: Cerebral low-grade gliomas (LGG) in adults are mostly composed of astrocytomas, oligodendrogliomas, and mixed oligoastrocytomas. There is at present no consensus in the policy of treatment of these tumors. We sought to determine the efficacy of radiotherapy and the presence of a dose-response relationship for these tumors in two multicentric randomized trials conducted by the European Organization for Research and Treatment of Cancer (EORTC). The dose-response study is the subject of this article.
title: Late cognitive and radiographic changes related to radiotherapy: initial prospective findings.
abstract: Assumptions about the damaging effects of radiotherapy (XRT) are based on studies in which total dose, dose fraction, treatment volume, degree of malignancy, chemotherapy, tumor recurrence, and neurologic comorbidity interact with XRT effects. This is a prospective, long-term study of XRT effects in adults, in which total dose and dose fraction were constrained and data related to tumor recurrence and neurologic comorbidity (e.g., hypertension) were excluded.
title: Phase II multicenter study of gene-mediated cytotoxic immunotherapy as adjuvant to surgical resection for newly diagnosed malignant glioma.
abstract: Despite aggressive standard of care (SOC) treatment, survival of malignant gliomas remains very poor. This Phase II, prospective, matched controlled, multicenter trial was conducted to assess the safety and efficacy of aglatimagene besadenovec (AdV-tk) plus valacyclovir (gene-mediated cytotoxic immunotherapy [GMCI]) in combination with SOC for newly diagnosed malignant glioma patients.
title: Prospective randomized trial of low- versus high-dose radiation therapy in adults with supratentorial low-grade glioma: initial report of a North Central Cancer Treatment Group/Radiation Therapy Oncology Group/Eastern Cooperative Oncology Group study.
abstract: To compare survival and toxicity in adult patients treated with low-dose (50.4 Gy/28 fractions) versus high-dose (64.8 Gy/36 fractions) localized radiation therapy (RT) for supratentorial low-grade astrocytoma, oligodendroglioma, and mixed oligoastrocytoma.
title: Health related quality of life and cognitive status in patients with glioblastoma multiforme receiving escalating doses of conformal three dimensional radiation on RTOG 98-03.
abstract: The Radiation Therapy Oncology Group (RTOG) embarked on a phase I/II study of patients suffering from glioblastoma multiforme (protocol 98-03) to assess the impact of dose escalation with 3-D conformal techniques. The primary endpoints were feasibility and survival. This report describes the outcome of secondary endpoints (quality of life and neurocognitive function). Patients with supratentorial GBM were treated with a combination of carmustine (BCNU) and conformal irradiation (dose levels: 66, 72, 78, 84 Gy, respectively). Quality of Life was assessed with the Spitzer Quality of Life Index. Neurocognitive function was determined by the Mini Mental Status Examination. The latter tests were administered at the start of irradiation, at the end of irradiation and then at 4 month intervals. Relatively high compliance was achieved with both of the tools (SQLI; MMSE). Overall rates of survival between baseline SQLI scores <7 and 7-10 were statistically significantly different [HR = 1.72, 95% CI (1.22, 2.4), P = 0.0015]. The significant impact of high SQLI score on survival was preserved in multivariate analysis. The component of this index which made the greatest contribution was the patient's independence. There was continual deterioration of neurocognitive function within the populations studied. No correlation was seen between dose escalation and the secondary endpoints studied. Radiation dose escalation and assessment of its impact on life quality and neurocognition can be carried out in a large international trial. Baseline SQLI is a statistically significant determinant of survival. Those who maintain independence have superior survival to those who are reliant on others.
title: Comparative evaluation of radiochemotherapy with temozolomide versus standard-of-care postoperative radiation alone in patients with WHO grade III astrocytic tumors.
abstract: Outcome after radiochemotherapy (RCHT) with temozolomide (TMZ) versus radiotherapy (RT) for WHO grade III astrocytic tumors was evaluated. No significant difference in overall survival or progression-free survival between both groups was calculated. RCHT seems not to result in an improved outcome. Further randomized studies are needed to support these results.
title: Patients with primary brain tumors.
abstract: The purpose of this prospective phase II/III trial was to study the effect of therapy intensification when combining procarbazine, lomustine, and vincristine (PCV) chemotherapy with a standard course of radiation therapy (RT) on cognitive functioning for patients with World Health Organization grade 2 low-grade gliomas (LGGs). Initial results of the trial demonstrated a progression-free survival benefit with adjuvant PCV, but no overall survival benefit in the intention-to-treat analysis. Because patients with LGGs have favorable prognostic indicators, the five-year overall survival rates range from 60%-70%. The effect of cancer treatment on neurocognitive function is a topic of increasing interest to healthcare providers and patients. The negative effect is commonly called "chemobrain" and refers to diminished concentration and compromised short-term memory following treatment. Chemobrain has been studied in other populations of patients with cancer (e.g., breast cancer) with associated statistically significant chemotherapy-associated compromised cognitive function when chemotherapy was added to RT.
title: NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide.
abstract: The standard of care for anaplastic gliomas is surgery followed by radiotherapy. The NOA-04 phase III trial compared efficacy and safety of radiotherapy followed by chemotherapy at progression with the reverse sequence in patients with newly diagnosed anaplastic gliomas.
title: Randomized trial on the efficacy of radiotherapy for cerebral low-grade glioma in the adult: European Organization for Research and Treatment of Cancer Study 22845 with the Medical Research Council study BRO4: an interim analysis.
abstract: There is no consensus on the treatment strategy for adult patients with cerebral low-grade glioma. The diagnosis and primary treatment are usually undertaken by surgery. Some investigators doubt the efficacy of postoperative radiotherapy (RT), whereas others advise routine postoperative RT. We report the primary results of a multicenter randomized trial on this controversy.
title: A randomized trial of radiotherapy versus radiotherapy plus CCNU for incompletely resected low-grade gliomas: a Southwest Oncology Group study.
abstract: Sixty adult patients with incompletely excised low-grade gliomas were randomly assigned to receive radiotherapy (55 Gy over a total of 6 1/2 to 7 weeks) either alone or with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU; 100 mg/sq m every 6 weeks). Pathological review showed that six patients were ineligible for the study. Evaluation of patient age, extent of surgery, tumor grade, and performance status showed no significant differences between the treatment arms. The response rate, as judged by the disappearance or reduction in size of the tumor on computerized tomography scans, was 79% for radiation therapy alone versus 54% for irradiation plus CCNU. The median survival time was 4.45 years for all patients, with no significant difference between treatment arms (p = 0.7). For the group as a whole, patient age and performance status were the most important prognostic parameters. The majority of patients receiving chemotherapy experienced moderate hematological toxicity. This study demonstrates that CCNU chemotherapy does not improve the results of radiation therapy in the treatment of incompletely excised low-grade gliomas.
title: Cognitive function after radiotherapy for supratentorial low-grade glioma: a North Central Cancer Treatment Group prospective study.
abstract: To evaluate the effects of cranial radiotherapy (RT) on cognitive function in patients with supratentorial low-grade glioma.
title: The early effects of radiotherapy on intellectual and cognitive functioning in patients with frontal brain tumours: the use of a new neuropsychological methodology.
abstract: Investigations of the effects of radiation on neuropsychological functions have revealed variable outcomes, ranging from no effect to severe cognitive impairment. However, many of the previous studies have relied on retrospective data or have been limited by methodological problems. In this study, prospective neuropsychological assessments were compared at baseline (after surgery and before radiotherapy) and within 4 months of completion of radiotherapy (except one case), to examine early-delayed effects of radiation on intellectual and cognitive functioning. Sixteen adult patients with either low- or high-grade brain tumours, 15 of whom were treated with radiotherapy, were compared with 8 control participants with nonmalignant brain tumours whom did not undergo radiotherapy. All participants had lesions situated mainly in the frontal lobes. All groups of patients had evidence of intellectual and cognitive impairment at baseline. The low- and high-grade brain tumour groups showed a differential pattern of performance following radiotherapy, with the low-grade tumour group's performance being more competent on all of the five main neuropsychological measures. Their pattern of improvement was very similar to that of the nonmalignant brain tumour group who had not undergone radiotherapy. The present study provides some preliminary information about the neuropsychological deficits associated with primary brain tumours, their severity, and the relationship between neuropsychological functioning and brain tumours and radiotherapy.
title: Neurocognitive effects of proton radiation therapy in adults with low-grade glioma.
abstract: To understand neurocognitive effects of proton radiation therapy (PRT) in patients with low-grade glioma, we evaluated 20 patients who received this therapy prospectively and over 5 years with a comprehensive neuropsychological battery. 20 patients were evaluated at baseline and at yearly intervals for up to 5 years with a battery of neuropsychological measures that assessed intellectual, attention, executive, visuospatial and memory functions as well as mood and functional status. We evaluated change in cognitive functioning over time. We analyzed the relationship between cognitive performance and tumor location and also examined whether patients' performance differed from that reported in a study of normative practice effects. Overall, patients exhibited stability in cognitive functioning. Tumor location played a role in performance; those with tumors in the left hemisphere versus in the right hemisphere were more impaired at baseline on verbal measures (p < .05). However, we found greater improvement in verbal memory over time in patients with left than with right hemisphere tumors (p < .05). Results of our study, the first to investigate, in depth, neurocognitive effects of PRT in adults with low-grade gliomas, are promising. We hypothesize that the conformal advantage of PRT may contribute to preservation of cognitive functioning, although larger sample sizes and a longer period of study are required. Our study also highlights the need to consider normative practice effects when studying neurocognitive functioning in response to treatment over time, and the need to utilize comprehensive neuropsychological batteries given our findings that differentiate patients with left and right hemisphere tumors.
title: Hippocampal dosimetry predicts neurocognitive function impairment after fractionated stereotactic radiotherapy for benign or low-grade adult brain tumors.
abstract: To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT).
title: Endocrine functions in long-term survivors of low-grade supratentorial glioma treated with radiation therapy.
abstract: Endocrine functions were studied in long-term survivors of low-grade glioma treated with radiotherapy. Hypothalamic-pituitary dysfunction has recently been reported to occur more frequently than generally considered. Because endocrine dysfunction is a treatable condition, careful testing and, if necessary, supplementary treatment may enhance quality of life. Thirteen adult patients treated with radiotherapy because of supratentorial low-grade glioma at least one year before (range 1-11.5 years) were tested. Focal brain radiotherapy (45-61.2 Gy), with calculated dose to the hypothalamic-pituitary area ranging from 0 to 50 Gy (mean 36.1) had been applied to all patients. Serum levels of pituitary hormones, cortisol and thyroid hormone were determined before and after stimulation with hypothalamic hormones. In 10 out of 13 patients one or more hormonal values were out of the normal range. Most disturbances were demonstrated in the pituitary-adrenal axis (8 patients) and the GH-axis (4 patients). None of the patients had clinical symptomatology of adrenal, thyroid or gonadal dysfunction. Careful endocrine testing after cranial radiotherapy may reveal (subclinical) hypothalamic-pituitary dysfunction in long-term survivors. Follow-up testing in these patients seems warranted.
title: A prospective study of cognitive functions following conventional radiotherapy for supratentorial gliomas in young adults: 4-year results.
abstract: To evaluate the effects of limited field conventional cerebral radiotherapy (RT) on cognitive functions of adults.
title: Joint modeling of longitudinal health-related quality of life data and survival.
abstract: In cancer research, outcome measures may co-vary. Treatment and treatment related impairment of health-related quality of life (HRQoL) may affect survival. When these effects are analyzed separately, bias may arise. Therefore, we investigated the combined effect of treatment and longitudinally measured HRQoL on survival.
title: Longitudinal cognitive follow-up in low grade gliomas.
abstract: Background In patients with low-grade glioma (LGG), the tumor and its treatment with conformal radiation therapy (RT) and chemotherapy can disrupt cognitive function. However, the contribution of disease and treatment to long-term cognitive outcome remains to be elucidated. In this study, we performed longitudinal cognitive follow-up in a subgroup of patients who received RT, chemotherapy, or no treatment. Methods Twenty-five LGG patients underwent neuropsychological evaluations at study entry, and 6 and 12 months subsequently; 9 patients had RT +/- chemotherapy prior to enrollment and 16 had no treatment. Results At the initial evaluation, treated patients had impaired performance on motor speed only, but scored 1 standard deviation below normative values on tests of executive functions; untreated patients had no cognitive impairment. Repeated measures analyses of variance showed a significant variation over time (P = 0.03) in nonverbal memory (delayed recall); treated patients' performance improved at the 6-month follow-up to a level comparable to untreated patients, but both groups declined slightly by the 12-month evaluation. In a subset of patients (N = 16) available for an additional cognitive evaluation, significant changes between the 12-month and the long-term follow-up were seen in phonemic verbal fluency, mood and quality of life; untreated patients seen at short intervals improved slightly while treated patients seen at longer intervals declined. Conclusions Longitudinal follow-up showed that both disease duration and treatment with RT +/- chemotherapy contributed to a mild decrement in nonverbal recall and in some aspects of executive functions and quality of life in this group of LGG patients.
title: Radiotherapy in low-grade glioma adult patients: a retrospective survival and neurocognitive toxicity analysis.
abstract: The treatment of low-grade glioma is still debated. Surgery is the first-line approach, and the correct timing of radiation therapy has not yet been defined since "early" radiation therapy improves relapse-free survival but not overall survival. Since a longer progression-free survival is desirable, the main issue related to radiotherapy is the incidence of late neurocognitive toxicity.
title: Effect of the addition of chemotherapy to radiotherapy on cognitive function in patients with low-grade glioma: secondary analysis of RTOG 98-02.
abstract: The addition of PCV (procarbazine, lomustine, and vincristine) chemotherapy to radiotherapy (RT) for patients with WHO grade 2 glioma improves progression-free survival (PFS). The effect of therapy intensification on cognitive function (CF) remains a concern in this population with substantial long-term survival.
title: Health-related quality of life in patients treated for anaplastic oligodendroglioma with adjuvant chemotherapy: results of a European Organisation for Research and Treatment of Cancer randomized clinical trial.
abstract: Little is known about the health-related quality of life (HRQOL) of patients treated for anaplastic oligodendrogliomas. The impact of combined procarbazine, CCNU (lomustine), and vincristine (PCV) chemotherapy after radiotherapy (RT) compared with RT alone on HRQOL in the randomized European Organisation for Research and Treatment of Cancer (EORTC) 26951 trial was studied.
title: Efficacy of Stereotactic Conformal Radiotherapy vs Conventional Radiotherapy on Benign and Low-Grade Brain Tumors: A Randomized Clinical Trial.
abstract: Evidence for application of stereotactic and other conformal radiotherapy techniques in treating brain tumors is largely based on data derived from dosimetric, retrospective, or small prospective studies. Therefore, we conducted a randomized clinical trial of stereotactic conformal radiotherapy (SCRT) compared with conventional radiotherapy (ConvRT) evaluating clinically meaningful end points.
title: Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial.
abstract: Anaplastic oligodendrogliomas are more responsive to chemotherapy than high-grade astrocytomas. We investigated, in a multicenter randomized controlled trial, whether adjuvant procarbazine, lomustine, and vincristine (PCV) chemotherapy improves overall survival (OS) in newly diagnosed patients with anaplastic oligodendrogliomas or anaplastic oligoastrocytomas.
title: Cognitive functioning in long-term survivors of high-grade glioma.
abstract: In a pilot study, two groups of patients with malignant glioma underwent sequential neuropsychological evaluations after successful tumor treatment. Group 1 included nine patients treated from 1981 to 1985; all patients received irradiation and eight underwent chemotherapy. The baseline neuropsychological assessment was performed 1 to 63 months after tumor diagnosis, with follow-up evaluations at irregular intervals over the next 3 to 7 years. Six patients in Group 1 exhibited impairment on most measures at baseline; subsequently, two patients developed profound cognitive impairment. Initially, three patients functioned in the average range on most tasks; thereafter, two deteriorated on one measure each. Group 2 was ascertained prospectively and included 16 patients treated from 1985 to 1987, all of whom received irradiation and chemotherapy. The first evaluation was performed 18 months after diagnosis, then every 6 months for 2 years, and then yearly. Compared to a control group, those in Group 2 had significant cognitive impairment at baseline. Cognitive performance did not change over the next 12 months in 10 patients who remained free of tumor, but within 2 years of baseline testing, deterioration on specific tasks was evident in two of seven disease-free survivors. When last tested, five of six disease-free survivors had deteriorated on one or more measures. Unlike Group 1, severe global cognitive impairment was not seen, perhaps because Group 2 was followed for a shorter time. Verbal and nonverbal composite scores derived from intelligence quotient (IQ) tests showed less impairment at baseline than did other measures and were more likely to remain stable subsequently. Verbal memory and sustained attention were the most impaired at baseline, and verbal learning and flexibility in thinking showed the greatest tendency to decline over time. Cognitive functioning in survivors of high-grade glioma is best measured and monitored by tests that probe a broader spectrum of abilities than IQ. Neuropsychological measures used in this analysis lacked sensitivity at the lower end of the impaired range. Future studies should use tests better able to discern cognitive differences at low performance levels. Based on this experience, the authors conclude that most long-term survivors of high-grade glioma will have significant cognitive difficulties, usually evident by the first assessment; some patients will develop profound impairment years later, and few are capable of fully independent living.
title: Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402.
abstract: Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) are treated with surgery and radiotherapy (RT) at diagnosis, but they also respond to procarbazine, lomustine, and vincristine (PCV), raising the possibility that early chemotherapy will improve survival. Furthermore, better outcomes in AO have been associated with 1p and 19q allelic loss.
title: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.
abstract: Glioblastoma, the most common primary brain tumor in adults, is usually rapidly fatal. The current standard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible, followed by adjuvant radiotherapy. In this trial we compared radiotherapy alone with radiotherapy plus temozolomide, given concomitantly with and after radiotherapy, in terms of efficacy and safety.
title: Effects of radiotherapy on cognitive function in patients with low-grade glioma measured by the folstein mini-mental state examination.
abstract: To assess the neurocognitive effects of cranial radiotherapy on patients with low-grade gliomas, we analyzed cognitive performance data collected in a prospective, intergroup clinical trial.
title: Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: initial results of RTOG 9802.
abstract: A prior Radiation Therapy Oncology Group (RTOG) clinical trial in anaplastic oligodendroglioma suggested a progression-free survival benefit for procarbazine, lomustine, and vincristine (PCV) chemotherapy in addition to radiation therapy (RT), as have smaller trials in low-grade glioma (LGG).
title: Effects of radiation and chemotherapy on cognitive function in patients with high-grade glioma.
abstract: The effect of radiotherapy on the long-term cognitive performance of patients treated for intracranial neoplasm is a major concern to clinicians and patients, particularly as long-term survival or cure is possible for a small minority of patients. To assess the effects of cranial radiotherapy and chemotherapy on the cognitive performance of high-grade glioma patients, we analyzed cognitive performance data collected in a series of prospective clinical trials.
title: Neuroanatomical target theory as a predictive model for radiation-induced cognitive decline.
abstract: In a retrospective review to assess neuroanatomical targets of radiation-induced cognitive decline, dose volume histogram (DVH) analyses of specific brain regions of interest (ROI) are correlated to neurocognitive performance in 57 primary brain tumor survivors.
title: Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402.
abstract: Anaplastic oligodendrogliomas, pure (AO) and mixed (anaplastic oligoastrocytoma [AOA]), are chemosensitive, especially if codeleted for 1p/19q, but whether patients live longer after chemoradiotherapy is unknown.
title: Radiation plus Procarbazine, CCNU, and Vincristine in Low-Grade Glioma.
abstract: Grade 2 gliomas occur most commonly in young adults and cause progressive neurologic deterioration and premature death. Early results of this trial showed that treatment with procarbazine, lomustine (also called CCNU), and vincristine after radiation therapy at the time of initial diagnosis resulted in longer progression-free survival, but not overall survival, than radiation therapy alone. We now report the long-term results.
title: Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial.
abstract: A pilot study of temozolomide (TMZ) given before radiotherapy (RT) for anaplastic astrocytoma (AA) and glioblastoma (GBM) resulted in prolonged survival compared to historical controls receiving RT alone. We therefore investigated neoadjuvant TMZ (NeoTMZ) in a randomized trial. During enrollment, concomitant and adjuvant radio-chemotherapy with TMZ became standard treatment. The trial was amended to include concurrent TMZ.
title: Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study.
abstract: The role of temozolomide chemotherapy in newly diagnosed 1p/19q non-co-deleted anaplastic gliomas, which are associated with lower sensitivity to chemotherapy and worse prognosis than 1p/19q co-deleted tumours, is unclear. We assessed the use of radiotherapy with concurrent and adjuvant temozolomide in adults with non-co-deleted anaplastic gliomas.