bluuebunny/crossref_metadata_2025_split huggingface dataset:
EXTH-85. EPHA3 CART: DUAL TARGETING OF GLIOBLASTOMA AND TUMOR MICROENVIRONMENT
Authors: Ruff Michael , Ogbodo Ekene , Siegler Elizabeth , Sakemura Leo , Sarkaria Jann , Kenderian Saad 
Published: November 2023

Abstract

BACKGROUND
In GBM, effective chimeric antigen receptor T-cell (CART) therapy remains a challenge; immunosuppressive components within the tumor microenvironment (TME) inhibit CART cells. EphA3 is a receptor tyrosine kinase with low expression in adult tissues but is highly expressed in tumor neovasculature and tumor stromal cells in GBM and other solid tumors.

METHODS
We performed RNA sequencing and Immunohistochemical staining for of EphA3 in a clinically annotated GBM PDX biobank and M01 M1 and M2 polarized macrophages. We then investigated the suppressive capability of M2 macrophage on EphA3-CART in an SNB-19 GBM cell co-culture. We tested the antiantitumor potential of EphA3-CART against luciferase+ SNB-19 GBM cells in vivo with flank and orthotopically engrafted NOD-SCID-ɣ-/- (NSG) mice. Engraftment was confirmed by bioluminescent imaging (BLI) and vernier caliber (flank) for 7-14 days post-injection. Mice were randomized to be treated with EphA3-CART or untransduced T-cells (UTD). Subsequently tumor size and mouse survival was monitored to determine the antitumor effect.

RESULTS
EphA3 was highly expressed on GBM PDX models as well as M2 macrophages. Compared to M0 and M1 macrophages, M2 macrophages significantly suppressed EphA3-CART However, despite the suppressive activity of the M2 macrophage, EphA3-CART exhibited significant antitumor activity . In both flank and orthotopically implanted mouse models, there was an observed reduction in tumor volume with EphA3-CART treated model compared to the UTD counterpart. EphA3-CART treatment resulted in significantly improved survival of the treated models compared to UTD models (hazard ratio = 0.053 **p = 0.005).

CONCLUSION
We demonstrate that EphA3 is expressed on GBM cells as well as on M2 macrophages. EphA3 CART is able to overcome and ameliorate the effect of a major component of the tumor microenvironment (TME), M2 macrophages. EphA3 CART appears effective in flank and orthotopic mouse models of GBM.
QLTI-09. INTEGRATION OF NEURO-ONCOLOGY CLINICAL PATHWAYS IN PROVIDENCE SOUTHERN CALIFORNIA CLINICAL RESEARCH NETWORK: UPDATED INFO AFTER 17 MONTHS OF UTILIZATION
Authors: Bott Thomas , Parseghian Nanor , Babcock Trisha , Sharma Akanksha , Wagle Naveed , Carrillo Jose , Juarez Tiffany , Kesari Santosh 
Published: November 2023

Abstract

INTRODUCTION
ClinicalPath is an evidence-based oncology decision support and analytics tool for cancer care. ClinicalPath’s treatment recommendations are prioritized based on efficacy, toxicity, and cost, by a nationwide committee of oncologists. The pathways are updated quarterly with the most recent evidenced-based treatment options that healthcare providers choose for adoption to help standardize therapy, improve quality, and decrease cost. The pathway system also allows for local clinical trial mapping to promote clinical trial awareness and help increase enrollment. ClinicalPath provides clinical pathways delivering personalized, evidence-based oncology guidance at the point of care. ClinicalPath’s network in North America serves more than 2,000 cancer physicians, within 54 practices in 31 states (15 academic medical centers, 29 hospital systems, and 9 community practices). Population: Our population is derived from multiple hospitals in Southern California within the Providence Health System. Methodology: Medical oncologists and Advanced Practice Providers received training on ClinicalPath before go-live. ClinicalPath was integrated into the Epic EHR in multiple Southern CA hospitals in a single month in Jan 2022.

RESULTS
On reviewing the utilization data within our Southern California region from Jan 2022-May 2023, 2681 treatment decisions were made across all cancers, with 86.7% of cancer patients treated on pathway. Of these decisions, 114 were made within the neuro-oncology specialty, and 70.2% of those cancer patients were treated on pathway.

CONCLUSION
We successfully integrated and initiated ClinicalPath in a multiple hospital-affiliated community oncology clinical trial network which included a strong neuro-oncology presence. We are actively working across our Southern California Region to map locally available clinical trials to promote awareness and increase enrollment. Provider utilization and patient on-pathway rates are actively monitored and will be updated.
QOL-16. GLIOBLASTOMAS LOCATED IN THE RIGHT INFERIOR PARIETAL LOBE CAUSE A POOR POSTOPERATIVE PERFORMANCE LEVEL
Authors: Nakada Mitsutoshi , Nakajima Riho , Kinoshita Masashi 
Published: November 2023

Abstract

OBJECTIVE
Managing quality of life has become more important for patients with glioblastoma (GBM). Maintaining independence levels should be given attention while treating GBM. Postoperatively, non-dominant hemispheric GBMs often decrease the Karnofsky Performance Status (KPS) score. This study aimed to investigate the factors that lead to poor KPS scores after tumor resection in non-dominant hemispheric GBM.

METHODS
Forty-one patients newly diagnosed GBM in the right cerebral hemisphere who underwent resection were included. Brain functions were assessed preoperatively and postoperatively. First, the KPS scores before and after surgery were compared. Second, univariate and multiple regression analyses and voxel-based lesion-symptom mapping (VLSM) were performed to analyze the functions and brain regions related to KPS, respectively. Third, factors associated with prognosis were analyzed using the log-rank test.

RESULTS
Compared with the preoperative status, KPS significantly decreased after the surgery (81.0% vs. 73.6%, p = 0.020). Brain functions affecting KPS include general cognitive function, processing speed, attention, memory, visuospatial cognition, emotion recognition, and executive function. Among these, multiple regression analysis revealed visuospatial cognition and emotion recognition to be significantly influenced KPS in the chronic postoperative phase (p = 0.030 and 0.048, respectively). VLSM demonstrated that resection of the inferior parietal lobe caused a significant decline in KPS. Visuospatial cognition and emotion recognition were impaired with a higher probability (p = 0.035 and 0.048, respectively) in patients with tumors located in the inferior parietal lobe. In addition, lesions in the inferior parietal lobe were associated with shorter overall survival (p = 0.046).

CONCLUSIONS
GBMs in the right inferior parietal lobe are more likely to result in poor postoperative KPS due to impairment of visuospatial cognition and emotion recognition, which relate to a poor prognosis.
QOL-21. TARGETING FEAR OF CANCER RECURRENCE IN GLIOMA: OPEN PILOT TRIAL RESULTS OF FEARLESS IN NEURO-ONCOLOGY
Authors: Loughan Ashlee , Braun Sarah , Lanoye Autumn , Davies Alexandria , Fox Amber , Kleva Chris , Zarrella Giuliana 
Published: November 2023

Abstract

BACKGROUND
Individuals with glioma endorse fear of cancer recurrence (FCR), but existing interventions for FCR are not entirely translatable to neuro-oncology. We consulted international FCR experts and advisory boards comprised of neuro-oncology professionals, patients, and caregivers to assist in creating a 6-module psychotherapy targeting FCR in glioma patients and caregivers: FearLess in Neuro-Oncology. Intervention modules will be discussed in-depth.

METHODS
The ongoing telehealth FearLess pilot aims to enroll 24 participants (6 glioma patients, 6 caregivers, 6 dyads) with clinical levels of FCR. Participants complete pre- and post-intervention surveys in addition to an exit interview. Data collection includes rates of screening, enrollment, module duration, session satisfaction, and intervention recommendations.

RESULTS
Of the 32 individuals screened, 16 enrolled (patients n = 6; caregivers n = 4; dyads n = 3), to date. All enrolled participants completed baseline assessments, with 15 trial initiators. 100% of trial initiators completed post-intervention surveys. Administration of the 6-module intervention averages 10 weekly, 60-minute sessions necessary for completion. All FearLess intervention completers have found it beneficial (100%) and would recommend to others (100%). Two patients recommended a shorter intervention duration and two caregivers recommended a longer duration. Preliminary analyses show reductions in FCR severity for 10 of 11 completed participants (MFCRI Reduction = 27.1, range = 4-50).

CONCLUSION
FearLess study procedures and intervention appear to be acceptable, thus far. Recruitment feasibility has been variable; caregiver participation is the primary concern given that caregiver and dyad arms remain open to accrual while the patient-only arm achieved its enrollment goal relatively quickly. Additional feasibility data is needed in order to understand how to best recruit caregivers of individuals with glioma into a psychological intervention targeting FCR. Despite the recruitment challenge, some caregivers recommended increased intervention duration, reinforcing the need for support in this vulnerable population. Continued optimization of FearLess in Neuro-Oncology is encouraged prior to larger-scale trials.
QOL-26. A RANDOMIZED, DOUBLE-BLIND PHASE 3 STUDY OF VORASIDENIB VS PLACEBO IN PATIENTS WITH MUTANT IDH1/2DIFFUSE GLIOMA (INDIGO): ANALYSIS OF HEALTH-RELATED QUALITY OF LIFE, NEUROCOGNITION AND SEIZURES
Authors: Peters Katherine , Mellinghoff Ingo , van den Bent Martin , Blumenthal Deborah , Touat Mehdi , Clarke Jennifer , Mendez Joe , Yust-Katz Shlomit , Mason Warren , Ducray Francois , Umemura Yoshie , Burt Nabors L , Holdhoff Matthias , Hottinger Andreas , Arakawa Yoshiki , Sepúlveda Juan , Wick Wolfgang , Soffietti Riccardo , Perry James , Giglio Pierre , de la Fuente Macarena , Maher Elizabeth , Bottomley Andrew , Zhao Dan , Pandya Shuchi , Steelman Lori , Hassan Islam , Wen Patrick , Cloughesy Timothy 
Published: November 2023

Abstract

INTRODUCTION
The Phase 3 INDIGO study (NCT04164901) is a randomized, double-blind evaluation of vorasidenib, an oral, brain-penetrant inhibitor of mutant isocitrate dehydrogenase (mIDH) 1/2 enzymes, compared with placebo, in patients with grade 2 mIDH1/2 diffuse gliomas, whose only prior treatment was surgery. The primary endpoint, radiographic progression-free survival by blinded independent review committee, and the key secondary endpoint, time-to-next-intervention, were significantly improved with vorasidenib versus placebo. As these patients are young, with several years’ life expectancy, impact of treatments on health-related quality of life (HRQoL), cognition and symptomatic burden is of interest.

METHODS
HRQoL, assessed by Functional Assessment of Cancer Therapy-Brain (FACTBr) questionnaire, was a secondary endpoint. FACT-Br was collected at baseline, Cycles 2 and 3, then every 3 months. Scores were interpreted using an estimate of clinically meaningful deterioration change from baseline for each arm. Exploratory endpoints included neurocognitive function, assessed by a validated battery of cognitive performance instruments, and seizure frequency and severity, assessed using a subject diary.

RESULTS
331 patients were randomized to vorasidenib (n = 168) or placebo (n = 163) (median age, 40.0 years; Karnofsky performance scale = 100, 53.5%; ongoing medical history of seizures, 54.1%). Median follow-up was 14.2 months. No clinically meaningful deterioration from baseline FACT-Br total score and subscales were observed at any timepoint through the median treatment duration (Cycle 13) in either arm. At baseline, active seizures (≥ 1 seizure in the previous 30 days) were reported in 20/168 (11.9%) vorasidenib patients and 20/163 (12.3%) placebo patients. On-treatment seizure frequencies and cognition outcomes will be presented by arm.

CONCLUSION
INDIGO is the first randomized Phase 3 study of targeted therapy in grade 2 mIDH1/2 diffuse glioma. HRQoL, as measured by FACT-Br, was maintained during treatment with vorasidenib. These data support the clinical benefit of vorasidenib in this patient population for whom chemotherapy and radiotherapy are being delayed.
QOL-28. THE LIVED EXPERIENCE OF PATIENTS WITH CHORDOMA – A RETROSPECTIVE CASE SERIES
Authors: Mauritson Emmaline , Nguyen Minhdan , Truong Judy , Chow Jared , Wagle Naveed , Carrillo Jose , Kesari Santosh , Juarez Tiffany , Barkhoudarian Garni , Kelly Daniel , Lekovic Gregory , Sharma Akanksha 
Published: November 2023

Abstract

BACKGROUND
Chordoma is a rare malignant tumor arising from the skull base or spine with limited treatment options and poor prognosis. Patients with chordoma experience significant physical and emotional symptoms deleterious to quality of life (QOL). Current literature detailing the experiences of patients with chordoma, including end of life, is limited. Each patient’s course differs depending on tumor location, lesion size, metastatic nature of disease, and treatments. We sought to better understand the lived journey of the chordoma patients seen in our center.

METHODS
This was a retrospective chart review that evaluated a cohort of chordoma patients seen at our center from March 2017 to May 2023. RESULTS/

CONCLUSION
A total of 18 patients were included. Average patient age at diagnosis was 53.3 years old (range: 23 to 87 years). Majority were female (67%) and 78% were White/Caucasian. Clival tumors were most common (55%), followed by spine (sacral (28%) and cervical (17%)). Nearly all tumors were recurrent (94%), almost half were metastatic (44%). All patients underwent tumor resection; the average number of surgeries underwent per patient was 2.7. Fifteen patients received radiation (83%) and sixteen patients participated in at least one clinical trial (88%). The average Karnofsky Performance Scale (KPS) at the initial outpatient visit was 80, which decreased to 72.2 by last outpatient visit. Most reported symptoms included emotional distress (78%), neuropathic pain (72%), muscular and bone pain (56%), vision changes (44%), dysphagia (39%), and headaches (39%). The average survival from diagnosis was 3.7 years (range: 2 to 23 years). Eight patients (45%) have passed, 5 of whom were enrolled on hospice at the time of death. Causes of death included seizures (1), respiratory failure due to tumor progression (3), bowel ischemia (1), medical aid in dying (1) and failure to thrive (1).
RBIO-03. BENEFICIAL CLOSTRIDIUM SPP ORAL SUPPLEMENTATION MITIGATES RADIATION-INDUCED COGNITIVE DYSFUNCTION WITH GUT MICROBIOTA MODULATION IN RICD MICE
Authors: Bekal Mahesh , Das Tushar , Blasco-Conesa Maria P , Jagadeesan Gayathri , Ballester Leomar , Ganesh Bhanu Priya , Esquenazi Yoshua 
Published: November 2023

Abstract
Radiation therapy (RT) a critical treatment for brain tumors; often leads to radiation-induced cognitive dysfunction (RICD), which significantly impacts patients' quality of life. The gut microbiome and its metabolites play a crucial role in regulating CNS function, RT disturbs the balance of the gut microbiota causing dysbiosis (imbalance in beneficial microorganisms), and Gut-dysbiosis have been linked to various cognitive disorders. This study aims to investigate the effects of RT on the gut-microbiome and cognitive function, C57BL/6 mice were exposed to Sham/9Gy/15Gy cranial irradiation and conducted cognitive tests using the Y-maze and Novel Object Recognition Test at different time points. Both 9Gy and 15Gy irradiation led to significant cognitive dysfunction at 10 and 30 days post-irradiation. We collected fecal samples before RT and at 10 and 30 days after RT to extract microbial DNA. The 16S rRNA gene was sequenced and analyzed using the ATIMA visualization toolkit. By comparing pre-irradiation samples with samples at 10 and 30 days post-irradiation, we observed significant gut dysbiosis in both 9Gy and 15Gy irradiated mice. The 15Gy group exhibited more pronounced and consistent changes in fecal microbiome diversity following RT. Notably, the Clostridium group at the order, family, and genus levels consistently decreased in the 15Gy irradiated mice. Certain Clostridium species are known as major producers of Short Chain Fatty Acids (SCFAs) in the gut. Based on this, we hypothesized that oral supplementation with beneficial SCFA-producing bacteria could ameliorate RICD. To test this hypothesis, a separate group of mice received 15Gy RT along with oral gavage containing a cocktail of Clostridium strains. After a 20-day post-irradiation, cognitive tests revealed that the group supplemented with Clostridium spp exhibited significantly improved cognitive performance. Our findings suggest that gut dysbiosis may contribute to RICD, and oral supplementation of SCFA-producing bacteria could be a potential strategy to mitigate RICD.
RBIO-06. COMBINING FLASH RADIOTHERAPY WITH GD2-CAR T CELL IMMUNOTHERAPY IN DIFFUSE INTRINSIC PONTINE GLIOMA
Authors: Soderholm Haille , Kiger Zara , Kim Wonju , Majzner Robbie , Lau Bonnie 
Published: November 2023

Abstract
Diffuse Intrinsic Pontine Glioma (DIPG) is the leading cause of brain tumor related deaths in pediatric cancers. DIPG is completely lethal, and palliative radiation therapy (RT) to control symptoms is currently the standard-of-care treatment for DIPG, therefore effective treatment is urgently needed. In recent phase 1 clinical trials, the promising potential for using chimeric antigen receptor T cell immunotherapy against the disialoganglioside GD2 (GD2-CART) has been established, where 75% of patients exhibited clinical and radiographic improvement. There has also been emerging evidence advocating for the combined use of GD2-CART therapy with conventional radiation (CONV-RT) to enhance the immune response in other solid brain tumors. Ultra-high dose rate radiotherapy, abbreviated as FLASH-RT, is an emerging radiation technique shown to reduce normal brain tissue damage while preserving tumor control, as compared to CONV-RT. It is currently unknown how FLASH-RT will affect CART therapy. We hypothesize that effective treatment for DIPG can be achieved by combining FLASH-RT with GD2-CART immunotherapy. We have shown FLASH-RT to equivocally kill DIPG cells as well as the standard-of-care, CONV-RT; Given the neurological tissue sparing effects of FLASH-RT, this radiotherapy alone could be an improvement for DIPG treatment. Additionally, we have validated that GD2 is highly expressed in our DIPG cell line, suggesting high GD2-CART target specificity. Additionally, we have found that GD2 expression on DIPG tumor cells remains unchanged upon treatment with FLASH-RT. Therefore, we can utilize FLASH-RT to target GD2 CART while sparing normal tissue and minimizing neurotoxicity, allowing for a promising avenue of combination treatment for this devastating pediatric cancer.
SURG-07. CLIVAL CHORDOMA: A COMPREHENSIVE META-ANALYSIS OF OPERATIVE MARGINS, PROGRESSION FREE SURVIVAL, AND OVERALL SURVIVAL
Authors: Brown Nolan , Kuo Cathleen , Nguyen Oanh , Neil Zachery , Gendreau Julian 
Published: November 2023

Abstract
Despite their precarious behavioral classification (histopathologically benign (low-grade), behaviorally malignant), great strides have been taken to improve prognostication and treatment paradigms for patients with skull base chordoma. However, due to the rarity of this tumor, prior investigations remain limited to small retrospective series. Accordingly, we performed a systematic review and meta-analysis in order to profile surgical and survival outcomes for skull base chordoma. Fixed and random-effect meta-analyses were performed for categorial variables including number of males, GTR, STR, 5-year OS, 10-year OS, 5-year PFS, and 10-year PFS. Following the systematic search and screen, 47 studies published between 1993-2020 reporting data for 2204 patients remained eligible for analysis. Sex distribution was comparable between males and females, with a slight predominance of male-identifying patients (0.5625 [0.5418;0.3909]). Average age at diagnosis was 42.4 ± 12.5 years, while average age of treatment initiation was 43.0 ± 10.6 years. Overall, there was a substantial degree of heterogeneity across the 47 studies (I^2=56.3% [44.0%; 65.9%]). With respect to operative margins, the rate of GTR was 0.3323 [0.2824; 0.3909], I^2 = 91.9% [90.2%; 93.4%], while the rate of STR was significantly higher at 0.5167 [0.4596; 0.5808], I^2 = 93.1% [91.6%; 94.4%]. Interestingly, 5-year OS rate was 0.7113 [0.6685; 0.7568], I^2 = 91.9% [90.0%; 93.5%]. Furthermore, 10-year OS rate was 0.4957 [0.4230; 0.5809], I^2 = 92.3% [89.2%; 94.4%], which was comparable to both 5-year PFS rate of 0.5054 [0.4394; 0.5813], I^2 = 84.2% [77.6%; 88.8%] and 10-yr PFS rate of 0.4949 [0.4075; 0.6010], I^2 = 14.9% [0.0%; 87.0%]. There were 55 reported deaths for a perioperative mortality rate of 2.5%. The most common complication was CSF leak(5.4%). Overall, these results indicate good 5-year outcomes; however, 10-year prognosis for skull base chordoma remains poor due to its radiotherapeutic resistance and high recurrence rate.
SURG-11. RISKS AND BENEFITS OF REPEATED RESECTION FOR GLIOBLASTOMA: A SINGLE INSTITUTION REVIEW OF CHARACTERISTICS AND OUTCOMES OF RESECTION OF RECURRENT GLIOBLASTOMA
Authors: D'Agostino Erin , Beach Isidora , Liebelt Brandon , Thomas Alissa 
Published: November 2023

Abstract
Maximal safe resection is standard for newly diagnosed glioblastoma, but for recurrent glioblastoma the value of resection is less clear. We performed a retrospective, single-institution analysis of sequential patients undergoing re-resection for recurrent glioblastoma and analyzed pre-operative risk factors, progression free and overall survival from time of re-resection to death or last follow-up (PFS/OS), and complication rates. Between 2017 and 2022, 38 patients underwent re-resection of glioblastoma (defined by 2016 WHO criteria, 86.8% IDH wild type) and were followed for an average of 157 weeks (range 17-553). The cohort had a mean age of 59.4 years (range 39-87), was 55% male, and included 68.4% MGMT unmethylated tumors. Preoperatively, median Karnofsky Performance Score (KPS) was 80 (range 50-100), and median modified frailty index (mFI-5) was 0 (range 0-4). Re-resection occurred an average of 55.3 weeks after initial resection (SD 59.6, range 5-314), 25.0 weeks after chemotherapy (SD 51.8), and 39.9 weeks after radiation (SD 45.1). Mean OS after re-resection was 67.4 weeks (SD 91.5, range 1-505 weeks), median 59.5 weeks. Average PFS was 24.5 weeks (SD 25.3, range 1-139). The complication rate was 34.2% (n = 15), including 6 patients (15.8%) with a wound infection and 5 (13.1%) with symptomatic hemorrhage. 12 (31.6%) patients had a new neurologic deficit. Postoperative KPS was lower than preoperative KPS (p = .002). Patients with &lt;20 weeks between surgeries, mFI &gt;1, or KPS &lt;80 had higher rates of complications (respectively p = .04, p = .03, p = .03). Patients with mFI &gt;1 or KPS &lt;70 were more likely to die within 30-days of surgery (respectively p = .014; p = .018). Re-resection demonstrated a survival benefit, especially for patients younger than 65 with a mFI of &lt; 2. Though complications were common, post-operative complications were not associated with a shorter overall survival. Consideration for age, frailty, KPS, and timing of surgery may guide selection of patients for re-resection.