bluuebunny/crossref_metadata_2025_split huggingface dataset:
LINC-40. VERY YOUNG PATIENTS AND CENTRAL NERVOUS SYSTEM TUMORS: A SINGLE-CENTER EXPERIENCE IN AN UPPER-MIDDLE-INCOME COUNTRY
Authors: Madrigal-Avila Claudia , Perez-Bañuelos Alfonso , Perez-Garcia Martin , Ruvalcaba-Sanchez Rafael , Vega-Vega Lourdes , Escamilla-Asiain Gabriela 
Published: December 2020

Abstract
Tumors of the central nervous system comprise nearly a quarter of all childhood cancers and are the most frequent solid tumor in the pediatric population. Primary central nervous system tumors (PCNST) are a rare and heterogeneous group of tumors responsible for high mortality and morbidity. Around 10% of primary CNS tumors occur during the first year of life with almost half of them during the first six months. About 18% of these tumors appear before the age of two years. Very young children differ from older children and adolescents regarding the incidence and location of different histological entities of CNS tumors. We aimed at providing descriptive epidemiological data and report the outcome in a tertiary center from December 2013 to January 2020 for all histological subtypes of primary central nervous system tumors in very young patients, defined as patients younger than three years. We collect data from 19 patients treated in an oncology exclusive tertiary center in Mexico between 2013 and 2020. This study aims to relate factors such as age, radiotherapy, surgery, chemotherapy with Lansky Performance Scale and determine the impact, not only in the overall survival but also in the quality of life.
LINC-42. EPIDEMIOLOGICAL OVERVIEW OF CHILDHOOD CNS TUMORS IN THE NEUROSURGICAL UNIT IN YEREVAN, ARMENIA
Authors: Karapetyan Nune , Danielyan Samvel , Tamamyan Gevorg , Tananyan Armen , Safaryan Liana , Martirosyan Margar , Saghatelyan Tatul , Bardakhchyan Samvel , Papyan Ruzanna , Arakelyan Jemma , Bedirian Karen , Harutyunyan Martin , Matevosyan Vahagn , Lalazaryan Nara , Asatryan Eduard 
Published: December 2020

Abstract

BACKGROUND
Central nervous system (CNS) tumors are the second most common malignant neoplasms among children worldwide. The current paper aims to analyze the situation in pediatric neuro-oncology in Armenia from the neurosurgical perspective.

METHODS
We have collected data of pediatric patients with CNS tumors treated in the Neurosurgery department of “Surb Astvasamayr” Medical Center from 01.01.2010 till 01.12.2019. Incidence by gender, age at diagnosis, and histopathology results were calculated. Survival rates were calculated based on the follow-up results performed until 30.12.2019.

RESULTS
Hospital-based data showed that during the previous 10 years 47 patients with CNS tumors received neurosurgical treatment in the unit, among them 66% were females. 38.3%, 31.9% and 29.8% of diagnosed patients were aged 0–4, 5–9, and 10–18 respectively. In 41 cases, the disease was not disseminated at diagnosis. The most common observed malignancies were low-grade gliomas (21.3%) and embryonal tumors (19.1%), followed by high-grade gliomas (14.9%) and ependymal tumors (8.5%). Follow-up information only for 33 patients is available. From them, 14 are dead and 19 alive. Survival rates in most common groups were 62.5%, 80%, 50%, and 50% respectively. The median follow-up time was 18 months (range 1–113 months).

CONCLUSION
Similar to the data reported in the literature, low-grade gliomas, and embryonal tumors are the most frequent pediatric CNS tumors in Armenia. On the other hand, the pediatric CNS tumor survival rates are lower compared to those reported in developed countries.
MBCL-02. ROLE OF PREOPERATIVE CHEMOTHERAPY IN METASTATIC MEDULLOBLASTOMA: A COMPARATIVE STUDY IN 92 CHILDREN
Authors: Guerrini-Rousseau Léa , Abbas Rachid , Huybrechts Sophie , Kieffer-Renaux Virginie , Puget Stéphanie , Andreiuolo Felipe , Beccaria Kevin , Blauwblomme Thomas , Bolle Stéphanie , Dhermain Frédéric , Longaud Audrey , Roujeau Thomas , Rose Christian Sainte , Tauziede-Esperiat Arnaud , Varlet Pascale , Zerah Michel , Valteau-Couanet Dominique , Dufour Christelle , Jacques Grill 
Published: December 2020

Abstract

BACKGROUND
Previous pilot studies have shown the feasibility of preoperative chemotherapy in patients with medulloblastoma, but benefits and risks compared with initial surgery have not been assessed.

METHODS
Two therapeutic strategies were retrospectively compared in 92 patients with metastatic medulloblastoma treated at Gustave Roussy, France, between 2002 and 2015: surgery at diagnosis (n=54; group A) and surgery delayed after carboplatin and etoposide-based preoperative therapy (n=38; group B). Treatment strategies were similar in both groups.

RESULTS
The rate of complete tumor excision was significantly higher in group B than in group A (93.3% versus 57.4%, p=0.0013). Post-operative complications, chemotherapy-associated side effects and local progressions were not increased in group B. Preoperative chemotherapy led to a decrease in the primary tumor size in all patients, 4/38 patients experiencing meanwhile a distant progression. The histological review of 19 matched tumor pairs (before and after chemotherapy) showed that proliferation was reduced and histological diagnosis feasible and accurate even after preoperative chemotherapy. The 5-year progression-free and overall survival rates were comparable between groups. Comparison of the longitudinal neuropsychological data showed that intellectual outcome tended to be better in group B (the mean predicted intellectual quotient value was 6 points higher throughout the follow-up).

CONCLUSION
Preoperative chemotherapy is a safe and efficient strategy for metastatic medulloblastoma. It increases the rate of complete tumor excision and may improve the neuropsychological outcome without jeopardizing survival.
MBCL-08. INTEGRATIVE MOLECULAR ANALYSIS OF PATIENT-MATCHED DIAGNOSTIC AND RELAPSED MEDULLOBLASTOMAS
Authors: Kumar Rahul , Deng Maximilian , Smith Kyle , Liu Anthony , Dhall Girish , Kleese Laura , Bowers Daniel , Chintagumpala Murali , Leary Sarah , Nazarian Javad , Orr Brent , Onar-Thomas Arzu , Pfister Stefan , Korshunov Andrey , Robinson Giles , Gajjar Amar , Jones David , Ramaswamy Vijay , Northcott Paul 
Published: December 2020

Abstract

INTRODUCTION
The next generation of clinical trials for relapsed medulloblastoma demands a thorough understanding of the clinical behavior of relapsed tumors as well as the molecular relationship to their diagnostic counterparts.

METHODS
A multi-institutional molecular cohort of patient-matched (n=126 patients) diagnostic MBs and relapses/subsequent malignancies was profiled by DNA methylation array. Entity, subgroup classification, and genome-wide copy-number aberrations were assigned while parallel next-generation (whole-exome or targeted panel) sequencing on the majority of the cohort facilitated inference of somatic driver mutations.

RESULTS
Comprised of WNT (2%), SHH (41%), Group 3 (18%), Group 4 (39%), primary tumors retained subgroup affiliation at relapse with the notable exception of 10% of cases. The majority (8/13) of discrepant classifications were determined to be secondary glioblastomas. Additionally, rare (n=3) subgroup-switching events of Group 4 primary tumors to Group 3 relapses were identified coincident with MYC/MYCN pathway alterations. Amongst truly relapsing MBs, copy-number analyses suggest somatic clonal divergence between primary MBs and their respective relapses with Group 3 (55% of alterations shared) and Group 4 tumors (63% alterations shared) sharing a larger proportion of cytogenetic alterations compared to SHH tumors (42% alterations shared; Chi-square p-value &lt; 0.001). Subgroup- and gene-specific patterns of conservation and divergence amongst putative driver genes were also observed.

CONCLUSION
Integrated molecular analysis of relapsed MB discloses potential mechanisms underlying treatment failure and disease recurrence while motivating rational implementation of relapse-specific therapies. The degree of genetic divergence between primary and relapsed MBs varied by subgroup but suggested considerably higher conservation than prior estimates.
MBCL-13. CORRELATION OF HISTOPATHOLOGY, CHROMOSOMAL MICROARRAY, AND NANOSTRING BASED 22-GENE ASSAY FOR MEDULLOBLASTOMA SUBGROUP ASSIGNMENT ON “HEAD START” 4 CLINICAL TRIAL
Authors: Dhall Girish , Patel Parth , Blue Megan , Biegel Jaclyn , Almiraz-Suarez Isabel , Hwang Eugene , Pierson Christopher , Boue Daniel , Finlay Jonathan 
Published: December 2020

Abstract
“Head Start” 4 (HS 4) is a prospective randomized clinical trial that tailors treatment based on medulloblastoma molecular subgroups and response to induction chemotherapy to compare efficacy of one versus three (tandem) cycles of myeloablative chemotherapy. Advances in RNA and DNA profiling have identified four molecular subgroups of medulloblastoma with prognostic significance: Sonic Hedgehog (SHH) subtype, WNT subtype, Group 3, and Group 4. In HS 4 trial, we utilize a combination of histopathology and immunohistochemistry (pathology/IHC), as well as chromosomal microarray analysis (CMA) utilizing OncoScanTM (Thermo Fisher) to classify medulloblastoma samples into either SHH, WNT, or non-WNT/non-SHH (Group 3/4) subgroups at the time of diagnosis. NanoString based 22-gene assay is performed retrospectively to test concordance. We have pathology/IHC, CMA, and NanoString data on 26 infants and young children with medulloblastoma enrolled on HS 4. Pathology/IHC was able to assign samples to SHH, WNT, and non-WNT/non-SHH subgroups in all but two cases: one case was classified as Group 3, and the second as SHH by both CMA and NanoString. CMA was indeterminate in six cases, of which, pathology/IHC was able to assign all six samples aforementioned three subgroups. NanoString was indeterminate in two cases: one case was classified as SHH by CMA and pathology/IHC, and the second case was indeterminate by CMA but was assigned as non-WNT/non-SHH on pathology/IHC. There is excellent correlation between NanoString and combination of histopathology and CMA for core medulloblastoma subgrouping on HS 4. Methylation studies are ongoing.
MBCL-24. CAN YOUNG CHILDREN WITH RELAPSED MEDULLOBLASTOMA BE SALVAGED AFTER INITIAL IRRADIATION-SPARING APPROACHES?
Authors: Erker Craig , Larouche Valérie , Margol Ashley , Cacciotti Chantel , Perreault Sébastien , Cohen Kenneth J , AbdelBaki Mohamed S , Hukin Juliette , Rassekh Shahrad Rod , Eisenstat David D , Wilson Beverly , Knipstein Jeffrey , Hoppmann Anna L , Sandler Eric S , Dorris Kathleen , Fay-McClymont Taryn B , Salloum Ralph , Harrod Virginia L , Crooks Bruce , Finlay Jonathan L , Bouffet Eric , Lafay-Cousin Lucie 
Published: December 2020

Abstract

INTRODUCTION
Irradiation-sparing approaches are used in young children with medulloblastoma (MB) given the vulnerability of the developing brain to neurocognitive impairment. Limited data are available following relapse for these patients. We aimed to describe the management and outcomes of young children with MB who relapsed after initial treatment without craniospinal irradiation (CSI).

METHODS
International retrospective study including patients with MB diagnosed between 1995–2017, ≤ 72 months old, initially treated without CSI, who subsequently relapsed.

RESULTS
Data are available for 52 patients (32 male). Median age at initial diagnosis was 27 months (range, 6–72) with 24 being metastatic. Initial therapy included conventional chemotherapy alone or high-dose chemotherapy (HDC) in 21 and 31 subjects, respectively. Three received upfront focal irradiation. Molecular subgrouping, available for 24 tumors, included 9 SHH and 15 non-WNT/non-SHH. Median time to relapse was 13 months (range, 3–63). Relapse was local, disseminated or combined in 20, 15, and 16, respectively. Salvage therapy with curative intent was given in 42/52 patients, including CSI in 28 subjects (median dose 36Gy, 18–41.4) or focal irradiation in 5 others. Three received HDC only. At a median follow-up time of 46 months (range, 4–255), 25 (48%) were alive, including 7/9 SHH and 7/15 non-WNT/non-SHH. The 2- and 5-year OS was 67% and 56% (SE, 7%), respectively. Two of 3 patients with SHH who did not receive salvage radiotherapy are survivors.

CONCLUSION
A substantial proportion of young children who relapse following irradiation-sparing strategies can be salvaged. Neurocognitive and ototoxicity outcomes are being evaluated.
MBCL-26. FACTORS ASSOCIATED WITH LONGER SURVIVAL AFTER FIRST RECURRENCE IN MEDULLOBLASTOMA BY MOLECULAR SUBGROUP AFTER RISK-BASED INITIAL THERAPY
Authors: Chintagumpala Murali , Terhune Colton , Tong Lin , Bouffet Eric , Bartels Ute , Fisher Michael , Hassall Tim , Gururangan Shridharan , Schroeder Kristin , Hansford Jordan , Quang Dong Anh Khuong , Cohn Richard , Kellie Stewart , McCowage Geoffrey , Smith Kyle , Northcott Paul , Robinson Giles , Gajjar Amar 
Published: December 2020

Abstract

OBJECTIVE
To evaluate differences in time to recurrence among molecular subgroups of medulloblastoma treated on a single protocol and to identify factors associated with survival after first recurrence.

METHODS
Time to recurrence following SJMB03 treatment was compared across methylation subgroups among relapsed patients. Therapies received subsequent to relapse were noted. Kaplan-Meier methods and log-rank tests were used for statistical analyses.

RESULTS
74 of 330 medulloblastoma patients developed recurrence after initial therapy. (38 Standard-Risk; 36 High-Risk). The 2- and 5-year survival after first recurrence was 30.4% and 14.6% respectively. DNA methylation-based subgroups from initial diagnosis were SHH (n=14), Group 3 (n=24), Group 4 (n=26), and unclassified (n=8). None of the pts with WNT MB had recurrent disease. Median time to first recurrence was 1.23, 0.91, and 3.09 years in SHH, Group3, and Group 4 respectively. Group 4 patients had longer post-recurrence survival than others (p-value=0.0169). Clinical risk at diagnosis (p-value=0.337), anaplasia (p-value=0.4032), TP53 (p-value=0.1969), MYC (p-value=0.8967), and MYCN (p value = 0.9404) abnormalities were not associated with post progression survival. Patients who received any therapeutic modality (chemotherapy, re-radiation and second surgery) had longer survival and those who had all three (n=10) had the best outcome (p-value&lt;0.0001).

CONCLUSION
Outcome after recurrence in medulloblastoma is dismal, however, association with subgroups is still present. Group 4 patients had a longer time to recurrence and post progression survival. No other prognostic factor at initial diagnosis was associated with outcome after recurrence. Patients who received all 3 types of conventional therapy had better survival.
MBCL-30. NOVEL SMO MUTATION IN DESMOPLASTIC/NODULAR MEDULLOBLASTOMA: A CASE REPORT
Authors: Wright Avery , Aguilar-Bonilla Ana , Pickle Emily Owens , Smith Amy A 
Published: December 2020

Abstract
Smoothened (SMO) is a transmembrane protein which is regulated by SHH (Sonic hedgehog) protein binding to PTCH1. SMO activation controls GLI which then translocates into the nucleus and activates target genes. The SHH subtype of medulloblastoma has been extensively studied to have mutations within the SHH signaling pathway, often in PTCH1, SUFU, and SMO. We present a case of desmoplastic/nodular medulloblastoma with the mutation SMO c.1810G&gt;A. The patient presented at 11 years old with a two-week history of headaches and morning vomiting. His neuroimaging revealed a T2 hyperintense, enhancing mass centered at the fourth ventricle. He underwent gross total resection and had no metastatic spread. There were no alterations in PTCH1, SUFU, Tp53, GLI2, MYC/MYCN, CTNNB1, or the WNT pathway. The SMO c.1810G&gt;A alteration has not been previously identified as a somatic mutation in a CNS tumor. The functional effect of this mutation has not been studied. It is known that desmoplastic/nodular histology in medulloblastoma is associated with the SHH subtype and given the fact that SMO is regulated by SHH signaling, this patient was ultimately diagnosed with SHH subtype medulloblastoma. Findings of novel somatic mutations in patients raises the question of whether the mutation is in fact the driver of neoplasia.
MBCL-38. UNUSUAL EXTRANEURAL METASTASIS OF PEDIATRIC EMBRYONAL TUMORS: TWO CASE REPORTS
Authors: Goldberg Aaron , Abongwa Chenue , Pathare Jody , Hoerig Clay , Muhonen Michael , Olaya Joffre , Gajjar Amar , Warren Krista , Patel Ramesh , Lai Hollie , Loudon William , Plant Ashley 
Published: December 2020

Abstract
We report two cases of unusual extraneural metastasis in patients with embryonal tumors without central nervous system disease progression and prolonged survival. The first patient presented at 16 years of age with atypical teratoid rhabdoid tumor of the cervical spine. The tumor was confirmed to have loss of INI1, SMARCB1 deletion of exons 1–3, and heterozygous deletion of 22q11.2. The patient received treatment initially per ACNS0333 with high dose chemotherapy and tandem autologous transplants. The patient developed a biopsy-confirmed liver metastasis six months from diagnosis and, subsequently, had disease progression including liver metastases, bony lesions, muscle involvement, and lung nodules. Two and a half years from diagnosis the patient has still not had a relapse in the CNS. The second patient presented with medulloblastoma isolated to the posterior fossa at 11 years of age and was treated on SJMB03 protocol with craniospinal irradiation and high dose chemotherapy. He had his first recurrence in the temporal lobe three years post treatment. He had multiple recurrences in the brain over the next five years treated with re-resections, adjuvant chemotherapy, and gamma knife radiotherapy. He then developed cervical lymphadenopathy, bony lesions, liver lesions, and lung nodules. Cervical lymph node biopsy confirmed medulloblastoma. Next generation sequencing from recurrent tumor showed somatic mutations in p53, KDM6A, and PPP2R1A. Fourteen years from treatment, he has now developed a temporal lobe lesion. These cases are notable for prolonged survival despite widely metastatic disease and genomics predicting poor prognosis as well as metastatic disease disproportionate to CNS disease.
MBCL-43. RECURRENT MEDULLOBLASTOMA – LONG-TERM SURVIVAL WITH A “MEMMAT” BASED ANTIANGIOGENIC APPROACH
Authors: Slavc Irene , Peyrl Andreas , Gojo Johannes , Holm Stefan , Blomgren Klas , Sehested Astrid M , Leblond Pierre , Czech Thomas 
Published: December 2020

Abstract

INTRODUCTION
Patients with recurrent medulloblastoma have a poor prognosis with only around 8% of patients surviving at 5 years irrespective of salvage therapy used. We report on 29 patients from four institutions treated with a “MEMMAT” based antiangiogenic combination therapy.

PATIENTS AND METHODS
From 11/2006 to 06/2016, 29 patients were diagnosed with a recurrent medulloblastoma (19 first, 10 multiple recurrences). Median age at start of antiangiogenic therapy was 10 years (range 1–27). Subgroup of medulloblastoma was available in 18 patients and was group 3 or 4 in all except two (one WNT, one SHH-infant). For their current relapse patients received an antiangiogenic combination therapy consisting of bevacizumab, thalidomide, celecoxib, fenofibrate, and etoposide, alternating with cyclophosphamide and augmented with intraventricular therapy (etoposide and liposomal cytarabine).

RESULTS
As of 01/2020, 8/29 patients are alive at a median of 44 months after recurrence. 6/8 surviving patients are currently in CCR between 66 and 134 months after recurrence that prompted MEMMAT therapy. Two patients are again in remission after intercurrent relapses 105 and 102 months after first starting MEMMAT therapy. Five patients died of another cause (accident, leukemia, septicemia). OS (median 44 months) was 44±10% at 5 years and 39±10% at 10 years, PFS was 33±10% at 5 years and 28 ±9% at 10 years. Therapy was well tolerated and toxicities were manageable.

CONCLUSION
Our results suggest that antiangiogenic metronomic chemotherapy has clinical activity in recurrent medulloblastoma. Further investigation with an international phase II study is ongoing (MEMMAT; ClinicalTrials.gov Identifier: NCT01356290).
MBCL-46. TREATMENT OF RECURRENT WINGLESS-ACTIVATED MEDULLOBLASTOMA (Wnt-MB) INCORPORATING MARROW-ABLATIVE THIOTEPA AND CARBOPLATIN CHEMOTHERAPY (HDCx) AND AUTOLOGOUS HEMATOPOIETIC PROGENITOR CELL RESCUE (AuHPCR): A DUAL REPORT
Authors: Harris Micah K , Funk Zachary N , Boué Daniel R , Pierson Christopher R , Jones Jeremy , Leonard Jeffrey , Abu-Arja Rolla , Auletta Jeffrey , Osorio Diana S , Shatara Margaret , Paul Stephan R , Finlay Jonathan L , AbdelBaki Mohamed S 
Published: December 2020

Abstract

BACKGROUND
Wnt-MB infers an excellent prognosis, and metastatic disease is rare. However, specific treatment strategies and patterns of failure for patients with recurrent Wnt-MB are unknown. We report two cases of recurrent beta-catenin nucleopositive Wnt-MBs treated with an irradiation-sparing strategy, incorporating HDCx/AuHPCR. PATIENT 1: A nine-year-old female experienced local recurrence of a non-metastatic Wnt-MB nine months after gross total resection (GTR) followed by 18Gy craniospinal irradiation (CSI) with primary site boost to 54Gy, accompanied by weekly vincristine, followed by a maintenance regimen of nine cycles of cisplatin/lomustine/vincristine alternating with cyclophosphamide/vincristine every third cycle. GTR of the relapsed tumor was followed by three cycles of HDCx/AuHPCR. She is disease-free for over three years following relapse treatment. PATIENT 2: A 17-year-old male initially underwent GTR, followed by 23.4Gy CSI with 54Gy posterior fossa boost with concomitant weekly vincristine, followed by a maintenance regimen that included nine alternating cycles of vincristine/lomustine/cisplatin and cyclophosphamide/vincristine. Isolated right frontal horn metastatic recurrence developed 19 months post-treatment; three cycles of irinotecan/temozolomide/bevacizumab and gamma-knife radiosurgery produced complete response. A second isolated metastatic recurrence within the left frontal horn occurred 13 months post-treatment, which was treated with two cycles of cyclophosphamide/etoposide followed by two cycles of HDCx/AuHPCR. MRI of the brain showed no residual tumor one month post-treatment. He currently awaits follow-up stereotactic radiosurgery.

CONCLUSION
Patients with recurrent Wnt-MB may be treated with curative intent using a multi-disciplinary approach that includes HDCx/AuHPCR, and minimization or avoidance of re-irradiation.
MBRS-02. BET BROMODOMAIN PROTEIN-KINASE INHIBITOR COMBINATIONS FOR THE TREATMENT OF MEDULLOBLASTOMA
Authors: Ayad Nagi , Suter Robert , Robbins David , Roussel Martine 
Published: December 2020

Abstract
Recent sequencing studies have implicated many epigenetic regulators in medulloblastoma. The epigenetic reader protein Brd4 has been implicated in various cancers including medulloblastoma. Brd4 controls expression of the medulloblastoma essential genes MYC in G3 medulloblastomas, which have poor prognosis as well as GLI1 and GLI2 levels in Sonic hedgehog (SHH) driven medulloblastomas, which have intermediate prognosis. Highly selective Brd4 inhibitors have been developed that reduce MYC, GLI1 and GLI2 levels. These inhibitors have gone into clinical trials for multiple cancer indications including medulloblastoma. However, resistance is common for Brd4 inhibitors warranting combination therapies for improved clinical outcome. We have developed a computational pipeline termed SynergySeq that predicts patient specific combinations of Brd4 inhibitors along with kinase inhibitors. We demonstrate that Brd4-kinase inhibitors robustly reduce proliferation of Shh and MYC driven medulloblastoma cells. Improved efficacy is related to dampening the adaptive kinome reprogramming response that occurs after Brd4 inhibition. Our findings suggest that SynergySeq can be utilized to inform patient selection for clinical trials utilizing Brd4 inhibitors in medulloblastoma and other brain tumors.