bluuebunny/crossref_metadata_2025 huggingface dataset:
PATH-20. CLINICAL FINDINGS AND PROGNOSIS OF ADULT GLIOBLASTOMA HARBORING ABRAF V600E MUTATION
Authors: Yamaguchi Shigeru , Ishi Yukitomo , Oki Sogo , Motegi Hiroaki , Nishioka Kentaro , Mori Takashi , Okada Hiromi , Tanei Zen-ichi , Tanaka Shinya , Fujimura Miki
Published: November 2024

BACKGROUND AND AIM

Although the BRAF V600E mutation is commonly associated with pediatric low-grade gliomas, glioblastomas (GB) with this mutation (BRAF-GB) have also been reported. The recent emergence of RAF and MEK inhibitors for BRAF V600E-positive tumors highlights the potential for targeted therapy in a subset of GB patients. This study aimed to characterize the clinical features and prognosis of BRAF-mutant glioblastomas.

MATERIALS AND METHODS

A retrospective analysis was conducted on a cohort of patients diagnosed with GB (confirmed by 2021 WHO criteria) above 16 years of age. Targeted genetic analysis for mutations in BRAF V600E, TERT promoter, and CDKN2A/B was performed on the GB samples. Clinical features of BRAF-GB were analyzed, and patients were further categorized into three groups: BRAF-GB, typical GB, and molecular GB. Subsequent analysis compared the prognosis among these groups.

RESULTS

Our study identified 11 cases (5.1%) harboring the BRAF V600E mutation among 215 adult GB patients. Patients with BRAF-GB exhibited a significantly younger median age of onset (38-year-old) compared to the typical GB (N = 167, 64-year-old) and molecular GB (N = 37, 61-year-old) groups. Further analysis of the BRAF-GB cohort (n=11) revealed a high prevalence (82%) of homozygous CDKN2A/B deletions, and only one case (9%) harbored a TERT promoter mutation. Interestingly, three BRAF-GB patients presented with hemorrhagic onset. Four cases showed evidence of prior lesions, with one case diagnosed histologically as a low-grade glioma 14 years earlier. The BRAF-GB group exhibited significantly longer median progression-free survival (32.8 months) and overall survival (84.2 months) compared to both the typical GB group (9.6 months and 18.9 months, respectively) and the molecular GB group (14.1 months and 32.1 months, respectively).

CONCLUSIONS

Early-age onset, with hemorrhagic onset or presence of prior lesions are factors that could lead to recommendation of BRAF analysis for adult GB patients.
PATH-25. CONSENSUS RECOMMENDATIONS FOR AN INTEGRATED DIAGNOSTIC APPROACH TO NERVE SHEATH TUMORS ARISING IN THE SETTING OF NEUROFIBROMATOSIS TYPE 1
Authors: Dehner Carina , Gross Andrea , Lazar Alexander , Lucas Calixto-Hope , Miettinen Markku , Pekmezci Melike , Perry Arie , Quezado Martha , Rodriguez Fausto , Romo Carlos , Stemmer-Rachamimov Anat , Viskochil David
Published: November 2024

NF1-associated nerve sheath tumors exist on a morphologically and molecularly diverse spectrum. Criteria for diagnosing neurofibroma, atypical neurofibromatous neoplasm of uncertain biologic potential (ANNUBP), and malignant peripheral nerve sheath tumor (MPNST) developed by consensus in 2017 were codified in recent WHO guidelines. However, incorporation of molecular strata should be formalized to aid in early identification and appropriate intervention for patients with lesions at increased risk for malignant transformation. Here, we assembled a multi-institutional expert pathology working group to review molecular literature and formalize classification recommendations. In collaboration with clinical/surgical, imaging, and pre-clinical working groups during the “Symposium on Atypical Neurofibroma: State of the Science” held April 2024, we reached consensus on a potential integrated diagnostic approach. Based on strong preclinical and clinical evidence, we propose CDKN2A homozygous deletion as a sufficient molecular feature for diagnosing ANNUBP and either SUZ12, EED, or TP53 inactivating mutations or significant aneuploidy as sufficient molecular features for diagnosing MPNST, even in the absence of high-grade histologic features. In the absence of MPNST-defining molecular alterations, we also recommend reclassifying “low grade MPNST” as “ANNUBP with increased proliferation”. To facilitate molecular characterization of concerning tumors, we recommend at least six core biopsies be obtained and divided into two cores per block at time of grossing. Worrisome immunohistochemical features including reduced SOX10 or S100 immunoreactivity, decreased CD34 lattice-like network, minimal p16 expression, loss of H3K27me3 immunoreactivity, p53 overexpression, and increased Ki-67 labeling can guide region selection. A comprehensive next-generation sequencing panel that includes copy number and zygosity assessment is the preferred single assay, though a combination of multiple molecular techniques may provide similar information. In the spirit of the prior 2017 consensus agreement, we hope this refined integrated diagnostic approach for NF1-associated nerve sheath tumors will continue to evolve alongside our understanding of the spectrum of these neoplasms.
PATH-34. IT NEVER RAINS BUT IT POURS - DIAGNOSING ANAPLASTIC PLEOMORPHIC XANTHASTROCYTOMA TWICE IN A FORTNIGHT - OUR EXPERIENCE IN A RESOURCE CONSTRAINED SETTING
Authors: Menon Durgapoorna , Menon Supriya , SB Vigneswar , Santosh Vani , G Kiron , Panikar Dilip , S Shyamsundar
Published: November 2024

Grade 3 Pleomorphic Xanthastrocytoma is a rare tumour (less than 1% of all astrocytic glial neoplasms). Present most commonly with seizures. Surgery and Radiation remain the mainstay of treatment with no clear role for traditional systemic chemotherapies; BRAF inhibitors show some benefit. We report two cases who were diagnosed within a month of each other - one was initially diagnosed in 2017- presented with altered smell, headache and diplopia. Found to have a well-defined lobulated heterogeneously enhancing suprasellar parasellar lesion. After Gross Total Resection, was diagnosed from various centers as Anaplastic Ependymoma WHO Grade III; Gllioblastoma WHO Grade IV; Anaplastic Pleomorphic Xanthastrocytoma WHO Grade III. Based on immunohistochemistry, was considered Anaplastic Ependymoma WHO Grade III. Spine screening was negative; received adjuvant Radiation 60Gy in 30 fractions. After a disease free interval of 6 years, developed a recurrence at the post op site. He underwent repeat decompression and the histopathology showed Grade 3 Pleomorphic Xanthastrocytoma. Immunohistochemistry- OLIG2: diffuse positive; R132H p.IDH1: negative; ATRX: intact nuclear expression; Mismatch repair proteins (MSH2, MSH6, MLH1, PMS2); intact nuclear expression; MIB-1 labelling index: 10-12%; H3 p.K27M: negative; GFAP: variable positivity; Podoplanin and p53 shows focal positivity; EMA, CD 34 are negative. He competed Reirradiation in January 2024. He is asymptomatic and on follow up. The second case -15 year old boy presented with episodes of absence seizures. Imaging showed a predominantly extraaxial lesion at tentorial apex. He underwent decompression and histopathology showed Grade 3 Pleomorphic Xanthastrocytoma. Immunohistochemistry - cells positive for S100 and variably positive for GFAP, OLIG2 and vimentin; ATRX: Retained expression, IDH1p.R132H, EMA, Synaptophysin, Neu N: Negative, p53: Focally positive, CD34: Positive in few tumour cells, Ki-67: 14-16 %.V600 mutation detected in the BRAF gene. Had Adjuvant RT 60 Gy in 30 fractions -completed in March 2024. MRI at 1 month - no significant change in overall tumour burden compared to post operative MRI. Was offered Dabrafenib with Trametinib.
PATH-40. CLINICAL CHARACTERIZATION OF H3K27M-MUTANT GLIOMAS
Authors: Takezaki Tatsuya , Kuroda Jun-ichiro , Shinojima Naoki , Kai Keitaro , Yamamoto Takahiro , Fujimoto Kenji , Inoue Hirotaka , Sueyoshi Hiroyuki , Matsuzaki Keisuke , Takeshima Yuki , Matsuura Jin , Mukasa Akitake
Published: November 2024

Diffuse midline gliomas, H3K27M-altered(DMGs) are a recently defined entity of gliomas, occur in midline, infiltrate diffusely and have poor prognosis. We reviewed our cases of DMGs to describe clinical, pathological, molecular characteristics, retrospectively. We detected 39 H3K27M-mutant cases of our 959 consecutive gliomas(4.1%). All H3K27M mutations were identified genetically. 23 datasets of these H3K27-mutant gliomas are available to detect their clinical, pathological, molecular characteristics. 5 young(8 - 18 y.o.) and 18 adult (28-80 y.o.) were included. All except one H3K27M-altered were WHO Grade III or IV pathologically. Most common location was thalamus(10/23, 43.4%), pons(6/23, 26.1%), brainstem(3/23, 13.0%). 2 non-midline gliomas were included. In this cohort, Median overall survival were 494 days in young patients, 464 days in adult patients. Current adjuvant chemotherapy and radiation-therapy have not prolonged poor prognosis of DMG patients. It is necessary to explore novel therapeutic targets.
PATH-43. MALIGNANT TRANSFORMATION OF MENINGEAL MELANOCYTOMA - GENETIC ALTERATIONS AND RESPONSE TO CHECKPOINT BLOCKADE IMMUNOTHERAPY
Authors: Silva Correia Carlos Eduardo , Kaplan Viktoria , Farooq Shama
Published: November 2024

INTRODUCTION

Meningeal melanocytomas are uncommon tumors that develop from leptomeningeal melanocytes. These tumors can exhibit aggressive behavior, leading to symptoms due to compression and potential invasion of nearby central nervous tissue. Case: In this report, we discuss the case of a 45-year-old man who was diagnosed 18 years ago with a meningeal melanocytoma in the right temporal region. He underwent complete resection with each recurrence and received focal intensity-modulated radiation therapy after a third recurrence in 2013. In May 2022, he developed progressive headaches and diplopia secondary to tumor recurrence on the right temporal region. Resection revealed that the tumor had progressed to malignant meningeal melanoma with 34 mitoses per 10 high-power fields. Next-generation sequencing (NGS) showed GNAQ mutation confirming tumor of central nervous system (CNS) origin, and also showed an SF3B1 mutation, indicating aggressive behavior. Several chromosomal abnormalities were also detected. Systemic workup revealed liver, lung, and bone metastasis. Liver biopsy confirmed meningeal melanoma of central origin. The patient received radiosurgery with a total of 30Gy over five fractions to intracranial surgical cavity, followed by three cycles of nivolumab and relatlimab. Unfortunately, the patient experienced severe intracranial and systemic progression, leading to his death six months after the malignant transformation.

DISCUSSION

Meningeal melanocytomas are rare however these tumors have a high recurrence rate with potential malignant transformation over time. NGS is a valuable tool for confirming the CNS origin of the tumor and predicting its aggressive behavior. Despite microscopic similarity with cutaneous melanomas, meningeal melanocytomas have different pathogenesis and do not seem to respond to immunotherapy, as observed in this case.
PATH-44. CLINICAL AND RADIOGRAPHIC PREDICTORS OF PROGNOSIS IN ASTROCYTOMA, IDH-MUTANT, WHO GRADE 4
Authors: Lasica Aleksandra B , Lan Zhou , Miller Julie J , Russ Alyssa , Westergaard Catharina , Lee Eudocia Q , Chukwueke Ugonma , Castro Luis Nicolas Gonzalez , Figueroa Jose Ricardo McFaline , Aquilanti Elisa , Nayak Lakshmi , Beroukhim Rameen , Batchelor Tracy , Nakhate Vihang , Lanman Tyler , Botero Juan Pablo Ospina , Stec Natalie , Reardon David A , Wen Patrick Y , Youssef Gilbert
Published: November 2024

BACKGROUND

Astrocytoma, IDH-mutant, WHO grade 4, are classified as a separate entity in the 2021 WHO classification of central nervous system tumors and have been poorly characterized in the literature. In this study, we report on the clinical outcomes in a large cohort of newly diagnosed grade 4 IDH-mutant astrocytoma.

METHODS

We retrospectively identified adult patients with astrocytoma, IDH-mutant, WHO grade 4, treated for their initial diagnosis at Dana-Farber Cancer Institute and Massachusetts General Hospital between 2010 and 2021. Clinical, molecular, and radiological characteristics were recorded, and their association with overall survival (OS) and progression-free survival (PFS) was measured by a log-rank test. If a proportional hazard assumption was violated, we compared the median OS and PFS between groups by the bootstrap method instead.

RESULTS

We identified 140 patients, with a median age at diagnosis of 37.9 years (range: 19-87) and male predominance (60.7%). MGMT promoter was methylated in 51.4%, and CDKN2A/B homozygous deletion was present in 40 cases (28.6%). Most tumors showed enhancement on the preoperative scan (n=108; 77.1%). Seventy percent of patients had subtotal resection, 25.7% had a gross total resection, and 4.3% had a biopsy. Most patients received standard chemoradiation followed by adjuvant temozolomide (n=103; 73.6%). The median OS was 6.9 years (95% CI: 4.5-9.2), and the median PFS was 3.3 years (95% CI: 2.1-4.4). OS and PFS were not associated with MGMT promoter methylation or the presence of enhancement on the preoperative scan. CDKN2A/B homozygous deletion was associated with worse OS (5.5 vs. 7.8 years, log-rank test-based p-value=0.036) but had no association with PFS (3.4 vs 2.6 years, bootstrap method-based p-value=0.488).

CONCLUSIONS

In our cohort of astrocytoma, IDH-mutant, WHO Grade 4, CDKN2A/B homozygous deletion had a negative prognostic impact, whereas MGMT promoter methylation status and enhancement on the preoperative scan did not affect survival outcomes.
NIMG-02. DEVELOPING A RADIOMIC HIERARCHICAL GAUSSIAN PROCESS BOOSTING MODEL TO PREDICT PRIMARY TUMOR ORIGIN FROM MULTICENTRIC LONGITUDINAL MRI DATA OF BRAIN METASTASES
Authors: Panchawagh Suhrud
Published: November 2024

Focal neurologic deficits due to brain metastases might be the initial presentation in patients with cancer. Common approaches to investigate the occult primary malignancy include a whole-body PET-CT, whole-body MRI, studying tumor markers, or histopathological examination. Most of these modalities are expensive, time-consuming, invasive, and delay treatment. The field of radiomics leverages quantitative features extracted from images to improve the decision-making process in clinical practices. Although not easily understandable, these features are proxies for the tumor’s shape, contour, texture, and intensity patterns. They can help understand tumor heterogeneity, predict tumor behavior, and assess treatment response. We propose a robust radiomic workflow using longitudinal MRI data from 914 high-resolution imaging studies from 12 different centers (Ocaña-Tienda et al. (2023), Ramakrishnan et al. (2023), Wang et al. (2023)) to predict the origin of brain metastases from brain MRI scans. After using ensemble feature selection methods, we trained three fixed-effects and one mixed-effects multiclass classification model to account for longitudinal data. Fixed-effects logistic regression and support vector kernel models performed the worst (AUC 0.74 and 0.75, respectively), while the random forest performed better (AUC 0.97). The mixed-effects hierarchical Gaussian process boosting (GPBoost) model performed the best with an accuracy of 85.8%, precision of 85.4%, sensitivity of 85.8%, specificity of 95.7%, and an AUC of 0.98. In one-versus-rest classification, the GPBoost model identified the primary tumor as melanoma with the highest accuracy (96.1%) and non-small cell lung cancer with the lowest accuracy (89.0%). Developing such models holds great promise in reducing patient and institutional costs, improving time to effective treatment, and enhancing overall survival rates through personalized therapy approaches. In the future, we hope that incorporating newer patient data and refining the model to improve external validity would enable more accurate and generalizable predictions, leading to better clinical outcomes across diverse populations.
NIMG-04. MASSIVE THORACIC MENINGOCELE IN A PATIENT WITH NF1
Authors: Dasgupta Pushan , McCutcheon Ian , Slopis John
Published: November 2024

Thoracic meningoceles are uncommon but when seen are often associated with neurofibromatosis 1 (NF1). Here we present a unique case where a massive thoracic meningocele presented with chest pain in a patient with NF1. A 56-year-old female with a diagnosis of NF1 presented with pain in the entire chest wall. She described the pain as circumferential around the entire chest “like a barrel”. Cardiology evaluation (with echocardiography) revealed no pulmonary hypertension or other cardiac disorder. MR angiogram of the chest also revealed no intrathoracic vascular structural abnormality. Inflammatory myopathy was considered to explain the pain but electromyography was unremarkable as were creatine kinase and erythrocyte sedimentation rate. MRI of thoracic spine demonstrated a large thoracic meningocele involving the spinal canal from T5-T10 and extending into the left hemithorax with measurements of 11.5 x 6.1 x 12.5 cm. Imaging was also notable for leftward displacement of the spinal cord toward the meningocele starting at the T6 level and extending to the T9 level with kyphosis of the thoracic spine centered on the block vertebral bodies forming the T7-T8 levels. Significant posterior scalloping was evident from T6-T10 with attendant dural ectasia. Neurosurgical consultation recommended no intervention to correct the meningocele as plication carried a risk of producing a subarachnoid-pleural fistula from the meningocele into the pleural space of the thoracic cavity. This case adds to our understanding of how unique and diverse the presentations of NF1 can be, and of the surgical challenges posed by NF1-associated meningoceles.
NIMG-06. AUTOMATED VOLUMETRY OF MENINGIOMAS IN CONTRAST-ENHANCED T1-WEIGHTED MRI USING DEEP LEARNING
Authors: Hirayama Ryuichi , Iwata Takamitsu , Yamada Shuhei , Yokota Chisato , KIjima Noriyuki , Kishima Haruhiko
Published: November 2024

BACKGROUND

With the widespread use of MRI equipment and brain docks, there are more opportunities to perform follow-up observation for meningiomas. In recent years, attempts have been made to predict prognosis by using tumor volume as a highly objective imaging biomarker. On the other hand, manual lesion extraction by a reader with anatomical knowledge is indispensable for volume measurement, which requires a certain amount of labor and time. This is a major barrier to the generation of evidence and clinical application in this field.

OBJECTIVE

To establish the clinical significance of tumor volume as an imaging biomarker in meningiomas, and to develop a simple and highly reproducible application for automated volume measurement using artificial intelligence, and to investigate its accuracy and potential for clinical application.

METHODS

178 patients with meningiomas who underwent MRI at Osaka University Hospital were included in the study. Contrast-enhanced T1-weighted images were used for manual lesion extraction by two neurosurgeons. These annotated image data were randomly divided into training (90%) and testing (10%). The deeplabV3 model was used to train the artificial intelligence, and leave-one-out cross-validation was used to train and validate the automated model. The test data were used for comparison, and the agreement rate (Dice index) on the images of the automatically extracted regions and the error rate of the calculated tumor volume (mean square error rate: RMSPE) were used as indices of measurement performance.

RESULTS

The average agreement rate between the automatically extracted area and the test data was 92.3±5.1%. The error rate of tumor volume was 9.5±1.2%.

CONCLUSION

This application using artificial intelligence was considered to have a certain validity in the accuracy of automatic lesion extraction. This method, which enables simple tumor volume measurement, is expected to create new imaging biomarkers that will contribute to the optimization and personalization of meningioma treatment.
NIMG-12. EVALUATING THE SUPER T2-FLAIR MISMATCH SIGN IN OLIGODENDROGLIOMA, IDH-MUTANT AND 1P/19Q CODELETED
Authors: Ozono Iori , Yamasaki Fumiyuki , Onishi Shumpei , Yonezawa Ushio , Taguchi Akira , Khairunnisa Novita Ikbar , Horie Nobutaka
Published: November 2024

BACKGROUND

We reported the super T2-FLAIR mismatch sign as a prognostic imaging biomarker for non-enhanced astrocytoma, IDH-mutant, CNS WHO grade 2 or 3. However, it remains unclear whether this novel imaging biomarker is applicable for oligodendroglioma, IDH-mutant and 1p/19q codeleted.

METHODS

We conducted a retrospective evaluation of non-enhanced oligodendroglioma, IDH-mutant and 1p/19q codeleted, including 14 cases from at our institute and 15 cases from TCGA/TCIA database. We defined “super T2-FLAIR mismatch sign” positivity as having a significantly strong low signal comparable to cerebrospinal fluid, rather than just a pale FLAIR low-signal tumor region as in regular T2-FLAIR mismatch. We evaluated the presence or absence of T2-FLAIR mismatch sign and super T2-FLAIR mismatch sign using preoperative MRI and statistically analyzed the progression-free survival (PFS) and overall survival (OS) using log-rank test.

RESULTS

The median age of this patient group was 47 (ranging 20-77) years and consisted with 16 males and 13 females. There were 27 cases of grade 2 and two cases of grade 3. The regular T2-FLAIR mismatch sign was observed in three cases (10%) (grade 2: 2 cases, grade 3: 1 case). While the super T2-FLAIR mismatch sign was observed in three cases (10%) (grade 2: 2 cases, grade 3: 1 case). One case had both regular and super T2-FLAIR mismatch signs. The mean follow-up period was 33.4 months, during which there were 3 cases of progression and 1 death. Both regular and super T2-FLAIR mismatch sign were not associated with PFS, OS.

CONCLUSIONS

The presence of the super T2-FLAIR mismatch sign was not associated with prognosis in oligodendroglioma, IDH-mutant and 1p/19q codeleted. Because the sample size was insufficient, further larger investigation through is needed to assess the utility of this sign.
NIMG-36. PERFUSION, DIFFUSION, AND ANATOMICAL MRI BIOMARKERS FOR ASSESSING HISTOLOGICALLY-CONFIRMED MALIGNANT TRANSFORMATION IN MOLECULAR SUBTYPES OF IDH-MUTANT GLIOMAS
Authors: Cho Nicholas , Le Vien , Teraishi Ashley , Liu Vicki , Sanvito Francesco , Nakajo Masanori , Wang Chencai , Oshima Sonoko , Eldred Blaine , Yao Jingwen , Nghiemphu Phioanh , Salamon Noriko , Lai Albert , Cloughesy Timothy , Ellingson Benjamin
Published: November 2024

BACKGROUND

Isocitrate dehydrogenase-mutant (IDHm) gliomas often initially present as low-grade (grade 2) gliomas but are expected to later progress into more aggressive higher-grade (grade 3-4) gliomas through malignant transformation (MT). MT is often determined non-invasively by emergence of contrast-enhancement on post-contrast T1-weighted magnetic resonance imaging (MRI), but contrast-enhancement is an imperfect surrogate for histologically-confirmed MT. This study explored perfusion, diffusion, and anatomical MRI biomarkers besides contrast-enhancement to study histologically-confirmed MT in IDHm 1p/19q-intact astrocytomas (IDHm-A) and IDHm 1p/19q-co-deleted oligodendrogliomas (IDHm-O).

METHODS

N=64 patients with initial histopathological grade 2 IDH-mutant glioma diagnosis who underwent repeated tissue sampling and were classified as histologically-confirmed MT (n=35) or non-MT (n=29) were retrospectively studied. Pre-surgical anatomical MRI (n=64) and, if available, diffusion-weighted imaging (n=61) and dynamic susceptibility contrast perfusion MRI (n=53) were analyzed. Tumor volumes of interest were segmented on the whole T2/FLAIR-hyperintense tumor. Measurable contrast enhancement (>1000mm3), tumor volume, sphericity, median apparent diffusion coefficient (ADC), and normalized relative cerebral blood volume (nrCBV) were compared between MT vs. non-MT IDHm-A and IDHm-O.

RESULTS

81% of contrast-enhancing IDHm-A and 100% of contrast-enhancing IDHm-O underwent MT, while 41% of MT IDHm-A and 62% of MT IDHm-O were non-enhancing. Tumor volumes were significantly larger in the MT vs. non-MT groups for both IDHm-A (P=0.02) and IDHm-O (P=0.04). Whole tumor nrCBV was significantly higher (P=0.002), whole tumor ADC trended lower (P=0.06), and non-enhancing tumor sphericity was significantly lower (P=0.03) in MT vs. non-MT IDHm-A. There were no significant differences in ADC, nrCBV, nor sphericity when comparing MT vs. non-MT IDHm-O (P>0.05).

CONCLUSIONS

Many MT IDHm-gliomas remain non-enhancing. Tumor volumes can determine MT for both IDHm-A and IDHm-O. Diffusion and perfusion MRI show differences for MT in IDHm-A but not IDHm-O, which may reflect the different tumor biology of these IDHm molecular subtypes and their need for separate imaging biomarkers.
NIMG-56. MAGNETIC RESONANCE SPECTROSCOPY IN THE POST-TREATMENT METABOLIC CHARACTERIZATION OF BRAIN TUMORS OF GLIAL ORIGIN OF CENTRAL NERVOUS SYSTEM
Authors: Acosta Pablo Moreno , Malaver Gina , Padin Trinidad González , Gamboa Oscar , Singh Carla , Rodriguez Cesar , Balart Josep , Zubieta Camilo , Bouleftour Wafa , Magné Nicolas , Penagos Pedro , Fino Daniel
Published: November 2024

BACKGROUND

and Purpose Central Nervous System tumors have a very low incidence worldwide, however they constitute an important source of mortality and morbidity. Treatment for these types of tumors in adults may include surgery, radiosurgery, radiation therapy, chemotherapy, and targeted treatment. These treatments in brain tumors of glial origen in adults can produce changes in the pathophysiology of the tumor. The purpose of this study was to characterize the different metabolic patterns as effect of treatment and identify tumor recurrences. Materials and

METHODS

A prospective study was conducted with patients with low- and high-grade tumors treated, subjecting them to the single-voxel MRS and multivoxel MRSI protocol at 1.5 T.

RESULTS

Of the 44 patients included, 21 were histopathologically diagnosed as low-grade tumors and 23 as high-grade tumors. Of the low-grade tumors, 11 were caracterized as low-grade (mean Cho/NAA and NAA/Cr ratios 1.49 ((p=0.036) and 0.92 (p=0.038) respectively), 8 cases presented gliosis (mean Cho/NAA and NAA/Cr ratios 1.57 (p=0.028) and 1.36 (p=0.026) respectively), and 4 cases presented radiation necrosis (mean Cho/Cr ratios 2.14 (p=0.03)), (mean Cho/Cr and NAA/Cr ratios 1.25 (p=0.01) and 1.25 (p=0.00)) respectively). Furthermore, tumor recurrence that presented high Cho/NAA ratio were observed in 11 cases. Of the high-grade tumors, 13 were caracterized as high-grade (mean Cho/NAA and Cho/Cr ratios 2.24 (p=0.026) and 4.48 (p=0.026) respectively), 13 cases presented gliosis (mean Cho/NAA and NAA/Cr ratios 1.82 (p=0.028) and 0.64 (p=0.026)) respectively) and radiation necrosis was detected in 10 cases (mean Cho/Cr ratio 1.47 (p=0.03), (mean Cho/Cr and NAA/Cr ratios 2.25 (p=0.01) and 0.97 (p=0.00) respectively). Moreover, tumor recurrence that presented high Cho/NAA ratio were observed in 9 cases.

CONCLUSION

MRS and MRSI contribute to identifying the recurrences, to characterizing the different metabolic patterns as an effect of the treatment and differentiate between low and high grade tumors.
NIMG-59. COMPARATIVE ANALYSIS OF LONG-TERM GLIOBLASTOMA SURVIVORS USING MACHINE LEARNING GENERATED RADIO-PATHOMIC METRICS
Authors: Aaronson Daniel , Bobholz Samuel , Duenweg Savannah , Kyereme Fitzgerald , Lowman Allison , Nath Biprojit , Winiarz Aleksandra , Connelly Jennifer , Mrachek E Kelly , Krucoff Max , Banerjee Anjishnu , LaViolette Peter
Published: November 2024

BACKGROUND

Glioblastoma (GBM) remains the most devastating central nervous system malignancy with poor overall survival (OS), even with gross total resection (GTR) and chemoradiation. Identifying factors associated with long-term survival (LTS) in GBM patients is challenging but crucial for improving prognostic models. This study compares an internal dataset of the top 10% long-term survivors of GBM (n=14) against a combined external cohort of 528 GBM patients who underwent GTR.

METHODS

We used a previously published machine learning-generated radio-pathomic model based on autopsy tissue as ground-truth to generate whole-brain maps of cell density and tumor probability maps (TPM) using conventional preoperative MRI sequences in both our internal dataset and a combined external cohort of GBM patients who underwent GTR from the UCSF-PDGM-v2 and UPenn-GBM databases. We then analyzed clinical and radio-pathomic metrics, including cell density and TPM values within contrast-enhancing (CE) and FLAIR hyperintense regions. Statistical comparisons were performed using t-tests.

RESULTS

Cell density metrics showed significant differences, with lower cell density in contrast-enhancing regions (t-value: 4.709, p<0.001; median: 1559 vs. 1959) and in FLAIR hyperintense regions (t-value: 3.585, p<0.001; median: 1356 vs. 1568) within the LTS group. TPM metrics also showed significant differences, with lower TPM values in contrast-enhancing regions (t-value: 3.312, p<0.001; median: 0.71 vs. 0.72) and in non-enhancing regions (t-value: 2.606, p<0.01; median: 0.68 vs. 0.69) in the LTS group.

CONCLUSION

Our comparative analysis reveals distinct radio-pathomic characteristics associated with long-term survival in GBM patients. Reduced cell density and lower TPM values in both contrast-enhancing and FLAIR hyperintense regions are significantly correlated with long-term survival. These findings suggest that integrating radio-pathomic data may enhance prognostic models and warrants further studies evaluating the relationship of these markers and OS.
NIMG-67. THE CURRENT STATE OF LARGE LANGUAGE MODELS AND NEURO-ONCOLOGY IMAGING
Authors: Aaronson Daniel , Zwagerman Nathan
Published: November 2024

INTRODUCTION

Large language models (LLM), such as chatGPT by OpenAI, exist at the intersection of machine learning and natural language processing, and are poised to transform healthcare with rapid growth in recent years. The ability of these models to process visual data has also advanced in recent years, with GPT-4 being the first model to publicly process visual data, and GPT-4o adding additional capabilities. There has been significant interest in the application of GPT-4o to healthcare image processing.

OBJECTIVE

This study sought to examine the ability of GPT-4o in determining a final diagnosis based on a single MRI image of an intracranial neoplasm. We then compared the performance to GPT-4, as well as to humans including neurosurgery residents, fellow, and attendings.

METHODS

GPT-4 and GPT-4o were given a standard prompt and an accompanying image requesting the most likely diagnosis for 20 brain MRI images, including 5 gliomas, 5 meningiomas, 5 pituitary tumors, and 5 sham non-tumor images. These were compared to a survey of neurosurgery attendings, fellows, senior residents, and junior residents.

RESULTS

GPT-4 supplied correct diagnoses in just 40% of the cases, while GPT-4o correctly identified the pathology in 70% of cases. Neurosurgeons yielded correct responses in 92% of cases, with neurosurgery senior residents faring the best (albeit with a small sample size).

CONCLUSION

GPT-4 and GPT-4o underperformed neurosurgery residents, fellows, and attendings in correctly identifying CNS malignancies. Still, with no additional training, GPT-4o yielded significantly better results than GPT-4, showing rapid advancement in the LLM over is predecessor in identifying intracranial neoplasms via single-image MRIs.
NIMG-68. A COMPREHENSIVE REVIEW OF THE USE OF FMRI IN EVALUATING FUNCTIONAL CONNECTIVITY AND ACTIVATION IN DISORDERS OF CONSCIOUSNESS
Authors: Leskinen Sandra , Mehta Neel H , Quelle Mica , Singha Souvik , D’Amico Randy S
Published: November 2024

PURPOSE

Disorders of consciousness (DoC) like vegetative and minimally conscious states pose significant diagnostic and prognostic challenges, compounded by the inherent limitations in communicating with affected patients. We performed a scoping review of the literature to examine the application of functional magnetic resonance imaging (fMRI) to the assessment of functional connectivity (FC) and activation in DoC.

METHODS

We searched the MEDLINE/PubMed, Web of Science, and Embase databases between the years 2004 and 2024 for English-language studies involving fMRI and DoC in adult populations, adhering to PRISMA guidelines. Included studies were evaluated for study design, DoC subtype, fMRI subtype, cohort size, and FC and/or activation findings.

RESULTS

Our initial search identified 17,475 results, of which 82 studies were ultimately included with a total of 3917 patients. Only one of the included studies was a randomized controlled trial, 24 were prospective cohort studies, three were retrospective cohort studies, and 54 were observational in design. The majority of studies utilized resting-state fMRI (n=54, 65.9%), and the most commonly investigated disorders of consciousness were minimally conscious states (31.9%), vegetative states (14.4%), and unresponsive wakefulness syndromes (12.9%). Among studies with higher levels of evidence like prospective and retrospective studies, FC and activation findings were heterogeneous, with several studies reporting abnormal connectivity in the default mode and auditory networks. Activation responses among patients also varied, with some patients of the same DoC displaying expected activation patterns while others did not. Normal patterns of connectivity and activation were associated with improved prognosis in eight prospective studies and one retrospective study.

CONCLUSIONS

These findings underscore the complexity of using fMRI to evaluate consciousness in DoC patients. Though fMRI has the potential to identify residual cognitive function, the variability in responses also indicates the need for personalized approaches and further research to standardize fMRI protocols for this purpose.
NIMG-75. SIMILARITY DISTANCES-BASED DELTA RADIOMICS (SDDR) ENABLES LONGITUDINAL MRI COMPARISONS FOR SURVIVAL PREDICTION IN GLIOMAS: A MULTI-INSTITUTIONAL VALIDATION
Authors: Pineda Gustavo , Veronesi Michael , Stuhlmiller Timothy J , Lee Hope , Ginn Sarah , Awawda Alaa , Cole Zachariah , Bhatia Ankush , Kesari Santosh , Ahluwalia Manmeet , Romero Eduardo , Ismail Marwa , Tiwari Pallavi
Published: November 2024

Radiomics (computerized feature analysis) on treatment-naive MRI scans has demonstrated great value in outcome prediction for Glioblastoma (GBM). However, delta radiomics (analysis of radiomic feature variation between different events, e.g., before and after treatment) has not been explored on account of challenges with precise spatial correspondences between pre- and post-operative scans. This work presents a survival prediction model for GBM, Similarity Distances-based delta radiomics (SDDR), based on the hypothesis that similarity distance-measures between radiomic features on pre-, and post-treatment images can accurately capture temporal changes within-and-around the tumor, and provide improved prediction of overall survival, compared to models based on a single timepoint. 150 patients from 2 publicly-available Glioma repositories (University of California San Francisco “UCSF” (n=48), LUMIERE (n=67)) and 2 two proprietary datasets (from xCures (n=13), and Cleveland Clinic (CCF) (n=74)) were obtained. UCSF and LUMIERE cohorts were used as separate hold-out sets, in each of which the remaining collections were used as discovery set. Following pre-processing, tumor segmentation into Edema (ED) and Enhancing tumor (ET) were performed. SDDR was then computed, which is the distance between probability densities functions from 156 gray co-occurrence (GLCM) and 52 gradient-based co-occurrences statistics (COLLAGE) features extracted from pre and-post-treatment MRI. Six statistical distances (e.g., Earth mover distance) normalized by the scanning interval (in weeks) yielded n=2496 SDDR measurements per tumor region (1248/region, 936 delta-GLCM, and 312 delta-COLLAGE). The same set of features were computed from pretreatment MRI (Pre-R) for comparison. Features were fed to LASSO-Cox regression for survival analysis. SDDR for GLCM features extracted from ET outperformed Pre-R, and demonstrated significant differences between high and low risk groups for both hold out tests: UCSF (p=0.0069, HR =2.8, C-index=0.69) and LUMIERE (p=0.0061, HR = 1.9, C-index 0.65). SDDR-based multi-institutional survival analysis demonstrated promise in reliable longitudinal risk-stratification in GBM.
NIMG-79. A RADIOMIC-RISK SCORE FOR SURVIVAL PREDICTION IN GLIOMA: A LARGE MULTI-INSTITUTIONAL RETROSPECTIVE VALIDATION STUDY
Authors: Pineda Gustavo , Veronesi Michael , Stuhlmiller Timothy J , Lee Hope , Ginn Sarah , Awawda Alaa , Cole Zachariah , Bhatia Ankush , Kesari Santosh , Ahluwalia Manmeet , Ismail Marwa , Tiwari Pallavi
Published: November 2024

Gliomas have dismal survival. Recently, radiomics has demonstrated success in developing non-invasive image-based biomarkers for survival prediction in gliomas. However, clinical applicability of radiomics-based biomarkers will ultimately require rigorous validation on large, multi-institutional data. This work attempts to evaluate a radiomic-based survival risk-assessment prognostic score on a multi-institutional cohort of Glioma patients. Our rationale is that optimizing and validating radiomic features that capture intensity-based textural variations and morphology-based changes (e.g., local curvature and global contour) on large multi-institutional cohorts can allow for robust risk assessment in Glioma. n=668 pre-operative T1w MRI scans for Glioma patients from 4 cohorts: University of California San Francisco “UCSF” (n=495), LUMIERE (n=86)), xCures (n=13), and Cleveland Clinic (CCF) (n=74) were analyzed. Subjects from UCSF, CCF, and xCures were used for training, whereas the LUMIERE cohort was used for hold-out testing. Following pre-processing, expert-vetted tumor segmentation into Edema (ED) and Enhancing tumor (ET) regions was performed. A total of n=1558 radiomic features were extracted from the tumor regions (779 per region), namely, 31 global contour, 20 curvature-based, 624 gradient co-occurrence statistics, and 104 Collage features. Cox regression model was employed to create a radiomic risk score (RRS) for every subject, which included radiomics features as well as on clinical and demographic variables (IDH, MGMT, sex, age), for survival analysis. RRS incorporated a total of 43 radiomic features, and the associated clinical and demographic variables (CDS), yielding significant differences between high and low risk groups in the training (RRS: p=0.043, HR = 2, CSD: p=0.0031, HR = 2.8) and testing sets (RRS: p=0.0096, HR = 1.8, CSD: p=0.0071, HR = 1.8). Combining RRS and CDS improved the OS prediction at group level (p=3.6e-6, 0.0011, HR=5.4, 2, for training and testing, respectively). Radiomics-based risk-stratification may be promising for reliable risk-stratification in glioma.
NIMG-86. DISSEMINATEDCRYPTOCOCCUS NEOFORMANS MIMICKING CENTRAL NERVOUS SYSTEM PROGRESSION OF DIFFUSE LARGE B-CELL LYMPHOMA
Authors: Baez Adolfo , Handley Guy , Mokhtari Sepideh , Shah Shivan , Phuoc Vania , Greene John
Published: November 2024

A 57-year-old male with stage IV diffuse large B-cell lymphoma (DLBCL), non-germinal center subtype, underwent 6 cycles of polatuzumab, rituximab, cyclophosphamide, doxorubicin, prednisone, and pegfilgrastim (Pola-R-CHP) then presented to the hospital with progressive confusion, double vision, hearing loss, and lower extremity weakness. MRI of the brain and spinal cord with and without IV contrast revealed extensive leptomeningeal enhancement along the brain, several cranial nerves, cervical and thoracic spinal cord with enhancement of the cauda equina. Cerebrospinal fluid (CSF) analysis studies revealed 41 nucleated cells/mm3, protein to 264 mg/dL, and an initial cryptococcal antigen titer of 1:1280; serial lumbar punctures peaked at an opening pressure of 39.5 cm H2O before improvement. Flow cytometry was negative on two CSF studies. Multiple cultures grew Cryptococcus neoformans before sterilization of CSF culture on day 13. He received induction therapy for 4 weeks with amphotericin B and flucytosine. Flucytosine treatment was limited due to cytopenias on day 9 and continued induction with amphotericin B and fluconazole. Fluconazole was switched for voriconazole based on minimal inhibitory concentrations by broth dilution, however, the drug was undetectable on therapeutic drug monitoring 2 weeks later and switched back to fluconazole. Subsequent positron emission tomography revealed ongoing hypermetabolic thoracic, mediastinal, and hilar lymph nodes compared to PET scans prior to chemotherapy for which he underwent transbronchial fine needle aspiration concerning for Cryptococcus involvement. He remained on fluconazole 800mg/day and MRI 11 months after the initial presentation demonstrated ongoing but slightly improved leptomeningeal enhancement. Due to persistent symptoms despite sterile CSF cultures, he underwent a three-day course of IV methylprednisolone 1000mg with some incomplete improvement in symptoms. The opening pressure normalized and the cryptococcal antigen titer decreased to 1:20 about 11 months after initial treatment. This case highlights the risk of opportunistic infections like cryptococcal meningitis in patients undergoing chemotherapy.
NCMP-02. UTILITY OF ICE PACK TEST FOR EARLY RECOGNITION OF IMMUNE CHECKPOINT INHIBITOR MEDIATED OCULAR WEAKNESS
Authors: Zahid Anza , Thatikonda Nithisha , Amador Dalton , Saeed Mujtaba , Tummala Sudhakar
Published: November 2024

INTRODUCTION

Immune checkpoint inhibitors (ICI) are associated with neurological immune-related adverse events (NiArE) such as myasthenia gravis (MG) and myositis. These conditions often present with overlapping symptoms, notably ptosis, dyspnea, and extremity weakness. Early recognition and treatment are warranted to prevent disease progression.

OBJECTIVE

To test the utility of simple bedside ice pack test (IPT) in early recognition and distinction of ICI-mediated MG and myositis ocular manifestations.

METHODS

We administered IPT in 14 patients who had received ICI in the past 6 months and presented with ptosis. Improvement in ptosis was considered positive IPT (non-fixed, fatigable ptosis) that is suggestive of Immune-mediated MG-predominant process. Work up included myasthenia antibodies, EMG, serum markers of muscle injury (creatine kinase, aldolase), myositis panel and muscle biopsy. Statistical analyses employed median for continuous and frequencies for categorical variables.

RESULTS

Positive IPT was found in 2 (14%) patients with positive myasthenia antibodies and neuromuscular junction dysfunction on EMG in one patient with repetitive nerve stimulation. These patients had mild elevation in creatine kinase (CK). Muscle biopsy did not reveal a myositic process. Twelve (86%) patients had negative IPT (fixed and non-fatigable ptosis) with significantly elevated CK (>4000), positive myositis panel and muscle biopsy consistent with myositic process. Six of these patients (42%) also had positive myasthenia antibodies. Concomitant myocarditis was observed in 5 (36%) patients.

CONCLUSION

Clinical overlap between myasthenia and myositis is observed in immune mediated toxicity that may be due to cross-reactivity of antibodies, however, IPT was able to distinguish MG vs myositis-predominant process, thus helping guide management.
NCMP-07. ADVERSE NEUROLOGIC COMPLICATIONS FOLLOWING IMMUNE CHECKPOINT INHIBITORS FOR TREATMENT OF MELANOMA: COMPARATIVE ANALYSIS OF PD-1 INHIBITOR MONOTHERAPY TO COMBINATION THERAPY WITH CTLA-4 INHIBITORS
Authors: Das Nikita , Dhamija Ravi , Kaelber David , Kelly Michael , Xie Peter , Reddy Deven
Published: November 2024

In the past decade, FDA approval of several novel immune checkpoint inhibitors (ICI) has revolutionized treatment of advanced melanoma. However, severe immune-related adverse events (irAEs) from these medications have been reported. This study examines whether PD-1/CTLA-4 inhibitor combination immunotherapy confers increased incidence of neurologic irAEs in melanoma patients compared to PD-1 inhibitor monotherapy. A retrospective, multicenter cohort study performed using TriNetX research platform identified adult patients diagnosed with melanoma. Cohort 1 (n=9,105) included melanoma patients treated with PD-1 inhibitor monotherapy (pembrolizumab or nivolumab). Cohort 2 (n=4,727) included melanoma patients treated with PD-1/CTLA-4 inhibitor combination therapy (PD-1 inhibitor + ipilimumab). Propensity Score Matching generated final cohorts (n=4,667) using covariates: gender, race, age at diagnosis, and history of nervous system disorders. Odds ratios (OR) were determined for the occurrence of neurologic irAEs at 3 years and 5 years following therapy initiation. Kaplan Meier analysis estimated survival probabilities for each irAE subtype, as defined by the 2021 Neuro irAE Disease Definition Panel. At 3 years post-diagnosis, there was increased risk of meningitis [OR: 2.8, 95% CI: (1.8, 4.2)], encephalitis [OR: 3.1, 95% CI: (1.9, 5.1)], demyelinating syndromes [OR: 2.7, 95% CI: (1.4, 5.2)], vasculitis [OR: 1.2, 95% CI: (0.5, 2.8)], peripheral neuropathy [OR: 1.3, 95% CI (1.1, 1.5)], neuromuscular junction disorders [OR: 1.1, 95% CI: (0.7, 1.8)], and myopathy [OR: 1.4, 95% CI: (1.1, 1.9)] in melanoma patients receiving combination immunotherapy compared to those receiving anti-PD-1 monotherapy. Increased incidence of neurologic irAEs corresponded with marginally lower, yet statistically significant decreases in survival probability (p<0.01), except for vasculitis (p=0.2) and neuromuscular junction irAEs (p=0.3). At 5 years following therapy initiation, these trends persisted. Melanoma patients receiving anti-PD-1/CTLA-4 combination therapies are at greater risk of neurologic irAEs than patients on anti-PD-1 monotherapy. Incidence of neurologic irAEs may confer worsened survival prognosis for these patients.
NCOG-03. DESCRIPTIVE ANALYSIS AND OUTCOME COMPARISON BETWEEN PATIENTS WITH GLIOBLASTOMA MULTIFORME WHO RECEIVE 15 VERSUS 30 FRACTIONS OF RADIOTHERAPY: A RETROSPECTIVE CHART REVIEW
Authors: Gnanasegaram Joshua , Paulin Gregory , Kutanzi Ethan , Kalyvas Maria , Mushonga Melinda , Genta Sofia , Purzner Teresa , Purzner James , Goldie Katie , Olding Timothy , de Moraes Fabio Ynoe
Published: November 2024

The morbidity and efficacy of abbreviated radiotherapy (RT) courses for Glioblastoma (GB) in patients over 60 years have been studied, however, outcomes in younger patients are not yet well-described. This study aims to characterize the outcomes of patients receiving either a standard versus abbreviated RT course. A retrospective chart review at Kingston Health Sciences Centre from June 2014 to March 2021 included patients with GB receiving either 40Gy in 15 fractions (Fr) or 60Gy in 30Fr. Data on age, ECOG score, and concurrent chemotherapy (Temozolomide, TMZ) were collected. Outcomes compared were treatment completion, hospital admission during treatment, progression-free survival (PFS), and overall survival (OS). Records of 156 patients (median age 61 years, range 25-87 years) were reviewed. Of these, 89 received 30Fr and 67 received 15Fr (p=0.51). MGMT methylation was recorded in 54 (35%) patients; of these, 27 received 15Fr and 27 received 30Fr. Median follow-up was 12 months. While PFS did not significantly differ between 15Fr vs. 30Fr (6 vs. 11 months, respectively; p=0.08), OS was significantly different (8 vs. 16 months, respectively; p<0.001). Patients receiving 15Fr vs 30F tended to have higher ECOG scores (p<0.001) and were older (median: 71 [range 45-87] vs. 57 [range 25-69] years; p<0.001). Individuals receiving TMZ were more likely to receive 30Fr (67.5% vs. 32.5% for 15Fr; p<0.001). Completion rates were higher for 30Fr (94.3%) than 15Fr (83.6%; p=0.03). Hospital admission rates did not differ (p=0.51). In summary, patients receiving 15Fr (40Gy) typically have poorer functional status, are less likely to receive chemotherapy, and less likely to complete treatment compared to those receiving 30Fr. Hospital admission rates during treatment are low (13%) and similar for both groups. OS, but not PFS, is better for patients receiving 30Fr compared to 15Fr.