bluuebunny/crossref_metadata_2025_split huggingface dataset:
INNV-19. LANGUAGE ACTIVATION AREAS AND PATHWAYS INTEGRITY ASSESSMENT FOLLOWING GLIOMA RESECTION AND SUBSEQUENT RADIATION TREATMENT
Authors: Haisraely Ory , Cohen Zvi , Anton Wohl , Livny Abigial , Tsarfaty Galia , Belenky Eugenia , Kaisman-Elbaz Thila 
Published: November 2023

Abstract

BACKGROUND
It is a well-established practice to perform brain-mapping scans of patients diagnosed with dominant frontal/temporal lesions to evaluate their language activation areas (LAAs) and pathways prior to surgical intervention. Dependent on the pathology, brain functional regions and their associated pathways may be exposed to post-operative radiation as part of the patient's treatment protocol. The post-radiation detrimental effect on cognition is well-known, however, the effect of surgical resection and subsequent radiation on LAAs and pathways' integrity is not well studied. Here, the impact of surgical resection and radiation on LAAs and pathways integrity is examined.

METHODS
8 patients that underwent surgical resection to frontal/temporal lesion located at their dominant hemisphere followed by radiation treatment with at least two brain-mapping scans in Sheba Medical Center between the years 2012 to 2021 were collected. Location of functional LAAs (such as Broca's and Wernicke’s areas) as well as that of structural fiber tracts (such as the arcuate fasciculus) were determined. Volumetric and tumor geometry data was measured and documented. Laterality index of activation and Fractional Anisotropy (FA) quantitative values were calculated and compared from the baseline scan to the post-treatments scan for each patient.

RESULTS
Patients’ demographics analysis showed that their median age-at-diagnosis was 41 years (range, 4-64). The median overall survival was 89 months (range, 19-130) and the median follow-up duration was 80 months (range, 16-129). Radiation mean dose was 57Gy (range 40.05-60) and Planning treatment volume was 315ml (range 123.3-456.5) Notably, the mean laterality index of LAAs was also affected by intervention (p=0.044). Additionally, the arcuate fasciculus’ FA values differed in the post-interventions scan compared to the pre-interventions scan

CONCLUSION
surgical resection and radiation treatment may cause changes in the lateralization of the LAAs that may represent an attempt to compensate for a significant brain injury.
INNV-23. HEALTH AND HEALTHCARE FACTORS THAT SHAPE THE GLIOMA PATIENT EXPERIENCE THROUGHOUT THE CANCER CONTINUUM: THE VALUE OF CARE COORDINATION AND COMMUNICATION
Authors: Ernster Alayna , Canzona Mollie , Hsu Fang-Chi , Weaver Kathryn , Hutchinson Angelica , Lesser Glenn , Houston Kristin , Marshall Alexandria , DeTroye Alisha , Strowd Roy 
Published: November 2023

Abstract

BACKGROUND
Cognitive or communication deficits from glioma may pose challenges in patients’ ability to manage their illness and navigate the healthcare system. Disease-specific barriers must be overcome to achieve patient-centered care and shared-decision making. This study identified health and healthcare factors that enhance or complicate the patient experience throughout the glioma-cancer continuum.

METHODS
Semi-structured interviews (N=8) or focus groups (N=6) were conducted in-person or via phone call with 23 glioma patients at any point during their cancer care. The constant comparative method was used to identify themes illustrating the healthcare factors that shape the glioma patient experience.

RESULTS
Three themes that facilitate the healthcare experience and six themes that complicate the healthcare experience were identified. Facilitating themes included (1) free exchange of information with healthcare providers (HCP), (2) HCP expectation setting and efforts to support patient agency, and (3) HCP relationship building efforts. Complicating themes included (1) early attempts to address initial symptoms in healthcare settings, (2) patient perception of initial symptoms, (3) long wait times and time-intensive appointment schedules, (4) accessing and navigating procedures for appointments and multiple locations, (5) timing and delivery of information during treatment, and (6) mixed messages about prognosis and treatment recommendations.

DISCUSSION
Health and healthcare factors that influence the glioma patient experience are concentrated around patients’ relationships and communication with HCP and the logistics of cancer care delivery. Logistical barriers to care delivery negatively affect the patient experience and highlight the need for interventions that aim to streamline care delivery, help patients manage care, fulfill healthcare information needs, and enhance team-based cross-disciplinary communication.
INNV-29. THE CLEARPOINT PRISM® LASER ABLATION SYSTEM: A NEW PLATFORM FOR LASER INTERSTITIAL THERMAL THERAPY (LITT) IN NEURO-ONCOLOGY
Authors: Wilson Hannah , Chen Clark 
Published: November 2023

Abstract

BACKGROUND
Laser interstitial thermal therapy (LITT) has advanced the surgical treatment of brain cancer. However, technical constraints in the first-generation laser ablation systems limit the full potential of this technology. ClearPoint Prism® Laser Ablation System was developed to overcome many of these limitations, including a larger ablation window, a faster refresh rate for magnetic resonance thermometry, and integration with an MRI-compatible stereotactic system. This system was FDA cleared for neurosurgical use in 2022.

METHODS
We prospectively followed the first three patients who underwent LITT using the ClearPoint Prism® Laser Ablation System in the U.S. to establish feasibility and safety of this technology platform.

RESULTS
Three patients underwent procedures involving MRI-guided needle biopsy followed by LITT. The radial error of stereotaxis relative to the intended target ranged 0.8-1.6 mm (with a median of 1.0 mm). Definitive diagnosis was achieved in all cases. The average time required to establish the trajectories was 98.7 + 16.6 minutes. The average time required to perform the biopsy and LITT was 110 + 19.3 minutes. These times are not statistically different from our published results for comparable procedures using other available LITT systems. The average LITT time required to achieve ablation of &gt; 1cm radius was 49 seconds (range: 29-133 seconds). There were no procedural complications. All patients were discharged home by postoperative day three. The postoperative MRIs demonstrated expected ablation findings consistent with intraoperative thermometric assessment. With a median follow-up of 219 days (range: 185-259 days), there were no 30-day readmission, 90-day emergency visits, or wound complications.

CONCLUSION
In this study, we provide the clinical outcome of the first three patients in the U.S. who underwent LITT through the FDA cleared ClearPoint Prism® Laser Ablation System. The system has distinct advantages that warrant consideration in further investigations and clinical applications.
INNV-34. A NOVEL APPROACH TO ADDRESSING THE UNIQUE NEEDS OF ADOLESCENT AND YOUNG ADULT (AYA) BRAIN TUMOR PATIENTS: A FRAMEWORK FOR A VIRTUAL PEER-LED YOUNG ADULT SUPPORT GROUP
Authors: Hines Dace , Scotford Katie , Bryson-Cahn Phoebe , Hoffer Naomi , Destri Mary , Greenstein Alexa , Chang Susan , Schulte Jessica 
Published: November 2023

Abstract

INTRODUCTION
Adolescent and young adult (AYA) patients (age 15-39) constitute 14.3% of new brain tumor diagnoses annually. While navigating cognitive and physical challenges from their tumor, these patients are also pursuing social independence, education, careers, relationships, and family planning. These patients have unique, and often unmet, psychosocial needs compared to older patients, requiring a new approach for comprehensive care.

METHODS
Three YA neuro-oncology patients from UCSF volunteered to facilitate a monthly virtual support group. Facilitators were trained in peer support mentorship and support group facilitation by a licensed psychologist. A program planning committee consisted of: a social worker, nurse practitioner, program manager, communications specialist, two neuro-oncologists, and the peer facilitators. Promotion was done through flyers, the UCSF and ABTA websites, and word-of-mouth. Feedback was collected via anonymous survey and informal discussions, and the planning committee met monthly to adapt to evolving group needs. Participants used a video chat app to stay connected between meetings.

RESULTS
Over one year, 73 patients registered, and 40 total participated (average 15/session). Participant age range was 19–44, and age at diagnosis was 10–43. From 19 survey responses, 84% preferred a mix of open and topic-driven discussions. Key topics desired for peer discussion included meditation/mindfulness (68%), cognitive changes (58%), symptom management (58%), relationships/sexual health (58%), exercise (58%), and anxiety (58%). By contrast, participants wanted healthcare providers to address tumor treatment (37%), cognitive challenges (37%), symptom management (32%), seizures (26%), nutrition (26%), and integrative health (21%). Qualitative feedback highlighted community and social support from similarly-aged peers facing similar challenges amongst the most valuable aspects.

CONCLUSIONS
AYA patients have different information and support needs from peers versus providers. Peer-led support groups effectively provide social support for AYA brain tumor patients. Successful implementation involves volunteer facilitators, training, regular planning committee meetings, and participant feedback.
INNV-37. BELZUTIFAN IMPACT ON VHL-ASSOCIATED CNS HEMANGIOBLASTOMAS
Authors: Demers Abigail , Abukhdeir Amal , Gatewood Tyra , Doynova Antoniya Marinova , Chahoud Jad , Spiess Phillippe , Malafa Mokenge , Iacono David , Sahebjam Solmaz , Tran Nam , Mokhtari Sepideh 
Published: November 2023

Abstract

INTRODUCTION
CNS hemangioblastomas are a leading cause of morbidity and mortality among patients with Von Hippel-Lindau (VHL) disease. Belzutifan, a selective hypoxia-inducible factor (HIF-2a) inhibitor, has been approved for the treatment of hemangioblastomas in VHL patients; however, long-term efficacy and safety data are lacking.

METHODS
The authors performed a retrospective chart review of all type Ia VHL with symptomatic CNS hemangioblastomas who were treated with Belzultifan at the Moffitt Cancer Center from August 2021 to June 2023. Patient demographics, clinical characteristics, tumor characteristics, and complications were assessed. Patients were re-evaluated with repeat CNS imaging every 3-6 months.

RESULTS
Eleven patients were identified. Median age is 35 years (IQR: 24-56) and 4/11 patients (36%) are female. Eight out of 11 patients had accessible genetic testing and 87.5% had a missense mutation in the VHL gene. Two patients (18%) had pathology-proven RCC and no patients had pheochromocytomas. One patient (9%) had complete response, eight (73%) had partial response, and two patients (18%) had stable disease at 6 months. Treatment was stopped on 8 patients once they reached stable response to treatment, with 1 patient at 6 months (12.5%), 5 patients at 1 year (62.5%), and 2 patients at 16 months (25%). Five out of 8 patients (62.5%) had sustained response (≥ 3 months) during the time Belzutifan was held. Treatment was restarted on the 3 patients who had progression of disease and all 3 had positive response to treatment at 3 months. All patients had anemia (CTCAE grade 1-2), but did not require blood transfusions, and 1 patient had visual disturbances after restarting Belzutifan.

CONCLUSION
All patients responded positively to Belzutifan based on surveillance CNS imaging, with no major side effects. The majority of patients had sustained response after having stopped the drug for 3 months.
INNV-39. INVESTIGATING MULTI-AGENT INTRATHECAL CHEMOTHERAPY AS A TREATMENT FOR PRIMARY AND SECONDARY CENTRAL NERVOUS SYSTEM LYMPHOMA: SAFETY AND EFFICACY RESULTS FROM AN INSTITUTIONAL COHORT STUDY
Authors: Wilding Hannah , Aastha Aastha , De Macedo Filho Leonardo Jose Monteiro , Bhanja Debarati , Heebner Madison , Khan Shahbaz , Mikolajewicz Nicholas , Ignatchenko Vladimir , Kislinger Thomas , Glantz Michael , Mansouri Alireza 
Published: November 2023

Abstract

INTRODUCTION
Despite exquisite responses to initial therapy for CNS lymphoma, relapse is common and overall responses are disappointing compared to non-CNS diffuse large B-cell lymphomas. Literature reports 1 and 3 year survival rates of 50% and 30-40% respectively, with standard treatment. Intravenous, high-dose-methotrexate-based therapies have become the standard of care, with many variations but no consensus. Incorporation of multi-agent intrathecal chemotherapy (MAITC) alongside systemic therapy is novel but not widely adopted. We report our institutional data on safety and efficacy of MAITC in CNS lymphoma.

METHODS
A retrospective review of patients with primary or secondary CNS lymphoma, treated with MAITC between August 2015 and December 2021, was conducted. Each cycle includes alternating combinations of 2-3 of the following drugs: methotrexate, rituximab, cytarabine, etoposide, topotecan, gemcitabine, and thiotepa, via ommaya reservoir. Log-rank tests and Cox regression were used to evaluate survival differences.

RESULTS
59 patients were reviewed (21 primary; 38 secondary CNS lymphoma). Median age at start of MAITC was 66 years (range 25-90). Only six patients received external beam radiation (EBRT). Median MAITC cycles was 8 (range 2-23). 76% of patients with primary and 66% with secondary CNS lymphoma were alive 1 year after starting MAITC. Of 37 eligible patients, 17 (46%) were alive 3 years after starting MAITC. After a median 19.2 months follow-up, median OS was not reached. No significant difference was noted in OS between primary and secondary CNS lymphoma. KPS &gt; 80 was positively while leptomeningeal disease, secondary CNS lymphoma, and EBRT were negatively associated with OS. Ommaya-related infections occurred in 8 patients (13.5%); only 1 required removal.

CONCLUSION
Based on our institutional data, MAITC can potentially offer a significant OS advantage with minimal safety concerns. Factors associated with poor survival were identified, which are being addressed in a larger dataset along with baseline CSF biomarkers.
INNV-40. DURABLE 10-YEAR RESPONSE TO VEMURAFENIB IN A PATIENT WITH CNS HAIRY CELL LEUKEMIA
Authors: Li Yi , Drappatz Jan , Mantica Megan 
Published: November 2023

Abstract
Hairy cell leukemia (HCL) is an uncommon form of chronic B-cell lymphoproliferative disease, accounting for approximately 2% of all cases of leukemias. Although there have been rare instances of HCL affecting the central nervous system (CNS), these cases usually involve highly fatal leptomeningeal disease or direct leukemic infiltration into the brain. The BRAF V600E mutation, leading to the constitutive activation of the MAPK/ERK signaling pathway, is recognized as a key activating mutation in HCL and is present in almost all HCL patients. First-line treatment for HCL remains purine analogs; however, up to 20% of patients only achieve a partial response. Vemurafenib, an oral inhibitor of BRAF V600E, has demonstrated strong anti-tumor activity in patients with systemic relapsed/refractory HCL and has good CNS penetration. In this case study, we present a 67-year-old patient with HCL who initially presented with multifocal cranial neuropathies In August of 2013. His brain MRIs demonstrated multiple enhancing leptomeningeal foci. While a combination of cytarabine, methotrexate, and rituximab initially prevented disease progression, he experienced multiple relapses over the course of 2 years and eventually became refractory to treatment. Subsequently, the patient was started on vemurafenib, which resulted in the complete resolution of all lesions observed on MRIs. This response has persisted for 10 years since starting the medication. We suggest that besides its high response rate in systemic relapsed/refractory HCL, vemurafenib may offer benefits for patients with CNS involvement who are refractory to conventional chemotherapies and can achieve a durable response. Further investigation is needed to potentially establish vemurafenib as a first-line treatment option for HCL patients with CNS involvement.
PATH-01. COMPARATIVE EVALUATION OF THE DIAGNOSTIC AND PROGNOSTIC PERFORMANCE OF CNSIDE™ VERSUS STANDARD CYTOLOGY FOR LEPTOMENINGEAL DISEASE
Authors: Appel Haley , Rubens Muni , Saxena Anshul , Roy Mukesh , Mohler Alexander , Kotecha Rupesh , Hall Matthew , Ahluwalia Manmeet , Mehta Minesh , Castaneda Serguei , Odia Yazmin 
Published: November 2023

Abstract

OBJECTIVE
We compared the real-world performance of the cerebrospinal fluid (CSF) CNSide™ versus cytology assays in diagnosing leptomeningeal disease (LMD).

METHODS
Consecutive patients with suspected LMD from January 2020 to December 2022 who underwent lumbar punctures for CSF cytology and CNSide™ analyses were reviewed. LMD diagnosis was defined by EANO criteria. We used descriptive statistics, confusion matrix, Kaplan Meier curves, and Cox proportional regression methods to analyze outcomes.

RESULTS
87 patients with median age of 63 years (range:23-93) were evaluated, of which 82 (94%) met EANO positive (possible, probable, or confirmed criteria) cohort. Of the EANO cohort, 33 (40%) had uncontrolled systemic disease and 25 (46%) were on systemic therapy with medium/high CNS penetrance. The median time from initial cancer diagnosis to LMD was 31 months (range:21-43). LMD was diagnosed by CSF cytology (EANO confirmed) in 23 cases, all identified by CNSide™. CNSide™ identified an additional 13 cases, increasing diagnostic yield by 56.5%. Commonest primary histologies in the EANO cohort were breast (36, 44.0%) and lung (34, 41.5%); 18 (53.0%) of lung cancers harbored actionable molecular alterations, while breast cancers expressed hormone receptors in 27 (75%) and HER2 alterations in 8 (22%). Median overall survival (OS) for the CNSide™ cohort was 19.5 weeks (95%CI:11.0-28.0) and 31 weeks (95%CI:21-43) for EANO positive cases. Median OS for breast patients in CNSide™ cohort was 42 (R: 15-65) weeks, about 7-fold that of lung (median 6.5, R: 2-20). There was no correlation between OS and cell density by CNSide™ (HR:1.000, 95%CI:0.999-1.001, p=0.909). OS was higher for cases treated with intrathecal chemotherapy (HR:0.189, 95%CI:0.053-0.672, p=0.010), but not statistically different by radiotherapy modality (HR, 0.583, 95%CI:0.264-1.287, p=0.181).

CONCLUSIONS
This retrospective, single-institution, real-world analysis of CNSide™ showed increased sensitivity versus cytology and provided clinically relevant, cell-based molecular CSF analyses.
PATH-05. PRIMARY AND SECONDARY GLIOSARCOMA: RADIOLOGICAL AND PROGNOSTIC DIFFERENCES USING COMPREHENSIVE MULTI-OMICS ANALYSIS
Authors: Chen Ko-Ting , Chang Ian Yi-Feng , Hsu Peng-Wei , Chuang Chi-Cheng , Huang Yin-Cheng , Chen Pin-Yuan , Chang Chen-Nen , Liu Hsuan , Tan Bertrand Chin-Ming , Jung Shih-Ming , Wei Kuo-Chen 
Published: November 2023

Abstract
Purpose Gliosarcoma (GS), a rare variant of glioblastoma (GB), is further classified into primary (de novo) gliosarcoma (PGS), and secondary gliosarcoma (SGS), which is defined as recurrence after a diagnosis of diffuse glioma. Poorer survival of SGS than PGS has been reported, however, the detailed mechanism remains unknown. METHODS: A retrospective retrieval of pathological confirmed GS was performed. All the clinical, radiological, and pathological comparisons were based on the diagnosis of GS. A multi-omics, including whole exome sequencing, transcriptome, proteome and phosphoproteome, approach was used to acquire the molecular profiles of these specimens. RESULTS: From 2003 to 2020, a total of 28 GSs were identified, including 19 PGSs and 9 SGSs. The age tended to be younger in SGS group than PGS group (52.1 ± 10.9 vs. 60.8 ± 11.5, p=0.069). SGSs tended to present with dural attachment (p=0.071) and were significantly associated with major vessel encasement (p=0.002) than PGSs. The Ki-67 index tended to be higher in SGSs than PGSs (p=0.081). The GS survival was significantly shorter in SGS group than PGS group (median: 7.9 vs. 32.4 months, p&lt; 0.001). The multi-omics analysis demonstrated SGSs had significantly higher expression of negative regulation of megakaryocyte differentiation, telomere capping, and DNA replication nucleosome assembly pathways than PGSs. Next, using proteome / phosphoproteome nonnegative matrix factorization analysis, PGS was categorized into two clusters (PGS_C1 versus PGS_C2) with distinct multi-omics features. Of which, PGS_C1 (n=4) tended to have shorter survival than PGS_C2 (n=15, p=0.054). Notably, the survival of patients in PGS_C1, who had similar multi-omics signature to SGS, were as poor as those of SGSs. CONCLUSIONS: In summary, this study provides, for the first time, in depth evidence for understanding GS and presents multi-omics biomarkers with prognostic significance. Further therapeutic translation should based on current findings to benefit GS patients.
PATH-06. HISTOPATHOLOGICAL CHARACTERISTICS OF TREATMENT-INDUCED EFFECTS VERSUS PROGRESSION IN 180 RE-RESECTION SAMPLES FROM IRRADIATED GLIOMAS GRADE 2-4
Authors: Flies Christina , Becker Aline , van Hecke Wim , Kobalka Peter , Robe Pierre , Snijders Tom 
Published: November 2023

Abstract
Histopathological studies of re-resected glioma tissue are considered the gold standard to distinguish actual tumor progression (TP) and treatment-induced effects (TIE) after radiotherapy. The objectives of this mono-center, retrospective cohort study were to provide detailed histopathological characterization of re-resected glioma tissue, and to correlate pathological findings with survival (data driven). Consecutive adults with a diffuse glioma (WHO grade 2-4), previously treated with (chemo-)radiation and progressive lesion were reviewed. New histological slides from the recurrent-resected tissue were prepared and stained with routine and exploratory immunohistochemical (IHC) stains. Two neuropathologists used a scoring sheet to independently assess 33 items on standard H&E and IHC stains. We included 180 samples, from 165 patients. Of these, 159 samples (88.3%) originated from a second resection (first re-resection). TIE were diagnosed in 34 (19%), a mixed TIE and TP lesion in 91 (51%), and TP in 55 (31%). Median survival after first re-resection for the groups TIE, mixed and TP were respectively 14.4 (interquartile range (IQR)=8.7-42.4), 7.6 (IQR=4-12.9) and 11.5 months (IQR=7.2-25.4). A diagnosis of TIE was associated with histological findings of hyalinization, endothelial thickening, cortical infiltration, (radio)necrosis, thrombosis, lymphocytic infiltration (CD3, CD8 positive), and positivity for CD34. Percentage of viable tumor and PTBP1 stain correlated negatively with TIE. Survival in the group TIE was significantly longer than in the groups with any viable tumor (p-value of log-rank test 0.008). In multivariable Cox regression analysis, hemorrhage and higher PTBP1 positivity were associated with a poor overall survival after re-resection. Dystrophic calcifications, IDH mutations, and a higher KPS correlated with improved survival. In conclusion, we confirm the previously described characteristics of treatment-induced effects in a large consecutive cohort of re-resected diffuse gliomas. However, none of these characteristics correlated with survival. PTBP1 could be a promising marker to differentiate TIE from TP in treated glioma samples.