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Background Hippocampal avoidance has been suggested as a strategy to reduce short-term memory decline in adults receiving whole-brain radiation therapy (RT). The purpose of this study was to determine whether the hippocampal dose in children and adolescents undergoing RT for low-grade glioma was associated with memory, as measured by verbal recall. Methods Eighty patients aged at least 6 years but less than 21 years with low-grade glioma were treated with RT to 54 Gy on a phase II protocol. Patients underwent age-appropriate cognitive testing at baseline, 6 months posttreatment, yearly through 5 years posttreatment, year 7 or 8, and year 10 posttreatment. Random coefficient models were used to estimate the longitudinal trends in cognitive assessment scores. Results Median neurocognitive follow-up was 9.8 years. There was a significant decline in short-delay recall (slope = −0.01 standard deviation [SD]/year, P < 0.001), total recall (slope = −0.09 SD/y, P = 0.005), and long-delay recall (slope = −0.01 SD/y, P = 0.002). On multivariate regression, after accounting for hydrocephalus, decline in short-delay recall was associated with the volume of right (slope = −0.001 SD/y, P = 0.019) or left hippocampus (slope = −0.001 SD/y, P = 0.025) receiving 40 Gy (V40 Gy). On univariate regression, decline in total recall was only associated with right hippocampal dosimetry (V40 Gy slope = −0.002, P = 0.025). In children Conclusion In this 10-year longitudinal study, greater hippocampal dose was associated with a greater decline in delayed recall. Such findings might be informative for radiation therapy planning, warranting prospective evaluation.

Background Low-grade gliomas (LGGs) and low-grade glioneuronal tumors (LGGNTs) diagnosed during the first year of life carry unique clinical characteristics and challenges in management. However, data on the treatment burden, outcomes, and morbidities are lacking. Methods A retrospective study of LGGs and LGGNTs diagnosed in patients younger than 12 months at St. Jude Children's Research Hospital (1986-2015) was conducted. Results For the 51 patients (including 31 males), the mean age at diagnosis was 6.47 months (range, 0.17-11.76 months), and the mean follow-up period was 11.8 years (range, 0.21-29.19 years). Tumor locations were hypothalamic/optic pathway (61%), hemispheric (12%), brainstem (12%), cerebellar (8%), and spinal (8%). There were 41 patients with histological diagnoses: 28 had World Health Organization grade 1 tumors, 6 had grade 2 tumors, and 7 had an LGG/LGGNT not definitively graded. Forty-one patients required an active intervention at diagnosis. Throughout their treatment course, 41 patients eventually underwent tumor-directed surgeries (median, 2 surgeries; range, 1-6), 39 received chemotherapy (median, 2 regimens; range, 1-13), and 21 received radiotherapy. Forty patients experienced disease progression (median, 2 progressions; range, 1-18). Ten patients died of progression (n = 5), malignant transformation (n = 2), a second cancer (n = 2), or a shunt infection (n = 1). The 10-year overall survival, progression-free survival, and radiation-free survival rates were 85% ± 5.3%, 16.9% ± 5.3%, and 51.2% ± 7.5%, respectively. Forty-nine patients experienced health deficits (eg, endocrinopathies, obesity, seizures, visual/hearing impairments, neurocognitive impairments, and cerebrovascular disease). Predictors of progression and toxicities were defined. Conclusions Infantile LGG/LGGNT is a chronic, progressive disease universally associated with long-term morbidities and requires multidisciplinary intervention.

BACKGROUND: Low-grade gliomas (LGG) are the most common central nervous system (CNS) tumors in children. Peru is an index country for the Global Initiative for Childhood Cancer (GICC). As part of the Initiative, a multidisciplinary brain tumor team was formed in 2020 that includes five national reference centers: National Institute of Neoplastic Diseases, National Children’s Health Institute-San Borja, National Children’s Health Institute-Breña, Edgardo Rebagliati Martins National Hospital and Guillermo Almenara Irigoyen National Hospital. This multicenter study sought to evaluate the survival and prognostic factors of patients younger than 18 years diagnosed with LGG, an index cancer for the GICC. METHODS: A retrospective study included all patients diagnosed with LGG in the five centers between 2014 and 2018. We analyzed clinical characteristics, histology, and treatment modalities. We used the Kaplan-Meier method for survival. RESULTS: 194 patients were registered; 136 patients were included. M/F ratio was 1.2, mean age 7 years old. The most frequent location was infratentorial (42.2%), supratentorial (34.9%), optic/chiasm/sellar (11%) and brainstem (11.9%). The most frequent histological types were pilocytic astrocytoma (61%), diffuse astrocytoma (10.3%), oligodendroglioma (5.2%), and other low-grade neoplasms (23.5%). Surgery was performed in 109 patients (83.2%). Chemotherapy alone was used in 17 (12.5%), while radiotherapy in 20 (14.7%). Overall survival at 5 years was 82.9% (95% CI 73.3 - 89.4). Age younger than 3 years (p=0.002), diffuse histological type (p=0.04), and location in the brainstem (p=0.001) were factors associated with a worse prognosis. CONCLUSIONS: Within the framework of the GICC, this work is one of the first steps to understand the current context of pediatric CNS tumor care in Peru. Although the reported survival rate is about the GICC goal of 60%, further improvements in care are needed to increase survival to level closer to high-resource setting and decrease long term morbidity.

To accurately evaluate the burden of pediatric central nervous system (CNS) tumors, estimate resources for cancer control, and monitor outcomes, a classification system that segregates tumors into clinically relevant groups is essential. The current classification of CNS tumors included in the third revision of the International Childhood Cancer Classification does not identify key clinical groups, such as low- and high-grade gliomas. To address this need, a novel classification was embarked upon using ICD-O-3 codes, CBTRUS grouping, incidence, survival, and treatment modalities as inputs. For each ICD-O-3 code with >50 new cases/year in CBTRUS from 2000 to 2016, 2 clinicians reached consensus defining the efficacy of three treatment modalities: surgical resection, radiotherapy, and chemotherapy. Then, patient level 5-year overall survival (OS) times were simulated based on total incidence and 5-year OS for each code. Subsequently, 5 factors were included as potential classifiers: tumor behavior, CBTRUS sub-group, and efficacy of the three treatment modalities. A “survival tree” was developed by using partitioning. Starting with the patient cohort (root), univariate cox proportional hazards model was used to identify statistically significant (P < 0.05) factors. The factors with the largest hazard ratio were selected manually to create child nodes. Within each child node, the partitioning process was repeated on remaining factors until no statistically significant factor remained. This clustering yielded 4 main groups (low-, intermediate-, high-, and very high-risk tumors) and 11 subgroups, including “embryonal tumors” and “low-risk glial and glioneuronal tumors”. Further validation of the classification will be sought through a structured consensus process using multidisciplinary experts. This systematic method to develop a classification for pediatric CNS tumors will allow for more relevant estimations of outcomes and better estimation of resource utilization. Furthermore, this strategy could be replicated for other disease groups.

BACKGROUND: Central nervous system (CNS) tumors in children are associated with a longer delay in diagnosis. One of the contributing factors is the lack of awareness regarding childhood CNS tumors presentation among health care providers. To evaluate the knowledge gap among health care providers, we conducted a cross-sectional survey that was distributed globally. METHODS: The survey was disseminated to health care practitioners via electronic mail in November 2018 and it was closed in March 2020. The participants were asked to complete a pre-test survey, requested to view a CNS tumor education seminar, and subsequently complete a post-test survey. The survey had nine questions focusing on CNS tumor symptoms, pre-diagnosis symptom interval (PSI), and imaging indication. The knowledge gap was evaluated with pre-test and post-test scores. RESULTS: 889 pre-test and 392 post-test responses were received. The majority of the respondents were from Asia, with a percentage of 73.1% and 87.5% in pre-test and post-test respectively. For the pre-test, the median score for accurate answers was 40.0% (range:13.1-92.9%). Interestingly, a high rate of correctness was achieved in the post-test with a median score of 77.1% (14.9-98.2%). In the pre-test, only 18.7% of the participants responded precisely that Cushing’s triad is a less common symptom and just 15.0% recognized that older children >10 years old are at risk for late diagnosis. Surprisingly, 21.9% falsely reported that patients with malignant tumors experience the longest PSI, and 54.5% of the respondents wrongly selected medulloblastoma as the commonest CNS tumor. Overall, the pre-test scores among pediatricians and professionals with >10 years of experience did not demonstrate improved knowledge when compared to other specialties. CONCLUSIONS: The survey analysis showed a significant knowledge gap regarding childhood CNS tumors among health care providers. Therefore, raising professional awareness is very important and can be achieved through targeted educational strategies.

BACKGROUND Since 2013, pediatric oncologists from Central and South America discuss neuro-oncology cases with experts from North America and Europe in a web-based "Latin American Tumor Board" (LATB). Here, we evaluate the feasibility of recommendations rendered by the Board. METHODS An electronic questionnaire was distributed to physicians who had received recommendations between October 2017 and October 2018. Physicians were asked regarding the feasibility of each recommendation given during the LATB discussion. Baseline case characteristics of all presented cases were obtained from anonymized minutes. RESULTS Of the 142 patients discussed, data on 103 patients from 15 countries were available, corresponding to 283 recommendations. Physicians followed 60% of diagnostic procedural recommendations and 69% of therapeutic recommendations. The most difficult recommendations to follow were genetic and molecular testing, pathology review, chemotherapy, surgery, and molecular targeted therapies. Histological diagnoses changed in eight of 18 cases in which a pathology review was undertaken. Fifty-four percent of the recommendations that could not be implemented were considered not feasible in the specific context of the patient, while 31% were not implemented due to a decision of the medical staff or the parents (15% not specified). However, 96% of respondents considered the recommendations useful. CONCLUSION Recommendations were frequently perceived as useful, and were applicable in the participating institutions. Nevertheless, limitations in availability of diagnostic procedures and treatment modalities affected the feasibility of some recommendations. Tele-oncology tumor boards offer physicians from low- and middle-income countries access to real-time, high-level subspecialist expertise and provide a valuable platform for worldwide information exchange.

PURPOSE To describe the trajectory of cognitive and adaptive functioning in pediatric patients with retinoblastoma from diagnosis through age 10. This is an extension of a previous report that discussed findings from diagnosis through age 5. PATIENTS AND METHODS Ninety-eight participants with retinoblastoma completed psychological assessments as part of their enrollment on an institutional treatment protocol, with 73 completing an additional assessment at age 10. Trajectories of adaptive and cognitive functioning were determined, with data analyzed by treatment strata, and patients with 13q- analyzed separately. RESULTS Longitudinal trajectories identified a significant change point in trends at age 5, with functioning declining from diagnosis through age 5 and then increasing from age 5 to age 10. This pattern was observed for all strata for adaptive functioning, but only for enucleation-only patients (strata C low) for cognitive functioning. Cognitive trajectories were also influenced by laterality and enucleation status. At age 10, overall functioning was generally within the average range, although estimated intelligence quotient was significantly below the normative mean for enucleation-only (C low) patients. Patients with 13q- demonstrated very low functioning, but few analyses were significant because of small sample size. CONCLUSION The results generally indicate that previously demonstrated declines in functioning from diagnosis through age 5 improve by age 10. However, these early declines, as well as the continuous difficulties observed in patients treated with enucleation only, suggest the need for early intervention services for young patients with retinoblastoma. Continuous monitoring of the psychological functioning of patients with retinoblastoma, increased awareness of risk factors such as unilateral disease, enucleation, race, and surgery-only treatment plans, and referral to Early Intervention for all patients are indicated.

The COVID-19 pandemic has been particularly devastating for Iran. Children with cancer are generally immunosuppressed and especially vulnerable to SARS-CoV-2 infections. We report the treatment and outcomes of pediatric oncology patients with COVID-19 at the MAHAK Pediatric Cancer Treatment and Research Center (MPCTRC) in Tehran. We enrolled pediatric oncology patients who experienced SARS-CoV-2 infections from March 18, 2020, to January 28, 2021. The COVID-19 diagnostic criteria at MPCTRC were based on imaging and clinical presentation because of specific challenges diagnosing SARS-CoV-2 infections with molecular testing, which was locally developed and conducted at centers other than MPCTRC. We enrolled nine outpatients and eight inpatients (mean age = 9 years), seven of whom had a diagnosis of leukemias, and five who had brain tumors. COVID-19 symptoms were mild in fourteen patients, and three patients were asymptomatic. Of twelve patients who received molecular testing for SARS-CoV-2 infection, eight were negative and four were positive. Of nine patients tested for IgG and IgM antibodies, one was positive. Three patients died of COVID-19, all of whom were hospitalized. Mild COVID-19 symptoms did not appear to affect the outcomes of the pediatric patients with cancer who received treatment at MPCTRC during the study period.

The interaction of coronavirus disease-2019 (COVID-19) and chemotherapy may result in worse outcomes. However, there may be more indirect effects of COVID. We report 3 cases in which treatment was delayed because of COVID-related inability or reluctance to travel. Oncology programs should consider such indirect effects when devising treatments.

Background Pediatric low-grade gliomas (pLGGs) are the most common childhood brain tumor. Progression-free survival (PFS) is much lower than overall survival, emphasizing the need for alternative treatments. Sporadic (without neurofibromatosis type 1) optic pathway and hypothalamic gliomas (OPHGs) are often multiply recurrent and cause significant visual deficits. Recently, there has been a prioritization of functional outcomes. Methods We present results from children with recurrent/progressive OPHGs treated on a PBTC (Pediatric Brain Tumor Consortium) phase II trial evaluating efficacy of selumetinib (AZD6244, ARRY-142886) a MEK-1/2 inhibitor. Stratum 4 of PBTC-029 included patients with sporadic recurrent/progressive OPHGs treated with selumetinib at the recommended phase II dose (25mg/m2/dose BID) for a maximum of 26 courses. Results Twenty-five eligible and evaluable patients were enrolled with a median of 4 (1-11) previous therapies. Six of 25 (24%) had partial response, 14/25 (56%) had stable disease, and 5 (20%) had progressive disease while on treatment. The median treatment courses were 26 (2-26); 14/25 patients completed all 26 courses. Two-year PFS was 78 ± 8.5%. Nineteen of 25 patients were evaluable for visual acuity which improved in 4/19 patients (21%), was stable in 13/19 (68%), and worsened in 2/19 (11%). Five of 19 patients (26%) had improved visual fields and 14/19 (74%) were stable. The most common toxicities were grade 1/2 CPK elevation, anemia, diarrhea, headache, nausea/emesis, fatigue, AST and ALT increase, hypoalbuminemia, and rash. Conclusions Selumetinib was tolerable and led to responses and prolonged disease stability in children with recurrent/progressive OPHGs based upon radiographic response, PFS, and visual outcomes.

Background Childhood acute lymphoblastic leukemia (ALL) is the most common pediatric cancer worldwide. Although children in high-income countries enjoy survival rates of ~90%, children in countries with limited resources suffer from survival rates of

Pediatric high-grade glioma (pHGG) is a major contributor to cancer-related death in children.In vitroandin vivodisease models reflecting the intimate connection between developmental context and pathogenesis of pHGG are essential to advance understanding and identify therapeutic vulnerabilities. We established 21 patient-derived pHGG orthotopic xenograft (PDOX) models and eight matched cell lines from diverse groups of pHGG. These models recapitulated histopathology, DNA methylation signatures, mutations and gene expression patterns of the patient tumors from which they were derived, and included rare subgroups not well-represented by existing models. We deployed 16 new and existing cell lines for high-throughput screening (HTS).In vitroHTS results predicted variablein vivoresponse to inhibitors of PI3K/mTOR and MEK signaling pathways. These unique new models and an online interactive data portal to enable exploration of associated detailed molecular characterization and HTS chemical sensitivity data provide a rich resource for pediatric brain tumor research.

Background: Iran has greatly suffered from the COVID-19 pandemic. Iranian children with cancer are especially vulnerable; therefore, we describe the care of patients with COVID-19 who received treatment at the MAHAK Pediatric Cancer Treatment and Research Center (MPCTRC) in Tehran. Patients and Methods: Children who experienced SARS-CoV-2 infections from March 18 to May 18, 2020, were enrolled in the study. Because of specific challenges diagnosing SARS-CoV-2 infections with molecular testing in Iran, the diagnostic criteria at MPCTRC were based on imaging and clinical presentation. We divided the patients into inpatient and outpatient cohorts according to the treatment they received and collected demographic, diagnostic, treatment, and outcome data. Molecular testing was developed locally and performed at centers other than MPCTRC. Results: Eleven patients (outpatient, n = 7) with a mean age of 9.2 years were enrolled in the trial. The most common cancer diagnoses were brain tumors (n = 4) and leukemias (n = 3). Eight patients had mild COVID-19 symptoms, and three were asymptomatic. Molecular testing of SARS-CoV-2 infections was performed for six patients, and all were negative. Only one child died of COVID-19. Discussion: In our small case series, mild COVID-19 symptoms did not appear to affect the outcomes of pediatric patients with cancer. Quality assurance of locally developed molecular testing of SARS-CoV-2 infections should also be considered.

To evaluate the efficacy of integrating a telemedicine-based twinning partnership and centralized care for retinoblastoma on survival and eye salvage.Four hundred seventy-eight retinoblastoma patients treated at a tertiary referral cancer center (King Hussein Cancer Centre [KHCC]) from 2003 through 2019.Four hundred seventy-eight retinoblastoma patients treated at KHCC after implementing a telemedicine-based program with St. Jude Children's Research Hospital.We reviewed the outcomes of retinoblastoma patients who were treated at KHCC after implementing a telemedicine-based eye salvage program with St. Jude Children's Research Hospital, and we compared that with outcomes for retinoblastoma patients who were treated before implementing a telemedicine-based retinoblastoma service at KHCC.We analyzed patient demographics, clinical characteristics, treatments received, consultation type and duration, and long-term patient outcomes before and after implementing the twinning program.Over 17 years, 813 eyes from 478 children with retinoblastoma were treated at KHCC. Three hundred thirty-five patients (70%) had bilateral disease. Six patients (4%) with unilateral disease and 66 patients (20%) with bilateral disease had a family history of retinoblastoma. After the twinning program was established in 2003, the mortality rate decreased from 38% to 5% (P 0.0001), and the overall eye salvage rate increased from 4% to 61% (98% for group A, 93% for group B, 81% for group C, and 48% for group D; P 0.0001). Initially, all cases were discussed via telemedicine, but as knowledge transfer increased, the proportion of cases that required discussion decreased to less than 3% 10 years later. Similarly, treatment changes based on consultations decreased from 70% to 7% after 10 years. Both survival and eye-salvage rates were comparable at the early and later stages of implementing the twinning program. At a median follow-up of 120 months, 5% of patients had died of metastases or secondary neoplasms, 81% were alive, and 14% were lost to follow-up.Centralization of care at a single center in developing countries can achieve patient outcomes comparable with those of developed countries via twinning and telemedicine. This benefit can extend to a large region because two thirds of patients treated at KHCC were non-Jordanians.

Pediatric low-grade gliomas (pLGG) are frequently driven by genetic alterations in the RAS-mitogen-activated protein kinase (RAS/MAPK) pathway yet show unexplained variability in their clinical outcome. To address this, we characterized a cohort of >1,000 clinically annotated pLGG. Eighty-four percent of cases harbored a driver alteration, while those without an identified alteration also often exhibited upregulation of the RAS/MAPK pathway. pLGG could be broadly classified based on their alteration type. Rearrangement-driven tumors were diagnosed at a younger age, enriched for WHO grade I histology, infrequently progressed, and rarely resulted in death as compared with SNV-driven tumors. Further sub-classification of clinical-molecular correlates stratified pLGG into risk categories. These data highlight the biological and clinical differences between pLGG subtypes and opens avenues for future treatment refinement.

PURPOSE: Low-grade gliomas (LGG) are a heterogeneous group of brain tumors, which are often assumed to have a benign course. Yet, children diagnosed and treated for LGG in infancy are at increased risk for neurodevelopmental disruption. We sought to investigate neuropsychological outcomes of infants diagnosed with LGG. METHODS: Between 1986 and 2013, 51 patients were diagnosed with LGG before 12 months of age and managed at St. Jude Children’s Research Hospital. Twenty-five of the 51 patients received a cognitive assessment (68% male; 6.8 ± 3.3 months at diagnosis; 10.5 ± 4.8 years at latest assessment). Approximately half the patients received radiation therapy (n = 12; aged 4.0 ± 3.0 years at radiation therapy), with a median of 2 chemotherapy regimens (range = 0 – 5) and 1 tumor directed surgery (range = 0 – 5). RESULTS: The analyses revealed performance below age expectations on measures of IQ, memory, reading, mathematics, and fine motor functioning as well as parent-report of attention, executive, and adaptive functioning. Following correction for multiple comparisons, a greater number of chemotherapy regimens was associated with lower scores on measures of IQ and mathematics. More tumor directed surgeries and presence of visual field loss were associated with poorer dominant hand fine motor control. Radiation therapy exposure was not associated with decline in neuropsychological performance. CONCLUSIONS: Children diagnosed with LGG in infancy experience substantial neuropsychological deficits. Treatment factors, including number of chemotherapy regimens and tumor directed surgeries, may increase risk for neurodevelopmental disruption and need to be considered in treatment planning.

Tectal glioma (TG) is a rare low-grade tumor occurring predominantly in the pediatric population. There has been no detailed analysis of molecular alterations in TG. Risk factors associated with inferior outcome and long-term sequelae of TG have not been well-documented. We retrospectively studied TGs treated or referred for review at St. Jude Children’s Research Hospital (SJCRH) between 1986 and 2013. Longitudinal clinical data were summarized, imaging and pathology specimen centrally reviewed, and tumor material analyzed with targeted molecular testing and genome-wide DNA methylation profiling. Forty-five patients with TG were included. Twenty-six (57.8%) were male. Median age at diagnosis was 9.9 years (range, 0.01–20.5). Median follow-up was 7.6 years (range, 0.5–17.0). The most common presenting symptoms were related to increased intracranial pressure. Of the 22 patients treated at SJCRH, 19 (86%) required cerebrospinal fluid diversion and seven (32%) underwent tumor-directed surgery. Five patients (23%) received radiation therapy and four (18%) systemic therapy. Ten-year overall and progression-free survival were 83.9 ± 10.4% and 48.7 ± 14.2%, respectively. Long-term morbidities included chronic headaches, visual symptoms and neurocognitive impairment. Lesion ≥3cm2, contrast enhancement and cystic changes at presentation were risk factors for progression. Among those with tumor tissue available, 83% showed growth patterns similar to pilocytic astrocytoma and 17% aligned best with diffuse astrocytoma. BRAF duplication (a marker of KIAA1549-BRAF fusion) and BRAF V600E mutation were detected in 25% and 7.7%, respectively. No case had histone H3 K27M mutation. DNA methylation profile of TG was distinct from other brain tumors. In summary, TG is an indolent, chronic disease with unique clinical and molecular profiles and associated with long term morbidities. Large size, contrast enhancement and cystic changes are risk factors for progression.

Abnormal expression ofPatients with ALL were divided into two separate groups, either the case group with relapsed ALL or the control group in which ALL patients have been in progression-free survival for at least 3 years A total of thirty-nine participants (23 with relapsed ALL; 16 controls) were enrolled over 26 months. To determine the levels ofOur findings showed elevated expression ofEvaluating the expression pattern of

Isolated optic nerve glioma is a rare tumor with no consensus for the best therapeutic approach. Therefore, tumor control and preservation of visual function remain a challenge. In this retrospective study, we describe our experience over 30 years in a single-institutional cohort of children with isolated optic nerve glioma, focusing on treatments and visual outcomes. Seventeen children were followed for a median period of 8 years (range, 2-22 years). Diagnosis was based on typical neuroradiologic findings, and 3 patients had histologic confirmation of their tumors. In our study, conservative management preserved the vision of most patients with neurofibromatosis type 1 (NF1). NF1-related optic nerve gliomas were less often treated but were associated with a lower probability of progression and with occasional spontaneous regression. Sporadic tumors more frequently exhibited aggressive clinical behavior with a higher propensity for posterior extension, often requiring surgical intervention.

PURPOSE: Incidence of BS primitive neuroectodermal tumors (BS-PNET) in children is not reported to date. Our main objectives were to estimate the incidence and report the outcome of BS-PNET in children. METHODS: Data was collected using the Surveillance Epidemiology and End Results cancer registry. RESULTS: From 1973 till 2013, we identified 83 pediatric patients (aged 0–21 years). Patients were divided into 2 age groups (0–3 years and 4–21 years). Median overall survival was 53 months. Patients in the older age group had a significant survival advantage (P

Background Hearing loss may occur in patients with posterior fossa low-grade glioma who undergo surgery. Methods We retrospectively reviewed 217 patients with posterior fossa low-grade glioma, including 115 for whom results of hearing tests performed after surgery and before chemotherapy or radiation therapy were available. We explored the association of UHL with age at diagnosis, sex, race, tumor location, extent of resection, posterior fossa syndrome, ventriculoperitoneal shunt placement, and histology. Results Of the 115 patients, 15 (13.0%: 11 male, 6 black, 8 white, 1 multiracial; median age 7 years [range, 1.3–17.2 years]) had profound UHL after surgery alone or before receiving ototoxic therapy. Median age at tumor diagnosis was 6.8 years (range, 0.7–14.1 years), and median age at surgery was 6.8 years (range, 0.7–14.1 years). Patients with UHL had pathology characteristic of pilocytic astrocytoma (n = 10), ganglioglioma (n = 4), or low-grade astrocytoma (n = 1). Of these 15 patients, 4 underwent biopsy, 1 underwent gross total resection, 1 underwent near-total resection, and 9 underwent subtotal resection. UHL was more frequent in black patients than in white patients (OR 7.3, P = .007) and less frequent in patients who underwent gross total resection or near-total resection than in those who underwent subtotal resection (OR 0.11, P = .02). Conclusions Children undergoing surgery for posterior fossa low-grade glioma are at risk for UHL, which may be related to race or extent of resection. These patients should receive postoperative audiologic testing, as earlier intervention may improve outcomes.

Angkor Hospital for Children (AHC) is a Cambodian pediatric teaching hospital providing free treatment. In addition to the many challenges faced by health workers in developing countries, Cambodia suffered the decimation of its medical workforce by the Khmer Rouge and subsequent civil war. In the

The clinical management of pediatric medulloblastoma requires a multidisciplinary approach, which can be challenging, especially in low- and middle-income countries. The aim of this study was to identify current challenges and describe the treatment and outcomes of Iranian pediatric patients with medulloblastoma who were referred to our center in Tehran, Iran. Our retrospective review included 126 patient records from April 2007 to May 2015. The records were analyzed for epidemiologic features, treatment modalities, overall survival, and progression-free survival. Data were analyzed using SPSS 22.0 software. Median age at diagnosis was 6 years (male:female ratio, 2.3:1). At the time of diagnosis, 7 patients were 2 years or younger, and 76 (60.3%) were categorized as having high-risk disease. Overall, 100 patients had gross or near-total surgical resection. Cerebral spinal fluid involvement was detected in 22.2% of the patients tested, and spinal involvement was detected in 25% of the patients who underwent spinal MRI. Metastasis stages at the time of diagnosis were as follows: M0: 48.4% patients, M1: 16.7%, M2: 5.5%, and M3: 21.4%. Median times of follow-up and progression-free survival were 16 and 12 months, respectively. Probability of 7-year overall survival and progression-free survival were 59 and 53.8%, respectively. Results of the current retrospective study emphasize the need for implementing measures to improve outcome for our patients with medulloblastoma. Such measures include a multidisciplinary approach, unified national treatment guidelines, better disease and metastasis staging, twinning initiatives, and seeking a second opinion when needed.

BACKGROUND Since 2013, pediatric oncologists from Latin America have discussed neuro-oncology cases with experts from North America and Europe in a web-based “Latin American Tumor Board” (LATB). This descriptive study evaluates the feasibility of the recommendations rendered during the Board. METHODS An electronic questionnaire was distributed to physicians who received recommendations between October 2017 and October 2018, two months after their case presentation on the LATB. Physicians were asked regarding the feasibility of each recommendation given during the Board. Baseline case characteristics of all presented cases were obtained from anonymized minutes prepared after the presentations. RESULTS 36 physicians from 15 countries answered 103 of 142 questionnaires (72.5%), containing 283 recommendations. Physicians followed 60% of diagnostic procedural recommendations and 70% of therapeutic recommendations. Overall, 96% of respondents considered the recommendations applicable and useful. The most difficult recommendations to follow were genetic and molecular testing, pathology review, locally adapted chemotherapy protocols administration, neurosurgical interventions and access to molecular targeted therapies. The most cited reasons for not implementing the recommendations were lack of resources, inapplicable recommendations to that low-to-middle income country (LMIC) setting, and lack of parental consent. CONCLUSION The recommendations given on the LATB are frequently applicable and helpful for physicians in LMIC. Nevertheless, limitations in availability of both diagnostic procedures and treatment modalities affected the feasibility of some recommendations. Virtual tumor boards offer physicians from LMIC access to real time, high-level subspecialist expertise and provide a valuable platform for information exchange among physicians worldwide.

BACKGROUND The Philippine General Hospital, a public national referral center, sees 60–80 pediatric brain tumor cases per year. Historically, the rate of post-operative ventriculitis has been high, resulting in treatment delays and poor outcomes. Starting in July 2019, as a means to decrease infections, patients were provided standardized bathing and wound care kits and caregivers were trained to follow a bathing and wound care protocol. METHODS This quality improvement study included patients younger than 18 years who underwent craniotomy at PGH were enrolled. The type of surgery, length of surgery, existence of post-operative CNS infection, length of stay and total cost of care was collected. The outcome of these interventions are analyzed 6 months after implementation. RESULTS Thirty-two 32 patients were included, with mean age of 7 years (1–16). The surgeries performed were: tumor resection (n=20), ventriculo-peritoneal shunt insertion (VPS) (n=3), endoscopic third ventriculostomy (n=3), resection with tube ventriculostomy (n=3), Ommaya reservoir placement (n=2), and resection with shunt (n=1). Median surgery time was 4 hours (1–10). Three patients (9.4%) developed ventriculitis. No surgical site infections occurred. Compared to historical controls, a lower rate of infections was noted (9.4% vs. 15.5%, runchart analysis). Patients without post-operative infections had a shorter length of stay (median 14 vs 48 days, p CONCLUSION Implementation of simple hygiene interventions effectively lowered post-operative CNS infections and hospital costs in a public hospital setting. Incorporation of these into standard clinical practices is urgently needed.

Rationale: Differentiating tumor recurrence or progression from pseudoprogression during surveillance of pediatric high-grade gliomas (PHGGs) using magnetic resonance imaging (MRI), the primary imaging modality for evaluation of brain tumors, can be challenging. The aim of this study was to evaluate whether 11C-methionine positron emission tomography ([11C]MET -PET), a molecular imaging technique that detects functionally active tumors, is useful for further evaluating MRI changes concerning for tumor recurrence during routine surveillance. Methods: We evaluated 27 lesions in 26 patients with new or worsening MRI abnormalities, where PHGG tumor recurrence was of concern during follow-up visits with [11C]MET -PET. We performed quantitative and qualitative assessments of both [11C]MET-PET and MRI data to predict the presence of tumor recurrence. Further, to assess for an association with overall survival we plotted the time from development of the imaging changes against survival. Results: Qualitative evaluation of [11C]MET-PET achieved 100% sensitivity, 60% specificity, and 93% accuracy to correctly predict the presence of tumors in 27 new or worsening MRI abnormalities. Qualitative MRI evaluation achieved sensitivity ranging from 86% to 95%, specificity ranging from 40% to 60%, and accuracy ranging from 85% to 89%. The interobserver agreement for [11C]MET-PET assessment was 100%, whereas the interobserver agreement was only 50% for MRI (P =

Iran lacks a national registry reporting the data of central nervous system (CNS) tumors in children. Consequently, treatment success and failure rates are unknown, and a centralized system for disease-management recommendations does not exist. To critically evaluate the current state of pediatric CNS tumor studies and reporting in Iran, we performed an extensive retrospective analysis of all known reports identified with multiple search engines. Of 409 initially retrieved articles, we evaluated 123 matching our inclusion criteria. We further narrowed these reports to 74 by excluding studies pertaining to adult patients only, non-CNS tumors, or brain metastases. We also excluded studies that were performed outside of Iran or that did not contain relevant data from our analysis. We divided the remaining studies into those describing exclusively pediatric patients (3484 patients) and those describing mixed populations of adults and children (18,641 patients). In total, our analysis included 22,125 patients. We identified many limitations in the reporting of studies describing the treatment or prevalence of CNS tumors in children in Iran. Our results may guide future efforts in Iran to improve the care for children with CNS tumors and may provide a valuable template for other comprehensive country- and disease-specific retrospective analyses.

Children with sporadic optic pathway glioma (OPG) commonly experience a decline in visual acuity (VA). This study aimed to quantify long-term VA outcomes after definitive radiation therapy (RT). From 1997 to 2017, 41 patients underwent RT for OPG and had baseline VA testing. All patients underwent serial VA testing every 3–6 months during the first 5 years and annually thereafter. The cumulative incidence of VA decline or improvement (per eye) was estimated using death as a competing risk. Mean follow-up was 5 years. Most tumors (93%) involved the postchiasmatic optic tracts and/or hypothalamus. Of the tumors tested for BRAF alterations (n = 15), 67% had a BRAF fusion. Median time to VA decline was 20 months in the eye with worse vision and 22 months in the better eye. For the worse eye, the 5-year cumulative incidences of VA decline and improvement were 17.9% [95% confidence interval (CI) 7–32.8%] and 13.5% (95% CI 4.7–26.7%), respectively. For the better eye, the 5-year cumulative incidences of VA decline and improvement were 11.5% (95% CI 3.5–30.7%) and 10.6% (95% CI 2.6–25.2%), respectively. Visual outcomes did not correlate with radiographic evidence of tumor progression. The 5-year cumulative incidence of VA decline was low. VA decline is most likely to occur within the first 2 years after RT and is not associated with radiographic progression of disease, highlighting the need for frequent ophthalmologic exams during this period.

BACKGROUND: Pediatric low-grade glioma (pLGG) is the most common CNS tumor of childhood. Progression-free survival (PFS) is much lower than overall survival emphasizing the need for alternative treatments. In addition, many children suffer functional morbidities such as visual and motor disturbances. Recently, there has been an appropriate prioritization of functional outcomes in children with pLGG. METHODS: We present the results of a PBTC phase II trial evaluating selumetinib, (AZD6244, ARRY-142886) a MEK-1/2 inhibitor, in children with recurrent/progressive pLGG on 2 strata, including visual outcomes. RESULTS: Stratum 3 enrolled Neurofibromatosis type 1 (NF1)-associated pLGG. Ten of 25 (40%) eligible patients had partial response (PR), 14/25 (56%) had stable disease (SD) and 1/25 (4%) had progressive disease (PD); 2-year PFS was 96+4%. Ten patients with optic pathway glioma (OPG) were evaluable for visual acuity (VA) at baseline and 1 year. VA improved in 2/10 patients (20%) and was stable in 8/10 (80%). One patient (10%) had improvement in visual fields (VF) and 9 patients (90%) had stable VF. Stratum 4 included patients with non-NF1-associated recurrent/progressive hypothalamic and OPG. Five of 25 (20%) eligible patients had PR, 16/25 (64%) had SD and 4 (16%) had PD; 2-year PFS was 78+8.5%. Nineteen of 25 patients were evaluable for VA. VA improved in 4/19 patients (21%), was stable in 13/19 (68%) and worsened in 2/19 (11%). Five patients (26%) had improved VF and 14 (74%) had stable VF. The most common toxicities included grade 1/2 CPK elevation, diarrhea, hypoalbuminemia and rash. Rare grade 3 toxicities included elevated CPK, rash and paronychia. CONCLUSIONS: Selumetinib was tolerable and effective in treating children with NF1-associated and sporadic recurrent/progressive hypothalamic and OPG based upon radiographic response and PFS. Twenty-seven of 29 (93%) evaluable patients had stable or improved vision based on VA and VF testing.

BACKGROUND: Pediatric low-grade glioma (pLGG) is the most common central nervous system tumor of childhood. Although overall survival is very good, many children suffer from multiple progressions and functional morbidities. There is no one universally accepted therapy for children with recurrent disease, however, standard cytotoxic chemotherapies are often utilized by most practitioners. The Pediatric Brain Tumor Consortium conducted a multi-institutional phase II study evaluating selumetinib (AZD6244, ARRY-142886), a MAP/ERK Kinase I/II inhibitor, in patients with recurrent, refractory or progressive pLGG assigned to numerous strata. The aim of the study was to evaluate the efficacy of selumetinib in these patients. METHODS: Eligibility required age 3–21 y/o, a Lansky or Karnofsky performance score greater than 60 and the presence of recurrent, refractory or progressive pLGG after at least one standard therapy. Stratum 1 included children with World Health Organization (WHO) grade I pilocytic astrocytoma (PA) harboring either one of the two most common BRAF aberrations (KIAA1549-BRAF fusion or the BRAF(V600E) mutation). Stratum 3 included children with any neurofibromatosis type 1 (NF1)-associated pLGG (WHO grades I and II). Selumetinib was provided as capsules given orally at the recommended phase II dose of 25 mg/m(2) twice daily. The primary endpoint was stratum-specific objective response rate assessd by the local site and sustained for at least 8 weeks. All responses were reviewed centrally and statistical analyses were done as per protocol. Although the trial (NCT01089101) is still ongoing in other strata, enrollment and planned follow-up is compete on both strata 1 and 3. FINDINGS: Between July 25, 2013, and June 12, 2015, 25 eligible and evaluable children were accrued to stratum 1, and between August 28, 2013, and June 25, 2015, 25 eligible and evaluable children were accrued to stratum 3. On stratum 1, 9/25 (36%) patients achieved a partial response (PR). The median follow-up for the 11 patients who have not yet experienced an event is 36.4 months (4.4–50.5; IQR=23.9). On stratum 3, 10/25 (40%) patients achieved a PR with a median follow-up of 48.6 months (8.6–59.1; IQR=12.2) for the 17 subjects without progressions. All patients evaluable for visual acuity had improved or stable vision. The most common attributable toxicities on both strata were grade 1 and 2 CPK elevation, hypoalbuminemia, dyspnea, rash, duodenal ulcer, anemia, dry skin, fatigue and diarrhea. Rare grade 3 toxicities included elevated CPK (n=5), maculopapular rash (n=5), neutropenia (n=3), nausea (n=3), paronychia (n=3), acneiform rash (n=2), diarrhea (n=2), elevated ALT (n=1), decreased ejection fraction (n=1), gastric hemorrhage (n=1), headache (n=1), skin infection (n=1), tooth infection (n=1) and weight gain (n=1). There was only one grade 4 toxicity, lymphopenia. There were no treatment-realted deaths. Patient reported outcomes and quality of life assessments were not part of the current study. INTERPRETATION: Selumetinib is active against recurrent, refractory or progressive PA harboring common BRAF aberrations and NF1-associated pLGG. To our knowledge, this is one of the first prospectively tested and successful molecularly-targeted agents in pLGG. These data not only provide an alternative to standard chemotherapy for these subgroups of patients, but this success has led to an interest in exploring efficacy in patients as a first-line therapy. In fact, these data have directly led to the development of two Children’s Oncology Group phase III studies in newly diagnosed pLGG patients both with and without NF1 comparing standard chemotherapy to selumetinib. The current trial was funded by a National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP) PBTC U01 Grant: 2UM1CA081457 (UM1) and by the American Lebanese Syrian Associated Charities.

Background Dysembryoplastic neuroepithelial tumors (DNETs) are uncommon neural tumors presenting most often in children and young adults and associated with intractable seizures. Rare midline neoplasms with similar histological features to those found in DNETs have been described near the septum pellucidum and termed "DNET-like neoplasms of the septum pellucidum." Due to their rarity, these tumors have been described in just a few reports and their genetic alterations sought only in small series. Methods We collected 20 of these tumors for a comprehensive study of their clinical, radiological, and pathological features. RNA sequencing or targeted DNA sequencing was undertaken on 18 tumors, and genome-wide DNA methylation profiling was possible with 11 tumors. Published cases (n = 22) were also reviewed for comparative purposes. Results The commonest presenting symptoms and signs were related to raised intracranial pressure; 40% of cases required cerebrospinal fluid diversion. Epilepsy was seen in approximately one third of cases. All patients had an indolent disease course, despite metastasis within the neuraxis in a few cases. Radiologically, the septum verum/septal nuclei were involved in all cases and are the proposed site of origin for septal DNET (sDNET). Septal DNET showed a high frequency (~80%) of mutations of platelet derived growth factor receptor A (PDGFRA), and alterations in fibroblast growth factor receptor 1 (FGFR1) and neurofibromatosis type 1 (NF1) were also identified. In a genomic DNA methylation analysis alongside other neural tumors, sDNETs formed a separate molecular group. Conclusions Genetic alterations that are different from those of cerebral DNETs and a distinct methylome profile support the proposal that sDNET is a distinct disease entity.

BACKGROUND Pediatric brain tumor classification has undergone significant evolution over the last decade requiring a high-level of expertise and diagnostic techniques. Such advances have created challenges for pathologists particularly in low-to-middle income countries (LMIC). We conduct weekly pediatric neuro-oncology teleconferences linking global pediatric neuro-oncologists from high-income countries (HIC) to review patients with pediatric subspecialists from Latin America. METHODS Three to five patients are discussed weekly and second neuropathology review is offered when a high-level of suspicion emerges of a questionable diagnosis based on clinical and radiographical information. Nationwide Children’s Hospital (NCH) provides second neuropathology review at no cost to institutions in Latin America that fulfill these criteria. RESULTS From July 2015 to December 2019 NCH reviewed 54 pathology samples from eleven Latin American countries. Of these, 33 (61.1%) cases resulted in diagnostic changes, of which 28 (51.8%) were significant, impacting treatment plans and overall patient outcomes. The remaining 21 (38.9%) confirmed institutional diagnosis; however, in eight of these 21 cases additional molecular information and/or further tumor subtyping unavailable in their home country at the time (eg: BRAF, RELA-fusion, medulloblastoma subtyping) was provided. CONCLUSIONS This study highlights the importance of centralized pathology review by institutions with the proper equipment, infrastructure and expertise in pediatric neuropathology. Furthermore, this documents the beneficial impact of teleconferencing for subspecialists in LMIC who must treat a wide variety of pediatric cancers with few resources and support. Additionally, our findings underscore the need for pediatric subspecialty training in LMIC.

The PBTC conducted a re-treatment study (NCT01089101) evaluating selumetinib (AZD6244, ARRY-142886), a MEK I/II inhibitor, in children with recurrent/progressive pLGG. Eligible patients must have previously enrolled on PBTC-029 or PBTC-029B and progressed after coming off treatment with selumetinib. Patients must have maintained stable disease (SD) for ≥12 courses or had a sustained radiographic response (partial or complete) during their first exposure to selumetinib. Thirty-five eligible patients (median age: 13.11 years [range 7.96–25.33]) were enrolled, 57% of whom had optic pathway or hypothalamic target lesions. At the time of submission, median duration of treatment was 18 courses (range 2–48) and 21 subjects remained on therapy. Best responses reported to date are 6/35 (17%) partial response, 22/35 (63%) SD and 7/35 (20%) progressive disease with a 2-year progression-free survival of 75.7 + 8.3%, which met the design parameters for success. The most common attributable toxicities were grade 1 diarrhea, elevated AST, hypoalbuminemia, elevated CPK, maculo-papular rash, fatigue, paronychia, ALT elevation, acneiform rash and grade 2 CPK elevation. Rare grade 3 toxicities included CPK elevation (3), lymphopenia (2), paronychia (2) and ALT elevation (2). There was only one grade 4 CPK elevation. Five patients (14%) required dose reductions due to toxicity. There does not appear to be a notable difference in toxicities observed during initial selumetinib therapy versus re-treatment. In pLGG that has recurred/progressed following treatment with selumetinib, re-treatment with selumetinib appears to be effective with 80% of patients again achieving response or prolonged stable disease. Long-term follow-up is ongoing.

Although approximately 90% of pediatric cancer cases exist in low- and middle-income countries, the magnitude of the global burden of pediatric central nervous system (CNS) tumors remains poorly quantified. METHODS: Data from International Incidence of Childhood Cancer-3 and CONCORD-3, which include observed incidence and survival from population-based cancer registries (PBCR), and from GLOBOCAN 2018 and Global Burden of Disease 2016, which produce burden estimates from observed and modelled data, were used to analyze epidemiologic characteristics and correlations for CNS tumors globally. Data from The World Bank were used for national macroeconomic variables. RESULTS: The majority of countries are not covered by PBCR, with information on incidence and survival available for 37% and 27% of countries, respectively. Survival data is not available for any low-income country. The incidence of CNS tumors varies markedly, from 0.4 to 49 x106 person-years, the greatest variability in pediatric cancer subgroups. Modelled data suggests that approximately 40,000 incident cases and 19,000 deaths occur from CNS tumors worldwide. When country-level data are segregated based on World Bank groups, a difference in incidence and survival exists (p

The success of the treatment of children with central nervous system (CNS) tumors relies on an effective multidisciplinary team, with up-to-date and broad knowledge and skills. The St. Jude Global Academy Neuro-Oncology Training Seminar was launched as course in globally applicable content in pediatric neuro-oncology with a focus on multidisciplinary teams in low- and middle-income countries (LMICs). To identify the content that is most relevant for the learners, a needs assessment survey that included evaluation of team dynamics, treatment capacity, existing knowledge, and educational goals was designed. Survey questions in 11 domains were answered by 24 sites in LMICs across the world. This information was used to create the course that consists of two components: a 9-week online course and a 10-day workshop at the St. Jude campus. 72 participants from 11 institutions enrolled in the online portion and 20 participants were selected based on grades to attend the workshop. A retrospective post-test evaluation established that learners improved their understanding of the barriers to care, possible solutions to improve care, understanding of diagnosis and treatment, and methodology to implement projects (p

BACKGROUND We report the human and material resources available in Chilean institutions providing pediatric neuro-oncology services. METHODS A cross-sectional survey was distributed to 17 hospitals providing pediatric neuro-oncology services (Programa Infantil Nacional de Drogas Antineoplásicas (PINDA) centers=11, Private=6). RESULTS Response rate was 71% (PINDA=8; Private=4). Pediatric neuro-oncology services were mainly provided within general hospitals (67%). Registries for pediatric central nervous system (CNS) tumors and chemotherapy-related toxicities were available in 100% and 67% of centers, respectively. Children with CNS tumors were treated by pediatric oncologists in 92% of institutions; none were formally trained in neuro-oncology. The most utilized treatment protocols were the national PINDA protocols followed by the Children’s Oncology Group protocols. All World Health Organization essential medicines for childhood cancer were available in more than 80% of participating institutions except for gemcitabine, oxaliplatin, paclitaxel, and procarbazine. The median number of pediatric neurosurgeons per institution was two (range,0–8). General neuro-radiologists were available in 83% of institutions. Pathology specimens were sent to pediatric neuropathologists (33%), neuropathologists (25%), adult pathologists (25%), and pediatric pathologists (16.7%). In-house pediatric radiation oncologists were available in 25% of centers. Intensity-modulated radiotherapy, conformal radiotherapy and cobalt radiotherapy were utilized by 67%, 58% and 42% of hospitals, respectively. Only one center performed autologous hematopoietic cell transplant for pediatric CNS tumors. CONCLUSIONS These results provide a glimpse into the pediatric neuro-oncology services available in Chile. A wide range of up-to-date treatment modalities is available for children with CNS tumors in Chile. Establishing formal pediatric neuro-oncology training may be beneficial.

BACKGROUND AND PURPOSE: Pilocytic astrocytomas, the most common posterior fossa tumors in children, are characterized by KIAA1549-BRAF fusions and shows excellent 5-year survival rates. Pilocytic astrocytoma with gangliocytic differentiation, a recently defined pilocytic astrocytoma variant that includes glial and neuronal elements similar to a ganglioglioma, may be distinguished from a classic ganglioglioma by molecular, radiologic, and histopathologic features. This study investigated whether imaging could distinguish posterior fossa pilocytic astrocytoma with and without gangliocytic differentiation. MATERIALS AND METHODS: Preoperative MRIs (± CTs) of 41 children (age range, 7 months to 15 years; mean age, 7.3 ± 3.7 years; 58.5% male) with pilocytic astrocytoma with gangliocytic differentiation (n = 7) or pilocytic astrocytoma (n = 34) were evaluated; differences in tumor location, morphology, and minimum relative ADC between tumor types were compared (Wilcoxon rank sum test, Fisher exact test). Histopathology and BRAF fusion/mutation status were reviewed. Associations of progression-free survival with diagnosis, imaging features, and BRAF status were examined by Cox proportional hazards models. RESULTS: Pilocytic astrocytoma with gangliocytic differentiation appeared similar to pilocytic astrocytoma but had lower minimum relative ADC (mean, 1.01 ± 0.17 compared with 2.01 ± 0.38 for pilocytic astrocytoma; P = .0005) and was more commonly located within midline structures (P = .0034). BRAF status was similar for both groups. Non-total resection (hazard ratio, 52.64; P = .0002), pilocytic astrocytoma with gangliocytic differentiation diagnosis (hazard ratio, 4.66; P = .0104), and midline involvement (hazard ratio, 3.32; P = .0433) were associated with shorter progression-free survival. CONCLUSIONS: Minimum relative ADC and tumor location may be useful adjuncts to histopathology in differentiating pilocytic astrocytoma with gangliocytic differentiation from pilocytic astrocytoma. Shorter progression-free survival in pilocytic astrocytoma with gangliocytic differentiation is likely due to a propensity for involvement of midline structures and poor resectability.

Background A total of 5–10% of patients with retinoblastoma (RB) harbor deletion of the long arm (q) chromosome 13 (13q-). The treatment-related toxicities in this population have not been described. Methods Sixty-eight RB patients on a single institutional protocol (RET5) from 2005 to 2010 were reviewed. Genetic screening identified 11 patients (seven female) with 13q-. Patients with early (Reese-Ellsworth [R-E] group I–III) disease (6/23 with 13q-) received eight courses of vincristine/carboplatin (VC). Patients with advanced (R-E group IV-V) bilateral disease (2/27 with 13q-) received two courses of vincristine/topotecan (VT) followed by nine courses of alternating VT/VC. Patients undergoing upfront enucleation received histopathology-based chemotherapy: intermediate risk (2/8 with 13q-) or high risk (1/10 with 13q-). Dose reductions were mandated for >7 day delay in two consecutive courses following hematologic toxicity. Grades 3 and 4 hematologic, infectious, and gastrointestinal toxicities were compared between RET5 patients with and without 13q-. Results Demographics were similar between groups. When present, prolonged neutropenia (median 7 days, range 0–14 days) delayed chemotherapy and resulted in more frequent dose reductions among 13q- patients (5/11) than non-13q- patients (4/57) (P < 0.01). GI toxicity was similar between groups (5/11 13q- vs. 13/57 non-13q-; P = 0.14), but halted chemotherapy in one 13q- patient. Infectious complications and disease outcomes were similar between groups. At follow-up, all patients are alive (median 6.1 years, range 7.6 months–9.5 years). Conclusions 13q- RB patients had a higher incidence of neutropenia requiring chemotherapy dose reductions, but did not have increased treatment failure.

Purpose Pediatric medulloblastoma (MB) treatment has evolved over the past few decades; however, treating children in countries with limited resources remains challenging. Until now, the literature regarding childhood MB in Malaysia has been nonexistent. Our objectives were to review the demographics and outcome of pediatric MB treated at the University Malaya Medical Center between January 1994 and December 2013 and describe the challenges encountered. Methods Fifty-one patients with childhood MB were seen at University Malaya Medical Center. Data from 43 patients were analyzed; eight patients were excluded because their families refused treatment after surgery. Results Headache and vomiting were the most common presenting symptoms, and the mean interval between symptom onset and diagnosis was 4 weeks. Fourteen patients presented with metastatic disease. Five-year progression-free survival (± SE) for patients ≥ 3 years old was 41.7% ± 14.2% (95% CI, 21.3% to 81.4%) in the high-risk group and 68.6% ± 18.6% (95% CI, 40.3% to 100%) in the average-risk group, and 5-year overall survival (± SE) in these two groups was 41.7% ± 14.2% (95% CI, 21.3% to 81.4%) and 58.3% ± 18.6% (95% CI, 31.3% to 100%), respectively. Children younger than 3 years old had 5-year progression-free and overall survival rates (± SE) of 47.6% ± 12.1% (95% CI, 28.9% to 78.4%) and 45.6% ± 11.7% (95% CI, 27.6% to 75.5%), respectively. Time to relapse ranged from 4 to 132 months. Most patients who experienced relapse died within 1 year. Febrile neutropenia, hearing loss, and endocrinopathy were the most common treatment-related complications. Conclusion The survival rate of childhood MB in Malaysia is inferior to that usually reported in the literature. We postulate that the following factors contribute to this difference: lack of a multidisciplinary neuro-oncology team, limited health care facilities, inconsistent risk assessment, insufficient data in the National Cancer Registry and pathology reports, inadequate long-term follow-up, and cultural beliefs leading to treatment abandonment.

Studies of epidemiology, treatment modalities, and outcomes of childhood central nervous system (CNS) tumors in Sudan are scarce. To address this shortcoming, we evaluated baseline information about the epidemiology, treatment types, and outcomes of childhood CNS tumors at the National Cancer Institute, University of Gezira (NCI-UG) in Wad Madani, Sudan. We performed a retrospective health facility-based study of children with CNS tumors who were treated at the NCI-UG from January 2000 to December 2015. A total of 62 (5.4% of all childhood cancers) pediatric patients with CNS tumors were identified over the study period. Tumors were more common among male children and involved the infratentorial compartment in 58% of cases. The median age at diagnosis was 9 years (range, 2–14 years). Approximately 60% (n = 37) of the study population had histology-determined diagnoses. Astrocytomas and medulloblastomas were the most common tumors in these cases. The mean time to diagnosis was 6 months (SD, 9). During the study period, the number of children with CNS tumors who were referred for treatment at the NCI-UG increased every year. Of the 37 patients who received surgical interventions, 8 received gross total resections, 20 received partial resections, and 24 received postoperative radiotherapy. The treatment abandonment rate was 11%. The 2-year and 5-year survival rates were 33% and 13%, respectively. Our findings reveal a high incidence of poor outcomes for patients with CNS tumors in Sudan, which is most likely due to many distinct factors.

The Latin American Brain Tumor Board (LATB) is a weekly teleconference connecting pediatric neuro-oncologists from referral centers in high-income countries with pediatric subspecialists from 20 Latin American countries since 2013. This survey explored the participants’ experience utilizing this resource. A cross-sectional electronic questionnaire was distributed to 159 participants through email and Cure4Kids. Ninety-five respondents (60%) from all the participating countries completed the survey. Sixty-one reported frequent-attendance (≥ 1 per month), 23 reported infrequent-attendance (