bluuebunny/crossref_metadata_2025 huggingface dataset:
NIMG-53. MRI-BASED RADIOMICS FOR DIFFERENTIATION BETWEEN PERIFOCAL EDEMA AND NON-CONTRAST-ENHANCING GLIOBLASTOMA FOCI
Authors: Thiele Frederic , Saviolli Felipe , Biczok Annamaria , Stöcklein Veit , Stöcklein Sophia , Schichor Christian , Thon Niklas , Weller Jonathan
Published: November 2024

OBJECTIVE

Various intracranial tumors can lead to the development of perifocal edema. Differentiating edema from tumor on MRI might be easy in metastases and meningiomas but can be challenging in patients with glioblastoma. We set out to compare and characterize perifocal edema and non-contrast-enhancing glioblastoma foci by means of radiomic feature analysis.

METHODS

In this single-center, retrospective study, patients with intracranial tumors and perifocal edema on preoperative T2/FLAIR-sequences were included. Patients diagnosed with brain metastasis, meningioma or glioblastoma were eligible. Tumor and edema volumes were semi-automatically segmented and extracted. After image registration, contrast-enhancing tumor and necrosis on T1-weighted sequences were subtracted from T2/FLAIR-hyperintense tumor and perifocal edema. Radiomic features were computed. Distribution of radiomic features were tested using the Shapiro-Wilk test. ANOVA or Kruskal-Wallis tests were applied to compare the features. Significant features were identified based on p-values (<0.05) and post-hoc Tukey’s Honest Significant Difference (HSD) tests were conducted.

RESULTS

The cohort comprised n=60 patients and was split in three groups according to histopathology (metastases, meningioma, glioblastoma). Each subgroup comprised n=20 patients (33.3%). 107 radiomic features of the T2-hyperintensity, after subtraction of contrast-enhancing tumor and necrosis, were tested for each patient. 18 radiomic features (17%) that mainly comprised measures of shape, texture and intensity distribution, e.g., sphericity (p<0.01), surface/volume (p<0.01), entropy (p<0.01), skewness (p<0.01) and kurtosis (p<0.01), showed no significant difference between metastases and meningiomas but differed significantly from the T2-hyperintensity of glioblastoma. The textual complexity of glioblastoma was significantly higher (p<0.01).

CONCLUSION

Radiomic feature analysis unraveled many features that might be helpful in differentiating perifocal edema from tumor infiltration. Future studies should aim at validating our results and further exploring the T2-hyperintensity of glioblastoma patients, e.g., suspected edema versus suspected tumor infiltration zone.
NIMG-61. TRANSVENTRICULAR MIGRATION OF CESIUM-131 BRACHYTHERAPY SEEDS TO THE SACRAL THECAL SAC IN A PATIENT TREATED FOR RECURRENT GLIOBLASTOMA
Authors: Islam Mahnoor , Varma Abhay , Rivers Charlotte , Godwin William , Takacs Istvan , Zukas Alicia
Published: November 2024

Cesium-131 brachytherapy (GammaTileTM) is a relatively new form of surgically targeted radiation therapy for recurrent glioblastoma. While seed migration is a well-documented complication of solid tumor brachytherapy, it has not been reported in the treatment of glioblastoma. Here, we describe a rare occurrence of seed migration in a 71-year-old patient treated for recurrent left temporal lobe glioblastoma. The GammaTile is comprised of a resorbable collagen matrix containing four titanium-encapsulated radioactive Cs-131 seeds. Each seed emits a localized dose of radiation with a 9.7-day half-life. To prevent displacement from the resection cavity, oxidized regenerated cellulose (SurgicelTM) was applied to the cavity surface under the tiles and fibrin sealant (TisseelTM) was applied over the tiles. Margins of the lateral ventricles were not breached during the surgery and surface was non-ulcerated. The tiles remained in place on follow-up imaging for at least 7 weeks. At least 97% of the prescribed dose was delivered before seed migration. Bevacizumab systemic treatment was initiated. Abdominal CT obtained after 3 months incidentally noted migration of 2 seeds to the sacral spinal canal. Additional seeds had migrated to the suprasellar region, left lateral ventricle, and lateral cerebellomedullary cistern. Despite seed migration, the patient maintained progression-free survival for at least 10 months, with at least 30 months of overall survival from the time of diagnosis. Although the patient did not experience any symptoms related to seed migration, this has the potential to cause radiation-related toxicity to healthy tissue, particularly if it occurs early after surgery. The use of bevacizumab may have contributed to penetration of the lateral ventricle. Despite meticulous surgical technique, the potential for seed migration should be considered during treatment planning when using anti-angiogenic therapies. Further research is needed to better understand the factors contributing to seed migration and to develop strategies for minimizing this risk.
NIMG-69. INTERROGATION OF GLIOBLASTOMA FATTY-ACID SYNTHESIS AND METABOLISM WITH DEUTERIUM METABOLIC IMAGING
Authors: Chang Andrew , Ge Xia , Cho Kevin , Nunez Elena , Patti Gary , Garbow Joel , Ippolito Joseph
Published: November 2024

Glioblastoma, an invariably lethal brain tumor, undergoes marked metabolic alterations during tumorigenesis and is extraordinarily difficult to treat. Detecting recurrence after treatment and understanding metabolic alterations within the tumor microenvironment are extremely challenging. An exciting and emerging imaging methodology, deuterium metabolic imaging (DMI), detects metabolic adaptations via non-radioactively labeled deuterated substrates. This study developed approaches to image lipid synthesis with deuterium oxide (D2O) and metabolism with D31-palmitate (D31-Pal) in glioblastoma. A fatty-acid phantom was generated for characterization of lipid DMI signal at 12 T. DMI was performed in mice orthotopically implanted with GL261 glioblastoma utilizing either orally administered D31-Pal or D2O and was correlated with pharmacokinetic metabolic measurements from mouse serum. Mice were either orally gavaged with an emulsion of D31-Pal prior to imaging or provided 16% D2O for ad libitum consumption following tumor implantation. Although D2O administration resulted in robust enrichment of lipid signal in GBM, D31-Pal uptake and metabolism were not significantly detected within intracranial tumors. Interestingly, D31-Pal uptake and metabolism were detected in normal tissues, indicating preferential utilization of fatty acids in non-neoplastic tissues. These findings suggest de novo lipogenesis within GBM, rather than uptake of administered long chain fatty acids, is the preferential pathway for cellular lipids. DMI can assist in interrogating GBM fatty-acid synthesis and metabolism, as well as furthering our understanding of lipid distribution within the body by providing a non-invasive scaffold for dynamic interrogation of fatty-acid distribution in an oncologic model. Developing a non-invasive method for characterization of tumor fatty-acid synthesis and metabolism may improve our understanding of tumor metabolism and could dynamically guide selection of patient-tailored metabolic therapies in the future.
NIMG-83. THE PROGNOSTIC VALUE OF PARAMETRIZED KI-67 MAPS DERIVED FROM CONVENTIONAL MRI AND MACHINE LEARNING IN A LARGE RETROSPECTIVE COHORT OF ADULT-TYPE DIFFUSE GLIOMAS
Authors: Dagher Samir-Anthony , Gates Evan , Wintermark Max , Long James , Fuentes David , Schellingerhout Dawid
Published: November 2024

BACKGROUND

Ki-67 is a well-established proliferation marker relied upon for glioma grade assessment. Advances in machine learning (ML) now allow researchers to non-invasively predict the voxelwise Ki-67 index with reasonable accuracy based on anatomical MRI.The purpose of this study is to evaluate the prognostic ability of these predictions in adult-type diffuse gliomas.

METHODS

We included adult patients with untreated gliomas of various histopathologic grades who underwent their first resection at a comprehensive cancer center from 1993 to 2018. Anatomic MR images were pre-processed, segmented, normalized, then run through a pre-trained ML algorithm to generate Ki-67 parametric maps. The maximum estimated Ki-67 (maxKi-67) for each patient was documented, and the optimal threshold stratifying the cohort into low- and high-risk patients was computed using 10-fold cross-validation. Kaplan-Meier survival curves were then generated for both risk groups and compared using the log-rank and Breslow tests. MaxKi-67 was correlated with OS using Cox proportional hazard regression analysis adjusted for age and preoperative KPS.

RESULTS

1,179 patients (age 52±15; 701 males) were included in this study. 727 tumors were histologic grade IV, while 246 and 206 were histologic grade III and II. The mean maxKi-67 was 15.9± 5.2. A maxKi-67 threshold of 13 was computed from the 10-fold cross-validation to dichotomize the cohort by OS. The low-risk group (maxKi-67<13) had a median OS = 2,435 days, significantly different from the high-risk group (maxKi-67>13) which had median OS = 551 days (p<.001). A maxKi-67 index above this threshold significantly increased the hazard of death: unadjusted HR = 2.53 [95% CI 2.17-2.96] and adjusted HR = 1.55 [1.31-1.83]. Age > 55 and preoperative KPS < 90 were also negative prognosticators in the Cox model: adjusted HR for age = 2.79 [2.36-3.31] and for KPS = 2.08 [1.77-2.46].

CONCLUSION

Image-based derivation of maxKi-67 index using ML accurately predicts survival in glioma patients with a cut-off of 13 segregating these patients into 2 risk groups.
NIMG-87. MULTIREGIONAL, MRI-LOCALIZED SAMPLING OF HIGH GRADE GLIOMAS REVEAL SEX-DISTINCT PATTERNS OF 5-ALA FLUORESCENCE AND IMAGING FEATURES
Authors: Green Destiny , Jackson Pamela , Curtin Lee , Singleton Kyle , Vogelbaum Michael , Quinones-Hinojosa Alfredo , Bendok Bernard , Swanson Kristin
Published: November 2024

High grade gliomas (HGGs) are aggressive brain tumors that are difficult to remove completely, leading to poor survival rates. Contrast enhancement on T1Gd magnetic resonance imaging (MRI) has traditionally been used to guide resection, however it often underestimates true tumor burden, adding a layer of uncertainty for surgeons during pre-operative planning. Fluorescence guided surgery using 5-aminolevulinic acid (5-ALA) has emerged as an intraoperative solution and understanding it in conjunction with MRI features can address the limitations of routine T1Gd imaging during surgical planning. Here we investigate sex-specific patterns in HGGs using 5-ALA fluorescence and imaging features. We analyzed a patient dataset of 202 multiregional MRI-localized biopsies from 42 HGG patients (20 male and 22 female). Data included patient demographics, 5-ALA status (positive or negative), MRI annotations (CE = contrast enhancement, NE = non-enhancement, BAT = brain around tumor non-enhancement), and survival outcomes. Statistical analyses included Wilcoxon rank-sum tests, Kruskal-Wallis tests, and chi-squared tests to assess differences in imaging annotations and 5-ALA positive vs negative status among sex cohorts. Among all samples, CE and BAT were associated with higher 5-ALA positivity, while NE was associated with higher 5-ALA negativity (p = 0.02119). Female patients were less likely to have detectable 5-ALA in their multiregional biopsy samples than males (p < 0.0001). CE at the biopsy location was more likely to be indicative of 5-ALA positivity in males than females (p = 0.001927); whereas NE was associated with higher 5-ALA negativity in females than males (p = 0.03426). BAT was associated with higher 5-ALA positivity in males than females (p = 0.03895). Our study reveals sex-specific patterns in 5-ALA fluorescence and image features among HGG patients. These unique features may serve as potential pre-surgical markers for tumor regions that are more likely to benefit from 5-ALA-guided resection.
NCMP-05. CLINICAL AND RADIOGRAPHIC IMPROVEMENT WITH REPLACEMENT OF FOLATE METABOLITES IN A PATIENT WITH INTRATHECAL METHOTREXATE-INDUCED MYELOPATHY
Authors: Kim Hannah , May Jasmine L , Mencacci Niccoló E , Dixit Karan S
Published: November 2024

Methotrexate (MTX)-induced myelopathy is a rare but serious adverse effect of intrathecal (IT) MTX, which may mimic subacute combined degeneration (SCD). MTX disrupts the normal synthesis of methionine, which plays an important role in maintaining myelin sheath integrity, resulting in degeneration of the dorsal columns. This degeneration does not respond to classic treatment with vitamin B12 and folate supplementation, unlike SCD. Here, we describe a case of a 45-year-old woman with Philadelphia-positive B-cell acute lymphoblastic leukemia treated with hyperCVAD regimen with ponatinib, who after 14 doses of prophylactic IT MTX, developed progressive lower extremity weakness, paresthesias, gait instability, saddle anesthesia, and bowel/bladder dysfunction. Her neurologic exam was also notable for diffuse hyporeflexia. The onset of symptoms followed a diarrheal infection, and an initial MRI spine showed no evidence of abnormal enhancement. She was initially treated with intravenous immunoglobulins for presumed acute inflammatory demyelinating polyneuropathy. She then re-presented one week later with progressively worsening symptoms. A repeat MRI spine revealed a new longitudinally extensive T2 hyperintense signal within the dorsal columns from T7 to T12. CSF results were notable for mild pleocytosis and increased myelin basic protein; the latter of which is often seen in MTX-induced myelopathy. The patient received high-dose administration of key metabolites of the methyl-transfer pathway including S-adenosylmethionine (PO 400mg three times daily), folinate (IV 20mg four times daily), cyanocobalamin (PO 1000mcg once daily) and methionine (PO 5mg once daily) for 7 days. This treatment regimen resulted in both clinical and radiographic improvement. Subsequent MRI spine demonstrated complete resolution of the abnormal signal in the thoracic cord. This case highlights (1) the diagnostic complexity of IT MTX-induced myelopathy (2) the role response to treatment plays in uncovering this diagnosis, and (3) how the replacement of folate metabolites facilitates both radiographic and clinical improvement in IT MTX-induced myelopathy.
NCMP-10. EFFECT OF EXTENT OF RESECTION ON GLIOMA SEIZURE OUTCOMES BASED ON MOLECULAR GROUPS
Authors: Xu Emily , Gersey Zachary , Sussman Jonathan , Amankulor Nduka
Published: November 2024

INTRODUCTION

Increased extent of resection (EOR) is a known predictor of seizure freedom in glioma patients. However, it is unknown how tumor genomic alterations affect EOR-induced seizure control.

OBJECTIVE

To evaluate the genotype-specific impact of EOR on post-operative seizure control

METHODS

Records of 553 glioma patients who underwent tumor resection from 2012-2023 were reviewed. All patient tumors were analyzed with next generation sequencing and FISH analysis. The unsupervised machine learning algorithm non-negative matrix factorization (NMF) was used to cluster the genomic data. Clinical variables including extent of resection of contrast enhancing tumor and non-enhancing tumor, temozolomide therapy, and radiation therapy were analyzed using Cox Proportional Hazards models.

RESULTS

NMF clustering of tumor sequencing data revealed four molecular groups: Group 1 (n=56): CDKN2a loss, EGFR copy number gain or mutation, TERT promoter (TERTp) mutation, and MGMT methylated; Group 2 (n=27): IDH mutation, TP53 mutation, and MGMT methylated; Group 3 (n=60): TP53 mutation, TERTp mutation and MGMT methylated; Group 4 (n=244): MGMT unmethylated. Thresholds in the post-operative residual non-enhancing tumor volume (NETV) were identified which marked the most difference in seizure control. For patients in Group 1, the NETV threshold that led to improved epilepsy outcomes was <94.7 cc (p=0.047), whereas the threshold for Group 4 was <89.1 cc (p=0.016). When analysis was conducted for Group 2, the threshold of 10.2 cc failed to reach significance (p=0.1). Interestingly, the threshold analysis for Group 3 found that having a NETV of > 10.1 cc showed improved seizure outcomes (p=0.016). A multivariable cox proportional hazard analysis found that twelve-month seizure freedom was predictive of better OS in group 1 (HR 0.02, p=0.05) and group 4 (HR 0.21, p=1.63e-9).

CONCLUSION

Our study reveals clinically distinct molecular groups of glioma that display different seizure responses. This data suggests a tumor-specific approach to aggressiveness of extent of resection in order to achieve optimal seizure control.
NCMP-12. AN ATYPICAL CASE OF POEMS WITH MACROFOCAL MYELOMA
Authors: La Janet , Graber Jerome
Published: November 2024

Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes (POEMS) syndrome is a rare paraneoplastic syndrome secondary to an underlying plasma cell dyscrasia. Symptoms of peripheral neuropathy dominate the clinical picture and is postulated to be related to serum vascular endothelial growth factor (VEGF) mediated altered permeability of the blood nerve barrier. The classic presentation includes a solitary osteosclerotic plasmacytoma and an elevation of VEGF. In this case, we present a patient with neither of these features who met diagnostic criteria for POEMS though had predominantly osteolytic lesions and was diagnosed with macrofocal myeloma, a unique subset of multiple myeloma. Our patient is a young male who presented with progressive leg numbness/weakness and was found to have marked ankle weakness, diffuse areflexia and unilateral gynecomastia on examination. EMG showed a motor predominant demyelinating polyneuropathy. Labs showed a serum IgG lambda M protein, low estradiol and low testosterone. He had a normal serum VEGF level though the lab was drawn after treatment initiation. Bone biopsy of a dominant osteolytic lesion was consistent with a plasma cell neoplasm (light chain restricted). Of note, he had mild cauda equina nerve root and ventral conus enhancement initially concerning for leptomeningeal involvement however, two lumbar punctures were negative for malignant cells. Spinal enhancement has been reported in POEMS. The patient underwent chemotherapy, radiation therapy and autologous stem cell transplantation. We present a patient diagnosed with MFMM, a rare subset of multiple myeloma, comprising only 3% of all cases, along with POEMS, a rare paraneoplastic syndrome. Interestingly, as osteolytic lesions can be seen in POEMS alone though not predominantly so, it is possible the patient could have atypical POEMS without underlying multiple myeloma. POEMS may remain under-recognized when presentations or setting are atypical.
NCMP-15. MULTIPLE HEMORRHAGIC CNS LESIONS IN A PATIENT WITH RELAPSED SYSTEMIC CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: Li Yi , Mantica Megan , Drappatz Jan
Published: November 2024

Although chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries, extramedullary CLL, characterized by the accumulation of clonal B cells outside of blood, bone marrow, and peripheral lymph nodes, remains rare. The central nervous system (CNS) is the most common site of extramedullary CLL involvement. However, clinically significant CLL in the CNS has been reported in fewer than 100 cases in the literature, and its true prevalence remains unknown with variable estimates. CLL in the CNS most often affects the meninges and usually spares the parenchyma unless there is a higher-grade/Richter transformation; in either case, it is typically not hemorrhagic. Furthermore, in the rare cases reported of hemorrhagic intraparenchymal CLL, patients present with isolated bleeding rather than multifocal hemorrhages. We present the case of a 63-year-old patient with multiply recurrent systemic CLL without Richter transformation who developed bilateral infratentorial and supratentorial micro and macrohemorrhages. Histopathology of a lesion showed focal subacute hemorrhage associated with reactive brain parenchyma containing CLL cells, though it was unclear whether the CLL predated the hemorrhage or if the hemorrhage introduced the CLL. Given the patient’s clinical stability, the lesions were ultimately attributed to coagulopathy in the context of CLL with subsequent secondary colonization of the hemorrhage by CLL cells. These lesions completely resolved after the patient underwent CLL-directed therapy three months after symptom onset. This case underscores the importance of considering bleeding risks associated with CLL and demonstrates that addressing the underlying CLL can lead to the improvement in bleeding sequelae.
NCMP-17. SPHENOID WING DIFFUSE LARGE B-CELL LYMPHOMA MIMICKING A MENINGIOMA: A RARE DIFFERENTIAL DIAGNOSIS
Authors: Campos Paiva Aline Lariessy , Araujo João Luiz Vitorino , Lovato Renan Maximillian , de Oliveira Jean Gonçalves , Veiga José Carlos Esteves
Published: November 2024

BACKGROUND

Meningioma is the most frequent dural lesion and in most cases have a benign course and surgery usually is curative. Nevertheless, there are several dural lesions, neoplastic and non-neoplastic that may mimic meningiomas. Radiological features could help to perform this differentiation. Primary dural lymphoma (PDL) is a rare entity in which adjuvant therapy is required for proper therapeutic approach.

CASE PRESENTATION

A 67-year-old female patient presented with a clinical complaint of left exophthalmos and headache. During investigation, it was noticed the presence of a hyperintense left sphenoid wing lesion with orbital invasion. The diagnosis of meningioma was initially considered and she underwent neurosurgical approach aiming maximal extension. However, histopathological investigation disclosure that was a primary dural lymphoma (diffuse large B type) and she was referred to adjuvant therapy with a proper control of the disease.

CONCLUSIONS

Dural lesions could have neoplastic and non-neoplastic origin. Although meningiomas have a high prevalence, it must be considered other pathologies during evaluation and consideration of the differential diagnosis. This help to improve therapeutic management of the patients.
NCMP-20. FACTORS RELATED TO PERMANENT AND TEMPORARY MOTOR DEFICITS IN PATIENTS UNDERGOING GLIOMA RESECTION: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Conway Brian , Armstrong Stephanie , Botros Nada , Tarima Sergey , Krucoff Max
Published: November 2024

Standard of care treatment for virtually all glioma subtypes starts with maximal safe resection. However, resections that result in motor deficits can negate any survival benefit from surgery and diminish quality of life. Because current evidence on functional outcomes following glioma resection often conflicts and is limited to a small number of case series, retrospective analyses, and reviews, here we performed the first PRISMA-compliant systematic review and meta-analysis of currently published data to identify factors related to permanent and temporary motor deficits after surgery. We searched Ovid Medline, Scopus, Web of Science, CINAHL/EBSCO, PsychInfo, Cochrane and Wiley for studies reporting motor outcomes following surgical resection of glioma. Outcomes were stratified by patient/tumor characteristics, pre-operative condition, and intra-operative factors for both permanent (≥3 months postop) and temporary (<3 months postop) motor deficits. Generalized estimating equations were used to generate odds ratios and 95% confidence intervals. A total of 1,162 titles and abstracts were reviewed for eligibility resulting in the evaluation of 211 full-text articles. Data were extracted from 55 studies including 1,801 patients with 223 (12%) permanent postoperative motor deficits, 428 (24%) temporary motor deficits, and the remaining 1,150 (64%) without motor deficit. Pre-operative deficit was the strongest predictor of permanent post-operative motor deficit (OR 10.56, CI 5.20-21.45, p=7.2E-11), while high pre-operative Karnofsky Performance Scale (KPS) (OR 0.98, CI 0.97-0.99, p=0.036) and subcortical tumor location (OR 0.15, CI 0.025-0.90, p=0.038) were associated with no permanent deficit. Supratotal resection was significantly associated with temporary motor deficits (OR 3.54E+12, CI 3.53+E13-3.56E+17, p<2E-16), and asleep craniotomies were associated with no deficit (OR 1.68E-01, CI 4.93E-02–5.71E-01, p=0.0043). Ultimately, this study represents the largest analysis of motor outcome data in glioma surgery to date.
NCOG-04. MEMORY TRACT SPARING USING DIFFUSE TENSOR IMAGING IN RADIATION PLANNING OF PRIMARY BRAIN TUMORS
Authors: Haisraely Ory , Mair Arnaldo , Lawerence Yaavoc , Taliansky Alicia
Published: November 2024

INTRODUCTION

Radiation therapy (RT) is a critical treatment modality for both primary and metastatic brain tumors, yet approximately 30% of patients experience cognitive decline post-radiotherapy. This cognitive toxicity is linked to low radiation doses affecting neural stem cells in the hippocampal dentate gyrus. Hippocampal Avoidance (HA)-Whole Brain Radiotherapy (WBRT) combined with Memantine has shown promising outcomes in preserving cognitive function and quality of life (QOL) in patients with brain metastases, suggesting it should be the standard of care for those with good performance status and no hippocampal metastases.

METHODS

We conducted a prospective trial approved by the IRB (SMC0307-23), including patients aged 18 and above with primary brain tumors post-resection or biopsy. Exclusion criteria included multifocal glioma crossing to the other hemisphere. RT was delivered to a total dose of 60Gy in 30 fractions with concomitant TMZ. Diffusion tensor imaging (DTI) was performed to map hippocampal-associated white matter tracts. Memory fiber tracts and hippocampi were contoured and integrated into RT planning using Eclipse treatment planning software. Dosimetric analyses compared two plans: one with memory fiber constraints and one without.

RESULTS

Twelve patients with low-grade gliomas were included, with successful contouring of memory fibers and hippocampi. VMAT treatment plans met dose constraints for memory fibers, with an average mean dose of 10.1 Gy. The average MoCA score before RT was 27.1 and 26.4 at six months post-treatment, with a p-value of 0.07. Excluding one patient, the scores were 27.1 and 26.6, respectively (p=0.13).

CONCLUSION

MRI planning using DTI for memory fiber detection and incorporation into RT planning via VMAT techniques enables hippocampal and associated white fiber sparing, potentially preserving cognitive function. Preliminary cognitive data are promising, supporting the need for further validation in a larger cohort.
NCOG-17. THE COMBAT PROJECT - CORE POST OPERATIVE MORBIDITY SET FOR PAEDIATRIC BRAIN TUMOURS
Authors: Krishna Sandhya Trichinopoly , Mallucci Conor , Pizer Barry , Gamble Carrol , Harman Nicola , Jenkinson Michael
Published: November 2024

BACKGROUND

Brain tumours are associated with high morbidity both from the tumour and the medical and surgical interventions used to treat them. Post operative morbidity reporting following surgery for paediatric brain tumours is poor due to the lack of a common language when reporting harms. One solution is to develop a core outcome set to stipulate the minimum post operative adverse outcomes that should be reported. The COMBAT (Core Post Operative Morbidity Set for Paediatric Brain Tumours) Project will develop a core outcome set that can be applied to post operative paediatric brain tumour patients to harmonise how adverse outcomes are measured and reported, enabling comparison between different trials, studies and clinical services. We aim to generate interest in The COMBAT Project and invite participation in the project from healthcare professionals and researchers experienced in paediatric neuro-oncology for the consensus process.

METHODS AND ANALYSIS

We will engage with national and international stakeholders including patients and their carers, healthcare professionals and researchers. A systematic review will identify harms reported in post operative paediatric brain tumour patients and how they are measured. Qualitative interviews with patients and carers will identify any harms of importance to them. A Delphi survey will be created from the harms identified. A consensus meeting will be held to finalise the core outcome set. The final core outcome set will be published and disseminated to encourage uptake.

DISCUSSION

There is a clear need for a common language to harmonise measurement and reporting of harms following surgery for paediatric brain tumour patients. This project will define post operative adverse outcomes that are of critical importance to key stakeholders. It will be used to standardise surgical morbidity outcome measurement and reporting in trials, studies and clinical practice and will inform future research in this field.
NCOG-23. CLINICIAN AND PATIENT REPORTED OUTCOMES IN YOUNG ADULTS WITH GLIOBLASTOMA: RESULTS FROM A MULTIMODAL PROSPECTIVE STUDY
Authors: Raheem Javeria , Roberto Katrina , Chan Aimee , Theriault Aimee , Machado Mikayla , Granovskaya Inga , Wong Andrea , Calabrese Eirena , Perry James , Lim-Fat Mary Jane
Published: November 2024

The median age for glioblastoma (GBM) is 65 years old, however, younger patients have a similarly dismal prognosis. The adolescent and young adult (AYA) population (15-39 years) is a unique and understudied population. Our study aimed to identify survivorship needs in adult patients in AYA population (<40 yrs) with GBM through analysis of patient and clinician-reported outcomes (PROs and CROs). The Molecular, Imaging and Neurological assessment Database (MIND-CNS) captures Neurological Assessment in Neuro-Oncology (NANO) scores, MDASI-BT and FACIT-SP12 responses at first clinic visit and follow-ups for patients with GBM. We tested associations of the two age groups (18-39 vs. 40 years and older) with each domain of NANO, MDASI-BT and FACIT-SP12 at baseline and at follow-up visits using multivariate logistic regression models, adjusting for MGMT promoter methylation and extent of resection. There were 104 patients with GBM enrolled, including 11 young adults, (median =30 years) and 93 older adults (median =65 years). Young and older adults scored similarly in the domains of NANO, MDASI-BT, and FACIT-SP12 at baseline. MDASI domains at follow-up showed statistically significant lower scores on weakness, fatigue, distress, irritability, drowsiness, and disturbed sleep in younger vs. older adults (adjusted p<0.05). Younger adults had less difficulty with memory and concentration, and their symptoms interfered less with work, walking, and overall enjoyment of life. They also reported feeling more peaceful, finding greater comfort and strength in their faith and beliefs. A comparison of NANO score at baseline and progression will be performed at data maturation. While PROs were similar at baseline, young adults reported lower severity in their physical symptoms and higher spiritual well-being compared to older adults at follow-up visits, highlighting different survivorship experiences. Data maturation will allow for deeper analysis to better inform supportive strategies.
NCOG-24. CHARACTERIZING NEUROTOXICITY ASSOCIATED WITH SYSTEMIC CHEMOTHERAPY IN PATIENTS WITH BREAST CANCER USING DOMAIN-SPECIFIC INTRA-INDIVIDUAL NEUROCOGNITIVE VARIABILITY
Authors: Sheppard David , Noll Kyle , Sullaway Catherine , Wefel Jeffrey
Published: November 2024

BACKGROUND

Systemic chemotherapy is associated with neurotoxicity and neurocognitive functioning (NCF) changes. Intra-individual neurocognitive variability (IIV) is an index of NCF spread/dispersion across neuropsychological tests and can be elevated in patients with breast cancer (BC) after systemic chemotherapy. This study investigated longitudinal IIV changes within NCF domains after chemotherapy to determine whether: (1) IIV for NCF domains are more sensitive to changes than traditional mean-based metrics, and (2) whether changes in domain-specific IIV are associated with changes in mood disturbance or quality of life (QOL).

METHODS

Prior to and during/shortly after chemotherapy, 37 women with BC were administered a standardized NCF battery including tests within domains of attention/speed of information processing (A/SoP), learning/memory (L/M), and executive functions (EF). Within each domain, the coefficient of variation (CoV) was computed using the standard deviation of normatively-adjusted T-scores while adjusting for intra-individual mean. Patients were assessed for QOL using Functional Assessment of Cancer Therapy-Breast and mood using the STAI and BDI.

RESULTS

Paired samples t-tests revealed that mean NCF performances declined for L/M (t[36])=-4.44,p<.001,Hedge’s g=.70) and improved for A/SoP (t[36]=3.21,p=.003,g=.29), while CoV increased/worsened for L/M (t[36]=3.82,p<.001,g=.76) but did not change for A/SoP (t[36]=-0.05,p=.959,g=.01). There was no change in EF mean or CoV (ps >.10). No domain mean or IIV change was associated with mood changes (ps>.10). Mean NCF changes were not associated with QOL (ps >.10). Increased/worsened L/M CoV was associated with improved FACT-Breast scale QOL (ρ=.40,p=.020).

CONCLUSIONS

Both mean- and IIV-based NCF worsened for learning/memory. Discrepancies between mean and IIV change for attention/speed of information processing may be due to differential susceptibility to practice effects. Unexpected associations between learning/memory IIV changes and QOL require further investigation. Future studies are needed to examine NCF dispersion changes across treatment status and in other cancer populations.
NCOG-33. MTOR INHIBITORS AS ADJUVANT TARGETED THERAPY IN PEDIATRIC PATIENTS WITH PROGRESSIVE OR REFRACTORY LOW-GRADE GLIOMA: A SINGLE-CENTER RETROSPECTIVE STUDY
Authors: Fan Aaron E , Cunningham Jonathan , McGovern Susan , McAleer Mary , Sandberg David I , Friedman Gregory K , Zaky Wafik
Published: November 2024

Low grade gliomas (LGG) represent about one-third of all pediatric central nervous system tumors, with about half having disease progression despite upfront surgery and adjuvant therapies. Current treatments for LGG progression either produce toxic side effects (i.e., radiation therapy) or do not generate durable responses. Targeted agents are an effective way of attacking tumors with identified genetic mutations, but in some cases, a complete response can be subverted by the heterogeneity of tumors. Additionally, most tumors do not carry any targetable mutations. Temsirolimus and everolimus are mTOR inhibitors that have previously been shown to be well-tolerated in early clinical studies in pediatric solid tumors. We performed a retrospective study to look at the toxicity profile of mTOR inhibitors when given in combination therapy and treatment response in patients with progressive or refractory LGG. We examined 20 patients with a diagnosis of LGG including mixed glioma and glioneuronal tumors who received treatment at our institution from 2016-2024 with targeted therapy, of which 8 patients also received temsirolimus or everolimus. Of these 8 patients, 2 had partial response, 2 had minor response, 3 had stable disease, and 1 had progressive disease. The average number of cycles received was 13.6 (range 3-24). Most observed side effects were grade 2 or less, including nausea, transaminitis, myelosuppression, diarrhea, and hyperlipidemia while grade 3/4 toxicities that required dose modification included mucositis, hyperglycemia, and hyperlipidemia. Overall, the addition of temsirolimus to treatment regimens of pediatric patients with heavily pretreated refractory LGG prolonged progression free survival by an average of 478 days with only one patient progressing while on therapy. These results demonstrate feasibility and preliminary efficacy of adding mTOR inhibitors as adjuvant therapy in this patient population. There is dire need of large prospective collaborative studies in the future.
NCOG-34. CORRESPONDENCE BETWEEN INTRAOPERATIVE GAMMA BAND ELECTROCORTICOGRAMS AND DIRECT ELECTRICAL STIMULATION ACROSS DIVERSE NAMING TASKS IN PATIENTS WITH LANGUAGE-ELOQUENT BRAIN TUMORS
Authors: Noll Kyle , Tasnim Israt , Asman Priscella , Swamy Chandra , Connelly Katherine , Muir Matthew , Hall Matthew , Pellizzer Guiseppe , Ince Nuri , Prabhu Sujit
Published: November 2024

BACKGROUND

Few studies have examined concordance between intraoperative electrocorticography (ECoG) and direct electrical stimulation (DES) language mapping, especially across varied naming tasks.

METHODS

Twelve patients (Mdn age=59; 75% HGG) underwent awake craniotomy with ECoG and DES language mapping. Mapping utilized iPad stimulus presentation coupled to a 4x8 electrode array for both ECoG and DES. Time-frequency ECoG gamma band activity (Early and Late) was visualized for 3 naming paradigms (Object, Action, Auditory). Bipolar DES was also conducted for each task at each electrode pair. ECoG activations and DES hits were overlayed on preoperative MRI. DES hits represented ground truth for eloquence. ECoG accuracy was examined for each task with 3 different criteria: exact (identical electrodes for ECoG activation and DES hits), adjacent (ECoG <1cm of DES hits), and adjacent within a predefined peritumoral region of interest (<2 cm from boundaries).

RESULTS

32 DES hits (40% Auditory, 32% Action, 28% Obj) were observed across patients. Exact ECoG-DES accuracy ranged from 78%-90% [Object: Sens=11%, Spec=91%, PPV=6%, NPV=95%; Action: Sens=40%, Spec=93%, PPV=24%, NPV=97%; Auditory: Sens=69%, Spec=78%, PPV=19%, NPV=78%]. Adjacent ECoG-DES accuracy ranged from 82%-91% [Object: Sens=33%, Spec=92%, PPV=18%, NPV=97%; Action: Sens=44%, Spec=93%, PPV=25%, NPV=97%; Auditory: Sens=91%, Spec=81%, PPV=37%, NPV=99%]. When restricted to the peritumoral region, adjacent ECoG-DES accuracy ranged from 94%-97% [Object: Sens=14%, Spec=99%, PPV=25%, NPV=97%; Action: Sens=25%, Spec=99%, PPV=25%, NPV=99%; Auditory: Sens=100%, Spec=94%, PPV=54%, NPV=100%]. For patients with DES hits (N=10), all had at least 1 task activation <1 cm of DES hits, with 7/10 having convergence of activations across at least 2 tasks.

CONCLUSIONS

Negative ECoG mapping is strongly predictive of non-eloquence confirmed by DES for all naming tasks. Additionally, gamma band activation elicited by auditory naming within the peritumoral region is strongly predictive of eloquence. Findings support task-based ECoG language mapping for prediction of eloquence and identification of targets for DES confirmation.
NCOG-39. EXPLORING THE POTENTIAL OF STEREOTACTIC RADIOSURGERY IN THE MANAGEMENT OF MENINGIOMAS
Authors: Sallese Greta , Kandhadai Anuttham , Brindley Paul
Published: November 2024

INTRODUCTION

Meningiomas present complex therapeutic challenges due to their potential impact on neurological function and quality of life. While the standard of care involves observation and surgical resection, stereotactic radiosurgery (SRS) is an alternative treatment modality. This study aimed to compare the relative efficacy of SRS and surgical resection in the management of meningiomas to inform evidence-based decision-making in this clinical context.

METHODS

A retrospective cohort study was conducted using the TriNetX database, comparing patients undergoing treatment for meningiomas with either stereotactic radiosurgery (SRS) or surgical resection. Cohorts were matched on comorbidities. Rates of mortality and malignant neoplasms of the brain within 5-years of treatment with either modality were compared. In addition, short-term outcomes were assessed at 3 months post-treatment.

RESULTS

After matching, there were 1,898 patients in each cohort. Patients receiving SRS exhibited a significantly lower risk of mortality (95% CI: 0.76-1.07) and a decreased risk of developing malignant neoplasms of the brain (RR: 0.68, 95% CI: 0.54-0.85) over 5 years, compared to surgical resection. At 3-months post treatment, patients treated with SRS demonstrated significantly lower relative risks for several outcomes, including cerebral infarction (RR: 0.27, 95% CI: 0.18-0.39), hydrocephalus (RR: 0.19, 95% CI: 0.11-0.32), cerebral edema (RR: 0.13, 95% CI: 0.10-0.18), seizures (RR: 0.27, 95% CI: 0.21-0.34), neurological deficits (RR: 0.19, 95% CI: 0.13-0.28), and post-procedural infection (RR: 0.14, 95% CI: 0.07-0.28).

CONCLUSION

This retrospective cohort study suggests that in the management of meningiomas, SRS may be associated with lower mortality rates, decreased risks of malignant neoplasms of the brain, and improved short-term outcomes compared to surgical resection. Further research is warranted to validate these results and explore long-term outcomes and potential adverse effects.
EXTH-12. POTENTIATING THE EFFICACY OF IMMUNE CHECK-POINT INHIBITORS IN GLIOBLASTOMA BY INHIBITION OF CXCL12
Authors: Makranz Chen Cam-El , Huguely Caitlin , Haynes Tuesday , Briceno Nicole , Zhang Meili , Davis Dionne , Song Hua , Zhang Wei , Gilbert Mark , Watanabe Masashi
Published: November 2024

BACKGROUND

The tumor immune microenvironment (TIME) in glioblastoma (GBM) is rich in CXCL12, a chemokine known for stimulating angiogenesis. CXCL12 also controls immune cell trafficking and promotes polarization to an immunosuppressive phenotype. We postulated that inhibiting CXCL12 will modulate the immunosuppressive TIME in GBM, thereby augmenting the efficacy of immunotherapy agents like immune checkpoint inhibitors (ICIs). We examined the immunomodulatory and therapeutic efficacy of CXCL12 inhibition, using a small molecule NOX-A12, with and without ICIs in pre-clinical murine GBM models.

METHODS

B6 immunocompetent mice bearing intracranial (i.c.) or subcutaneous (s.c.) SB28 tumors received either vehicle, NOX-A12, anti-PD1 and anti-CTLA4 (dual ICI) or NOX-A12 + dual ICI (combination). Tumor growth was measured by IVIS imaging and immune cells in brain were analyzed using high dimensional flow cytometry. Survival was analyzed using Kaplan-Meier curves and log rank test.

RESULTS

Combination treatment resulted in tumor regression and long-term survival in 40% of s.c. tumor bearing mice compared to 10% treated with dual ICI only. Three of 4 mice rechallenged with contralateral s.c. tumor remained tumor free while all naive mice reached endpoint. TIME from treated s.c. tumors revealed increase in CD4 and effector memory CD8 T cells by combination treatment compared to dual ICI. In i.c. GBM tumors, while no survival benefit or growth inhibition was seen, combination treatment induced an early increase in effector memory CD8 T cells and PD-L1+ B cells, and a later increase in MHC-II+ microglia compared to dual ICI.

CONCLUSION

Inhibition of CXCL12 enabled the increase of effector cytotoxic T cells by ICI, improving survival in the s.c. GBM model, but not in i.c. GBM model. This might be due to differences in CXCL12 effect between extra and intra-CNS tumor or due to robust immune response causing excessive brain edema and death. These will be further explored in ongoing and future studies.
EXTH-15. AN EGFRVIII RNA-LNP VACCINE PROTOTYPE ACHIEVES TUMOUR CLEARANCE IN A GBM MOUSE MODEL
Authors: Snelling Shannon , Nechanitzky Robert , Lun Xueqing , Ellestad Kristofer , Pyczek Joanna , Olsen Kirsten , Wu Yu , Karpov Yury , Liu Jun , Gold Matthew , Menon Haritha , Tan Yilin , Krishnan Rajesh , Mahoney Douglas , Martin-Orozco Natalia , Chan Jennifer A
Published: November 2024

Glioblastoma (GBM) is an aggressive high-grade glioma that is fatal despite standard-of-care therapy. Recurrent somatic alterations that form neoantigens represent opportunities for targeted therapeutic intervention. Using human EGFRvIII as a prototypical structural alteration and neoantigen, we tested the potential of a mRNA-LNP vaccine approach to improve the survival of mice with EGFRvIII-driven GBM. To generate the model, we used in vivo electroporation to introduce genetic alterations (EGFRvIII-OE/CDKN2A-KO/PTEN-KO) into periventricular cells of early postnatal C3H mice, then propagated cells from the subsequent tumours to create implantable cell lines. Following orthotopic implantation, the resulting syngeneic tumours faithfully recapitulate histologic features of GBM with infiltrative growth, mitoses, necrosis, and vascular proliferation. Also like human GBM, the models are sensitive to but not cured by temozolomide chemotherapy and are resistant to immune checkpoint blockade. We delivered mRNA-LNP vaccines against EGFRvIII into the thigh muscle of tumour-bearing mice on days 7, 10, 14, 21, and 36 after tumour cell implant. We observed no tumour in vaccine-treated mice compared to significant tumour burden in control vector-treated animals by MR imaging at day 30 post-tumour cell implant. By day 37, all control-treated mice had died, whereas vaccine-treated mice cleared their tumours with no tumour burden detectable by histology at day 150 (N= 5 per group, **p= 0.0023). In a follow-up experiment with vaccine or control treatment on days 10, 14, 18, and 25 post-cell implants, all control mice had died by day 39. Further, vaccine-treated surviving animals were re-challenged with tumour cell implant into the contralateral hemisphere on day 42 and remain alive as of day 90. Our ongoing proof-of-principle work demonstrates that neoantigen driver mutations in high-grade glioma models can be targeted with an mRNA lipid vaccine. We hope this pre-clinical work will lead to early-phase clinical trials.
EXTH-55. ANTI-TUMOR ACTIVITY OF A NEW ONCOLYTIC ADENOVIRUS DELTA-24-RGDOX-IL15 CO-EXPRESSING OX40L AND IL-15
Authors: Jiang Hong , He Jiasen , Duran Alejandra , Fan Xuejun , Shin Dong Ho , Parthasarathy Akhila , Gillard Andrew , Lopez-Rivas Andres , Moure Marc Garcia , Lang Frederick , Gomez-Manzano Candelaria , Fueyo Juan
Published: November 2024

Accumulating evidence show that the interaction between oncolytic viruses (OVs) and host immune system plays an essential role in cancer virotherapy. Compared to lytic potency of OVs, enhancement of OV-mediated anti-tumor immunity has become a more attractive strategy to improve OV efficacy. To this end, we have reported that the third-generation oncolytic adenovirus (OA), Delta-24-RGDOX, which expresses the immune co-stimulator OX40 ligand (OX40L), is more potent to elicit anti-tumor immunity than the second-generation OA Delta-24-RGD. Since IL-15 activates T and NK cells and promotes persistence of CD8+ memory T cells, we hypothesize that co-expression of OX40L and IL-15 by OAs will further potentiate their efficacy. For this purpose, we constructed the next generation OA Delta-24-RGDOX-IL15. In cultured human and murine tumor cell lines, this new virus effectively expressed the two molecules and displayed comparable potency in viral replication and oncolysis as OAs expressing either of the two (Delta-24-RGDOX, Delta-24-RGD-IL15). Then, we tested the anti-tumor activity of Delta-24-RGDOX-IL15 (two doses, intratumorally, one week interval) in two syngeneic tumor models in C57BL/6 mice: 1) intracranial (i.c.) gliomas from GL261-5 cells; 2) subcutaneous (s.c.)/i.c. melanomas from B16 cells (virus injected into s.c. tumors only). We found Delta-24-RGDOX-IL15 was more efficacious than the other two OAs to inhibit tumor growth of both treated tumor and the untreated i.c. tumors in the second model, leading to long-term survivors (p < 0.05). Different from adoptive cell therapies with cells engineered to express IL-15, we haven’t observed any obvious toxicity with this new virus when it was injected intratumorally into either the i.c. or s.c. tumors. Further studies are in progress to analyze the modifications of the tumor microenvironment induced by the addition of IL-15 to Delta-24-RGDOX. We expect this virus to be a good candidate to be combined with CAR T cell therapies.