Central Nervous System Tumors In Children Research Articles

Unlocking delays: revealing barriers to early diagnosis of childhood central nervous system tumors in an upper-middle-income country.

Childhood central nervous system (CNS) tumors tend to have a longer time interval until diagnosis than other pediatric malignancies. The aim is to describe the time to diagnosis among Brazilian pediatric patients treated at a tertiary center and explore associated factors. Cross-sectional study; application of questionnaires to parents of children with CNS tumors during outpatient visit or inpatient care. One hundred parents participated between August and November 2023. The median age of the children at diagnosis was 7.2years old. Low-grade glioma (LGG) was the most common tumor type (37%), followed by medulloblastoma (24%). The most frequent symptoms were morning and/or persistent vomiting and headache. The mean prediagnostic symptomatic interval (PSI) was 150days. The mean parental interval was shorter than the medical (58.1days vs 92.8days). LGGs and tumors located in the central area had longer intervals to diagnosis than other tumors (296 vs 54days) (p = 0.005) and (206 vs 155days) (p = 0.007), respectively. Despite 81% of the patients undergoing pediatric routine follow-up, 87% of them had been diagnosed at an emergency department. Children attended by the same physician had a shorter mean interval (18.2 vs 88.3days) than those assisted by different professionals (p = 0.015). The mean time for referral to our specialized center was 23days. This study is a crucial step in recognizing barriers to early diagnosis of CNS tumors in a middle-income country as low awareness of signs/symptoms by parents and health professionals, aiming to provide opportunities for intervention strategies to reduce the time to diagnosis.

CAR T cell therapy for pediatric central nervous system tumors: a review of the literature and current North American trials.

Central nervous system (CNS) tumors are the leading cause of cancer-related death in children. Typical therapy for CNS tumors in children involves a combination of surgery, radiation, and chemotherapy. While upfront therapy is effective for many high-grade tumors, therapy at the time of relapse remains limited. Furthermore, for diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma (DMG), there are currently no curative therapies. Chimeric antigen receptor T (CAR T) cell therapy is a promising novel treatment avenue for these tumors. Here, we review the preclinical evidence for CAR T cell use in pediatric brain tumors, the preliminary clinical experience of CNS CAR T cell trials, toxicity associated with systemic and locoregional CAR T cell therapy for CNS tumors, challenges in disease response evaluation with CAR T cell therapy, and the knowledge gained from correlative biologic studies from these trials in the pediatric and young adult population.

Racial/ethnic disparities in all-cause and cause-specific death among children with malignant central nervous system tumours: a registry-based cohort retrospective analysis

It is generally recognized that there is unequal mortality in childhood central nervous system (CNS) malignancy in the United States (US), but little is known about the trends and contributors of racial/ethnic disparities in death. We assessed the trends of racial/ethnic disparities in all-cause and cause-specific death, and the contributions of tumour, treatment and socioeconomic factors to this disparity. This registry-based cohort study included children (aged ≤19 years) diagnosed with malignant CNS tumours, using data from the US population-based cancer registry in the Surveillance, Epidemiology, and End Results (SEER) Program. The clinical outcomes were all-cause and cause-specific death for each racial/ethnic group (White, Black, Hispanic, non-Hispanic Asian/Pacific Islander [API], and non-Hispanic American Indian/Alaska Native [AI/AN] children). We quantified absolute disparities using absolute rate difference in 5-year cumulative incidence of death. Cox proportion risk models were used to estimate the relative racial/ethnic disparities, and the contribution of factors to disparities in death. In this study, data from 14,510 children with malignant CNS tumours (mean [SD] age, 8.5 [5.7]; 7988 [55.1%] male) were analysed. Overall, the cumulative incidence of death from CNS tumours across four racial/ethnic groups decreased from 2001 to 2020. Black patients had the highest risk of death from all causes and CNS tumours between 2001 and 2020, with adjusted hazard ratios (HR) of 1.52 (1.38-1.68) and 1.47 (1.31-1.64), respectively. The absolute disparity in all-cause death between Hispanic and White patients increased slightly (from 8.2 percentage points [ppt] to 9.4ppt), and the relative disparity in death from CNS tumours increased from 1.33 (1.15-1.55) in 2001-2005 to 1.78 (1.44-2.20) in 2016-2020. The absolute disparities in death from CNS tumours between Black and White patients (from 11.8ppt to 4.3ppt) and between API and White patients (from 10.1ppt to 5.1ppt) decreased from 2001-2005 to 2011-2015. Race/ethnicity disparities in death from CNS tumours among childhood malignant CNS tumours had reduced from 2001 to 2020, and quantifying the contribution of factors to this disparity in death could provide a basis for decreasing mortality among racial/ethnic minority patients. Shenyang Young and Middle-aged Science and Technology Innovation Talent Support Program.

Hjernetegn.dk-The Danish Central Nervous System Tumor Awareness Initiative Digital Decision Support Tool: Design and Implementation Report.

Childhood tumors in the central nervous system (CNS) have longer diagnostic delays than other pediatric tumors. Vague presenting symptoms pose a challenge in the diagnostic process; it has been indicated that patients and parents may be hesitant to seek help, and health care professionals (HCPs) may lack awareness and knowledge about clinical presentation. To raise awareness among HCPs, the Danish CNS tumor awareness initiative hjernetegn.dk was launched. This study aims to present the learnings from designing and implementing a decision support tool for HCPs to reduce diagnostic delay in childhood CNS tumors. The aims also include decisions regarding strategies for dissemination and use of social media, and an evaluation of the digital impact 6 months after launch. The phases of developing and implementing the tool include participatory co-creation workshops, designing the website and digital platforms, and implementing a press and media strategy. The digital impact of hjernetegn.dk was evaluated through website analytics and social media engagement. hjernetegn.dk was launched in August 2023. The results after 6 months exceeded key performance indicators. The analysis showed a high number of website visitors and engagement, with a plateau reached 3 months after the initial launch. The LinkedIn campaign and Google Search strategy also generated a high number of impressions and clicks. The findings suggest that the initiative has been successfully integrated, raising awareness and providing a valuable tool for HCPs in diagnosing childhood CNS tumors. The study highlights the importance of interdisciplinary collaboration, co-creation, and ongoing community management, as well as broad dissemination strategies when introducing a digital support tool.

Motor and sensory impairment in survivors of childhood central nervous system (CNS) tumors in the St. Jude Lifetime Cohort (SJLIFE).

Survivors of childhood central nervous system (CNS) tumors can develop motor and sensory impairment from their cancer and treatment history. We estimated the prevalence of motor and sensory impairment in survivors compared with controls through clinical assessment and identified associated treatment exposures and functional, quality of life (QOL), and social outcomes. Survivors of childhood CNS tumors from the St. Jude Lifetime Cohort (n = 378, median [range] age 24.0 [18.0-53.0] years, 43.4% female) ≥5 years from diagnosis and controls (n = 445, median [range] age 34.0 [18.0-70.0] years, 55.7% female) completed in-person evaluation for motor and sensory impairment using the modified Total Neuropathy Score. Impairment was graded by modified Common Terminology Criteria for Adverse Events. Multivariable models estimated associations between grade ≥2 motor/sensory impairment, individual/treatment characteristics, and secondary outcomes (function by Physical Performance Test, fitness by physiologic cost index, QOL by Medical Outcomes Survey Short Form-36 physical/mental summary scores, social attainment). Grade ≥2 motor or sensory impairment was more prevalent in survivors (24.1%, 95% Confidence Interval [CI] 19.8%-29.4%) than controls (2.9%, CI 1.4-4.5%). Among survivors, in multivariable models, motor impairment was associated with vinca exposure <15 mg/m2 versus none (OR 4.38, CI 1.06-18.08) and etoposide exposure >2036 mg/m2 versus none (OR 12.61, CI 2.19-72.72). Sensory impairment was associated with older age at diagnosis (OR 1.09, CI 1.01-1.16) and craniospinal irradiation versus none (OR 4.39, CI 1.68-11.50). There were lower odds of motor/sensory impairment in survivors treated in the year 2000 or later versus before 1990 (Motor: OR 0.29, CI 0.10-0.84, Sensory: OR 0.35, CI 0.13-0.96). Motor impairment was associated with impaired physical QOL (OR 2.64, CI 1.22-5.72). In survivors of childhood CNS tumors, motor and sensory impairment is prevalent by clinical assessment, especially after exposure to etoposide, vinca, or craniospinal radiation. Treating motor impairment may improve survivors' QOL.

QOL-10. PHYSICAL ACTIVITY LEVELS AND PATTERNS IN SURVIVORS OF CHILDHOOD CENTRAL NERVOUS SYSTEM TUMOURS

Abstract BACKGROUND Engaging in regular physical activity (PA) has multiple positive health benefits and for survivors of childhood cancer can additionally result in reduced severity of late-effects. There is a lack of objectively measured PA data in survivors of childhood central nervous system (CNS) tumours. The aims of this study were to objectively measure PA levels and patterns in survivors of childhood CNS tumours and to determine whether survivors were meeting the World Health Organisation (WHO) recommended PA guidelines of 60 minutes of moderate to vigorous intensity physical activity (MVPA) daily. METHODS Survivors of childhood CNS tumours aged between 6-17 years, between 3 months and 5 years post treatment, were provided with Actigraph GT3X accelerometers to assess their PA patterns over a seven day recording period. RESULTS Twenty-six participants were recruited with a mean age of 12.75 (SD 3.29) years. Participants met the WHO PA guidelines for a mean of 3.18 (SD 2.56) days during the assessment week. Participants spent a mean daily time of 591.77 (SD 146.91) minutes in sedentary behaviour and 129.45 (SD 54.14) minutes in light intensity PA. A significant association was found between PA and age (p&amp;lt;0.001, CI[-8.48, -3.05]), child participants engaged in significantly less sedentary time and significantly more MVPA daily than adolescent participants. No significant differences in PA patterns were identified between participants in early survivorship versus those in late survivorship (≥ 2 years post treatment), (p=0.095 – p=0.513). CONCLUSIONS The majority of survivors of childhood CNS tumours do not meet the WHO recommended daily PA guidelines and lead significantly sedentary lives. PA patterns differed significantly between child and adolescent participants. Further research is required on interventions to support engagement in PA particularly for adolescent survivors of CNS tumours, with a focus on how this can be implemented into clinical practice.

LGG-37. A PHASE III STUDY COMPARING TWO CARBOPLATIN CONTAINING REGIMENS FOR CHILDREN AND YOUNG ADULTS WITH PREVIOUSLY UNTREATED LOW-GRADE GLIOMA

Abstract BACKGROUND Low-grade glioma (LGG) is the most common childhood central nervous system tumor. Carboplatin/vincristine (CV) is a standard of care regimen used for incompletely resected tumors. Monthly carboplatin is an alternative regimen that has not been prospectively compared to CV previously in untreated patients. METHODS Patients ≤ 21 years with LGG and no treatment besides surgery were eligible. Patients were stratified according to NF1 status and randomized to Arm A (carboplatin/vincristine) or Arm B (carboplatin monthly). The primary endpoint was 3-year progression-free survival (PFS). Secondary endpoint analysis is underway and includes quality of life, tumor response rates, toxicity and association of molecular alterations on outcomes. Analyses included log-rank test and descriptive statistics. RESULTS There were 95 evaluable patients with a median age of 5 (range 0-18) years; 67 non-NF1 subjects (32 Arm A, 35 Arm B) and 28 NF1 subjects (14 Arm A, 14 Arm B). Three-year PFS was superior for patients without NF1 treated on Arm A (58%; 95% CI: 38%, 74%) versus Arm B (33%; 95% CI: 18%, 49%) (p=0.04). In patients with NF1, there was no statistical difference in PFS between those treated on Arm A (71%; 95% CI: 41%, 88%) and Arm B (93%; 95% CI: 59%, 99%) (p=0.08). Grade 3/4 toxicity neutropenia was more commonly seen in Arm A patients compared to Arm B for both NF and non-NF1 patients. Peripheral neuropathy was also more commonly seen in non-NF1 patients (Grade 1-4; 32%) compared to NF1 patients (7%) for patients treated on Arm A. There were 15 carboplatin reactions (Grade 1-4); 7 non-NF1 on Arm A, 3 non-NF1 on Arm B, and 5 NF1 on Arm A. CONCLUSIONS Non-NF1 patients treated with carboplatin and vincristine show statistically significant improved PFS compared to monthly carboplatin. Patients with NF1 are statistically underpowered due to low accrual.

OTHR-09. HEALTHCARE PROVIDERS’ PERSPECTIVES ON MALAYSIA-SINGAPORE VIRTUAL PEDIATRIC NEURO-ONCOLOGY TUMOR BOARD MEETING

Abstract BACKGROUND Virtual pediatric neuro-oncology tumor board meetings have been reported to be highly beneficial in improving the delivery of high-quality care for childhood central nervous system (CNS) tumors. However, such meetings are lacking in the Asia Pacific region. Hence, we initiated the first pediatric neuro-oncology online platform in the Asia Pacific region in January 2019, and we aimed to describe the participants’ perception of the virtual tumor board meetings. METHODS We retrospectively reviewed all cases from January 2019 to December 2023 and conducted a web-based survey to all participants in December 2023. Centers that presented more than five cases were invited to assess the impact of virtual meetings. RESULTS Fifty-four meetings have been conducted over five years. A total of 160 cases were presented by 20 institutions from six Asian countries, which include Malaysia, Singapore, Philippines, Vietnam, India, and Taiwan. Thirty participants responded to the survey. Majority of them attended the meetings to enhance their knowledge in pediatric neuro-oncology (96.7%), to learn evidence-based management (83.3%), and to build connections with regional colleagues and international experts (53.3%). Almost all concluded that tumor board meetings improved treatment decisions, addressed challenges of complex CNS tumor cases, and promoted continuity of care with appropriate post-surgical chemotherapy administration and surveillance investigations after completion of treatment. The main reason for case discussion was diagnostic difficulties followed by multimodal treatment advice (85.7%). More than 25% of management changes were observed in pathological diagnosis and treatment approaches. All the hospitals reported that the online case discussions improved pediatric neuro-oncology service delivery capacity and increased local team competence. CONCLUSION Virtual pediatric neuro-oncology tumor board meetings facilitated improvement in pathological diagnosis and multimodal treatment approach. The establishment of virtual CNS tumor board meetings is an effective way to seek international expert advice and promote pediatric neuro-oncology education in our region.

EPID-02. A CLINICALLY RELEVANT SURVIVAL COMPARISON OF PEDIATRIC CENTRAL NERVOUS SYSTEM TUMORS FOR 31 EUROPEAN COUNTRIES – POPULATION-BASED RESULTS FROM THE EUROCARE-6 PROJECT

Abstract BACKGROUND Survival outcomes of pediatric central nervous system (CNS) tumors have been reported to vary largely across countries and regions in Europe. This is the first time the EUROCARE-6 database was used to study survival outcomes for clinically relevant groups of pediatric CNS tumors in Europe. METHOD Survival data of 14,689 children (&amp;lt;15 years) diagnosed with a CNS tumor between 2008 and 2013 from 31 European countries was analyzed. Multivariable cox regression model was used to compare adjusted risks of dying (HR) from major groups of CNS tumors between countries using Germany as reference. RESULTS Five-year observed survival (OS) of low-grade gliomas (LGGs) for most countries was &amp;gt;90%. Three countries with comparable hazard ratios (2.6-2.7) showed to have a significantly higher risk of dying compared to Germany. Large variation in survival was seen for high-grade gliomas (HGGs); 0%-70%. When analyzing HGGs, six countries had a significantly higher risk of dying with hazard ratios ranging from 1.2 to 4.2. When excluding malignant gliomas, NOS (ICD-O-M9380/3) from the HGGs the risk of dying became comparable for two out of the six countries. For HGGs, only one country had a significant lower risk of dying. For Medulloblastomas, 5-year OS within the majority of countries ranged between 40-70% but with some countries having no patients surviving their disease. Seven countries had significantly worse survival outcomes with hazard ratios ranging from 1.7-3.2. No countries were found to have better survival outcomes. CONCLUSIONS This population-based study provides an insightful comparison of survival from CNS tumors in children between European countries corrected for potential incompleteness of non-malignant CNS tumors and misclassification of NOS tumors. Survival disparities were still seen for all tumor groups.

Emotional Repercussions of Grandparents Facing the Illness and Treatment of Cancer in Pediatric Oncology at a Reference Hospital.

Childhood cancer, especially leukemias and central nervous system tumors, deeply impacts families, requiring important decisions during treatment. Parents, overwhelmed with increasing responsibilities, can rely on the crucial support of grandparents, both in providing significant emotional support and in actively participating in caring for their grandchildren, even if it affects their own daily activities and quality of life. Therefore, we sought to analyze the emotional repercussions of grandparents facing the illness and treatment of cancer. It was based on a qualitative cross-sectional study conducted at a reference hospital of the Unified Health System (SUS) in Pernambuco, Brazil, from December 2023 to February 2024. Data collection was performed through semi-structured and audio-recorded interviews, with participants' consent, transcribed in full, and analyzed using the Bardin technique. Five grandmothers participated in the study, all of them female, aged 52 to 68 years, with a mean age of 61.2 years. The study highlights the importance of grandparents in caring for their grandchildren, emphasizing the emotional challenges present in diagnosis and treatment.

Registration, incidence patterns, and survival trends of central nervous system tumors among children in Germany 1980-2019: An analysis of 40years based on data from the German Childhood Cancer Registry.

Tumors of the central nervous system (CNS) are the second most common type of pediatric cancer in Germany. We aimed to describe registration practice, incidence, and survival patterns for childhood CNS tumors in Germany for the past 40years. Including all CNS tumor cases in children diagnosed at ages 0-14years registered at the German Childhood Cancer Registry (GCCR) in 1980-2019 (for survival analysis 1980-2016), we calculated age-specific and age-standardized incidence rates (ASIR) over time, average annual percentage changes (AAPC), and 1- and 5-year overall survival. While we observed a pronounced increase in ASIR after the establishment of the GCCR during the 1980s, ASIR for all pediatric CNS tumors combined continued to increase markedly from 28.6 per million in 1990-1999 to 43.3 in 2010-2019 (AAPC=2.7% in 1991-2010, AAPC=0.3% in 2010-2019). The 5-year overall survival from CNS tumors improved from 63% in the 1980s, 70% in the 1990s to 79% in 2010-2016. These improvements have occurred across all age groups. Children diagnosed with ependymomas and choroid plexus tumors experienced the strongest increase (from 54% to 81%). Observed increases in incidence rates for pediatric CNS tumors are likely only partially caused by actual increasing case numbers. The majority is a function of improved registration and, to a minor extent, improvements in diagnostics. Survival from pediatric CNS tumors has, by and large, improved consistently, leading to a growing population of childhood cancer survivors with diverse health biographies and risk of lifelong adverse impact on health and wellbeing.

Tumor volume features predict survival outcomes for patients diagnosed with diffuse intrinsic pontine glioma.

Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood central nervous system tumor. Diagnosis and monitoring of tumor response to therapy is based on magnetic resonance imaging (MRI). MRI-based analyses of tumor volume and appearance may aid in the prediction of patient overall survival (OS). Contrast-enhanced T1- and FLAIR/T2-weighted MR images were retrospectively collected from children with classical DIPG diagnosed by imaging (n = 43 patients). MRI features were evaluated at diagnosis (n = 43 patients) and post-radiation (n = 40 patients) to determine OS outcome predictors. Features included 3D tumor volume (Twv), contrast-enhancing tumor core volume (Tc), Tc relative to Twv (TC/Twv), and Twv relative to whole brain volume. Support vector machine (SVM) learning was used to identify feature combinations that predicted OS outcome (defined as OS shorter or longer than 12 months from diagnosis). Features associated with poor OS outcome included the presence of contrast-enhancing tumor at diagnosis, >15% Tc/Twv post-radiation therapy (RT), and >20% ∆Tc/Twv post-RT. Consistently, SVM learning identified Tc/Twv at diagnosis (prediction accuracy of 74%) and ∆Tc/Twv at <2 months post-RT (accuracy = 75%) as primary features of poor survival. This study demonstrates that tumor imaging features at diagnosis and within 4 months of RT can predict differential OS outcomes in DIPG. These findings provide a framework for incorporating tumor volume-based predictive analyses into the clinical setting, with the potential for treatment customization based on tumor risk characteristics and future applications of machine-learning-based analysis.

Profile of childhood central nervous system tumors in Iraq experience of children&amp;#39;s welfare teaching hospital in medical city, Baghdad

Profile of childhood central nervous system tumors in Iraq experience of children&amp;#39;s welfare teaching hospital in medical city, Baghdad

Childhood and Adolescent Central Nervous System Tumours in Spain: Incidence and Survival over 20 Years: A Historical Baseline for Current Assessment.

Central nervous system (CNS) neoplasms are highly frequent solid tumours in children and adolescents. While some studies have shown a rise in their incidence in Europe, others have not. Survival remains limited. We addressed two questions about these tumours in Spain: (1) Is incidence increasing? and (2) Has survival improved? This population-based study included 1635 children and 328 adolescents from 11 population-based cancer registries with International Classification of Childhood Cancer Group III tumours, incident in 1983-2007. Age-specific and age-standardised (world population) incidence rates (ASRws) were calculated. Incidence time trends were characterised using annual percent change (APC) obtained with Joinpoint. Cases from 1991 to 2005 (1171) were included in Kaplan-Meier survival analyses, and the results were evaluated with log-rank and log-rank for trend tests. Children's survival was age-standardised using: (1) the age distribution of cases and the corresponding trends assessed with Joinpoint; and (2) European weights for comparison with Europe. ASRw 1983-2007: children: 32.7 cases/106; adolescents: 23.5 cases/106. The overall incidence of all tumours increased across 1983-2007 in children and adolescents. Considering change points, the APCs were: (1) children: 1983-1993, 4.3%^ (1.1; 7.7); 1993-2007, -0.2% (-1.9; 1.6); (2) adolescents: 1983-2004: 2.9%^ (0.9; 4.9); 2004-2007: -7.7% (-40; 41.9). For malignant tumours, the trends were not significant. 5-year survival was 65% (1991-2005), with no significant trends (except for non-malignant tumours). CNS tumour incidence in Spain was found to be similar to that in Europe. Rises in incidence may be mostly attributable to changes in the registration of non-malignant tumours. The overall malignant CNS tumour trend was compatible with reports for Southern Europe. Survival was lower than in Europe, without improvement over time. We provide a baseline for assessing current paediatric oncology achievements and incidence in respect of childhood and adolescent CNS tumours.

Pediatric low-grade glioma: State-of-the-art and ongoing challenges.

The most common childhood central nervous system (CNS) tumor is pediatric low-grade glioma (pLGG), representing 30%-40% of all CNS tumors in children. Although there is high associated morbidity, tumor-related mortality is relatively rare. pLGG is now conceptualized as a chronic disease, underscoring the importance of functional outcomes and quality-of-life measures. A wealth of data has emerged about these tumors, including a better understanding of their natural history and their molecular drivers, paving the way for the use of targeted inhibitors. While these treatments have heralded tremendous promise, challenges remain about how to best optimize their use, and the long-term toxicities associated with these inhibitors remain unknown. The International Pediatric Low-Grade Glioma Coalition (iPLGGc) is a global group of physicians and scientists with expertise in pLGG focused on addressing key pLGG issues. Here, the iPLGGc provides an overview of the current state-of-the-art in pLGG, including epidemiology, histology, molecular landscape, treatment paradigms, survival outcomes, functional outcomes, imaging response, and ongoing challenges. This paper also serves as an introduction to 3 other pLGG manuscripts on (1) pLGG preclinical models, (2) consensus framework for conducting early-phase clinical trials in pLGG, and (3) pLGG resistance, rebound, and recurrence.

1 Ototoxicity and Cognitive Outcomes among Children Treated for Brain Tumors in Infancy

Objective:Treatment of childhood central nervous system (CNS) tumors can lead to sensorineural hearing loss (SNHL), with prior research indicating associations between SNHL and cognitive difficulties. Infants (0-3 years) treated for CNS tumors are at particular risk for neurocognitive deficits due to increased vulnerability of the developing brain and missed developmental opportunities secondary to prolonged treatment. This study expands upon existing research by examining the association between treatment-related SNHL and later neurocognitive outcomes among infants.Participants and Methods:Serial audiology and neurocognitive assessments were conducted as part of a prospective, multisite, longitudinal trial (SJYC07). Children with newly diagnosed CNS tumors were treated with chemotherapy, with or without focal proton or photon radiation therapy (RT). SNHL was dichotomized based on hearing in the better ear as present versus not present (Chang grade ≥1a vs. &lt;1a). Neurocognitive assessments included intellectual functioning (IQ), and parent ratings of executive functioning and behavioral functioning. Demographic and clinical variables investigated included: sex, age at diagnosis (years), treatment type (chemotherapy only vs. chemotherapy + RT), risk group (low vs. intermediate vs. high), and socioeconomic status (SES, continuous). Logistic regression models were used to identify factors associated with SNHL. Change point longitudinal models were used to examine the effect of each covariate individually and the potential impact of SNHL on trajectories of neurocognitive outcomes.Results:Of 135 patients (median age at diagnosis= 1.5 years), 67% had mild-to-severe SNHL as defined by Chang grade ≥1a at last follow-up. SNHL occurred early after treatment with a 1-year cumulative incidence 63.0% ±4.3%. SNHL was associated with age at diagnosis (p &lt;.001) but not sex, treatment exposure or study risk arm (p &gt;.10). At pretreatment baseline, IQ was associated with age at diagnosis (older age= higher IQ) and SES (higher SES= higher IQ) with a change in the trajectory of IQ after SNHL (stable prior to SNHL and declined 1.46 points/year after SNHL), which was impacted by tumor location (patients with supratentorial tumors stable prior to SNHL and declined 2.84 points/year after SNHL; whereas, patients with infratentorial tumors increased 1.93 points/year prior to SNHL and were stable after SNHL). At pre-treatment baseline, adaptive functioning was associated with age at diagnosis (older age= higher skills) with a change in adaptive functioning after SNHL that varied by age. There was a change in trajectory of attention problems (stable before SNHL and worsening 1.39 points/year after SNHL). SNHL was not associated with parent report of emerging executive functioning.Conclusions:Children with brain tumors experience SNHL and cognitive difficulties early in treatment that can worsen over time. Younger age at diagnosis is associated with greater risk for SNHL and cognitive difficulties. Analyses of the time course between the emergence of SNHL and cognitive late effects suggests even mild SNHL is associated with a clinically signficant decline in IQ and attention problems. These findings have notable implications with respect to refining monitoring guidelines, informing modifications to treatment, advocating for interventions, and helping educate parents, teachers, and providers about the significant impact of mild SNHL.

Evaluation of Neurofibromatosis Type 1 Associated Optic Pathway Gliomas

Background/Aims: Optic pathway gliomas (OPGs) are low-grade gliomas histologically represented by pilocytic astrocytoma (PA) in 90% of cases, can develop from any part of the visual pathways such as optic nerve, chiasm, optic tract, or optic radiations which frequently involve the hypothalamus. OPGs account for 3–5% of childhood central nervous system (CNS) tumors and about 2% of pediatric glial lesions. OPGs are believed to be the most prevalent intracranial tumor in patients with neurofibromatosis type 1 (NF-1) and can occur in 15–20% of NF-1 cases. The aim of this study is to evaluate the clinical features and treatment response in patients diagnosed with optic glioma and NF-1.&#x0D; Methods: All cases diagnosed with OPG and received treatment in the Pediatric Oncology Department, between January 2015 to January 2021 were retrospectively evaluated. Inclusion criteria include children and adolescents with OPG aged between 0 and 18 years. The medical records (gender, age, tumor entity, tumor location) of patients, as well as their treatment history and magnetic resonance imaging (MRI) scans, were examined. The diagnosis of OPG was made clinically and radiologically by the tumor board. The recommendations of the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group were used in the diagnosis and evaluation of treatment response. Patients received intravenous chemotherapy with SIOP LGG 2004 (vincristine- carboplatin) with or without bevacizumab (10 mg/kg, started every 2 weeks), therapy or vinblastine (3 mg/m2, weekly). &#x0D; Results: This study included 27 cases during the study period from January 2015 to January 2021. In this study there were 14 male (51.8 %) and 13 female (48.1 %) patients. The median age was 4.8 (range: 0.5–14.9) years. Biopsy was performed in three patients and the diagnosis was low-grade glioma (pilocytic astrocytoma) for all of them. Chemotherapy was administered to 22 cases in total. Twelve patients received vincristine-carboplatine, 5 patients received vincristine-carboplatin with bevacizumab and 5 patients received vinorelbine. Radiological response was evaluated in all 22 patients at 3 months MRI. No patient had a radiological complete respons, 11 patients (50%) had partial response, 2 patients (9%) presented with a progressive disease, showing an increase in measurements of 35% and 9 patients(40.9%) had stable disease at the 3-month evaluation.&#x0D; Conclusions: Systemic and visual problems play a significant role in the selection of treatment for pediatric patients with optic gliomas. An essential treatment option for improving symptoms and reducing tumor size is systemic chemotherapy. A crucial therapy option for enhancing vision is bevacizumab for the patients with NF-associated OPG.

Childhood, adolescent, and adult primary brain and central nervous system tumor statistics for practicing healthcare providers in neuro-oncology, CBTRUS 2015-2019.

The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention (CDC) and National Cancer Institute (NCI), is the largest aggregation of histopathology-specific population-based data for primary brain and other central nervous system (CNS) in the US. CBTRUS publishes an annual statistical report which provides critical reference data for the broad neuro-oncology community. Here, we summarize the key findings from the 2022 CBTRUS annual statistical report for healthcare providers. Incidence data were obtained from the CDC's National Program of Cancer Registries (NPCR) and NCI's Surveillance, Epidemiology, and End Results Program for 52 central cancer registries (CCRs). Survival data were obtained from 42 NPCR CCRs. All rates are per 100 000 and age-adjusted using the 2000 US standard population. Overall median survival was estimated using Kaplan-Meier models. Survival data for selected molecularly defined histopathologies are from the National Cancer Database. Mortality data are from the National Vital Statistics System. The average annual age-adjusted incidence rate of all primary brain and other CNS tumors was 24.25/100 000. Incidence was higher in females and non-Hispanics. The most commonly occurring malignant and predominately non-malignant tumors was glioblastoma (14% of all primary brain tumors) and meningioma (39% of all primary brain tumors), respectively. Mortality rates and overall median survival varied by age, sex, and histopathology. This summary describes the most up-to-date population-based incidence, mortality, and survival, of primary brain and other CNS tumors in the US and aims to serve as a concise resource for neuro-oncology providers.

Pesticide exposure and risk of Central Nervous System tumors in children: a systematic review with meta-analysis.

Central Nervous System (CNS) tumors represent more than half of all childhood malignant neoplasms. The aim of this study was to determine the relationship between environmental exposure to pesticides and the development of CNS tumors in children. We conducted a systematic review of the literature in the PubMed/MEDILINE, Embase, Web of Science, Scopus, and CINAHL databases. The inclusion criteria were cohort and case-control studies investigating the association between exposure to pesticides and CNS tumors (all histological types included in group III of the WHO Classification of Childhood Cancer) in children aged 0-14 years. The meta-analysis was performed using a random effects model and the Mantel-Haenszel method. Strength of association was measured using odds ratios (OR). The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under identification number CRD42021209354. The search identified 1,158 studies, 14 of which were included in the review. There was evidence of an association between the development of astrocytomas and exposure to all classes of pesticides (OR 1.50; 95%CI 1.15-1.96; p=0.03). The synthesis of the evidence pointed to a relationship between exposure to pesticides and some histological types of CNS tumors in childhood.

Treatments associated with all-cause mortality among children with primary brain and central nervous system tumors: a retrospective cohort study from the SEER database.

Evidence on treatment modalities and survival in childhood primary brain and central nervous system (CNS) tumors remains contradictory, with previous studies often lacking sufficient patient cohort sizes to assess the differences in histological subtypes. This cohort study based on a large population investigated the effects of various treatments on the mortality of patients with different histological types of primary brain and CNS tumors from the Surveillance, Epidemiology, and End Results (SEER) database. Data of demography, primary tumor site, histology, tumor grade and treatments from all pediatric patients with primary brain and CNS tumors were extracted in this retrospective cohort. The outcomes were overall, 1-, 5-, and 10-year all-cause mortality. Multivariate Cox proportional hazards models were to explore the associations of treatment with overall, 1-, 5-, and 10-year all-cause mortality, with hazard ratios (HRs) and 95% confidence intervals (CIs). Totally 10,994 children were included, with the mean age at diagnosis of 7.3 years, and the median follow-up time of 5.0 years. Of which, 2,003 (18.2%) were diffuse astrocytoma, 3,188 (29.0%) were embryonal tumors, and 3,691 (33.5%) were malignant glioma. Then 4,333 (39.41%) children died during the follow-up. For diffuse astrocytomas and malignant gliomas, patients who received all other treatments were associated with overall, 1-, 5- and 10-year all-cause mortality compared to those only received resection. Embryonal tumors patients receiving resection with radiation only and those receiving resection with both chemotherapy and radiation were associated with lower odds of overall, 1-, 5- and 10-year all-cause mortality compared to patients who only received resection. For ependymal tumors, no surgery/only biopsy with chemotherapy, resection with chemotherapy only, resection with both chemotherapy and radiation, and other treatments had increased risks of overall all-cause mortality compared with resection. The risk of 1-year all-cause mortality increased in ependymal tumors with treatment involving resection and radiation. However, resection with both chemotherapy and radiation was not significantly associated with the 1- nor 5-year all-cause mortality. Resection may be recommended for children with diffuse astrocytoma, ependymal tumors, and malignant glioma, while resection with radiotherapy or chemoradiation may be recommended for children with embryonal tumors.