Demographic profile and outcome in primary pediatric brain tumors. A single tertiary institute experience in India

Introduction: Pediatric brain tumors are the most common tumor in children after hematological malignancies. There is very few data about the epidemiology of pediatric brain tumors in India. Methods - This was a prospective and retrospective study in pediatric patients who had undergone surgery in our institute (JIPMER,Pondicherry). 80 cases were recruited and followed up for minimum follow up period of 1 year. The demographic profile was analysed and IHC markers were done for embroyonal tumors and glioma. Result(s): Pediatric brain tumors was equally distributed among male and females. (1:1) .Mean age of presentation was 10 years . 27.5 % of our cases were embryonal tumors,low grade glioma (16.25 % ) ,high grade glioma ( 12.5 % ) ,ependymoma and craniopharyngioma comprised 15 % of our cases each. Medulloblastoma comprised 23.75 % of cases Out of which 31.5 % had craniospinal metastasis at time of diagnosis. The most common location of SHH pathway medulloblastoma was cerebellar hemisphere and non WNT/non SHH was fourth ventricle. 45.45 % of patients with high grade glioma had recurrence .50 % of ependymoma cases were infratentorial. we had 2 cases of ganglioglioma ,one in the midbrain and other in temporal lobe .Gross total resection was achieved in 30 % ,Subtotal resection in 46.25 % and partial resection in 20 % of our cases. Outcome of patients at the end of 1 year for low and high grade glioma, ependymoma and craniopharyngioma were similar to western literature. Two patients acquired COVID 19 and died while undergoing treatment. Molecular markers like INI1, LIN28 A was highly sensitive and specific for diagnosing atypical teratoid rhabdoid tumor (ATRT) and embryonal tumor with multilayered rosettes (ETMR )respectively. Conclusion(s): Our study emphasizes the need of standardized and systemic cancer registries in India. (Figure Presented).

Neurooncology: 2021 update.

This article briefly presents 10 topics that were selected by the author as 'top 10 discoveries' published in 2020 in the broader field of neurooncological pathology including neurosciences as well as clinical neurooncology of interest for neurooncological pathology. The selected topics concern new information on the molecular characteristics of gliomas (infratentorial IDH-mutant diffuse astrocytomas, pediatric low-grade gliomas, infant-type high-grade gliomas, hypermutation in gliomas), the immunological aspects of the brain tumor microenvironment (TME), the impact of the TME on preclinical glioma models, and the importance of lymphatic drainage on brain tumor surveillance. Furthermore, important papers were published on two 'new' genetic syndromes predisposing to medulloblastoma, on liquid biopsy-based diagnosis of central nervous system (CNS) tumors, and on the 'microbiome' in glioblastomas (and other cancers). In the last part of this review, a dozen of papers are given as examples of papers that did not make it to the top 10 list of the author, underscoring the subjective component in the selection process. Acknowledging that 2020 will be remembered as the year in which the world changed because of the COVID-19 pandemic, some of the consequences of this pandemic for neurooncological pathology are briefly discussed as well. Hopefully, this review forms an incentive to appreciate the wealth of information provided by the papers that were used as building blocks for the present manuscript.

Neurological manifestations in pediatric patients with COVID-19: A case series

In this case series of two male and one female patient with an age range of 2-12 years, only one patient had a history of neurological disorder and underwent ventriculoperitoneal shunt for a medulloblastoma, which describes coronavirus disease-associated neurological manifestations in pediatric patients, among which seizures and sensory disturbances are noticeable. In order to describe the various clinical and neurological manifestations that appeared earlier or developed over the course of illness, a series of cases of pediatric patients with coronavirus disease was documented. Copyright © 2022, Indian Association of Biomedical Scientists. All rights reserved.

Craniospinal Reirradiation Using Proton Beam Radiotherapy in the Treatment of Pediatric Recurrent Medulloblastoma

Craniospinal irradiation (CSI) is an essential part of medulloblastoma treatment even without any evidence of leptomeningeal metastasis. In case of recurrence, it is important to assess several factors to consider reirradiation course. These factors include prior radiation doses, time interval between radiotherapy courses and cumulative dose. In cases of leptomeningeal dissemination reirradiation of the entire craniospinal axis is needed, but may be accompanied by severe toxicity. Proton therapy may reduce toxicity without reducing treatment doses. Proton beam craniospinal reirradiation (CSRI) course was conducted to 18 patients with recurrent medulloblastoma. Median dose to craniospinal axis during primary treatment was 30.6 Gy (24-36). Sixteen patients had additional local boost to recurrent and metastatic sites. In all cases we've made a dose gradient in the border zone to avoid irradiation of vertebral bodies. Eight patients had High Dose Chemotherapy (HDCT) before CSRI. The minimal interval between HDCT and CSRI was 2 months. Median dose at primary CSI was 23.7 Gy (23.4-36). Seven patients had reirradiation previously, two of them had CSRI with total dose of 18 Gy. Median time between two CSI courses was 33 months (19-126). Median follow-up period was 9 months (2-18). Six patients had disease progression, five of them died because of progression during the next 1.5 years after CSRI. Average time to progression was 13.3 ± 1.6 months (95% CI 10.1-16.4). During treatment we observed strong evidence of progressing thrombocytopenia (avg = 95 * 109) with minimal values occurring during third week (p < 0.001). There was a non-significant decrease of hemoglobin and neutrophiles level (p hemoglobin =0.4, p neutrophiles =0.07). One patient had severe bone marrow hypoplasia during the treatment which required blood and platelet transfusion and neutrophil stimulation. The rest of the patients' hematological toxicity resolved without medical intervention. Only one patient had interruption during treatment because of COVID-19 infection. All the patients except one received chemotherapy after CSRI. None of them had any evidence of radiation necrosis or other radiological changes during the whole follow-up period. CSRI is mostly used for medulloblastoma patients with refractory disease and leptomeningeal progression. Proton therapy may help to deliver curative doses with limited hematological toxicity and to minimize or completely avoid gastrointestinal toxicity. Probably it may lead to long-term disease control for such group of patients. [ FROM AUTHOR] Copyright of International Journal of Radiation Oncology, Biology, Physics is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

The impact of the COVID-19 pandemic on 30-day survival in pediatric cancer patients in low, middle, and high-income countries: an international, observational cohort study

Objectives: To conduct the first international cohort study to ascertain the short-term outcome for pediatric oncology patients who underwent treatment across 16 high-income countries (HICs) and 23 low-and-middle-income countries (LMICs) during the COVID-19 pandemic. The hypotheses being tested was that the COVID-19 pandemic had affected paediatric cancer care, and that the outcomes of children were worse in LMICs. Design: A multicenter, international, collaborative cohort study. Setting: 91 hospitals and cancer centers in 39 countries providing cancer treatment to pediatric patients between March and December 2020. Participants: Patients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukemia, Non-Hodgkin lymphoma, Hodgkin lymphoma, Wilms Tumor, Sarcoma, Retinoblastoma, Gliomas, Medulloblastomas or Neuroblastomas, in keeping with the World Health Organization Global Initiative for Childhood Cancer. Main outcome measure: All-cause mortality at 30 days and 90 days Results: 1660 patients were recruited. Over 30 days, 45 LMIC patients (4.3%;95% CI: 3.1 to 5.5) and 2 HIC patients (0.4%;95% CI: -0.1 to 0.9) died. 219 children had their treatments delayed, interrupted, or modified. LMIC patients had 11.7 (95% CI: 10.3 to 13.1) and 7.4 (95% CI: 6.5 to 8.3) times the risk of death at 30 days and 90 days respectively (p < 0.001). After adjusting for confounders, pediatric cancer patients in LMICs had 35.7 times the odds of death at 30 days (p < 0.001). Conclusions: The COVID-19 pandemic has affected pediatric oncology service provision. It has disproportionately affected patients in LMICs, highlighting and compounding existing disparities in healthcare systems globally that need addressing urgently. However, most pediatric cancer patients continued to receive their normal standard of care. This speaks to the adaptability and resilience of health-care systems and healthcare workers globally.

IMPACT OF THE COVID-19 PANDEMIC ON 30-DAY MORTALITY AND UNPLANNED REOPERATION RATES FOR PEDIATRIC CENTRAL NERVOUS SYSTEM TUMORS

INTRODUCTION: Unplanned reoperations and mortality within 30 days are important indicators when evaluating the quality of care provided by surgical systems. We reviewed these outcomes among children with primary central nervous system (CNS) tumors treated during the COVID- 19 pandemic. METHODS: This is a retrospective study of all pediatric patients who underwent neurosurgery for primary CNS tumors at the Philippine General Hospital, the national university hospital, from January 1, 2020 until December 31, 2021. Their clinical presentation, perioperative course, and outcomes were analyzed. During this time, our hospital concurrently served as a COVID-19 referral center, thus, the workforce was restructured, and resources were reallocated to care for COVID-19 patients. RESULTS: A total of 92 pediatric patients with CNS tumors underwent 140 neurosurgical operations during the study period. Two-thirds of the patients were males, and mean age was 9.3 ± 5.0 years (range: 3 months to 18 years). Average preoperative length of stay was 3.9 ± 2.6 days. Tumor resection was performed in 73 patients (79%). Most common histologic diagnoses were medulloblastoma (20%) and low-grade glioma including pilocytic astrocytoma (20%). Overall, the 30-day mortality and unplanned reoperation rates were 12% and 22%, respectively. Eight patients died from brain herniation and/or tumor progression. Reasons for unplanned reoperations were postoperative hydrocephalus (20%), infection (9%), hematoma (7%), and tumor residual (3%). DISCUSSION: Worldwide, the COVID-19 pandemic has altered hospital protocols and shifted resources considerably. The observed high rates of death and reoperation are likely due to delays in seeking care leading to worse neurologic status at presentation, delays in performing essential surgery within the hospital, and shortage of health workers providing specialist care. It is important to periodically assess perioperative outcomes to improve the quality of surgical care given to children with CNS tumors, who remain a vulnerable population during the COVID-19 pandemic.

CHALLENGES IN THE NEUROSURGICAL CARE OF PEDIATRIC PATIENTS WITH CENTRAL NERVOUS SYSTEM TUMORS DURING THE COVID-19 PANDEMIC

INTRODUCTION: Central nervous system (CNS) tumors account for 20 - 30% of all childhood cancers. The Philippines is a lower-middle income country, wherein brain centers are located mostly in urban areas. We aimed to identify challenges that pediatric patients with CNS tumors encountered during the COVID-19 pandemic, which aggravated delays in their diagnosis and treatment. METHODS: This is a retrospective review of all pediatric patients who underwent neurosurgery for CNS tumors at the Jose R. Reyes Memorial Medical Center, a tertiary referral center, from January 2020 until December 2021. We summarized patients' demographic data, clinical course, and perioperative outcomes. RESULTS: A total of 38 pediatric patients underwent neuro-oncologic surgery in our center during the study period. There were 18 males and 20 females, with a mean age of 7.5 ± 4.9 years. Tumor was biopsied and/or resected in 35 cases (92%). The most common histologic diagnoses were medulloblastoma (n=8, 21%) and high-grade glioma/glioblastoma (n=5, 13%). Median preoperative length of stay and total length of stay were 10 (IQR: 17) and 28 (IQR 33.75), respectively. There was a high perioperative mortality rate in 2020 (71%), but this decreased to 20% in 2021. Six patients (16%) developed COVID-19 infection during the perioperative period. There were nine patients (24%) who had documented tumor progression because of delays in adjuvant therapy. DISCUSSION: Aside from geographic barriers and catastrophic health expenditure, the major challenges that disrupted the care of pediatric patients with CNS tumors in our center during the COVID-19 pandemic were delays in neuroimaging for diagnosis, unavailability of operating room slots, deficiency in critical care beds, and workforce shortage due to COVID-19 infection among health workers. Health care systems must adapt to the changes brought about by the pandemic, so that children with CNS tumors are not neglected.

A CASE SERIES OF PEDIATRIC PATIENTS WITH BRAIN TUMORS AND PERIOPERATIVE COVID-19 INFECTION

INTRODUCTION: Surgery in patients diagnosed with COVID-19 is associated with increased risk of morbidity and mortality, especially within 6 weeks of SARSCoV- 2 infection. Furthermore, most studies have focused on adults, and little is known about perioperative outcomes in children with COVID-19. METHODS: We reviewed the operative census of the Division of Neurosurgery of Philippine General Hospital from March 2020 until December 2021. We identified all pediatric patients with brain tumors and confirmed COVID-19 infection within two weeks of their neuro-oncologic surgery. Their clinical course and outcomes are described herein. RESULTS: Four patients were included in this case series: three had tumors in the cerebellum, one in the pineal region. All of them were boys, with ages ranging from 4 months to 13 years. All tumors were malignant, and two were confirmed to be medulloblastoma after tumor resection. COVID-19 infection was diagnosed by the presence of SARS-CoV-2 RNA through a nasopharyngeal swab. Three patients acquired the virus post-operatively, likely from nosocomial transmission. In the remaining patient, it was community-acquired. All the patients had chest radiographs consistent with pneumonia but none had marked elevation of serum inflammatory markers. No patient received remdesivir or tocilizumab. At the time of their presentation, either the COVID-19 vaccine was not yet available in the country, or the patient was not yet eligible for vaccination. One patient died because of brain herniation from tumor progression, two were discharged and eventually underwent adjuvant therapy, and one remained in-hospital as of this writing. DISCUSSION: COVID-19 infection resulted in delays in the management of patients with pediatric CNS tumors. Given the high risk of these patients for potential complications, consensus guidelines must be established to achieve good outcomes and prolong survival.

Functional Genomics of PRUNE1 in Neurodevelopmental Disorders (NDDs) Tied to Medulloblastoma (MB) and Other Tumors.

We analyze the fundamental functions of Prune_1 in brain pathophysiology. We discuss the importance and maintenance of the function of Prune_1 and how its perturbation influences both brain pathological conditions, neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (NMIHBA; OMIM: 617481), and tumorigenesis of medulloblastoma (MB) with functional correlations to other tumors. A therapeutic view underlying recent discoveries identified small molecules and cell penetrating peptides to impair the interaction of Prune_1 with protein partners (e.g., Nm23-H1), thus further impairing intracellular and extracellular signaling (i.e., canonical Wnt and TGF-ß pathways). Identifying the mechanism of action of Prune_1 as responsible for neurodevelopmental disorders (NDDs), we have recognized other genes which are found overexpressed in brain tumors (e.g., MB) with functional implications in neurodevelopmental processes, as mainly linked to changes in mitotic cell cycle processes. Thus, with Prune_1 being a significant target in NDDs, we discuss how its network of action can be dysregulated during brain development, thus generating cancer and metastatic dissemination.