bluuebunny/crossref_metadata_2025 huggingface dataset:
QLTI-06. EVALUATING TWO DECADES OF GLIOBLASTOMA CARE IN THE UNITED STATES VETERANS HEALTH ADMINISTRATION
Authors: Johnson Margaret O , Tseng Chin-Lin , Rowe Kerry , Passero Vida A , Kelley Michael J , Ahmed Sara T , Mooney Michael A
Published: November 2023

BACKGROUND

The Veterans Health Administration (VHA) provides healthcare for U.S. military Veterans, including specialized care for glioblastoma (GBM). This study aimed to understand patterns of care and outcomes for Veterans with GBM.

METHODS

We derived a retrospective cohort of U.S. Veterans with histological diagnosis of GBM in 2000-2021 from the VHA cancer registry system (CRS), with follow-up times through May 31, 2022. Data sources were patient-level electronic health records, CRS, and other data from the VHA corporate data warehouse. Using descriptive statistics, we describe demographics, treatments, clinical outcomes, referral patterns, and overall survival (OS).

RESULTS

We identified 3,802 Veterans with GBM (median per year = 176, range 76-225). Among the 465 veterans diagnosed in 2018-2021, 192 (41%) had unknown IDH mutational status. The median age at diagnosis was 66 years (range 20-101), most were male (97%), non-Hispanic (78%) and white (70%). 32% were considered rural and 2% highly rural. 71% received radiation and 61% (n = 2,301) received systemic therapy with the most common being temozolomide (96%), bevacizumab (16%), and lomustine (6%). First use of Novo-TTF was February 2020 with a total of 25 total users to-date. Between 2018-2021, 57% (range 54-63%) of veterans received cancer-related community referrals (i.e. medical oncology, radiation oncology, or neurosurgery). The yearly rate of palliative care referrals remained ≥40% since 2008 and was highest in 2021 (64%). Median OS was 6.9 months (95% CI:6.6-7.3).

CONCLUSIONS

Using the largest cohort of Veterans with GBM, we identified gaps in molecular testing data and note a large fraction that received community care referrals. Patterns of cancer-directed therapy appear consistent with best practices, although the unadjusted median OS for Veterans was shorter than reported in other populations. In response to these findings, VHA is developing strategies to improve access, quality and research for Veterans with GBM.
QLTI-12. ADULT NEURO-ONCOLOGY TRIAL LANDSCAPE IN THE UNITED STATES OVER FIVE DECADES
Authors: Smith Emily , Naik Anant , Goel Mahima , Wen Patrick , Lim Michael , Chang Susan , Germano Isabelle
Published: November 2023

PURPOSE

The unmet therapeutic needs in neuro-oncology remain significant due to the biological and clinical challenges. Clinical trials are important to close the gap between therapeutic unmet needs and scientific advances. This study aims at analyzing the landscape of neuro-oncology trials to identify completion and failures and guide strategies for the path forward.

METHODS

US-registered adult neuro-oncology clinical trials were extracted from www.clinicaltrials.gov (1966-2019) to include funding source, trial type, scope, phase, and subjects’ demographics. Trial failures comprised “terminated,” “withdrawn,” and/or “suspended” trials. Univariate and multivariate analysis were used to detect differences across factors and over time.

RESULTS

Our search yielded 4522 trials, 1257 eligible for this study. In 25 US States, neuro-oncology trials availability is < 0.85/100,000 population. Over time, completed trials have decreased with a significant increased percentage of trial failures from 22% to 36% (p < 0.001). Overtime, NIH funding decreased from 47% to 24% (p < 0.001). Inclusion of subjects ≥ 65-year-old and women increased in the last decade (p < 0.001) while inclusion of Hispanic subjects has decreased (p < 0.001). The top two reasons for failure included accrual and operational difficulties. Industry-funded trials had a trend toward higher failure rate than NIH-funded. A larger proportion of women (p < 0.001), non-Hispanic subjects (p = 0.001), and older adult (p < 0.001) patients were enrolled in completed trials than in failed trials.

CONCLUSION

Our study is the first report on the neuro-oncology clinical trial landscape in the US over time. The data support the concept that strategies to further the availability of clinical neuro-oncology trials within the US are necessary. As these are developed, attention is needed to identifying and modifying factors contributing to clinical trial failures.
QOL-08. LONGITUDINAL EFFECTS OF A PSYCHOLOGICAL INTERVENTION FOR CAREGIVERS OF PATIENTS WITH PRIMARY MALIGNANT BRAIN TUMORS: SECONDARY ANALYSIS OF A RANDOMIZED CONTROLLED TRIAL
Authors: Strander Sumita , Podgurski Alyx , Datta Shibani , Pintro Kedie , Horick Nora , Greer Joseph , Traeger Lara , El-Jawahri Areej , Sannes Timothy , Temel Jennifer , Jacobs Jamie , Forst Deborah
Published: November 2023

BACKGROUND

Caregivers of patients with primary malignant brain tumors (PMBT) experience high rates of anxiety. In our randomized controlled trial assessing the effects of a caregiver-directed, telehealth-based psychological intervention (“NeuroCARE”), NeuroCARE participants had significantly lower anxiety symptoms (primary outcome) and depression symptoms, and better self-efficacy and coping immediately post-intervention compared to usual care (UC). We subsequently examined the longitudinal effects of NeuroCARE on caregiver-reported outcomes across all study timepoints.

METHODS

We enrolled and randomized 120 caregivers of patients with PMBT to NeuroCARE (N = 60) versus usual supportive care (N = 60). Eligible participants had significant baseline anxiety symptoms (Generalized Anxiety Disorder-7 score ≥ 5). We collected caregiver-reported anxiety symptoms (Hospital Anxiety and Depression Scale (HADS)–Anxiety Subscale), depression symptoms (HADS–Depression Subscale), self-efficacy (Lewis Cancer Self-Efficacy scale), coping (Measure of Current Status), quality of life (QOL; CareGiver Oncology Quality of Life survey), caregiver burden (Caregiver Reaction Assessment) and post-traumatic stress disorder (PTSD) symptoms (PTSD Checklist for DSM-5) at baseline, 11 weeks (immediately post-intervention) and 16 weeks (one-month post-intervention). We used mixed effects linear regression models to assess longitudinal intervention effects on study outcomes.

RESULTS

Enrolled caregivers had a mean age of 53 years; the majority were female (99/120; 82.5%) and were the patient’s spouse/partner (84/120; 70%). NeuroCARE participants experienced greater improvement than UC in depression symptoms (change/week [slope]: -0.09 vs. -0.01, p = 0.041), self-efficacy (slope: 0.64 vs. -0.17, p = 0.006) and coping (slope: 0.31 vs. -0.01, p < 0.001). We observed non-statistically significant differences between NeuroCARE and UC for change in anxiety symptoms (slope: -0.13 vs. -0.05, p = 0.059) and QOL (slope: 0.26 vs. 0.04, p = 0.050). Study arms did not differ in longitudinal trajectories for caregiver burden or PTSD symptoms.

CONCLUSIONS

NeuroCARE participants experienced greater improvements over time in depression symptoms, self-efficacy, and coping than UC participants, highlighting the sustained benefits of this caregiver-directed supportive intervention.
QOL-23. BASELINE TOTAL BRAIN VOLUME PREDICTS FOR POORER QOL AND REDUCED OVERALL SURVIVAL AFTER CRANIAL RADIOTHERAPY IN OLDER PATIENTS WITH GLIOBLASTOMA (GBM): RESULTS FROM THE PROSPECTIVE BRITER STUDY
Authors: Lorimer Cressida , Chalmers Anthony , Mills Samantha , Thompson Gerard , Glendenning Jennifer , Coombes Isobelle , Brock Juliet
Published: November 2023

GBM incidence peaks in the 7th and 8th decades of life with prognosis worsening with age. Short-course partial brain radiotherapy, +/- chemotherapy, extends survival but there is no validated evidence for prediction of individual risk of acute radiotherapy related side effects. BRITER, a prospective multicentre observational trial, recruited patients with newly diagnosed GBM aged ≥ 65 planned for cranial radiotherapy. Baseline MRI scans were analysed for 5 putative markers of brain resilience including relative total brain volume (ratio of cerebrospinal fluid (CSF) volume to total intracranial volume (TIV)) and their relationship to change in QoL. 126 patients were enrolled; mean age 72 years (range 65-83); 67% men, 33% women. 4% had a radiological diagnosis, 19% biopsy and 77% had debulking surgery. 21% received palliative radiotherapy alone (25% 30Gy/6#, 75% 40Gy/15#), 79% received radiotherapy with concurrent TMZ (47% 40Gy/15#, 53% 60Gy/30#). Median OS was 11.3 months. After accounting for age, sex, treatment and baseline MoCA score, there was a significant relationship between baseline CSF:TIV ratio and change in QoL score at 8 weeks post treatment. For each unit point of increase in CSF:TIV ratio, there was a corresponding decrease in EORTC QLC C30 QoL score by a factor of 1.27 (coefficient -1.27, 95% CI -3.24 to -0.19 p = 0.02). 35 participants were too unwell to complete questionnaires or had died by the 8 week follow up visit. In this subgroup, post hoc logistic regression showed baseline CSF:TIV ratio was related to risk of non-attendance (OR 1.35, 95% CI 1.01-1.80, p = 0.04). Cox regression models were fitted for time to death in 88 participants who had analysable baseline MRI sequences. Baseline CSF:TIV was associated with worsened OS (HR 1.41, 95% CI 1.19-1.66, p < 0.001). This unique prospective study indicates that baseline imaging parameters can predict the impact of cranial radiotherapy on QoL and OS.
QOL-29. ILLNESS UNDERSTANDING AND RELIGIOUSNESS IN PATIENTS WITH RECURRENT GLIOBLASTOMA
Authors: Fortunato John , Walsh Leah , Polacek Laura , Panageas Katherine , Reiner Anne , Walbert Tobias , Thomas Alissa , Buthorn Justin , Sigler Allison , Prigerson Holly , Applebaum Allison , Diamond Eli
Published: November 2023

BACKGROUND

Glioblastoma (GBM) is an aggressive neurologic malignancy with invariably poor prognosis. However, there is evidence that patients with GBM often have unrealistic perceptions of their prognosis. Strong religious beliefs have been shown to be associated with limited illness understanding (IU) in patients with advanced cancer, but IU and religiousness have not been investigated in patients with GBM.

METHODS

Patients enrolled in a prospective multi-center study of recurrent GBM (Coping with Glioblastoma; NCT02375841) completed surveys after a clinical encounter with their oncologist revealing GBM progression. Psychometrically validated measures assessed parameters of IU and religiousness. IU was compared between participants with at least a moderate or high degree of religiousness (vs. not) using Fishers-exact test.

RESULTS

Twenty-four adult patients (median age 57) completed surveys. Fifteen (63%) identified their illness as terminal. Six patients (25%) correctly identified their life expectancy (months), eight patients predicted life expectancy of years (33%) and ten (42%) did not know or answer. Eleven (46%) reported being moderately or very religious, while nine (38%) were slightly or not at all religious. There was significantly less frequent awareness of terminal illness amongst patients identifying as religious, spiritual, or as feeling God’s presence (all p < 0.05). There was significantly less frequent IU amongst patients identifying as spiritual or believing in miracles (both p < 0.05).

CONCLUSION

IU is infrequent in recurrent GBM and is significantly less frequent in patients endorsing religiousness and spirituality. Strategies to improve IU, broadly and in alignment with religious and spiritual beliefs, are warranted.
RBIO-11. BASAL BCL-2-INTERACTING MEDIATOR OF CELL DEATH (BIM) RESPONSIVENESS CORRELATES WITH RADIOSENSITIVITY IN MENINGIOMA
Authors: Harary Maya , Fernandez Elizabeth , Casaos Joshua , Vitte Jeremie , Nathanson David , Na Brian , Prins Robert , Giovannini Marco , Everson Richard
Published: November 2023

INTRODUCTION

Radiotherapy remains the primary adjunctive treatment for recurrent or progressive meningioma. Nevertheless, varied clinical response to radiotherapy in meningioma remains a challenge, particularly in higher grade tumors. Currently there is a paucity of predictors of radio-sensitivity. Bim peptide is an intrinsic mediator of apoptosis, and Bim-responsiveness has been postulated as a metric of general sensitivity to apoptotic stress. Herein we investigated its utility as a metric of radio-sensitivity in meningioma.

METHODS

In an in vitro model of meningioma, a number of immortalized human and murine meningioma cell lines and patient-derived primary cultures (WHO grades 1 + 2), were exposed to ionizing radiation at range of doses (0, 2, 4, 8, 16Gy); cells were counted (Celigo, Nexelcom) to assess for growth. Separately, cultures were irradiated at 4Gy and apoptosis was analyzed 24H later using Annexin/PI staining by flow cytometry (Attune NxT). Lastly, untreated cultures were exposed to Bim peptide as a range of doses (0.01uM-10uM); induction of apoptosis was assessed via cytochrome C staining by flow cytometry.

RESULTS

We were able to recapitulate a wide range of radio-sensitivities both by growth metrics and radiation-induced apoptosis. Immortalized lines showed more radiation-induced growth inhibition relative to primary cultures (p = 0.03). Activation of apoptosis in response to Bim exposure demonstrated a similarly wide range of basal apoptotic sensitivities, akin to that seen for radio-sensitivity. In fact, there was a significant correlation (Pearson, p < 0.01) between Bim-responsiveness and levels of radiation-induced apoptosis.

CONCLUSIONS

We identify basal state Bim-responsiveness as a potential predictor of radio-sensitivity in meningioma. Further work in this vein may shed light on mechanisms of radio-resistance in meningioma, particularly with respect to the interaction of Bim with the anti-apoptotic members of the Bcl-2 family.
RTID-06. THE PIVOTAL METIS (EF-25) STUDY OF TUMOR TREATING FIELDS (TTFIELDS) THERAPY FOR BRAIN METASTASES FROM NON-SMALL CELL LUNG CANCER (NSCLC) FOLLOWING RADIOSURGERY
Authors: Mehta Minesh , Brown Paul , Harat Maciej , Roberge David , Ahluwalia Manmeet
Published: November 2023

INTRODUCTION: TTFields are electric fields that disrupt processes necessary for cancer cell survival and can stimulate an antitumor immune response in preclinical NSCLC models. TTFields therapy is a noninvasive and locoregional treatment approved for glioblastoma, which has recently demonstrated a survival benefit when applied to the thorax with standard of care (SOC) systemic therapy in patients with metastatic NSCLC that progressed on/after platinum. Here we describe the pivotal METIS study (EF-25, NCT02831959) evaluating the efficacy and safety of TTFields therapy applied to brain metastases from NSCLC. TRIAL DESIGN: Patients (270) with 1–10 brain metastases from NSCLC will receive stereotactic radiosurgery (SRS), followed by 1:1 randomization to TTFields (NovoTTF-200M [150 kHz] applied to the head ≥ 18 h/day) with best SOC, or best SOC alone. Key inclusion criteria are life expectancy ≥ 3 months, a new diagnosis of 1 inoperable or 2–10 supra and/or infratentorial brain metastases from NSCLC, that are amenable to SRS. Patients who had prior whole brain radiotherapy, or have single operable, leptomeningeal, or recurrent brain metastases, certain genetic mutations, or severe comorbidities or contraindications, are not eligible. The primary endpoint is time to first intracranial progression. Secondary endpoints include time to neurocognitive failure, overall survival, radiological response rate, time to second intracranial progression, time to first/second intracranial progression by modified RECIST v1.1, rate of intracranial progression, time to distant progression, rate of cognitive decline, quality of life, neurocognitive failure-free survival, and safety. The study is powered at 80% (2-sided alpha of 0.05) to detect a hazard ratio of 0.57. In July 2021, an independent Data Monitoring Committee reviewed the study data and recommended continuation. The study includes 128 sites in Europe, Israel, mainland China, North America, and Hong Kong. The final patient was enrolled in March 2023.
SURG-02. SURGICAL OUTCOME OF SUPRATENTORIAL MENINGIOMA PATIENTS AGED ≥80 YEARS – RETROSPECTIVE INTERNATIONAL MULTICENTER STUDY
Authors: Schwartz Christoph , Rautalin Ilari , Grauvogel Jürgen , Bissolo Marco , Masalha Waseem , Steiert Christine , Schnell Oliver , Beck Juergen , Ebel Florian , Bervini David , Raabe Andreas , Eibl Thomas , Steiner Hans-Herbert , Shlobin Nathan A , Nandoliya Khizar R , Youngblood Mark W , Chandler James P , Magill Stephen , Romagna Alexander , Lehmberg Jens , Fuetsch Manuel , Spears Julian , Rezai Arwin , Ladisich Barbara , Demetz Matthias , Griessenauer Christoph J , Niemelä Mika , Korja Miikka
Published: November 2023

BACKGROUND

Demographic changes will lead to an increase in old patients, a population with significant risk of postoperative morbidity and mortality, requiring neurosurgery for meningiomas, Objective: To evaluate outcome of supratentorial meningioma patients aged ≥80 years. This multicenter study aims to report neurofunctional status after resection, to identify factors associated with outcome, and to validate a previously proposed decision support tool.

METHODS

Neurofunctional status was assessed by the Karnofsky Performance Scale (KPS). Patients were categorized in poor (KPS ≤40), intermediate (KPS 50-70), and good (KPS ≥80) preoperative subgroups. Volumetric analyses of tumor and peritumoral brain edema (PTBE) were performed; volumes were scored as small (< 10 cm3), medium (10-50 cm3), and large ( >50 cm3).

RESULTS

The study population consisted of 262 patients. Median age at surgery was 83.0 years. Median preoperative KPS was 70; 117 (44.7%) patients were allotted to the good, 113 (43.1%) to the intermediate, and 32 (12.2%) to the poor subgroup. Median tumor and PTBE volumes were 30.2 cm3 and 27.3 cm3; large PTBE volume correlated with poor preoperative KPS status (P = .008). The 90-day and 1-year mortality rates were 9.0% and 13.2%. Within the first postoperative year, 101 (38.5%) patients improved, 87 (33.2%) were unchanged, and 74 (28.2%) were functionally worse (including deaths). Each year-increase of age associated with 44% (23–70%) increased risk of 90-day and 1-year mortality. In total, 111 (42.4%) patients suffered from surgery-associated complications. Maximum tumor diameter ≥5cm (odds ratio 1.87 (1.12–3.13)) and large tumor volume (odds ratio 2.35 (1.01–5.50)) associated with an increased risk of complications. Among patients with poor preoperative status and large PTBE, most (58.3%) benefited from surgery.

CONCLUSION

Patients with poor preoperative status and large PTBE most often showed postoperative improvements. The decision support tool may be of help in identifying cases that most likely benefit from surgery.
SURG-03. SURVIVAL STRATIFICATION OF IDH-WILDTYPE GLIOBLASTOMA IN THE MOLECULAR ERA: A RECURSIVE PARTITIONING ANALYSIS INCORPORATING EXTENT OF RESECTION OF CONTRAST-ENHANCING AND NON-ENHANCING TUMORS
Authors: Park Yae Won , Choi Kyu Sung , Park Ji Eun , Ahn Sung Soo , Chang Jong Hee
Published: November 2023

METHODS

This multicenter cohort study included a development cohort of 622 IDH-wildtype glioblastoma patients from a single institution (diagnosed between 2001 and 2021) and 445 patients as validation cohorts from two institutions. All patients completed radiotherapy plus concurrent temozolomide and had complete information on IDH mutation and MGMT promoter methylation status. EOR of CE and NE tumors were evaluated. A RPA analysis was performed on behalf of results of the Cox proportional hazards model. The RPA model was compared with a previous RTOG RPA model.

RESULTS

In the developmental cohort, older age (hazard ratio [HR] = 1.02, P < 0.001), MGMT methylation (HR = 0.51, P < 0.001), KPS (HR = 0.98, P < 0.001), and EOR of CE and NE tumors (GTR of CE tumor and non-GTR of NE tumor, HR = 1.82, P < 0.001; non-GTR of both CE and NE tumor, HR = 2.05, P < 0.001; reference group as GTR of both CE and NE tumor) were independent prognostic factors on multivariable analysis. The novel RPA consisting of age, MGMT methylation, KPS, and EOR of CE and NE tumors revealed greater separation of prognostic classes compared with the previous RTOG RPA model. The prognostic significance of the novel RPA model was subsequently confirmed in the validation cohorts.

CONCLUSION

The RPA model in IDH-wildtype glioblastoma patients incorporating EOR of CE and NE tumors is a valid model. This simple RPA model has the potential to contribute to improving the accurate assessment of prognostic groups in IDH-wildtype glioblastoma patients and to influence clinical decision-making.
SURG-04. FAST DETECTION OF GLIOMA INFILTRATION USING LABEL-FREE OPTICAL MICROSCOPY AND DEEP NEURAL NETWORKS
Authors: Kondepudi Akhil , Pekmezci Melike , Scotford Katie , Jiang Cheng , Chowdury Asadur , Hou Xinhai , Wang Lin , Al-Holou Wajd , Camelo-Piragua Sandra , Lee Honglak , Freudiger Christian , Berger Mitchel , Hervey-Jumper Shawn , Hollon Todd
Published: November 2023

INTRODUCTION

Fast and accurate detection of tumor infiltration is a central challenge in the comprehensive management of diffuse glioma patients. Despite our best real-time tumor detection strategies, such as intraoperative MRI and fluorescence-guided surgery, dense and safely resectable tumor infiltration remains at the surgical margin in over 85% of diffuse glioma patients. Patterns of treatment failure demonstrate that glioma recurrence occurs at the surgical margin in the majority of patients due to residual tumor burden. Objective Here, we present FastGlioma, an artificial intelligence (AI)-based intraoperative diagnostic system for fast (< 10 seconds) detection of diffuse glioma infiltration at microscopic resolution without the need for tumor-specific markers. Method FastGlioma is trained using large-scale, self-supervised visual feature learning on stimulated Raman histology (SRH), a rapid, label-free, optical microscopy technique, and a GPT-style whole slide SRH tumor infiltration scoring method. We pushed the performance limits of FastGlioma by investigating the trade-off between imaging speed versus accuracy for microscopic tumor detection.

RESULTS

In a large prospective external testing cohort of diffuse glioma patients (180 patients, 935 surgical margin specimens) who underwent intraoperative SRH imaging, we demonstrate that FastGlioma was able to detect and quantify microscopic tumor infiltration with an average AUROC of 92.1 +/- 0.0%, performing on par with three expert neuropathologists on the same task. FastGlioma is over 10X faster than previous SRH-based methods and 100X faster than conventional H&E histology. Finally, we demonstrate that FastGlioma was > 20% more accurate at detecting dense tumor infiltration when compared to radiologic features or 5-aminolevulinic fluorescence (98.0% versus 77.8% accuracy) for both IDH-mutant diffuse gliomas and IDH-wildtype glioblastomas.

CONCLUSION

Our results demonstrate how intraoperative optical imaging and deep neural networks can achieve fast and accurate tumor detection, unlocking the role of AI in improving the surgical management of brain tumor patients.
SURG-09. TARGETING A SHARED GLIOBLASTOMA CELL STATE THROUGH ADAPTIVE NATURAL KILLER CELLS AUGMENTED WITH TRISPECIFIC KILLER CELL ENGAGER (TRIKE) IMMUNE-MODULATOR AGAINST CD276
Authors: Ning Jianfang , Davis Zachary , Zhu Shan , Miller Jeffrey , Chen Clark
Published: November 2023

INTRODUCTION

T and NK (Natural Killer) cells have emerged as promising platforms for immunotherapy. While T cells require antigen priming and complex MHC-dependent interactions, NK cells exhibit limited persistence and limited antigen specificity. Trispecific Killer cell Engagers (TriKEs) are constructs developed to address these limitations, combining interleukin 15 (IL15, to enhance persistence), a single-chain antibody fragment against CD16 (to immune-activate NK), and a second fragment targeting a tumor surface marker. Objective: In this study, we identified CD276 (B7H3) as the surface marker optimal for an anti-glioblastoma TriKE and tested its effect on the anti-glioblastoma activity of NK cells. Method: Mass-spectrometry, RNA-Seq, and single cell RNA-Seq profiling of glioblastoma lines. Laboratory characterization and murine modeling Result: Orthogonal analysis of mass-spec identified cell surface molecules enriched in glioblastoma lines and RNA-seq of lines with defined sensitivity to NK cells identified surface proteins highly expressed in NK-resistant lines. Screening of these candidates for genes that showed poor survival association using the TCGA identified CD276. qPCR analysis confirmed higher CD276 expression in the NK-resistant lines, though expression is also detected in NK-sensitive glioblastoma lines. Western blotting analysis and TCGA analysis showed higher level CD276 expression in all glioblastoma subtypes (proneural, neural, mesenchymal, and classical) relative to normal brain. Single cell RNA-Seq of clinical specimens confirmed high expression of CD276 in glioblastoma cells in OPC-like, NPC-like, AC-like, and MES-like cell states. Co-incubation of a IL15, CD16, and CD276 targeting TriKE with either adaptive or iPS derived NK cells enhanced anti-glioblastoma cytotoxicity against cells otherwise refractory to NK treatment in vitro. Synergy between these reagents were also observed in vivo upon orthotopic injection.

CONCLUSION

Our results suggest that a therapeutic strategy combining intra-tumoral injections of NK cells and a B7H3 specific TriKE holds promise and warrants clinical trial consideration.
SURG-23. THE INFLUENCE OF PRE-OPERATIVE VARIABLES ON SURVIVAL OF PATIENTS WITH GLIOBLASTOMA
Authors: Begley Sabrina , Pelcher Isabelle , Schulder Michael
Published: November 2023

BACKGROUND

Glioblastoma (GBM) is both the most common and most aggressive brain tumor in adults. Despite treatment advances, prognosis remains poor and is influenced by numerous factors.

METHODS

Patients treated at our institution for glioblastoma were reviewed to identify pre-treatment factors that could increase survival time. 183 treated for high-grade GBM between 2017 and 2021 with complete follow-up data were included. Overall (OS) and progression-free survival (PFS) were calculated with Kaplan-Meier analysis. Cox regression analysis identified the influence of several pre-treatment factors (age, Karnofsky performance status (KPS), radiographic distribution of tumor, and MGMT methylation status) on survival time.

RESULTS

Average age was 64.9 years. At presentation, 69.9% of patients had KPS > 80. Multifocal tumors occurred in 24.6% of patients, involving an average of 2 distinct regions (either multifocal or unifocal lesions). MGMT methylation was confirmed in 17.5% of patients. Recurrence occurred in 46.4% of patients. Median OS was 21.6 (14.3 – 28.9) months and PFS was 13.4 (10.6 – 16.1) months. MGMT methylation was associated with significantly longer median OS (36.9 vs. 17.0 months, p = 0.012) and PFS (20.0 vs. 10.3 months, p = 0.002) compared to those without. Cox regression confirmed MGMT methylation to be significantly associated with longer PFS (HR -0.883, p = 0.004) and OS (HR -0.785, p = 0.014). Age (HR 0.03, p = 0.003) and KPS > 80 (HR -0.7, p = 0.006) significantly impacted OS, but not PFS. Tumor extent did not impact survival.

CONCLUSIONS

We found that multifocal tumor, greater number of involved regions. and older age were associated with shorter OS, while MGMT methylation was associated with longer OS. Similar correlations were found for PFS. In upcoming trials, these factors may need to be controlled for between groups in order to accurately determine the effect of new treatments.
SURG-26. HYDROCEPHALUS IN LEPTOMENINGEAL DISEASE: TANDEM OMMAYA RESERVOIR-SHUNT FOR INTRATHECAL CHEMOTHERAPY ADMINISTRATION
Authors: Valeri Amber , Etame Arnold , Beer-Furlan Andre , Liu James , Yu Hsiang-Hsuan Michael , Oliver Daniel , Pina Yolanda , Vogelbaum Michael A , Forsyth Peter , Mokhtari Sepideh , Sahebjam Solmaz , Tran Nam
Published: November 2023

INTRODUCTION

Leptomeningeal disease (LMD) is a rare late-stage manifestation of disease progression in solid and hematologic malignancies. Although advances in intrathecal therapeutic (IT) provide treatment options beyond the traditional WBRT, these IT treatment strategies are limited when LMD patients develop associated hydrocephalus. CSF shunting can improve quality of life but may lead to decreased exposure time of IT therapies, with overall survival remaining less than 4 months. Our institution implemented placement of an Ommaya reservoir with ventricular shunt for administration of intrathecal chemotherapy while allowing for concomitant CSF diversion.

METHODS

The authors performed a retrospective chart review on all patients who underwent placement of Ommaya reservoir with a ventricular shunt for treatment of hydrocephalic LMD from Sept 2011 to Feb 2021. LMD secondary to primary glial neoplasm were excluded. Patient demographics, clinical characteristics, tumor characteristics, systemic and IT chemotherapy regimen, length of survival and complications were assessed.

RESULTS

Forty-one patients were included in the study: 18 breast, 12 lung, 5 melanoma, 2 gastric, 2 diffuse large B cell lymphoma, 1 AML, 1 pancreatic. 33.3% of breast cancer were HER-2 positive, while 40% melanoma were BRAF mutated. Patients receiving IT + shunt and WBRT (n = 22) had mean survival time of 350 days from LMD diagnosis compared with 182 days for shunt and WBRT alone (n = 19; p = 0.07). Breast and melanoma patients with IT (n = 16) had improved survival compared with patients with shunt and WBRT (n = 7) alone (419 vs 91 days, p = 0.03). Kaplan-Meier survival analysis demonstrates a positive trend towards increased survival in IT + shunt and WBRT group.

CONCLUSION

This treatment strategy of Ommaya reservoir and shunt prolongs survival in patients with LMD and associated elevated intracranial pressures. This may be very important as we enter the era of cellular immunotherapies for LMD.
SURG-29. APPROACH SELECTION FOR COMPLEX, MULTI-COMPARTMENTAL PETROCLIVAL MENINGIOMAS: A SYSTEMATIC REVIEW OF ENDOSCOPIC AND TRANSCRANIAL APPROACHES TO AN EXCEEDINGLY DIFFICULT CLASS OF SKULL BASE LESIONS
Authors: Brown Nolan , Musmar Basel , Kuo Cathleen , Nguyen Oanh , Neil Zachery , Gendreau Julian
Published: November 2023

INTRODUCTION

Petroclival meningiomas are among the most formidable and technically challenging tumors in skull base surgery owing to their deep-seated location and proximity to critical neurovascular structures. Herein, we seek to understand why skull base surgeons preoperatively plan the staged excision of petroclival meningiomas.

METHODS

Three databases were queried per PRISMA to identify studies describing the indications for staging surgical resection of petroclival meningiomas.

RESULTS

Fourteen studies describing 187 patients (59.3% female, age range: 5 – 81 years) met inclusion criteria. The most common presenting symptom at diagnosis was headache (24.6%). Other common symptoms included cerebellar signs (16.0%) and gait disturbances (13.4%). Petroclival meningiomas were most commonly observed extending to the cavernous sinus (52.88%) and meckel’s cave (49.04%). With respect to critical neurovasculature, the trigeminal nerve was involved in a majority (54.59%) of petroclival meningiomas, while other relevant cranial nerves with tumor involvement included the facial (16.22%) and vestibulococcular (12.43%). Additionally, the most commonly involve vascular structures were the basilar (2.16%) superior cerebellar arteries (1.62%). Of the 187 patients who underwent surgical resection of petroclival meningioma, 144 (77%) underwent surgery involving a single stage, while 43 (23%) underwent surgery in which a two-stage approach was used. The most common single-stage approaches were the retrosigmoid (n = 35) and transpetrosal (n = 22), while the most common approaches employed in a multi-stage fashion were the subtemporal (n = 6), pterional (n = 5), and suboccipital (n = 4) approaches. To clarify, these approaches were each performed as one half of a two-stage surgery involving a second, separate approach.

CONCLUSION

Common approaches used in multi-stage procedures included the retrosigmoid, anterior petrosectomy, posterior petrosectomy, orbitozygomatic, translabrynthine, and various combinations thereof. Indications for performing surgery in this manner include coexistence of lesion in both middle and posterior skull base compartments, absence of meaningful hearing function, tumor size, and surgeon preference.
SURG-30. CLINICAL CONSIDERATIONS, APPROACH SELECTION, AND OUTCOMES ASSOCIATED WITH TREATMENT STRATEGIES FOR FALCOTENTORIAL MENINGIOMAS: SYSTEMATIC REVIEW AND META-ANALYSIS OF THE CURRENT EVIDENCE
Authors: Brown Nolan , Musmar Basel , Kuo Cathleen , Gendreau Julian
Published: November 2023

INTRODUCTION

Meningiomas at the falcotentorial (FT) junction are rare, as they account for only 0.3%-1.1% of all intracranial meningiomas. Clinical management of FT meningiomas can be challenging.

METHODS

The authors queried three databases per PRISMA guidelines to identify all studies reporting indications for surgical resection of FT meningioma.

RESULTS

Thirty studies reporting 224 FT patients met pre-specified inclusion criteria. Patients diagnosed with FT meningioma demonstrated a predilection for headache on initial examination (p = 0.030).Headache was the mostly commonly reported symptom, present more often than visual disturbance (RR 2.28 [1.59, 3.26], I2=0%, P < 0.00001), ataxia or imbalance (RR 0.21 [0.08, 0.35], I2= 0%, P = 0.002), and cognitive disturbance (RR 0.34 [0.20, 0.47], I2 = 12%, P < 0.00001). An overwhelming majority of lesions (n = 97, 80.2%) were benign, WHO Grade I. The primary arterial feeders supplying the FT lesions were reported in 13 studies; most commonly, these arterial feeders included the distal branches of the ICA (n = 29), ECA (n = 25), and vertebrobasilar vasculature (n = 35). Visual deficits (n = 32, 14.3%) were the most common postoperative complication.Bassiouni classification of the tumors was reported in 10 studies, with 27 (31.8%) classified as type I, 16 (18.8%) as type II, 37 (43.5%) as type III, and five (5.9%) as type IV FT meningiomas.Simpson Grade I resection (n = 76, 43.7%) was achieved in slightly less than half of cases. Cases involving multi-stage resections appeared to confer greater risk (RR 1.42 [0.72, 2.80], I2=0%, P = 0.31) for STR (failure to achieve GTR or Simpson Grade I resection).

CONCLUSION

The primary objective when treating FT meningiomas is to achieve gross total resection (GTR) or Simpson Grade 1 resection. Grade 2 resection is also regarded as a good outcome for these lesions. This goal should be pursued while minimizing cerebellar retraction and protecting vital vascular structures, such as the Galenic venous system.
SURG-35. SURVEY ASSESSMENT OF UTILITY IN THE PREOPERATIVE MAGNETIC RESONANCE (MR) TRACTOGRAPHY SURGICAL PLANNING
Authors: Sharma Mayur , Chen Clark
Published: November 2023

BACKGROUND

While tractography guided surgery is used by many surgeons as a matter of preference, there is controversy in the published literature as it relates to its clinical utility. The current literature consists of experiences of select surgeons. Here we adopted a survey-based approach with the goal of attaining a broader view of how tractography influence pre-operative planning in a sampling of practicing neurosurgeons.

METHODS

Three cases were prepared where the presence of a tumor distorted the optic radiation (case 1), the arcuate fasciculus (case 2), and corticospinal tract (case 3). This survey was administered at the Medtronic Cranial Consortium attended by twenty practicing neurosurgeons. To avoid commercial bias, we used both the Brainlab and the Medtronic platform to compute tractography. Each participant is asked to vote on a surgical trajectory prior to and after seeing the tractography images as well as whether tractography added value in validating their surgical approach.

RESULTS

In the three cases surveyed, 16-44% of the surgeons changed the surgical corridor selected after seeing the tractography images. The most common finding associated with a change in surgical corridor involved intersection of the surgical corridor with visualized tracts. Consistently, >80% of the surgeons surveyed felt that tractography added value in their surgical planning. These findings suggest tractography added value even in cases where the surgeon did not change their surgical approach, likely by confirming their prediction in the location of the pertinent tracts.

CONCLUSION

The clinical utility of tractography in pre-operative planning vary as a function of surgeon and the tumor anatomy, with > 80% of the participating consider that tractography added value in pre-operative surgical planning.
SURG-37. ONCOGENIC MUTATIONS AND TUMOR CHARACTERISTICS IN OLFACTORY GROOVE MENINGIOMAS: IMPLICATIONS FOR PERSONALIZED TREATMENT STRATEGIES
Authors: Prilop Insa , Beyer Friederike , Herold Sylvia , Alkhatib Majd , Cahill Daniel , Wakimoto Hiroaki , Brastianos Priscilla , Eyuepoglu Ilker , Schackert Gabriele , Juratli Tareq
Published: November 2023

OBJECTIVE

To investigate the correlation between clinical and radiologic features of olfactory groove meningiomas (OGM) and their tumor molecular profiles, focusing on oncogenic mutations identified through genomic studies.

METHODS

Targeted next-generation sequencing analyses were conducted on 54 patients with OGM (37 females and 17 males) to determine the frequency of SMO, AKT1, PIK3CA, and other mutations. The molecular results were then correlated with clinical and radiographic tumor features.

RESULTS

Among the OGM patients, SMO mutations were found in 16 (29.6%) cases, AKT1 mutations in 13 (24.1%), and PIK3CA/PIK3R1 mutations in 9 (16.7%) cases. Less common mutations in POLR2A, SUFU, and NF1 were observed in 8 (14.8%) cases, while 8 OGM (14.8%) did not have identifiable driver mutations (Wild-type group, WT). The median age at first diagnosis was 64.1 years (25-87 years), with the youngest group represented by PIK3CA-mutant patients at 52 years (49-78 years). The sex distribution was similar across the SMO-, AKT1- and PIK3CA-mutant groups (F:M = 2.1:1). OGM with SMO mutations exhibited larger tumor volumes (329.4 ± 323.0 cm3) compared to AKT1-mutant tumors (283.3 ± 156.2 cm3). Tumor infiltration of the ethmoid cells was found in 10 cases (22.2%), with the highest rate observed in PIK3CA-mutant OGM (40%), followed by 25% in SMO-mutant OGM. Tumor-associated hyperostosis of the sphenoid planum was common in OGM (72.2%), with the highest rate in the SMO group (75.0%) and the lowest rate in the AKT1-mutant group (30.8%). The majority of cases (n = 45, 83.3%) were classified as WHO grade 1 meningioma, while the remaining nine cases were WHO grade 2 (n = 8) and 3 (n = 1).

CONCLUSIONS

Overall, our data demonstrate the presence of clinically actionable mutations in the majority of olfactory groove meningiomas, and suggest a correlation between molecular status and common clinical and radiologic tumor features.
SURG-39. EVALUATING THE EFFECTIVENESS OF NON-NAVIGATED 2D INTRAOPERATIVE ULTRASOUND IN GLIOMA SURGERY: RECONSIDERING THE PUSH FOR MORE COMPLEX INTRAOPERATIVE IMAGING
Authors: Cepeda Santiago , García-García Sergio , Arrese Ignacio , Sarabia Rosario
Published: November 2023

INTRODUCTION

In the swiftly evolving domain of neurosurgical technology, conventional methodologies like the non-navigated two-dimensional intraoperative ultrasound (nn-2D-IOUS) might be at risk of being overlooked. This research investigates the clinical effectiveness and surgical significance of nn-2D-IOUS, particularly for glioma removal procedures.

METHODS

This retrospective research, conducted at a single healthcare institution, reviewed 99 unselected patients diagnosed with both high and low-grade gliomas. The main objective was to examine the competency of nn-2D-IOUS in delivering satisfactory image quality, recognizing leftover tumor tissue, and its impact on the extent of tumor removal. Early postoperative MRI data were used as a reliable comparison measure to verify these findings.

RESULTS

nn-2D-IOUS exhibited notable efficiency, generating superior image quality in nearly 79% of analyzed cases. It showcased a sensitivity of 68% and a remarkable specificity of 100%, thus affirming its instrumental role in intraoperative tumor identification. In scenarios where complete tumor excision was intended, a resection surpassing 95% of the original tumor volume was accomplished in 86% of patients. Moreover, when the nn-2D-IOUS didn't detect residual tumor, the average volume of overlooked tumor tissue was significantly small, approximately 0.27 cm³.

CONCLUSION

Our research presents persuasive evidence emphasizing the critical role and effectiveness of nn-2D-IOUS in glioma surgeries. The findings underline the potential of leveraging cost-efficient, traditional technologies like nn-2D-IOUS to attain superior surgical results, even when compared to more sophisticated alternatives. This understanding has profound implications, especially for resource-limited environments, underscoring the need to maximize the usage of available tools to enhance patient care in a practical, economical manner.
SURG-43. SURGICAL TREATMENT FOR SPINAL CORD HEMANGIOBLASTOMA - DIFFERENCE IN SURGICAL INDICATION FROM CEREBRAL HEMANGIOBLASTOMA
Authors: Takayanagi Shunsaku , Takami Hirokazu , Tanaka Shota , Saito Nobuhito
Published: November 2023

Objective

Spinal cord hemangioblastoma (HB) is a tumor with abundant blood flow with feeders and drainers, and is often accompanied by large cysts and syringomyelia. About 25% of HB cases are said to be von Hippel-Lindau (VHL) disease cases, which is a hereditary tumor disease. In VHL disease, multiple surgeries are often performed because HB occurs frequently. To consider whether spinal cord HB requires a different surgical indication from brain HB cases, this report analyzed the treatment results of HB cases at our hospital.

Methods

From 1988 to 2021, 85 patients with HB underwent surgery at our hospital investigated.

Results

There were16 cases of spinal cord, 58 of cerebellum, and 10 of brainstem. Of these, 46 cases (13 families, 21 patients) had VHL disease. There were 13 cases (81%) with syringomyelia and 8 cases (50%) with cysts in spinal cord HB. The mean tumor volume at spinal cord, cerebellum and brainstem were 3.2, 15.9 and 5.8 cm3, respectively. Changes in mRS before and after surgery were as follows; spinal cord HB: improvement 10 (63%)/deterioration 3 (19%), cerebellar HB: improvement 35 (60%)/deterioration 7 (12%), brainstem HB: improvement 7. (70%)/0 deterioration. In spinal cord HB, total resection was achieved in all cases, and no significant complication was observed. Conversely, 12 patients (17%) underwent shunting for postoperative hydrocephalus in cerebellum/brain stem HB. In spinal cord HB, no local recurrence was observed during the follow-up period of median 54 months (4-188 months).

Conclusion

Spinal cord HB was operated when the tumor volume was smaller than that of brain HB, but there was no significant difference in the symptom improvement rate. However, there were a certain number of patients who deteriorated after surgery, and it was thought that further analysis would be necessary in the future regarding appropriate surgical indications for spinal cord HB.
SURG-44. VENTRICULAR CEREBROSPINAL FLUID SAMPLING IN PEDIATRIC DIFFUSE MIDLINE GLIOMA PATIENTS: INSTITUTIONAL EXPERIENCE AND REVIEW OF THE LITERATURE
Authors: Li Daphne , Stellpflug Wendy , Romanski Kathleen , Speck Stacy , Saratsis Amanda
Published: November 2023

BACKGROUND

Increasing evidence suggests that circulating biomarkers may serve diagnostic and longitudinal monitoring purposes in pediatric neuro-oncology. Mutant tumor DNA is detectable in the cerebrospinal fluid (CSF) of pediatric diffuse midline glioma (DMG) patients and quantity can reflect disease burden. CSF sampling (“liquid biopsy”) via a CSF access device could therefore play a role in DMG management. Therefore, we set to evaluate the incidence of hydrocephalus (HCP) in DMG patients, and to characterize ventricular reservoir placement and access practices.

METHODS

A single institution retrospective review of DMG patients <21-years-old was performed (1984-2019). MEDLINE searches for reports of ventricular reservoir or shunt placement in DMG, and reservoir access for intraventricular chemotherapy (IVC) were performed.

RESULTS

At our institution, 62.6% of DMG patients (67/108) required intervention for HCP: 19.4% provided transient CSF access (ETV alone n = 3, EVD n = 8, unspecified n = 2), and 80.6% permanent CSF access (ETV + reservoir n = 13, shunt n = 41). Further, 22/34 patients with initially transient CSF devices required conversion to a permanent device. Five devices were revised for malfunction, one for infection. Seventeen articles cited HCP in 22% to 100% of DMG patients. IVC administration was described in 632 patients (seven articles), with 42 infectious and 63 non-infectious complications.

CONCLUSIONS

Management of HCP is often necessary in children with DMG. Given the low rate of clinical risk associated with VAD placement and access, and the potential utility of longitudinal disease monitoring via CSF analysis, VAD placement could be considered in future clinical trials to guide DMG treatment.
TMET-01. THERAPEUTIC TARGETING OF CROSSTALK BETWEEN MITOCHONDRIAL FITNESS AND CELL ADHESION/MIGRATION IN DIFFUSE MIDLINE GLIOMA (DMG)
Authors: Cartaxo Rodrigo , Ji Sunjong , Schwark Kallen , Koschmann Carl
Published: November 2023

Diffuse midline gliomas (DMGs) are aggressive tumors characterized by infiltration into normal midline brain tissue, hindering surgical resection and contributing to overall morbidity and mortality. To study which genes are driving this invasive phenotype, we established a novel two-step pooled whole genome CRISPR-Migration screen for DMG primary cell cultures (n = 3) derived from patients. After selecting for genes critical for cell survival, each cell line was seeded in the upper chamber of a transwell assay optimized for DMG cells to promote complete serum-free cell attachment and migration through laminin, one of the major components of the blood vessels basement membrane. Following sgRNA library sequencing of low and high-migratory populations, we found a strong positive correlation with genes directly involved in the focal adhesion machinery (ITGB1, CRKL, RAPGEF1, PARVA, PTK2, FERMT2). Stable CRISPR knockout of these genes validated significant reduction in adhesion/migration, without affecting proliferation. Interestingly, we also identified in the screen genes controlling different aspects of mitochondrial function (NDUFAF6, PITRM1, MINOS1, MICU3, LIPT1, MRPL38), especially affecting outer-inner mitochondrial membrane integrity. This finding is in line with the higher sensitivity of multiple DMG cell cultures to Bcl-2 family inhibitors, readily prompting apoptosis in combination with sub-lethal doses of various drugs. Agents that specifically modulate mitochondrial oxidative phosphorylation (OXPHOS) (Rotenone, Oligomycin A, Antimycin A) reduced DMG cell migration without affecting proliferation. Surprisingly, silencing of ITGB1 and CRKL led to a marked decrease in glycolysis and OXPHOS levels, again without any changes in proliferation. Additionally, silencing of ITGB1 (primarily responsible for cell adhesion to laminin) led to the decreased expression (RNA) of multiple mitochondrial NADH dehydrogenases, pointing to an intricate bi-directional mechanism connecting mitochondrial fitness to DMG cell migration. Studies are underway to validate these findings in vivo and to determine an optimal therapeutic disruption of this critical DMG malignant phenotype.