bluuebunny/crossref_metadata_2025_split huggingface dataset:
INNV-24. METASTATIC HEMANGIOPERICYTOMA TO THE LIVER: DEFINING THE IMPORTANCE OF NAB-STAT2 FUSION
Authors: Sefler Megan , Khagi Simon 
Published: November 2021

Abstract

BACKGROUND
Meningeal hemangiopericytoma (HPC) is a rare and aggressive vascular tumor which typically occurs in younger adults and has a tendency for local recurrence with delayed metastases outside the CNS. HPC is considered a variant of solitary fibrous tumor (SFT), and is associated with the presence of the fusion oncoprotein NAB2-STAT6. This fusion results in over-expression of the EGR1 gene and results in tumorigenesis.

CASE REPORT
We present a case of a 49 y/o female with a remote history of left occipital lobe HPC, initially treated with resection and radiotherapy in 2007, who presented with symptoms of right upper quadrant abdominal pain. She was found to have a hypervascular 7 cm mass in the right upper lobe of the liver on magnetic resonance imaging (MRI) studies and subsequently underwent hepatectomy for removal of the mass. Histopathological findings revealed metastatic HPC with features consistent with her primary meningeal tumor that was removed over 13 years agoearlier. Presence of the NAB2-STAT6 fusion was confirmed by targeted genomic analysis. MRI revealed a small focus of nodular enhancement abutting the confluence of the superior sagittal sinus and transverse sinus. This was considered her source of disease and possible dissemination. She was treated with stereotactic radiosurgery to target the lesion.

DISCUSSION
Given the rarity and often remote medical history of the primary intracranial HPC, this report suggests that 1) long term follow up of HPC is essential and 2) detection of the NAB2-STAT6 fusion can identify and confirm recurrent HPC at metastatic sites. In regards to the latter, distinguishing HPCs from other more benign spindle cell tumors that may mimic SFT (such as fibroblastic meningiomas) is also of therapeutic significance as HPCs typically require adjuvant treatment, (i.e. radiotherapy) as opposed to surgical resection alone.
INNV-28. POTENTIAL EFFECTIVE CONSOLIDATION THERAPY WITH SINGLE AGENT IBRUTINIB FOR A CASE WITH PRIMARY CNS LYMPHOMA AFTER INITIAL HD-MTX AND RITUXIMAB INDUCTION THERAPY
Authors: Du Steven , Ko Uvin , Bota Daniela , Kong Xiao-Tang 
Published: November 2021

Abstract

INTRODUCTION
Primary CNS Lymphoma (PCNSL) is a rare and aggressive cancer that originates from lymphocytes and develops in the central nervous system. Standard induction therapy involves high-dose methotrexate (HD-MTX)-based chemotherapy, which achieves complete or partial response in most PCNSL patients. However, there is no standard consolidation therapy. We report one case in which ibrutinib, a Bruton’s tyrosine kinase inhibitor, replaced low-dose WBRT as consolidation therapy after induction by HD-MTX and rituximab. Ibrutinib treatment yielded good tolerance and further resolution of small residue lymphoma.

CASE REPORT
The patient is a 77-year-old female who presented with slurred speech, right-sided weakness, and difficulty word-finding in early 2020. Brain MRI found multifocal lesions, and biopsy of the largest lesion near the left lateral ventricle revealed diffuse large B cell lymphoma. The patient began HD-MTX at 6 g/m2 for the first cycle of induction therapy. She continued HD-MTX every two weeks, but dosage was reduced every cycle due to worsening renal function. Ultimately, MTX was discontinued after 6 cycles. Brain MRI showed significant response after HD-MTX except for small residue lymphoma at the biopsy area. 2nd line regimen rituximab and temozolomide was given to complete induction. Brain MRI was stable, but the small enhancing residue lymphoma at left peri-ventricle area was persistent after the induction therapy (uCR). Ibrutinib as consolidation therapy began after discussion with the patient. The patient tolerated 560 mg ibrutinib for 6 cycles initially, then switched to a reduced dose of 420 mg for cycles 7 and 8 due to neutropenia. Brain MRIs have been stable with resolution of the small lymphoma residue after 6 cycles of ibrutinib. The patient continues ibrutinib for the goal of one year of consolidation therapy.

DISCUSSION
Our case highlights the potential of single-agent ibrutinib as consolidation therapy for PCNSL after HD-MTX and rituximab/temzolomide induction therapy.
INNV-29. BILATERAL PARIETAL LYMPHOMA LESIONS RESPONDED DIFFERENTLY TO HD-MTX AND RITUXIMAB/TEMOZOLOMIDE THERAPY
Authors: Kong Xiao-Tang , Du Steven , Choi Yoon Jae , Bota Daniela 
Published: November 2021

Abstract

INTRODUCTION
Primary CNS lymphoma is a rare aggressive hematological malignancy. Current chemotherapy for induction phase is HD-MTX single agent or HD-MTX based combination regimen. We report a rare case whose left and right parietal lymphoma lesions in the brain responded to different induction therapy regimens during the induction phase.

CASE REPORT
A 43-year-old female presented with seizure and her brain MRI showed bilateral parietal brain lesions in January of 2020. Biopsy and work-up revealed primary CNS diffuse large B-cell lymphoma (DLBCL). The patient underwent HD-MTX therapy. Brain MRI showed clear progression of left parietal lymphoma but stable right parietal lymphoma after two cycles of HD-MTX at 8 g/m2. The treatment was switched to a rituximab 750 mg/m2 weekly and temozolomide 150 mg/m2 daily one-week-on and one-week-off regimen. After 8 weeks, her brain MRI showed nearly complete response of her left parietal lymphoma to rituximab/temozolomide but progression of her right parietal lymphoma. She was switched back to HD-MTX and completed total 8 cycles. Her right parietal lymphoma lesion showed complete response to HD-MTX. The patient is doing well and has been off the treatment over the past 10 months and is waiting for consolidation therapy with autologous stem cell transplantation that has been postponed due to the COVID pandemic.

DISCUSSION
Our case highlights the very rare heterogenous feature of primary CNS lymphoma responding to different treatment regimen. Biopsy of bilateral heterogeneous lesions may be indicated to compare the different molecular features of the lymphoma to find underlying mechanism if they respond to treatment differently. Specific treatment regimen should be selected based on the responsiveness of CNS lymphoma lesions or combination therapy is selected to cover the heterogeneous susceptibility to chemotherapy regimens.
INNV-32. ACCESS TO SPECIALTY RADIATION CARE FOR PATIENTS WITH RESECTABLE BRAIN TUMORS
Authors: Choi Mehee , Martin Brian , Zabramski Joseph , Misell Lisa , Brachman David 
Published: November 2021

Abstract

INTRODUCTION
Many patients with brain tumors face challenges with access to care. For rural patients, prolonged travel times may limit access to appropriate radiotherapy. Radiation centers (RCs) offering specialized brain radiotherapy, e.g., stereotactic radiosurgery (SRS), are geographically limited. Brain brachytherapy at the time of resection offers an option for such patients, but technical challenges have limited the adoption. To address the limitations of traditional brachytherapy, a device with Cs-131 seeds embedded in a bioresorbable collagen tile (GammaTile (GT), GT Medical Technologies, Tempe, AZ) was developed. The device is FDA-cleared for permanent implantation at the time of resection for all recurrent intracranial tumors and newly diagnosed malignant intracranial neoplasms. To investigate if wider availability of this treatment could possibly lower the geographic barrier to access to care, we mapped the US population against existing RCs with brain tumor expertise and neurosurgery centers (NSCs) performing craniotomies.

METHODS
We analyzed 2018 CMS claims data using CPT codes for single- and multi-fraction SRS to identify RCs with brain tumor treatment expertise and mapped these against the population. Using similar methodology, using CPT codes for craniotomies, we identified NSCs, as any facility performing craniotomies is potentially eligible to implant the device.

RESULTS
135 RCs used CPT codes for SRS. 193-, 119-, 82-, and 52-million Americans lived &gt;30-, &gt;60-, &gt;90-, and &gt;120-minutes from one of these centers, respectively. 530 NSCs preform craniotomies, including ≥ 1 in every state, a 4-fold increase over the number of RCs offering SRS.

CONCLUSIONS
For many patients, substantial travel distances limit access to RCs with brain tumor treatment expertise. In contrast, the 530 craniotomy-performing NSCs have far greater geographic dispersion. The option of undergoing brain radiation with GT implantation at the time of brain tumor craniotomy brings treatment closer to millions, ensures compliance, and reduces additional travel for follow-up radiation treatment.
INNV-33. THE IMPACT OF COVID-19 ON NEURO-ONCOLOGY CLINICAL TRIALS DURING WAVE 1 AND WAVE 2 AT A FRONTLINE DETROIT HEALTH CARE SYSTEM
Authors: Alton Joshua , Griffin Carmen , Wigand Amanda , Winters Kenneth , Krozek Emily , Scarpace Lisa , Walbert Tobias , Snyder James 
Published: November 2021

Abstract
In the wake of the Coronavirus disease outbreak (COVID-19), clinical trial operations were significantly impacted following the shutdown of elective healthcare services and even emergency operations. When the pandemic hit Detroit, Michigan in March 2020, the Hermelin Brain Tumor Center (HBTC) at Henry Ford Health System was consumed in COVID-19 emergency care which affected patient enrollment, conduct of trial activities, therapeutic treatment, deviation from protocol requirements, and sponsor-study site contact. The first Metro-Detroit COVID-19 case was confirmed March 10th 2020. At that time there were 18 active brain tumor clinical trials (phase 1 - phase 3) providing anti-cancer therapies. Trial modifications included decentralized operations to buildings with clinic and radiology access away from inpatient COVID-19 care, utilization of telemedicine for non-essential visits, shipping of investigational products to patient home, and in some cases utilization of local results in place of central histopathological confirmation. By April 2020, trials were ranked based on availability of alternative therapies and subject safety in 4 tiers that correlated with subject benefit and impact on care. Trials were given a prioritization level to commence enrollment with priority given to trials where no standard of care exists. Of the HBTC trials, one was graded Tier 1 and most were graded Tier 2. All patients already enrolled continued on study. As restrictions eased, trials were opened in a sequential manner. Changes that were made during the first wave of the pandemic helped to minimize its effect on clinical trial operation and enrollment during the second wave in Fall 2020. Thus, leading toward a decrease in trial deviations and increased enrollment during the 2nd wave. The changes made during the first wave helped to safely continue enrollment and treatment during the second wave and will have a longstanding impact on how clinical trials will be conducted in the future.
INNV-36. NON-INTRUSIVE, NON-INVASIVE AND PATIENT FRIENDLY FOCUSED ULTRASOUND DEVICE AS A DELIVERY VEHICLE FOR CNS TUMORS
Authors: Ramamurthy Bhaskar , Keralapura Mallika , Marshall John , Need Daniel , Dittamore Ryan , Kesari Santosh , Fonkem Ekokobe 
Published: November 2021

Abstract
A major impediment to treatment of brain cancers is the inability to transport drugs across the blood-brain barrier (BBB). The development of an effective, targeted, and non-invasive method to penetrate the BBB to deliver cancer therapeutics is an unmet need in the treatment of brain cancers. Large molecular weight chemo- and immuno-therapies such as doxorubicin and others may be potentially effective against brain cancers if such drugs are sufficiently bioavailable in the brain. Focused ultrasound techniques can safely and transiently open the BBB but current techniques require invasive/intrusive or expensive and high-touch procedures and are not optimal for wide adoption. To address this unmet need, we are developing an innovative technique to non-intrusively, non-invasively and transiently open the BBB in a specified location within the brain using guided ultrasound (US). Our device consists of a proprietary US generator that is controlled by a highly portable system that has a small physical footprint, enabling the US generator and system to be placed in confined spaces such as chemotherapy infusion centers. The US generator is cap-shaped device that is placed on a patient’s head that includes multiple sets of ultrasound transducers that are distributed within the cap according to the anatomy of the skull. With our proprietary technique, we calculate the position of the cap in relation to the internal anatomy in a real-time manner and in a non-intrusive and a non-invasive manner. We have recently concluded an extensive study that resulted in algorithms that can accurately guide the US to various targets within the brain across a spectrum of patients. We also have completed a pilot preclinical study on a large animal demonstrating our ability to open the BBB non-invasively and deposit a drug proxy (gadolinium and Evans Blue).
INNV-37. XCELSIOR: A REAL-TIME, REAL-WORLD LEARNING PLATFORM FOR PATIENTS WITH ADVANCED CANCER
Authors: Stuhlmiller Timothy , Shapiro Mark , Wasserman Asher , Osking Zachary , Shrager Jeff , Federowicz Bryan , Warner Matthew , Friedland Julie , Musella Al , Blondin Nicholas , Fonkem Ekokobe , Wong Eric , Kesari Santosh 
Published: November 2021

Abstract
xCures operates a direct-to-patient, real-world evidence platform for decentralized clinical research. The platform leverages a nationwide observational research protocol (XCELSIOR, NCT03793088) to aggregate, normalize, and analyze N-of-1 clinical outcomes to continuously learn from and inform treatment decisions. Individual data elements are extracted directly from medical documents such as clinic notes, and radiology, genomics, and pathology reports. The data elements are standardized to established biomedical ontologies and stored in a validated and part 11 compliant electronic database, suitable for statistical analyses and regulatory filings. This permits comparison of patient outcomes across institutions and removes the burden of data entry from oncologists and their staff. As an extremely efficient real-world data solution, we have utilized this platform to accelerate both academic- and commercial-sponsored clinical research, prospectively integrating diagnostics and algorithms with interventional treatments. For each patient that participates in XCELSIOR, artificial intelligence-powered clinical decision support algorithms suggest testing and treatment options. These options and supporting treatment rationales are sourced from key opinion leaders, tumor boards, clinical researchers, practicing oncologists, and published literature, and ranked using the real-world outcomes data from the registry. At the conference, we will present an overview of this real-time learning infrastructure and report on clinical case studies for pharma and non-profit groups including over 75 virtual tumor boards and real-world evidence generated from over 150 patients with CNS cancers that we have helped in partnership with Cancer Commons and The Musella Foundation for Brain Tumor Research and Education. Outcomes analyses stratified by therapeutic interventions and biomarkers will be reported, including frequency of adverse events, time to treatment failure, time to disease progression, and overall survival. Interventions include standard-of-care chemotherapies as well as therapies accessed by clinical trial, expanded access, and off-label prescription.
PATH-04. LEPTOMENINGEAL DISEASE IN PATIENTS WITH HISTONE-MUTANT GLIOMAS
Authors: Diaz Maria , Correia Carlos Eduardo Silva , Lin Andrew , Miller Alexandra , Pentsova Elena 
Published: November 2021

Abstract

INTRODUCTION
The 2016 WHO classification describes a subtype of midline gliomas harboring histone 3 (H3) K27M mutations, and the upcoming 2021 edition may include a new subtype of hemispheric diffuse gliomas with H3 G34R/V mutations. Since we began to perform molecular profiling at Memorial Sloan Kettering Cancer Center (MSKCC) we have observed an increased prevalence of leptomeningeal disease (LMD) in this population. However, the incidence and clinical behavior of LMD has not been well defined.

METHODS
This is a retrospective study of patients with H3-mutant gliomas at MSKCC diagnosed from 01/2012 to 02/2021, either by tumor biopsy or by cerebrospinal fluid (CSF). Histone mutations were identified through next-generation sequencing (NGS).

RESULTS
We found 40 patients (pts) harboring H3 mutations (K27M mutations in 31 pts, G34R/V in 8, and both in one), with 2/40 (5%) mutations identified through CSF NGS only and rest in tumor tissue. Median age was 20.5 years (4-70); 25 were male. Tumor location was midline for K27M-mutant tumors (thalamus [N=15], brainstem [N=10], spine [N=5], pineal gland [N=1]) and hemispheric for G34R/V-mutant tumors; tumor with both mutations was thalamic. LMD was diagnosed in 22/40 (55%) pts radiographically, including 19/31 (61%) of K27M-mutant pts and 3/8 (38%) of G34R/V-mutant pts (patient with both mutations did not develop LMD). At analysis, 10 patients remain alive. Median time from diagnosis to LMD was 8.8 months (0-44.4), with median OS of 6.5 months (0.3-34) after LMD diagnosis.

CONCLUSION
More than half of patients with histone-mutant gliomas develop LMD, including over a third of patients with G34R/V mutations. Neuroaxis imaging should be performed in conjunction with CSF studies in histone-mutant gliomas. Besides, CSF NGS represents an important tool to identify molecular profile of tumors when biopsy is not feasible or there is limited tissue for analysis.
PATH-07. INFRATENTORIAL HIGH-GRADE GLIOMAS: NEUROSURGICAL CASE SERIES WITH MOLECULAR ANALYSIS
Authors: Stopa Brittany , Truman Kyla , Villa Genaro , Peruzzi Pierpaolo , Gormley William , Iorgulescu Bryan , Smith Timothy 
Published: November 2021

Abstract

INTRODUCTION
Most high grade gliomas (HGG) are located supratentorially, while less than 1% arise infratentorially. Growing evidence suggests that infratentorial HGGs (iHGG) represent a collection of distinct molecular entities and that further elucidation of their molecular features can help guide management. We perform here a clinical and molecular analysis of our institutional iHGG case series.

METHODS
We retrospectively reviewed iHGG patients treated surgically at Brigham and Women’s Hospital (1992-2020), and evaluated their history of prior malignancies, tumor location, treatment, molecular profile, tumor recurrence, and survival. iHGG were identified by review of pathology records, using WHO Histologic Grading Criteria as grade III-IV gliomas located infratentorially. Molecular analysis data was obtained from pathology records.

RESULTS
Among 37 iHGGs, 16 (43%) were glioblastomas, 11 (30%) were anaplastic astrocytomas, 2 (5%) were diffuse midline gliomas, 2 (5%) were infiltrating gliomas, 2 (5%) were anaplastic ependymomas, 1 (3%) was an anaplastic oligodendroglioma, and 3 (8%) were HGG not otherwise specific. Sixteen (43%) patients were female, median age was 49 years. Fifteen patients had history prior malignancy, 11 of which received radiation and 8 chemotherapy. Surgical resection of iHGG included gross total resection in 4 (11%) and subtotal in 33 (89%). Twenty-one patients (57%) received adjuvant radiation and 19 (51%) chemotherapy. At follow-up, 13 (35%) patients demonstrated symptomatic deterioration, 15 (41%) were stable, and 7 (19%) were improved. Seven patients (19%) experienced recurrence at a mean time of 19 months, and one-year survival was 35%. Molecular analysis revealed 7/15 (47%) tumors were MGMT promoter methylated, IDH was mutated in 3/24 (13%), EGFR was amplified in 3/10 (30%), CDKN2A/B homozygous deletion in 4/7 (57%), TP53 was mutated in 14/15 (93%), and H3K27M was present in 4/10 (40%).

CONCLUSIONS
iHGGs demonstrate substantial distinction from their supratentorial counterparts. Herein we examined their clinical course, molecular features, management, and outcomes.
PATH-08. PROGNOSTIC IMPLICATIONS FROM LONG-TERM SURVIVORS (LTS) OF GLIOBLASTOMA
Authors: Briceno Nicole , Abdullaev Zied , Vera Elizabeth , Choi Anna , Christ Alexa , Grajkowska Ewa , Leeper Heather , Levine Jason , Lindsley Matthew , Reyes Jennifer , Boris Lisa , Burton Eric , Lollo Nicole , Panzer Marissa , Penas-Prado Marta , Pillai Valentina , Theeler Brett , Wu Jing , Polskin Lily , Papanicolau-Sengos Antonios , Quezado Martha , Aldape Kenneth , Gilbert Mark , Armstrong Terri 
Published: November 2021

Abstract
Glioblastoma (GBM) is the most aggressive primary brain malignancy with &lt; 45% living a year beyond diagnosis which drops to 7% at five years. However, there have been reports of long-term survivors (LTS) living three to ten years beyond diagnosis. Few studies have reported on molecular factors in tumors from LTS cohorts. We identified GBM (IDH1/2 wildtype) patients living at least 3 years post diagnosis (N=25), including 16 with pre-treatment tumor tissue, from our Natural History Study. Available pre- or post-treatment tumors were analyzed with targeted panel sequencing and methylation analysis for classification, MGMT promoter status and copy number changes. Classical clinical prognostic features such as limited resection or older age did not preclude long-term survival as patients with tumor biopsy (n=1) or subtotal resection (n= 5) and patients &gt; 60 were included in the LTS cohort. Furthermore, tumors with molecular features typically associated with poor prognosis were also in this GBM LTS group. MGMT promoter was unmethylated in 17% of tumors; EGFRvIII mutation in 13%, EGFR amplification in 33%, CDKN2A homozygous loss in 30% and complete chromosome 7 gain with 10 loss in 55%. Additionally, the methylation classifier found a higher-than-expected incidence of mesenchymal tumors (29%) and RTK II (57%). Tumors had a higher percent of TP53 mutations (44%) but lower pTERT (76%) compared to TCGA. These data suggest an individual patient’s prognosis cannot easily be predetermined based on classical clinical and molecular data. This underscores the need for further analyses to discover additional factors leading to their unexpected, prolonged survival and elucidate the role of factors typically associated with poor prognosis. Future work will include RNA-sequencing and germline whole genome sequencing to determine tumor specific gene expression and identify any possible genomic alterations that confer improved survival.