bluuebunny/crossref_metadata_2025_split huggingface dataset:
INNV-04. A MULTI-INSTITUTIONAL CLINICAL AND MRI REPOSITORY OF NEUROFIBROMATOSIS TYPE 1-ASSOCIATED PERIPHERAL NERVE SHEATH TUMORS
Authors: Ly Ina , Hirbe Angela , Jordan Justin , Michaels Olivia , Kwon Daniel , Borcherding Dana , Srihari Divya , Dombi Eva , Widemann Brigitte , Pollard Kai , Pratilas Christine , Boswell Demetrius , de Blank Peter , Melecio-Vázquez Mairim , Chi Ping , Salamon Johannes , Mautner Viktor , Mulder Zachary , Steensma Matthew , Lee Shernine , Korf Bruce , Blakeley Jaishri , Plotkin Scott 
Published: November 2021

Abstract

BACKGROUND
Individuals with neurofibromatosis type 1 (NF1) frequently have peripheral nerve sheath tumors (PNST), including plexiform neurofibromas (PNF), atypical neurofibromas (ANF), and malignant peripheral nerve sheath tumors (MPNST). These tumors reflect a histologic spectrum from benign to malignant. Various clinical and MRI-based features are proposed as risk factors for MPNST development based on small single-institution studies. A major barrier to study these risk factors is collation and annotation of multi-center serial MRIs. To address this, we created a standardized database of clinical data and longitudinal MRIs from NF1-associated PNST from nine international NF1 referral centers.

METHODS
Clinical data from NF1 patients are collected in Research Electronic Data Capture databases housed at Massachusetts General Hospital and Washington University, including demographic information, genotype, disease course, treatment history, and survival. ANF and MPNST require histologic confirmation whereas a diagnosis of PNF can also be made based on clinical/radiographic stability. Longitudinal MRIs predating the histologic diagnosis are uploaded to a HIPAA-compliant cloud-based system.

RESULTS
Data from 200 patients (87 females, 113 males) with 217 tumors (75 PNF, 40 ANF, 102 MPNST) have been collected. 280 regional and 108 whole-body MRIs have been identified. Median age at the time of histologic diagnosis is 30 years (range 5-64). All tumors are histologically confirmed except for 6 PNF which remained stable over time. Median follow-up time is 32 months. Of 147 patients with available survival data, 32 (21.7%) have died from MPNST progression; estimated median overall survival is 20 months.

CONCLUSIONS
In this ongoing work, we have assembled one of the largest systematically annotated clinical and MRI repositories of NF1-associated PNST from pediatric and adult NF1 patients. The data will be accessible to outside researchers which will promote interdisciplinary and multi-center collaborations. Active efforts include the identification of radiomic MRI features to differentiate between PNF and MPNST.
INNV-21. COMPLETE RESPONSE TO ADJUVANT TEPOTINIB IN A PATIENT WITH NEWLY DIAGNOSED DISSEMINATED GLIOBLASTOMA (GBM) HARBORING MET AMPLIFICATION
Authors: Pham Lily , Gann Claudia , Schumacher Karl Maria , Vlassak Soetkin , Swanson Todd , Highsmith Kaitlyn , Ou Alexander , Clarke Nathan , Aaroe Ashley , Robell Lindsay , O'Brien Barbara , Nash Sebnem , DeGroot John , Majd Nazanin 
Published: November 2021

Abstract
MET oncogene encodes a receptor-tyrosine-kinase which drives cell proliferation, invasion and angiogenesis in a number of solid cancers including GBM where the incidence of MET amplification is 2-5%. Tepotinib is a highly selective blood-brain-barrier penetrant oral c-MET inhibitor recently FDA approved for MET-exon-14 altered non-small cell lung cancer (NSCLC). Here, we report complete radiographic response to tepotinib in a patient with newly-diagnosed disseminated GBM harboring MET amplification. A 29-years-old male presented with progressive headache. MRI brain showed a large heterogeneously enhancing intraventricular mass with epicenter in the right lateral ventricular trigone and enhancing nodules in bilateral cerebellum. MRI spine showed multifocal enhancement along the periphery of the cervicothoracic spinal cord and cauda equina concerning for leptomeningeal disease. He underwent right temporal lobectomy and subtotal resection of the mass. His KPS was 90 post-surgery due to dizziness. Pathology was consistent with GBM, IDH wild-type, MGMT-unmethylated and MET amplification at 7q31.2. He completed proton craniospinal irradiation at 3600cGy followed by boost to the tumor bed at 2400cGy without concurrent temozolomide (TMZ) due to the large radiation field. He completed two cycles of adjuvant TMZ which was put on hold due to myelosuppression. He subsequently started tepotinib monotherapy at 1000mg daily obtained on a compassionate IND. MRIs after one month of therapy showed resolution of areas of enhancement in the brain and spine. He had grade 1 creatinine elevation and abdominal discomfort and dose was reduced to 500mg daily after two cycles. Nineteen weeks after initiation of tepotinib, his complete response persists, and he remains clinically stable with mild chronic dizziness. Trials of targeted therapy in molecularly-unselected GBM have been largely disappointing, however, this case demonstrates the promise of targeting MET using tepotinib in GBM. A clinical trial of tepotinib in MET-amplified GBM and NSCLC brain metastasis is currently underway at MD Anderson.
INNV-26. NCI-CONNECT PROGRAM PROVIDES RESOURCES TO IMPROVE CARE FOR PEOPLE WITH RARE CENTRAL NERVOUS SYSTEM (CNS) TUMORS
Authors: Odom Kristin , Cordeiro Brittany , Wall Kathleen , Chambers Claudia , Mentges Kelly , Penas-Prado Marta , Wu Jing , Barnholtz-Sloan Jill , Kruchko Carol , Patrick Lorna , Saucedo Linda , Gilbert Mark , Armstrong Terri 
Published: November 2021

Abstract
The National Cancer Institute Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) program focuses on improving approaches to care and treatment for 12 rare CNS tumors, each with &lt; 2,000 diagnoses per year. To reach this rare population, the primary objective was to develop a website to share educational resources that provide patients direct access to clinical care and trials. METHODS: The NCI-CONNECT website uses the Drupal platform within NCI’s framework and the content is free to syndicate. A multidisciplinary team developed tumor-specific content in English and Spanish, clinical trial information, and survivorship resources using evidence-based sources. The Central Brain Tumor Registry of the United States provided statistics on incidence and prevalence of rare tumors. Population reach was calculated using Adobe Experience Cloud website analytics. NCI-CONNECT referrals and study participation data were collected prospectively. RESULTS: The English website launched in September 2018 and visits have increased 2,384%. The Spanish website launched in March 2020 and visits have increased 1,137%. From April 2020 to March 2021, top website page views by English page views / Spanish page views / people living with this disease include oligodendroglioma (43,859 / 8,241 / 11,757), ependymoma (31,579 / 12,684 / 13,294), meningioma (30,261 / 19,507 / 2,692), medulloblastoma (28,487 / 9,999 / 3,840), diffuse midline gliomas (23,064 / 3,851 / 6,033), and pineal region tumors (19,939 / 9,973 / 1,297). Referral rates and participation have accelerated – 45% of patients visiting the Neuro-Oncology Clinic at NIH have a rare CNS tumor and 409 patients enrolled in an NCI-CONNECT study. CONCLUSION: Patient-focused websites can provide guidance to those affected by rare cancers outside of in-person health care visits. The NCI-CONNECT website is an educational and clinical resource for patients and families affected by rare CNS tumors and was created to raise awareness and improve patient outcomes.
INNV-30. USE OF MULTIDISCIPLINARY TEAMS AND MULTIMEDIA APPROACHES TO DEVELOP AND DISSEMINATE SYMPTOM AND DISEASE EDUCATIONAL MATERIALS FOR RARE CENTRAL NERVOUS SYSTEM (CNS) TUMOR PATIENTS
Authors: Maher Molly , Odom Kristin , Acquaye Alvina , Celiku Orieta , Cordeiro Brittany , Gilbert Mark , Armstrong Terri 
Published: November 2021

Abstract

BACKGROUND
Primary CNS tumors represent less than 2% of all cancers, with the majority of patients receiving care outside of specialty centers. Patients are highly symptomatic while trying to navigate care for their rare disease and evidence-based tumor and symptom education is limited. Our primary objective was to create and disseminate patient-centered content utilizing multidisciplinary teams and health communication to improve access to content.

METHODS
The multidisciplinary team of neuro-oncology scientists and health care providers developed content from evidence-based sources. The team partnered with communication specialists to ensure health literacy and established outreach strategies for use on social media, e-newsletters, and web- and app-based programs. Web analytic tools assessed outreach and efficacy.

RESULTS
Educational content for 12 rare tumors and 6 self-care topics was created using evidence-based sources and multidisciplinary team review. Content was published on the National Cancer Institute Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) website and disseminated via multimedia platforms, including e-newsletters and social media (private Facebook group and Twitter). Since launching the website in September 2018, visits have increased 2,384%. The content was also shared directly to 6,156 newsletter subscribers, 4,897 Twitter followers with greater than 1 million impressions per year, 407 Facebook members, 9 non-profit advocacy partners, and thousands of attendees at more than 10 patient-focused neuro-oncology events. This outreach approach is now being replicated for symptom management content on the NCI-CONNECT website and a symptom tracking and self-care mobile application launching in 2021.

CONCLUSIONS
By marrying patient-centered health communication, education, and outreach, our team successfully created highly sought content that reflects the unique needs of CNS tumor patients and their families. This material can educate neuro-oncology patients on their specific tumor, promote self-care, facilitate symptom management, and empower families to advocate for their unique needs, reaching outside traditional health care systems.
PATH-22. GENETIC VARIATION BETWEEN IDH MUTANT AND IDH WILD-TYPE GLIOMA
Authors: Li shaoqun , Lai Mingyao , Zhou Jiangfen , Zhen junjie , Cai Linbo 
Published: November 2021

Abstract

OBJECTIVE
The prognosis of IDH mutant glioma was significantly different from that of IDH wild-type glioma. In order to explore the differences between them at the genetic level, we analyzed the genetic results of IDH mutant and IDH wild-type glioma.

METHODS
This study analyzed the clinical data and genetic results of 45 glioma patients from Jan. 2017 to Dec. 2019, exploring relevant prognostic indicators and the difference in genetic profile between IDH mutant glioma and IDH wild-type glioma.

RESULTS
45 patients were included in this study, including 15 IDH mutant glioma patients and 30 IDH wild-type glioma patients. Genetic analysis showed that there was no difference in tumor mutation burden (TMB) and microsatellite instability (MSI) between IDH mutant glioma and IDH wild-type glioma. But somatic mutation between IDH mutant and IDH wild-type glioma was different. The expressions of IDH1, CIC, SYNE1 and TP53 were different in the two groups, among which IDH1 and CIC were more significantly different. Copy number variations (CNV) was also different between IDH mutant glioma and IDH wild-type glioma. STIL occured more frequently in IDH wild-type gliomas. Genetic analysis also showed the difference in variant allel frequence (VAF). IDH mutant gliomas were more likely to be combined with ATRX and TP53 mutations, while IDH wild-type gliomas, in addition to the combination of TP53 mutations, often also combined with the mutations of NF1, BRAF and PTEN. In survival analysis, glioma with IDH mutation has a good prognosis, and IDH wild-type patients have a poor prognosis. In IDH wild-type patients, patients with PTEN mutation have a worse prognosis.

CONCLUSION
There is an obvious genetic difference between IDH mutation and IDH wild-type glioma, and PTEN mutation is a poor prognostic factor for IDH wild-type patients.
PATH-33. MOLECULAR TYPING AND MUTATION SPECTRUM OF CHINESE CHILDREN WITH MEDULLOBLASTOMA WERE IDENTIFIED BY NEXT-GENERATION SEQUENCING
Authors: Li Juan , Lai Mingyao , Hu Qingjun , Ai Ruyu , Cai Linbo 
Published: November 2021

Abstract
There are few reports on molecular typing and mutation spectrum of Chinese children with medulloblastoma. Here, we aimed to update the clinical manifestations and MB transcriptional mutation spectrum in Chinese Mb patients. Medical records of 59 Mb patients were reviewed. Genomic DNA was extracted from pathological tissues of children. Mutation analysis of whole coding regions, promoter regions and flanking splice sites in whole genome sequencing was performed. Nine cases (15%)with WNT subtype: CTNNB1 mutation was found in all specimens, and TP53 mutation was found in 33.3%. DDX3X mutation occurred in 33.3%. 33.3% had SMARCA4 mutations. Chr6 - associated large fragment deletion occurred in 88.9s. Comparison results between 19 cases (32%) with SHH data and previous studies: The proportion of SHH-TP53 mutants was11% ( 2/19).The proportion of SHH-TP53 wild-type was 89%.The prognosis of the mutated SHH-TP53 was worse than that of the wild-type SHH-TP53, and patient follow-up information could be integrated for comparison. Secondly, PTCH1 is more prevalent in patients with SHH (16%). The DDX3X mutation proportion was 11%. The mutation ratio of Gli2 amplification5%.The mutation ratio of MYCN amplification was 5%.Comparison results of 3 cases with G3 subtype data and previous studies: Variations mainly occur at the chromosomal level. Only one G3 patient had a genetic mutation (TP53 mutation). The proportion of Chr17q+ was 33.3%. CHR7 + proportion was 33.3%. The incidence rates of CHR10Q and CHR11Q were 66.7%.No MYC amplification was found. For 28 cases with G4 subtype: Chr17q +, Chr7 +, Chr18 +, and Chr8 - are the major chromosomal mutations. The incidence rate of CHR17Q + was 61%, and CHR7 + was 61%. CHR8- occurred in 11%. The above results are consistent with previous reports. The Chinese population and other population have similar molecular genotyping gene variation map on medulloblastoma.
PATH-38. APC MUTATION AS A DRIVER ONCOGENE IN NON-CTNNB1 MUTANT ADAMANTINOMATOUS CRANIOPHARYNGIOMAS
Authors: Hong Christopher , Erson-Omay Zeynep , Omay S Bulent 
Published: November 2021

Abstract
Craniopharyngiomas arise from the embryonic remnants of Rathke’s pouch in the craniopharyngeal duct. Their invasive capacity and geographic proximity to the optic apparatus, pituitary gland and stalk, third ventricle, and the hypothalamus can cause progressive visual, hormonal, and neurological deficits and transform these lesions into behaviorally malignant tumors. The classic subtypes of craniopharyngiomas, adamantinomatous and papillary, have conventionally been approached similarly in regards to therapeutic strategies. However, recent exome sequencing studies have revealed mutually exclusive pathways for their genetic origins. Recurrent mutations in BRAF (V600E), a regulator of MAP kinase/ERK signaling pathway have been observed in 95% of papillary craniopharyngiomas and may be amenable to targeted therapies with BRAF inhibitors. However, CTNNB1 mutations are observed in only 75%–96% of adamantinomatous craniopharyngiomas, revealing a gap in the classic genetic-histological correlation. We describe a 74-year-old male who underwent resection of a craniopharyngioma with suprasellar and third ventricular involvement. The pathology demonstrated adamantinomatous craniopharyngioma with aberrant nuclear beta-catenin activity on immunohistochemistry. Whole-exome sequencing, performed in accordance with an institutional review board-approved protocol on the tumor and blood, revealed wildtype CTNNB1 but notably two somatic stop-codon mutations in APC (rs786201856:c.C793T:p.R265X and rs587779780:c.1159T:p.R387X), considered pathogenic variants in other reported cancer types. Loss of APC leads to constitutive activation of the Wnt signaling pathway, similar to the observed downstream effects of activating CTNNB1 mutations in adamantinomatous craniopharyngioma. Our case suggests that craniopharyngiomas may arise from somatic loss of APC, which previously was only described in a handful of individuals with familial adenomatous polyposis, harboring germline APC mutations. This report adds new insight into the pathogenesis of adamantinomatous craniopharyngiomas, particularly those that are otherwise wildtype for CTNNB1. Based on accumulating evidence, we propose that along with BRAF and CTNNB1, APC should also be routinely checked in cranipharyngiomas, especially if the former two have been negative.
NIMG-06. CHARACTERIZATION OF LONG-TERM METABOLIC CHANGES OF IRRADIATED BRAIN METASTASES USING SERIAL DYNAMIC FET PET IMAGING
Authors: Galldiks Norbert , Stoffels Gabriele , Werner Jan , Bauer Elena , Baues Christian , Celik Eren , Ruge Maximilian , Fink Gereon , Langen Karl-Josef , Lohmann Philipp 
Published: November 2021

Abstract

BACKGROUND
In the present study, we characterized the long-term metabolic changes of brain metastases irradiated with stereotactic radiosurgery (SRS) by sequential dynamic PET imaging using the radiolabeled amino acid O-(2-[18F]-fluoroethyl)-L-tyrosine (FET). We hypothesized that this approach is of considerable clinical value to diagnose delayed radiation-induced changes.

PATIENTS AND METHODS
From 2010-2021, we retrospectively identified patients with brain metastases from solid extracranial primary tumors who (i) were treated with SRS with or without concurrent immunotherapy using checkpoint inhibitors, (ii) had equivocal or progressive MRI findings after SRS, and (iii) subsequently underwent at least two additional dynamic FET PET scans during follow-up for long-term evaluation. Mean tumor-to-brain ratios (TBR) and the dynamic FET PET parameter time-to-peak were obtained. Diagnostic performances were calculated using receiver operating characteristic curve analyses. Diagnoses were confirmed histologically or clinicoradiologically.

RESULTS
We identified 36 patients with 98 FET PET scans (median number, 3; range, 2-6). Concurrent to SRS, 8 patients (22%) were treated with checkpoint inhibitors. Following SRS, suspicious MRI findings occurred after a median time of 11 months (range, 2-64 months). Subsequently, FET PET scans were acquired over a median period of 13 months (range, 5-60 months). The overall median follow-up time was 26 months (range, 8-101 months). Twenty-one patients (58%) had delayed radiation-induced changes. TBRs calculated from the last available FET PET scan showed the highest accuracy (92%) to identify delayed radiation-induced changes (threshold, 1.95; P&lt; 0.001).

CONCLUSIONS
FET PET has a high diagnostic accuracy for characterizing the long-term changes of irradiated brain metastases.
NIMG-21. VARIABLE RESOLUTION HYPERPOLARIZED [2-13C]PYRUVATE MRI IN HEALTHY VOLUNTEERS AND PATIENTS WITH IDH-MUTANT GLIOMA
Authors: Vaziri Sana , Kim Yaewon , Autry Adam , Chen Hsin-Yu , Gordon Jeremy , LaFontaine Marisa , Hu Jasmine , Lupo Janine , Clarke Jennifer , Villanueva-Meyer Javier , Oberheim-Bush Nancy Ann , Chang Susan , Xu Duan , Larson Peder , Vigneron Daniel , Li Yan 
Published: November 2021

Abstract

INTRODUCTION
Mutations in isocitrate dehydrogenase (IDH) have been investigated as a prognostic biomarker in glioma. The presence of the IDH mutation (IDHm) is associated with 2-hydroxyglutarate (2HG) production and inhibition of glutamate synthesis (McBrayer, Cell 2018). Hyperpolarized carbon-13 (HP-13C) MRI enables dynamic measurements of in-vivo metabolism using a [2-13C]pyruvate labeled probe that undergoes conversion to [2-13C]lactate and [5-13C]glutamate. Here, we present HP [2-13C]pyruvate data from healthy volunteers and patients with IDHm diffuse glioma. Due to its intrinsic low signal-to-noise ratio (SNR), we demonstrate the ability of post-processing denoising to improve its utility and aid in detection of metabolic changes associated with IDHm.

METHODS
Dynamic HP 13C data were acquired following intravenous injection of [2-13C]pyruvate from five healthy volunteers and one patient with IDHm grade III astrocytoma. A novel multi-resolution frequency specific multislice EPI sequence was used to obtain [2-13C]pyruvate, [5-13C]glutamate, and downfield and upfield [2-13C]lactate signals (3s temporal resolution, pyruvate/lactate/glutamate spatial resolutions = 0.75x0.75cm2/ 2.25x2.25cm2/ 2.25x2.25cm2, 5 slices 3cm thick). Following phase correction, patch-based tensor decomposition denoising was applied to metabolite images. Metabolite differences between normal-appearing white matter (NAWM) and T2 lesion were examined for the patient data.

RESULTS
HP [2-13C]pyruvate imaging is able to simultaneously probe glycolytic ([2-13C]lactate) and oxidative ([5-13C]glutamate) metabolism. Denoised pyruvate/lactate/glutamate signals achieved a 4-9/3-6/3-7 fold increase in SNR. T2 lesion exhibited decreased glutamate-to-pyruvate and glutamate-to-lactate AUC ratios versus contralateral NAWM (p&lt; 0.018, p &lt; 1.5e-5), consistent with IDH mutant status.

CONCLUSION
We successfully demonstrated the feasibility of applying variable resolution HP [2-13C]pyruvate metabolic imaging to detect IDHm specific metabolism. This technique addresses a major hurdle in HP 13C MRI by improving SNR while permitting robust metabolism quantification. Future studies will optimize methods for acquiring and processing data to evaluate further data acquired from IDHm glioma patients. Supported by NIH T32 CA151022, P01 CA118816, and NICO.