bluuebunny/crossref_metadata_2025_split huggingface dataset:
PATH-05 Challenge and clinical relevance of a non-matching classifier output in genome-wide DNA methylation analysis for CNS neoplasms in pediatric and adolescent patients
Authors: Drexler Richard , Eckhardt Alicia , Bode Helena , Lamszus Katrin , Westphal Manfred , Schüller Ulrich , Mohme Malte 
Published: June 2022

Abstract
OBJECTIVE: The molecular classification of CNS tumors has revolutionized our understanding of the biological heterogeneity and diversity of tumor subtypes. DNA methylation-based classification allows to discriminate subtypes. Although DNA methylation-based classification can diagnose tumors with high specificity, there are tumors which cannot be classified. We aimed to gain further insight into these challenging cases. METHODS: Overall, 21 patients with a CNS tumor that was non-classifiable (confidence score &lt;0.3), or had a low confidence score (&lt;0.9) using the DNA methylation-based classifier version 11b4, were included. Tumors were re-classified using version (v12.3), and clinical data were analyzed. RESULTS: A total of 21 pediatric and adolescent brain tumors with a calibrated score below 0.9 in the classifier output were identified. Of these, 11 patients (52.4 %) were assigned to the “no matching methylation class” with a score below 0.3. IDH-wild type glioblastoma (23.8 %), ETMR (14.3 %), and DMG (14.3 %) were the most common histological diagnoses. Surgical and clinicopathological features as well as DNA input and tumor purity did not influence the confidence score. Cases with non-classifiable tumors had a significantly longer time until a decision for adjuvant therapy (p&lt;0.01). Application of the latest classifier version v12.3 led to a re-classification of 9 (42.9 %) cases, of which 5 cases (55.6 %) had an improved calibrated score. CONCLUSION: Our study presents unclassifiable cases and the possible clinical impact when waiting for the accurate diagnosis in these challenging cases. Even though DNA methylation profiling significantly contributes to advanced CNS tumor diagnostics, clinicians should be aware of a prolonged interval to treatment initiation, especially for highly malignant brain tumors. Therefore, we would recommend to schedule adjuvant treatment as early as possible, if surgical and histological results are suspicious for this disease.
PATH-10. Nanopore sequencing reveals novel ALK fusion with interposed element in a neonate with hemispheric glioma
Authors: Liu Anthony P Y , Chan Chris T L , Ma Edmond S K , Ho Wilson W S , Ku Dennis T L , Shing Matthew M K , Kan Amanda N C , Chan Godfrey C F , Ng Ho-Keung 
Published: June 2022

Abstract
Here we describe the clinical course and unique molecular findings in a female neonate with infantile hemispheric glioma (IHG). The patient presented at the age of 17 days with macrocephaly and suboptimal weight gain. MRI brain revealed an 8.5cm mass over the right frontal region with significant mass effect and entrapment of ventricles. Urgent ventriculoperitoneal shunt insertion and biopsy of the highly vascular lesion was performed. Pathology was compatible with glioblastoma multiforme. Methylation profiling classified the sample as inflammatory tumor tissue (MNP v11b4), while panel RNA-sequencing revealed a fusion event between HMBOX1 and ALK which has not been described in primary CNS tumors. Long-read sequencing with the Nanopore system further revealed complex genomic rearrangement involving an interposed genomic fragment from a third chromosome with validation by Sanger sequencing. Based on an integrated diagnosis of IHG, the patient went on to receive neoadjuvant chemotherapy per the CNS-14 protocol (cyclophosphamide, carboplatin, etoposide) with significant tumor shrinkage. Near total removal of the lesion was achieved after 4 cycles of chemotherapy and adjuvant treatment with 4 additional cycles was given. The patient tolerated therapy well other than self-limiting transaminitis. At the end of treatment, the patient enjoyed intact neurology and satisfactory developmental progress. Our case report illustrates the value a multi-pronged approach to characterizing rare pediatric CNS tumors. The precise delineation of breakpoints in fusion-driven tumors might be of value in the design of cfDNA-based assays. (APYL and CTLC contributed equally to the submission)
PATH-13. Methylation analysis in the diagnosis of pediatric CNS tumors; a single center experience
Authors: Filippidou Maria , Binenbaum Ilona , Glentis Stavros , Roka Kleoniki , Vlachou Antonia , Avgerinou Georgia , Stefanaki Kalliopi , Selt Florian , Milde Till , Sahm Felix , Witt Olaf , Jones David T , Pfister Stefan M , Kattamis Antonis 
Published: June 2022

Abstract
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 (&gt;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.
PATH-16. Noninvasive diagnosis of gliomas through CSF cfDNA sequencing in pediatric and adolescent and young adult (AYA) patients
Authors: Hill Katherine , Miller Alexandra M , Li Bryan Kincheon , Bouvier Nancy , Li Shanita , Alano Tina , Doe-Tetteh Seyram , Huereca Claudia , DiNapoli Sara , Lee Alex , Szalontay Luca , Riviere-Cazaux Cecile , Burns Terry C , Haque Sofia , Bale Tejus , Benhamida Jamal , Dogan Snjezana , Vanderbilt Chad , Ross Dara , Chang Jason , Donzelli Maria , Dunkel Ira J , Sait Sameer Farouk , Khakoo Yasmin , Gilheeney Stephen , Souweidane Mark , Greenfield Jeffrey , Berger Michael , Benayed Ryma , Arcila Maria E , Ladanyi Marc , Mellinghoff Ingo , Karajannis Matthias 
Published: June 2022

Abstract
PURPOSE: A subset of pediatric, adolescent and young adult (AYA) gliomas are located in the brainstem, eloquent locations, or present with diffuse/leptomeningeal disease, and are associated with high risk and low yield of biopsy. At the same time, accurate molecular diagnosis is necessary to direct optimal therapy. In such cases, analysis of cell free DNA (cfDNA) form cerebral spinal fluid (CSF) may represent a diagnostic alternative to biopsy. METHODS: We investigated the utility of CSF cfDNA sequencing through a stepwise approach, using clinically validated, targeted molecular assays. Testing was performed using a broad hybrid capture next generation sequencing assay (MSK-IMPACT) and subsequent targeted digital droplet PCR in a subset of cases. RESULTS: We analyzed 17 CSF samples from 17 pediatric (n=6) and AYA (n=11) glioma patients with primary or recurrent disease. Thirteen had tumors located within the brainstem, and four had leptomeningeal involvement. Somatic alterations were detected in 12/17 samples (71%). In 3/4 patients with leptomeningeal involvement, cfDNA testing revealed a BRAF fusion consistent with the diagnosis of diffuse leptomeningeal glioneuronal tumor (DLGNT). Among the 13 patients with brainstem involvement, four had somatic H3 K27M mutations, three had IDH mutations, and one had TP53 and ATRX mutations; five patients had no detectable mutations. CONCLUSION: In our analysis, we found that established glioma hotspot mutations were able to be detected within the CSF. We propose that in patients for whom tissue biopsy is high risk, not feasible, or tissue was nondiagnostic, CSF cfDNA sequencing has a substantial diagnostic yield and should be considered as a valuable novel diagnostic tool. Ongoing research is aiming to further increase the sensitivity of cfDNA testing, especially in patients with very low levels of CSF cfDNA.
LINC-02. Gamma Knife Radiosurgery as an efficacious treatment for Pediatric Central Nervous System Tumors: A Retrospective Study of 61 Neoplasms
Authors: Pahwa Bhavya , Agrawal Deepak 
Published: June 2022

Abstract
PURPOSE: Brain tumors have an incidence of 1.15 to 5.14 cases per 100,000 children and are associated with significant morbidity and mortality. Radiosurgery has become a promising approach to manage these pediatric CNS tumors. The aim of the present study was to analyse the efficacy of radiosurgery in the treatment of a variety of pediatric tumors of CNS METHODS: This retrospective study was conducted from 1997-2012 at a single Neurosurgery centre. All paediatric patients (≤ 18 years of age) with CNS tumours who were treated with gamma knife radiosurgery (GKRS) and had a minimum follow up of 6 months were included in the study. Patients with lesions other than tumours were excluded. Clinical, radiological and GKRS planning data was collected and analysed in all patients. RESULTS: A total of 76 children with brain tumors had GKRS during the study period. Of these, 40 children (with 61 neoplasms) had follow up available and were included in the study. The mean age was 16 years (6-18 years). 17 patients received primary GKRS, 20 patients received secondary and 3 patients received both. The median tumor volume was 3.3cm3 (0.14 - 38.9 cm3). The mean dose was 12.56 Gy at 50% isodose line. The majority of the tumors were Meningioma (n=20) followed by Acoustic Schwannoma (n=17). The mean treatment time was 67.04 minutes. 33 tumors responded favourably to GKRS, 24 showed a stable size, 3 had no response while 1 progressed requiring surgery. CONCLUSION: GKRS has the potential to become an indispensable tool in the management of pediatric brain neoplasms
LINC-06. Prevalence and outcomes of Autoimmune encephalitis in a tertiary hospital in Baguio City, Philippines
Authors: Sagay Jaidi 
Published: June 2022

Abstract
INTRODUCTION: Autoimmune Encephalitis is a debilitating neurological disorder that develops as a rapidly progressive encephalopathy, occurring usually less than 6 weeks, caused by brain inflammation. There are limited data on the autoimmune cases in the locality. This study aims to determine the prevalence and outcomes of patients with Autoimmune encephalitis cases admitted in a tertiary hospital in Baguio City, Philippines. METHODOLOGY: This is a descriptive retrospective cross-sectional study that reviewed health records of patients managed as autoimmune encephalitis in a tertiary hospital from January 2015 to December 2020. Descriptive Statistics using frequencies and percentages were employed in the study. RESULTS: A total of 21 patients were included in the study, majority of which were adolescent patients, with male predominance and are residing in rural areas. The most common clinical manifestation presented were fever, behavioral changes, generalized motor seizures, orofacial and limb dyskinesias. EEG revealed abnormal results in 14 patients (66.67%). Majority of patients had normal CSF analysis, while 2 (38.1%) revealed elevated CSF protein levels. Eight patients (38.1%) tested positive for anti-NMDAR titers. Most patients had normal ultrasound and cranial CT Scan (47.62%). The length of stay was more than 2 weeks and majority (80.95%) of patients were discharged improved. CONCLUSION: The prevalence of autoimmune encephalitis is 5/10,000 pediatric population in a span of 6 years which was noted to be increasing over time. The demographic and clinical profile maybe used as predictors of outcome of autoimmune encephalitis, hence, it can help in the management of the said disease.
LINC-09. Coexisting glioneuronal tumor and adrenal ganglioneuroma
Authors: Shahbandi Ataollah , Atashpanjeh Saeid , Azari-Yam Aileen , Nejat Farideh , Habibi Zohreh 
Published: June 2022

Abstract
BACKGROUND: While both glial/glioneuronal neoplasia and ganglioneuroma have been reported as components of multiple primary neoplasms, no patient has been diagnosed with multiple primary neoplasms of cerebral glial/glioneuronal tumors with oligodendroglioma-like features and adrenal ganglioneuroma up to now. CASE: A previously healthy five-year-old girl was admitted with a two-week history of headaches and vomiting. Brain Magnetic resonance imaging (MRI) showed a massive heterogenous multi-cystic enhancing lesion in the right temporoparietal area with substantial vasogenic edema. The patient underwent craniotomy and tumor gross total resection. The intra-operative histomorphological assessment of the tumor was well-matched with a glial tumor. The patient developed systolic hypertension during postoperative care in the Intensive Care Unit. Subsequent abdominal CT scan unveiled a calcified mass of the left adrenal gland origin. Blood and urine catecholamine tests, vanillylmandelic acid (VMA), were within the normal range. The surgical excision specimen exhibited a clear cell neoplasm with diffuse infiltrative growth. A distinguishing combination of oligodendroglioma-like perinuclear haloes, clear cell appearance and vascular proliferation rendered the diffuse Glioneuronal tumor with Oligodendroglioma-like features. With the combination of oligodendroglial-like appearance, negative 1p/19q codeletion, Wild IDH, no BRAF mutation, weak GFAP, and positive synaptophysin altogether, the tumor was compatible with the novel diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC). The patient underwent laparotomy and tumor resection subsequently. Morphologic histopathological examinations of the adrenal mass were in line with ganglioneuroma. After discharge, no pathological uptake was identified with iodine-131 meta-iodobenzylguanidine scan (MIBG scan). No tumor residue was apparent on postoperative brain MRI. The patient received no adjuvant therapy for brain and adrenal tumors and underwent close surveillance for both tumors. No clinical or radiologic recurrence was recognized after six months of follow-up. CONCLUSIONS: Concurrent glioneuronal tumor and ganglioneuroma can be managed safely when diagnosed timely, leading to favorable outcomes.
LINC-13. Subependymal giant cell astrocytoma in a child with tuberous sclerosis complex: a case report
Authors: Estetika Citra , Rahmartani Ludi Dhyani , Soebadi Amanda , Gunawan Kevin , Susanto Eka , Amal Muhammad Yanuar 
Published: June 2022

Abstract
INTRODUCTION: Tuberous sclerosis complex (TSC) is an autosomal-dominant genetic disorder causing the formation of hamartomas in many organs, including the brain. It is generally benign but can block the flow of cerebrospinal fluid that increases intracranial pressure and leads to severe neurologic and behavioural changes. Subependymal giant cell astrocytoma (SEGA) occurs in 10-15% of TSC patients. Routine brain surveillance is important to look for SEGA in all TSC patients. CASE: We report a girl who was previously diagnosed with TSC at the age of two. She had hypomelanotic macules, facial angiofibroma, and a shagreen patch. Her first brain magnetic resonance imaging (MRI) was normal. She had routine consultation until she complained of recurrent headaches, walking instability, and seizures six years later. Her brain MRI showed a solid heterogenous intraventricular mass suggestive SEGA, with multiple subcortical hyperintense lesions (subcortical tubers), and hydrocephalus. She underwent emergency ventriculoperitoneal shunt (VP shunt) and tumor removal surgery. The histopathology examination matches SEGA, World health organization (WHO) grade I. It consists of polygonal to spindle cells with abundant eosinophilic cytoplasm. There are also large to multinucleated cells. After surgery, she had significant clinical improvement, and the seizure was controlled with valproic acid. CONCLUSION: It is essential to do brain evaluation using brain scan or MRI every 1-3 years as surveillance recommendation in all TSC patients. Early detection dramatically increases the chance of giving early treatment or surgery to lower complications and provide better outcomes.
Keywords: Subependymal giant cell astrocytoma, tuberous sclerosis complex, surveillance, early diagnosis
LINC-20. Impact of the COVID-19 pandemic on 30-day mortality and unplanned reoperation rates for pediatric central nervous system tumors
Authors: Jovett Sanchez Diana , Gaspi Sally Andrea , Talan Ceri Jane , Alcasabas Ana Patricia , Baticulon Ronnie 
Published: June 2022

Abstract
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.
LINC-22. Primary central nervous system (CNS) germ cell tumors (GCT) in Central America and the Caribbean region: an AHOPCA 20-year experience
Authors: Veronica Giron Ana , Calderon Patricia , Pineda Estuardo , Montero Margarita , Lizardo Yamel , Bartels Ute , Osorio Diana S 
Published: June 2022

Abstract
BACKGROUND: Primary CNS GCT are rare neoplasms in pediatrics. Treatment depends on histological subtype and extent of disease. Overall survival (OS) is above 85% in high-income countries (HIC). OBJECTIVE: To describe the experience in treating CNS GCT in 4 of 8 countries, members of AHOPCA (Asociación de Hemato-Oncología Pediátrica de Centro América) and 5-year OS. DESIGN/METHODS: We conducted a retrospective chart review of patients treated for CNS GCT. Epidemiological, clinical characteristics, histology, treatment modalities and outcome were analyzed. RESULTS: From 2001 to 2021, 45 patients were included. Guatemala: 22, Nicaragua: 15, Dominican Republic: 3 and El Salvador: 5. Thirty (66.6%) were male, mean age at diagnosis was 8.6 years (range 12 months to 17 years). Presenting symptoms were headaches/vomiting (n=26, 57.7 %), visual disturbances (n=15, 33.3%), diabetes insipidus (n=7, 15.5%). Two patients (NGGCT) presented with precocious puberty. Upfront surgery was done in 33 cases (73.33%); 21 (63.6%) germinomas, 9 (27.2%) NGGCT and 3 (9%) CNS GCT. Eight patients were diagnosed and treated based on CSF tumor marker elevation; four germinomas (BHCG 11.32-29.41mUI/mL) and four NGGCT (BHCG 84.43-201.97mUI/mL or positive AFP&gt;10 ng/mL). Tumor locations included suprasellar (n=15, 33.3%), pineal (n=14, 31.1%), thalamus/basal ganglia (n=5, 11%), other (n=6, 13.3%); and one bifocal. Four (8.8%) had metastatic disease, 6 with positive CSF, staging data was incomplete in 25 patients (55.5%). Patients were treated with varied chemotherapy and radiotherapy modalities. Nine patients had incomplete data regarding treatment. Five-year OS was 65% (61.5% for germinoma and 56% for NGGCT). Two patients with histologically confirmed germinoma relapsed. CONCLUSIONS: Germinoma was the most common histology and there was a male predominance. More than half patients had incomplete staging data and treatment was variable. OS is lower compared to HIC. Standardized treatment protocols will aid in adequate staging, treatment planning, prevent complications and improve survival.