tbuckley/cabot-search huggingface dataset:
NIMG-42. ANALYSIS OF TUMOR RELAPSE PROBABILITY AND OVERALL SURVIVAL PREDICTION FOLLOWING TEMOZOLOMIDE CHEMORADIATION USING FET PET INCLUDING RADIOMICS IN PATIENTS WITH GLIOBLASTOMA
Authors: Isabelle Stetter, Jan-Michael Werner, Michael Wollring, Garry Ceccon, Philipp Lohmann, Keith George Ciantar, Gabriele Stoffels, Felix M Mottaghy, Gereon R Fink, Karl-Josef Langen, Norbert Galldiks
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Early after surgery and completion of first-line concomitant chemoradiation with temozolomide, the evaluation of tumor relapse probability and overall survival prediction is of considerable interest for the management of patients with glioblastoma METHODS Sixty-three newly diagnosed patients with glioblastoma (age range, 19-82) who received static and dynamic PET imaging using the radiolabeled amino acid O-(2-[18F]fluoroethyl)-L-tyrosine (FET) after surgery or biopsy and completion of concomitant chemoradiation with temozolomide were evaluated. Static FET PET parameters such as maximum and mean tumor-to-brain ratios (TBRmax, TBRmean) and metabolic tumor volumes (MTV), and the dynamic FET PET parameter time-to-peak (TTP) were obtained. Additionally, FET PET radiomics features (n=1,303) were extracted for each patient and a test-retest analysis was performed to identify robust features prior to feature selection. The prognostic value of FET PET parameters and radiomics features was evaluated using receiver-operating-characteristic (ROC) analyses with regard to a significantly prolonged progression-free and overall survival (PFS, OS). Subsequently, univariate and multivariate survival estimates were performed to assess the prognostic value of these parameters to predict a significantly longer PFS and OS RESULTS ROC analyses revealed that the parameter TBRmax was a powerful parameter to predict both a significantly longer PFS (20.3 vs. 8.9 months; P=0.002; threshold, 2.75) and OS (34.9 vs. 18.7 months; P=0.005; threshold, 2.75). MTV had a similar prognostic value for both PFS (16.7 vs. 7.2 months; P=0.002; threshold, 34.0 mL) and OS (30.6 vs. 14.8 months; P=0.002; threshold, 32.6 mL). After feature selection, 3 of 15 selected radiomics features predicted a significantly longer PFS and OS in univariate analyses. TBRmax, MTV, and one of 15 radiomics features remained significant in multivariate survival analysis (all P≤0.03) CONCLUSION Our results suggest that FET PET and radiomics parameters were highly prognostic in this group of patients at an early stage of first-line therapy.
SURG-40. PEDIATRIC LOWER GRADE GLIOMA SURGERY IN THE ERA OF GENOMIC MEDICINE
Authors: Akira Gomi
Journal: Neuro-Oncology (2024)

Abstract INTRODUCTION In the 2021 WHO Brain Tumor Classification, pediatric-type gliomas are distinctly categorized from their adult counterparts. The continual evolution of cancer genomics has significantly broadened the spectrum of available treatment options. Here we would like to consider surgery for pediatric low-grade gliomas. METHODS We retrospectively analyzed 41 cases of low-grade gliomas or glioneuronal tumors in pediatric patients who underwent surgery at our institute from 2002 to 2023. We discussed surgical strategies based on molecular classification. RESULTS Among the cases, there were 34 gliomas and 7 glioneuronal tumors. According to the new WHO classification, they corresponded to 1) Adult-type diffuse gliomas, 2) Pediatric-type diffuse low-grade gliomas, 3) Circumscribed astrocytic tumors, or 4) Glioneuronal and neuronal tumors. Cases without molecular diagnosis were also considered in light of the new WHO classification. Among molecularly diagnosed astrocytomas involving the cerebral hemisphere, brain stem, spinal cord, there were no cases of 1), and 2) 3) were the main cases. It is important in surgical selection to note that these cases generally have a more favorable prognosis compared to the adult type and have usefulness in diagnosing MAPK pathway abnormalities leading to the selection of molecularly targeted drugs. 3) includes pilocytic astrocytoma, subependymal giant cell astrocytoma, and pleomorphic xanthoastrocytoma. Among these, in the treatment of pilocytic astrocytoma of the visual tract and hypothalamus, biopsy is essential for molecular diagnosis and therapeutic agent selection. 4) is mainly an epilepsy-related tumor. While their removal contributes to genetic diagnosis and epileptic seizure control, total removal may not always be deemed necessary. CONCLUSION Based on the new WHO classification, a reevaluation of treatment strategies for pediatric brain tumors is necessary.
NIMG-10. THE ROLE OF FIBROBLAST ACTIVATION PROTEIN IN GLIOBLASTOMA AND GLIOSARCOMA – A COMPARISON OF TISSUE, 68GA-FAPI-46 POSITRON EMISSION TOMOGRAPHY AND SURVIVAL DATA
Authors: Christoph Oster, Lukas Kessler, Tobias Blau, Kathy Keyvani, Kim M Pabst, Wolfgang P Fendler, Pedro Fragoso Costa, Lazaros Lazaridis, Teresa Schmidt, Jonas Feldheim, Daniela Pierscianek, Hans-Ulrich Schildhaus, Ulrich Sure, Yahya Ahmadipour, Christoph Kleinschnitz, Nika Guberina, Martin Stuschke, Cornelius Deuschl, Björn Scheffler, Ken Herrmann, Sied Kebir, Martin Glas
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Despite their unique histological features,gliosarcomas belong to the group of glioblastomas and are treated according to the same standards. Fibroblast-activation-protein(FAP) is a component of a tumor-specific subpopulation of fibroblasts that play a critical role in tumor growth and invasion.However,the prognostic impact of FAP in glioblastoma and gliosarcoma is unclear. METHODS In a retrospective analysis,patients diagnosed with glioblastoma without sarcomatous differentiation and gliosarcoma were enrolled.Histological examination was performed using immunohistochemical FAP-staining and quantitative analysis with a standardized FAP-score.In a subset of patients,FAPI46-PET has been performed.The SUV-values are planned to be correlated with FAP-expression in the tumor tissue.Data obtained from immunohistochemical analysis and SUV-values are planned to be brought into perspective with clinically relevant prognostic factors,including survival estimates. RESULTS We enrolled 61 patients,including 13 diagnosed with gliosarcoma.Our analysis revealed that gliosarcomas exhibit significantly higher FAP-expression (median FAP-score: 3) compared to glioblastomas without sarcomatous differentiation (median FAP-score: 0.5, p&amp;lt;0.0001),where FAP was predominantly observed in the perivascular space.In gliosarcomas,FAP was also expressed by neoplastic cells.Moreover,a significant relationship was established between the immunohistochemical FAP-scores and the SUVmean and SUVpeak values on PET,suggesting that the PET tracer uptake accurately reflects the tumor’s FAP-expression.However,the differential expression of FAP suggests its potential as both a diagnostic marker and a therapeutic target.This hypothesis is further supported by the application of 68Ga-FAPI-46-PET in a 66-year-old female patient with recurrent gliosarcoma,alongside immunohistochemical analysis of tumor tissue.Both methods identified elevated FAP-expression and uptake,underscoring the feasibility of FAP as a target for nuclear medicine therapies in brain tumors. CONCLUSIONS Our study establishes a significant correlation between SUVmean/SUVpeak in 68Ga-FAPI-46 PET scans and FAP-expression in glioblastoma.Gliosarcomas express significantly more FAP than other glioblastomas. These insights suggest FAP’s potential as a theranostic target.We plan to investigate the effectiveness of FAP-specific tracers in treating recurrent gliosarcoma,aiming to open new therapeutic avenues.
RADT-04. SEQUENCING OF CHECKPOINT INHIBITORS AND RADIOTHERAPY IN MELANOMA BRAIN METASTASES: A META-ANALYSIS OF COMPARATIVE STUDIES
Authors: Philip Haddad, Deepti Kantamani, Ankita Gupta
Journal: Neuro-Oncology (2024)

Abstract OBJECTIVE Melanoma brain metastases significantly worsen prognosis, with incidence rates as high as 50%. While both immunotherapy and radiotherapy improve survival, the optimal sequencing remains undetermined. This meta-analysis aims to define the most effective treatment sequence for improving progression-free survival (PFS) and overall survival (OS). METHODS A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of melanoma brain metastases, comparative studies of immune checkpoint inhibitors given before or after radiotherapy, and those that reported overall (OS) and progression-free (PFS) survival. Studies that reported mixed data that included concurrent immune checkpoint inhibitors with radiotherapy were excluded. A meta-analysis using the fixed effects and random effects models was conducted. RESULTS Our analysis included six retrospective studies encompassing 213 patients, with a median age of 62 years and follow-up of 22 months. The results indicate a clear disadvantage in PFS when immunotherapy precedes radiotherapy (HR=1.77; 95% CI 1.21-2.60; p=0.003; I2=13.5%). Similarly, initiating treatment with immune checkpoint inhibitors followed by radiotherapy showed a trend towards poorer OS compared to the reverse sequence, although this finding was of borderline significance (HR=1.39; 95%CI 0.97-1.99; p=0.07; I2=0%). CONCLUSIONS This meta-analysis, the first and largest to date, provides compelling evidence that initiating treatment with radiotherapy followed by immune checkpoint inhibitors significantly improves PFS with a trend for a better OS in patients with melanoma brain metastases. These findings suggest that radiotherapy should precede immunotherapy to optimize clinical outcomes in this patient population. Further research, particularly prospective studies, is necessary to confirm these results.
CTIM-01. OUTCOMES AND IMMUNE RESPONSES AFTER PEPTIDE VACCINATION TARGETING HUMAN CYTOMEGALOVIRUS ANTIGEN PP65 IN CHILDREN AND YOUNG ADULTS WITH RECURRENT HIGH-GRADE GLIOMA AND MEDULLOBLASTOMA: RESULTS OF A PHASE 1 TRIAL
Authors: Eric Thompson, David Ashley, Kathy Ayasoufi, Pam Norberg, Gerald Archer, Evan Buckley, James Herndon, Ashley Walter, Bridget Archambault, Bea Balajonda, Charlene Flahiff, Denise Jaggers, Laura Gorski, Gordana Vlahovic, Elizabeth Reap, Kristin Schroeder, Annick Desjardins, Margaret Johnson, Katherine Peters, Mustafa Khasraw, Duane Mitchell, John Sampson, Daniel Landi
Journal: Neuro-Oncology (2024)

Abstract INTRODUCTION The human cytomegalovirus (CMV) antigen pp65 is ubiquitously expressed in high-grade glioma (HGG) and medulloblastoma but not in adjacent brain. The primary objective of this phase I trial (NCT03299309) was to assess the safety and feasibility of a novel peptide vaccine targeting pp65 (PEP-CMV) in children/young adults with recurrent medulloblastoma and HGG. METHODS PEP-CMV is comprised of a synthetic long peptide of 26 amino acids and is administered as an emulsion in Montanide ISA 51. Patients receive a 5-day course of temozolomide to induce lymphopenia, tetanus/diphtheria toxoid site preconditioning to promote dendritic cell migration, then PEP-CMV intradermally in the groin every two weeks for 3 doses, then monthly. RESULTS 42 patients were enrolled. The mean age was 23.2 ± 9.3 years. 55% of patients were male. The median KPS was 80. The median number of prior chemotherapy regimens was 4 (range 1-15). Of the 38 patients who received PEP-CMV, the maximum grade adverse events (AE) possibly, probably, or definitely related to PEP-CMV were: 17 (45%) Grade 1 AEs, 16 (42%) Grade 2 AEs, 2 (5%) Grade 3 AEs (encephalopathy and pyramidal tract syndrome), and one (3%) Grade 4 AE (cerebral edema). One patient developed cytokine release syndrome (Grade 2). The median PFS was 2.5 months (95% CI:2.2, 3.2) and median OS was 6.4 months (95% CI:3.4, 7.9). The 12-month OS was 26.6% (95% CI:14, 41.1%). Of the 21 patients with evaluable immune monitoring data (received ≥3 vaccines/known CMV status), T cell reactivity on IFNγ pp65 ELISpot was increased after PEP-CMV delivery (median 2 vs 22, P=0.01). PFS and OS were significantly better in patients with low levels of CD56brightCD16dim phenotype NK cells: P=0.029 and P=0.047, respectively. Patients with naïve CD8+ counts over the median had significantly better PFS (P=0.006). CONCLUSIONS PEP-CMV is well-tolerated and elicits an antigen-specific immune response in heavily pretreated, multiply recurrent patients with a 12-month OS of 26.6%.
SURG-41. OPTIMIZING PATIENT OUTCOMES IN PETROCLIVAL MENINGIOMA TREATMENT: EVALUATING SURGICAL, RADIOSURGICAL, RADIOTHERAPY AND COMBINED TREATMENT APPROACHES
Authors: Shagun Nasta, Amit Persad, Elaheh Shaghaghian, Yusuke Hori, Sara Coleman Emrich, Louisa Ustrzynski, Armine Tayag, David Park, Steven Chang
Journal: Neuro-Oncology (2024)

Abstract Petroclival meningiomas pose a formidable challenge due to their proximity to critical neurovascular structures, necessitating complex surgical interventions with a high risk of complications. Stereotactic radiosurgery (SRS) offers an alternative or complementary treatment option, yet the optimal treatment strategy remains undefined. We aimed to evaluate the local control rates following surgical resection, radiotherapy, and SRS for petroclival meningiomas and to assess the incidence of cranial nerve palsies associated with each treatment modality. This retrospective study reviewed medical records of patients treated for petroclival meningiomas at Stanford University between 1980-April 2024. Pre- and post-treatment radiological data were analyzed to assess local control. Cranial nerve function was evaluated pre- and post-treatment, and at last follow-up. A total of 171 patients (129 females; median age 54.65 years) diagnosed with petroclival meningioma were identified. Treatment modalities included: 31 patients underwent surgical resection alone, 27 received SRS alone, 11 received radiotherapy alone, 36 underwent combined surgical resection and SRS, 28 received combined surgical resection and radiotherapy, 9 were treated with a triad of surgical resection, SRS, and radiotherapy, and 29 were managed with serial imaging alone. The percentage change of tumor volume from diagnosis to follow-up for these groups was -55.6%, 28.9%, 73.0%, -64.9%, -12.0%, 35.3%, and -8.8%, respectively. The incidence of new cranial nerve palsies was highest (68%) in patients who underwent surgical resection. The percentage of worsening pre-existing palsies was greater in patients receiving single-modality non-surgical treatment. Surgery, radiotherapy, and SRS demonstrated promising local control rates for specific patient cohorts with petroclival meningiomas. Patients receiving combination therapies generally fared better than those receiving single-modality treatments, with surgery followed by SRS yielding the best outcome. The incidence of cranial nerve palsies was lower following SRS and radiotherapy compared to surgery. Future research should focus on refining multi-modal treatment strategies to minimize complications and improve patient quality of life.
EXTH-51. ENHANCING GLIOBLASTOMA TREATMENT: ALLOGENEIC CAR-T CELLS OVERCOMES FUNCTIONAL DEFICITS OF PATIENT-DERIVED AUTOLOGOUS PRODUCTS
Authors: Muhammad Vaseem Shaikh, Sabra K Salim, William T Maich, Alisha Ananad, Jeffrey Wei, Minomi K Subapanditha, Yujin Suk, Manoj Singh, Zoya Tabunshchyk, Katie Chen, Parvez Vora, Chitra Venugopal, Jason Moffat, Sheila K Singh
Journal: Neuro-Oncology (2024)

Abstract Glioblastoma (GBM) is the most common primary brain malignancy in adults, with a dismal prognosis despite an intensive standard of care. Recently, chimeric antigen receptor T-cell (CAR-T) therapy has shown promising outcomes in treating liquid malignancies. However, clinical trials targeting various tumor antigens in GBM failed to show durable clinical benefit. Though this may stem from various tumor-intrinsic immune evasion strategies typical of GBM, there has been little work investigating whether the problem lies in the quality of the CAR-T products treatment itself. Currently, CAR-T cells for clinical studies are produced in an autologous setting, where T-cells are extracted from patients, engineered ex-vivo, and then re-infused. However, peripheral T-cells taken from GBM patients have shown qualitative and functional deficits, which may contribute to suboptimal treatment outcomes. Thus, we aimed to explore whether CAR-Ts generated from GBM patients had any functional deficits in comparison to healthy donors, utilizing our previously validated CD133 CAR-T. In this study, we show pre-treatment exhaustion, poor tumor control, and reduced survival advantage in autologous, patient-derived CD133-targeting CAR-T cell products using an orthotopic xenograft model of human GBM. To address the functional and logistical considerations of autologous therapy, we also sought to generate an “off-the-shelf” allogeneic CD133 CAR-T. Using CRISPR gene editing technology, we generated TCR-knockout CAR-T cells with comparable pre-clinical efficacy to our healthy donor derived autologous models. Ultimately, this work highlights the need to reevaluate autologous CAR-T therapy for GBM and consider allogeneic approaches as biologically-informed therapeutic alternatives.
NIMG-82. DEVELOPMENT AND VALIDATION OF AN MRI-BASED DEEP LEARNING MODEL TO DIFFERENTIATE<i>IDH</i>-WILDTYPE GLIOBLASTOMA AND TUMEFACTIVE MULTIPLE SCLEROSIS
Authors: Gian Marco Conte, Mana Moassefi, Paul Decker, Matthew Kosel, Christina McCarthy, Mah Fereidan, Yalda Nikanpour, Heather Pump, Robert Jenkins, Daniel Lachance, Bradley Erickson, W Oliver Tobin, Jeanette Eckel-Passow
Journal: Neuro-Oncology (2024)

Abstract Clinical management of IDH wildtype glioblastoma (GBM) and tumefactive multiple sclerosis (tMS) is drastically different. GBM requires maximal safe resection followed by chemoradiation, while tMS outcome is worsened by surgery and radiotherapy. Noninvasive methods are needed to help with accurate diagnosis of tumor and non-tumor etiologies. To develop an MRI-based classification model, tMS subjects diagnosed prior to January 1, 2020, were matched to tMS by age at diagnosis, sex, index MRI date, and 2D/3D acquisition. Inclusion criteria included one cm minimal lesion size and pre-operative post-contrast T1 and T2 images available for analysis. A 3D-DenseNet121 was used to develop a classification model using prespecified parameters: 650 epochs, batch size 16, learning rate 10-3, cross-entropy loss, and AdamW optimizer. The stopping rule was defined as three sequential differences in epoch cross-entropy loss &amp;lt;0.02. Models were developed using both T1gd and T2, as well as from only T1gd and only T2. Training included 220 subjects (110 GBM, 110 tMS). A 2-stage validation design was used, which included both retrospective and prospective cohorts. Stage 1 consisted of 272 retrospective GBM (diagnosed prior to January 1, 2020). Stage 2 consisted of 69 and 34 prospective (diagnosed after January 1, 2020) GBM and tMS, respectively. External validation on the 272 retrospective GBM demonstrated accuracy of 91%, 84%, and 78% for T1gd+T2, T1gd only, and T2 only, respectively. External validation on the 69 prospective GBM demonstrated an accuracy of 87%, 64%, and 67% for T1gd+T2, T1gd only, and T2 only, respectively. The 34 prospective tMS demonstrated accuracy of 76%, 76%, and 82% for T1gd+T2, T1gd only, and T2 only, respectively. This shows the feasibility of deep learning to aid in differential diagnosis of brain lesions. Future work entails the integration of germline variants into the classification model, including variants associated with the risk of glioma or MS.
NIMG-03. USE OF ARTERIAL SPIN LABELING TO DIFFERENTIATE ICTAL PHENOMENON FROM TUMOR PROGRESSION IN HIGH GRADE ASTROCYTOMA
Authors: Anza Zahid, Nithisha Thatikonda, Prachi Dubey, Ivo Tremont-Lukats
Journal: Neuro-Oncology (2024)

Abstract A 39-year-old female with grade-3 left parietal IDH-mutant astrocytoma following resection presented with convulsive status. EEG showed electrographic seizures arising from the left parietal region. MRI-brain showed the left temporoparietal post-treatment bed without any contrast enhancement (Fig-1A). Arterial spin labeling (ASL) – MR perfusion showed markedly increased cerebral blood flow (CBF) in the left temporoparietal lobe (Fig-1 C, D) with corresponding diffusion restriction (Fig-1B). Repeat imaging two weeks after the seizure control showed complete resolution (Fig-2) suggesting the imaging abnormalities to be a peri-ictal phenomenon.1 ASL-MR perfusion is a highly sensitive marker of increased CBF with its emerging application in distinguishing tumor progression (increased CBF) from post-treatment changes such as radiation necrosis (reduced CBF).1,2 This case highlights the utility of ASL-MR perfusion in differentiating peri/post-ictal phenomenon (increased CBF without T1-contrast enhancement) from tumor progression (increased CBF with T1-contrast enhancement) when employed routinely in clinical oncology practice.
TMOD-16. ZUCLOPENTHIXOL REDUCES ACTIVITY-DEPENDENT GLIOBLASTOMA PROLIFERATION
Authors: Mikias Negussie, Saritha Krishna, Andy Daniel, Cesar Nava Gonzales, Shawn Hervey-Jumper
Journal: Neuro-Oncology (2024)

Abstract A major challenge in modeling glioblastoma in the laboratory is the complex microenvironment in which tumors evolve in humans. The varied architecture and immune privilege of the brain limits the external validity of many experiments performed in modern cell biology laboratories. Organotypic human cortical slices present an opportunity to model glioblastoma and test the effect of drugs against glioma in ex-vivo human tissue. Cortical slice cultures maintain the cellular organization of the human brain, more closely approximating glioblastoma proliferation in patients. In this study, we test the effect zuclopenthixol, a repurposed antipsychotic inhibitor of glioblastoma-induced neuronal hyperexcitability, on the proliferation of glioblastoma cells in an organotypic human cortical slice culture. Primary patient-derived glioblastoma cultures were established, and human cortical tissues were emersed in oxygenated ACSF agarose gel before preparing 250 µm thick slices. Slices were either exogenously seeded with glioblastoma cells or stained for endogenous tumor infiltration. Slices with either endogenous or exogenous seeding were then treated with zuclopenthixol or regular media change and cultured for 10 days. Proliferation was measured with Ki67 staining and quantified via automated pixel summation using the Pillow library in Python. 0.1 µM zuclopenthixol treated slices had significantly lower proliferation index in both the endogenous tumor condition (0.04 vs 0.30, P &amp;lt; 0.05) and the exogenous seeding condition (0.0013 vs 0.028, P = 0.033). Reduced tissue integrity was observed beginning day 8 of culture, as tissue surrounding tumor seeding sites eroded. Here, we model glioblastoma proliferation in live human tissue and quantify the anti-proliferative effect of zuclopenthixol. We show that zuclopenthixol treatment significantly reduced the proliferation index. Our experimental model allowed the optimization of organotypic human cortical slice cultures for immunofluorescence studies and live-cell imaging.