bluuebunny/crossref_metadata_2025_split huggingface dataset:
INNV-25. POST-OPERATIVE LOW DOSE VERSUS STANDARD DOSE DEXAMETHASONE FOR MANAGEMENT OF CEREBRAL EDEMA: A RANDOMIZED, DOUBLE-BLINDED FEASIBILITY STUDY IN PATIENTS WITH PRIMARY OR METASTATIC BRAIN TUMORS UNDERGOING CRANIOTOMY FOR TUMOR RESECTION
Authors: Portnow Jana , Filipov Aleksandr , Blanchard M Suzette , Stiller Tracey , Kilpatrick Julie , Kelii Danalle , Feldman Lisa , Badie Behnam 
Published: November 2024

Abstract

INTRODUCTION
Although dexamethasone is effective for controlling cerebral edema during the peri-operative period, its immunosuppressive properties can inhibit responses to immunotherapy. We hypothesized that patients with mild to moderate cerebral edema could be safely managed post-operatively with lower doses of dexamethasone.

METHODS
Eligible patients with brain tumors who had less than 10 mm of midline shift on their pre-operative brain MRIs were randomized 1:1 to the standard or low dose dexamethasone arm, each tapering double blinded through post-op day 8. The double blind was maintained using equivalent volumes for IV doses and capsules containing dexamethasone or placebo. By post-op day 9, participants received the same dose of dexamethasone and continued tapering to off by day 14. Additional doses of dexamethasone were allowed if needed, based on specified symptom criteria. Lack of feasibility was defined as a participant requiring 18 mg or more of dexamethasone in addition to the planned total dose of dexamethasone (low dose: 49 mg; standard dose: 112 mg). Brain MRIs were performed on post-operative days 1, 3, and 8 to evaluate changes in cerebral edema. Manual segmentation and computer-assisted techniques were used to quantitatively measure cerebral edema volume.

RESULTS
Twenty-six patients were randomized and treated within tumor type strata (primary versus metastatic), of which 25 were evaluable. None of the participants on the low dose dexamethasone arm met the criteria for lack of feasibility. The quantitative assessment of differences in cerebral edema between the arms is ongoing and will be presented.

CONCLUSIONS
Administration of lower doses of dexamethasone post-operatively to brain tumor patients with mild to moderate cerebral edema is feasible. Treatment with lower doses of dexamethasone post-operatively should be considered in this patient population when peri-operative administration of immunotherapy is planned.
INNV-27. TEMOZOLOMIDE FOR PATIENTS WITH AGGRESSIVE PITUITARY TUMORS: A CASE SERIES
Authors: White Jessica , Baykal Duru , Ser Hazal , Uhm Joon , Ruff Michael , Lachance Daniel , Neth Bryan , Van Gompel Jamie , Giannini Caterina , Raghunathan Aditya , Erickson Dana , Sener Ugur 
Published: November 2024

Abstract

BACKGROUND
Pituitary adenomas are often effectively managed with medical therapy, surgery, and radiation therapy. However, up to 15% of pituitary neoplasms exhibit rapid growth, invasive behavior, or, rarely, metastasize despite optimal standard treatments. Temozolomide is associated with a survival benefit for patients with these aggressive pituitary tumors.

METHODS
We present a case series of 8 patients with an aggressive pituitary tumor (APT) or pituitary carcinoma (PC) treated with temozolomide.

RESULTS
Eight patients (3 female, median age at diagnosis 44) with APT (n=6) or PC (n=2) were treated. A variety of pituitary tumor types were represented (1 prolactinoma, 5 corticotroph adenomas, 1 gonadotroph adenoma, 1 thyrotropinoma). Prior to temozolomide initiation, patients underwent a median 5 treatments including medical management (n=4), surgery (n=7), radiation therapy (n=7). Temozolomide was started at median 3.5 recurrence. Median treatment duration was 6 cycles (n=6, 150-200 mg/m2 days 1-5, 28-day cycles; n=1, 75 mg/m2, days 1-21, 28-day cycles). Seven patients experienced progression after temozolomide treatment, median progression-free survival (PFS) was 4 months. One patient remains on treatment, progression-free at 5 months. MGMT methylation status was assessed for 3 tumors. Among 2 patients with MGMT promoter methylated tumors, PFS was 4 months for one patient, the other remains on treatment. For one patient with MGMT promoter unmethylated corticotroph adenoma, PFS was 9 months. No ≥ grade 4 toxicities were noted. Most common toxicities were nausea (n=5), thrombocytopenia (n=3), and fatigue (n=2).

CONCLUSION
In this group of heavily pretreated patients, temozolomide monotherapy was well-tolerated and associated with median PFS of 4 months. Interestingly, PC patients had longer PFS at 9 months and 24 months. Our findings support use of single-agent temozolomide chemotherapy for patients with APT/PC, but further prospective analysis is needed to identify patients more likely to benefit from treatment and optimal timing of chemotherapy initiation.
INNV-29. PATIENT BARRIERS AND PREFERENCES FOR EXERCISE FOLLOWING A BRAIN TUMOR DIAGNOSIS
Authors: Fogh Shannon , Mishra Kavita , Hoffer Naomi , Destri Mary , Chang Susan , Taylor Jennie 
Published: November 2024

Abstract

BACKGROUND
Exercise has shown benefit in patients with cancer, however patients with brain tumors often experience deficits in cognition, motor skills and other symptoms, further exacerbated by treatment, which can make exercise challenging. Yet, the literature supports positive impact of exercise on symptoms and prognosis within this patient population. Our study aims to understand patient’s motivations and preferences for exercise.

METHODS
We surveyed patients with primary brain tumors within a single, quaternary medical center. Questions were extrapolated from published questionnaires and were accessed through flyers containing a QR code. Questions assessed current practices, attitudes, knowledge, motivating factors and barriers for integrating exercise into treatment.

RESULTS
Twenty-nine patients completed the survey. Nearly 70% reported that exercise has been important throughout their life in maintaining good health and quality of life. Walking emerged as the predominant mode of physical activity (55%). Thirty-one percent of patients reported the intensity of their current routine was light activity, 24% moderate activity, and 7% vigorous activity.The primary motivators for patients initiating or sustaining an exercise regimen included having someone monitor their progress (28%), complimentary access to a workout facility (21%) and awareness of the beneficial impact of exercise on symptoms and prognosis (51%). The most prevalent physical barriers to exercise included trouble with balance (34%), fatigue (34%) and headaches (21%). Other barriers included lack of transportation (38%), space (21%), cost (21%) and time (14%). Sixty-six percent of patients were more likely to participate in an exercise program if mentioned by their healthcare provider or healthcare team during a visit.

CONCLUSION
Findings from this study help to expand our understanding of barriers and facilitators to incorporating exercise interventions into brain cancer treatment and can inform the implementation of a structured exercise programs.
INNV-30. TOXICITIES AND OUTCOME AFTER CD19-DIRECTED CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY FOR NEUROLYMPHOMATOSIS
Authors: Kaulen Leon D , Karschnia Philipp , Doubrovinskaia Sofia , Wick Wolfgang , Martinez-Lage Maria , Shankar Ganesh , Abramson Jeremy S , Frigault Matthew J , Dietrich Jorg 
Published: November 2024

Abstract

BACKGROUND
Lymphomatous infiltration of the peripheral nervous system (PNS), termed neurolymphomatosis, represents a distinct extranodal non-Hodgkin lymphoma variant with dismal outcome. CD19-directed chimeric antigen receptor (CD19-CAR) T-cell therapy has emerged as a safe and effective treatment for B-cell lymphomas. We aimed to assess toxicity and efficacy of CD19-CAR T-cells in neurolymphomatosis.

METHODS
Neurolymphomatosis treated with CD19-CAR T-cells were retrospectively identified at Massachusetts General Hospital over a six-year period. Toxicities were graded according to the ASTCT classification. Management, and response rates were recorded.

RESULTS
Eleven neurolymphomatosis cases, who had received a median 2 prior PNS-directed treatments (range: 1-3) before CD19-CAR T-cell exposure, were identified. Neurolymphomatosis localized to the nerve roots (8/11, 73%), plexus (5/11, 45%), peripheral (4/11, 36%) and cranial nerves (5/11, 45%). Low grade cytokine release syndrome was detected in 8/11 (73%; grade 1: N = 7; grade 2: N =1) cases. Low- and high-grade immune cell-associated neurotoxicity syndrome were recorded in 5/11 (45%; grade 1: N = 4; grade 2: N = 1) and 1/11 (9%; grade 4) patients, respectively. Seven of eleven neurolymphomatosis patients (64%) responded to CD19-CAR T-cells. Complete remissions were achieved in three cases (27%), of which two are still sustained now 9 and 46 months after CD19-CAR T-cell infusion. All radiographic responses were associated with remission of neurological symptoms.

CONCLUSIONS
CD19-CAR T-cell treatment was well tolerated and yielded promising efficacy in recurrent neurolymphomatosis, a difficult to treat condition with unmet medical need. Findings suggest that CD19-CAR may sufficiently penetrate the blood-nerve barrier, and toxicity and outcomes were overall similar to CAR-T cell therapy in CNS lymphoma.
INNV-33. ADVANCING PRECISION TREATMENT FOR DIFFUSE MIDLINE GLIOMA: THE DMG LEARNING HUB INITIATIVE
Authors: Lyons Nicole , Mehta Misha , Ward Lisa 
Published: November 2024

Abstract
Diffuse Midline Glioma (DMG) poses a significant challenge in neuro-oncology due to its heterogeneous presentation and limited therapeutic options. Clinical trials often serve as the primary avenue for treatment, yet families encounter numerous barriers in navigating and selecting appropriate trials. Health disparities, including disparities in medical literacy and access to specialized medical centers, further complicate decision-making processes. Existing registries lack comprehensive data integration, focusing on isolated perspectives of either research or clinical data, neglecting the holistic patient profile. Evaluation of treatment endpoints beyond Progression-Free Survival (PFS) and Overall Survival (OS) remain inconsistent, despite being a priority for families. The DMG Learning Hub emerges as a transformative platform designed to empower families by offering informed options and guidance while fostering a collaborative environment where patient families actively contribute to shaping the landscape of clinical trials. Leveraging AI-assisted matching, the platform assists families in navigating the complex decision-making process surrounding clinical trial participation. The inclusion of a patient-reported outcome journal feature enables families to track vital information such as symptom changes and supplement usage, with autonomy over the timing of shared data. Using real-time data sharing facilitates invaluable insights for researchers, bridging gaps that would otherwise be overlooked and enriching the collective understanding of DMG. Harmonizing molecular, imaging, and clinical data within the platform equips care teams with comprehensive, near-real-time information crucial for personalized treatment strategies. This integrated approach not only supports the inclusion of n-of-1 arms in current trials but also extends therapeutic opportunities to patients previously ineligible for studies due to specific disease markers or progression patterns. The DMG Learning Hub represents a significant stride towards precision oncology by synergizing patient-centric priorities with cutting-edge technology, integrating harmonized data, and fostering collaborative efforts, the initiative heralds a promising era of personalized treatment for DMG and beyond the neuro-oncology community.
INNV-35. DATA-DRIVEN MODELING OF EMERGING TRENDS AND COLLABORATIVE NETWORKS ACROSS BRAIN METASTASES RESEARCH: THE PAST DECADE OF INNOVATION
Authors: Durrani Sulaman , Cote Ian , Carpintieri Sabrina , Martinez Joseph , Metzler Ashley , Graciolli Joacir , Shah Ashish , Oermann Eric , Komotar Ricardo , Ivan Michael , Benjamin Carolina , Sheehan Jason , Kondziolka Douglas , Tecle Najib El 
Published: November 2024

Abstract
With recent significant growth in brain metastases literature output, more comprehensive research is necessary to understand emerging trends and novel methods of diagnosis and treatment. We aimed to address this by providing a contemporary systematic global analysis of emerging brain metastases research in the last decade while visually depicting the international collaborative environment among its researchers. Data mining was performed on all brain metastases publications across the last decade indexed in Elsevier’s Scopus database. Our Scopus search revealed 6,362 publications from 1,184 sources from 2013-2022. Of those, 252 were identified as high-impact articles with an annual citation rate (CR) &gt; 10. The compounded annual growth rate (CAGR) of brain metastases publications was 7.2% per year since 2013. There was an acceleration of scientific production, from 5.9% CAGR across 2013-2018 to 9.6% across 2019-2022. Authors per document increased from 7.2% to 8.5% while international co-authorships increased from 16.6% to 18.3% in the same periods, respectively. Recent trending topics were noted to be artificial intelligence, understanding the brain microenvironment, exosomes, novel mechanisms of diagnosis (such as circulating tumor cells), and targeted treatments. High-impact articles tended to revolve around specific therapies or biomarkers as opposed to general synopses. Clustering analysis revealed three separate pivotal collaborative communities centered around Brown PD/Sahgal A, Ahluwalia MS, and Wang Y, with Brown PD as most notable for high impact research. While the top institutional collaborative group centered around Mayo Clinic, the highest impact research centered around the Dana-Farber Cancer Institute. Sub-analyses revealed that studies involving multiple countries tended to have a higher impact. The median overall survival of brain metastases, by primary source, was illustrated across the last five decades. Overall, significant growth in scientific production is driven by the integration of novel technologies (such as artificial intelligence), interdisciplinary approaches, and collaboration across global communities.
PATH-08. MOLECULAR DIVERGENCE RATES DIFFER BETWEEN BRAIN METASTASES AND EXTRACRANIAL DISEASE SITES ACROSS PRIMARY TUMOR HISTOLOGIES
Authors: Morshed Ramin , Khela Harmon , Nguyen Minh , Young Jacob , Goldschmidt Ezequiel , McDermott Michael , Malik Noor , Parney Ian , Chang Edward , Berger Mitchel , Theodosopoulos Philip , Hervey-Jumper Shawn , Huppert Laura , Aghi Manish , Vasudevan Harish 
Published: November 2024

Abstract
Genomic alterations and molecular subgroups between extracranial disease sites and brain metastases often differ, yet the prevalence and clinical significance of divergent evolution in brain metastases is not fully understood. This study examined genomic alterations and molecular subgroup divergence rates between matched brain metastases and extracranial disease sites. A retrospective, two-center study was conducted on patients who underwent resection of brain metastases between 2014-2022 with clinical and matched genomic data and/or molecular markers available. The overall cohort comprised 256 patients with matched tumors from multiple cancer types, most commonly from breast (n=108, 42.2%), melanoma (n=83, 32.4%), and NSCLC (n=43, 16.8%). Targeted next-generation sequencing of over 500 oncogenes was performed on resected tumors as part of clinical care (n=41 patients with matched specimens). Molecular subgroups for breast, melanoma, and non-small cell lung cancer were also assessed by immunohistochemistry to evaluate rates of molecular subgroup discordance between sites. Subgroup discordance by immunohistochemistry was observed most frequently across breast cancer (22.2%, n=24/108) with loss of the estrogen receptor (ER) and progesterone receptor (PR) and gain of HER2 most frequently observed within brain metastases. Molecular subgroup discordance was rare within melanoma (7.3%, n=6/82) and NSCLC (14.0%, n=6/43) patients. When evaluating oncogenomic alterations from targeted DNA sequencing in 41 patients with matched specimens, 80.5% (33/41) of brain metastases demonstrated a unique oncogene alteration profile compared to an extracranial disease site. Fourteen patients (34.1%) had a gain of at least 1 targetable alteration within a brain metastasis that was not observed in an extracranial disease site. Brain metastases demonstrated high rates of genomic divergence compared to primary and extracranial metastatic disease sites. This data supports obtaining brain metastasis tissue and conducting molecular profiling of this tissue to help select optimal CNS penetrant systemic therapies for each patient.
PATH-11. TECTAL GLIOMA: CLINICAL, PATHOLOGICAL, AND MOLECULAR FEATURES
Authors: Imoto Ryoji , Otani Yoshihiro , Ishida Joji , Hirano Shuichiro , Kemmotsu Naoya , Suruga Yasuki , Mizuta Ryo , Kegoya Yasuhito , Inoue Yohei , Washio Kana , Yanai Hiroyuki , Tanaka Shota , Satomi Kaishi , Ichimura Koichi , Date Isao 
Published: November 2024

Abstract
Tectal glioma (TG) is a rare lower-grade glioma (LrGG) that occurs in the tectum, mainly affecting children. The clinical course is usually indolent, with common symptoms including headache, gait disturbance, and ataxia resulting from obstructive hydrocephalus. TG shares pathological similarities with pilocytic astrocytoma (PA), but recent genetic analyses have revealed distinct features, such as alterations in KRAS and BRAF. Here, we report the clinical, radiological, pathological, and molecular characteristics of TG cases in our hospital. We conducted a retrospective review of cases clinically diagnosed as TG and surgically treated at our institute between January 2005 and March 2023. Molecular analysis, including genome-wide DNA methylation profiling, was performed. Six cases were identified and the median age at diagnosis was 30.5 years (range: 6–45 years). The mean tumor diameter was 22.8 mm (range: 14.7–33.2 mm), with obstructive hydrocephalus observed in all cases. Contrast enhancement of the tumor was noted in four cases and cyst formation occurred in two cases. Four patients underwent biopsy or biopsy with endoscopic third ventriculostomy, and two patients underwent tumor resection. Postoperatively, three patients received radiotherapy and two were treated with chemotherapy. The median overall survival was 6.2 years (range: 1.4–7.3 years), and the median progression-free survival was 3.4 years (range: 1.4–7.3 years). Histological diagnoses included three cases of PA, one case of astrocytoma, and two cases of high-grade glioma. Among the three patients who underwent molecular evaluation, including genome-wide methylation analysis, two had KRAS mutation and one had H3-3A K27M mutation. Our results demonstrate the diverse histological and molecular characteristics of TG distinct from other LrGGs. Given the heterogeneous pathological background and the risk of pathological progression in TG, we emphasize the importance of comprehensive diagnosis, including molecular evaluation.
PATH-15. DIGITAL PCR ANALYSIS FOR DETECTINGTERT PROMOTOR MUTATION IN MENINGIOMAS
Authors: Shimizu Yuzaburo , Kodama Takuma , Miyahara Ryo , Suzuki Mario , Akiyama Osamu , Ogino Ikuko , Kondo Akihide 
Published: November 2024

Abstract
The WHO Classification of Brain Tumors 5th edition requires the evaluation of TERT promoter mutations and CDKN2A/B homozygous deletions for the diagnosis of malignant meningiomas. Digital PCR (dPCR) is an emerging method for highly sensitive quantitative analysis. In this study, we performed TERT promoter mutation analysis using Pyrosequencing and dPCR in specimens with atypical and anaplastic meningiomas to investigate its utility and clinical significance. Adult patients diagnosed with atypical or anaplastic meningiomas after tumor resection between January 2009 and June 2023 were included. Genomic DNA was extracted from the excised specimens. TERT promoter mutations was analyzed by using the Pyrosequence and dPCR methods and compared with the clinical course. A total of 37 meningioma cases (13 males and 24 females) with 64 specimens were included. Atypical meningioma, grade II (WHO 2016) at diagnosis was 53 specimens (83%) and anaplastic meningioma, grade III (WHO 2016) was 11 specimens (17%). Of these, 7 (10%) were diagnosed with TERT promoter mutations by pyrosequencing, and one case with a low frequency (15%) of mutations by dPCR that tested negative by pyrosequencing had repeated recurrences in a short period of time. The dPCR method is highly sensitive in detecting low frequency TERT promoter mutations in tumor cell subpopulations and may contribute to the determination of treatment by predicting the malignant course of the disease. The results suggest that dPCR could contribute to therapeutic decision-making by detecting low-frequency TERT promoter mutations in tumor cell subpopulations.
PATH-16. MOLECULAR ALTERATIONS IN IDH-MUTANT ASTROCYTOMA: A MULTI-INSTITUTIONAL RETROSPECTIVE STUDY
Authors: Lam Keng , Ozkizilkaya Hanim , Den Milton ái , Dono Antonio , Kumar Vinodh , Johnson Jason , Esquenazi Yoshua , Patel Chirag , Ballester Leomar 
Published: November 2024

Abstract

BACKGROUND
Many molecular alterations are being identified for diagnosis and prognosis in patients with isocitrate dehydrogenase (IDH)-mutant astrocytoma. However, contemporary survival data for these tumors with respect to their molecular alterations are lacking. Moreover, the prognostic value of histologic grading in IDH-mutant astrocytomas remains controversial.

METHODS
This was a retrospective study of adult IDH-mutant diffuse astrocytoma patients in whom clinical and molecular alteration data were collected. Overall survival (OS) was estimated using the Kaplan-Meier method. Group differences in OS were assessed by the log-rank test and associations between OS and measures of interest were evaluated using Cox proportional hazards regression models.

RESULTS
We identified 241 eligible patients with median age of 33 years (range, 16-73 years). The most frequent mutations were in IDH1 (98%), TP53 (91%), ATRX (70%), ARID1A (8%), BRCA2 (6%), TSC2 (6%), CDKN2A (6%), and CREBBP (6%). IDH2 mutations were identified in 2% of cases. By univariate analysis, age &gt;40 years (hazard ratio [HR], 2.02; 95% CI, 1.19-3.43; P =.009) was associated with worse OS. BRCA2 wild-type status compared with mutated BRCA2 (HR, 0.42; 95% CI, 0.20-0.90; P =.024) and histology-based grade 2 compared with grade 3 astrocytoma (HR, 0.41; 95% CI, 0.23-0.74; P =.003) were associated with improved OS. In multivariable analysis, age&gt;40 years (HR, 2.14; 95% CI, 1.22-3.75; P =.008) was associated with worse OS. Patients with WHO grade 2 astrocytoma remained associated with improved OS compared to those with grade 3 disease (HR, 0.45; 95% CI, 0.24-0.84; P =.013).

CONCLUSIONS
Age and histological grade remain essentials for risk stratification among IDH-mutant astrocytoma patients. Further studies are warranted to determine the role of BRCA2 mutation in prognosis.