Case of embryonal tumor multilayered rosettes in a patient with neurofibromatosis type 1.

BACKGROUND: ETMR is a unique and highly malignant brain tumor mostly occurring in infants. This report provides a comprehensive overview of the clinical presentation, histological aspects, radiological features, and therapeutic options of ETMR. Being the first report on the co-occurrence of NF1 with ETMR, it highlight the challenges of managing a patient with complex medical conditions. CASE REPORT: We present a case of a 3 and 1/2-year-old girl with neurofibromatosis type 1 (NF1), later diagnosed with a supratentorial brain tumor reported as an embryonal tumor with multilayered rosettes (ETMR), along with possible co-occurrence of constitutional mismatch repair deficiency (CMMRD) on immunohistochemistry (IHC); however, germline testing was not performed. Even though NF1 can be associated with tumors such as gliomas, the literature has no previous case reports of ETMR coexisting with NF1. CONCLUSION: Exploring the link between NF1 and ETMR with CMMRD is crucial to improving and establishing more treatment protocols. Therefore, reporting each case's unique features would be essential in developing appropriate treatment protocols.

Pediatric neuropathology practice in a low- and middle-income country: capacity building through institutional twinning.

Background: Accurate and precise diagnosis is central to treating central nervous system (CNS) tumors, yet tissue diagnosis is often a neglected focus in low- and middle-income countries (LMICs). Since 2016, the WHO classification of CNS tumors has increasingly incorporated molecular biomarkers into the diagnosis of CNS tumors. While this shift to precision diagnostics promises a high degree of diagnostic accuracy and prognostic precision, it has also resulted in increasing divergence in diagnostic and management practices between LMICs and high-income countries (HICs). Pathologists and laboratory professionals in LMICs lack the proper training and tools to join the molecular diagnostic revolution. We describe the impact of a 7-year long twinning program between Canada and Pakistan on pathology services. Methods: During the study period, 141 challenging cases of pediatric CNS tumors initially diagnosed at Aga Khan University Hospital (AKUH), Karachi, were sent to the Hospital for Sick Children in Toronto, Canada (SickKids), for a second opinion. Each case received histologic review and often immunohistochemical staining and relevant molecular testing. A monthly multidisciplinary online tumor board (MDTB) was conducted to discuss the results with pathologists from both institutions in attendance. Results: Diagnostic discordance was seen in 30 cases. Expert review provided subclassification for 53 cases most notably for diffuse gliomas and medulloblastoma. Poorly differentiated tumors benefited the most from second review, mainly because of the resolving power of specialized immunohistochemical stains, NanoString, and targeted gene panel next-generation sequencing. Collaboration with expert neuropathologists led to validation of over half a dozen immunostains at AKUH facilitating diagnosis of CNS tumors. Conclusions: LMIC-HIC Institutional twinning provides much-needed training and mentorship to pathologists and can help in infrastructure development by adopting and validating new immunohistochemical stains. Persistent unresolved cases indicate that molecular techniques are indispensable in for diagnosis in a minority of cases. The development of affordable alternative molecular techniques may help with these histologically unresolved cases.

Capacity building for pediatric neuro-oncology in Pakistan- a project by my child matters program of Foundation S.

Introduction: Initiated in June 2019, this collaborative effort involved 15 public and private sector hospitals in Pakistan. The primary objective was to enhance the capacity for pediatric neuro-oncology (PNO) care, supported by a My Child Matters/Foundation S grant. Methods: We aimed to establish and operate Multidisciplinary Tumor Boards (MTBs) on a national scale, covering 76% of the population (185.7 million people). In response to the COVID-19 pandemic, MTBs transitioned to videoconferencing. Fifteen hospitals with essential infrastructure participated, holding monthly sessions addressing diagnostic and treatment challenges. Patient cases were anonymized for confidentiality. Educational initiatives, originally planned as in-person events, shifted to a virtual format, enabling continued implementation and collaboration despite pandemic constraints. Results: A total of 124 meetings were conducted, addressing 545 cases. To augment knowledge, awareness, and expertise, over 40 longitudinal lectures were organized for healthcare professionals engaged in PNO care. Additionally, two symposia with international collaborators and keynote speakers were also held to raise national awareness. The project achieved significant milestones, including the development of standardized national treatment protocols for low-grade glioma, medulloblastoma, and high-grade glioma. Further protocols are currently under development. Notably, Pakistan's first pediatric neuro-oncology fellowship program was launched, producing two graduates and increasing the number of trained pediatric neuro-oncologists in the country to three. Discussion: The initiative exemplifies the potential for capacity building in PNO within low-middle income countries. Success is attributed to intra-national twinning programs, emphasizing collaborative efforts. Efforts are underway to establish a national case registry for PNO, ensuring a comprehensive and organized approach to monitoring and managing cases. This collaborative initiative, supported by the My Child Matters/Foundation S grant, showcases the success of capacity building in pediatric neuro-oncology in low-middle income countries. The establishment of treatment protocols, fellowship programs, and regional tumor boards highlights the potential for sustainable improvements in PNO care.

Predictors of neurocognition outcomes in children and young people with primary brain tumor presenting to tertiary care hospitals of Karachi, Pakistan: a prospective cohort study.

INTRODUCTION: Primary brain tumors are a common cause of morbidity and mortality in children and young people (CYP) globally. Impaired neurocognitive function is a potential severe consequence in primary brain tumor (PBT) survivors. There are no in-depth studies from low- and middle-income countries (LMICs) to inform management and follow-up. The research questions of this study were as follows: Are the sociodemographic factors (lower age of CYP, female gender, low socioeconomic status, low parental education), disease-related factors (high grade of tumor, presence of seizures, presence of hydrocephalous), and treatment-related factors (adjuvant therapy, no surgical intervention, post-treatment seizures, placement of shunts) associated with decline in neurcognition outcomes 12 months post-treatment in CYP with PBTs? METHODS: A prospective cohort study was conducted from November 2020 to July 2023 at the Aga Khan University Hospital and Jinnah Postgraduate Medical Centre, tertiary care hospitals in Karachi, Pakistan. All CYP aged 5 to 21 years with a newly diagnosed PBTs were eligible. The neurocognition assessment was undertaken by a psychologist at two points, i.e., pre-treatment and at 12 months post-treatment using validated tools. The verbal intelligence was assessed by Slosson Intelligence tool, revised 3rd edition (SIT-R3), perceptual reasoning by Raven's Progressive Matrices (RPM), and the Processing Speed Index by Wechsler Intelligence Scale (WISC V) and Wechsler Adult Intelligence Scale (WAIS-IV). The data were analyzed by STATA version 12 software. Generalized estimating equation (GEE) was used to determine the factors associated with the mean change in 12 months post-treatment verbal and non-verbal neurocognition scores. Unadjusted and adjusted beta coefficients with their 95% confidence intervals were reported. RESULTS: A total of 48 CYPs with PBTs were enrolled, 23 (48%) of them were lost to follow-up and 10 (21%) died. The remaining 25 (52%) were reassessed 12 months after treatment. On multivariable analysis, a significant decline in verbal intelligence scores at 12 months was predicted by post-treatment seizures beta = - 20.8 (95% CI, - 38.2, - 3.4), mothers having no formal educational status and lower household monthly income. Similarly, a significant decline in perceptual reasoning scores was also predicted by post-treatment seizures beta = - 10.7 (95% CI, - 20.6, - 0.8), mothers having no formal education and having lower household monthly income. Worsening of processing speed scores at 12 months post-treatment were predicted by tumor histology, post-treatment seizures beta = - 33.9 (95% CI, - 47.7, - 20.0), lower educational status of the mother, and having lower household monthly. However, an improvement was seen in processing speed scores after surgical tumor resection. CONCLUSION: In this novel study, the post-treatment mean change in verbal and non-verbal neurocognition scores was associated with sociodemographic, tumor, and treatment factors. These findings may have potential implications for targeted early psychological screening of higher risk CYP with PBTs. Identification of these predictors may serve as a foundation for developing more cost-effective treatment thereby alleviating the burden of neurocognitive morbidity. However to establish generalizability, future research should prioritize larger-scale, multicountry studies. (Trial registration: ClinicalTrials.gov Identifier: NCT05709522).

Global pediatric craniopharyngioma management modalities and outcomes.

INTRODUCTION: Pediatric craniopharyngioma is a complex pathology, with optimal management involving a multidisciplinary approach and thoughtful care coordination. To date, no studies have compared various treatment modalities and outcomes described in different global regions. We conducted a comprehensive systematic review to compare demographics, clinical presentation, treatment approach and outcomes of children diagnosed with craniopharyngioma globally. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Search terms included "craniopharyngioma" and country-specific terms. Inclusion criteria included full-text studies published between 2000-2022, primarily examining pediatric patients 18-years old or younger diagnosed with craniopharyngioma, and reporting management and outcomes of interest. Data extracted included country of origin, demographical data, initial presentation and treatment modality, and outcomes. Descriptive statistics and between-group comparisons based on country of origin were performed. RESULTS: Of 797 search results, 35 articles were included, mostly originating from high-income countries (HIC) (n = 25, 71.4%). No studies originated from low-income countries (LIC). When comparing HIC to middle-income countries (MIC), no differences in patient demographics were observed. No differences in symptomatology at initial presentation, tumor type, surgical approach or extent of surgical resection were observed. HIC patients undergoing intracystic therapy were more likely to receive bleomycin (n = 48, 85.7%), while the majority of MIC patients received interferon therapy (n = 10, 62.5%). All MIC patients undergoing radiation therapy underwent photon therapy (n = 102). No statistically significant differences were observed in postoperative complications or mean follow-up duration between HIC and MIC (78.1 ± 32.2 vs. 58.5 ± 32.1 months, p = 0.241). CONCLUSION: Pediatric craniopharyngioma presents and is managed similarly across the globe. However, no studies originating from LICs and resource-poor regions examine presentation and management to date, representing a significant knowledge gap that must be addressed to complete the global picture of pediatric craniopharyngioma burden and management.

Pediatric craniopharyngioma: a 20-year study on epidemiological features, clinical presentation, and survival outcomes in a tertiary care center from LMIC.

INTRODUCTION: Craniopharyngioma constitutes approximately 10% of primary brain tumors in children. It can cause considerable morbidity and mortality due to the local aggressiveness of the tumor itself or its management affecting the hypothalamus-pituitary axis and optic pathway involvement. There is very scarce data available from LMIC which makes the management controversial where multidisciplinary teams are already not available in most of the centers. This is a single-center cross-sectional retrospective review of 20-year record of 49 patients with craniopharyngioma treated between 2001 and 2020 at Aga Khan University Hospital, a tertiary care center in Karachi, Pakistan. METHODS: We have assessed the epidemiological data of children presenting with the diagnosis of craniopharyngioma, treatment modalities used, and neurological, endocrine, and hypothalamic complications in these patients. The assessment involved a retrospective review of medical records and medical follow-up. RESULTS: Out of a total of 49 patients, 26 (53%) were male, and 23 (46.9%) were female. The mean age was 9.5 years (SD ± 4.5 years). Most common symptoms at initial presentation were headache 41 (83.6%), visual deficit 40 (81.6%), nausea and vomiting 26 (53%), and endocrine abnormalities 16 (32%). Treatment modalities used at our center include gross total resection 11 (22%) and subtotal resection 38 (77%) out of total, while 6 (12.2%) patients received intracystic interferon. Histopathologic findings of the majority of patients (40 (81%)) revealed an adamantinomatous type of tumor. Only 23 (46.9%) children followed in clinic post-op. Median follow-up after craniopharyngioma presentation was 5 years (± 2.1 SD, range: 2-10 years). Pituitary hormone deficiencies (98%) and visual disturbances (75%) were the most common long-term health conditions observed. CONCLUSIONS: Since pituitary hormone deficiencies and visual disturbance were the most common long-term health conditions observed in our study, these patients require a multidisciplinary team follow-up to improve their quality of life.

Paediatric choroid plexus carcinoma: a retrospective case series from Karachi.

The objective of this study is to report clinical, radiological, and histopathological characteristics of three paediatric patients diagnosed as Choroid plexus carcinoma seen at our hospital, between 2015 and 2020. Three patients were diagnosed with choroid plexus carcinomas between 2015 and 2018. The mean age at diagnosis was 1.3 years (range 8 months to 1.5 years). All the three patients had subtotal resection and received adjuvant chemotherapy. One patient also received adjuvant radiotherapy. Despite these treatment measures, residual disease was noted in all three patients and two patients were subsequently treated on palliative care grounds. The average duration of follow-up after the first surgery for all three patients was approximately 33 months. Attaining satisfactory outcome in patients with CPC is challenging. Our case series reflects the difficulty in achieving gross total resection and ensuring that the disease does not recur.

Evolution of Systemic Therapy in Medulloblastoma Including Irradiation-Sparing Approaches.

The management of medulloblastoma in children has dramatically changed over the past four decades, with the development of chemotherapy protocols aiming at improving survival and reducing long-term toxicities of high-dose craniospinal radiotherapy. While the staging and treatment of medulloblastoma were until recently based on the modified Chang's system, recent advances in the molecular biology of medulloblastoma have revolutionized approaches in the management of this increasingly complex disease. The evolution of systemic therapies is described in this review.

Socio-demographic and antenatal risk factors of brain tumor in children and young people: A matched case-control study from Karachi, Pakistan.

Background: Brain tumors are a common cause of morbidity, disability, cognitive deterioration and mortality in children, even after treatment. Little is know about the specific causes. The study aimed to assess potential socio-demographic and antenatal factors in primary brain tumor (PBTs) in children and young people (CYP) in Karachi, Pakistan. Designs and methods: A single center hospital based matched case control study in Karachi, Pakistan. Cases were defined as CYP aged between 5 and 21 years with any histological type and grade of primary brain tumor of any histology, stage or grade. Data were collected from parents of 244 patients at the selected center between 2017 and 2021 via telephonic interview. Controls were 5-21 years old CYP admitted with non-oncological diagnoses matched on age and sex. Matched Odds Ratios for predictors of brain tumor in children were derived. Those of statistical significance were included in a multivariable logistic regression model. Results: In the adjusted model, lower paternal education (matched adjusted odds ratio (maOR) 2.46; 95% CI 1.09-5.55), higher household monthly income (maOR 3.4; 95% CI 1.1-10.2), antenatal paternal use of addictive substances (maOR 19.5; 95% CI 2.1-179.8), and antenatal maternal use of analgesics during pregnancy (maOR 3.0; 95% CI 1.2-7.9) were all independently predictive of brain tumors. Conclusion: This matched case-control study found novel associations between maternal use of analgesics, paternal use of addictive substances, higher household income, and lower paternal education and Primary Brain Tumors in Children and Young People. Longitudinal multicenter studies will be required to test these associations prospectively.

Pakistan National Guidelines for Pediatric High-Grade Gliomas.

Pediatric high-grade glioma (pHGG) is highly malignant central nervous system tumor and constitute 10% of the pediatric gliomas. Effective treatment needs a functioning multi-disciplinary team including pediatric neuro oncologist, neurosurgeon, neuroradiologist, neuropathologist and radiation oncologist. Despite surgical resection, radiotherapy and chemotherapy, most HGG will recur resulting in early death. A significant proportion of HGG occurs in context of cancer predisposition syndromes like Constitutional Mismatch Repair Deficiency (CMMRD) also known as Biallelic Mismatch Repair Deficiency (bMMRD) characterized by high mutational burden. The incidence of HGG with CMMRD is one per million patients. bMMRD is caused by homozygous germline mutations in one of the four Mis Match Repair (MMR) genes (PMS2, MLH1, MSH2, and MSH6). The use of TMZ is now avoided in CMMRD related HGG due to its limited response and known ability to increase the accumulation of somatic mutations in these patients, increasing the risk of secondary tumors. HGG should be managed under the care of multidisciplinary team to receive optimum treatment. This is particularly important for low middle-income countries (LMIC) with limited resources like Pakistan.

Karachi Cancer Registry (KCR): Consolidated Data of 5-years 2017-2021.

OBJECTIVE:  To collect and analyse epidemiologic data of all malignancies by age group and gender for the Karachi population to estimate the cancer incidence of 5-years (2017-2021) and identify major risk factors for setting priorities towards cancer control programs. STUDY DESIGN: Observational study. Place and Duration of the Study: Karachi Cancer Registry (KCR) Secretariat, Pakistan Health Research Council (PHRC), JPMC, Karachi, from 2017-2021. METHODOLOGY: Cancer data of seven tertiary care hospitals of Karachi submitted to KCR during the study period were analysed including age, gender, date of first contact, primary site and ICD coding. All the data was cleaned, merged, and analysed. All patients 0-14 years were classified as 'children', all aged 15-19 years were classified as 'adolescents', and those age 20-years and above as 'adults'. Age standardised incidence rates (ASIR) were determined for both genders. RESULTS: During the last five years (2017-2021), a total of 65,886 malignant cases were received. The distributions seen amongst males and females were 33,510 (51%) and 32,376 (49%), respectively with 60,145 (91.3%) tumours found in adults (≥20 years), 4844 (7.3%) in children, and 897 (1.4%) in adolescents. The three most common tumour sites were oral, liver, and colorectal in males; breast, oral and ovary in females; bone, brain and connective tissue in adolescents; and leukaemia, brain and bone in children. The overall ASIR (%) in males was 89.20 for adults, 9.19 for children, and 1.61 for adolescents. The overall ASIR (%) in females was 93.44 for adults, 5.45 for children, and 1.11 for adolescents. CONCLUSION: Oral cancer, a largely preventable cancer is the leading cancer in males while breast cancer is the leading cancer in females followed by oral cancer. In adolescents and children, the incidence closely matches most of the world. KEY WORDS: Karachi, Cancer registry, Oral cancer, Breast cancer, Age-standerdised ratio.

SIOP PODC-adapted treatment guidelines for craniopharyngioma in low- and middle-income settings.

Pediatric craniopharyngioma is a rare tumor with excellent survival but significant long-term morbidities due to the loco-regional tumor growth or secondary to its treatment. Visual impairment, panhypopituitarism, hypothalamic damage, and behavioral changes are among the main challenges. This tumor should be managed under the care of a multidisciplinary team to determine the optimum treatment within the available resources. This is particularly important for low middle-income countries where resources are variable. This report provides risk-stratified management guidelines for children diagnosed with craniopharyngioma in a resource-limited setting.

Impact of dedicated pediatric neuro-oncological services in a developing country: A single-institution, Pakistani experience.

INTRODUCTION: Brain tumors are the most common solid neoplasms and the second most common malignancy in the pediatric age group. Due to the complexity of their management, pediatric central nervous system (CNS) tumors are not a priority in low- and middle-income countries (LMICs). METHODS: In an attempt to improve the survival rate and overall care, we introduced a dedicated pediatric neuro-oncology service in our institute and evaluated its impact by dividing the pre- and post-era into two cohorts and comparing them: 1998-2013 (16 years: cohort A) and 2014-2019 (6 years: cohort B, after the start of dedicated neuro-oncology services). RESULTS: We observed that after the implementation of a proper neuro-oncology service, the proportion of patients treated with curative intent increased, and survival improved in cohort B. The patient volume also increased from 15.5 per year in cohort A to 44.8 per year in cohort B. The percentage of children given radiation therapy also increased significantly, while the proportion of children treated with chemotherapy remained stable. CONCLUSION: A dedicated multidisciplinary team trained and knowledgeable in the specialty of pediatric neuro-oncology can enhance and improve outcomes, and supportive care and help can provide good quality of life to children and their families with brain neoplasms.

Evaluating blinatumomab implementation in low- and middle-income countries: a study protocol.

BACKGROUND: The recent implementation of novel therapies has accelerated progress in pediatric cancer care. Despite the significantly poorer survival of patients in low- and middle-income countries (LMICs), administation complexities and other significant resource barriers have limited the translation of these novel therapies in these regions. This study aims to develop a model that can be used to support the implementation of novel therapies, such as blinatumomab (bispecific antibody therapy for B-cell acute lymphoblastic leukemia [B-ALL]) in LMIC centers, with the long-term goal of developing an implementation framework for similar future efforts. METHODS: In this study, mixed methods will be applied to understand the key contextual considerations that can be accounted for through a training program and prospectively designed implementation activities. The Consolidated Framework for Implementation Research will guide the activities related to implementation evaluation in parallel with a drug donation program. A multidisciplinary research team comprising high- and low-middle income healthcare professionals, industry, and implementation scientists has been assembled with the common goal of improving safe access to blinatumomab. To assess the factors affecting blinatumomab administration, semi-structured interviews with diverse collaborators and quantitative assessments of organizational characteristics will be conducted, together with quantitative and qualitative assessments of feasibility, acceptability, appropriateness, and cost of blinatumomab implementation. A quantitative assessment of stakeholder perceptions of different implementation strategies used as part of the multifaceted approach will also be performed. Finally, we will examine the key domains and processes used and construct the implementation roadmap for translation of novel therapies. DISCUSSION: This study will rigorously develop an implementation roadmap for translation of novel therapies in low-resource settings. The knowledge gained in the formative assessment will reveal the priority areas and key implementation strategies. Thereby, the resultant roadmap will facilitate future scale-out strategies for novel therapies in LMICs, thus increasing access, building capacity for management, and ultimately improving the care for children in LMICs.

Building the ecosystem for pediatric neuro-oncology care in Pakistan: Results of a 7-year long twinning program between Canada and Pakistan.

BACKGROUND: Low- and middle-income countries sustain the majority of pediatric cancer burden, with significantly poorer survival rates compared to high-income countries. Collaboration between institutions in low- and middle-income countries and high-income countries is one of the ways to improve cancer outcomes. METHODS: Patient characteristics and effects of a pediatric neuro-oncology twinning program between the Hospital for Sick Children in Toronto, Canada and several hospitals in Karachi, Pakistan over 7 years are described in this article. RESULTS: A total of 460 patients were included in the study. The most common primary central nervous system tumors were low-grade gliomas (26.7%), followed by medulloblastomas (18%), high-grade gliomas (15%), ependymomas (11%), and craniopharyngiomas (11.7%). Changes to the proposed management plans were made in consultation with expert physicians from the Hospital for Sick Children in Toronto, Canada. On average, 24% of the discussed cases required a change in the original management plan over the course of the twinning program. However, a decreasing trend in change in management plans was observed, from 36% during the first 3.5 years to 16% in the last 3 years. This program also led to the launch of a national pediatric neuro-oncology telemedicine program in Pakistan. CONCLUSIONS: Multidisciplinary and collaborative efforts by experts from across the world have aided in the correct diagnosis and treatment of children with brain tumors and helped establish local treatment protocols. This experience may be a model for other low- and middle-income countries that are planning on creating similar programs.

Childhood Medulloblastoma.

Medulloblastoma is the most common malignant brain tumour in children and is a major cause of mortality and morbidity, particularly in low- and middle-income countries. It has been risk-stratified on the basis of clinical (age, metastasis and extent of resection) and histological subtypes (classic, desmoplastic and anaplastic). However, recently medulloblastoma has been sub-grouped by using a variety of different genomic approaches, such as gene expression profiling, micro-ribonucleic acid profiling and methylation array into 4 groups, namely Wingless, Sonic hedgehog, Group 3 and Group 4. This new sub-grouping has important therapeutic and prognostic implications. After acute leukaemia, brain tumour is the second most common malignancy in the paediatric age group. The improvement in outcome of acute lymphoblastic leukaemia in low- and middle-income countries reflects the relative simplicity of diagnostic procedures and management. Unlike leukaemia, the management of brain tumours requires a complex multidisciplinary approach, including neuro-radiologists, neurosurgeons with a paediatric expertise, neuropathologists, radiation oncologists and neuro-oncologists. In addition, the equipment required for the diagnosis (magnetic resonance imaging scan, histological, molecular and genetic techniques) and the management (operating room, radiation facilities) is a limiting factor in countries with limited resources. In Pakistan, there are very few centres able to treat children with brain tumours. The current literature review was planned to provide an update on the management of this tumour.

Cerebellar Mutism Syndrome after surgical resection of posterior fossa neoplastic lesions.

Cerebellar Mutism Syndrome (CMS) is a well-described clinical entity that complicates surgeries for posterior fossa tumours; more so in children than adults. This review focuses on the current understanding of CMS, its incidence and risk factors. Incidence showed a variable range in retrospective studies due to variety of definitions. Risk factors can be classified as either modifiable including surgical technique, or non-modifiable which include tumour related factors. A positive correlation has been associated between tumour pathology, brain stem invasion and size of tumour at time of presentation with development of CMS.

Outcomes of BRAF V600E Pediatric Gliomas Treated With Targeted BRAF Inhibition.

PURPOSE: Children with pediatric gliomas harboring a BRAF V600E mutation have poor outcomes with current chemoradiotherapy strategies. Our aim was to study the role of targeted BRAF inhibition in these tumors. PATIENTS AND METHODS: We collected clinical, imaging, molecular, and outcome information from patients with BRAF V600E-mutated glioma treated with BRAF inhibition across 29 centers from multiple countries. RESULTS: Sixty-seven patients were treated with BRAF inhibition (pediatric low-grade gliomas [PLGGs], n = 56; pediatric high-grade gliomas [PHGGs], n = 11) for up to 5.6 years. Objective responses were observed in 80% of PLGGs, compared with 28% observed with conventional chemotherapy (P < .001). These responses were rapid (median, 4 months) and sustained in 86% of tumors up to 5 years while receiving therapy. After discontinuation of BRAF inhibition, 76.5% (13 of 17) of patients with PLGG experienced rapid progression (median, 2.3 months). However, upon rechallenge with BRAF inhibition, 90% achieved an objective response. Poor prognostic factors in conventional therapies, such as concomitant homozygous deletion of CDKN2A, were not associated with lack of response to BRAF inhibition. In contrast, only 36% of those with PHGG responded to BRAF inhibition, with all but one tumor progressing within 18 months. In PLGG, responses translated to 3-year progression-free survival of 49.6% (95% CI, 35.3% to 69.5%) versus 29.8% (95% CI, 20% to 44.4%) for BRAF inhibition versus chemotherapy, respectively (P = .02). CONCLUSION: Use of BRAF inhibition results in robust and durable responses in BRAF V600E-mutated PLGG. Prospective studies are required to determine long-term survival and functional outcomes with BRAF inhibitor therapy in childhood gliomas.

Impact of the coronavirus disease 2019 (COVID-19) pandemic on pediatric oncology care in the Middle East, North Africa, and West Asia region: A report from the Pediatric Oncology East and Mediterranean (POEM) group.

BACKGROUND: Childhood cancer is a highly curable disease when timely diagnosis and appropriate therapy are provided. A negative impact of the coronavirus disease 2019 (COVID-19) pandemic on access to care for children with cancer is likely but has not been evaluated. METHODS: A 34-item survey focusing on barriers to pediatric oncology management during the COVID-19 pandemic was distributed to heads of pediatric oncology units within the Pediatric Oncology East and Mediterranean (POEM) collaborative group, from the Middle East, North Africa, and West Asia. Responses were collected on April 11 through 22, 2020. Corresponding rates of proven COVID-19 cases and deaths were retrieved from the World Health Organization database. RESULTS: In total, 34 centers from 19 countries participated. Almost all centers applied guidelines to optimize resource utilization and safety, including delaying off-treatment visits, rotating and reducing staff, and implementing social distancing, hand hygiene measures, and personal protective equipment use. Essential treatments, including chemotherapy, surgery, and radiation therapy, were delayed in 29% to 44% of centers, and 24% of centers restricted acceptance of new patients. Clinical care delivery was reported as negatively affected in 28% of centers. Greater than 70% of centers reported shortages in blood products, and 47% to 62% reported interruptions in surgery and radiation as well as medication shortages. However, bed availability was affected in <30% of centers, reflecting the low rates of COVID-19 hospitalizations in the corresponding countries at the time of the survey. CONCLUSIONS: Mechanisms to approach childhood cancer treatment delivery during crises need to be re-evaluated, because treatment interruptions and delays are expected to affect patient outcomes in this otherwise largely curable disease.