bluuebunny/crossref_metadata_2025_split huggingface dataset:
MODL-29. EVALUATING TUMOR-IMMUNE INTERACTIONS IN MOUSE MODELS OF DIFFUSE INTRINSIC PONTINE GLIOMA
Authors: Furnish Robin , Bear Heather , Wei Xin , Phoenix Timothy 
Published: December 2020

Abstract

BACKGROUND
While adult gliomas show some level of immune cell infiltration, diffuse intrinsic pontine glioma (DIPG) is characterized as having an “immune cold” state. We have developed new immunocompetent mouse models of DIPG. These models faithfully recapitulate the pathological hallmarks of DIPG and provides a unique platform to investigate immune modulatory therapies and potential therapeutic benefits of check point inhibitor combination therapies.

METHODS
To evaluate the effects of CDK4/6 inhibition (CDK4/6i) on cell proliferation and immune interactions we performed a series of in vitro and in vivo studies using DIPG mouse models. In vitro assays included dose response curves, transcriptional profiling, and MHC1 expression. In vivo preclinical studies treated mouse models with CDK4/6i with or without immune check-point inhibitors (ICI). We also examined other candidate immune modulatory therapies in vitro.

RESULTS
CDK4/6i (Abemeciclib) reduced proliferation of DIPG cells derived from mouse models, and displayed a modest increase in immune activation by MHC1 expression and transcriptome. Pilot in vivo preclinical studies did not show any significant changes in DIPG proliferation or immune changes with CDK4/6i treatment, ICI treatment, or the combination of CDK4/6i + ICI. In vitro testing of other immune-modulatory drugs identified additional candidates that can be tested in vivo.

CONCLUSION
CDK4/6i displayed in vitro action, but lacked efficacy in DIPG mouse models in vivo. Further use of spontaneous DIPG mouse models will provide a rapid preclinical platform to evaluate in vivo tumor-immune interactions, drug efficacy, and mechanisms of resistance.
MODL-31. RADIATION-DERIVED TREATMENT-RESISTANT PDX AND CELL CULTURE MODELS RECAPITULATE THE CHARACTERISTICS OF MATCHED PRIMARY/RECURRENT PEDIATRIC HIGH-GRADE GLIOMA
Authors: Knox Aaron J , Flannery Patrick , Zukosky Anjali , DeSisto John , Sanford Bridget , van Court Benjamin , Donson Andrew , Lemma Rakeb , Chatwin Hannah , Karam Sana D , Vibhakar Rajeev , Jones Ken , Green Adam L 
Published: December 2020

Abstract

BACKGROUND
Pediatric high-grade glioma (pHGG) is the most common cause of childhood cancer death. Recurrence after therapy is a major challenge, since recurrent pHGG proliferates aggressively and resists therapy. We developed and validated preclinical models of matched primary and recurrent tumors, providing a method to study recurrence and potential therapies.

METHODS
We irradiated H3K27M thalamic pHGG cells (BT245) (8 Gy/week,2Gy fractions x3 weeks) and propagated the surviving cells (BT245R). We developed a murine recurrence model by orthotopically implanting BT245 cells, irradiating the resultant tumors (4 Gy/day x2d) and propagating irradiated (BT245RM) or control (BT245CM) tumor cells at endpoint. We performed phenotypic analyses, RNA-Seq, and drug testing.

RESULTS
BT245R cells were more stemlike than BT245, with an 8-fold greater rate of neurosphere formation (p&lt;0.03). Geneset enrichment analysis showed similar molecular changes in BT245RM cells and primary/recurrent H3K27M pHGG patient sample pair, including relaxation of the G2/M cell cycle checkpoint (Hallmark_G2M_Checkpoint: BT245RM NES=-5.95, FDR=0.0; patient NES=-5.86, FDR=0.0), downregulation of MYC targets (Hallmark_MYC_Targets_V1: BT245RM NES=-7.43, FDR=0.0; patient NES=-5.86, FDR=0.0), and decreased differentiation (Go_Regulation_of_Stem_Cell_Differentiation: BT245RM NES=-3.35, FDR=0.0; patient NES=-3.15, FDR=0.0). Enrichment of the protein_kinase_C_signaling in BT245RM (NES=2.18,FDR=0.03) suggested response to MAPK pathway inhibition. BT245R cells were twice as sensitive as BT245 cells to the MEK inhibitor trametinib (p&lt;0.05).

CONCLUSIONS
Our neurosphere and murine orthotopic patient-derived xenograft models recapitulate gene expression changes of matched primary/recurrent pHGG. RNA-Seq analysis validated the model against patient samples and identified trametinib as potentially effective in recurrent pHGG.
NFB-02. TREATMENT OF PAIN AND TUMOR GROWTH IN NF2
Authors: Hemenway Molly , Nellan Anan , McMahon Kate , Foreman Nicholas , Reddy Kartik , Nellan Anan , Suttman Alexandra 
Published: December 2020

Abstract

BACKGROUND
Neurofibromatosis Type 2 (NF2) is an autosomal dominant disorder characterized by multiple nervous system tumors. Chronic pain affects the majority of patients with NF2 and is the primary factor that contributes to decreased quality of life. There are limited therapies that effectively reduce pain in NF2, but intravenous (IV) bevacizumab has been reported to provide significant relief to patients suffering from debilitating pain.

CASE STUDY
James is a 24-year-old who initially presented with manifestations of NF2 at age 10, and by 15 years old had developed daily pain affecting his neck, back, and lower extremity. He has multiple CNS schwannomas, meningiomas, neurofibromas, and meets clinical NF2 criteria. While genetic testing did not reveal a mutation in his gDNA, low level skipping of exon 4 via RNA supports (likely mosaic) NF2. James’s pain was poorly controlled with multiple oral medications, including opioids. James started IV bevacizumab at age 16 that improved his pain. He was critically dependent on bevacizumab for pain control and required continuous IV pain medication when bevacizumab was held for a surgical procedure. Following five years of bevacizumab he developed worsening toxicities including hypertension, proteinuria, and elevated hemoglobin. James transitioned to therapy with trametinib, a MEK inhibitor, and was able to wean off bevacizumab six months later. Treatment of NF2 related pain with trametinib instead of bevacizumab has improved his QOL with decreased medical visits, improved pain management, and decreased side effects. FUTURE IMPLICATIONS: Treatment of NF2 tumor related pain can be managed with MEK inhibitors.
NFB-09. ENROLLMENT AND CLINICAL CHARACTERISTICS OF NEWLY DIAGNOSED, NEUROFIBROMATOSIS TYPE 1 ASSOCIATED OPTIC PATHWAY GLIOMA (NF1-OPG): PRELIMINARY RESULTS FROM AN INTERNATIONAL MULTI-CENTER NATURAL HISTORY STUDY
Authors: Fisher Michael J , Liu Grant T , Ferner Rosalie E , Gutmann David H , Listernick Robert , de Blank Peter , Zeid Janice , Ullrich Nicole J , Heidary Gena , Bornhorst Miriam , Stasheff Steven F , Rosser Tena , Borchert Mark , Ardern-Holmes Simone , Flaherty Maree , Hummel Trent R , Motley W Walker , Bielamowicz Kevin , Phillips Paul H , Bouffet Eric , Reginald Arun , Wolf David S , Peragallo Jason , Van Mater David , El-Dairi Mays , Sato Aimee , Tarczy-Hornoch Kristina , Klesse Laura , Hogan Nick , Foreman Nick , McCourt Emily , Allen Jeffrey , Ranka Milan , Campen Cynthia , Beres Shannon , Moertel Christopher , Areaux Ray , Stearns Duncan , Orge Faruk , Crawford John , O’Halloran Henry , Brodsky Michael , Esbenshade Adam J , Donahue Sean , Cutter Gary , Avery Robert A 
Published: December 2020

Abstract

INTRODUCTION
Because treatment and clinical management decisions for children with NF1-OPG remain challenging, we sought to establish evidence-based guidelines. We prospectively enrolled children with newly-diagnosed NF1-OPGs, and gathered standardized clinical neuro-oncology and ophthalmology assessments.

METHODS
Only children with NF1 and newly diagnosed OPGs, confirmed by central review, were eligible. Indications for obtaining the initial MRI, as well as factors associated with the decision to treat with chemotherapy or observe without treatment, were obtained. Quantitative visual acuity (VA), other ophthalmic features, and imaging were captured at standard time points. Goal enrollment is 250 subjects.

RESULTS
One-hundred thirty-three children (52% female) from 20 institutions met inclusion criteria, and were included in this preliminary analysis. Eighty-six percent of subjects were able to perform quantitative VA testing at enrollment. The most common reasons for the diagnostic MRI included screening related to NF1 diagnosis (36.8%), ophthalmologic concerns (29.3%), and non-ophthalmologic concerns (24.8%), such as headache. To date, twenty subjects have initiated treatment with chemotherapy, twelve (9%) at the time of the initial OPG diagnosis. Median age at OPG diagnosis was 3.1 years. Age and sex distribution were similar in subjects immediately entering the observation and treatment arms (median age 3.0 versus 3.5 years, respectively).

CONCLUSION
Most children with NF1-OPGs are observed at time of their initial OPG diagnosis, rather than treated. Importantly, a large proportion of children are able to complete quantitative VA testing at enrollment. Once enrollment is complete, these data will help to establish evidence-based guidelines for clinical management of NF1-OPGs.
NURS-04. COMBINATION OF NEURO-ONCOLOGY AND DERMATOLOGY CLINICS IMPROVE THE MANAGEMENT AND KNOWLEDGE OF SKIN-RELATED TOXICITIES WITH MEK AND BRAF TARGETED THERAPY
Authors: McKeown Tara , Lara-Corrales Irene , Cote Andrea 
Published: December 2020

Abstract

BACKGROUND
The recent advancement in treating pediatric low grade glioma has led to upfront use of MEK and BRAF (MAPK) inhibitor therapy. At the Hospital for Sick Children we are the National leaders in treating pediatric oncology diagnosis with MAPK therapies. DESIGN: After treating several patients on MAPK inhibitors with various degrees of skin toxicity, we found we had poor and inconsistent access to dermatology services and as oncology practitioners had limited front-line knowledge about skin management. It was determined that a more formalized expertise and time with dermatology was needed. In 2018, in combination with the dermatology team, our new agents and innovative therapy and the nursing team we collaborated to develop a combined oncology and dermatology clinic. This clinic occurs twice a month to give our families and oncology teams better front-line access to dermatology knowledge and care.

RESULTS
The dermatology and oncology team have collaborated to provide information sessions for the oncology medical team about current research, skin grading and education. This combined approach has allowed us to ensure that each new family starting MAPK inhibitor therapy undergoes a baseline skin assessment, education on prophylactic skin measures and easier access to dermatology within their oncology clinic. We are also developing guidelines to consistently treat common skin related toxicities.

CONCLUSION
The early involvement of the dermatology clinic and increase knowledge with the nursing and medical team has allowed our families to gain confidence in managing skin related complication and reducing the need to hold targeted therapies as a result of dermatological toxicity.
NURS-06. NURSING PROFESSIONALS AND THEIR AID IN RESEARCH BIOBANKING
Authors: Hancock Lauren , Kambhampati Madhuri 
Published: December 2020

Abstract
Nursing teams play an integral role in the care of patients with brain tumors; however nurses do not often see themselves as essential contributors to translational research. Recent development of nurse-researcher relationships and involvement of the multidisciplinary team have led to successful biobanking strategies. Though there are challenges associated with fostering these relationships, their vital role has significantly enhanced participant recruitment and sample collection at one large urban Children’s Hospital. Researchers at the institution have established a biobank to collect samples from pediatric brain tumor patients at diagnosis, during therapy, and post mortem using conventional methods. However, a collaborative environment between nursing and research teams greatly enhanced the growth of the biobank. We have increased patient recruitment by more than 50% in the past four years and supported different types of specimen collection. Our success entails: 1) development of nurse-researcher relationships, 2) an efficient consent process, 3) streamlined sample collection, and 4) appreciation of the vital role of the nursing team in clinical data collection pertinent to molecular analysis. Additionally, the support of nursing is valuable during post mortem consents and provides emotional support to the family to fulfil their wish to donate. Nurses play a major role in coordination of the post-mortem donation process, and assist in the formation of partnerships within the community to promote this opportunity to families. As biobanking continues to be an important part of bench research, all institutions should recognize and support the vital role that nurses can have in enhancing this endeavor.
NURS-12. MAKING SURVIVORS HEALTHIER: A MULTIDISCIPLINARY APPROACH TO HYPOTHALAMIC OBESITY
Authors: Hemenway Molly , Dorris Kathleen , Rydin Amy , Inge Thomas , Kelsey Megan , Hankinson Todd , Paul Suzanne , Haemer Matthew , Moore Jaime 
Published: December 2020

Abstract

BACKGROUND
Pediatric survivors of hypothalamic/suprasellar tumors have significant morbidities that greatly impact their quality of life. Management of hypothalamic obesity has traditionally fallen between multiple subspecialties without a timely and comprehensive approach.

METHODS
A multidisciplinary group of key players from neuro-oncology, endocrinology, nutrition, neurosurgery, and bariatric surgery were identified. Through this collaboration, a clinical algorithm for early identification of and intervention for hypothalamic obesity was developed. The goal of the quality improvement process is to increase the number of encounters with a registered dietitian (RD) with earlier and more consistent referrals to a specialized, multidisciplinary weight management program [Lifestyle Medicine; (LM)] for counseling and pharmacologic interventions. Indications for referral to LM were BMI &gt;95th percentile, crossing &gt;2 BMI percentiles on growth curve and/or hyperphagia symptoms. A retrospective review of pediatric patients who have suprasellar/ hypothalamic tumors was also conducted. Data collected included demographics, tumor type, BMI, RD visit, and LM clinic referral/visit.

RESULTS
Fifty patients were identified for analysis six months following clinical algorithm institution. Thirty-three (66%) patients had craniopharyngioma, 15 (30%) had low-grade gliomas, and two (4%) had germ cell tumors. Thirty-three (66%) patients were noted to be obese (defined as BMI &gt;95th percentile) at review. The median BMI of the entire cohort was 93rd (range, 1st-137th) percentile. Thirty-four (68%) patients had been seen by an RD. Twenty-seven (82%) of the obese patients had been referred to LM.

CONCLUSIONS
The development and implementation of the process for hypothalamic obesity prevention and intervention will be discussed.
OTHR-12. ANEURYSMAL BONE CYST RESEMBLING A POSTERIOR FOSSA TUMOR
Authors: Navarro Luis Angel Arredondo , Campo Regina Malinali Navarro Martin Del , Livier Gutierrez Oliva Lorelay , Mercado Valeria Estefania Aguilar , Luis Juan , Mancilla Soto 
Published: December 2020

Abstract
We presented the case of a 6-year-old boy who was seen in the emergency room because of signs of intracranial hypertension and left cerebellar syndrome. The CT scan revealed a heterogeneous lesion within the left hemisphere displacing the fourth ventricle and eroding the occipital bone. The MRI showed the same heterogeneous lesion majorly cystic, involving the bone and displacing the left cerebellar hemisphere. A minor hydrocephalus was evident in both studies. A suboccipital craniectomy was done and a cystic epidural tumor remodeling and eroding the bone was noted. The histopathological diagnosis corresponded to an aneurysmal bone cyst. Aneurysmal bone cyst is a rare benign tumor accounting for 3–6 % of tumors of the cranial base. We discuss the unusual location of the lesion.
PATH-05. A CASE OF PILOCYTIC ASTROCYTOMA HARBORING THE FGFR1 GENE MUTATION WITH A PREDOMINANT OLIGODENDROGLIOMA-LIKE COMPONENT
Authors: Sasaki Nobuyoshi , Chiba Tomohiro , Saito Kuniaki , Kobayashi Keiichi , Shiokawa Yoshiaki , Shibahara Junji , Nagane Motoo 
Published: December 2020

Abstract
Pilocytic astrocytomas rarely present with oligodendroglioma-like morphological features, which gives rise to a diagnostic challenge. In this report we present a case of pilocytic astrocytoma harboring the FGFR1 mutation, accompanied with a predominant oligodendroglioma-like component, thus initially diagnosed as oligodendroglioma. A 14-year-old female presented with syncope and simple partial seizure involving her right upper limb. Contrast-enhanced MRI revealed an enhancing lesion with substantial cystic portion and perifocal edema in the left parietal lobe. Open surgery was performed and a gross total resection of the tumor was achieved. On initial histopathological diagnosis, tumor cells with monotonous round nuclei and perinuclear halo predominated with branching capillaries, which were strongly suggestive for oligodendroglioma. Immunohistochemically, IDH1 R132H was negative, and Ki-67 index was around 5%. The patient was thus initially diagnosed as oligodendroglioma, WHO grade II, based on the 2007 WHO classification criteria. However, histopathological re-review revealed a minor astrocytic component with Rosenthal fibers and rare eosinophilic granular bodies, thus the diagnosis was changed as pilocytic astrocytoma. FGFR1 K654E mutation was confirmed by Sanger sequencing. Although she postoperatively developed mild sensory disturbance in her right hands, finger agnosia, and left-right disorientation, her symptoms had gradually improved, and she was discharged on day 17 with a Karnofsky performance status (KPS) of 90 and no cognitive decline. Without any adjuvant therapies, she has remained recurrence-free for 85 months. While the diagnosis of pilocytic astrocytoma with predominant oligodendroglioma-like component can be challenging, analysis of IDH1 and FGFR1 mutations can be beneficial in certain cases.
PATH-10. PROGNOSTIC RELEVANT IMMUNOPHENOTYPES OF PEDIATRIC HIGH-GRADE NON-BRAINSTEM GLIOMAS
Authors: Mikhaleuskaya Taisiya , Konoplya Natalya , Valochnik Alena 
Published: December 2020

Abstract
Pediatric diffuse astrocytomas comprise a wide range of malignancies with variable prognosis. The 4th grading system used now not always correctly characterizes the biological behavior of these tumors. We collected 24 pediatric supratentorial non-brainstem high grade glioma cases. Patient age ranged from 1 to 18 years old (median 11y). Main tumor locations were as follows: parietal lobe 8 cases; temporal lobe, 10 cases; frontal lobe, 3 cases; occipital lobe 3 cases. Eight of them were totally removed. All patients were treated with standard CT and RT. The main objective was to assess the prognostic impact of histopathological and molecular criteria on progression-free(PFS) and overall survival (OS) of high grade gliomas. The following criteria were analyzed: IDH1 R132H, BRAF V600E expression, ALT-phenotype, CDKN2A deletion, 1p/19q co-deletion, glial and neuronal markers expression. RESULTS: IDHR132H mutation was identified in 3 cases. 4 cases carried BRAFV600E mutation with CDKN2A deletion and displayed PXA phenotype. 5 cases showed undifferentiated glial morphology and ALT–phenotype. Also there was a group of tumors without any of the above mentioned genetic changes. Interestingly 3 of them were post radiation tumors. Statistical analysis showed that low OS correlated with ALT-phenotype(p-0.015), absence of neuronal markers expression and absence of molecular changes (p-0.03). Mutation of IDH1R132H was a favorable prognostic factor as in the adult population. PFS was affected only by the presence of neuronal expression (p-0.015). Employing immunohistochemical analysis with surrogate molecular markers in complex with FISH can provide additional prognostic information in case of pediatric high grade gliomas.
PATH-24. MOLECULAR CLASSIFICATION OF HIGH RISK INFANT EMBRYONAL BRAIN TUMORS ENROLLED IN THE ACNS0334 TRIAL: A REPORT FROM THE CHILDREN’S ONCOLOGY GROUP
Authors: Li Bryan K , Burger Peter , Judkins Alexander R , Ho Ben L B , Kang Guolian , Gossett Jeffrey , Leary Sarah , Pollack Ian , Gajjar Amar , Fouladi Maryam , Kellie Stewart J , Mazewski Claire , Huang Annie 
Published: December 2020

Abstract
Young children with embryonal brain tumors including medulloblastoma (MB), supratentorial primitive neuro-ectodermal tumor, or pineoblastoma have historically been considered high-risk patients with poor outcomes despite the use of intensive radiation-sparing treatment. In the ACNS0334 phase III trial, 91 consented children &lt;36 months old with the above diagnoses were randomized to intensive induction chemotherapy with or without methotrexate followed by consolidation with stem cell rescue. Here we present the results of a centralized integrated molecular analysis including global methylation profiling (65/91), and whole exome sequencing of tumor (46/91) and germline (35/91) DNA. Unsupervised clustering analyses of methylation profiles using multiple orthogonal methods against a reference dataset of 1200 pediatric brain tumors, revealed known and new molecular entities. For tumors diagnosed as MB on central pathology review, 7.3% (3/41) had a non-MB molecular diagnosis (2 embryonal tumor with multiple rosettes/ETMR, 1 group MYC pineoblastoma), with the remainder as MB Group SHH (11/41), Group3 (25/41), and Group4 (2/41). Among histologic non-MBs, 3/24 (12.5%) were molecular entities not intended for trial inclusion (1 each for ATRT, pleomorphic xanthoastrocytoma, and high-grade glioma). ETMR, historically considered a rare entity, was molecularly identified in a significant proportion (14/65; 21.5%) of samples. Among MB-SHH, we detected deleterious PTCH1 mutations in 6/9 tumors but none among 5 germline samples tested; a germline SUFU frameshift mutation with tumor LOH was also observed in MB-SHH. Correlation of these and other molecular features to the parallel clinical analysis will yield important markers of risk stratification and predictors of treatment response.