bluuebunny/crossref_metadata_2025 huggingface dataset:
INNV-25. PROLONGED FOLLOW-UP OF AN OLIGODENDROGLIOMA PATIENT WITH HISTORY OF TUMOR TREATING FIELDS (TTF) AS POST CHEMO-RADIATION MAINTENANCE THERAPY
Authors: Ko Uvin , Fu Beverly Dan , Myung Joon , Kong Xiao-Tang
Published: November 2023

INTRODUCTION: Recurrence of low and high-grade gliomas are common after radiation and chemotherapy. Despite continued research on glioma’s management, there is limited knowledge regarding the role of maintenance treatment after standard radiation and chemotherapy therapy. Tumor Treating Fields as maintenance therapy after radiation and chemotherapy may potentially help prevent recurrence of oligodendroglioma. Case Report: A 35-year-old male developed headaches and a non-enhancing mass was detected on his brain MRI in 2011. Observation was advised by his surgeon. The patient presented with seizures in early 2014, and his brain MRI found the mass developed new enhancement. In late 2014, the patient had multiple seizures, and significant progression of the tumor was discovered. The patient underwent craniotomy and biopsy in the middle cerebral artery distribution area in early 2015. Pathology reported grade II oligodendroglioma; however, a biopsy might have missed the high-grade glioma region. His brain MRI showed a significant enhancing lesion, which was clinically also consistent with grade III oligodendroglioma due to rapid growth. Radiation was conducted followed by 6 cycles of PCV chemotherapy throughout 11 months. Post-radiation-chemotherapy brain MRI was stable with a moderate size residue tumor at the right insula region. Following patient wishes, NovoTTF-100A, or Optune, was administered 6 weeks after completion of chemotherapy as maintenance therapy for 2 years to prevent tumor progression. Now, after 5 years being off Optune, the patient is full-functional, and his brain MRI is stable without tumor progression. Discussion: Our case highlights the potential effect of Tumor Treating Fields as maintenance therapy after initial radiation and chemotherapy for lower and higher grade oligodendrogliomas. The patient had rapid tumor progression on brain MRI prior to treatment and only underwent a biopsy without resection, yet uncommonly, remains survival and full functional since initial image diagnosis 12 years ago and tissue diagnosis 8 years ago.
INNV-26. THE CHALLENGE OF TREATING ADULTS WITH MEDULLOBLASTOMA – THE CANON EXPERIENCE
Authors: Bennett Julie , Lim-Fat Mary-Jane , Roberto Katrina , Massey Natalie , Ramaswamy Vijay , Sahgal Arjun , Mason Warren , Morgan Erin , Ironside Sarah , Ahmed Osama , Tsang Derek , Das Sunit , Tabori Uri , Hawkins Cynthia , Climans Seth
Published: November 2023

INTRODUCTION

Medulloblastoma (MB) is the most common malignant brain tumor in children, but relatively rare in adults. Pediatric treatment paradigms may be applied to young adults despite a paucity of data in this population. Here we aim to describe the characteristics of adults with MB presented at the Canadian Adolescent and Young Adult Neuro-Oncology Network (CANON) multi-disciplinary national rounds along with provider’s current practices in treating these patients.

METHODS

Cases presented at national rounds between April 2021 – June 2023 including young adults with MB were analyzed to describe patient characteristics and themes of the questions posed. In addition, a survey was sent to all Canadian neuro-oncologists asking about current practice patterns and we describe responses.

RESULTS

A total of 15 young adults with MB were discussed in this time frame. There were 13 males and 2 females with a median age of 30 years (range 20-61). Subgrouping was available on 12/15, with 7 (46.7%) SHH-activated, 3 (20%) WNT-activated and 3 (20%) Group 4 MB. Ten of the patients presented were new diagnoses with discussion regarding treatment including dose of radiation and chemotherapy protocol. In addition, 4/10 had an incomplete resection and there was discussion regarding a second look surgery. Three patients were presented at time of recurrence, with 2/3 being extra-cranial recurrence. There were a total of 25 responses to the Canadian survey on medulloblastoma, showing variation in practice. Most patients got craniospinal irradiation with 36 Gy. There was wide variation in terms of chemotherapy regimens offered.

CONCLUSION

There are differences in treatment practices for adults with MB across Canada with many questions regarding what treatment should be offered, specifically related to chemotherapy regimen. This highlights the desperate need to harmonize practice and examine adults as a unique cohort.
PATH-04. TRANSFORMATION OF GRADE 2 OLIGODENDROGLIOMA TO GLIOSARCOMA WITH RAPID AND EXTENSIVE PROGRESSION: CASE REPORT.
Authors: Jani Ronak , Casinelli Eric , Goyal Abhishek , Prabhu Vikram , Chundury Anupama , Borys Ewa , Barton Kevin , Thakkar Jigisha
Published: November 2023

Transition of WHO grade 2 oligodendroglioma to gliosarcoma is rare. We report a case of a 40 year-old gentleman with WHO grade 2 oligodendroglioma, isocitrate dehydrogenase enzyme (IDH)-mutant, 1p/19q co-deletion positive, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylated, tumor mutational burden of 5 mutations/megabase, with microsatellite stability. He underwent rapid and extensive transformation to WHO grade 4 glioblastoma with gliosarcomatous features, mesenchymal subclass on DNA methylation, IDH-wild type, 1p/19q co-deletion negative, MGMT promoter methylated. He was diagnosed with bi-hemispheric multifocal partially enhancing, T2-FLAIR hyperintense lesions. Pathology revealed WHO grade 2 oligodendroglioma. He enrolled on a clinical trial to receive proton radiation (45 Gray in 25 fractions) to the involved tumor sites. Three weeks after initiation of radiation, he developed headache, imbalance, and confusion. MRI brain 3 weeks after completion of radiation revealed worsening enhancement, edema, and a new region of non-enhancing T2-FLAIR hyperintensity. Bevacizumab was added for presumed pseudo-progression; followed by chemotherapy with procarbazine and lomustine (PC). Four cycles of PC were completed with observations of gradual clinical and radiographic worsening after each cycle. Re-resection of multifocal tumor for tissue diagnosis and tumor debulking revealed progression to WHO grade 3 oligodendroglioma with high mitotic activity and regions of palisading necrosis. Two weeks postoperatively, malignant cerebral edema developed, requiring left sided decompressive craniectomy. Despite early introduction of 2nd-line chemotherapy with temozolomide, his disease continued to progress and he succumbed 1.5 years after initial diagnosis. Autopsy revealed extensive bi-hemispheric involvement of WHO grade 4 glioblastoma. Our patient demonstrated unusually rapid clinical and radiographic progression within one month after completion of radiation. Other reported cases in the literature have documented progression at 1 to 5 years after initial treatment. Both IDH mutation and 1p19q co-deletion were lost in the gliosarcomatous transformation. This tumor did not respond to alkylating agents despite the MGMT promoter-methylated status.
PATH-07. GENOMIC AND IMMUNE ANALYSIS OF PRIMARY REPLICATION-REPAIR DEFICIENT (RRD) GLIOMAS REVEALS THREE SUBGROUPS WITH DISTINCT DRIVERS AND RESPONSE TO IMMUNOTHERAPY: AN IRRDC REPORT.
Authors: Fernandez Nicholas , Chang Yuan , Lee Caitlin , Dimayacyac Jose , Levine Adrian , Negm Logine , Aamir Zoya , Nobre Liana Figueiredo , Bianchi Vanessa , Stengs Lucie , Crump Owen , Gattoni Emma , Chung Jiil , Nunes Nuno , Edwards Melissa , Bouffet Eric , Hawkins Cynthia , Das Anirban , Tabori Uri
Published: November 2023

BACKGROUND

Replication-repair deficiency (RRD) caused by germline/somatic defects in mismatch repair (MMRD) and/or polymerase-proofreading genes (PPD) drives 5-10% of high-grade gliomas in children, adolescents, and young adults (CAYA). Despite harbouring high mutation-burden (TMB), the basis of their heterogenous responses to immune-checkpoint inhibitors (ICI) is unknown.

METHODS

We performed multi-omic and immune analyses on human RRD-glioma specimens and developed murine models to investigate their differential responses to ICI.

RESULTS

RRD-gliomas in 202 CAYA-patients uniformly harbored high genomic microsatellite-instability and hypermutation (median TMB: 302-mutations/megabase), with specific MMRD mutational signatures contributing to frequent mutations in TP53 (88%), ATRX (83%), RAS/MAPK (77%) and IDH1/2 (17%). Strikingly, common pediatric mutations (K27M, G34R/V and BRAF;p.V600E) unrelated to MMRD signatures were absent, and a unique methylation profile distinct from non-RRD gliomas was observed. Molecularly, RRD-gliomas segregated into three genomic subgroups: RRD1 (MMRD+PPD; 56%), RRD2 (MMRD-only; 27%), and RRD3 (MMRD+IDH1/2; 17%). RRD1 included glioblastomas that developed early in germline CMMRD patients across the cerebral hemispheres and posterior-fossa, harbored extreme TMB (median: 420-mutations/megabase), balanced copy-number profiles, and immunogenic PPD signatures. RRD3 predominated in Lynch syndrome, presented in older children, were located in the forebrain, harbored lower TMB (median: 31-mutations/megabase) and demonstrated specific chromosomal gains/losses. Enrichment for immune-resistant JAK-STAT signalling in the RRD2/RRD3 transcriptome, and presence of high CD8+ T-cells in RRD1-glioma microenvironment, correlated with significantly improved 24-month post-ICI survival of 75% in RRD1 versus 43% and 33% for RRD2/3, respectively (p < 0.0001). Genetically engineered mouse models recapitulated the immuno-genomic phenotype and ICI-responses of the human RRD-subgroups, allowing successful preclinical testing of combinatorial checkpoint-inhibition strategies. Significant temporal and spatial heterogeneity linked to genomic instability and post-therapy immune-escape were observed.

CONCLUSION

Our data emphasizes an immediate need to distinguish RRD-glioma subgroups in clinical practice and translate our preclinical discoveries to subgroup-specific ICI-based combinatorial clinical trials.
PATH-11. POOLED IN VIVO ASSAY TO CHARACTERIZE GLIOBLASTOMA INVASION AT THE SINGLE-CELL RESOLUTION
Authors: Hara Toshiro , Chanoch-Myers Rony , Bussema Lillian , Greenwald Alissa , Behnan Jinan , Wakimoto Hiroaki , Galli Rossella , Tirosh Itay , Suva Mario
Published: November 2023

Tumor cell invasion is the main characteristic of glioblastoma and one of the obstacles to successful treatments. Nonetheless, molecular features of invading glioblastoma cells remain elusive and poorly characterized, such as their gene expression states and microenvironmental influences. Recently, we described cell state heterogeneity in glioblastoma by single-cell RNA-sequencing (scRNA-seq) and uncovered the contribution of immune cells to the heterogeneity. However, it is unclear whether the cell states observed in clinical specimens are implicated in invading glioblastoma cells in the surgically inaccessible brain parenchyma. It is also unclear whether the cell states are correlated to the non-immune microenvironment. As a tool for probing these questions, we developed an in vivo approach with mixtures of human glioblastoma spheroid lines for mouse intracranial xenografts. We validated this with 20 patient-derived models and identified, by scRNA-seq, in vivo models capable of infiltrating along the periphery of either neurons or blood vessels. We profiled and characterized programs, states, and clonality of invading glioblastoma cells by comparing cells from the contralateral invasive edge to their counterparts at the original bulk tumor. This comparative analysis showed evidence of a bi-directional transitioning model for cells residing in different spatial niches. Importantly, presence of an OPC-like state was significantly associated with invasion phenotype regardless of the infiltration routes. Our results suggest that cellular plasticity may be a prerequisite for the invasive phenotypes, urging further assessment to identify critical regulators of the cell states. In conclusion, this work describes pooled in vivo assays for the rapid interrogation of patient-derived xenografts, coupling the gene expression phenotypes with cellular functions such as invasion.
PATH-26. A RARE CASE OF EXOPHYTIC PILOCYTIC ASTROCYTOMA DIAGNOSED VIA MOLECULAR TESTING
Authors: Chee Michelle , McGranahan Tresa
Published: November 2023

INTRODUCTION

Pilocytic astrocytoma (PA) is a WHO grade 1 neoplasm that can share histological and radiological features with more malignant entities, including high grade astrocytoma with piloid features. In cases where the differential remains broad after histopathological examination, DNA methylation analysis and next generation sequencing can contribute significantly to making an accurate diagnosis. Machine learning has also played a role in developing multiple classifying algorithms which group tumors by their methylation status.

CASE

We report a case of an exophytic left frontal mass with adjacent bone erosion that preoperatively was favored to be a meningioma. Intraoperatively, the mass was found to be cortically based. With histopathologic review at two centers, the diagnosis remained IDH wildtype low-grade glioma not otherwise specified. The clinical treatment team interpreted the post-operative increase in T2 signal as radiographic progression consistent with high grade glioma and planned to proceed with chemoradiation. Patient elected for further evaluation; methylation array profiling and next generation sequencing identified a KIAA1549::BRAF fusion, consistent with a final diagnosis of pilocytic astrocytoma, a WHO Grade 1 Glioma. Given the favorable prognosis following gross total resection, the patient was recommended active surveillance and radiation and chemotherapy treatment planning was stopped.

DISCUSSION

This is a rare case of an exophytic pilocytic astrocytoma in which the tumor’s atypical histologic and radiographic appearance increased the likelihood of diagnostic errors. This case illustrates the clinical importance of utilizing methylation array profiling and next-generation sequencing to confirm a diagnosis.
PATH-39. INTERPRETABLE IDH CLASSIFICATION FROM H&E-STAINED HISTOLOGY SLIDES
Authors: Innani Shubham , Baheti Bhakti , Nasrallah MacLean P , Bakas Spyridon
Published: November 2023

BACKGROUND

Infiltrating gliomas are the most common primary adult brain tumors. Isocitrate dehydrogenase (IDH) mutation is a key driver of gliomagenesis in 25–30% of infiltrating gliomas and correlates with favorable prognosis when compared with the histologically-similar but biologically-distinct IDH-wildtype glioblastoma. We sought an interpretable computational pipeline to predict IDH status from digitized histopathology glioma sections (Whole Slide Images - WSI) and identify associated cell-level morphology. Materials and

METHODS

We identify 799/1122 TCGA-GBM and TCGA-LGG tumors (1534 WSIs) with available IDH status. 379 of these tumors (756 WSI) are IDH-wildtype and 420 tumors (778 WSI) are IDH-mutant. Each H&E-stained WSI undergoes comprehensive curation to remove artifactual content before classification. Our interpretability mechanism is based on weakly-supervised attention-based multiple-instance-learning. IDH-associated morphology in each WSI is evaluated by a HoverNet model from the 50 highest-attention tiles. Classification performance was assessed using 10-fold cross-validation, with training (80%), validation (10%), and test (10%) sets stratified on the patient/tumor level, without controlling for grade. An additional out-of-sample hold-out test set of 82 IDH-wildtype and 32 IDH-mutant tumors from the University of Pennsylvania Health System was further used for independent evaluation.

RESULTS

Quantitative performance evaluation revealed AUC=0.92 and Balanced Accuracy=0.84 on the TCGA test set, and AUC=0.88 and Balanced Accuracy=0.80 on the independent hold-out UPenn set. When comparing identified IDH-wildtype with IDH-mutant tumors (and while excluding glioblastoma with lower-grade histology), the former shows significantly (p< 0.00005) higher distribution of neoplastic and necrotic cells and significantly (p< 0.00003) lower distribution of inflammatory and connective cell type tissue.

CONCLUSION

Histological prediction of IDH status represented an ideal prototype to interrogate WSI towards identifying clinically-relevant tumor biomarkers. Detailed interpretation of results reveals computational predictions being driven by human-identifiable features at the patch level. This study robustly identifies morpho-IDH correlates and could enable further prognostic refinement of patients.
PATH-54. CDC42BPA::BRAF REPRESENTS A NOVEL FUSION IN DESMOPLASTIC INFANTILE GLIOMA
Authors: Guinle Maria Isabel Barros , Nettnin Ella A , Nasajpour Emon , Nirschl Jeffrey , Garcia Cesar A , Vogel Hannes , Yeom Kristen , Prolo Laura , Petritsch Claudia
Published: November 2023

Desmoplastic infantile ganglioglioma/desmoplastic infantile astrocytomas (DIG/DIA), although rare, are low-grade glioneuronal tumors that typically affect patients < 1 year old, and generally carry a good prognosis. Often successfully cured with surgical excision, DIG/DIA still carry the potential for malignant transformation or recurrence. Whilst pediatric low grade glioma (LGG) survival rates are >95%, tumor grade does not correlate well with outcomes in infant LGG (iLGG), thus highlighting the need for investigation into molecular mechanisms of tumor progression. We describe a novel CDC42BPA-BRAF fusion in a DIA in a three-month old patient, and its detection via Next Generation Sequencing. Future studies will investigate whether this novel fusion can function as a target for BRAF and MAPK pathway inhibitors, which have recently been FDA-approved for pLGG.
PATH-63. NEXT GENERATION SEQUENCING FOR CNS TUMORS IN CHILDREN; DOES IT ADD VALUE IN A MIDDLE-INCOME COUNTRY SETUP?
Authors: Amayiri Nisreen , Al-Hussaini Maysa , Maraqa Bayan , Alzoubi Qasem , Musharbash Awni , Ibrahimi Ahmad , Sarhan Nasim , Obeidat Mouness , Hawkins Cynthia , Bouffet Eric
Published: November 2023

INTRODUCTION

Advances in molecular diagnostics led to improved targeted interventions in the treatment of pediatric CNS tumors. However, the capacity to do these diagnostics is limited in LMICs, and consequently their value is questionable.

METHODS

We reviewed our experience of Next Generation Sequencing (NGS) testing (TruSight RNA Pan-Cancer seq panel) for pediatric CNS tumors at KHCC/Jordan (March/2022- April/2023). Paraffin blocks’ scrolls were shipped to Sickkids laboratory based on local multidisciplinary team recommendations. We reviewed patients’ clinical characteristics, tumor types and the impact on treatment.

RESULTS

There were 16 boys and 16 girls; median age at time of testing was 9.5 years (range, 0.9- 21.9 years). Twenty samples were sent at diagnosis and twelve upon tumor progression. Main diagnoses were Low-grade glioma (15), High-grade glioma (10), and other tumors (7). Reasons for NGS testing were: to find a molecular target (20), and to characterize more tumor/behavior (12). The median time from shipping the samples to receive the NGS result was 22 days (range, 15-49 days) at a cost of US$1000. Twenty (63%) tumors had targetable alterations (MAPK/PI3K inhibitors (16), NTRK inhibitors (2), check point inhibitors (2)). Two rare BRAF mutations were identified (BRAFp.G469A, BRAFp.K601E). One tumor diagnosed initially as undifferentiated round-cell sarcoma found to have NAB2::STAT6 fusion and re-diagnosed as aggressive metastatic solitary fibrous tumor. Eight patients received targeted therapy; Dabrafenib/Trametinib (5), Pembrolizumab (2), Entrectinib (1), while radio-chemotherapy was used in the others. Three patients died from disease progression (one used Entrectinib).

CONCLUSIONS

Sent abroad NGS testing was feasible, however local capacity building is necessary. In this highly selected tumor cohort, high percentage of targetable alterations were identified. NGS was helpful to characterize tumors more and to offer alternative therapies. Nevertheless, interpretation of the significance of NGS results and access to those “new” therapies continues to be a challenge in LMICs
NIMG-05. CHARACTERIZATION OF LONG-TERM METABOLIC CHANGES OF BRAIN METASTASES AFTER TREATMENT WITH STEREOTACTIC RADIOSURGERY USING SERIAL FET PET IMAGING
Authors: Wollring Michael , Lowis Carsten , Stoffels Gabriele , Werner Jan-Michael , Celik Eren , Baues Christian , Ruge Maximilian , Ruess Daniel , Fink Gereon , Langen Karl-Josef , Lohmann Philipp , Galldiks Norbert
Published: November 2023

BACKGROUND

In the present study, we characterized the long-term metabolic changes of brain metastases after treatment with stereotactic radiosurgery (SRS) by serial PET imaging using the radiolabeled amino acid O-(2-[18F]-fluoroethyl)-L-tyrosine (FET). We hypothesized that this approach is of considerable clinical value in differentiating between radiation-induced changes and local brain metastasis relapse. Patients and

METHODS

From 2010-2020, we retrospectively identified patients with brain metastases from solid extracranial primary tumors who (i) were treated with SRS with or without concurrent immunotherapy using checkpoint inhibitors, (ii) had equivocal MRI findings after SRS, and (iii) subsequently underwent two or more additional FET PET scans during follow-up for long-term evaluation. Mean tumor-to-brain ratios (TBR) were obtained. Diagnostic performances were calculated using receiver operating characteristic curve analyses. Diagnoses were confirmed by neuropathological evaluation (29%) or clinicoradiologically (71%).

RESULTS

We identified 14 patients with 42 FET PET scans (median number, 3; range, 2-4). Concurrent to SRS, 4 patients (29%) were treated with checkpoint inhibitors. Following SRS, equivocal MRI findings occurred after a median time of 7 months (range, 2-62 months). Subsequently, FET PET scans were acquired over a median 16 months (range, 7-99 months). Nine patients (64%) had radiation-induced changes, and five had local brain metastases relapse. TBRs calculated from the last available FET PET scan showed the highest accuracy (93%) in identifying radiation-induced changes (threshold, 1.95; P=0.011). In lesions consistent with local brain metastases relapse, TBR increased considerably over time (median increase, 17%; range, 11% - 32%). In contrast, in lesions considered as radiation-induced changes, TBR remained stable or even decreased (median change, -4%; range, -44% - 11%). The TBR evolution over time significantly differed between the two groups (P=0.011).

CONCLUSIONS

Serial FET PET imaging has a high diagnostic accuracy for characterizing long-term changes of brain metastases after treatment with stereotactic radiosurgery.
NIMG-18. MULTI-PARAMETRIC MRI AND SPECT ASSESSMENT OF TREATMENT DOSE AND EFFICACY IN RESPECT-GBM FOR RECURRENT GLIOBLASTOMA (RGBM)
Authors: Huang Shiliang , Brenner Andrew , Bao Ande , Michalek Joel , Moore Melissa , Hedrick Marc , LaFrance Norman
Published: November 2023

BACKGROUND

We have previously shown a dose-dependent association with survival for patients receiving Rhenium-186-nanoliposome (186RNL) for rGBM. This study aim, applying 3D-dosimetry and advanced-MRI features to outcome assessment, was to extend those findings.

METHODS

SPECT/CT images were acquired at mid-fusion, end-of-infusion, 24-hour, 120-hour, and 192-hour post-186RNL infusion. Baseline MRI was performed within 7days of treatment, at 28d, and every 56d until progression with: T1-3D pre-/post-contrast agent, DSC, DWI. SPECT images were processed using MIM software with treatment volumes corresponding to the 100Gy isodose curve exported as treatment-ROI. Difference (delta T1) between standardized pre-contrast (T1) and post-contrast (T1_C) anatomic images were used to measure tumor volume (IB Rad Tech). Within the tumor, various MRI-derived parameters, such as standardized-relative-cerebral-blood-volume (srCBV), time to maximum (Tmax), time to peak (TTP), were calculated.

RESULTS

Perfusion analysis(n=8) revealed significant decreases in the mean nrCBF, nrCBV, rCBF, rCBV, and srCBV with dose [nrCBF: -0.25 95% CI -0.37 to -0.14, p=0.005, nrCBV: -0.23 95% CI -0.34 to -0.13, p=0.005, rCBF: -3.5 95% CI -5.37 to -1.63, p=0.01, rCBV: -11.91 95% CI -20.45 to -3.38, p=0.03, srCBV: -0.14 95% CI -0.23 to -0.05, p=0.02], and a significant increase in the mean Tmax [1.88 95% CI 0.58 to 3.17, p=0.03]. The mean volume (n=10) not covered by treatment (-1.59 95% CI -4.81 to 1.63, p=0.36), Tumor volume (-0.76 95% CI -5.23 to 3.72, p=0.75), Treated volume (3.31 95% CI -0.44 to 7.06, p=0.12), and Tumor Volume covered by treatment (0.84 95% CI -1.2 to 2.87, p=0.44) did not vary significantly with dose although may gain significance with a larger data set.

CONCLUSION

MRI radiographic features proved valuable in assessing treatment efficacy and guiding treatment considerations. Image processing is ongoing, and the complete data set will be presented.
NIMG-25. CLINICAL FEASIBILITY OF AI-BASED T2 FLAIR SEGMENTATION FOR DETECTION OF PROGRESSION IN NON-ENHANCING LOWER GRADE GLIOMA
Authors: Luks Tracy , Damasceno Pablo , Gleason Tyler , Hawkins James , Avalos Lauro , Hervey-Jumper Shawn , Majumdar Sharmila , Lupo Janine , Crane Jason , Villanueva-Meyer Javier
Published: November 2023

Radiological assessment of progression in patients with non-enhancing lower grade gliomas (LrGG: grade 2 and 3) is primarily based on increase in lesion size on anatomical T2-weighted fluid-attenuated inversion recovery (T2 FLAIR) magnetic resonance imaging (MRI) sequences. We evaluated whether an AI-based method could be used routinely as part of patient care to assist in detecting non-enhancing glioma progression. The software offers the ability for real-time quality control and editing, choice of baseline exam and threshold for progression, and shows 3D image segmentations side-by-side with lesion volume graphs. The model was trained to create T2 FLAIR abnormality segmentations. The 515 training images included pre-surgical scans of newly diagnosed and recurrent patients, and post-surgical surveillance scans of patients. Clara Deploy was used for inference and to handle communication between PACS and an XNAT server, where results were stored and displayed. Following RANO criteria, lesions were marked as ‘progressed’ if volume changes were larger than 40% between baseline and the MRI of interest. The 124 AI-based segmentation model test volumes were compared to manual segmentation volumes, and achieved a mean DICE score of 0.87 ± 0.20. The sensitivity and specificity of the RANO progression assessment based on the model was compared with RANO progression assessment based on manual segmentation in 16 patients (6 serial MRIs each), with 85% sensitivity, 82% specificity. This work presents the first steps toward clinical deployment of AI-based real-time quantitative detection of LrGG progression by RANO criteria. This quantitative assessment provides supplementary information to the radiologist and can be shared with the patient’s neuro-oncologist, neurosurgeon, and other clinical team members for consideration in treatment planning.
NIMG-44. RADIOMIC FEATURES OF CONTRAST ENHANCED T1 MRI SEQUENCES PREDICT SURVIVAL IN PRIMARY GLIOBLASTOMA PATIENTS WHO UNDERWENT ADJUVANT RADIATION THERAPY
Authors: Flatley Michael , Duenweg Savannah , Bobholz Samuel , Lowman Allison , Stebbins Margaret , Winiarz Aleksandra , Nath Biprojit , Kyereme Fitzgerald , Connelly Jennifer , Coss Dylan , Agarwal Mohit , Banerjee Anjishnu , Krucoff Max , LaViolette Peter
Published: November 2023

PURPOSE

Glioblastoma (GBM) is an aggressive primary brain tumor that is monitored through magnetic resonance imaging (MRI). Radiomic analysis offers valuable insight into better understanding the imaging features of these tumors. We tested the hypothesis that changes in radiomic features following radiation treatment predicts overall survival. Radiomic features we were interested in included 2D and 3D shape features, first order features evaluating patterns of voxel intensity within the mask regions, and higher order GLCM features.

METHODS

Data from 19 patients from our brain bank diagnosed with a GBM at autopsy and underwent radiation therapy were used for this study. T1C tumor masks were created by manually annotating contrast enhancing tumor for patients on pre- and post-treatment MRIs. Pyradiomics was used to extract radiomic features within both pre- and post-radiation tumor masks, including 14 shape features, 18 first order features, and 75 higher order features were compared across timepoints and the difference for each variable was correlated with overall survival.

RESULTS

Of the tested radiomic features, only the following shape features were found to be correlated with overall survival: Major Axis Length (R = -0.55, p =.02), Maximum 2D Diameter Row (R= -.56, p =.02), Maximum 2D Diameter Slice (R= -.52, p =.03), and Maximum 3D Diameter (R= -.47, p = .04).

CONCLUSIONS

These results show a decrease in the Major Axis Length, Maximum 2D Diameter, Maximum 2D Diameter, and Maximum 3D diameter of the T1C masks post-radiation correlate with an overall increase in survival. These inverse trending radiomic variables may be useful to assess tumor response to radiation therapy, specifically through assessment of shape features within the contrast-enhancing tumor region. Future research should determine how tumor changes in response to other treatment modalities and/or correlates with other prognostic variables.
NIMG-47. LONGITUDINAL TRAJECTORIES FROM SERIAL SURVEILLANCE MRI IMAGING OF PROGRESSIVE IDH MUTANT LOW-GRADE GLIOMA PATIENTS
Authors: Fetcko-Fayad Kaleigh , Zheng Xiaojun , Godfrey Devon , Kirveslahti Henry , Mukherjee Sayan , Lafata Kyle , Thomas Jennifer , Peters Katherine , Ryser Marc
Published: November 2023

BACKGROUND

Most patients with isocitrate dehydrogenase mutant (IDHm) low-grade glioma (LGG) undergo active MRI surveillance after initial surgery. Timely biopsy referral during surveillance is a complex trade-off between avoiding the harms of unnecessary surgery and early detection of transformation. Serial surveillance MRIs could be leveraged to develop dynamic imaging markers, yet prior research has primarily focused on the prognostication of pre-treatment images. We piloted the feasibility of an automated pipeline using patient-specific imaging trajectories.

METHODS

We retrospectively identified 12 progressive IDHm LGG patients and collected serial surveillance MRIs. A previously developed segmentation model was fine-tuned on a subset of T2/FLAIR images (n=49) before automated tumor segmentation was performed on all MRIs. We extracted geometric and topological tumor features, including volume, cross product, and Euler Characteristic Transform, from each MRI. We used piecewise linear regression to quantify feature trajectories and identify change points in feature growth rates.

RESULTS

Twelve patients received 14 biopsies/repeat resections (10 with transformation, 4 without) and 282 MRIs (median per patient: 17, range: 10-40). All biopsies/repeat resections were preceded by a change point in tumor volume trajectory, indicating an increase in tumor growth rate preceding clinician-determined MRI progression and biopsy referral. The mean increase in volume growth rate, pre to post change point, was 2.3cm3/month (SE: 0.9) in biopsies/repeat resections with transformation, compared to 1.1cm3/month (SE: 0.6) in biopsies/repeat resections without transformation. Among the ten patients with transformation, the median time from IDHm LGG diagnosis to transformation was 64.8 months (range: 38.6-141.1), and the median time between volume change point and transformation was 15.6 months (range: 4.6-28.2).

DISCUSSION

This pilot study suggests that feature trajectories from serial MRIs of IDHm LGG patients may advance the detection and treatment of transformed lesions by 12-18 months. Larger studies can corroborate these findings and inform clinical decision-making.
NIMG-70. TRACKING CELLULAR SOCIAL BEHAVIOR OF PATIENT-DERIVED PRIMARY CELL LINES TO GATHER NEW INSIGHTS FOR BETTER STRATIFICATION OF GLIOBLASTOMA PATIENTS
Authors: Ferri Gianmarco , Morelli Mariangela , Lessi Francesca , Franceschi Sara , Pieri Francesco , Gambacciani Carlo , Aretini Paolo , Pasqualetti Francesco , Santonocito Orazio Santo , Stefano Anna Luisa Di , Mazzanti Chiara Maria
Published: November 2023

Glioblastoma is one of the most frequent and aggressive brain tumors. The average life of these patients is on average less than 15 months, due to the proliferation and invasiveness of the tumor cells, which not only constitute the tumor mass but which also infiltrate the normal parenchyma brain to form new cancerous sites. Knowing the specific behavior of the cell types that make up the tumor of every single patient, in terms of volume, shape, motility, and cell-cell interaction could be informative for patients’ tumor stratification. Here we developed a protocol that integrates imaging and image processing algorithms, to accurately and quantitatively identify the morphological and behavioral characteristics of tumor cells cultured in vitro and track their movement over time. This approach enables quantifying important biological processes such as cell migration and cell growth, both of which play a major role in the development of diseases. The cell tracking method combines segmentation methods with spatiotemporal optimization to analyze microscopy images. The method also determines various information about cell movements such as movement paths, speed, and distance covered. Knowing the behavior of the malignant glioma cells of a specific patient, in terms of shape and motility (e.g. direction and speed of movement), also in relation to other cells could be informative in the context of dynamic precision medicine. In this context, we created a model that integrates the characteristics of each patient's tumor cells and provides a new way of stratifying patients that can be correlated with clinical data.
NIMG-78. USE OF ARTERIAL SPIN LABELING TO DETECT METASTASIS OF MENINGEAL SOLITARY FIBROUS TUMORS
Authors: Costanza Katelyn , Oztek Alp , Andre Jalal , McGranahan Tresa
Published: November 2023

Meningeal solitary fibrous tumors (SFT), formerly known as hemangiopericytoma, are rare, highly vascular, mesenchymal dural based neoplasms. Meningeal SFT require lifelong imaging surveillance given high risk of recurrence and metastasis, even decades after initial diagnosis. Often these metastases are initially small, nodular dural masses that are difficult to detect with standard brain tumor imaging protocols. Given SFT are highly vascular tumors, we hypothesized that recurrent meningeal SFT would have elevated cerebral blood flow using Arterial Spin Labeling (ASL) perfusion imaging. ASL is a noninvasive MRI technique used to detect cerebral blood flow in high grade neoplasms and hyper vascular meningiomas without intravenous contrast. We evaluated ASL in two patients with recurrent meningeal SFT. In both patients the recurrent meningeal SFT demonstrated elevated perfusion by ASL. In one patient, the elevated ASL signature enabled identification of a small metastasis that was not initially appreciated on structural imaging. Following treatment with antiangiogenic therapy, ASL was no longer elevated while enhancement did not change. To our knowledge, this is the first study reporting utility of ASL imaging in detecting intracranial recurrence of meningeal SFT. We propose further study of sensitivity of ASL to detect recurrent meningeal SFT.
NCMP-13. CONCURRENT WOUNDED GLIOMA SYNDROME AND DISTANT WOUNDED GLIOMA SYNDROME FOLLOWING A GROSS TOTAL RESECTION OF GLIOBLASTOMA MULTIFORME – A CASE REPORT
Authors: Calubayan John Michael , Opinaldo Paul Vincent
Published: November 2023

Surgery is the initial form of treatment for glioblastoma, and a maximum resection without impairing neurological function improves survival. Wounded Glioma Syndrome (WGS) is a clinical picture observed after the resection of high-grade tumors. This syndrome, developing within hours or a few days after glioma surgery, is characterized by hemorrhage into the surgical bed and cerebral edema, and at times occurring in areas distant from the site of the resection, i.e., Distant WGS. We report a case of an elderly male presenting with an acute-onset left leg weakness, with a large peripherally-enhancing mass with central non-enhancement suggestive of necrosis in the right frontal lobe. A gross total resection of the tumor was done, and the histopathologic evaluation yielded a high-grade glioma, favoring a diagnosis of Glioblastoma WHO Grade-IV. During the postoperative period, he was drowsy and was able to move the right extremities. He had a series of generalized tonic-clonic seizures three hours after the operation. After eight hours, the patient became comatose with signs of increasing intracranial pressure. A cranial CT revealed diffuse cerebral edema, and hemorrhage into the operative site in the right frontal lobe, as well as subarachnoid hemorrhages in the bilateral fronto-parietal sulci. There were also small hemorrhages seen in the left caudate head, midbrain and left hemipons. Death occurred the following day. This case report demonstrates an unusual case of a WGS with a concurrent Distant WGS in the brainstem after a gross total resection of a frontal lobe glioma. This case shows a significant uncommon sequela that a patient undergoing glioma surgery can present, leading to rapid deterioration and death. Resection of a glioma carries a significant risk, and its impact in the immediate postoperative period merits evaluation when planning the perioperative management, taking prompt action if these syndromes occur.
NCMP-15. AMYLOID-BETA AND TAU-PATHOLOGY IN THE GLIOMA VICINITY
Authors: Greutter Lisa , Miller-Michlits Yelyzaveta , Schnitzenlehner Lisa , Klotz Sigrid , Krause Elena , Platzek Stephan , Kiesel Barbara , Widhalm Georg , Stepper Peter , Nenning Karl-Heinz , Langs Georg , Baumann Bernhard , Woehrer Adelheid
Published: November 2023

With aging societies the incidences of brain cancer and neurodegenerative disease are increasing. Although biological associations were suggested between glioma and Alzheimer's disease (AD), the rate of comorbidity is ill-defined. We here screened the tumor-adjacent cortex of a representative patient cohort for tau and Amyloid-beta deposits and correlated the results with imaging biomarkers. A total of 290 patients (37 astrocytoma, IDH-mutant, CNS-WHO grades 2-4, median-age: 39; 48 oligodendroglioma, IDH-mutant and 1p-19q-co-deleted, CNS-WHO grades 2-3, median-age: 50; 205 glioblastoma, IDH-wildtype, median-age: 65) were included. Whole-slide quantifications were performed using a digital pathology pipeline based on Matlab and QuPath codes. For a subset of 48 patients with glioblastoma 280 longitudinal MRI volumes were available for segmentation and volumetric analysis of tumor ipsi- and contralateral hippocampuses. Overall, 160 patients (55%) displayed Amyloid-beta and/or tau-pathology in tumor-adjacent cortex. AD protein deposits correlated significantly with age (p< 0.001), and showed topographic variability across brain regions. Amyloid-beta plaques were commonly observed in the occipital cortex in glioblastoma (50%, n= 10/20), while tau-pathology was commonest in the temporal lobe in both IDH-mutant and -wildtype tumors (71%, n= 10/14; 56% n= 44/79). Remarkably, isolated tau-pathology was more prevalent in IDH-mutant glioma (48% vs. 18%, p< 0.001, median age: 45). Median cell density in tumor-infiltrated cortex was highest in glioblastoma (1895 cells/mm²), and associated with reduced neuronal counts and AD protein deposits (p< 0.001). In glioblastoma, hippocampal atrophy correlated with AD-type pathology at time of diagnosis and remained stable during follow-up in the majority of patients. In sum, our data suggests frequent co-morbidity of glioma and AD-type pathology, which increases with age. Isolated tau-pathology was more pronounced in IDH-mutant tumors. In tumor-adjacent cortex, increased tumor cell infiltration paralleled neuronal loss and diminished AD-type pathology.
NCMP-19. OUTCOMES FOLLOWING PALLIATIVE CEREBROSPINAL FLUID DIVERSION FOR NEOPLASTIC LEPTOMENINGEAL DISEASE: A SYSTEMATIC REVIEW
Authors: Wu Adela , Zhou James , Skirboll Stephen
Published: November 2023

BACKGROUND

Leptomeningeal disease (LMD)—cancer involvement of meninges or disseminated through the cerebrospinal fluid (CSF) system—indicates widespread or advanced cancer. LMD leads to symptomatic hydrocephalus, for which palliative CSF diversion may be indicated. We conducted a systematic review exploring published literature on outcomes of permanent CSF diversion for hydrocephalus among pediatric and adult patients with LMD from primary brain tumor or systemic cancers.

METHODS

We searched PubMed, Embase, and Web of Science from database inception until 8/20/2022, using search terms including but not limited to ‘cancer’, ‘hydrocephalus’, and ‘shunt’. Preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed. Inclusion criteria were English-language, quantitative studies of patients with LMD and hydrocephalus, with at least five subjects.

RESULTS

We screened 2440 abstracts and 152 full-text articles to yield a final cohort of 23 articles. The retrospective studies reported outcomes for 2895 patients, among which 995 patients (34.3%) specifically had LMD on presentation. Fourteen studies reported proportions of patients with LMD and hydrocephalus who underwent surgery for permanent CSF diversion (range: 9.9-100%), including endoscopic third ventriculostomy, ventriculoperitoneal or lumboperitoneal shunts. Postoperative complication rates were 0-37.7% with no cases of extraneural metastases via shunt. Rates of symptomatic relief following CSF diversion ranged from 50-100% in studies that reported data. In 14 studies, median overall survival ranged from 2.1-17.1 months. Three studies reported median survival after shunt surgery for LMD (2-3.3 months).

CONCLUSION

A rare entity with dismal prognosis, LMD and disseminated tumor can present as symptomatic hydrocephalus in patients with cancer. Symptom relief can be achieved with palliative surgery for permanent CSF diversion with relatively low complication rates. Prospective studies are needed to further assess outcomes and needs of this patient population.
NCMP-23. EVALUATION OF IMMUNOTHERAPY EFFECTS IN CANCER PATIENTS ON EPILEPTIFORM ACTIVITY
Authors: Wong Kaela , Thakur Ayush , Zuidema Elizabeth , Avila Edward , Chen Xi , Lai George , Mao David
Published: November 2023

BACKGROUND/OBJECTIVE

Immune checkpoint inhibitors are associated with increased risk of autoimmune neurologic conditions, both in the peripheral and central nervous system. Increased activation of the immune system can lower seizure threshold, potentially increasing a patient’s risk of seizures. We hypothesize that patients treated with immune checkpoint inhibitors have a higher rate of seizures.

METHODS

We retrospectively reviewed 465 cancer patients undergoing electroencephalography (EEG) monitoring performed at Memorial Sloan Kettering Cancer Center from January 2022 to March 2023. Data was gathered from an EEG RedCap database containing patient demographic and seizure data. Patients were separated based on whether they had received immune checkpoint inhibitors (+ICI) prior to seizure occurrence or were never exposed to immune checkpoint inhibitors (-ICI) and had a seizure. Patient cancer type and presence of brain lesions (primary or metastases) were also reviewed.

RESULTS

Out of 465 patients, 109 received immune checkpoint inhibitors (+ICI) during their treatment. Seven of those patients were reported to have had at least one seizure (7/109, 6.42%) following treatment with ICI. The remaining 356 patients did not undergo immune checkpoint inhibitor treatment (-ICI), of which 30 were reported to have had at least one seizure (30/356, 8.43%). Of the +ICI patients who were experiencing seizures, 5 of them had brain lesions; 4 had primary brain tumors and 1 had brain metastases. Of –ICI patients, 21 patients had brain lesions; 15 had primary brain tumors and 6 had brain metastases.

DISCUSSION

Although immune checkpoint therapy may lead to increased activation of the immune system, our data did not reveal a higher incidence of seizures. Limitations to our study include its retrospective design, low number of patients, and low overall number of seizures captured on EEG.
NCMP-26. PANCEREBELLITIS ASSOCIATED WITH CISPLATIN THERAPY IN A PATIENT WITH OROPHARYNGEAL/ NASOPHARYNGEAL SQUAMOUS CELL CARCINOMA
Authors: Li Yi , Abualia Mohammad , Drappatz Jan , Mantica Megan
Published: November 2023

Cisplatin, a platinum-based drug, is one of the oldest and most widely used chemotherapeutic agents. It exerts its anti-tumor effect by forming DNA inter-strand and intra-strand cross-links, resulting in lesions that eventually activate apoptotic pathways. Cisplatin remains widely used for the treatment of several solid tumors, though this is often limited by its toxicity which can affect many organ systems, including nephrotoxicity, hepatotoxicity, ototoxicity, and neurotoxicity. A dose-dependent peripheral sensory neuropathy is the most reported cisplatin-induced neurotoxicity. Central nervous system (CNS) toxicity is less common, likely due to the large molecular size of cisplatin preventing its passage through the blood-brain barrier (BBB). There have been reports of cognitive impairment, posterior reversible encephalopathy syndrome, and optic neuritis associated with cisplatin. We present a case of a 38-year-old patient who was treated with concurrent cisplatin and radiation therapy for oropharyngeal/nasopharyngeal squamous cell carcinoma, and around a month after the end of therapy, was found to have imaging findings concerning for pancerebellitis. Extensive workup into infectious causes of cerebellitis was negative. Although there are no reports in the literature of cerebellitis due to cisplatin, it could be the culprit in this case. Animal studies have shown cerebellar dysfunction occurring in the setting of cisplatin exposure. Moreover, it is thought that the drug can reach the CNS if there is a disruption of the BBB, this is supported by the fact that CNS toxicity is more seen in patients who have primary CNS neoplasia, CNS metastatic disease, radiation exposure to the head, among other mechanisms that could potentially disrupt the BBB. Thus, it is important to consider CNS adverse effects, including cerebellitis, in patients receiving cisplatin, especially among those with a potentially compromised BBB.