Alveolar rhabdomyosarcoma has superior response rates to vinorelbine compared to embryonal rhabdomyosarcoma in patients with relapsed/refractory disease: A meta-analysis.

BACKGROUND: Patients with alveolar rhabdomyosarcoma (ARMS) have inferior outcomes compared to patients with embryonal rhabdomyosarcoma (ERMS) and more effective chemotherapy options are needed for these patients. Vinorelbine is a semisynthetic vinca alkaloid that has clinical activity in relapsed rhabdomyosarcoma (RMS) when used alone or in combination with cyclophosphamide. AIMS: The goal of our study was to evaluate whether RMS histology subtype influences response rate to vinorelbine alone or in combination. MATERIALS & METHODS: Five Phase 2 trials that enrolled RMS patients were included in the meta-analysis. Two studies evaluated vinorelbine alone, two studies evaluated vinorelbine in combination with low dose oral cyclophosphamide, and one study evaluated vinorelbine and intravenous cyclophosphamide in combination with temsirolimus or bevacizumab. All RMS patients had relapsed or refractory disease and had received at least one prior therapy. Response was reported according to RECIST1.1 and was defined as a complete or partial response. Response data was obtained from published results or from trial principal investigator. RMS NOS patients were grouped with ERMS patients for this analysis. Summary estimates comparing differences between ARMS and ERMS response rates were generated using a random-effects model to account for heterogeneity among the studies. RESULTS: One hundred fifty-six enrolled patients evaluable for response were included in the meta-analysis, 85 ARMS, 64 ERMS and 7 RMS-NOS. The combined effect generated from the random-effects model demonstrated a 41% increase (p = 0.001, 95% CI; 0.21-0.60) in response to vinorelbine as a single agent or in combination in patients with ARMS compared to patients with ERMS. There was no significant difference in the rate of progressive disease between patients with ARMS compared to ERMS (p = 0.1, 95%CI; -0.26-0.02). DISCUSSION: Vinorelbine is an active agent for the treatment of relapsed or refractory RMS and a meta-analysis of Phase 2 studies shows that radiographic responses in patients with ARMS were significantly higher than ERMS or RMS-NOS. CONCLUSION: These data support further investigation of vinorelbine in newly diagnosed patients with RMS particularly those with alveolar histology.

Predictors of cognitive function in pediatric brain tumor patients: Pre-surgery through 24-month follow-up.

The aim of this study was to examine the feasibility of cognitive assessment from pre-surgery through 2-year follow-up in a sample of pediatric brain tumor (BT) patients. We sought to investigate cognitive function over the course of diagnosis and treatment, and as a function of presenting problems, tumor location, treatment type, and tumor severity. Using a prospective, longitudinal design, standardized IQ measures were administered to pediatric BT patients (ages 6-16) prior to surgery (n = 25), 6 months post-diagnosis (n = 24), and 24 months post-diagnosis (n = 23). Group differences emerged based on tumor severity and treatment type at multiple time points, including prior to surgical intervention; children with high grade tumors performed more poorly than children with low grade tumors, and children receiving surgery plus adjuvant therapy performed more poorly than children who received surgery only. When considered together, an analysis of covariance demonstrated that tumor grade significantly accounted for variability in cognitive functioning, while treatment type did not. Although there is overlap clinically between tumor severity and treatment received, results suggest that tumor severity is an important factor contributing to variability in cognitive functioning and should also be considered when monitoring risk for cognitive deficits in children diagnosed with BT.

Associations among diffusion tensor imaging and neurocognitive function in survivors of pediatric brain tumor: A pilot study.

The purpose of this study was to determine associations among neurocognitive outcomes and white matter integrity in the inferior fronto-occipital fasciculus (IFOF), uncinate fasciculus (UF), and genu of the corpus callosum (gCC) in survivors of pediatric brain tumor and healthy controls (HCs). Eleven survivors (ages 8-16; >2 years post-treatment) and 14 HCs underwent MRI; diffusion tensor imaging tractography (DSI Studio) was used to assess white matter integrity. Participants completed neuropsychological assessment of overall cognitive ability, executive function, processing speed, divided attention, and memory. As previously reported, survivors performed significantly worse than HCs on measures of overall IQ, working memory, processing speed, and executive function (ps < .01), but not on measures of long-delay memory. Mean fractional anisotropy was significantly lower in survivors than HC in the right IFOF, left UF, and gCC (ps < .05). Correlations with the total sample revealed a number of significant positive associations among white matter tracts and scores on neurocognitive measures. Survivors show deficits on measures of cognitive function and decreased white matter integrity compared to HCs. Results revealed a more general pattern of associations among white matter pathways and neurocognitive outcomes than initially hypothesized. It is possible that survivors with diffuse pathology from treatment effects (i.e., hydrocephalus or posterior fossa syndrome) show more general decreases in cognitive functioning and white matter integrity. Additional research with a larger and more diverse group of survivors is needed to better understand white matter integrity and neurocognitive outcome associations in this population.

Eutectic mixture of lidocaine and prilocaine versus 1% lidocaine injection for lumbar punctures in pediatric oncology patients.

BACKGROUND: The role of local analgesics for lumbar punctures (LPs) in pediatric oncology patients has not been specifically studied. AIM: To compare the efficacy of eutectic mixture of local anesthetics (EMLA) cream to 1% lidocaine injection for LPs. METHOD: This was a retrospective observational study of all patients receiving either EMLA cream (EMLA group) or 1% lidocaine subcutaneous injection (lidocaine group) in addition to fentanyl and propofol for LPs over 18 months. Demographics, vital parameters, procedural and recovery times, propofol and fentanyl doses, and adverse events were studied. RESULTS: Two hundred ninety LPs in 49 children were studied: 148 in the EMLA group and 142 in the lidocaine group. There was no difference in demographics or preprocedural parameters between the two groups. LPs in the EMLA group were completed in a shorter time (7.5 minutes [CI 7.0-8.1] vs 9.4 minutes [CI 8.9-9.9]) with a faster recovery time (38.7 minutes [CI 36.9-40.9] vs 43.9 minutes. [CI 41.9-45.9]) as compared with the lidocaine group (P < 0.001). The EMLA group required less maintenance doses (0.54 mg/kg [CI 0.47-0.62] vs 1.14 mg/kg [CI 1.06-1.21]) and total doses (2.58 mg/kg [CI 2.42-2.75] vs 3.12 mg/kg [CI 2.95-3.29]) of propofol as compared with the lidocaine group (P < 0.0001). Adverse events in the EMLA group were less (19% vs 41%) as compared with the lidocaine group (P < 0.0001). CONCLUSION: The addition of EMLA cream for procedural sedation for LPs in pediatric oncology patients significantly improves pain management in comparison with 1% lidocaine injection.

Fronto-limbic white matter microstructure, behavior, and emotion regulation in survivors of pediatric brain tumor.

PURPOSE: After treatment, pediatric brain tumor survivors (PBTS) face emotional and behavioral challenges, perhaps due to tumor or treatment-related changes in brain structures involved in emotion regulation, including those with fronto-limbic connections. We hypothesized that relative to healthy controls (HCs), PBTS would exhibit greater difficulties with behavior and emotional functioning, and display reduced mean fractional anisotropy (mFA) in white matter tracts with fronto-limbic connections including the cingulum bundle (CB), inferior fronto-occipital fasciculus (IFOF), and uncinate fasciculus (UF). We further predicted that mFA would account for variance in the relationship between group and emotional/behavioral outcome. METHODS: Eleven 8-16 year old PBTS and 14 HCs underwent MRI, including diffusion tensor imaging to assess white matter microstructure. Tractography quantified mFA of selected tracts. Parents rated children's emotional and behavioral functioning. RESULTS: Compared to HCs, caregivers of PBTS reported poorer behavioral regulation and greater internalizing and externalizing symptoms. Relative to HCs, PBTS had lower mFA within the bilateral CB, IFOF, and UF (ds = 0.59-1.15). Across groups, several medium-to-large correlations linked tract mFA and increased internalizing, externalizing, and poor behavioral regulation. Tract mFA also accounted for significant variance in the group-outcome association. CONCLUSIONS: Reduced mFA in fronto-limbic associated tracts may be associated with reduced behavioral regulation following pediatric brain tumor. PBTS with treatment known to impact white matter may be most susceptible. Research with larger, longitudinal samples should clarify this relationship, allow for multiple mediators across time, and consider factors like tumor and treatment type.

A Congenital Case of Ependymoblastoma: A Rare and Aggressive Brain Tumor.

Congenital brain tumors are rare, representing <2% of all childhood brain tumors. Of these, ependymoblastoma is a profoundly aggressive embryonal brain tumor that is included in the diagnostic entity known as an embryonal tumor with multilayered rosettes. This report of a congenital ependymoblastoma diagnosed at birth aims to highlight how much remains unknown about embryonal tumor with multilayered rosettes and the devastating prognosis of this condition. Despite recent advancements made in identifying molecular targets for therapy, this tumor continues to have a high rate of recurrence with few successful treatment options, especially when diagnosed in the newborn period.

Early Testing of Serum Ferritin Facilitates Hemophagocytic Lymphohistiocytosis Diagnosis in Children.

The clinical and laboratory features of hemophagocytic lymphohistiocytosis (HLH) are nonspecific that makes the definitive diagnosis of HLH very challenging. The disease is almost universally fatal in the absence of early recognition and appropriate therapy. Elevated serum ferritin level is one of the diagnostic markers of HLH disease. We report the value of testing serum ferritin level early in the disease process in 3 pediatric patients who presented with persistent fever and sepsis-like features. Detection of elevated serum ferritin levels facilitated further testing to confirm the diagnosis of HLH and initiate early therapy with good outcomes.

Dynamic re-immunization of off-treatment childhood cancer survivors: An implementation feasibility study.

There are no universally approved re-vaccination guidelines for non-transplant pediatric cancer survivors. We hypothesized that by utilizing a response-based re-vaccination schedule, we could tailor vaccine schedules in off-treatment cancer survivors. Pre-vaccination antibody levels were obtained in 7 patients at an average of 20 days after the end of treatment date. In those without protective antibody levels, we administered vaccines 3 months after completion of treatment. Revaccinating patients 3 months after the end of treatment date resulted in protective antibody levels for most vaccines. We showed, on a preliminary basis, that vaccinating non-transplanted pediatric cancer survivors can be dynamically implemented in children with recovering immune function.

Functional neuroimaging of working memory in survivors of childhood brain tumors and healthy children: Associations with coping and psychosocial outcomes.

PURPOSE: Pediatric brain tumors are the second most common cancer diagnosis in individuals under age 20 and research has documented significant neurocognitive, psychosocial, and emotional late effects. Associations among these deficits have not been adequately considered and the role of survivors' coping with stress in relation to deficits is unknown. Further, research has yet to examine neurobiological processes related to neurocognitive, psychosocial, and emotional difficulties in survivors through the use of functional neuroimaging. METHOD: Questionnaire measures and functional neuroimaging were used to examine the neurocognitive, psychosocial, and emotional functioning and coping responses of survivors of pediatric brain tumors (N = 17; age 8-16) and healthy children (N = 15). RESULTS: Survivors experienced elevated levels of psychosocial and behavioral/emotional difficulties relative to healthy controls and normative data. Increases in brain activation in prefrontal and other anterior regions in response to a working memory task were associated with better psychosocial functioning, use of engagement coping strategies, and less use of disengagement coping strategies. Regression analyses suggest coping accounts for a significant portion of the association between brain activation and behavioral/emotional functioning. CONCLUSIONS: This study extends late-effects research by examining neurobiological processes associated with psychosocial and emotional difficulties. These findings contribute to our understanding of difficulties in survivors and provide a foundation for research exploring these associations and mediators of deficits in future longitudinal studies.

Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations.

Individuals harboring germ-line DICER1 mutations are predisposed to a rare cancer syndrome, the DICER1 Syndrome or pleuropulmonary blastoma-familial tumor and dysplasia syndrome [online Mendelian inheritance in man (OMIM) #601200]. In addition, specific somatic mutations in the DICER1 RNase III catalytic domain have been identified in several DICER1-associated tumor types. Pituitary blastoma (PitB) was identified as a distinct entity in 2008, and is a very rare, potentially lethal early childhood tumor of the pituitary gland. Since the discovery by our team of an inherited mutation in DICER1 in a child with PitB in 2011, we have identified 12 additional PitB cases. We aimed to determine the contribution of germ-line and somatic DICER1 mutations to PitB. We hypothesized that PitB is a pathognomonic feature of a germ-line DICER1 mutation and that each PitB will harbor a second somatic mutation in DICER1. Lymphocyte or saliva DNA samples ascertained from ten infants with PitB were screened and nine were found to harbor a heterozygous germ-line DICER1 mutation. We identified additional DICER1 mutations in nine of ten tested PitB tumor samples, eight of which were confirmed to be somatic in origin. Seven of these mutations occurred within the RNase IIIb catalytic domain, a domain essential to the generation of 5p miRNAs from the 5' arm of miRNA-precursors. Germ-line DICER1 mutations are a major contributor to PitB. Second somatic DICER1 "hits" occurring within the RNase IIIb domain also appear to be critical in PitB pathogenesis.

Neuroimaging of executive function in survivors of pediatric brain tumors and healthy controls.

OBJECTIVE: Research on the long-term sequelae of treatment for pediatric brain tumors has identified significant neurocognitive deficits experienced by many survivors. Despite indications of deficits based on cognitive assessment, the identification of specific neurobiological mechanisms of these deficits using neuroimaging techniques has yet to be considered. METHOD: This study used norm-referenced standardized assessment and functional MRI (fMRI) to examine attention and executive functioning deficits of survivors of pediatric brain tumors, as compared with healthy children. RESULTS: Survivors of pediatric brain tumors performed more poorly than healthy children on measures of overall cognitive ability, attention, and executive function during testing, as well as on a working memory task during fMRI. Survivors showed lower blood-oxygen level dependent (BOLD) signal in bilateral frontal regions associated with sustained attention (BA6/8) and greater BOLD signal in left cingulate regions associated with complex problem-solving and performance monitoring (BA32) during working memory task completion. Both group and brain activation accounted for significant variance in neurocognitive functioning. CONCLUSIONS: Survivors of pediatric brain tumor and healthy children differed in brain activation during completion of a working memory task, and brain activation was associated with deficits noted in testing. These findings may improve understanding of mechanisms of cognitive deficits and avenues for intervention for children with brain tumors.

Neurocognitive late effects of pediatric brain tumors of the posterior fossa: a quantitative review.

Deficits in neurocognitive functioning are an important area of late effects in survivors of pediatric brain tumors; however, a quantitative analysis of the magnitude of these deficits in survivors of brain tumors of the posterior fossa has not been conducted. Despite tumor locations in the posterior regions of the brain, individual studies have documented deficits in a variety of domains, reflective of impairment in other brain regions. The current study provides a comprehensive meta-analysis of literature on neurocognitive late effects found in survivors of posterior fossa tumors. Results indicated significant deficits in both specific and broad indices of neurocognitive functioning, and the overall magnitude of effects across domains ranged from medium to large (g = -0.62 to -1.69) with a large mean overall effect size (g = -1.03). Moderator analyses indicated significantly greater effects for survivors diagnosed at a younger age and those who received radiation therapy. These findings underscore the importance of monitoring neurocognitive late effects in survivors of pediatric brain tumors of the posterior fossa, as well as the need for more consistent consideration of demographic, diagnostic, and treatment-related variables to allow for examination of factors that moderate these deficits.

A quantitative meta-analysis of neurocognitive sequelae in survivors of pediatric brain tumors.

BACKGROUND: Deficits in neurocognitive functioning are an important area of late effects in survivors of pediatric brain tumors, but a quantitative analysis of the magnitude of these deficits has yet to be conducted. PROCEDURE: The purpose of the current article is to provide a comprehensive meta-analysis of the literature on long-term neurocognitive effects found in these survivors. RESULTS: Results indicated significant deficits in both narrow and broad indices of neurocognitive functioning, and the overall magnitude of the effects across all domains ranged from small to large in magnitude (g = -0.45 to -1.43) with a large mean overall effect size of g = -0.91. CONCLUSIONS: These findings underscore the importance of monitoring the neurocognitive late effects in survivors of pediatric brain tumors, and the need for more consistent consideration of demographic, diagnostic, and treatment-related variables in future research to allow for examination of factors that may moderate these deficits.

Phase II evaluation of intravenous vinorelbine (Navelbine) in recurrent or refractory pediatric malignancies: a Children's Oncology Group study.

BACKGROUND: A Phase II trial was developed to determine the efficacy and toxicity of intravenous vinorelbine, a semi-synthetic vinca alkaloid, in children, adolescent, and young adults with recurrent or refractory solid malignancies. PROCEDURES: Fifty patients were enrolled among three strata: soft tissue sarcomas [rhabdomyosarcoma (RMS), non-rhabdomyosarcoma, primitive neuroepithelial tumor] (20 patients); brain tumors [astrocytoma (4 patients), medulloblastoma (2 patients), other (16 patients)] (22 patients); neuroblastoma (8 patients). Vinorelbine was given weekly for 6 consecutive weeks during an 8-week interval. The response rate and toxicity profile was assessed. RESULTS: Among the first 35 patients treated at 33.75 mg/m(2)/dose, 25 experienced grades 3-4 neutropenia (75%). The dose was decreased to 30 mg/m(2)/dose in the remaining 15 patients. The median age was 10 years (range, 1-25). Four responses (one complete, three partial) occurred within the soft tissue sarcoma strata (all with RMS) and two occurred in the brain tumor group (medulloblastoma and astrocytoma). The most common toxicities were hematological and neurological. CONCLUSION: Vinorelbine at dose of 30 mg/m(2) can be safely administered to children with recurrent or refractory solid malignancies. The study design identified vinorelbine to be active in the sarcoma category, with a response rate of 36% (4/11) among RMS patients.

Utility of FDG-PET/CT in follow-up of children treated for Hodgkin and non-Hodgkin lymphoma.

Positron emission tomography using F-flurodeoxyglucose (FDG-PET) is considered an excellent tool for staging and monitoring disease status in adults with lymphoma. We retrospectively reviewed results of PET/CT and diagnostic computed tomography (CT) scans performed during follow-up after completion of therapy in 41 children <18 years of age with Hodgkin lymphoma and non-Hodgkin lymphoma. PET/CT scan with uptake greater than that of the liver was considered positive. Uptake that increased over the background but less than in the liver was equivocal. Clinical outcomes were obtained from medical records. Thirteen (32%) had a positive PET/CT scan and an equal number had equivocal scans in a median follow-up of 2.3 years. Diagnostic CT scans revealed new findings in 13 (32%) and persistent abnormalities in 21 (51%) of the children. Five children developed recurrent disease, and one developed a second cancer. No children with equivocal positivity developed recurrent disease. PET/CT scan was 95% sensitive, with a positive predictive value (PPV) of 53%. Diagnostic CT was 79% sensitive, with a PPV of 52%. We conclude that a negative PET/CT scan during routine follow-up for lymphoma in children strongly suggests absence of recurrence but a positive PET/CT and diagnostic CT scans have low PPV and should be interpreted with caution in this setting.

Phase I and pharmacokinetic study of thalidomide with carboplatin in children with cancer.

PURPOSE: Tumor growth and metastasis is believed to depend on the tumor's ability to induce neovascularization. Recent studies have indicated that thalidomide inhibits angiogenesis. We performed a phase I and pharmacokinetic study of thalidomide with carboplatin in children with refractory solid tumors. PATIENTS AND METHODS: Carboplatin was administered as a single intravenous dose once every 21 days at a target area under the concentration-time curve of 6 mg/mL.min. Thalidomide was administered daily by mouth. The initial dose level was 100 mg/m(2)/d with intrapatient dose escalation to a maximum dose of 300 mg/m(2)/d. The next cohort of patients started at a dose of 300 mg/m(2)/d, with intrapatient dose escalation to a maximum dose of 500 mg/m(2)/d. Standard response and adverse event criteria were used. Serial blood samples for thalidomide pharmacokinetics studies were obtained after the first dose. RESULTS: Twenty-two patients received 56 cycles of therapy. The maximum tolerated thalidomide dose was 400 mg/m(2)/d. The dose-limiting toxicity was somnolence. There were no objective responses. Thalidomide's apparent clearance was 55 +/- 16 mL/min/m(2) and the terminal half-life was 5.9 +/- 2.8 hours. There was no evidence of dose-dependent pharmacokinetics in the narrow range studied. CONCLUSION: Thalidomide at a dose of 400 mg/m(2)/d can be safely administered to children with solid tumors in combination with carboplatin. Somnolence is the major toxicity. In addition, we have characterized the pharmacokinetic behavior of thalidomide in children. This study can serve as the basis for future investigation of thalidomide as an anticancer agent in children.

Pathologically proven cavernous angiomas of the brain following radiation therapy for pediatric brain tumors.

Lesions consistent with cavernous angiomas (CAs) of the brain are sometimes seen on MRI scans of the brains of patients who received radiation therapy for brain tumors as children. The lesions appear years later within brain tissue that was included in radiation fields. It is unclear whether these MRI-detected lesions are true CAs or a pathological variant. This study reports the clinical, radiographical, and pathological findings in 3 cases of radiation-induced CAs of the brain. From 1995 to 1997, 3 patients previously treated with radiation therapy (45-55 Gy) for pediatric brain tumors (medulloblastoma, ependymoma, and a presumed midbrain astrocytoma) underwent resections of symptomatic and enlarging lesions that were consistent with a CA of the brain. All of the lesions occurred within fields of prior irradiation. None of the patients had received chemotherapy as part of their cancer treatment. CA-presenting symptoms included seizures, cranial nerve deficits, and headaches. The lesions appeared 7-19 years after radiation therapy and slowly enlarged on subsequent imaging studies. MRI scans of the lesions revealed characteristics typical of CA. The lesions became symptomatic 1-5 years after they were initially noted. Surgical resection was performed 1-2 years after symptoms began. The age at resection ranged from 15 to 23 years (10-21 years after radiation therapy). Pathological analysis of the three lesions showed typical CA characteristics. Some CAs may be caused by radiation therapy for pediatric brain tumors. They are radiologically and pathologically similar to sporadically occurring CAs of the brain and may enlarge over time and become symptomatic. CAs can be safely resected using standard microsurgical techniques.

Triiodothyronine supplementation for hypothalamic obesity.

Patients with suprasellar lesions develop profound hypothalamic obesity and listlessness with no effective treatment. We added triiodothyronine (T(3)) supplementation in 3 such patients and present their response. All had previous nutritional counseling without benefit. All were treated for diabetes insipidus (DI) and hypopituitarism; serum free thyroxine (T(4)) level was normal. A 24-year-old woman (pineal tumor and astrocytoma) had weight gain (4.7 kg/yr for 3 years), cold intolerance, fatigue, dry skin, and constipation; after T(3), she lost 14 kg over 27 months and reported overall improvement. Her bone mineral density also improved. A 10.6-year-old boy (optic glioma) was gaining 6 kg/yr for 4 years; after T(3) supplement, he lost 4.3 kg over 11 months. A 12-year-old girl (mixed germ cell tumor) had weight gain (8.3 kg/yr for 3 years) and listlessness; after T(3), she lost 8.1 kg over 16 months and had improved alertness. All patients were asymptomatic despite supraphysiologic T(3) levels. We suggest that T(3) may serve as a simple and effective supplement, which can promote weight loss and improve the well being of these patients with hypothalamic obesity.

A phase II study of temozolomide in patients with newly diagnosed supratentorial malignant glioma before radiation therapy.

Temozolomide is a novel second-generation oral alkylating agent with demonstrated efficacy and safety in patients with recurrent glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA). A multicenter phase II trial was conducted to determine the efficacy and safety of temozolomide before radiotherapy in patients with newly diagnosed GBM and AA. Fifty-seven patients (51 adult, 6 pediatric) with newly diagnosed supratentorial GBM or AA were treated with temozolomide (200 mg/m ( 2 ) per day for 5 consecutive days every 28 days) for a maximum of 4 cycles. All patients were then treated with external beam radiotherapy. Twenty-two patients (39%) achieved objective response, including 6 (11%) with complete response (CR) and 16 (28%) with partial response (PR). Additionally, 18 (32%) patients had stable disease (SD). Of 21 patients (18 adult, 3 pediatric) with AA, 2 (10%) achieved CR, 5 (24%) achieved PR, and 8 (38%) had SD. Among adult patients with AA, the median progression-free and overall survival rates were 7.6 and 23.5 months, respectively. Among 36 patients (33 adult, 3 pediatric) with GBM, 4 (11%) had CR, 11 (31%) had PR, and 10 (28%) had SD. The median progression-free and overall survival rates among adult patients with GBM were 3.9 and 13.2 months, respectively. Temozolomide was safe and well tolerated in adult and pediatric patients. Grades 3 and 4 adverse events were reported in 16 (28%) and 7 (12%) patients, respectively. Temozolomide was safe and effective in treating newly diagnosed GBM and AA before radiotherapy. This pre-irradiation treatment approach appears promising, but will require additional evaluation in comparative studies.