tbuckley/cabot-search huggingface dataset:
QLTI-11. PREDICTORS OF PROLONGED LENGTH OF STAY IN LASER INTERSTITIAL THERMAL THERAPY FOR INTRACRANIAL PATHOLOGIES: A SINGLE CENTER EXPERIENCE
Authors: Chandler Berke, Maxon Knott, Adham Khalafallah, Ashish Shah, Michael Ivan, Ricardo Komotar
Journal: Neuro-Oncology (2024)

Abstract INTRODUCTION Laser interstitial thermal therapy (LITT) offers a minimally invasive approach for treating intracranial pathologies, often with shorter hospital stays than traditional craniotomies. Yet, some patients still face prolonged length of stay (PLOS), highlighting the need to identify contributing factors and improve post-LITT outcomes. OBJECTIVE To evaluate factors contributing to PLOS following LITT for intracranial pathologies. METHODS A retrospective review was conducted between 2013-2023 for patients undergoing LITT for intracranial pathology at a tertiary care center. PLOS was defined as discharge &amp;gt;2 days. Multivariate logistic regression analyzed variables as contributors to PLOS including ICU LOS (hours), preoperative maximum tumor diameter (cm), lesion location, lesion pathology (high grade glioma (HGG)/glioblastoma (GBM) vs. other), and mFI-11 score (binary ≥ or &amp;lt; 75th percentile). RESULTS The cohort consisted of 288 patients, with 29% (83/288) and 71% (205/288) having PLOS and non-PLOS, respectively. Mean age was similar between the PLOS (63-years) and non-PLOS (60-years) groups (p=0.09). The PLOS group had a 55% male predominance compared to 57% female in the non-PLOS group. Greater mFI-11 scores showed increased risk of PLOS [4.01, (2.11, 7.60), p&amp;lt;0.000]. Lesions having a subcortical location [3.43 (1.70, 6.95), p=0.001] or diagnosis of HGG or GBM [2.87 (1.54, 5.34), p=0.001] had increased risk of PLOS. Importantly, maximum pre-operative diameter did not significantly alter risk of PLOS [1.05 (0.98, 1.13), p=0.151]. CONCLUSION For the first time, we show that patient comorbidities, subcortical lesion location, HGG/GBM pathology, and greater time spent in the ICU portend increased risk of PLOS following LITT. Future work should validate our model with the goal of optimizing post-operative patient management and resource allocation.
QOL-06. OPTIMIZING NEUROFIBROMATOSIS CARE: A COMPREHENSIVE ECONOMIC EVALUATION OF A SPECIALIZED EXPERTISE CENTER’S IMPACT ON PATIENT OUTCOMES
Authors: Sara Boubekri, Nicolas Greciet, Maria Annani, Julien Rousseau, Moujahed Labidi, Zaki El Haffaf, Isabelle Boudreau, Issam Saliba, Emma de Haan, Danny Tremblay, Sarah Lapointe
Journal: Neuro-Oncology (2024)

Abstract Neurofibromatosis type 1 (NF1), NF2-related schwannomatosis (NF2) and other schwannomatoses represent a spectrum of genetic disorders characterized by the development of tumors on nerve tissues, profoundly impacting patients’ quality of life and posing complex challenges. Recognizing the imperative for comprehensive care delivery, we undertook to implement a Neurofibromatosis Expertise Center (CE) at the Centre hospitalier de l’Université de Montréal (CHUM), Quebec, Canada. Employing a robust analysis framework, we aimed to assess the economic viability of the CE by quantifying the Quality-Adjusted Life Years (QALYs) gained through centralized multidisciplinary neurofibromatosis care (cost-utility ratio = CAD/QALY gained). Leveraging data from validated questionnaires including the SF-6D, our preliminary analysis revealed significant enhancements in patients’ quality of life across diverse domains, including physical pain, visible cutaneous lesions, cognitive dysfunction, hearing loss, malignancies, psychiatric comorbidities, unemployment, physical disability, and social isolation. Notably, among the respondents (N = 115), patients receiving CE services reported a 12% increase in general health compared to a 25% decline among those without CE services. Moreover, 28% of CE patients reported improved overall health compared to 12% of those without CE services. Using the Work Productivity and Activity Impairment questionnaire (WPAI-GH), we found that cohorts followed in CE for ≥ 1 year (N = 45) experienced less work productivity losses compared to the most recent cohort (N = 32), which presented scores exceeding 6 on a 1-to-10 scale. We hypothesize that the establishment of the CE will yield profound improvements in patient health outcomes and alleviate financial strains on the Ministère de la Santé et des Services Sociaux du Québec (MSSS). Therefore, our next steps include discussing a strategy for funding application to the MSSS to ensure the accessibility of necessary care for patients. Continuing data collection and analysis will also provide a more comprehensive overview of patient characteristics and needs.
RADT-17. FRACTIONATED REIRRADIATION OF RECURRENT IDH WILDTYPE GLIOBLASTOMA: HIGHER REIRRADIAITON DOSE AND SAFETY
Authors: Michael LeCompte, Neil Vuppala, Juan Reyes, Brandi Page, Victoria Croog, Ellen Huang, Kristin Redmond, Lawrence Kleinberg
Journal: Neuro-Oncology (2024)

Abstract The optimal regimen, normal tissue tolerances, and appropriate indications for reirradiation for recurrent glioblastoma (GBM) are uncertain. We evaluate outcomes and toxicity after fractionated reirradiation. Patients with recurrent IDH wildtype GBM after prior standard radiotherapy during 2007-2022 were retrospectively reviewed. All patients initially received conventionally fractionated radiotherapy. Radiation necrosis (RN) was determined by imaging or pathology. Overall survival (OS) was estimated using Kaplan-Meier methodology. Univariate and multivariate Cox proportional hazard models for OS were constructed. Bivariable associations with RN were estimated using fisher exact tests. 99 patients (median age 56 yrs, median KPS 80) were treated with reirradiation (median followup 7.4 mo). Median time between initial and reirradiation was 20 months (range, 2 – 214 mo). Median received dose at reirradiation was 41.4 Gy (30.6 – 60 Gy) to a median planning target volume (PTV) of 183 cc (16 – 825 cc). Median cumulative maximum dose to the optics and brainstem were 54 Gy (4 – 103 Gy) and 76 Gy (5 – 146 Gy), respectively. Median OS was 9 mo (95% CI 6.2 – 10.6 mo). On univariate analysis, time between initial and reirradiation ≥24 mo (HR 0.58, CI 0.36 – 0.94) and reirradiation dose ≥41.4 Gy (HR 0.56, CI 0.35 – 0.88) were associated with longer OS. On multivariate analysis, interval between radiation sessions (HR 0.56, CI 0.34 – 0.91) and higher reirradiation dose (HR 0.55, CI 0.35 – 0.87) remained associated with OS. No cases of radiation injury to the optics or brainstem were reported. 10% of patients experienced RN. Reirradiation dose ≥41.4 Gy, reirradiation PTV ≥200 cc and interval between radiation sessions &amp;lt; 24 mo were not significantly associated with RN. These data support the safety and efficacy of fractionated reirradiation for recurrent GBM including for large tumors. This study suggests that higher reirradiation dose may be feasible, including for large treatment volumes.
QLTI-17. COMPARATIVE ANALYSIS OF LUMBAR PUNCTURE UTILITY IN DIAGNOSIS OF PRIMARY VERSUS SECONDARY CNS LYMPHOMA: A RETROSPECTIVE STUDY
Authors: Mainak Bardhan, Amina Namrouti, Tiba Al Sagheer, Yuliya Linhares, Muni Rubens, Yazmin Odia, Manmeet S Ahluwalia, Zhijian Chen
Journal: Neuro-Oncology (2024)

Abstract OBJECTIVES Central nervous system lymphoma (CNSL) is a subtype of non-Hodgkin lymphoma, which affects the brain, spinal cord, leptomeninges, or eyes. It includes primary (PCNSL) and secondary CNSL (SCNSL). CNSL diagnosis relies on neuroimaging, cerebrospinal fluid (CSF) analysis (cytology, flow cytometry), and/or tissue biopsy. Lumbar punctures (LP) aid in investigating leptomeningeal involvement. Positive findings confirm CNS involvement and guide treatment decisions. This study seeks to determine the effectiveness of CSF analysis via LP in diagnosing SCNSL compared to PCNSL. METHODS This retrospective study comprised patients who received treatment with HD-MTX treated at our center from July 2020 to January 2024. Data was retrospectively collected from electronic medical records (EMR). Pathology reports from tissue biopsy and enhancement of CNS visualized on imaging were utilized to diagnose and differentiate PCNSL and SCNSL. CNS cytology and flow cytometry from LP were analyzed to determine the diagnostic accuracy of LP CSF cytology results in diagnosing CNSL. Descriptive statistical and comparative analysis was conducted to analyze the results. RESULTS The sample included 70 patients, 35 each diagnosed with PCNSL and SCNSL. Of these, only 49 patients underwent LP, with a significantly higher proportion of patients in the SCNSL group, 33 (67%), compared to the PCNSL group, 16 (33%) (P&amp;lt;0.001). Among those who underwent LP, CSF cytology and/or flow cytometry were positive in 19 cases, with significantly higher detection rates among the SCNSL cases (16 of 33, 48.5%) compared to the PCNSL cases (3 of 16, 18.8%; p=0.045). CONCLUSION Our findings indicate that LPs play a crucial role in diagnosing SCNSL, with a significantly higher CSF detection rate than PCNSL. LP has a limited impact on diagnosing PCNSL, suggesting that tissue biopsy should be prioritized to avoid increased time for PCNSL diagnosis. This study underscores the importance of tailored diagnostic approaches for suspected PCNSL and SCNSL, emphasizing the utility of LP in diagnosing SCNSL and tissue biopsy for PCNSL.
RADT-14. EARLY OUTCOMES FROM PROTON CRANIOSPINAL IRRADIATION FOR LEPTOMENINGEAL METASTASIS FROM SOLID TUMORS
Authors: Keng Lam, Lewis Nasr, Clark Andersen, Kathryn Marqueen, Jing Li, Chenyang Wang, Nazanin Majd, Ashley Aaroe, Monica Loghin, Susan McGovern, Barbara O’Brien
Journal: Neuro-Oncology (2024)

Abstract INTRODUCTION Treatment options for leptomeningeal metastasis (LM) are limited. A phase II study found that proton craniospinal irradiation (pCSI) was well-tolerated and improved survival. We report our experience with pCSI for solid-tumor LM. METHODS This is a retrospective review of patients treated with pCSI for solid-tumor LM from December 2020 to January 2024 at our center. Patient characteristics were summarized using descriptive statistics. Median overall survival (OS) and median central nervous system progression-free survival (CNS-PFS) from the first day of pCSI were estimated using Kaplan-Meier survival curves. RESULTS We identified 45 patients who completed pCSI. Median age was 54 years (range, 23-79); 73% were female, and 53% lived more than 100 miles from our center. Breast cancer (53%), lung cancer (20%), and melanoma (9%) were the most common primary cancers; 51% of patients had stable systemic disease at LM diagnosis. All had imaging evidence of LM, and 64% were confirmed by cytologic examination of the cerebrospinal fluid. Eighty percent had symptomatic LM, and the median Karnofsky Performance Scale (KPS) at LM diagnosis was 80. The median time from primary cancer diagnosis to LM diagnosis was 23.1 months (range, 0-221.3). Fifty-three percent of patients had active brain metastasis at LM diagnosis. At the first visit following pCSI, median KPS was 70. Seventy-six percent reported new or worsening nausea, 51% headache, and 31% fatigue. Following pCSI, 18% received LM surveillance, 4% intrathecal chemotherapy, 67% systemic therapy, 9% hospice care, and 2% lost to follow-up. Median OS was 13.7 months (95% confidence interval [CI], 11.2 to infinity), and median CNS-PFS was 6.5 months (95% CI, 4.9 to 12.8). CONCLUSIONS The outcomes in our cohort are comparable to those recently reported in a phase II trial. Further study is indicated to determine the optimal candidates for pCSI and sequential therapies.
QOL-04. THE UNDER-UTILIZATION OF PALLIATIVE CARE SERVICES BY PATIENTS WITH GLIOBLASTOMA HIGHLIGHTS THE IMPORTANCE OF DISCUSSIONS AROUND PALLIATIVE CARE: A CROSS-SECTIONAL STUDY WITH CARE PARTNERS OF PATIENTS WITH GBM RECRUITED FROM FACEBOOK SUPPORT GROUPS
Authors: Lauren Robbins, Elizabeth James, Samantha Ennis, Marlee Wallace, Anna Vreeling, Barbara Lutz, Laurie Minns
Journal: Neuro-Oncology (2024)

Abstract Glioblastoma (GBM) is a terminal brain cancer that has a rapid onset and results in symptoms such as headaches, vomiting, seizures, anxiety, depression, agitation, speech impairment, memory impairment, infections, brain bleeds, mobility changes, changes in sleep patterns, and cognitive changes. Palliative care helps patients diagnosed with an incurable or chronic disease manage physical, social, and psychological symptoms and has been shown to increase survival for patients with cancer. Previous data of former care partners of patients with GBM indicated only 30% of patients used palliative care whereas 90% used hospice. To better understand the reasons for underutilization of palliative care patients with GBM, 38-question survey about the use of palliative care, type of medical center where treatment occurred, and discussions with care team members about palliative care was given to current care partners recruited from Facebook support groups in February 2024. Inclusion criteria: current primary care partner of a patient with GBM, over the age of 18, and willing to participate (IRB exempt; H24-0393). The care partner was excluded if their patient was no longer living. Of the 77 current care partners, 56 reported they did not use palliative care as part of their care team. The use of palliative care was similar among care facilities (community hospital, major medical center, university hospital, brain tumor center). When care team members discussed palliative care with patients and their care partners (n=21), 71% of the dyads used palliative care. When care team members did not discuss palliative care (n=56), the use of palliative care was much lower at 7%. Interestingly, 55% of respondents reported they would benefit from knowing more about ways to increase physical and emotional support. This data suggests discussions around palliative care increase the use of palliative care services among patients with GBM and their care partners.
SURG-43. PATTERNS OF FAILURE FOLLOWING REIRRADIATION WITH GAMMA KNIFE STEREOTACTIC RADIOSURGERY FOR RECURRENT HIGH-GRADE GLIOMAS
Authors: Shivani Bindal, Brandon Gonzalez, Yoshua Esquenazi, Antonio Dono, Roy Riascos, Jay Zhu, Sigmund Hsu, Nitin Tandon, Magda Martir, Angel Blanco, Mark Amsbaugh
Journal: Neuro-Oncology (2024)

Abstract Re-irradiation with stereotactic radiosurgery (SRS) is an increasingly used treatment for recurrent high-grade glioma (HGG). We analyzed the patterns of failure and outcomes of salvage Gamma Knife SRS for recurrent HGG to better identify which patients would most benefit. We reviewed all patients who received SRS for recurrent HGG from January 2008 to May 2020. Pattern of failure was defined by the distance of recurrence from the SRS isodose line as follows: in-field local, marginal local, regional local, and distant failure. Overall survival (OS), progression-free survival (PFS), and local-failure free survival (LFS) were estimated using Kaplan-Meier methods, and regression model analysis was performed to analyze clinical predictors of failure. A total of 146 patients with HGG underwent SRS treatment to 410 target lesions. The median target volume was 3.3 cm3 and median total dose was 18 Gy. Sixty-one (41.8%) patients developed progression following SRS. PFS at 6 and 12 months were 65.8% and 37.3% respectively. Median OS was 12.4 months from salvage SRS. There were 113 (79.5%) local failures (53.1% in-field, 45.1% marginal, and 1.8% regional), 2 (1.4%) distant, and 27 (19%) concomitant local and distant failures. LFS at 6 and 12 months was 82.9% and 66.6%, respectively. Non-white race (HR = 0.37), SRS dose ≥ 20 Gy (HR = 0.34), age &amp;lt; 60 years (HR = 0.43), and KPS ≥ 70 (HR = 0.44) were associated with longer time to local failure. Non-white race (HR = 5.55) and SRS dose ≥ 20 Gy (HR = 5.62) were associated with more distant failure. No grade 4 or 5 toxicity was observed. In conclusion, the dominant pattern of failure remains local and in-field despite conformal dose distribution with SRS and infiltrative tumor histology. This supports the role of reirradiation with SRS in well selected patients with recurrent HGG.
QLTI-18. TREATMENT AND OUTCOMES OF FRAIL PATIENTS WITH NEWLY DIAGNOSED HIGH-GRADE GLIOMAS: SHOULD WE CONSIDER CHANGING OUR TREATMENT APPROACH?
Authors: Neil Sielski, Anne Reiner, Lauren Schaff, Brandon Imber, Luke Pike, Alan Carver, Elena Pentsova
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Patients with newly diagnosed high-grade glioma (HGG) and low Karnofsky Performance Status (KPS) often face challenges in receiving cancer-directed therapy. They are excluded from prospective trials, limiting the chance of developing novel therapeutic approaches. METHODS We retrospectively reviewed charts of patients with functional debility and newly diagnosed HGG who received radiotherapy (RT) while admitted to the inpatient service at Memorial Sloan Kettering between 2013 and 2023. Multivariable analyses were performed which associated patient demographics, KPS, histology, genetic and molecular pathology, RT duration and dose, chemotherapy, palliative/supportive care consultation, and advanced care planning documentation with overall survival (OS) and discharge location, separately. RESULTS Fifty-four patients were identified; median age was 68 years (range:21-86) and 28 (52%) were women. Median KPS was 50 (range:30-70). Per WHO 2021 criteria, 47 (87%) were glioblastoma, IDH wild-type and 7 (13%) were HGG not otherwise specified, diagnosed by biopsy in 30 (56%), subtotal resection in 23 (43%), and gross total resection in one. MGMT promoter methylation was performed in 39/54 and was hypermethylated in 15 (38%). All patients received RT and 52 (96%) with concurrent temozolomide; 47/54 (87%) completed planned RT, with the median dose of 4,005 cGy in 15 fractions. 13 (24%) received bevacizumab. The median length of stay (LOS) was 29 days (range:20-65). Only 17 (31%) had palliative care consultation prior to discharge. The median OS (mOS) from the last radiation treatment was 4.21 months (95% CI: 2.73, 6.63). In multivariable Cox and logistic regression, respectively, lower KPS remained the sole factor significantly associated with increased risk of death (p=0.004) and decreased chance of return home (p=0.040). CONCLUSION In our patient cohort, treatment was associated with prolonged LOS and poor outcomes. A clinical trial should be considered to evaluate shorter RT courses and early palliative care consultation in this patient population.
TMET-32. THE ROLE OF HOXC10 IN DRIVING GLIOBLASTOMA AGGRESSIVENESS
Authors: Raghupathy Vengoji, Balaji Perumalsamy, Anand Thiraviyam, Ayoola Ogunleye, Maneesh Jain, Moorthy Ponnusamy, Surinder Batra, Nicole Shonka
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Glioblastoma (GBM) is an aggressive malignancy, with a tumor doubling time of just 49.6 days. Despite maximal safe surgical resection, radiation, and temozolomide, median survival is only 14.6 months. Homeobox gene, homeobox C10 (HOXC10), a transcription factor of the HOX10 family, is pivotal in neuronal development, upregulated in several cancers, including glioma, and correlates with poor survival. METHODS RNA sequencing analysis was done on our mouse glioma syngeneic cell lines. HOXC10 expression analysis was done on human and mouse GBM cell lines and tissues by immunoblotting and immunohistochemistry, respectively. HOXC10 and p16-/-silencing were done using 4 unique 29mer shRNA constructs in the GFP vector, respectively. Gene Ontology predicted HOXC10 functions. HOXC10 and pyrroline-5-carboxylic acid reductase 1 (PYCR 1), a proline biosynthetic enzyme co-expression was studied using immunofluorescence analysis. RESULTS HOXC10 is highly expressed in human and mouse GBM tissues. HOXC10 was upregulated only in the high-grade/aggressive cell line [EGFRvIII; p16-/- &amp; GFAP Cre] and demonstrated increased expression with p16 deletion in the mouse glioma cell line. Compellingly, TCGA analysis of GBM correlated the negatively prognostic p16 homozygous deletion (HD) with HOXC10 upregulation. Gene Ontology supports the role of HOXC10 for proline biosynthesis and metabolism. Immunofluorescence on mouse GBM sections revealed co-expression of HOXC10 and PYCR1. HOXC10 silencing significantly decreased GBM cell line proliferation, induced apoptosis, and decreased PYCR1 expression in vitro. CONCLUSIONS HOXC10 expression is increased in GBM and with p16 HD. HOXC10 silencing significantly decreased GBM cell line proliferation and decreased PYCR1 expression. HOXC10-mediated proline biosynthesis may present a novel target to improve GBM survival.
TMET-20. A METABOLIC BIOMARKER IN GLIOBLASTOMA: A PROMISING APPLICATION OF CO-POLARIZED [1-13C]PYRUVATE AND [1-13C]DEHYDROASCORBATE
Authors: Elizabeth Coffee, Paola Porcari, Nathaniel Kim, Saket Patel, Marjan Berishaj, Kofi Deh, Kayvan Rahimi-Keshari
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Noninvasive biomarkers for treatment response in glioblastoma are needed to improve patient outcomes. Our understanding of redox biology in treatment resistance is rapidly evolving, and interrogation of tumor metabolism represents an ideal opportunity to meet this need. In this study, the utility of co-hyperpolarized [1-13C]pyruvate and [1-13C]dehydroascorbate (HP PA/DHA) to simultaneously evaluate brain tumor metabolism and oxidative stress in orthotopically implanted mice is investigated. METHODS To characterize HP PA/DHA, mice were treated with 0-4mM diethyl maleate and 1D slab dynamic acquisitions were performed over the mouse brain. As an initial evaluation of the utility of HP DHA/PA in brain tumors, athymic nude mice (n=8) underwent orthotopic U87 glioblastoma implantation. After treatment with 8Gy in one fraction, mice were injected with HP DHA/PA dissolved in D2O. T2-weighted and 13C Chemical Shift Imaging sequences were obtained on a 3T MRI using a quadrature double-tuned 1H/13C volume coil. RESULTS HP DHA/PA detected differential lactate and vitamin C generation over the mouse brain. Treatment with diethyl maleate, which depletes the cofactor glutathione, diminished fractional vitamin C generation (0.1 vs 0.03, p=0.0009). Elevation in tumor lactate generation was seen in untreated (125.1±17.6µM, p=0.005) and radiated mice (149.4±32.6µM, p=0.01). Treatment with radiation generated higher vitamin C concentrations in tumors relative to contralateral brain (46.8±4.8µM, p=0.002). Radiated tumors were distinguished by higher ratio of lactate to vitamin C compared to untreated tumor controls (3.7 vs 2.5, p=0.07), and the same relationship was preserved between treated and untreated non-tumor brain. CONCLUSION The ratio of vitamin C/lactate detects the metabolic effects of radiation in brain tumors, inspiring its’ potential as a biomarker for treatment response. To further characterize these findings, examination of survival and modulation of radiosensitivity are ongoing.