Outcomes of Infants and Young Children With Relapsed Medulloblastoma After Initial Craniospinal Irradiation-Sparing Approaches: An International Cohort Study.

PURPOSE: Infant and young childhood medulloblastoma (iMB) is usually treated without craniospinal irradiation (CSI) to avoid neurocognitive late effects. Unfortunately, many children relapse. The purpose of this study was to assess salvage strategies and prognostic features of patients with iMB who relapse after CSI-sparing therapy. METHODS: We assembled a large international cohort of 380 patients with relapsed iMB, age younger than 6 years, and initially treated without CSI. Univariable and multivariable Cox models of postrelapse survival (PRS) were conducted for those treated with curative intent using propensity score analyses to account for confounding factors. RESULTS: The 3-year PRS, for 294 patients treated with curative intent, was 52.4% (95% CI, 46.4 to 58.3) with a median time to relapse from diagnosis of 11 months. Molecular subgrouping was available for 150 patients treated with curative intent, and 3-year PRS for sonic hedgehog (SHH), group 4, and group 3 were 60%, 84%, and 18% (P = .0187), respectively. In multivariable analysis, localized relapse (P = .0073), SHH molecular subgroup (P = .0103), CSI use after relapse (P = .0161), and age ≥ 36 months at initial diagnosis (P = .0494) were associated with improved survival. Most patients (73%) received salvage CSI, and although salvage chemotherapy was not significant in multivariable analysis, its use might be beneficial for a subset of children receiving salvage CSI < 35 Gy (P = .007). CONCLUSION: A substantial proportion of patients with relapsed iMB are salvaged after initial CSI-sparing approaches. Patients with SHH subgroup, localized relapse, older age at initial diagnosis, and those receiving salvage CSI show improved PRS. Future prospective studies should investigate optimal CSI doses and the role of salvage chemotherapy in this population.

Features Associated With Weight Loss and Growth Stunting for Young Children During Cancer Therapy.

Features associated with malnutrition are poorly elucidated in pediatric cancer care. We aimed to better understand characteristics associated with weight-for-height (WHZ) and height-for-age (HAZ) changes for infants and young children during cancer treatment. This retrospective study included 434 patients diagnosed <3 years old from 2007 to 2015 at a large pediatric cancer center. Patients starting treatment outside our center, those with relapsed or secondary malignancies, or with inaccurate information were excluded. Abstracted weights and heights for a 24-month period after treatment initiation were converted to sex-specific and age-specific z scores. Although not statistically different at baseline, patients with hematologic malignancies gained weight over time, while other tumor types did not. Higher treatment intensity and younger age at diagnosis increased odds of clinically significant weight loss. Older children had higher HAZ at diagnosis and HAZ also significantly decreased over time for all examined risk factors, which is distinctly different from patterns in WHZ over time. In conclusion, WHZ and HAZ are affected differently by cancer treatment in infants and young children. We identify key risk factors for weight loss and growth stunting which will be necessary to develop prospective trials to examine anthropometric, biochemical, and patient recorded outcomes around nutrition.

Impact of executive functioning on health-related quality of life of pediatric brain tumor survivors.

BACKGROUND: Brain tumor survivors are at risk for significant late effects following treatment completion that may adversely impact health-related quality of life (HRQOL). The current study examines the relationship between executive functioning (EF) and HRQOL in pediatric brain tumor survivors within a longitudinal framework. We hypothesized that early deficits in EF would be related to less optimal HRQOL in this population. PROCEDURE: The current study utilized retrospective medical chart review to identify neurocognitive correlates of HRQOL in 137 youth previously treated for a pediatric brain tumor. Participants completed the Pediatric Quality of Life Inventory (PedsQL) and neuropsychological assessment, including a well-validated measure of executive functioning (Behavior Rating Inventory of Executive Function; BRIEF). General linear regression and multivariate models were utilized to examine the relationship between child executive functioning and HRQOL. RESULTS: Multiple domains of child executive functioning, as reported by parents on the BRIEF, significantly predicted parent-proxy reported HRQOL after controlling for demographic and medical covariates, including child intellectual functioning (IF). Similarly, after controlling for covariates, the BRIEF Cognitive Regulation Index was a significant predictor of self-reported physical and school functioning domains of HRQOL. CONCLUSION: Current data demonstrate EF is a significant predictor of HRQOL during survivorship for youth previously diagnosed with a pediatric brain tumor. Results suggest that opportunities may exist to intervene and improve HRQOL of pediatric brain tumor survivors by targeting EF.

Normalized measures and patient characteristics to identify undernutrition in infants and young children treated for cancer.

BACKGROUND: Various measures and definitions for undernutrition are used in pediatrics. Younger children treated for cancer are at high risk, but lack well-defined risk-based screening and intervention. METHODS: A retrospective study collected weight longitudinally for patients less than three years-old over two years after initiating cancer treatment. We included those diagnosed 2007-2015 at a large pediatric cancer center. Exclusion criteria included treatment starting outside our system, secondary or relapsed malignancy, or incomplete information. A decrease ≥1 in weight-for-age or weight-for-height z-score signified clinically significant weight loss. Univariate and multivariate models assessed hazards for developing first episode of clinically significant weight loss. RESULTS: Of 372 patients, only 24.6% of patients lost 10% of weight, but 58.6% lost weight-for-age z-score ≥1 and 64.8% lost ≥1 weight-for-height z-score within two years of treatment initiation. Patients who lost weight were younger (median age 15 vs. 24 months, p < 0.001). Compared to patients diagnosed in the first year of life, those diagnosed 24-35 months were less likely to lose weight (HR 0.62, p < 0.001) and lost weight later (median time to weight loss 144 vs. 35 days). Higher treatment intensity increased weight loss risk (HR 2.30, p < 0.001) and decreased time to weight loss (35 vs. 154 days). No differences were found based on sex, diagnosis, enteral or parenteral nutrition, gastroenterology consults, or intensive care admissions. CONCLUSIONS: Using normalized z-scores is more sensitive for identifying weight loss. Younger children are more likely to lose weight with higher intensity cancer therapy. Patient and treatment specific information should be used in risk stratifying weight loss screening and nutritional interventions.

Efficacy of High-Dose Chemotherapy and Three-Dimensional Conformal Radiation for Atypical Teratoid/Rhabdoid Tumor: A Report From the Children's Oncology Group Trial ACNS0333.

PURPOSE: Atypical teratoid/rhabdoid tumor (AT/RT) is an aggressive, early-childhood brain tumor without standard effective treatment. To our knowledge, we conducted the first AT/RT-specific cooperative group trial, ACNS0333, to examine the efficacy and safety of intensive postoperative chemotherapy and focal radiation to treat AT/RT. PATIENTS AND METHODS: Patients from birth to 22 years of age with AT/RT were eligible. After surgery, they received 2 courses of multiagent chemotherapy, followed by 3 courses of high-dose chemotherapy with peripheral blood stem cell rescue and involved-field radiation therapy. Timing of radiation was based on patient age and disease location and extent. Central testing of tumor and blood for SMARCB1 status was mandated. Tumor molecular subclassification was performed retrospectively. The primary analysis was event-free survival (EFS) for patients < 36 months of age compared with a cooperative groups' historical cohort. Although accrual was based on the therapeutic question, potential prognostic factors, including age, tumor location, M stage, surgical resection, order of therapy, germline status, and molecular subtype, were explored. RESULTS: Of 65 evaluable patients, 54 were < 36 months of age. ACNS0333 therapy significantly reduced the risk of EFS events in patients < 36 months of age compared with the historical cohort (P < .0005; hazard rate, 0.43; 95% CI, 0.28 to 0.66). Four-year EFS and overall survival for the entire cohort were 37% (95% CI, 25% to 49%) and 43% (95% CI, 31% to 55%), respectively. Timing of radiation did not affect survival, and 91% of relapses occurred by 2 years from enrollment. Treatment-related deaths occurred in 4 patients. CONCLUSION: The ACNS0333 regimen dramatically improved survival compared with historical therapies for patients with AT/RT. Clinical characteristics and molecular subgrouping suggest prognostic differences. ACNS0333 results lay a foundation on which to build future studies and incorporate testing of new therapeutic agents.

A Review of Chronic Leukoencephalopathy among Survivors of Childhood Cancer.

Currently, there are an estimated 400,000 long-term survivors of childhood cancer in the United States. Chronic leukoencephalopathy is a potential devastating late effect that can manifest as a range of neurological and neurocognitive sequelae. Survivors of the acute lymphocytic leukemia, central nervous system tumors, and stem cell transplant have frequently been exposed to cranial radiation, systemic and intrathecal chemotherapy, which places them at risk of developing chronic leukoencephalopathy. Defining leukoencephalopathy and its neuroimaging characteristics, the population of survivors at risk, its long-term consequences, and identifying prevention and intervention strategies can potentially mitigate the morbidity of these survivors. Better understanding of those at risk of leukoencephalopathy and its symptoms can lead to an improved quality of life for these cancer survivors.

Guidelines for Treatment and Monitoring of Adult Survivors of Pediatric Brain Tumors.

OPINION STATEMENT: Pathologies of pediatric brain tumors are more varied than those diagnosed in adults and survival outcomes more optimistic. Therapies for pediatric brain tumors are also diverse and treatment options are expanding. The growing number of adult survivors of childhood brain tumors is quite diverse. Medical management of these adults requires understanding the tumor diagnosis and location, the modalities used to treat the tumor, the age of the survivor at the time of diagnosis and treatment, any complications of treatment, and, most importantly, the baseline medical condition and neurological function of each adult survivor. A network of medical, neurological, and mental health providers is critical in the care of a child with a brain tumor. A comparable network should be available to survivors of these tumors since they may transition to adulthood with medical and neurological deficits and can acquire additional late effects of treatments as they age. Optimally, each survivor will have an individualized survivor health plan (SHP) that concisely summarizes the tumor, treatments, potential late effects, and screening that may identify evolving late effects before they impact mental, social or physical functioning. This plan helps patients, families, and the medical team advocate for surveillance aiming to optimize the survivor's quality of life. Failure to support the health and function of these heroic cancer survivors renders the medical advances, the courage, and the struggle that permitted survival meaningless.

Clinical responses of patients with diffuse leptomeningeal glioneuronal tumors to chemotherapy.

INTRODUCTION: Diffuse leptomeningeal glioneuronal tumors (DLGT) have been recognized in the most recent WHO classification as a distinct entity. OBJECTIVE: We describe seven pediatric cases of DLGT and the responses to therapy and outcome. METHODS: We conducted a retrospective review of charts from 1985 to 2013. RESULTS: DBS is an effective therapeutic modality for intractable TLE, particularly in patients with lateralized EEG A total of seven patients were identified. Median age at diagnosis was 3 years. Three months was the median time from symptom development to diagnosis. Common MRI findings included diffuse leptomeningeal thickening, nodularity, or coating of the subarachnoid or ependymal surfaces. The leptomeningeal lesions often appear cystic and contrast enhancement was variable. Six patients had leptomeningeal involvement of the brain and spine. All patients had a negative CSF cytology. Biopsies demonstrated thickened meninges infiltrated by a monotonous population of oligodendrocyte-like cells. Immunohistochemistry revealed variable features of neuronal and/or glial differentiation. All samples were negative for BRAF V600E mutation by immunohistochemistry. Therapy included one patient treated with craniospinal irradiation followed by vincristine, etoposide, cyclophosphamide, and cisplatin with stable disease for 164 months. Six patients received carboplatin and vincristine with a median duration of response of 20+ months (15-122+). Three patients received temozolomide upfront and progressed at 3, 4, and 27 months. No patients demonstrated complete or partial responses to any chemotherapy regimens. Progression-free survival ranged from 3 to 164+ months; 4/7 patients remained free of progression. All patients are alive. CONCLUSIONS: DLGT are rare tumors that lack imaging responses; however, there was clinical/ symptom improvement in 100% of the patients. A better understanding of the tumor biology is necessary to improve the diagnosis and treatment of this rare disease.

Morbidity and Mortality Associated With Meningioma After Cranial Radiotherapy: A Report From the Childhood Cancer Survivor Study.

Purpose Little is known about neurologic morbidity attributable to cranial radiotherapy (CRT) -associated meningiomas. Materials and Methods From 4,221 survivors exposed to CRT in the Childhood Cancer Survivor Study, a diagnosis of meningioma and onset of neurologic sequelae were ascertained. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% CIs to evaluate the factors associated with neurologic sequelae after subsequent meningioma. Results One hundred ninety-nine meningiomas were identified among 169 participants. The median interval from primary cancer to meningioma diagnosis was 22 years (5 to 37 years). The cumulative incidence of a subsequent meningioma by age 40 years was 5.6% (95% CI, 4.7% to 6.7%). CRT doses of 20 to 29.9 Gy (HR, 1.6; 95% CI,1.0 to 2.6) and doses ≥ 30 Gy (HR, 2.6; 95% CI, 1.6 to 4.2) were associated with an increased risk of meningioma compared with CRT doses of 1.5 to 19.9 Gy ( P < .001). Within 6 months before or subsequent to a meningioma diagnosis, 20% (30 of 149) reported at least one new neurologic sequela, including seizures (8.3%), auditory-vestibular-visual deficits (6%), focal neurologic dysfunction (7.1%), and severe headaches (5.3%). Survivors reporting a meningioma had increased risks of neurologic sequelae > 5 years after primary cancer diagnosis, including seizures (HR, 10.0; 95% CI, 7.0 to 15.3); auditory-vestibular-visual sensory deficits (HR, 2.3; 95% CI, 1.3 to 4.0); focal neurologic dysfunction (HR, 4.9; 95% CI, 3.2 to 7.5); and severe headaches (HR, 3.2; 95% CI, 1.9 to 5.4). With a median follow-up of 72 months after meningioma diagnosis (range, 3.8 to 395 months), 22 participants (13%) were deceased, including six deaths attributed to a meningioma. Conclusion Childhood cancer survivors exposed to CRT and subsequently diagnosed with a meningioma experience significant neurologic morbidity.

Nonrandomized comparison of neurofibromatosis type 1 and non-neurofibromatosis type 1 children who received carboplatin and vincristine for progressive low-grade glioma: A report from the Children's Oncology Group.

BACKGROUND: To evaluate tumor responses, event-free survival (EFS), overall survival (OS), and toxicity of chemotherapy, children with neurofibromatosis type 1 (NF1) and progressive low-grade glioma were enrolled into the Children's Oncology Group (COG) A9952 protocol and treated with carboplatin and vincristine (CV). METHODS: Non-NF1 patients were randomized to CV or thioguanine, procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, and vincristine in COG A9952. NF1 patients were assigned to CV only. NF1 patients and non-NF1 patients who were treated with CV were compared with respect to baseline characteristics, toxicity, tumor responses, EFS, and OS. RESULTS: A total of 127 eligible patients with NF1 were nonrandomly assigned to CV: 42 NF1 patients (33%) had events, and 6 (4.7%) died. The 5-year EFS rate was 69% ± 4% for the CV-NF1 group and 39% ± 4% for the CV-non-NF1 group (P < .001). In a univariate analysis, NF1 children had a significantly higher tumor response rate and superior EFS and OS in comparison with CV-treated children without NF1. NF1 patients and non-NF1 patients differed significantly in amount of residual tumor, extent of resection, tumor location, and pathology. According to a multivariate analysis, NF1 was independently associated with better EFS (P < .001) but not with OS. NF1 patients also had a decreased risk of grade 3 or 4 toxicities in comparison with non-NF1 patients. Three second malignant neoplasms occurred in NF1 patients receiving CV (CV-NF1 group) at a median of 7.8 years (range, 7.3-9.4 years) after enrollment, but there were none in the non-NF1 group. CONCLUSIONS: Children with NF1 tolerated CV well and had tumor response rates and EFS that were superior to those for children without NF1. Cancer 2016;122:1928-36. © 2016 American Cancer Society.

Successful Retreatment of a Child with a Refractory Brainstem Ganglioglioma with Vemurafenib.

A child with brainstem ganglioglioma underwent subtotal resection and focal radiation. Magnetic resonance imaging confirmed tumor progression 6 months later. Another partial resection revealed viable BRAF V600E-positive residual tumor. Vemurafenib (660 mg/m(2) /dose) was administered twice daily, resulting in >70% tumor reduction with sustained clinical improvement for 1 year. Vemurafenib was then terminated, but significant tumor progression occurred 3 months later. Vemurafenib was restarted, resulting in partial response. Toxicities included Grade I pruritus and Grade II rash. Vemurafenib was effectively crushed and administered in solution via nasogastric tube. We demonstrate benefit from restarting vemurafenib therapy.

Clinical Outcomes Among Children With Standard-Risk Medulloblastoma Treated With Proton and Photon Radiation Therapy: A Comparison of Disease Control and Overall Survival.

PURPOSE: The purpose of this study was to compare long-term disease control and overall survival between children treated with proton and photon radiation therapy (RT) for standard-risk medulloblastoma. METHODS AND MATERIALS: This multi-institution cohort study includes 88 children treated with chemotherapy and proton (n=45) or photon (n=43) RT between 2000 and 2009. Overall survival (OS), recurrence-free survival (RFS), and patterns of failure were compared between the 2 cohorts. RESULTS: Median (range) age was 6 years old at diagnosis (3-21 years) for proton patients versus 8 years (3-19 years) for photon patients (P=.011). Cohorts were similar with respect to sex, histology, extent of surgical resection, craniospinal irradiation (CSI) RT dose, total RT dose, whether the RT boost was delivered to the posterior fossa (PF) or tumor bed (TB), time from surgery to RT start, or total duration of RT. RT consisted of a median (range) CSI dose of 23.4 Gy (18-27 Gy) and a boost of 30.6 Gy (27-37.8 Gy). Median follow-up time is 6.2 years (95% confidence interval [CI]: 5.1-6.6 years) for proton patients versus 7.0 years (95% CI: 5.8-8.9 years) for photon patients. There was no significant difference in RFS or OS between patients treated with proton versus photon RT; 6-year RFS was 78.8% versus 76.5% (P=.948) and 6-year OS was 82.0% versus 87.6%, respectively (P=.285). On multivariate analysis, there was a trend for longer RFS with females (P=.058) and higher CSI dose (P=.096) and for longer OS with females (P=.093). Patterns of failure were similar between the 2 cohorts (P=.908). CONCLUSIONS: Disease control with proton and photon radiation therapy appears equivalent for standard risk medulloblastoma.

Endocrine outcomes with proton and photon radiotherapy for standard risk medulloblastoma.

BACKGROUND: Endocrine dysfunction is a common sequela of craniospinal irradiation (CSI). Dosimetric data suggest that proton radiotherapy (PRT) may reduce radiation-associated endocrine dysfunction but clinical data are limited. METHODS: Seventy-seven children were treated with chemotherapy and proton (n = 40) or photon (n = 37) radiation between 2000 and 2009 with ≥3 years of endocrine screening. The incidence of multiple endocrinopathies among the proton and photon cohorts is compared. Multivariable analysis and propensity score adjusted analysis are performed to estimate the effect of radiotherapy type while adjusting for other variables. RESULTS: The median age at diagnosis was 6.2 and 8.3 years for the proton and photon cohorts, respectively (P = .010). Cohorts were similar with respect to gender, histology, CSI dose, and total radiotherapy dose and whether the radiotherapy boost was delivered to the posterior fossa or tumor bed. The median follow-up time was 5.8 years for proton patients and 7.0 years for photon patients (P = .010). PRT was associated with a reduced risk of hypothyroidism (23% vs 69%, P < .001), sex hormone deficiency (3% vs 19%, P = .025), requirement for any endocrine replacement therapy (55% vs 78%, P = .030), and a greater height standard deviation score (mean (± SD) -1.19 (± 1.22) vs -2 (± 1.35), P = .020) on both univariate and multivariate and propensity score adjusted analysis. There was no significant difference in the incidence of growth hormone deficiency (53% vs 57%), adrenal insufficiency (5% vs 8%), or precocious puberty (18% vs 16%). CONCLUSIONS: Proton radiotherapy may reduce the risk of some, but not all, radiation-associated late endocrine abnormalities.

Mandibular condyle erosion and sclerosis in pediatric patients treated with radiotherapy to the head and neck region.

Head and neck radiotherapy in children is associated with significant acute and late morbidities. Temporomandibular joint dysfunction and trismus has been widely reported in patients receiving radiotherapy for sarcomas and nasopharyngeal carcinoma; however, erosion of the mandibular condyle is a rare sequela of modern radiotherapy techniques. In this report, we present three cases of erosion of the temporomandibular joint amongst pediatric patients treated with radiotherapy for distinct head, neck and brain malignancies.

Response of subependymal giant cell astrocytoma with spinal cord metastasis to everolimus.

BACKGROUND: Brain subependymal giant cell astrocytomas (SEGAs) in patients with tuberous sclerosis have been reported to respond to everolimus. METHODS: A 15-year-old male patient with intractable seizures and multiple SEGAs of the brain developed leptomeningeal enhancement and multiple metastatic, histologically confirmed SEGAs of the spinal cord. He received daily everolimus at a dose of 3 mg/m for 6 weeks, which was then increased to 6 mg/m. RESULTS: Magnetic resonance image of the brain and spine showed significant reduction in the size of SEGAs after 6 weeks of treatment. The patient has remained free of progression for 24 months. Additional benefits included: excellent seizure control, decrease in the size of cardiac rhabdomyomas, and improved quality of life. CONCLUSIONS: We describe a rare case of metastatic SEGA, which was successfully treated with everolimus.

Diffuse leptomeningeal neuroepithelial tumor: 9 pediatric cases with chromosome 1p/19q deletion status and IDH1 (R132H) immunohistochemistry.

Leptomeningeal dissemination in children is typical of high-grade, and occasionally low-grade, neoplasms. Rare cases of widely disseminated oligodendroglia-like leptomeningeal tumors, sometimes with associated spinal cord lesions, have been described that respond to treatment and follow an indolent course. Whether these lesions represent an established tumor category or are a unique entity remains to be established. We present 9 pediatric cases of such diffuse leptomeningeal neuroepithelial tumors (DLNT), 8 with assessment of 2 common genetic alterations seen in oligodendrogliomas, 1p and 19q chromosomal deletions and isocitrate dehydrogenase-1 (IDH1) R132H mutations. Four patients were male and 5 female, with a mean age at presentation of 4 years (range, 2 to 7 y). All presented with signs of increased intracranial pressure and diffuse contrast enhancement of the leptomeninges by magnetic resonance imaging. Three had a cervical or upper thoracic spinal cord tumor, and another had a small cerebellar lesion. Leptomeningeal biopsies showed a thickened and fibrotic arachnoid infiltrated by monotonous cells with round nuclei and prominent perinuclear clearing. All cases were strongly immunoreactive for S100 protein, and most showed faint granular synaptophysin reactivity. Six of 8 cases showed deletions of chromosome arm 1p by fluorescence in situ hybridization, 2 of which also had loss of 19q. None of the lesions reacted with IDH1-R132H antibodies. Although the clinicopathologic features show overlap of these DLNT lesions with oligodendroglioma and extraventricular neurocytoma, they do not exactly match either one, suggesting that DLNTs are a distinct tumor entity.

Response to bevacizumab, irinotecan, and temozolomide in children with relapsed medulloblastoma: a multi-institutional experience.

PURPOSE: Chemotherapy for relapsed medulloblastoma has been inadequate, and most patients succumb to disease. METHODS: We retrospectively reviewed nine cases of relapsed medulloblastoma treated with bevacizumab, irinotecan, ± temozolomide. Patients received one to three prior therapeutic regimens. Five patients received 10 mg/kg bevacizumab and 125-150 mg/m(2) irinotecan IV every 2 weeks, with temozolomide, starting at a median dose of 150 mg/m(2) orally for 5 days monthly. Two patients received bevacizumab and irinotecan, but not temozolomide, due to provider preference. Two of nine patients received 15 mg/kg bevacizumab IV, 90 mg/m(2) irinotecan orally for five consecutive days, 100 mg/m(2)/day temozolomide IV for 5 days, and 1.5 mg/m(2) vincristine IV, each administered every 21 days. RESULTS: Median time to progression was 11 months. Median overall survival was 13 months. Objective tumor response at 3 months was 67 %, including six patients with partial response (PR) and three patients with stable disease (SD). At 6 months, objective response was 55 %, with two patients with PR and three with complete response. Additionally, one patient had SD and three had PD. Two patients remain alive and progression free at 15 and 55 months; another is alive with disease at 20 months. Toxicities included two patients with grade III neutropenia, two with grade III thrombocytopenia, one with grade III elevation of liver function tests, and one patient with grade III diarrhea. CONCLUSIONS: The combination of bevacizumab and irinotecan, with or without temozolomide, produces objective responses with minimal toxicity in children with recurrent medulloblastoma. Prospective clinical trials are needed to evaluate the efficacy of this strategy.

Prolonged survival after treatment of diffuse intrinsic pontine glioma with radiation, temozolamide, and bevacizumab: report of 2 cases.

BACKGROUND: Diffuse intrinsic pontine gliomas have poor prognosis. OBSERVATION: We report on 2 patients with diffuse intrinsic pontine glioma treated with radiation, followed by temozolamide 200 mg/m/d for 5 days every 28 days and bevacizumab 10 mg/kg/dose every 14 days. Both patients have ongoing PFS of 37 and 47 months from diagnosis. A decrease in tumor size by >65% was observed in both the patients. Both patients continue treatment. No steroid requirement since 10 weeks after radiation. Quality of life is excellent and the chemotherapy regimen is well tolerated. CONCLUSIONS: A clinical trial in an expanded cohort is warranted to determine the toxicity and evaluate response.

Intracranial metastatic neuroblastoma treated with gamma knife stereotactic radiosurgery: report of two novel cases.

Intracranial metastasis of neuroblastoma (IMN) is associated with poor survival. No curative therapy for the treatment of IMN currently exists. Unfractionated radiotherapy may be beneficial in the treatment of IMN given the known radiosensitivity of neuroblastoma as well as its proclivity to metastasize as discrete lesions. We present two patients with IMN treated with Gamma Knife stereotactic radiosurgery (SRS). Single-fraction radiotherapy yielded temporary reduction of tumor burden and stability of disease in both patients. SRS may be a useful palliative tool in the treatment of IMN and expands the overall treatment options for this disease.