tbuckley/cabot-search huggingface dataset:
CTNI-21. PIVOTAL, PHASE 2B RENEU TRIAL OF MIRDAMETINIB IN CHILDREN AND ADULTS WITH NEUROFIBROMATOSIS TYPE 1-ASSOCIATED PLEXIFORM NEUROFIBROMA (NF1-PN): A SPOTLIGHT ON PATIENTS ACHIEVING DEEP RESPONSE
Authors: Timothy Gershon, Christopher Moertel, Rene McNall-Knapp, Hans Shuhaiber, Lauren Weintraub, Fouad Hajjar, Molly Nickerson, Michael Weber, Armend Lokku, Dusica Babovic-Vuksanovic, Angela Hirbe
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Patients with NF1-PN in the phase 2b ReNeu trial (NCT03962543) of mirdametinib in adults (N=58, ≥18y) and children (N=56, 2-17y) had a deeper median (range) best reduction (adults: -41% [-90% to 13%]; children: -42%, [-91% to 48%]) from baseline in target PN volume than previously published in trials of other agents in NF1-PN. METHODS In the 24-cycle (1-cycle=28d) treatment phase, objective response rate (ORR) was the percentage with confirmed objective responses (OR) of ≥20% target PN volume reduction from baseline on consecutive MRIs (by blinded independent central review). This analysis includes patients achieving deep response (&amp;gt;50% best reduction from baseline in target PN volume) regardless of OR and inclusive of patients in the long-term follow-up. Exploratory analysis of baseline characteristics compared patients with deep response and patients with ≤50% volume reduction. RESULTS ORR was 41% (24/58) in adults and 52% (29/56) in children treated with mirdametinib. 62% (15/24) of adults and 52% (15/29) of children who achieved OR had deep response. To further characterize deep response, 2 adults and 3 children with deep response without confirmation or in long-term follow-up were included. Of those with a deep response, 35% (6/17) of adults and 72% (13/18) of children were investigator-defined as having progressing PN. Patients achieved deep response regardless of baseline age, sex, target PN volume, tumor location, or progression status. For adults and children, median time to best percent change from baseline in PN volume for patients achieving deep response was 25.4 and 21.8mo; for patients with reductions of ≥20% to ≤50% was 15.3 and 15.2mo; for patients with reductions of &amp;lt;20% was 7.8 and 4.2mo, respectively. CONCLUSIONS Patients had a similar likelihood of achieving deep response across assessed baseline characteristics. A trend between deep response and longer treatment duration suggests a benefit of prolonged therapy with mirdametinib.
BIOM-35. COMPREHENSIVE IDENTIFICATION OF MRNA ISOFORMS AND THEIR DIAGNOSTIC POTENTIAL IN GLIOMAS
Authors: Pallavi Goel, Subhashini Sadasivam, Yashoda Ghanekar, Vijaylaxmi Roy, Vijay Sreegiriraju, Neha Kumari, Surya Madiraju, Amit Ray
Journal: Neuro-Oncology (2024)

Abstract Most genes generate multiple mRNA isoforms which may differ in their protein-coding capacity. Also, cancer and its prognosis are associated with the altered expression of specific isoforms of a variety of genes as cancer cells can manipulate regulatory mechanisms to express isoforms that provide a survival advantage and/or resistance to therapy. However, the underlying mechanisms behind their pathology are poorly understood. Fifty seven glioma samples that could be categorized unambiguously into Astrocytoma (n=17), Oligodendroglioma (n=16) and Glioblastoma (n=24) based on pathology reports and according to WHO standards were selected for this analysis. Total RNA-Sequencing (RNA-Seq) was performed on RNA isolated from these 57 samples. RNA-Seq data analysis was performed using the DRAGEN RNA application in Illumina BaseSpace and transcript counts were generated after alignment. From these counts, isoforms that were significantly differentially expressed in Astrocytoma (Astro) vs Oligodendroglioma (Oligo), and Astrocytoma vs Glioblastoma (GBM) were identified using the R package, IsoformSwitchAnalyzeR. Approximately 93,000 transcripts were screened in both comparisons of which 4388 and 44 transcript switches were identified as significant at FDR&amp;lt;0.05 in the Astro vs GBM and Astro vs Oligo comparisons, respectively. Applying an additional cut-off based on the difference in isoform fraction or dIF of a transcript between the two groups being compared (dIF&amp;gt;1.0 and dIF&amp;lt;-0.1), the most significant top switches were identified.. Similarly, in the Astro vs GBM comparison, the isoform switch in genes such as MDF1 and RER1 whose overexpression is known to be involved in tumorigenesis and metastasis were among the 155 top switches. Among the six top switches in the Astro vs. Oligo comparison were transcripts of the RENBP and GCNT2 genes which play an important role in the progression of melanoma, gastric and lung cancers. These results indicate that there may be isoform-specific dysregulation within gliomas, and further suggest that their biological significance and diagnostic potential can be explored.
NIMG-55. DEVELOPING A COMPUTATIONAL PIPELINE TO FORECAST AND SPATIALLY MAP HIGH-GRADE GLIOMA RESPONSE TO RADIOTHERAPY USING BIOPHYSICAL MODELS AND DATA-DRIVEN STATISTICAL ANALYSIS
Authors: Sophia Ty, Jeanne Kowalski-Muegge, Maguy Farhat, Bikash Panthi, Holly Langshaw, Mihir D Shankar, Wasif Talpur, Sara Thrower, Jodi Goldman, James Custer, Thomas E Yankelov, Caroline Chung, David A Hormuth, II
Journal: Neuro-Oncology (2024)

Abstract High-grade glioma (HGG) presents significant treatment challenges, particularly in identifying less responsive tumor areas to target with adaptive radiotherapy (RT). This study introduces a patient-specific computational pipeline designed to predict and spatially map HGG response to RT, focusing on regions demonstrating resilience to RT. Our computational pipeline is centered around a family of 3D biophysical models describing tumor cell invasion, proliferation, and response to RT which can be personalized for individual patients using longitudinal multiparametric MRI data. Utilizing longitudinal multiparametric MRI data reporting on cell density (diffusion weighted MRI) and the extent of disease (T2-FLAIR and contrast-enhanced T1-weighted MRIs) from 21 patients, ranging from baseline to three weeks into RT, we calibrated a family of biophysical models to forecast tumor cell density up to the final week of RT and one-month follow-up. By employing pareto tail analysis on empirical cumulative distribution function fits of voxel-wise changes in apparent diffusion coefficient maps (ΔADC) between the future images (end of RT, one-month follow-up) and pre-treatment images, we identified areas of increased tumor cellularity on both the ground truth and model predicted cellularity maps. The analysis differentiated tumor voxels into “non-responding” and “responding” categories, based on cutoffs determined through ROC analysis across various conditions—including assessments of both enhancing and non-enhancing tumor regions at different time points. Optimal ΔADC cutoffs for predicted and measured data were established, leading to high area under curve (AUC; ranging from 0.803 to 0.934) values and significant Youden’s index scores (ranging from 0.526 to 0.765) across all conditions. Our findings demonstrate the feasibility of this novel pipeline in delineating biologically relevant RT targets, offering a potential tool for enhancing the efficacy of adaptive RT strategies in treating HGG.
INNV-29. PATIENT BARRIERS AND PREFERENCES FOR EXERCISE FOLLOWING A BRAIN TUMOR DIAGNOSIS
Authors: Shannon Fogh, Kavita Mishra, Naomi Hoffer, Mary Destri, Susan Chang, Jennie Taylor
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Exercise has shown benefit in patients with cancer, however patients with brain tumors often experience deficits in cognition, motor skills and other symptoms, further exacerbated by treatment, which can make exercise challenging. Yet, the literature supports positive impact of exercise on symptoms and prognosis within this patient population. Our study aims to understand patient’s motivations and preferences for exercise. METHODS We surveyed patients with primary brain tumors within a single, quaternary medical center. Questions were extrapolated from published questionnaires and were accessed through flyers containing a QR code. Questions assessed current practices, attitudes, knowledge, motivating factors and barriers for integrating exercise into treatment. RESULTS Twenty-nine patients completed the survey. Nearly 70% reported that exercise has been important throughout their life in maintaining good health and quality of life. Walking emerged as the predominant mode of physical activity (55%). Thirty-one percent of patients reported the intensity of their current routine was light activity, 24% moderate activity, and 7% vigorous activity.The primary motivators for patients initiating or sustaining an exercise regimen included having someone monitor their progress (28%), complimentary access to a workout facility (21%) and awareness of the beneficial impact of exercise on symptoms and prognosis (51%). The most prevalent physical barriers to exercise included trouble with balance (34%), fatigue (34%) and headaches (21%). Other barriers included lack of transportation (38%), space (21%), cost (21%) and time (14%). Sixty-six percent of patients were more likely to participate in an exercise program if mentioned by their healthcare provider or healthcare team during a visit. CONCLUSION Findings from this study help to expand our understanding of barriers and facilitators to incorporating exercise interventions into brain cancer treatment and can inform the implementation of a structured exercise programs.
CTNI-38. SINGLE-CENTER COMPARATIVE ANALYSIS ABOUT OUTCOMES OF MULTI-AGENTS CHEMOTHERAPY FOR PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA; R-MPV SHOWED A FAVOR RESULT
Authors: Yasuhide Makino, Etsuko Yamamoto, Shigeki Takada, Noritaka Sano, Masahiro Tanji, Yohei Mineharu, Yoshiki Arakawa
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Primary central nervous system lymphoma (PCNSL) is a malignant tumor in the brain, spinal cord, and eyes. Radiotherapy may cause delayed leukoencephalopathy so that the first-line treatment is methotrexate (MTX)-based multi-agent chemotherapy. We had used the Bonn protocol based on MTX and cytarabine, but since 2020, we have adopted the R-MPV protocol. This study analyzes the outcomes of patients treated initially at our institution. METHODS AND RESULTS We reviewed 57 out of 88 newly diagnosed PCNSL patients treated with chemotherapy alone between December 2005 and January 2023. Initial treatments included the Bonn protocol in 25 patients (12 with rituximab, forming R-Bonn) and R-MPV in 26 patients. High-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) was given as consolidation in 4 Bonn and 9 R-MPV patients. The Bonn protocol was completed by 20 patients (80%) with a complete response (CR) in 19 (76%). The R-MPV protocol was completed by 23 patients (88%) with CR in 22 (85%). Post-treatment outcomes were compared using survival analysis. Median progression-free survival (mPFS) had not been reached in the R-MPV group and was significantly better than 33.1 months in the Bonn protocol and 58.6 months in the R-Bonn protocol (log-rank test; p=0.0296, 0.0036). Overall survival (OS) did not show significant differences. PBSCT’s impact on outcomes suggested improvement in PFS and OS after R-MPV, but this was not statistically significant. DISCUSSION We examined the efficacy of different chemotherapy regimens for PCNSL at our institution. The R-MPV protocol showed superior completion rates, response rates, and treatment efficacy. Consolidation with PBSCT may improve outcomes, though further investigation with more cases and longer observation is necessary.
NCMP-12. AN ATYPICAL CASE OF POEMS WITH MACROFOCAL MYELOMA
Authors: Janet La, Jerome Graber
Journal: Neuro-Oncology (2024)

Abstract Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes (POEMS) syndrome is a rare paraneoplastic syndrome secondary to an underlying plasma cell dyscrasia. Symptoms of peripheral neuropathy dominate the clinical picture and is postulated to be related to serum vascular endothelial growth factor (VEGF) mediated altered permeability of the blood nerve barrier. The classic presentation includes a solitary osteosclerotic plasmacytoma and an elevation of VEGF. In this case, we present a patient with neither of these features who met diagnostic criteria for POEMS though had predominantly osteolytic lesions and was diagnosed with macrofocal myeloma, a unique subset of multiple myeloma. Our patient is a young male who presented with progressive leg numbness/weakness and was found to have marked ankle weakness, diffuse areflexia and unilateral gynecomastia on examination. EMG showed a motor predominant demyelinating polyneuropathy. Labs showed a serum IgG lambda M protein, low estradiol and low testosterone. He had a normal serum VEGF level though the lab was drawn after treatment initiation. Bone biopsy of a dominant osteolytic lesion was consistent with a plasma cell neoplasm (light chain restricted). Of note, he had mild cauda equina nerve root and ventral conus enhancement initially concerning for leptomeningeal involvement however, two lumbar punctures were negative for malignant cells. Spinal enhancement has been reported in POEMS. The patient underwent chemotherapy, radiation therapy and autologous stem cell transplantation. We present a patient diagnosed with MFMM, a rare subset of multiple myeloma, comprising only 3% of all cases, along with POEMS, a rare paraneoplastic syndrome. Interestingly, as osteolytic lesions can be seen in POEMS alone though not predominantly so, it is possible the patient could have atypical POEMS without underlying multiple myeloma. POEMS may remain under-recognized when presentations or setting are atypical.
NIMG-65. SYNTHETIC MRI GENERATION TO FACILITATE AUTOSEGMENTATION OF PEDIATRIC BRAIN TUMORS IN LIMITED DATA SCENARIOS
Authors: Dimosthenis Chrysochoou, Deep Gandhi, Ariana Familiar, Arastoo Vossough, Phillip Storm, Adam Resnick, Christos Davatzikos, Ali Nabavizadeh, Anahita Fathi Kazerooni
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND The availability of standard multiparametric MRI sequences, including pre-contrast T1w (T1w-pre), post-contrast T1w (T1w-post), T2w, and FLAIR images, is essential for accurate segmentation of tumor subregions and subsequent response assessment in pediatric brain tumors (PBTs). However, clinical MRI sets are often incomplete due to imaging artifacts or inconsistent acquisition protocols across different centers. This study leverages Generative Adversarial Networks (GANs) to synthesize missing FLAIR and T1w-pre images from T2w and T1w-post images, respectively, to facilitate tumor segmentation in PBTs. METHODS We developed two GAN models based on the pix2pix framework, trained, validated, and tested on FLAIR-T2w and T1w-post-T1w-pre pairs from a multi-histology and multi-institutional cohort of 476 subjects with PBTs from the Children’s Brain Tumor Network (CBTN). The perceptual quality of the synthesized T1w-pre and FLAIR images was evaluated using the Structural Similarity Index (SSI; ideal value = 1). The robustness of the synthesized sequences to replace missing MRI sequences was evaluated by comparing the segmentation performance (Dice score) of our pre-trained autosegmentation model using all real modalities versus replacing real sequences with their synthesized counterparts. RESULTS The T1w-pre and FLAIR synthesis GANs achieved mean SSI values of 0.95 and 0.93, respectively. Median Dice scores for segmentation of whole tumor (WT), enhancing tumor (ET), and tumor core (TC) were calculated for real sequences: 0.90, 0.83, 0.89, replacing real FLAIR with synthetic: 0.86, 0.81, 0.86, and replacing real T1w-pre with synthetic: 0.90, 0.75, 0.89. No statistical significance (p&amp;gt;0.05) was observed in segmentation performance for WT, TC, ET when replacing real T1w-pre with synthetic, and for ET when replacing real with synthetic FLAIR sequences. CONCLUSION This method achieves robust segmentation performance in limited data scenarios by synthesizing missing MRI sequences. Future work includes improving FLAIR synthesis and segmentation performance for WT and ET by implementing and comparing other GAN architectures.
CTNI-26. A PHASE II STUDY OF SACITUZUMAB GOVITECAN IN RECURRENT GLIOBLASTOMA
Authors: William Kelly, Christine Cordova, Brian Vaillant, Henriette Balinda, Joel Michalek, Andrea Gilbert, John Floyd, Andrew Brenner
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Glioblastoma (GBM) is the most aggressive and common form of primary brain cancer. GBM expresses trophoblast cell-surface antigen 2 (Trop2) which correlates with proliferation rate, microvessel density, histological grade and clinical survival. Sacituzumab Govitecan (SG) is an antibody-drug conjugate targeting Trop2 with a chemotherapy payload, SN-38. This drug has been approved for triple-negative and hormone-receptor positive metastatic breast cancer. METHODS We conducted multi-center (UT Health San Antonio, Cleveland Clinic, Texas Oncology in Austin), open-label, single-arm phase 2 study using a 2-stage adaptive Bayesian design. Patients with recurrent GBM (rGBM), IDH wild-type, following standard-of-care chemoradiation, received SG (10mg/kg IV, days 1 and 8 every 21 days). Patients were assessed by RANO and CTCAE v5. The primary endpoint was PFS of patients on SG as compared to a historical control of lomustine. RESULTS As of interim analysis cutoff, 24 patients have been screened with 20 patients enrolled. The average age was 58.8 years. 65% of patients identified as male. 95% were Caucasian with 20% identifying as Spanish, Hispanic or Latino. Adverse events (AE) include lymphopenia (40%), neutropenia (40%), hypokalemia (35%), elevated alkaline phosphatase (30%), anemia (30%) with most AE being grade ≤ and no grade 5 observed. 4 patients had grade ≥3 neutropenia attributable to SG. 20% had stable disease as best response with the rest being progressive disease. The mean PFS and OS were 7.0 and 2.0 months, respectively. Of 19 evaluable samples, 63% had positive Trop2 expression (H-Score ≥100, mean 123.6±74 [0.6, 269.2]). A post-hoc analysis of OS log survival time vs H-Score (n=19) using an accelerated failure time model showed that survival correlated with H-Score (p=0.0361). CONCLUSIONS In the interim analysis of this study of patients with rGBM, Sacituzumab was found to be well-tolerated. Further study of those patients bearing tumors with elevated H-scores may be warranted.
RADT-08. THIRD RECURRENT WHO 1 SPINAL MENINGIOMAS. CASE SERIES AND CLINICAL OUTCOMES FOLLOWING SURGERY OR DEFINITIVE RADIOTHERAPY
Authors: Ory Haisraely
Journal: Neuro-Oncology (2024)

Abstract INTRODUCTION Spinal meningiomas (SM) account for approximately 1.2–12.7% of all meningiomas and 25% of spinal cord tumors. Most are benign (WHO grade 1), but a small percentage are atypical (WHO grade 2) or anaplastic (WHO grade 3). These tumors are typically solitary and non-invasive with low recurrence rates post-surgery. This study aims to compare the efficacy of definitive radiotherapy (RT) versus third surgery for recurrent SM WHO grade 1, focusing on local control, progression-free survival (PFS), and toxicity. METHODS A retrospective review approved by the Institutional Review Board included patients diagnosed with recurrent SM WHO grade 1 who underwent second surgery between 2008-2020. Patients who received radiation after the first surgery or upgraded to WHO grade 2 or 3 were excluded. Data on demographics, tumor characteristics, surgical techniques, and radiation therapy details were analyzed using descriptive and inferential statistics. RESULTS The study included 48 cases of third progression SM WHO grade 1. The median age was 53 years, and 70.8% were female. Tumor locations were primarily thoracic (75%). There was no significant difference in PFS between the third surgery and RT groups, with 36-month PFS rates of 77.4% and 76.4%, respectively. RT-related toxicities were manageable, and neurological improvements were noted in both groups, with more pronounced improvements in the surgical group. RT showed better pain control outcomes. CONCLUSION Both definitive RT and third surgery are effective for managing recurrent SM WHO grade 1, with comparable PFS. RT is a viable alternative, especially for high-risk surgical patients, providing effective pain control and manageable toxicities. Further studies with larger cohorts and longer follow-ups are recommended to validate these findings and refine treatment protocols for recurrent SM, ultimately improving patient outcomes and quality of life.
CTNI-25. TUMOR TREATING FIELDS (TTFIELDS) THERAPY WITH CHEMORADIATION, FOLLOWED BY MAINTENANCE TTFIELDS THERAPY/TEMOZOLOMIDE (TMZ), IN NEWLY DIAGNOSED GLIOBLASTOMA (NDGBM). RESULTS OF PHASE II CLINICAL STUDY
Authors: Rachel Grossman
Journal: Neuro-Oncology (2024)

Abstract INTRODUCTION Tumor-Treating Fields (TTFields) are electric fields that exert physical forces to disrupt cancer cell function and tumor progression via a multimodal mechanism of action. Following the phase 3 pivotal EF-14 study, TTFields therapy concomitant with temozolomide (TMZ) maintenance therapy became approved for newly-diagnosed glioblastoma (ndGBM). Pre-clinical data and pilot clinical studies suggests synergistic effect of concomitant TTFields treatment with radiotherapy (RT). OBJECTIVE To assess the efficacy and safety of first line TTFields therapy concomitant with RT/TMZ vs RT/TMZ alone in adult patients with ndGBM. Design: 69 patients with ndGBM and KPS≥70 stratified by MGMT status, extent of resection, and age, were randomized 1:1. The experimental arm received TTFields therapy from the first day of chemoradiation, the control arm started 4 weeks after completion of chemoradiation. Patients continued TTFields therapy until second disease progression or 24months. The primary endpoint was 1-year PFS rate, and secondary endpoints included PFS, OS, and safety. Kaplan-Meier estimates were used to assess whether PFS and OS were improved with first line TTFields therapy/RT/TMZ vs RT/TMZ with delayed TTFields therapy. RESULTS Overall, 46 patients received maintenance chemotherapy and TTFields therapy. Mean age was 62 years (range:27–77). One-year PFS rate was 36% and 19% in the experimental and control arms, respectively (p-value=0.10). Median PFS was 9.9 and 5.6 months (HR 0.53, p-value 0.049). Median OS was 25.9 and 17 months (HR 0.85, p-value=0.6). Two-year OS rates were 52% and 31% (p-value 0.07). Among patients with high TTFields usage (≥75%) 2-year OS rates were 78% and 34% (p=0.01). CONCLUSIONS The addition of concomitant TTFields to standard treatment with temozolomide and RT for patients with ndGBM appears to be another step in improving the outcome of this patients population. This is further investigated in the large-scale TRIDENT study.