bluuebunny/crossref_metadata_2025 huggingface dataset:
NIMG-32. ORAL ADMINISTRATION OF DEUTERATED CHOLINE AS A NEW APPROACH TO PROVIDE HIGH TUMOR-TO-BRAIN IMAGE CONTRAST IN DEUTERIUM METABOLIC IMAGING (DMI)
Authors: Osoliniec Victor , Thomas Monique , de Graaf Robin , De Feyter Henk
Published: November 2024

BACKGROUND

Metabolic imaging using FDG-PET is a key component of disease management in many cancers outside of the brain, but in brain tumors it often shows low tumor-to-brain contrast because of high background signal from normal brain. We explore generating cancer-specific metabolic image contrast using Deuterium Metabolic Imaging (DMI), which is a novel 2H magnetic resonance spectroscopic imaging-based technique. DMI was applied after oral administration of deuterated choline, an essential nutrient needed for membrane synthesis whose uptake is often increased in tumors.

METHODS

Total choline (tCho) DMI was performed in an orthotopic model of glioblastoma, F344 rats (n=11) implanted with RG2 cells, on an 11.7 tesla MRI scanner, with isotropic spatial resolution of 2.5 mm. tCho-DMI data were collected for 36 min during intravenous infusion (IV, n=6) or after 3 days of oral administration (PO, n=5) of [2H9]-choline chloride dissolved in sterile water. At a dose of 285 mg/kg body weight, bolus-continuous IV infusion via the tail vein required 1.57 ml for a 250-gram rat. PO administration via gavage on 3 consecutive days used the max daily dose recommended for human adults, 50 mg/kg. Results - In the PO group, average tumor tCho concentration was 0.78±0.14 mM and 0.20±0.05 mM in contralateral normal brain. In the IV group, the tCho concentration was 0.88±0.18 mM in the tumor, and 0.18±0.03 mM in normal brain (PO vs. IV: p=0.52). Tumor-to-brain contrast was 5.9±1.2 in PO-administered animals, and 7.1±3.3 for animals receiving IV 2H-choline, (p=0.54).

CONCLUSIONS

- In a preclinical GBM model oral administration of [2H9]-choline resulted in comparably high tumor-to-brain image contrast on tCho-DMI-based maps as during IV infusion. Work is ongoing to identify the different choline metabolites that contribute to the tCho signal. Because oral administration of choline is very safe, this approach could facilitate the translation of tCho-DMI to human subjects.
NIMG-35. IMPACT OF RESECTION AT TIME OF FIRST RECURRENCE IN WHO GRADE 2 IDH-MUTANT GLIOMAS
Authors: Ospina Juan Pablo , Viera Maya , Wetzel Ethan , Cahill Daniel , Gerstner Elizabeth R , Miller Julie J
Published: November 2024

INTRODUCTION

Maximal safe resection standard of care treatment of IDH-mutant gliomas and is associated with improved overall survival (OS). However, the impact of extent of resection (EOR) at first recurrence is not well established and there are no data on its impact on prognosis.

METHODS

We retrospectively collected clinical data on patients with IDH-mutant WHO grade 2 astrocytoma and oligodendroglioma treated at our institution from 1997 to 2023. To assess the impact of EOR at first recurrence, we excluded patients who exclusively underwent diagnostic biopsy. Dates of progression were determined by the treating neuro-oncologist or tumor board consensus. Volumetric measurements of contrast-enhancing (CE) tumor and total T2/FLAIR pre- and post second surgery were obtained with BrainLab SmartBrush tool.

RESULTS

One-hundred patients with recurrent astrocytoma and 35 patients with recurrent oligodendroglioma were identified, of whom 57 and 25, respectively, underwent a second resection and had imaging available for volumetric analysis. In patients with astrocytoma, 13/57 had CE at diagnosis, and 28/57 at first recurrence. EOR of T2/FLAIR and CE volume correlated with improved OS. In multivariate regression analyses, T2/FLAIR EOR at first recurrence correlated with improved OS adjusted for gender, preoperative T2/FLAIR volume, prior radiotherapy or chemotherapy, and initial CE (HR 0.977, p< 0.001). In patients with CE, contrast-EOR correlated with OS adjusted for gender, initial CE, preoperative contrast volume, and prior radiotherapy or chemotherapy (HR 0.929, p< 0.001). Conversely, in patients with WHO grade 2 oligodendroglioma, T2/FLAIR EOR did not significantly impact OS (EOR> 90% p= 0.92, EOR> 20% p= 0.13). Only 5/25 patients had CE at first recurrence precluding further analysis.

CONCLUSIONS

The EOR of CE and total FLAIR hyperintensity at first recurrence appears to positively impact prognosis in patients with WHO grade 2 astrocytoma but not in oligodendroglioma. These findings should be evaluated in prospective trials.
NIMG-37. “SYNTHETIC” PERFUSION MRI WITH ADJUSTABLE ACQUISITION PARAMETERS IN BRAIN TUMORS USING DYNAMIC SPIN-AND-GRADIENT-ECHO ECHOPLANAR IMAGING
Authors: Sanvito Francesco , Yao Jingwen , Cho Nicholas , Raymond Catalina , Telesca Donatello , Pope Whitney , Everson Richard , Salamon Noriko , Boxerman Jerrold , Cloughesy Timothy , Ellingson Benjamin
Published: November 2024

INTRODUCTION

Dynamic susceptibility contrast (DSC) perfusion MRI can assess normalized relative cerebral blood volume (nrCBV) and percentage of signal recovery (PSR) in brain tumors, which can aid in differential diagnosis, molecular profiling, and identification of disease progression. However, CBV-optimized and PSR-optimized protocols differ in terms of acquisition parameters. Additionally, DSC dependency on acquisition parameters limits the universalizability of diagnostic cutoffs for nrCBV and PSR across institutions and scanners. This study aims to generate “synthetic” DSC datasets with adjustable synthetic acquisition parameters using dynamic spin-and-gradient-echo echoplanar imaging (dynamic SAGE-EPI) to: 1) simultaneously generate nrCBV and PSR with optimal acquisition parameters, 2) compare DSC datasets with heterogeneous external cohorts.

METHODS

Thirty-eight patients with contrast-enhancing brain tumors were prospectively imaged with dynamic SAGE-EPI during a non-preloaded single-dose contrast injection. Multiple synthetic DSC datasets with desired pulse sequence parameters were generated using the Bloch equations applied to the dual-echo gradient-echo (GE) data extracted from dynamic SAGE-EPI datasets, with or without optional preload simulation. For each patient, synthetic protocols were set to match guideline-compliant CBV-optimized protocols, PSR-optimized protocols, and protocols used in external cohorts from the literature, for comparison.

RESULTS

Dynamic SAGE-EPI allowed for simultaneous generation of CBV-optimized and PSR-optimized DSC datasets with a single contrast injection. Conversely, suboptimal PSR computation from guideline-compliant CBV-optimized protocols resulted in rank variations within the cohort (Spearman’s ρ=0.83-0.89, i.e. 31%-21% rank variation). Treatment-naïve glioblastoma exhibited lower parameter-matched PSR compared to the external cohorts of treatment-naïve primary CNS lymphomas (PCNSL) (p<0.0001), supporting a role of synthetic DSC for multicenter comparisons.

CONCLUSIONS

Dynamic SAGE-EPI allows for simultaneous generation of CBV-optimized and PSR-optimized DSC data with a single injection, facilitating use of a single perfusion protocol for all DSC applications. This approach may also be useful for comparisons of perfusion parameters across heterogeneous multicenter datasets.
NIMG-41. MULTI-SITE, PROSPECTIVE TRIAL EVALUATING FET-PET IN GLIOBLASTOMA (FIG) STUDY (TROG 18.06): PRELIMINARY RESULTS OF CENTRAL NUCLEAR MEDICINE REVIEW OF FET-PET BIOLOGIC TARGET VOLUME DELINEATION FOR RADIATION PLANNING
Authors: Koh Eng-Siew , Francis Roslyn , Lee SzeTing , Lau Eddie , Thomas Elizabeth , Whitehead Angela , Cook Olivia , Dykyj Rachael , Moore Alisha , Rossi Alana , Thomas Paul , Pattison David , Akhurst Tim , Alipour Ramin , Hsiao Edward , Schembri Geoffrey , Lin Peter , Yap June , Ly Tam , Kirkwood Ian , Vallat Wilson , Krishna Dayanethee Krishna , Khan Shahroz Khan , Ngai Stanley Ngai , Yu Chris , Beuzeville Scott , Yeow Tow Chan , Barry Nathaniel , Ebert Martin , Gan Hui , Moffat Bradford , Fitt Greg , Ng Sweet Ping , Pinkham Mark , Bailey Dale , Scott Andrew M
Published: November 2024

BACKGROUND

To provide an update from the multi-site trial evaluating O-(2-[18F]-fluoroethyl)-L-tyrosine Positron Emission Tomography (FET-PET) in Glioblastoma (FIG) study and 2) assess the impact of central Nuclear Medicine physician (NMP) review of prospective FET-PET1 delineation of the biological target volume (BTV) for radiotherapy (RT) planning. Material and methods Up to 210 adult GBM participants across 11 Australian sites will undergo FET-PET post-surgery/pre-chemo-RT [CRT] (FET-PET1), one month post CRT (FET-PET2) and at suspected progression (FET-PET3). Group 1 participants enter at timepoint 1 (FET-PET1 with MRI1), with Group 2 entering at timepoint 2. Adjuvant RT target volumes are derived per standard contrast MRI with hybrid post-hoc RT volumes then incorporating the FET-PET1 NM-derived BTV utilising MiM version 7.0. All trial sites and NMP have passed credentialling which included three benchmarking cases involving BTV delineation.

RESULTS

Trial recruitment commenced in January 2021, with 189 (n=126 Group 1 and n=63 Group 2) participants enrolled to date, with a target of 140 Group 1 participants. During trial credentialling, results demonstrated variations in FET-PET1-derived BTV in 25/72 (34.7%) - 13 minor and 12 major.Currently, 42 of 112 participant FET-PET1 with BTV delineation cases across 10 sites have undergone central review, with 7/42 (16.7%) requiring resubmission. Reasons for resubmission/protocol deviation included incorrect imaging sequence selection within the MiM workflow (n=3), Static GTV overcontouring (n=3) and dynamic volume of interest change in size/position during MiM workflow use (n=1).

CONCLUSION

The FIG trial will complete recruitment in 2024 with analyses planned at one year post CRT completion. Despite improvements in resubmission rates compared to the credentialling phase, central review of prospective FET-PET1-derived BTV delineation remains important in ensuring protocol adherence. The FIG study is the largest prospective multi-site study of its kind addressing FET-PET’s impact on adjuvant radiation planning and its role in management of pseudoprogression and prognostication.
NIMG-47. MULTI-INSTITUTIONAL VALIDATION OF AN AI-BASED MODEL FOR PREDICTION OF TUMOR INFILTRATION AND FUTURE RECURRENCE IN PATIENTS WITH GLIOBLASTOMA: RESULTS FROM THE RESPOND CONSORTIUM
Authors: Mohan Suyash , Garcia Jose , Akbari Hamed , Kwak Sunwoo , Baik Kyunglok , Shalaby Mahmoud , Matsumoto Yuji , Bakas Spyridon , Kamel Peter , Tippareddy Charit , Badve Chaitra , Lee Matthew , Barnholtz-Sloan Jill , Sloan Andrew , Chakravarti Arnab , Palmer Joshua , Dicker Adam , Flanders Adam , Shi Wenyin , Jain Rajan , LaMontagne Pamela , Marcus Daniel , Sotiras Aris , Balana Carmen , Capellades Jaume , Puig Josep , Cepeda Santiago , Stefano Anna Luisa Di , Wiestler Benedikt , Woodworth Graeme , ORourke Donald , Nasrallah MacLean , Davatzikos Christos
Published: November 2024

BACKGROUND

Glioblastoma is an infiltrative primary brain tumor with poor prognosis despite multimodal therapy. Recurrence is inevitable secondary to tumor cell infiltration in the peritumoral tissues, beyond contrast enhancing margins, which is the target for surgical resection. We hypothesize that a machine learning model constructed from a diverse, inter-institutional dataset can improve accuracy of generated tumor infiltration maps, thus guiding precision targeted therapies.

METHODS

731 MRI scans of treatment-naïve glioblastoma patients from 10 institutions were included. All patients had pre-operative multiparametric-MRI (T1, T1Gd, T2, T2-FLAIR, ADC), and underwent complete resection of the enhancing tumor followed by standard-of-care chemoradiotherapy. 42 patients were used as an independent validation set, and 689 were used for training. Of these 239 patients had histopathologically confirmed recurrence with corresponding MRI scans, which were used as ground-truth for evaluating the location of recurrence using a leave-one-site-out (LSO) method. An AI model combining deep learning and SVM was used to develop a predictive model for infiltration. We validated the generalizability of our results in an unseen, multi-institutional data set.

RESULTS

Our model predicted locations of recurrence with odds ratio (99% CI) 37.6 (37.1-38.1) on the LSO testing set and 24.3 (23.4-25.2) on the validation set, indicating that areas labeled highly infiltrated were over 37 and 24 times more likely to coincide with future recurrence respectively.

CONCLUSIONS

We demonstrate that AI-based pattern analysis from multiparametric-MRI can predict tumor infiltration in peritumoral regions with high likelihood of recurrence by decrypting the visually imperceptible heterogeneity of peritumoral tissue. Model performance improved from training on a larger/diverse dataset and combining results of multiple AI methods. Independent validation confirmed the model’s ability to generalize to unseen data. We believe this will serve to advance AI-based biomarkers for predicting future recurrence and facilitate development of multi-modal targeted therapies in this era of precision neuro-oncology.
NIMG-48. MEASURABLE DISEASE AS BASELINE CRITERION FOR RESPONSE ASSESSMENT IN GLIOBLASTOMA TRIALS – A COMPARATIVE STUDY OF MRI-BASED (RANO 2.0) VERSUS PET-BASED (PET RANO 1.0) ASSESSMENT
Authors: Johanna Müller Katharina , Forbrig Robert , Reis Jonas , Wiegand Lilian , Barci Enio , Kunte Sophie , Kaiser Lena , Schönecker Stephan , Schichor Christian , Harter Patrick , Thon Niklas , von Baumgarten Louisa , Preusser Matthias , Albert Nathalie Lisa
Published: November 2024

Response assessment in glioblastoma relies on measuring contrast enhancement on MRI according to RANO 2.0 criteria, and ‘measurable disease’ often serves as inclusion criterion for clinical trials. Recently, criteria based on amino acid PET have been proposed for response assessment in clinical trials (PET RANO 1.0). Here, we compare ‘measurable disease’ as defined by PET RANO 1.0 with the standard MRI-based RANO 2.0 criteria in glioblastoma patients. In this retrospective single-center study, we identified patients with newly diagnosed IDH-wildtype glioblastoma who underwent [18F]FET PET and MRI after resection or biopsy and before chemoradiotherapy. Two independent investigators analyzed ‘measurable disease’ according to PET RANO 1.0 versus MRI-based RANO 2.0 criteria. Additionally, lesion size and uptake intensity, including maximal and mean target-to-background ratio, were assessed. We evaluated 136 patients with 76 cases after biopsy and 60 after microsurgical resection. Using RANO 2.0, 35/76 patients (46.1%) had measurable disease in the biopsy group, and 25/60 (41.6%) in the resected group (median sum of maximum cross-sectional diameters: 39.7mm and 28.0mm, respectively). Utilizing PET RANO 1.0, a significantly higher proportion (overall 123/136, 90.4%; 66/76 (86.8%) after biopsy; 57/60 (95.0%) after resection) had measurable disease (p<0.001). None of the 10 patients in the biopsy group nor of the 3 patients in the resected group without measurable disease on PET had measurable disease on MRI. Contrariwise, 32/41 patients (73.2%) in the biopsy group and 30/35 (85.7%) in the resected group without measurable disease on MRI exhibited measurable disease on PET. PET RANO 1.0 identifies a significantly higher number of patients with ‘measurable disease’ compared to conventional MRI-based criteria in the perioperative period of glioblastoma. PET-based assessment may thus serve as a novel baseline parameter for evaluating treatment response in glioblastoma trials, that may allow the enrollment of larger patient populations. Further validation in prospective trials is warranted.
NIMG-51. PROSPECTIVE CASE CONTROL STUDY OF HYPOXIA FMISO PET/MRI AS A DIAGNOSTIC FEATURE OF GLIOBLASTOMA IMMUNOTHERAPY FAILURE
Authors: Barajas Jr Ramon , Mallak Nadine , Choudhary Gagandeep , Szidonya Laszlo , Stoller Jared , Thurston Brian , Raslan Ahmed , Dogan Aclan , Randy Woltjer , Wood Matthew , Sanusi Olabisi , Walker Josh , Rooney Bill , Fu Rochelle , Muldoon Leslie , Holland Samantha , Neuwelt Edward , Nehmeh Sadek , Ivanidze Jana , Ambady Prakash
Published: November 2024

BACKGROUND

Hypoxia is a prognostic biological feature of glioblastoma. 18F-fluoromisonidazole (FMISO) PET quantifies tumor hypoxia. Efficacy of checkpoint immunotherapy is being investigated, but specific response assessment criteria remain unknown. We hypothesized that tumor hypoxia is a defining feature of immunotherapy failure in patients with glioblastoma.

METHODS

A prospective case control study was undertaken in patients with newly diagnosed IDH wildtype glioblastoma (NCT03649880). Cases were concurrently enrolled in a phase II study (NCT03347617) of pembrolizumab immunotherapy (200 mg IV every 3 weeks) combined with Stupp protocol temozolomide-based chemoradiotherapy following maximal safe resection. Controls did not receive pembrolizumab. FMISO PET/MRI (3.7 MBq/kg, 90 min uptake) was performed at time of mRANO presumed progression. Hypoxic volume (HV) was defined by pixels with FMISO uptake ≥1.2x that of mean cerebellar uptake. MRI-Gd enhancing volume was segmented using a semi-automated approach. Hypoxic fraction (HF) was defined as the HV-to-MRI enhancing volume ratio. Disease progression or pseudoprogression (Psp) was confirmed through surgery or follow-up MRI. T-test and receiver operator characteristic (ROC) analysis assessed differences and diagnostic performance.

RESULTS

18 patients (14 cases [11 progression and 3 Psp] and 4 controls [3 progression and 1 Psp]) provided evaluable disease. For all patients, HF was significantly elevated with progression (1.44 ± 0.8; N=14) compared to Psp (0.31 ± 0.3; N= 4; P=0.01). HV was not different (P=0.10). No difference in HV or HF was observed between Cases and Controls (P> 0.42). Use of HF yielded an AUROC of 0.96 with an optimal cut off of 0.74, to differentiate progression from Psp.

CONCLUSION

At mRANO presumed progression HF with FMISO PET/MRI accurately distinguishes tumor progression from neuroinflammatory Psp, irrespective of prior pembrolizumab immunotherapy. The incorporation of FMISO PET/MRI in larger prospective therapeutic clinical trials in patients with glioblastoma is underway and likely to improve response assessment criteria.
NIMG-60. SUBTYPING GLIOBLASTOMA FROM JOINT CLUSTERING OF IMAGING AND GENOMIC DATA
Authors: Guo Jun , Fathi-Kazerooni Anahita , Toorens Erik , Akbari Hamed , Yu Fanyang , Matsumoto Yuji , Sako Chiharu , Mamourian Elizabeth , Shinohara Russell , Koumenis Constantinos , Verginadis Ioannis , Bagley Stephen , Morrissette Jennifer , Binder Zev , Brem Steven , Mohan Suyash , Lustig Robert , O’Rourke Donald , Ganguly Tapan , Bakas Spyridon , Aboian Mariam , Nasrallah MacLean , Davatzikos Christos
Published: November 2024

PURPOSE

To comprehensively unravel the heterogeneity of glioblastoma, we developed a subtyping method using integrated imaging and genomic data.

METHODS

We assembled a retrospective cohort of 571 IDH-wildtype glioblastoma patients, obtaining pre-operative multi-parametric MRI (T1, T1-GD, T2, T2-FLAIR, DSC, DTI) scans (available for 462 patients) and targeted next-generation sequencing (NGS) data (available for 355 patients). We extracted 971 radiomic features from these MRI scans, selecting 12 significant dimensions through L21-norm minimization guided by 13 key driver genes from the five most frequently altered pathways in glioblastoma compared to healthy controls (RB1, P53, MAPK, PI3K, and RTK). Subtypes were identified using a joint clustering approach that integrated radiomics and genomics.

RESULTS

Our method identified three glioblastoma subtypes with distinct risk levels: high-risk (subtype 1), medium-risk (subtype 2), and low-risk (subtype 3), each characterized by their differential overall survival outcomes (Kaplan-Meier analysis, p < 0.05). The intensities of axial diffusivity in enhancing tumor regions and radial diffusivity in non-enhancing cores increased across three subtypes. All subtypes shared a common tendency for more frequent mutation co-occurrence pattern in [TP53,RB1] but exhibited unique molecular characteristics. For example, subtype 1 displayed a relatively high frequency of co-occurring mutations in [TP53,KDR] and [NOTCH2,MDM4]; subtype 2 had six co-occurring pairs [TP53,KDR], [PTPN11,NF1], [RB1,FUBP1], [PTEN,CIC], [PTEN,KRAS], and [NOTCH2,CDKN2A]; subtype 3 showed six co-occurring pairs [PTPN11,NF1], [PDGFRA,NF1], [NTRK1,NOTCH2], [MET,ATRX], [KRAS,KDR], and [FGFR2,DNMT3A] plus four significant patterns of mutual exclusivity in [TP53,PTPN11], [TP53,EGFR], [EGFR,RB1], and [EGFR,NF1].

CONCLUSION

Our study discovered distinct glioblastoma subtypes, revealing complex patterns and structures across multiple data modalities without relying on prior clinical assumptions. This is promising to help enhance the precision of diagnosis and treatment of glioblastoma.
NIMG-71. T2 RELAXIVITY AND DIFFUSION TENSOR METRICS IN THE PREDICTION OF PROGRESSION-FREE SURVIVAL IN NON-RECURRENT HIGH GRADE GLIOMA
Authors: Rulseh Aaron , Zajickova Heidrun , Vymazal Josef
Published: November 2024

High grade glioma (HGG) is the most common primary brain tumour; we aimed to evaluate T2 relaxivity and diffusion tensor imaging (DTI) metrics in the prediction of progression-free survival. Seventy-two non-recurrent HGG subjects (IDH: MUT=10, Unknown=20) followed at our institution after surgery and combined chemo-radiotherapy were included. All data used were prior to progression as per RANO criteria; only the first 2 years of follow up was included in the analyses. T2 relaxation rates (1/T2) were calculated voxel-wise assuming mono-exponential decay. Diffusion data were corrected from two opposite phase encode acquisitions and DTI metrics evaluated included FA, MD, p, q, and L1. Whole- and half-brain (ipsilateral/contralateral) masks were generated by brain extraction and registration; data extracted from these masks were analyzed using python 3.8 with the exception of numerous histogram features extracted using fsl tools. Radiomics features were also extracted using the pyradiomics package. The lofo-importance package was used for feature selection. A multi-level approach was used to reduce the initial 32,000 MRI features to a final number of 443; from these, the 50 highest-ranked features were used further. Within-subject feature engineering was then performed including 1–4 step forward and backward lag, lag difference, as well as area, maximum, mean and cumulative sum. Non-MRI features included available demographic, histological and treatment-related data. A LightGBM classification model was used for the prediction of progression within 90 days; the data were grouped by subject, such that each subject was present only in training or testing datasets. Hyperparameters were tuned using randomized search cross validation, and the final model using 5-fold cross validation reached a mean ROC-AUC of 0.89. Our results show the potential of quantitative MRI features derived from qualitatively unremarkable images within the progress-free interval to identify subjects at risk of imminent progression.
NIMG-85. RADIATION DOSE IS ASSOCIATED WITH CHANGE IN MAGNETIC RESONANCE FINGERPRINTING PROPERTIES OF ANATOMICALLY DISTINCT REGIONS OF INTEREST IN GLIOBLASTOMA MULTIFORME PATIENTS
Authors: Lee Joan , Arsenault Theodore , Gongala Sree , Hodges Tiffany , Ma Dan , Newton Herbert , Badve Chaitra , Vempati Prashant
Published: November 2024

Magnetic Resonance Fingerprinting (MRF) is an investigational imaging technique that provides spatially-resolved quantification of tissue properties, in contrast to qualitatively weighted conventional MR imaging. Intentional sequential variation of acquisition parameters throughout the MRF acquisition produces a unique quantitative signal timecourse for each tissue, which generates a spatial “fingerprint” for individual voxels. This study applies MRF to quantitatively correlate radiation dose with MR signal intensity changes, specifically T1, T2, and M0 maps across regions of interest (ROIs) that are involved in cognitive speed and processing. Three patients who underwent radiation therapy for resected glioblastoma multiforme participated in this study. MRF scans were conducted at pre-radiotherapy (pre-RT), mid-radiotherapy (mid-RT), and post-radiotherapy (post-RT) timepoints. ROIs (bilateral hippocampi, amygdalae, dorsolateral prefrontal cortices, and corpus callosum) were contoured and radiation dose to the ROI contours at mid-RT and post-RT timepoints were obtained using MIM treatment planning software (MIM Software, Beachwood, OH). Spearman’s rank correlation test was conducted in MATLAB (MATLAB R2024a, Natick, MA) for mean radiation dose to ROIs against MRF T1 relaxation time, T2 relaxation time, and M0 proton density. Mean radiation dose exhibited statistically significant correlation with absolute changes from pre-RT to post-RT T1 relaxation time, T2 relaxation time, and M0 proton density values across the ROIs. Mid-RT scans showed intermediate changes, suggesting a progressive alteration in tissue characteristics with accumulating radiation dose. The hippocampus and amygdala received lower radiation doses than other ROIs and exhibited less pronounced changes in T1, T2, and M0 values. These results demonstrate a novel application of MRF in quantitative characterization of imaging changes in anatomically distinct ROIs. The correlation between radiation dose and absolute changes in MRF signal values from pre-RT to post-RT MRF scans reflect progressive changes as a result of radiation exposure.
NIMG-88. EVALUATION OF DIFFUSION AND PERFUSION MRI FEATURES FOR DIFFERENTIATING RECURRENT BRAIN METASTASES AND RADIATION NECROSIS
Authors: Shao Guowen , Sanvito Francesco , Kim Won , Ellingson Benjamin , Yao Jingwen
Published: November 2024

BACKGROUND

Brain metastases (BM) are a frequent and serious complication of cancer. Differentiating between BM and radiation-induced necrosis (RN) after radiotherapy remains challenging. Diffusion-weighted imaging (DWI) derived apparent diffusion coefficient (ADC) maps and perfusion-weighted imaging (PWI) derived relative cerebral blood volume (rCBV) have the potential to distinguish between BM and RN. Despite the potential of these imaging modalities, previous studies have been limited by the absence of histopathological confirmation. In this study, we utilized a patient cohort that underwent stereotactic biopsy as part of their Laser Interstitial Thermal Therapy (LITT) following suspicious radiographic progression. This allowed us to evaluate the efficacy of ADC and rCBV imaging features with histopathological validation.

METHODS

In this study, 29 patients underwent MRI scans (3 with 1.5T, 26 with 3T) prior to LITT. Pathology confirmed 11 patients with BM and 18 with RN. Regions of interest (ROIs) in the contrast-enhanced lesion and T2 hyperintensity lesion were identified using post-contrast T1-weighted images and fluid-attenuated inversion recovery (FLAIR) images. Mean values and histogram-based features (standard deviation, 10%, 90%) of lesion volume, ADC, and rCBV within tumor ROIs were compared between the BM and RN using the Wilcoxon rank-sum test.

RESULTS

Our findings indicated that the mean values of ADC in the enhancing and non-enhancing lesion ROIs did not significantly differ between BM and RN patients. However, in the contrast-enhanced lesion regions, we observed a significant difference in the standard deviation of rCBV (p<0.05), and the 90th percentile value of rCBV also suggested potential differences between BM and RN (p=0.069). In the T2 hyperintensity lesion regions, lesion volume (p<0.05) and the mean of rCBV (p<0.05) show significant differences between BM and RN.

CONCLUSION

This study demonstrates the potential of using rCBV to aid in the clinical diagnosis of BM. Additionally, our findings indicate that T2 hyperintensity regions, beyond just contrast-enhancing lesions, may provide valuable information for differential diagnosis.
NCMP-03. ASSOCIATION OF PROGESTERONE CONTRACEPTION WITH TUMOR-RELATED VISUAL IMPAIRMENT IN PREMENOPAUSAL WOMEN WITH MENINGIOMA REFERRED FOR RADIATION
Authors: Bailey Morgan , Avery Chace , Pater Luke , Struve Timothy , Vatner Ralph , Frankart Andrew , Sittenfeld Sarah , Shiue Kevin , Yogendran Lalanthica , Chaudhary Rekha , Forbes Jonathan , Andaluz Norberto , Hagen Matthew , Kendler Ady , Rossi Rocco , Breneman John , Wang Kyle
Published: November 2024

BACKGROUND

Meningiomas express ER/PR, but hormonal risk is poorly characterized and not always considered. We hypothesized that hormonal contraceptives lead to tumor-related visual deficits in premenopausal women referred for radiation.

METHODS

We conducted a retrospective case-control study with primary endpoint visual deficit prior to radiation for meningioma in women age ≤55. Key risk factors determined included age, grade, skull base location, hormonal supplementation / contraception, and neurofibromatosis / prior radiation (NF/priorRT). Univariate and multivariate (including factors with p<0.05 on univariate) logistic regression was performed to analyze associations with visual deficit.

RESULTS

64 women (median age 46) receiving RT from 2012-2024 at a single academic institution were included. 45 (70%) had skull base tumors, 33 (52%) used estrogen or progesterone, and 23 (36%) used unopposed progesterone only, 15 specifically medroxyprogesterone acetate (Provera). Visual deficit was present in 35 patients (55%) and was independently associated with both skull base location (p=0.002, OR 11.5) and unopposed progesterone only use (p=0.008, OR 12) but not estrogen or progesterone use on multivariate analysis. Proportion with progesterone only use was 57% vs. 11% in patients with vs. without visual deficit (chi-sq p<0.001). In 5 with ER/PR testing, 3 were PR+ (all with visual deficits and history of medroxyprogesterone acetate) and 2 were PR- (neither with visual deficits nor hormone use). 13 women (20%) were actively using progesterone during RT. 17 women have been contacted at time of analysis, and 4 discontinued progesterone.

CONCLUSIONS

Progesterone increases risk for meningioma-related visual deficits in premenopausal women referred for radiotherapy, with a disproportionate number on Provera specifically. These data highlight the importance of age-appropriate counseling, consistent pathologic assessment of ER/PR status, and greater awareness of this issue amongst neurosurgeons and radiation oncologists.
NCMP-28. CASE REPORT: REFRACTORY MYASTHENIA GRAVIS FLARE INDUCED BY IMMUNE CHECK POINT INHIBITOR
Authors: Mokhtari Sepideh , Nguyen Kelly , Brohl Andrew , Jaffer Muhammad , Peguero Edwin , Gatewood Tyra , Vu Tuan
Published: November 2024

Immune checkpoint inhibitors (ICIs) are used for treating many types of cancers. Neurological adverse effects are uncommon (incidence of 7.2%), however these effects can have life-threatening outcomes when they occur. We present a case of a 78-year-old male with an existing diagnosis of Myasthenia Gravis (MG) with metastatic Basal Cell Carcinoma (BCC). He was diagnosed in 2015 with ocular myasthenia gravis that was acetylcholine receptor antibody positive. He developed an exacerbation with double vision, fatigue, and upper extremity weakness that resolved with intravenous immunoglobulin (IVIG). During this year, he also had a thymectomy and he was controlled on Mestinon. Five months after his MG diagnosis, he was diagnosed with BCC and was given Vismodegib, however he had metastasis to the spine and lymph nodes. Unfortunately, he had no other treatment options besides immunotherapy, thus Cemiplimab was given in 2023. Ten days after receiving his 2nd dose, he developed left eye ptosis, neck weakness, shortness of breath, dysphagia, bilateral lower extremity weakness, and urinary retention. Workup additionally revealed concern for myocarditis and myositis. He received IVIG and intravenous methylprednisolone initially, and then had maintenance IVIG 1g/kg every 2 weeks with a prednisone taper. Due to ongoing symptoms, he got Rituximab which improved most of the symptoms except for dysphagia. He then received Efgartigimod alfa-fcab (Vyvgart) but had no improvement in dysphagia. Later, plasmapheresis (PLEX) was trialed but there was a partial response. Unfortunately, he obtained a PEG tube for dysphagia and declined significantly due to disease progression and multiple medical comorbidities. Myasthenia Gravis crisis from ICI therapy is a rare but serious treatment complication. In addition to the challenging nature of treating this condition, our case highlights the importance of a comprehensive work up to include consideration of overlap syndromes, such as myocarditis and myositis as identified in this case.
NCOG-01. VOCATIONAL STATUS OF PATIENTS WITH GLIOMA AT 5 YEARS AFTER DIAGNOSIS
Authors: Figuracion Karl Cristie , Donald Christine Mac , Hunt David , McGranahan Tresa , Lewis Frances , Rockhill Jason , Goldberg Myron , Halasz Lia , Thompson Hilaire
Published: November 2024

BACKGROUND

Glioma (WHO grade 2-3) commonly affects adults, with a mean age at diagnosis of 41 years old. Given the demographic age of these brain tumor (BT) survivors, employment is the primary source of income, medical benefits, and financial stability. Unfortunately, job performance problems can occur at any time after diagnosis. This study aims to describe the vocational status and symptoms of these patients approximately five years following diagnosis.

METHODS

The study employed a cross-sectional cohort design among persons with glioma treated with radiation approximately 5 years from the original diagnosis. Vocational-Independence Scale was used to ascertain employment status. Patients were asked about their experience returning to work after treatment. Symptoms were measured using the MDASI-BT Module.

RESULTS

Thirty-nine participants completed the study. The median age was 44 years old (range 26-78). Nineteen were diagnosed with oligodendroglioma, 18 with astrocytoma. Thirty-seven (95%) were working full-time at the time of diagnosis. Approximately five years following diagnosis, only 49% of participants are employed, working at least 15 hours per week (n=19). The remainder are unemployed (n=15, 39%), in a volunteer position (n=2, 5.1%), or working <15 hours per week (n=3, 7.7%). Interview data suggest those who are unemployed (n=9, 23%), retired early (n=2, 5%), or had reduced roles (n=11, 28%), were unable to return to prior roles due to symptoms they were experiencing 1-2 years after treatment. The frequently reported symptoms were fatigue (n=29, 74%), sleep disturbance (n = 24, 62%), distress (n = 25, 64%), drowsiness (n = 26, 67%), sadness (n = 25, 64%), issues with speaking (n = 25, 64%), short-term memory issues (n=35, 90%), and difficulty with concentration (n=20, 74%).

CONCLUSION

In addition to financial stability, employment is a valuable contributor to the quality of life, maintenance of identity, and physical and emotional health. Future research should examine and evaluate interventions that promote the return to work or engagement in the community.
NCOG-05. HEALTH-RELATED QUALITY OF LIFE (HRQOL) IN THE PHASE 2 FIREFLY-1 (PNOC026) TRIAL OF THE TYPE II RAF INHIBITOR TOVORAFENIB IN RELAPSED/REFRACTORY (R/R) PEDIATRIC LOW-GRADE GLIOMA (PLGG)
Authors: Peipert John (Devin) , Baxter Patricia A , Yu Sandie , Oestreicher Nina , Zelt Susan , Driever Pablo Hernáiz , Bailey Simon , McCowage Geoffrey , Ziegler David S , Witt Olaf , Kang Hyoung Jin , Hassall Timothy E , Han Jung Woo , Franson Andrea T , Oren Michal Yalon , Toledano Helen , Larouche Valérie , Abdelbaki Mohamed S , Jabado Nada , Gottardo Nicholas G , Gerber Nicolas U , Whipple Nicholas S , Segal Devorah , Chi Susan N , Oren Liat , Tan Enrica E K , Mueller Sabine , Kilburn Lindsay B , Nysom Karsten , Khuong-Quang Dong-Anh , Landi Daniel B , van der Lugt Jasper , Leary Sarah E S , Perreault Sébastien , Waanders Angela J , Hargrave Darren , Kline Cassie , McKenna Chris , Manley Peter , Raju Sandya Govinda , Hansford Jordan R
Published: November 2024

BACKGROUND

Despite favorable long-term survival, ongoing disease and treatment-related morbidity substantially impact the HRQOL of patients with pLGG. Tovorafenib is a selective, CNS-penetrant, type II RAF inhibitor. Results from the ongoing FIREFLY-1 (NCT04775485) phase 2 study (Kilburn LK, et al. Nat Med. 2023) showed clinically meaningful responses and a manageable safety profile in pLGG. Vision remained stable or improved in 89% of evaluable patients with optic pathway gliomas (Nysom K, et al. Neuro-Oncol. 2023).

METHODS

FIREFLY-1 arm 1 patients 6 months–25 years of age with RAF-altered r/r pLGG received tovorafenib 420 mg/m2 weekly (600 mg max) in 28-day cycles. Exploratory measures included longitudinal assessment of PedsQL in patients ≥2 years of age. PedsQL 3.0 Cancer Module child self-reports Total Score and 8 subscales were used to assess HRQOL from 0 (worst)–100 (fewer problems/symptoms) (as of December 22, 2022) baseline (BL) to cycle 13 (C13) in patients ≥5 years of age.

RESULTS

For the PedsQL 3.0 Cancer Module, 51 completed self-reports at BL, and 32 at C13 due to continued attrition over time. Median Total Score was 81.5 (range: 46.3-100) at BL and 85.2 (range: 50-100) at C13. At C4, 16% worsened (decrease >10 points) and 11% improved (increase >10 points); by C13, 11% worsened and 33% improved. For Cognitive Problems, patients scored a median of 75 (range: 5-100) at BL and 85 (range: 20-100) at C13, with 11% and 26% improved at C4 and C13, respectively. A similar trend was seen with Nausea. Pain and Hurt remained even throughout (median: 87.5). Treatment Anxiety was not a major concern (median: 100, C1-C13); Procedural Anxiety improved over time (median: 58.3 BL; 79.2 at C13).

CONCLUSIONS

HRQOL generally remained stable, or improved, in the majority of patients with r/r pLGG during the first year of treatment with tovorafenib.
NCOG-09. ASSOCIATIONS OF COGNITIVE FUNCTION WITH BRAIN STRUCTURE, COMT GENOTYPE, AND PSYCHOLOGICAL FACTORS IN MELANOMA PATIENTS PRIOR TO ADJUVANT IMMUNE CHECKPOINT INHIBITOR THERAPY
Authors: Danielsen Josefine T , Zachariae Robert , Schmidt Henrik , Kallehauge Jepser F , Thomadsen Julie K , Wefel Jeffrey S , Wu Lisa M , Amidi Ali
Published: November 2024

BACKGROUND

Cancer-related cognitive impairment (CRCI) presents a significant concern in cancer patients. Yet, limited research addresses its prevalence and potential underlying risk factors in melanoma patients, including neurobiological, genetic, and psychological factors.

METHODS

We assessed cognitive functioning, cognitive complaints, brain gray matter (GM) properties, COMT genotype, and psychological factors (fatigue, anxiety, depression, insomnia severity, sleep difficulties, quality of life) in malignant melanoma patients (MMPs) before treatment with immune checkpoint inhibitors (ICIs) and compared with matched healthy controls (HCs). A total of 47 MMPs and 53 HCs were enrolled. Between-group differences were tested, and statistical associations between cognitive function and brain GM properties, COMT polymorphisms, and psychological factors were explored.

RESULTS

MMPs exhibited significantly lower levels of cognitive functioning compared with HCs across multiple cognitive tests (all p’s<.05), with a high prevalence of clinically significant CRCI (68.1% VS 26.4%). Analysis of GM properties revealed volumetric differences in the left cuneus between MMPs and HCs with MMPs having smaller volume compared to HCs. In MMPs but not in HCs, statistically significant associations were found between WAIS-IV Coding and right precentral cortical thickness, TMT-A and left inferior parietal cortical thickness, and BVMT-R Delayed Recall and right postcentral GM volume (all p’s<.01). COMT polymorphisms were associated with self-reported cognitive complaints but not with objective cognitive performance. Compared with HCs, MMPs reported higher levels of fatigue, anxiety, insomnia severity, and sleep difficulties, and lower levels of quality of life (all p’s ≤.009). Additionally, self-reported cognitive complaints in MMPs were associated with different cognitive test performances (all p’s<.05), fatigue (p<.001) and anxiety (p<.045).

CONCLUSIONS

These findings underscore the importance of comprehensive cognitive and psychological assessments in MMPs referred for adjuvant ICI therapy. Understanding the complex array of symptoms including CRCI in this population can inform tailored interventions to improve quality of life and treatment outcomes.
NCOG-12. TREATMENT AND MORTALITY OF PRIMARY BRAIN TUMORS: A SINGLE CENTER OBSERVATIONAL STUDY OF GLIOBLASTOMAS AND ASTROCYTOMAS
Authors: Santare John , Sosidko David , Dawyot Claire , Aiad Mina , Bhalala Harsh , Forget Elizabeth , Starner Sophia , Deeb Meriam , Wilson Melissa
Published: November 2024

Glioblastoma multiforme (GBM) is a WHO grade IV malignant tumor with a relatively poor prognosis (median survival of 15 months). Astrocytomas are WHO grade I-III tumors with a better prognosis than GBM; their median survival ranging from 2-10 years. We assessed the response to various mainstay treatment modalities in patients with GBM and astrocytoma, expecting to find that surgery and stereotactic radiation (SRS) treatment confer greater survival benefits than non-surgical and whole brain radiation (WBRT) options. We analyzed 108 patients at St. Luke’s University Health Network (SLUHN) who were previously diagnosed with a primary brain tumor consistent with GBM (90) or astrocytoma (18) prior to January 1, 2023. Mainstays of treatment were surgery with or without different radiation modalities (WBRT and SRS, and WBRT+SRS). Glioblastoma typically affected older patients (65.5), had mostly single lobe involvement (86.7%), and was predominantly located in the frontal (41.1%) and temporal lobes (37.7%). Astrocytoma was slightly younger (51.2), less often single lobe (72.2%), and mostly involved the frontal (44.4%), temporal (44.4%), and parietal lobes (33.3%). GBM found the greatest benefit from WBRT (without co-occurring SRS) with an increase of 16.4 months to 20.2 months (p=.789). Surgery, regardless of radiation status, appeared to provide the greatest benefit for patients with astrocytoma increasing average lifespan from 36.7 months to 53.6 months (p=.181). Patients with glioblastoma that underwent surgery also had increased survival of 18.2 months compared with nonsurgical patients at 12 months (p=0.097). While we were interested to see the impact these treatment modalities had on patient survival, our sample size was small and our results lacked statistical significance. Future studies with greater sample sizes would help determine whether statistical significance is correlated with meaningful clinical outcomes.
NCOG-15. CONNECTOME-BASED APPROACHES FOR PRESERVING COGNITIVE FUNCTION AND MINIMIZING DELIRIUM DURING GLIOMA RESECTION: A PILOT STUDY
Authors: Mut Melike , Fuchs Kathleen , Rosen Jordan , Donahue Joseph , Lunardi Nadia , Reon Brian , Zawar Ifrah , Schiff David
Published: November 2024

AIM

The surgical treatment of gliomas poses significant challenges due to the involvement of complex neural networks critical for cognitive functions. This study reviews the application of connectome-based approaches to minimize cognitive impairments and delirium during glioma resection, focusing on networks related to cognitive functions: the Default Mode Network (DMN), Dorsal Attention Network (DAN), Salience Network (SN), and Central Executive Network (CEN).

METHODS

Ten patients underwent surgery utilizing cloud-based connectomics software (Quicktome®), which maps the brain’s structural and functional connectivity. Preoperative MRIs with structural and functional connectome were performed for preoperative planning and intraoperative navigation. Preoperative neuropsychological assessments were conducted for elective cases. Only one patient was able to undergo awake craniotomy due to various medical, neurological and psychological limitations. Intraoperatively, with connectome-navigation guidance, a connectomics-based approach was conducted to preserve the networks. A semiquantitative analysis was performed as described (https://pubmed.ncbi.nlm.nih.gov/36719613). Pre- and postoperative (inpatient and 2 week follow up) RASS and NuDESC delirium screenings were performed, with long-term cognitive evaluations and repeat connectomics imaging planned.

RESULTS

Three out of ten patients presented with rapid functional deterioration and needed urgent surgical decompression had postoperative delirium. Connectome analysis showed involvement of cognition-related networks in these patients. Two out of 3 patients showed improvement in delirium scores at a two-week follow-up after tumor resection.

CONCLUSION

This pilot study suggests that factors such as acute presentation, emergency surgery, and tumor location involving and disrupting the DMN, SN, DAN, and CEN networks may contribute to early postoperative delirium. The study may pave the way for the efficacy of connectomics in preserving cognitive functions post-operatively, particularly when awake craniotomy is not possible. This approach holds promise for improving surgical outcomes, survival, and the quality of life for patients with gliomas by mitigating the cognitive impacts of tumor resection and postoperative complications.
NCOG-19. FUNCTIONAL OUTCOME AFTER RE-RESECTION OF TUMOR PROGRESSION, MIXED LESION OR TREATMENT-ASSOCIATED EFFECTS IN IRRADIATED DIFFUSE GLIOMAS (GRADE 2-4): IDENTIFYING CLINICAL AND RADIOLOGICAL DETERMINANTS
Authors: Kortman Maud , Kreek Maarten , de Jong Anouk , Flies Christina , Becker Aline , Dankbaar Jan-Willem , Robe Pierre , Verhoeff Joost , Snijders Tom
Published: November 2024

In cases of radiological progression in patients with irradiated diffuse gliomas, recurrence-resection is frequently performed. In our previous histological evaluation 19% of these re-resection cases were found to be due to treatment-associated effects (TAE). Limited literature substantiating which patients will benefit from surgery and which patients will deteriorate postoperatively is available. We aim to (a) describe the functional outcomes after re-resection of an irradiated diffuse glioma in adult patients; (b) compare early functional outcomes between patients with TAE versus progressive disease; (c) identify predictors of early functional outcome. In this single-center, retrospective, cohort study, we included consecutive adult patients with diffuse glioma who underwent first-line radiotherapy and, upon radiological progression, a re-resection. Re-resection tissue was classified histologically (based on mitosis presence/absence) and by the multidisciplinary tumor board as tumor progression, TAE or mixed lesion. The primary endpoint was the functional outcome 30 days postoperatively, expressed as the Karnofsky Performance Scale (KPS). Univariable and multivariable logistic regression were used to identify clinicoradiological predictors of KPS deterioration of any severity. Of 159 included patients, 41 (25.8%) experienced mild KPS deterioration (10 points) and 25 (15.9%) a clinically relevant KPS deterioration (20 or more). KPS improvement (10 points or more) occurred in 31 patients (19.4%). Histological diagnosis groups did not differ significantly in KPS outcome. Pre-operative steroid usage (any dose) was an independent predictor of KPS deterioration (OR 2.46, 95%CI 1.12-5.39, p=0.025). Analysis of pre-operative radiological determinants is in progress. In conclusion, in this large single-center cohort of diffuse gliomas undergoing re-resection with systematic clinical evaluation, clinically relevant deterioration after re-resection occurred in 15.9% of all patients. Risk of deterioration is comparable in all histological diagnosis groups. Pre-operative steroid usage was identified as predictor for deterioration (of any severity). These results may provide clinical guidance in identifying which patients will benefit from re-resection.