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BACKGROUND/OBJECTIVES: Aggressive clinical and biological behavior, high morbidity and mortality are the main characteristics of pediatric high-grade-gliomas (HGG). Our aim was to study patients (pts) with ΗGG or diffuse-intrinsic-pontine-glioma (DIPG), diagnosed in the largest pediatric neurooncology Center in Greece. DESIGN-METHODS: We performed a retrospective-review of newly-diagnosed pts with HGG or DIPG during 2014-2021. Gender, age, location, resectability, type of surgery, histological and molecular characteristics, management and outcome were analyzed. RESULTS: During the study-period, 38pts (18females), median age:9.35y(range:3days-16.9y), were diagnosed in our center. The most common tumor-location were pons (17/38 pts) and parietal lobe (11/38 pts). DIPG based on imaging-studies was diagnosed in 16pts. Surgical approach was performed in 32pts (VP-shunt insertion:8, biopsy:12, partial resection:6, subtotal: 6). In 23pts(5 brainstem-tumors) a histological-diagnosis was feasible. Astrocytoma grIV was found in 60.8% and grΙΙΙ in 26.1%(14 and 6 respectively). Of notice, 3 additional pts with histological findings of low-grade(2grII and 1gr1), were upgraded in grIV after molecular-studies and DNA-methylation analysis. Furthermore, 17.3% of the pts (4/23, 3 located in the midline) carried a Η3Κ27Μ-mutation (diffuse midline glioma, DMG), 17.3% a Η3F3A-mutation and 8.6% showed ΕGFR-overexpression. All patients>3years of age were treated upfront according to HIT-HGG2013 with radiotherapy-temozolomide (29/32pts). In 5DIPG pts, reirradiation after disease-progression resulted in temporary symptomatic improvement. HGG-pts upon progression were treated with bevacizumab-irinotecan. Of the 38pts, 6pts elected to receive treatment in other countries. Overall-survival was 75.1%,15.1% and 3.7% at 1,2 and 3 years post-diagnosis respectively. Patients with DIPG/ DMG and non-midline HGG had a median overall-survival of 1.10 years and1.34 years, respectively. CONCLUSIONS: The experience of our unit concurs with worldwide published series and shows that pediatric HGG and DIPG have a dismal prognosis. Re-irradiation may offer short survival prolongation. ASKNOWLEDGEMENTS: Authors asknowledge the contribution of KiTZ-Heidelberg in molecular diagnostics through collaboration with ACCC.

BACKGROUND: Gliomatosis cerebri (GC), a radiologically defined diffusely infiltrating glioma, is no longer considered a distinct entity since the 2016 WHO classification for tumors of the CNS. Due to its rarity and dismal prognosis treatment recommendations in children remain ambiguous. Using central neuroradiological review, we performed a multi-institutional, retrospective study of GC providing comprehensive radiological, clinical, and (epi)genetic characterization. RESULTS: We included 104 patients between 1-19 years. Within a median follow-up of 15.5 months (range, 2.3-138.8), 93 patients (89.4 %) had died, 4 (3.8 %) were lost to follow-up and 7 (6.8 %) were alive with stable/progressive disease. Median progression-free- (PFS) and overall survival (OS) were 8.6 months (interquartile range, 4.3-14.0) and 15.5 months (10.9-27.7), respectively. Former WHO grading correlated significantly with median OS: WHO °II: 47.8 months (25.2-55.7); WHO °III: 15.9 months (11.4-26.3); WHO °IV: 10.4 months (8.8-14.4) (p

BACKGROUND/OBJECTIVES:Optic-pathway-glioma(OPG) represents the most common central-nervous tumor in children with neurofibromatosis type-1(NF1), occurring at an incidence of 15-20%. It is estimated that 1/3 of NF1 patients(pts) with OPG will need treatment. DESIGN-METHODS:We performed a retrospective-review of all NF1-pts examined in the First Hellenic Multidisciplinary-Clinic – Center of Expertise for Neurocutaneous-disorders. Gender, age, MRI-radiological and ophthalmological findings, presence of OPG, management and outcome were analyzed. RESULTS:Since the establishment of the Clinic in 2016, 198pts with clinical diagnosis of NF1 based on NIH1988-criteria were evaluated and of them, 165(73 females, median age:5.5y, range:0.3-17.1y), who had imaging studies were included in this analysis. Eighty three pts(50.3%) had NF1-positive genetic-testing and 45NF1-family-history(27.3%). Imaging-findings from optic pathway were found in 55/165pts(28females). Percentage of pts with findings were 51.7% for 10y, respectively. The median age of their first brain-MRI imaging was 2.82y. Upon 1stMRI-imaging, 70.9% presented thickness of the optic nerves(ON)(25,4%bilateral, 20% optic chiasm,18.1% right ON, 10.0% left ON), 14.5%ON-tortuosity, 38.1%OPG(43,5% in the optic-chiasm) and 34.5% contrast enhancement. Of notice, 14pts presented an OPG after a median follow-up time of 1.79y. According to LGG2004-protocol indications for treatment, only 15/55pts had to be treated(27,2%, 5pts with family history, 33.3% between 5-10y). Severe vision-loss with need for immediate start of treatment upon 1stMRI imaging was found in 4pts, of whom 75% had family-history and first evaluation after the 5th year of age. Of notice, only 2pts

INTRODUCTION-BACKGROUND: Cognitive, learning and/or behavioral disorders are common (up to 70%) complications of neurofibromatosis (NF). The first multidisciplinary-clinic for neurocutaneous-disorders was established at the Aghia Sophia Children’s Hospital in Athens, Greece, in 2016. Since then, more than 200 children and adolescents with NF have been examined. SCOPE: Acknowledging and indicating awareness on the devastating life-long consequences (poor academic performance, behavioral problems, and limited career prospectives) that can result from cognitive impairment, a research collaboration with educational specialists was recently implemented to examine the neurocognitive functions of children and adolescents with NF. MATERIALS: Children and adolescents aged 7-14 years who suffer from NF type I or type II, were eligible for study entry. The third edition of the Wechsler Intelligence Scale (WISC-III) was used to measure participants’ cognitive function. RESULTS: Preliminary results of this ongoing study are presented. Patients’ recruitment was limited by the coronavirus disease 2019 (COVID-19) restrictions. At this stage, the research involved 10 participants suffering from NF, with mean (± SD) age of 11.55 (± 1.80) years and a male-to-female ratio of 1. The mean (± SD) full-scale intelligence quotient (IQ) was 85.50 (± 18.80), corresponding to the 0.3rd to 73th percentile range. The mean (± SD) scores of performance IQ and verbal IQ were 84.90 (± 17.43) and 89.40 (± 17.23) respectively, corresponding to the 1st to 73rd percentile range for both subscales. CONCLUSION: Significant cognitive deficits, according to the percentile scores of WISC-III, were demonstrated in the small number of children and adolescents suffering from NF (type I or type II). Cognitive assessment, as part of the multidisciplinary approach of these patients is warranted, to aid timely educational interventions and improve patient learning outcomes.

BACKGROUND: Tumors of Central Nervous System (CNS) comprise major cause of cancer-related morbidity and mortality during childhood. Recent advances in genome and epigenome research allow for molecular classification of CNS tumors, treatment stratification and therapeutic target identification. In many countries, including Greece, this integrated diagnosis is not possible, yet, in a routine setting due to financial and infrastructural reasons. DESIGN/METHODS: We analyzed the results from the methylation profiling performed on tumor samples from newly diagnosed and selected retrospective patients followed in our unit. Analyses were performed through the PTT2.0 and MNP2.0 Studies, as part of a collaboration project between ACCC (Athens Cancer Comprehensive Center) and DKFZ (German Cancer Research Center). RESULTS: Methylation arrays from 50 patients (mean age: 8years, range: 0-17years) have been analyzed. High calibrated score (>0.9) was achieved in 38 patients (76%) and in 33 (86%) of these, the histological diagnosis matched the methylation class. The remaining 5 cases, diagnosed by the local pathologist as ganglioneuroma, primitive neuroectodermal tumor, anaplastic astrocytoma, pineoblastoma and oligodendroglioma, were classified according to the methylation profiling as dermatofibrosarcoma protuberans, medulloblastoma group 3, high-grade glioma H3.3G34mutant, high-grade neuroepithelial tumor with BCOR alteration and glioneuronal tumor, respectively. Only four cases had no match in the classifier, while seven cases received low score (0.5-0.8). In 6 out of the 7 cases with low score, the diagnosis was confirmed with the use either of the copy-number profile inferred from the methylation array or by additional testing for gene fusions and mutations. In 25 medulloblastomas, methylation profiling provided molecular classification, according to the 2021 WHO Classification. CONCLUSIONS: Our experience on the first 50 cases suggests that methylation array needs to be considered as an integral part of the diagnostic process of pediatric patients with CNS tumors and highlights the importance of international collaboration programs in pediatric neuro-oncology.

BACKGROUND/OBJECTIVES: Low-grade-gliomas(LGGs) encompass a heterogeneous set of tumors of different histologies. They are the most common type of pediatric brain tumors accounting almost 30-50% of them. This is the first attempt to describe characteristics of Greek-LGG-patients diagnosed in the largest Pediatric Brain Tumors National Center. DESIGN-METHODS: We performed a retrospective review of newly-diagnosed LGG-patients during 2015-2017. Gender, age, symptoms, location, leptomeningeal infiltration, histological type, BRAF-status, NF-status, management and outcome were analysed. RESULTS: During the study period, 42 LGG-patients(22males) were diagnosed. Median age was 6.3years(range:40days-15.8years). Nearly 80% of the patients had symptoms of raised intracranial-pressure (headache/vomiting). The most common locations were: posterior-fossa(38.0%) followed by optic-pathway(26.2%). Surgical intervention was possible in 30 patients(26 subtotal/total excision, 2 partial excision, 2 biopsy). Leptomeningeal infiltration at diagnosis was detected in 2 patients. Histological type was mostly astrocytoma (23pts, 54.8%), especially pilocytic type (69.5% of astrocytomas). NF1 was diagnosed in 23.8% of the patients. In 16non-NF1 patients RT-PCR was performed for KIAA1549/BRAF-fusion and was positive in 5 patients and BRAFV600Emutation was detected in 3 patients. Treatment according to LGG2004-protocol was administered in 13 patients, of which 5 needed treatment-modification (3 due to carboplatin allergic reaction and 2 due to progressive disease) Radiotherapy was administered in 2 patients. One patient had a malignant transformation to glioblastoma multiforme, 16 months after initial diagnosis and died. At the end of treatment, visual and mobility problems were noted in two and one patients respectively. CONCLUSIONS: The most common histologic type was pilocytic astrocytoma. Overall survival was 97,6%. Our findings agree with those of internationally published studies.

CNS tumors are the second most common neoplasms in children and primary cause of childhood cancer morbidity. With the increase of 5-year survival rate, the diagnosis of long-term consequences is necessary. Recent studies suggest that childhood CNS tumors are associated with IQ decline and deficits in specific cognitive functions. Factors such as localization, age at diagnosis and therapeutic modalities influence the range and severity of the neuropsychological deficits. OBJECTIVE: This work presents the results of the first systematic evaluation of neuropsychological performance of Greek children with CNS tumors. METHODS: 72 children underwent neuropsychological testing between September 2015 and December 2017. Forty five children (29 boys, 64%) with mean age of 10.5 (range: 5.3-16.1) years were included in the study. Eighteen (40%) patients had low grade tumors. All patients underwent a comprehensive neuropsychological assessment, covering all domains of cognitive functioning. Impairment was defined as a performance of one standard deviation below the normative mean. RESULTS: Poor neurocognitive performance was found regarding attention (-2sd), speed of processing (-1.5sd), verbal memory (-2sd), learning (-1.5sd) and executive functions (-2sd). Despite the abovementioned deficits, intellectual efficiency was relatively preserved and fell within low average levels (>16%ile). CONCLUSIONS: Our results are in line with previous reports suggesting that children who have been treated for CNS tumors present with a wide range of long-term effects on cognitive functioning. Longer follow-up and expansion of the sample may give for further insights on the factors associated with poor neurocognitive outcome and allow appropriate intervention for optimal outcome.