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Purpose: The study aims were to determine the prevalence of balance impairments in adult survivors of pediatric central nervous system (CNS) tumors, and to identify predictors of and limitations associated with balance impairments., Methods: Participants were adult survivors (N = 329) of pediatric CNS tumors. Balance was considered impaired among those with composite scores < 70 on the sensory organization test. Potential predictors of impaired balance were evaluated with generalized linear regression. Multivariable logistic regression was used to evaluate associations between balance impairment and function., Results: Balance impairment was observed in 48% of survivors, and associated with infratentorial tumor location (OR = 4.0, 95% CI, 2.0-7.6), shunt placement (OR = 3.5, 95% CI, 1.8-6.7), increased body fat percentage (OR = 1.1, 95% CI, 1.0-1.1), hearing loss (OR = 11.1, 95% CI, 5.6-22.2), flexibility limitations (OR = 2.0, 95% CI, 1.0-3.9), peripheral neuropathy (OR = 2.4, 95% CI, 1.2-4.5), and cognitive deficits (OR = 2.2, 95% CI, 1.1-4.7). In adjusted models, impaired balance was associated with limitations in overall physical performance (OR = 3.6, 95% CI, 2.0-6.3), mobility (OR = 2.6, 95% CI, 1.5-4.4), diminished walking endurance (OR = 2.9, 95% CI, 1.7-5.0), and non-independent living (OR = 2.0, 95% CI, 1.0-4.3)., Conclusions: Nearly half of adult survivors of pediatric CNS tumors have impaired balance, which is associated with mobility and physical performance limitations. Interventions to address the complex needs of this population should be prioritized., Implications for Cancer Survivors: Survivors with identified risk factors should be closely evaluated for presence of balance impairment. Interventions tailored to improve balance also can positively affect function and mobility in survivors.

Introduction: Children with brain tumors may develop inattention, slow processing, and hypersomnia. Stimulant medications improve these problems, but their effect on growth, heart rate, and blood pressure (BP) are inadequately explored., Procedure: We retrospectively studied children with brain tumors treated at our institution that had data available for 1 year pre and 2 years on stimulant treatment. Tumor location, gender, radiation treatment (RT), age at RT, drug type, and hormone therapy were variables of interest., Results: We identified 65 children (35 males) that fulfilled eligibility criteria. Focal RT was utilized in 58; 11 additionally had whole brain RT; and seven received no RT. Thirty were treated for hypersomnia and inattention, eight for hypersomnia alone, and rest for inattention. Modafinil was the first drug in 18 (27.7%), and methylphenidate in the others. Forty-seven (72.3%), 45 (69.2%), and 49 (75.4%) were on thyroxine, cortisone, and growth hormones, respectively. There was no difference in pre- and post-stimulant body mass index (BMI), heart rate, and BP. There was also no difference between modafinil and methylphenidate groups. Rate of height acquisition slowed on stimulants (P = .0096). Thyroxine treatment correlated with increase in BMI after stimulants (P = .04). Younger age (P = .0003) and higher prestimulant BMI (P = .0063) correlated with increased heart rate on stimulants, while higher age at RT (P =.016) correlated with elevated systolic BP on stimulants. No associations were found with height acquisition and diastolic BP., Conclusion: Stimulants are well tolerated by children with brain tumors that are appropriately managed for endocrine deficiencies, but may reduce the trajectory of height attainment., (© 2020 Wiley Periodicals LLC.)

Purpose Beyond survival, achieving independence is a primary goal for adult survivors of pediatric CNS tumors. However, the prevalence of and risk factors for failure to achieve independence, assessed with multiple concurrent indicators, have not been examined. Patients and Methods Functional and social independence was assessed in 306 survivors (astrocytoma [n = 130], medulloblastoma [n = 77], ependymoma [n = 36], and other [n = 63]; median current age, 25.3 years [range, 18.9 to 53.1 years]; time since diagnosis, 16.8 years [range, 10.6 to 41.8 years]). Six observed indicators were used to identify latent classes of independence, which included employment, living independently, assistance with personal care, assistance with routine needs, obtaining a driver's license, and marital status. Physical performance impairments were defined as scores < 10th percentile on measures of aerobic capacity, strength, flexibility, balance, mobility, and adaptive function. Multinomial logistic regression estimated odds ratios (ORs) and 95% CIs were calculated for associations of disease/treatment exposures and impairments in physical performance with nonindependence. Results Three classes of independence were identified as independent (40%), moderately independent (34%), and nonindependent (26%). In multivariable models, craniospinal irradiation (OR, 4.20; 95% CI, 1.69 to 10.44) and younger age at diagnosis (OR, 1.24; 95% CI, 1.14 to 1.35) were associated with risk of nonindependence versus independence. Beyond impaired IQ, limitations in aerobic capacity (OR, 5.47; 95% CI, 1.78 to 16.76), flexibility (OR, 3.66; 95% CI, 1.11 to 12.03), and adaptive physical function (OR, 11.54; 95% CI, 3.57 to 37.27) were associated with nonindependence versus independence. Nonindependent survivors reported reduced physical but not mental health-related quality of life compared with independent survivors. Conclusion Sixty percent of survivors of pediatric CNS tumors do not achieve complete independence as adults. Reduction in intensity of primary therapies and interventions that target physical performance and adaptive deficits may help survivors to achieve greater independence.

Daytime sleepiness is recognized in childhood brain tumor survivors. Our objective was to determine prevalence, risk factors for PSG/MLST proven hypersomnia/narcolepsy, and response to stimulants in childhood brain tumor survivors. Standard PSG/MSLT criteria were used to diagnose hypersomnia/narcolepsy. Medical records of brain tumor survivors having undergone a PSG/MSLT were reviewed for the diagnostic code of hypersomnia/narcolepsy. Survivors with hypersomnia/narcolepsy were matched with 2-3 survivors without reported hypersomnia/narcolepsy by age at tumor diagnosis, gender, and time from tumor diagnosis. Between January 2000 to April 2015, 39 of the 2336 brain tumor patients treated at our institution were diagnosed with hypersomnia/narcolepsy for a prevalence rate of 1670/100,000. Hypersomnia/narcolepsy was diagnosed at a median of 6.1 years (range 0.4-13.2) from tumor diagnosis and 4.7 years (range - 1.5 to 10.4) from cranial radiation. Midline tumor location (OR 4.6, CI 1.7-12.2, p = 0.002) and anti-epilepsy drug (AED) use (OR 11, CI 2.4-54) correlated with hypersomnia/narcolepsy while radiation dose > 30 Gray trended towards significance (OR 1.8, CI 0.9-3.6); posterior fossa tumor location reduced the risk (OR 0.1, CI 0.04-0.5, p = 0.002). AED use also correlated with midline tumor location. Thirty-seven survivors were treated with stimulants and reported improved wakefulness and school performance [response rate CI 0.97 (0.86-0.99) and 0.83 (0.65-0.94)]. Prevalence of hypersomnia/narcolepsy among childhood brain tumor survivors was higher than the general population. Tumor location and radiation dose were possible risk factors, and stimulants were reported to be beneficial.

Background: We studied the outcomes of movement disorders that were associated with childhood thalamic tumors., Methods: We retrospectively reviewed 83 children with thalamic tumors treated at our institution from 1996 to 2013 to document the incidence and outcome of movement disorders. Magnetic resonance imaging was used to analyze the involvement of thalamic nuclei, and three instruments were used to rate the severity of the disorders., Results: Nine (11%) patients had one or more of the following movement disorders: postural tremor, resting tremor, ballism, dystonia, myoclonus, and athetosis. Median age at tumor diagnosis was seven years (range, 0.25 to 11 years), and the average age at movement disorder onset was eight years (range, 1.5 to 11 years). Movement disorders developed at a median of 1.5 months (range, 0 to 4 months) after surgical resection. The severity of the disorders was either unchanged or slightly improved during follow-up. The red nuclei were the only thalamic structures that showed tumor involvement in all nine patients., Conclusions: No specific injury of the thalamic nuclei was associated with movement disorders in children with thalamic tumors, and the severity of these disorders did not change over time., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: In children, CNS-directed cancer therapy is thought to result in decreased cerebral white matter volumes (WMV) and subsequent neurocognitive deficits. This study was designed as a prospective validation of the purported reduction in WMV, associated influential factors, and its relationship to neurocognitive deficits in a very large cohort of both acute lymphoblastic leukemia (ALL) and malignant brain tumors (BT) survivors in comparison to an age similar cohort of healthy sibling controls., Procedures: The effects of host characteristics and CNS treatment intensity on WMV were investigated in 383 childhood cancer survivors (199 ALL, 184 BT) at least 12 months post-completion of therapy and 67 healthy siblings that served as a control group. t-Tests and multiple variable linear models were used to assess cross-sectional WMV and its relation with neurocognitive function., Results: BT survivors had lower WMV than ALL survivors, who had less than the control group. Increased CNS treatment intensity, younger age at treatment, and greater time since treatment were significantly associated with lower WMV. Additionally, cancer survivors did not perform as well as the control group on neurocognitive measures of intelligence, attention, and academic achievement. Reduced WMV had a larger impact on estimated IQ among females and children treated at a younger age., Conclusions: Survivors of childhood cancer that have undergone higher intensity therapy at a younger age have significantly less WMV than their peers and this difference increases with time since therapy. Decreased WMV is associated with significantly lower scores in intelligence, attention, and academic performance in survivors., (© 2014 Wiley Periodicals, Inc.)

Objective: To investigate the methylphenidate (MPH) response rate among childhood survivors of acute lymphoblastic leukemia (ALL) and brain tumors (BTs) and to identify predictors of positive MPH response., Methods: Cancer survivors (N = 106; BT = 51 and ALL = 55) identified as having attention deficits and learning problems participated in a 3-week, double-blind, crossover trial consisting of placebo, low-dose MPH (0.3 mg/kg), and moderate-dose MPH (0.6 mg/kg). Weekly teacher and parent reports on the Conners' Rating Scales were gathered., Results: Following moderate MPH dose, 45.28% of the sample was classified as responders. Findings revealed that more problems endorsed prior to the medication trial on parent and teacher ratings were predictive of positive medication response (p < .05)., Conclusions: MPH significantly reduces attention problems in a subset of childhood cancer survivors. Parent and teacher ratings may assist in identifying children most likely to respond to MPH so prescribing may be optimally targeted.

Objectives: To investigate the frequency and severity of side effects of methylphenidate among childhood survivors of acute lymphoblastic leukemia and brain tumors and identify predictors of higher adverse effect levels., Methods: Childhood cancer survivors (N = 103) identified as having attention and learning problems completed a randomized, double-blind, 3-week, home-crossover trial of placebo, low-dose methylphenidate (0.3 mg/kg; 10 mg twice daily maximum) and moderate-dose methylphenidate (0.6 mg/kg; 20 mg twice daily maximum). Caregivers completed the Barkley Side Effects Rating Scale (SERS) at baseline and each week during the medication trial. Siblings of cancer survivors (N = 49) were recruited as a healthy comparison group., Results: There was a significantly higher number and severity of symptoms endorsed on the SERS when patients were taking moderate dose compared with placebo or low dose, but not low dose compared with placebo. The number of side effects endorsed on the SERS was significantly lower during all 3 home-crossover weeks (placebo, low dose, moderate dose) when compared with baseline symptom scores. The severity of side effects was also significantly lower, compared with baseline screening, during placebo and low-dose weeks but not moderate-dose weeks. Both the number and severity of symptoms endorsed at baseline were significantly higher for patients compared with siblings. Female gender and lower IQ were associated with higher adverse effect levels., Conclusions: Methylphenidate is generally well tolerated by childhood cancer survivors. There is a subgroup at increased risk for side effects that may need to be closely monitored or prescribed a lower medication dose. The seemingly paradoxical findings of increased "side effects" at baseline must be considered when monitoring side effects and designing clinical trials.

Objective: To study risk factors for the development of postoperative neurological deficits after brain tumor resection and to define prognostic factors for recovery., Methods: We prospectively studied 82 brain tumor patients undergoing tumor resection. Pre- and postoperative neurological examination, functional and performance status, cancer treatment, cardiovascular risk factors, seizure history, and blood pressure and oxygen saturation were recorded perioperatively. Postoperative magnetic resonance imaging scans were obtained within 72 hours of surgery, and the radiologist was blinded to the patient's status. Abnormalities on magnetic resonance diffusion weighted images were classified as new if they extended beyond the tumor cavity margins and were absent before surgery., Results: Of the 80 assessable patients, 24 had a new or increased postoperative deficit by at least one point on the National Institutes of Health Stroke Scale. Presence of preoperative neurological deficits predicted development of postoperative deficits, whereas a new diffusion weighted imaging lesion after craniotomy predicted incomplete recovery of a new postoperative deficit., Conclusion: Postoperative diffusion magnetic resonance imaging is useful in predicting early functional recovery from new deficits after brain tumor surgery.

Object: The goals of this study were to define the incidence of seizures in children with low-grade tumors, study seizure outcome after lesionectomy in these children, and identify risk factors for poor seizure outcome., Methods: The authors performed a retrospective chart review of children who harbored low-grade brain tumors, experienced seizures, and were treated in a single institution. Statistical analyses included step-wise as well as single-variable binary logistic regression analyses. Fifty-five children (20%) with seizures were identified in a cohort of 280 children with low-grade tumors. Of these 55 children, 35 harbored cortical cerebral tumors and 20 had noncortical lesions, including six whose tumors were in the posterior fossa. Seizures were defined as controlled if there was no seizure in the 12 months preceding the last clinic visit. All cortical tumors were treated by lesionectomy as an initial procedure. Of the 27 children with cortical tumors whose seizures began before tumor diagnosis, 23 had complete resection and 52% of these 23 experienced no further seizures after surgery. Seizures are presently controlled in 84% of the total 55 patients at a median follow-up time of 4.5 years after the first seizure (range 1-17.4 years). Only two variables, a pericavity hyperintense signal on T2-weighted magnetic resonance (MR) images and at least 10 seizures prior to therapy for seizures, were associated with uncontrolled seizures., Conclusions: Lesionectomy may be appropriate in children with low-grade brain tumors. A large number of seizures before therapy and a hyperintense area around the tumor cavity on postresection MR images are associated with uncontrolled seizures. Medical therapy and tumor resection will control seizures in the majority of children with low-grade tumors.

Purpose: To study seizure outcome after antiepilepsy drug (AED) withdrawal in brain tumor patients and to analyze risk factors for seizure recurrence., Methods: Brain tumor patients with seizures and at least one attempt at AED discontinuation were identified from the hospital database and neurology clinic records. After defining study variables, patient charts were abstracted for clinical and demographic data. Statistical analyses used log-rank tests and multivariable Cox proportional hazards models., Results: Sixty-two patients discontinued AEDs at a median time of 5.6 years from the first seizure (range, 1.2-19.6 years). Median time since AED withdrawal was 2.3 years (range, 0.4-15.1 years). Seizures recurred in 17 (27%) patients within a median time of 0.8 years (range, 0.06-7.7 years). Median seizure-free period before AED withdrawal was 1.3 years (range, 0.1-11 years). More than one tumor resection and whole-brain radiation treatment (WBRT) were associated with seizure recurrence, whereas posterior fossa tumor location was correlated with reduced seizure recurrence risk. At seizure recurrence, control was easily reestablished in 10 patients with AED reinstitution and after dose adjustment in five; two patients with poor drug compliance continue to have seizures. In 48 patients who had an EEG before AED withdrawal, spikes or slow waves did not correlate with seizure recurrence., Conclusions: AED withdrawal can be successfully achieved in majority of carefully selected patients. WBRT and multiple tumor resections seem to be associated with an increased hazard for seizure recurrence.

Purpose: To estimate the incidence and long-term outcome of brain tumor related seizures in children and to identify risk factors for adverse seizure outcome., Methods: Analysis of medical records of children treated for brain tumor and seizures in a single institution. Children were identified from hospital database and neurology clinic records. Seizure status was characterized for the 6 months prior to most recent follow-up., Results: Median follow-up after first seizure of the 157 analyzed children was 3.3 years. Tumor location was supratentorial in 81% and posterior fossa in 19%. Initial anti-epileptic drugs were phenytoin (n=52), carbamazepine (n=38), phenobarbital (n=14), gabapentin (n=31), or others (n=22). Seizures were controlled in 65% of the children and uncontrolled in 35% (17% intractable). Gabapentin showed a trend toward better seizure control (p=0.06). Neurologic deficit, T2 peri-cavity hyperintensity, and EEG slow waves were independently predictive of uncontrolled seizures by multivariate analysis., Conclusions: T2 peri-cavity hyperintensity, focal neurologic deficits, and EEG slow waves predict poor seizure control in children with brain tumors. Seizures can be controlled in most patients with brain tumors. Gabapentin use as first anti-epileptic drug needs to be studied prospectively.

Object: The aim of this study was to investigate the cause and outcome of intracranial hemorrhage (ICH) in children with cancer., Methods: The charts of 51 children who underwent treatment for both cancer and ICH between January 1985 and January 2003 were retrospectively reviewed. Assessment tools included the Karnofsky Performance Scale (KPS), Glasgow Coma Scale (GCS), and the Fisher exact and Student t-tests. Among the 51 cases, 30 involved brain tumors, 19 leukemia, and two lymphoma. The treatment group (Group 1) comprised 36 patients who suffered ICH during cancer treatment; the posttreatment group (Group 2) consisted of the 15 patients who suffered ICH after the completion of cancer treatment. The types of ICH included 22 cortical, four subcortical, 17 subdural, five brainstem, one subarachnoid, one epidural, and one ventricular. Thrombocytopenia was present in nine patients (25%) in Group 1. More patients in Group 2 (87%) than in Group 1 (44%) underwent cranial radiation treatment. Patients in Group 1 experienced a higher incidence of coagulopathy (37%) and ICH-related death (25%) than those in Group 2 (0 and 7%, respectively). Decrease in KPS and GCS scores of greater than 30 and greater than 3, respectively, at the time of ICH were indicators of increased mortality. Of the 17 children with subdural ICH, 13 suffered the hemorrhage following treatment for hydrocephalus and three patients suffered ICH associated with thrombocytopenia. In the 33 children alive at the 3-month follow-up examination after the ICH, no difference existed in the mean KPS scores pre- and post-ICH., Conclusions: Treatment for hydrocephalus, coagulopathy, thrombocytopenia, and hemorrhage into the tumor were the most probable causes of ICH among patients in Group 1. Radiation-induced vasculopathy was a possible cause of ICH in the patients in Group 2. Significant decline in the patient's neurological status at the time of ICH is a poor prognostic factor, but those patients who survive cancer and ICH are likely to regain neurological function.

Introduction: Some children treated for cancer become critically ill because of immune suppression and sepsis requiring prolonged intensive care support and assisted ventilation., Methods: Over a 3-year-period, we have identified six children (four with brain tumors) who developed a generalized movement disorder during a protracted intensive care unit stay. Median age was 2 years (range 1-6 years). Movement disorder developed while receiving multiple medications., Results: Sedation was achieved with midazolam and opioid infusions. Dystonic posturing of limbs, jaw movements, tongue thrusting, and intermittent eye deviations were present in all. Movements increased if the child was stimulated and an electroencephalogram performed in five children excluded seizures., Conclusions: This movement disorder should be differentiated from seizures to prevent inappropriate treatment. Exacerbation with stimulation is a clinical clue to the correct diagnosis and an electroencephalogram can help differentiate this movement disorder from seizures.

Purpose: Children surviving acute lymphoblastic leukemia (ALL) and malignant brain tumors (BTs) have a higher incidence of attention and learning problems in school than do their healthy peers. The present study tests the hypothesis that the psychostimulant methylphenidate (MPH) improves cognitive and social functioning among these patients., Patients and Methods: We report on 83 long-term survivors of ALL and BT identified as having attentional deficits on behavioral testing and parent or teacher report, and problems with academic achievement. The 47 male and 36 female patients ranged from 0.6 to 14.3 years (median, 5.4 years) of age at diagnosis and 6.7 to 17.9 years (median, 11.9 years) of age at participation. The patients (40 ALL, 43 BT) participated in a randomized, double-blind, 3-week home cross-over trial of placebo (bid), low-dose MPH (0.3 mg/kg; maximum dose, 10 mg bid), and moderate-dose MPH (0.6 mg/kg; maximum dose, 20 mg bid). The primary end points were weekly teacher and parent reports on the Conners' Rating Scales and Social Skills Rating System., Results: Compared to placebo, significant improvement with MPH was reported by teachers and parents on the Conners' Rating Scales and by teachers on the Social Skills Rating System. However, no consistent advantage of moderate dose over low dose was observed. Of those participating, 66 (79.5%) of the 83 patients continued on best clinical management., Conclusion: Treatment with MPH can at least temporarily reduce some attentional and social deficits among survivors of childhood ALL and BT. Long-term follow-up will reveal those subsets of patients who are more likely to benefit from MPH.

Purpose: We conducted a phase II trial of conformal radiation therapy (CRT) for localized childhood ependymoma to determine whether the irradiated volume could be reduced to decrease CNS-related side effects without diminishing the rate of disease control., Patients and Methods: Between July 1997 and January 2003, 88 pediatric patients (median age, 2.85 +/- 4.5 years) received CRT in which doses (59.4 Gy to 73 patients or 54.0 Gy after gross-total resection to 15 patients younger than 18 months) were administered to the gross tumor volume and a margin of 10 mm. Patients were categorized according to extent of resection (underwent gross total resection, n = 74; near-total resection, n = 6; subtotal resection, n = 8), prior chemotherapy (n = 16), tumor grade (anaplastic, n = 35), and tumor location (infratentorial, n = 68). An age-appropriate neurocognitive battery was administered before and serially after CRT., Results: The median length of follow-up was 38.2 months (+/- 16.4 months); the 3-year progression-free survival estimate was 74.7% +/- 5.7%. Local failure occurred in eight patients, distant failure in eight patients, and both in four patients. The cumulative incidence of local failure as a component of failure at 3 years was 14.8% +/- 4.0%. Mean scores on all neurocognitive outcomes were stable and within normal limits, with more than half the cohort tested at or beyond 24 months., Conclusion: Limited-volume irradiation achieves high rates of disease control in pediatric patients with ependymoma and results in stable neurocognitive outcomes., (Copyright 2004 American Society of Clinical Onocology)

Brain necrosis and edema develop in a proportion of brain tumor patients treated with radiosurgery. Surgical resection and corticosteroids have considerable morbidity. Two metastatic melanoma brain lesions in a 14-year-old girl were treated with radiosurgery and whole-brain radiation treatment. Both lesions became symptomatic from radiologic features of necrosis and edema and were unresponsive to oral corticosteroids. The larger lesion was resected, but the other lesion continued to enlarge. Cyclooxygenase-2 (COX-2) inhibitor was started, and the child improved clinically and radiologically. The usefulness of COX-2 inhibitors in treating radiation necrosis and edema, as suggested by this report, requires further study.

Atonic seizures are part of some childhood epilepsy syndromes and can also result from acquired central nervous system insult. Of 93 survivors of childhood cancer with uncontrolled seizures, 10 (11%) with atonic seizures form the basis for this report. Seven survived acute leukemia, and three survived brain tumors. The median age at cancer diagnosis was 9 months (range 2-52). Nine received systemic and six intrathecal chemotherapy; cranial irradiation was given to seven. All have learning difficulties, abnormal brain magnetic resonance images, and an abnormal electroencephalogram; six are developmentally delayed. All have difficult-to-control seizures, but six improved on myoclonus-specific drugs accelerated development in two younger patients. Atonic seizures in cancer survivors are associated with difficult-to-control seizures and pervasive cognitive impairments. Young age at cancer diagnosis and cranial irradiation may predispose the patient to development of this syndrome. Recognition and appropriate treatment of atonic seizures in cancer survivors could improve seizure control, neurologic development, and quality of life.

Temozolomide is an effective agent in the treatment of recurrent malignant gliomas. The standard dosage is 150-200 mg/m2 per day for 5 days in a 28-day cycle. A prior phase I study established a chronic daily temozolomide dose that significantly increased the total dose administered and suggested a superior response rate. In a prospective phase II trial, we treated 35 patients with recurrent malignant gliomas with temozolomide 75 mg/m2 per day for 42 consecutive days in a 70-day cycle. Median age was 55 years (range, 27-73 years) and median Karnofsky performance score was 70 (range, 60-90). Twenty-eight (79%) patients had glioblastoma multiforme, 3 (9%) anaplastic astrocytoma, 2 (6%) anaplastic oligodendroglioma, and 2 (6%) anaplastic oligoastrocytoma. All but one had prior radiotherapy, and 27 had prior chemotherapy. There were 2 partial (anaplastic astrocytoma) and 3 minor (glioblastoma multiforme) radiographic responses; 17 patients had progressive disease at the end of the first cycle. In 55 cycles of temozolomide, there were 8 episodes of asymptomatic drug-related grade 3 toxicity: 6 lymphopenia, 1 neutropenia, and 1 thrombocytopenia. Median progression-free survival and overall survival were 2.5 and 8.7 months (2.3 and 7.7 months in glioblastoma multiforme patients). At 6 months, progression-free survival and overall survival rates were 27% and 67% (19% and 60% in glioblastoma multiforme). Quality of life scores did not change significantly during treatment. We conclude that the extended low-dose schedule of temozolomide is well tolerated in heavily pre-treated patients; however, our results do not support an improved rate of response or survival.