Case report: Turcot syndrome type 2 in a developing country within the Caribbean.

Medulloblastoma is the most common malignant pediatric brain tumor and has been linked to known cancer predisposition syndromes. We report a case of medulloblastoma of a 12-year-old Indo-Trinidadian female with a strong family history of colorectal carcinoma. In collaboration with the SickKids-Caribbean Initiative (SCI), her tumor was confirmed to be a WHO grade 4 medulloblastoma - Wnt subtype. Genetic testing further confirmed the presence of a pathogenic APC gene variant [c.3183_3187del (p.Gln1062*)] which led to a diagnosis of Turcot syndrome type 2. The index patient received multimodal therapy which included surgery, radiation and chemotherapy and is currently post end-of-treatment and in remission. This case report aims to highlight the complexity of diseases and the need for expertise in identifying them in low-and-middle income countries, the need for access to specialized testing and the benefits of collaborating between low-and-middle income and high-income countries when managing complex oncology patients.

Optimizing an exercise training program in pediatric brain tumour survivors: Does timing postradiotherapy matter?

Background: While exercise training (ET) programs show positive outcomes in cognition, motor function, and physical fitness in pediatric brain tumor (PBT) survivors, little is known about the optimal timing of intervention. The aim of this work was to explore the feasibility and benefits of ET based on its timing after radiotherapy. Methods: This retrospective analysis (ClinicalTrials.gov, NCT01944761) analyzed data based on the timing of PBT survivors' participation in an ET program relative to their completion of radiotherapy: <2 years (n = 9), 2-5 years (n = 10), and > 5 years (n = 13). We used repeated measures analysis of variance to compare feasibility and efficacy indicators among groups, as well as correlation analysis between ET program timing postradiotherapy and preliminary treatment effects on cognition, motor function and physical fitness outcomes. Results: Two to five years postradiotherapy was the optimal time period in terms of adherence (88.5%), retention (100%), and satisfaction (more fun, more enjoyable and recommend it more to other children). However, the benefits of ET program on memory recognition (r = -0.379, P = .047) and accuracy (r = -0.430, P = .032) decreased with increased time postradiotherapy. Motor function improved in all groups, with greater improvements in bilateral coordination (P = .043) earlier postradiotherapy, and in running (P = .043) later postradiotherapy. The greatest improvement in pro-rated work rate occurred in the < 2-year group (P = .008). Conclusion: Participation in an ET program should be offered as part of routine postradiotherapy care in the first 1-2 years and strongly encouraged in the first 5 years.

Proton Therapy Mediates Dose Reductions to Brain Structures Associated With Cognition in Children With Medulloblastoma.

PURPOSE: Emerging evidence suggests proton radiation therapy may offer cognitive sparing advantages over photon radiation therapy, yet dosimetry has not been compared previously. The purpose of this study was to examine dosimetric correlates of cognitive outcomes in children with medulloblastoma treated with proton versus photon radiation therapy. METHODS AND MATERIALS: In this retrospective, bi-institutional study, dosimetric and cognitive data from 75 patients (39 photon and 36 proton) were analyzed. Doses to brain structures were compared between treatment modalities. Linear mixed-effects models were used to create models of global IQ and cognitive domain scores. RESULTS: The mean dose and dose to 40% of the brain (D40) were 2.7 and 4.1 Gy less among proton-treated patients compared with photon-treated patients (P = .03 and .007, respectively). Mean doses to the left and right hippocampi were 11.2 Gy lower among proton-treated patients (P < .001 for both). Mean doses to the left and right temporal lobes were 6.9 and 7.1 Gy lower with proton treatment, respectively (P < .001 for both). Models of cognition found statistically significant associations between higher mean brain dose and reduced verbal comprehension, increased right temporal lobe D40 with reduced perceptual reasoning, and greater left temporal mean dose with reduced working memory. Higher brain D40 was associated with reduced processing speed and global IQ scores. CONCLUSIONS: Proton therapy reduces doses to normal brain structures compared with photon treatment. This leads to reduced cognitive decline after radiation therapy across multiple intellectual endpoints. Proton therapy should be offered to children receiving radiation for medulloblastoma.

Combined Immunotherapy Improves Outcome for Replication-Repair-Deficient (RRD) High-Grade Glioma Failing Anti-PD-1 Monotherapy: A Report from the International RRD Consortium.

Immune checkpoint inhibition (ICI) is effective for replication-repair-deficient, high-grade gliomas (RRD-HGG). The clinical/biological impact of immune-directed approaches after failing ICI monotherapy is unknown. We performed an international study on 75 patients treated with anti-PD-1; 20 are progression free (median follow-up, 3.7 years). After second progression/recurrence (n = 55), continuing ICI-based salvage prolonged survival to 11.6 months (n = 38; P < 0.001), particularly for those with extreme mutation burden (P = 0.03). Delayed, sustained responses were observed, associated with changes in mutational spectra and the immune microenvironment. Response to reirradiation was explained by an absence of deleterious postradiation indel signatures (ID8). CTLA4 expression increased over time, and subsequent CTLA4 inhibition resulted in response/stable disease in 75%. RAS-MAPK-pathway inhibition led to the reinvigoration of peripheral immune and radiologic responses. Local (flare) and systemic immune adverse events were frequent (biallelic mismatch-repair deficiency > Lynch syndrome). We provide a mechanistic rationale for the sustained benefit in RRD-HGG from immune-directed/synergistic salvage therapies. Future approaches need to be tailored to patient and tumor biology. SIGNIFICANCE: Hypermutant RRD-HGG are susceptible to checkpoint inhibitors beyond initial progression, leading to improved survival when reirradiation and synergistic immune/targeted agents are added. This is driven by their unique biological and immune properties, which evolve over time. Future research should focus on combinatorial regimens that increase patient survival while limiting immune toxicity. This article is featured in Selected Articles from This Issue, p. 201.

Postoperative cerebellar mutism syndrome is an acquired Autism-like network disturbance.

BACKGROUND: Cerebellar mutism syndrome (CMS) is a common and debilitating complication of posterior fossa tumour surgery in children. Affected children exhibit communication and social impairments that overlap phenomenologically with subsets of deficits exhibited by children with Autism spectrum disorder (ASD). Although both CMS and ASD are thought to involve disrupted cerebro-cerebellar circuitry, they are considered independent conditions due to an incomplete understanding of their shared neural substrates. METHODS: In this study, we analyzed post-operative cerebellar lesions from 90 children undergoing posterior fossa resection of medulloblastoma, 30 of whom developed CMS. Lesion locations were mapped to a standard atlas, and the networks functionally connected to each lesion were computed in normative adult and paediatric datasets. Generalizability to ASD was assessed using an independent cohort of children with ASD and matched controls (n=427). RESULTS: Lesions in children who developed CMS involved the vermis and inferomedial cerebellar lobules. They engaged large-scale cerebellothalamocortical circuits with a preponderance for the prefrontal and parietal cortices in the paediatric and adult connectomes, respectively. Moreover, with increasing connectomic age, CMS-associated lesions demonstrated stronger connectivity to the midbrain/red nuclei, thalami and inferior parietal lobules and weaker connectivity to prefrontal cortex. Importantly, the CMS-associated lesion network was independently reproduced in ASD and correlated with communication and social deficits, but not repetitive behaviours. CONCLUSIONS: Our findings indicate that CMS-associated lesions result in an ASD-like network disturbance that occurs during sensitive windows of brain development. A common network disturbance between CMS and ASD may inform improved treatment strategies for affected children.

A qualitative exploration of parental caregivers' experience caring for children who have survived medulloblastoma.

BACKGROUND: Approximately 70% of children diagnosed with a medulloblastoma will become long-term survivors. Medulloblastoma therapy frequently causes long-term morbidities in survivors, which places a considerable burden on parental caregivers. We aimed to explore the experience of parental caregivers caring for medulloblastoma survivors. METHODS: We conducted a qualitative study using grounded theory thematic analysis. We used semi-structured parental caregiver interviews to explore family experiences, social circumstances, and family-reported impact within families of children who had survived medulloblastoma. Parental caregivers were recruited from specialized survivor clinics at two large quaternary centers in Toronto, Canada. RESULTS: Sixteen of 22 eligible families participated, and 20 parental caregiver interviews were completed. Survivors were a median age of 6 years (range: 1-9 years) at diagnosis, and were 9.5 years (range: 5-12 years) from treatment at the time of the interview. Three major themes and associated subthemes emerged: (i) parental caregivers described significant long-term challenges associated with their child's survivorship. Subthemes included medical treatment sequelae, school issues and behavioral concerns, and surveillance and access to care. (ii) Parental caregivers recognized the impact that their child's quality of life (QOL) had on both their personal and family QOL. Subthemes included parental QOL, parental mental health and coping, spousal relationships, and effects on the family unit as a whole. (iii) Parental caregivers reported experiencing conflicting emotions related to their child's survivorship status and long-term effects. Subthemes included feeling happiness with concurrent worry, fear, and stress, as well as concerns about the future. CONCLUSIONS: Parental caregivers of medulloblastoma survivors experience long-term challenges, with personal and family impacts. Further work is needed to improve care models and support systems for families with a child who has survived medulloblastoma.

Supraorbital minicraniotomy for open Ommaya reservoir placement in pediatric craniopharyngiomas: a case series and technical report.

OBJECTIVE: Craniopharyngiomas with a predominant cystic component are often seen in children and can be treated with an Ommaya reservoir for aspiration and/or intracystic therapy. In some cases, cannulation of the cyst can be challenging via a stereotactic or transventricular endoscopic approach due to its size and proximity to critical structures. In such cases, a novel placement technique for Ommaya reservoirs via a lateral supraorbital incision and supraorbital minicraniotomy has been used. METHODS: The authors conducted a retrospective chart review of all children undergoing supraorbital Ommaya reservoir insertion from January 1, 2000, to December 31, 2022, at the Hospital for Sick Children, Toronto. The technique involves a lateral supraorbital incision and a 3 × 4-cm supraorbital craniotomy, with identification and fenestration of the cyst under the microscope and insertion of the catheter. The authors assessed baseline characteristics and clinical parameters of surgical treatment and outcome. Descriptive statistics were conducted. A review of the literature was performed to identify other studies describing a similar placement technique. RESULTS: A total of 5 patients with cystic craniopharyngioma were included (3 male, 60%) with a mean age of 10.20 ± 5.72 years. The mean preoperative cyst size was 11.6 ± 3.7 cm3, and none of the patients suffered from hydrocephalus. All patients suffered from temporary postoperative diabetes insipidus, but no new permanent endocrine deficits were caused by the surgery. Cosmetic results were satisfactory. CONCLUSIONS: This is the first report of lateral supraorbital minicraniotomy for Ommaya reservoir placement. This is an effective and safe approach in patients with cystic craniopharyngiomas, which cause local mass effect but are not amenable to traditional Ommaya reservoir placement stereotactically or endoscopically.

An update on multimodal management of craniopharyngioma in children.

Craniopharyngioma (CP) represent 1.2-4.6% of all intracranial tumors in children and carry a significant morbidity due to their lesional intimacy with structures involved in neurological, visual, and endocrinological functions. Variable treatment modalities being available, including surgery, radiation therapy, alternative surgeries, and intracystic therapies or combinations of them, their common goal is to reduce immediate and long-term morbidity while preserving these functions. Multiple attempts have been made to re-evaluate surgical and irradiation strategies in order to optimize their complication and morbidity profile. However, despite significant advances in "function sparing" approaches, such as limited surgery and improved technologies of radiation therapies, achieving interdisciplinary consensus on the optimal treatment algorithm remains a challenge. Furthermore, there remains a significant span of improvement given the number of specialties involved as well as the complex and chronic nature of CP disease. This perspective article aims to summarize recent changes and knowledge gains in the field of pediatric CP, outlining updated treatment recommendations, a concept of integrative interdisciplinary care and the implication of novel potential diagnostic tools. A comprehensive update on the multimodal treatment of pediatric CP is presented, focusing on "function-preserving" therapies and their implications.

Time to dismiss boost? Outcomes of children with localized and metastatic germinoma.

PURPOSE: To determine long-term outcomes of a cohort of children with germinoma treated with chemotherapy and radiation therapy without primary tumor boost even in the absence of complete response to chemotherapy METHODS: This retrospective study analyzed the outcome of patients with germinoma consecutively diagnosed and treated at a tertiary care center from January 2000 to December 2021. MRIs were reviewed by two radiologists, blinded to patient data. Tumor location at diagnosis, tumor response to chemotherapy and at completion of radiation therapy and site of relapse were assessed. Tumor response was assessed radiologically by determining the tumor size and response on diffusion-weighted imaging, in addition to biochemical, cytological parameters and neurological status. RESULTS: Of 46 pediatric germinoma patients, 29 children (14 male; median age 12.8 years) received no primary tumor boost. Median follow-up was 63 months (range 9-187 months). Twenty-five children had localized disease and tumor location was suprasellar (n = 11), pineal (n = 10), bifocal (n = 3) and basal ganglia (n = 1) while 4 children had metastatic disease at presentation. All patients completed multi-agent chemotherapy followed by either ventricular irradiation (VI) (23.4 Gy) (n = 23), whole brain (WBI) (23.4 Gy) (n = 5) or craniospinal radiation (CSI) (23.4 Gy) (n = 1). Two children, who had localized disease at presentation and received VI after chemotherapy, relapsed 9 months and 32 months after completion of treatment respectively. No patient had a local relapse. Location of relapse was distant, outside (n = 1) and out- and inside (n = 1) the irradiation field. Five-year progression free survival (PFS) was 91% and overall survival (OS) was 100%. CONCLUSIONS: In this case series, excellent 5-year PFS and OS rates were achieved with chemotherapy followed by radiation therapy of 23.4 Gy delivered without primary tumor boost. No local relapse was observed despite omitting primary tumor boost in patients with localized and metastatic germinoma.

Nivolumab with or without ipilimumab in pediatric patients with high-grade CNS malignancies: Safety, efficacy, biomarker, and pharmacokinetics-CheckMate 908.

BACKGROUND: Therapeutic options are limited in pediatric CNS malignancies. CheckMate 908 (NCT03130959) is an open-label, sequential-arm, phase 1b/2 study investigating nivolumab (NIVO) and NIVO + ipilimumab (IPI) in pediatric patients with high-grade CNS malignancies. METHODS: Patients (N = 166) in 5 cohorts received NIVO 3 mg/kg every 2 weeks (Q2W) or NIVO 3 mg/kg + IPI 1 mg/kg every 3 weeks (4 doses) followed by NIVO 3 mg/kg Q2W. Primary endpoints included overall survival (OS; newly diagnosed diffuse intrinsic pontine glioma [DIPG]) and progression-free survival (PFS; other recurrent/progressive or relapsed/resistant CNS cohorts). Secondary endpoints included other efficacy metrics and safety. Exploratory endpoints included pharmacokinetics and biomarker analyses. RESULTS: As of January 13, 2021, median OS (80% CI) was 11.7 (10.3-16.5) and 10.8 (9.1-15.8) months with NIVO and NIVO + IPI, respectively, in newly diagnosed DIPG. Median PFS (80% CI) with NIVO and NIVO + IPI was 1.7 (1.4-2.7) and 1.3 (1.2-1.5) months, respectively, in recurrent/progressive high-grade glioma; 1.4 (1.2-1.4) and 2.8 (1.5-4.5) months in relapsed/resistant medulloblastoma; and 1.4 (1.4-2.6) and 4.6 (1.4-5.4) months in relapsed/resistant ependymoma. In patients with other recurrent/progressive CNS tumors, median PFS (95% CI) was 1.2 (1.1-1.3) and 1.6 (1.3-3.5) months, respectively. Grade 3/4 treatment-related adverse-event rates were 14.1% (NIVO) and 27.2% (NIVO + IPI). NIVO and IPI first-dose trough concentrations were lower in youngest and lowest-weight patients. Baseline tumor programmed death ligand 1 expression was not associated with survival. CONCLUSIONS: NIVO ± IPI did not demonstrate clinical benefit relative to historical data. The overall safety profiles were manageable with no new safety signals.

Radiomic Features Based on MRI Predict Progression-Free Survival in Pediatric Diffuse Midline Glioma/Diffuse Intrinsic Pontine Glioma.

Purpose: Biopsy-based assessment of H3 K27 M status helps in predicting survival, but biopsy is usually limited to unusual presentations and clinical trials. We aimed to evaluate whether radiomics can serve as prognostic marker to stratify diffuse intrinsic pontine glioma (DIPG) subsets. Methods: In this retrospective study, diagnostic brain MRIs of children with DIPG were analyzed. Radiomic features were extracted from tumor segmentations and data were split into training/testing sets (80:20). A conditional survival forest model was applied to predict progression-free survival (PFS) using training data. The trained model was validated on the test data, and concordances were calculated for PFS. Experiments were repeated 100 times using randomized versions of the respective percentage of the training/test data. Results: A total of 89 patients were identified (48 females, 53.9%). Median age at time of diagnosis was 6.64 years (range: 1-16.9 years) and median PFS was 8 months (range: 1-84 months). Molecular data were available for 26 patients (29.2%) (1 wild type, 3 K27M-H3.1, 22 K27M-H3.3). Radiomic features of FLAIR and nonenhanced T1-weighted sequences were predictive of PFS. The best FLAIR radiomics model yielded a concordance of .87 [95% CI: .86-.88] at 4 months PFS. The best T1-weighted radiomics model yielded a concordance of .82 [95% CI: .8-.84] at 4 months PFS. The best combined FLAIR + T1-weighted radiomics model yielded a concordance of .74 [95% CI: .71-.77] at 3 months PFS. The predominant predictive radiomic feature matrix was gray-level size-zone. Conclusion: MRI-based radiomics may predict progression-free survival in pediatric diffuse midline glioma/diffuse intrinsic pontine glioma.

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.

Response assessment in pediatric craniopharyngioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) Working Group.

BACKGROUND: Craniopharyngioma is a histologically benign tumor of the suprasellar region for which survival is excellent but quality of life is often poor secondary to functional deficits from tumor and treatment. Standard therapy consists of maximal safe resection with or without radiation therapy. Few prospective trials have been performed, and response assessment has not been standardized. METHODS: The Response Assessment in Pediatric Neuro-Oncology (RAPNO) committee devised consensus guidelines to assess craniopharyngioma response prospectively. RESULTS: Magnetic resonance imaging is the recommended radiologic modality for baseline and follow-up assessments. Radiologic response is defined by 2-dimensional measurements of both solid and cystic tumor components. In certain clinical contexts, response to solid and cystic disease may be differentially considered based on their unique natural histories and responses to treatment. Importantly, the committee incorporated functional endpoints related to neuro-endocrine and visual assessments into craniopharyngioma response definitions. In most circumstances, the cystic disease should be considered progressive only if growth is associated with acute, new-onset or progressive functional impairment. CONCLUSIONS: Craniopharyngioma is a common pediatric central nervous system tumor for which standardized response parameters have not been defined. A RAPNO committee devised guidelines for craniopharyngioma assessment to uniformly define response in future prospective trials.

Adolescent and young adult glioma: systematic review of demographic, disease, and treatment influences on survival.

Background: Prognostic factors in adolescent and young adult (AYA) glioma are not well understood. Though clinical and molecular differences between pediatric and adult glioma have been characterized, their application to AYA populations is less clear. There is a major need to develop more robust evidence-based practices for managing AYA glioma patients. Methods: A systematic review using PRISMA methodology was conducted using multiple databases with the objective of identifying demographic, clinical, molecular and treatment factors influencing AYA glioma outcomes. Results: 40 Studies met inclusion criteria. Overall survival was highly variable across studies depending on glioma grade, anatomic compartment and cohort characteristics. Thirty-five studies suffered from high risk of bias in at least one domain. Several studies included older adults within their cohorts; few captured purely AYA groups. Despite study heterogeneity, identified favorable prognosticators included younger age, higher functional status at diagnosis, low-grade pathology, oligodendroglioma histology and increased extent of surgical resection. Though isocitrate dehydrogenase (IDH) mutant status was associated with favorable prognosis, validity of this finding within AYA was compromised though may studies including older adults. The prognostic influence of chemotherapy and radiotherapy on overall survival varied across studies with conflicting evidence. Conclusion: Existing literature is heterogenous, at high risk of bias, and rarely focused solely on AYA patients. Many included studies did not reflect updated pathological and molecular AYA glioma classification. The optimal role of chemotherapy, radiotherapy, and targeted agents cannot be determined from existing literature and should be the focus of future studies.

Feasibility of treating pediatric intracranial germ cell tumors in a middle-income country: The Jordanian experience.

BACKGROUND: Pediatric intracranial germ cell tumors (iGCT) are rare, with limited data available from Arabic countries. METHODS: We retrospectively reviewed the medical charts of children <18 years diagnosed with iGCT at King Hussein Cancer Center/Jordan (January 2003 to December 2020) for clinical characteristics, treatment, and morbidities. RESULTS: Sixteen patients had germinoma; median age was 6.9 years and median symptoms duration 8 months. Nine tumors were suprasellar, five pineal, and two bifocal. Four were metastatic. Eight patients had slightly elevated beta subunit human chorionic gonadotropin and 11 patients had resection/biopsy. Fifteen patients received chemotherapy; mostly carboplatin (450 mg/m2 )/etoposide, which had low toxicity. All patients received radiotherapy (different doses and fields). At median follow-up of 7.7 years, one tumor recurred (progression-free survival: 91% ± 8%). Twelve patients who continued follow-up had stable visual and endocrine deficits to their initial presentation. Five finished or are finishing diploma and seven had poor school performance (four left school). Six patients were diagnosed with nongerminomatous germ cell tumor; median symptom duration was 1 month. Three tumors were pineal, two suprasellar, and one at quadrigeminal plate. Three were metastatic. Five tested patients had high tumor markers and four had resection/biopsy. All patients received chemotherapy, and then five received craniospinal radiation. Two patients are alive, two died with tumor progression, one died in remission with electrolyte imbalance, and one developed leukemia and died with septic shock. CONCLUSIONS: We achieved excellent survival in treating germinoma using a feasible protocol for low middle-income countries. However, patients encountered significant morbidities exacerbated by delayed diagnosis and unnecessary surgical interventions despite abnormal tumor markers. Raising awareness on iGCT symptomatology and diagnosis may help limit these morbidities.

Preservation of endocrine function after Ommaya reservoir insertion in children with cystic craniopharyngioma.

INTRODUCTION: Children with craniopharyngiomas (CP) can experience significant morbidities caused by extensive surgery and/or radiation. Ommaya reservoir insertion (ORI) into cystic CP represents a minimally invasive approach allowing immediate decompression and aims to avoid additional injuries. The purpose of this study was to determine the surgical outcome and relevance of upfront ORI (± intracystic treatment) for preservation of endocrine function. METHODS: We performed a retrospective chart review of children with CP treated at the Hospital for Sick Children between 01/01/2000 and 15/01/2020. Endocrine function was reviewed at the time of initial surgery and throughout follow-up. New endocrinological deficits related to the index procedure were defined as immediate failure (IF), whereas postoperative duration of endocrinological stability (ES) was analyzed using the Kaplan-Meier method. The rate of IF and ES was compared between the treatment groups. RESULTS: Seventy-nine patients were included and had a median age of 8.3 years (range 2.1-18.0 years); 31 were males. Fifty-three patients with upfront surgical treatment, including 29 ORI and 24 gross total or partial resections had sufficient endocrinological follow-up data. Endocrine dysfunction occurring immediately after the index procedure (IF) was observed in 15 patients (62.5%) in the resection group compared to two patients (6.8%) in the ORI group, odds ratio: 0.05 (CI: 0.01-0.26, p < 0.0001). Excluding those with immediate endocrinological deficits, mean ES after ORI was 19.4 months (CI: 11.6-34.2), compared to 13.4 months (CI:10.6-NA) after surgical resection. CONCLUSIONS: Endocrine function was preserved in patients with upfront ORI (± intracystic treatment), which was confirmed as a minimally invasive procedure with an overall low morbidity profile.

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.

Prognostic factors related to overall survival in adolescent and young adults with medulloblastoma: A systematic review.

Background: Medulloblastoma is a rare diagnosis among adolescents and young adults (AYA). Though prognostic factors and treatment are well characterized among children with medulloblastoma, equivalent data for AYA are sparse. We conducted a systematic review to identify predictors of survival among AYA with medulloblastoma. Methods: We searched for primary studies of AYA (age 15-39 at diagnosis) with medulloblastoma in high-income countries within OVID MEDLINE, EMBASE, and EBM Reviews-Cochrane library databases from inception to August 2020. Patient demographics, primary outcomes, and univariate and multivariable data on all prognostic factors were collected from included studies. Prognosticators were characterized as patient, disease, or treatment-related. Results: We identified 18 articles. 5-year overall survival ranged between 40% and 89%, while disease-free survival ranged from 49% to 89%. Study quality was low as assessed by the Quality in Prognostic factor Studies tool. Though meta-analyses were not possible due heterogeneity, narrative summaries suggested that lower disease burden, superior postoperative functional status, and higher doses and larger fields of radiation were associated with improved survival. Reported chemotherapy regimens were heterogeneous in timing, agents, and relationship with radiation, precluding meaningful comparisons. Only one study included molecular subgroups for analysis, with the majority (76.5%) of tumors classified as Sonic Hedgehog (SHH). Conclusions: Prognostication and treatment of AYA medulloblastoma is limited by a dearth of primary evidence and lack of specificity for patients aged 15-39. Dedicated prospective trials to delineate the benefit of various chemotherapy and radiation regimens are required in this population to identify prognosticators and ideal treatment regimens.

Characteristics of children ≤36 months of age with DIPG: A report from the international DIPG registry.

BACKGROUND: Children ≤36 months with diffuse intrinsic pontine glioma (DIPG) have increased long-term survival (LTS, overall survival (OS) ≥24 months). Understanding distinguishing characteristics in this population is critical to improving outcomes. METHODS: Patients ≤36 months at diagnosis enrolled on the International DIPG Registry (IDIPGR) with central imaging confirmation were included. Presentation, clinical course, imaging, pathology and molecular findings were analyzed. RESULTS: Among 1183 patients in IDIPGR, 40 were eligible (median age: 29 months). Median OS was 15 months. Twelve patients (30%) were LTS, 3 (7.5%) very long-term survivors ≥5 years. Among 8 untreated patients, median OS was 2 months. Patients enrolled in the registry but excluded from our study by central radiology review or tissue diagnosis had median OS of 7 months. All but 1 LTS received radiation. Among 32 treated patients, 1-, 2-, 3-, and 5-year OS rates were 68.8%, 31.2%, 15.6% and 12.5%, respectively. LTS had longer duration of presenting symptoms (P = .018). No imaging features were predictive of outcome. Tissue and genomic data were available in 18 (45%) and 10 patients, respectively. Among 9 with known H3K27M status, 6 had a mutation. CONCLUSIONS: Children ≤36 months demonstrated significantly more LTS, with an improved median OS of 15 months; 92% of LTS received radiation. Median OS in untreated children was 2 months, compared to 17 months for treated children. LTS had longer duration of symptoms. Excluded patients demonstrated a lower OS, contradicting the hypothesis that children ≤36 months with DIPG show improved outcomes due to misdiagnosis.