bluuebunny/crossref_metadata_2025 huggingface dataset:
NIMG-56. PHENOTYPIC ANALYSIS OF RADIO-PATHOMIC MAPS IN DE-NOVO GLIOBLASTOMA IDENTIFIES DIFFERENCES IN BEVACIZUMAB TREATMENT RESPONSE
Authors: Bobholz Samuel , Lowman Allison , Duenweg Savannah , Winiarz Aleksandra , Kyereme Fitzgerald , Cochran Elizabeth , Connelly Jennifer , Mueller Wade , Agarwal Mohit , Banerjee Anjishnu , LaViolette Peter
Published: November 2022

PURPOSE

Bevacizumab (Bev) treatment for recurrent glioblastoma ceases tumor angiogenesis, which changes tumor appearance on Gd enhanced T1-weighted imaging. However, little is known about how non-angiogenic portions of tumor are affected by Bev. Therefore, this study tested the hypothesis that patients with specific tumor appearance phenotypes outside contrast enhancement, as identified using autopsy tissue-based radio-pathomic maps, would show differences in survival benefit from Bev treatment.

METHODS

Previously published methods were used to create machine learning models that generate whole-brain maps of cellularity (Cell), extracellular fluid (ECF) and cytoplasm (Cyt) using glioma autopsy tissue aligned to the patient’s last MRI as ground truth (Bobholz et al. 2022). These maps were then generated for an independent dataset of glioblastoma patients (n=80) using baseline imaging acquired prior to treatment. Patients were then graded for qualitative characteristics of the non-enhancing margin, with phenotypes including Well-Circumscribed (WC) patients with no abnormal tissue surrounding the core, Hypercellular Front (HF) patients with areas of hypercellularity extending from the core, Necrotic Front (NF) patients with areas of necrosis extending from the core, and Hybrid Front (HYF) patients with both hypercellular and necrotic presence beyond the enhancing region. Kaplan Meier analysis was then used to compare survival outcomes between patients who did and did not receive Bev treatment within each phenotype to assess differences in treatment efficacy.

RESULTS

Only patients with NF or HYF showed significant survival increase with bevacizumab treatment (HR=2.35, p=0.02; and HR=2.45, p=0.03, respectively), with no significant or trending difference in survival observed for WC and HF patients.

CONCLUSION

Radio-pathomic phenotypes identify patients who show the greatest survival benefit from Bev treatment, which could be used to direct clinical decision-making.
NIMG-59. EVALUATION OF THE RESPONSE ASSESSMENT CRITERIA IN NEWLY DIAGNOSED AND RECURRENT GLIOBLASTOMA
Authors: Youssef Gilbert , Rahman Rifaquat , Bay Camden , Wang Wei , Lim-Fat Mary Jane , Arnaout Omar , Bi Wenya Linda , Cagney Daniel , Chang Yuh-Shin , Cloughesy Timothy , DeSalvo Matthew , Ellingson Benjamin , Gerstner Elizabeth , Castro Luis Nicolas Gonzalez , Guenette Jeffrey , Kim Albert , Lee Eudocia , McFaline-Figueroa J Ricardo , Potter Christopher , Reardon David A , Huang Raymond , Wen Patrick Y
Published: November 2022

BACKGROUND

We sought to compare the Response Assessment in Neuro-Oncology (RANO), modified RANO (mRANO), and immunotherapy RANO (iRANO) in a large population of patients with newly diagnosed (nGBM) and recurrent (rGBM) glioblastoma.

METHODS

Bidimensional measurements of enhancing disease and FLAIR sequence evaluation were performed by two independent readers on brain MRIs of consecutive patients with IDH-wildtype nGBM and rGBM treated at a single institution. Discrepancies were evaluated by a third reader. Dates of disease progression (PD) were identified using RANO, mRANO, iRANO, and other response assessment criteria variations. Spearman’s correlations between PFS and OS were calculated using iterative multiple imputations for censored observations.

RESULTS

526 nGBM and 580 rGBM cases were included. Spearman’s correlations were not significantly different between RANO and mRANO in nGBM (0.69 [95% CI 0.62 to 0.75] vs. 0.67 [0.60, 0.73]) and rGBM (0.48 [0.40, 0.55] vs. 0.50 [0.42, 0.57]). Evaluation of FLAIR did not improve the correlation in patients who received antiangiogenic therapy. Acquisition of confirmation scans was associated with increased correlation only when PD was identified within 12 weeks of completion of radiation in nGBM. The use of the post-radiation MRI as a baseline was associated with increased correlation compared to use of the pre-radiation MRI in nGBM (0.67 [0.60, 0.73] vs. 0.53 [0.42, 0.62]). The correlation with iRANO was similar to RANO and mRANO among 98 patients with nGBM and 175 patients with rGBM who received immunotherapy.

CONCLUSIONS

RANO and mRANO demonstrated similar correlations between PFS and OS. The evaluation of FLAIR can be omitted, while confirmation scans were only beneficial in nGBM in the first 12 weeks after completion of radiation. There was a trend in favor of the post-radiation MRI as the baseline scan in nGBM. The use of iRANO criteria did not add a significant benefit in patients who received immunotherapy.
NIMG-66. CANNY EDGE DETECTION ALGORITHM FOR QUANTITATIVE DIFFERENTIATION BETWEEN DIFFUSE AND CIRCUMSCRIPT GLIOMA GROWTH PATTERNS ON MRI
Authors: Thiele Frederic , Weller Jonathan , Katzendobler Sophie , Trumm Christoph , Thon Niklas , Tonn Joerg-Christian
Published: November 2022

BACKGROUND

Lower grade gliomas show heterogenous appearance on T2-weighted MRI. Some tumors grow diffusely along axonal structures whereas others distort adjacent brain tissue through local mass effect. The diagnostic, therapeutic and prognostic implication of differential growth patterns on MRI remain unknown and are difficult to assess quantitatively.

METHODS

A web-based application allowing for image preprocessing and providing a comprehensive edge detection tool by means of quantifying tumor border delineation on T2-weighted images based on the canny edge detection algorithm was developed. A sigma value between 1 and 100 determined the threshold where tumor borders where not detected anymore, with 1 equating to the lowest threshold and thus detection of all edges contained in the image. Two experienced faculty members assigned sigma values to axial T2 images of a random sample of 20 WHO grade 2 astrocytomas, IDH-mutant and 1p/19q-non-codeleted. The sigma values were then compared with a binary, subjective rating by the same faculty staff according to the perceived predominant growth pattern (diffuse versus circumscript) of each glioma.

RESULTS

When subjectively categorizing tumors binarily (diffuse versus circumscript), there was moderate interrater variability between observers (cohen’s kappa=0.6). Raters agreed in 16 of 20 cases, terming 7 gliomas unanimously diffuse and 9 gliomas circumscript. In 4 cases, the raters opinions diverged. The sigma values differed significantly between diffuse and circumscript tumors in both raters (rater 1, p=0.002; rater 2, p=0.018). For rater 1, the mean sigma difference between diffuse and circumscript tumors was 10.7 and 9.3 for rater 2. The mean overall sigma value was 13.3 for rater 1 and 18.7 for rater 2 (p=0.005).

CONCLUSION

Edge detection algorithms can be efficiently applied on MRI scans and are highly accurate in differentiating diffuse from circumscript gliomas. Objectification demands defining imaging criteria for diffuse and circumscript appearance of lower grade gliomas on MRI.
NIMG-71. REAL-WORLD ASSESSMENT OF IDH1 INHIBITOR IVOSIDENIB IN IDH MUTANT LOWER GRADE GLIOMAS – THE JOHNS HOPKINS EXPERIENCE
Authors: Puri Sushant , Shi Jessica , Blair Lindsay , Blakeley Jaishri , Laterra John , Kamson David
Published: November 2022

BACKGROUND

As clinical trials are ongoing to establish the role of IDH inhibitors in the treatment of lower-grade gliomas, long-term data is not yet available. Hence, here we share our real-world experience with off-label ivosidenib.

METHODS

In this single-institution retrospective analysis, we included chemo/radiotherapy-naïve, gadolinium non-enhancing WHO Grade 2/3 IDH1-mutated astrocytomas (AS) and oligodendrogliomas (OG) that were treated with off-label ivosidenib for ≥ 5 months for active tumor growth. We performed semi-automated volumetric analyses on T2/FLAIR images in 3D Slicer v4.11. Annualized growth-rates before and on ivosidenib were calculated, and time to initial response (reduction in growth-rate), growth arrest (growth-rate ≤ 0cc/yr) and shrinkage in patients with confirmatory data available (≥ 1 confirmatory follow-up scan). Progression-free survival (PFS), at 6 and 12 months were assessed (progression defined as ≥ 40% volume increase per RANO 3D).

RESULTS

We studied 12 patients (2F, median age 46yrs [range 26-60], 8/4 AS/OG; 4 grade 3) with an average of 17.2 months (5-33) follow-up on ivosidenib. Eleven (92%) patients had confirmatory data. Response rate was 82% (9/11) with median time of 4.9 (3.5-6.3) months to initial response and 11.1 (4.1-21.4) months to growth arrest. Growth arrest occurred 3-folds faster in OG than in AS (4.2±0.8 vs.12.5±4.2 months, p=0.014). Mean best response was 11.4±12.8% volume reduction, after a median of 12.1±9.3 months on ivosidenib. Mean PFS was 24.4 months (CI95%18.8-29.9). PFS-6 and PFS-12 were 91%, and 88% (7/8), respectively. No major toxicity was noted. There were 3 discontinuations, two for radiographic progression, one for increased seizure frequency.

CONCLUSIONS

In this small cohort, ivosidenib was well-tolerated with a high response rate; however, responses took up to a year to become evident and seemingly faster in oligodendrogliomas. These data suggest that ivosidenib might require more than 5 months of commitment and volumetrics may help the detection of early response.
NIMG-73. PREDICTING PERITUMORAL GLIOBLASTOMA INFILTRATION USING QUANTITATIVE MAGNETIC RESONANCE FINGERPRINTING RADIOMICS
Authors: Zhao Walter , Deng Shengwen , Chen Yong , Kazerooni Anahita Fathi , Davatzikos Christos , Couce Marta , Wang Xiaofeng , Sloan Andrew , Ma Dan , Badve Chaitra
Published: November 2022

PURPOSE

Standard clinical magnetic resonance (MR) imaging of glioblastoma (GB) cannot identify malignant infiltration into the peritumoral non-enhancing region. This work implements quantitative MR fingerprinting (MRF) based radiomics to predict infiltrative regions of GB.

METHODS

Pre-operative MRF T1 and T2 maps along with multiparametric MR (mpMR) images (T1w, T2w, T1w-Gd, FLAIR, and ADC) from GB patients (n = 10) were analyzed. All subjects had histologically confirmed sites of non-enhancing peritumoral infiltration as identified by intra-operative 5-ALA fluorescence-guided tissue resection. These locations (n = 40) were manually annotated on pre-operative FLAIR by a board-certified neuroradiologist and labeled as “infiltration” (INF). For each patient, another FLAIR region ( > 3 cm from the enhancing tumor margin) was identified and labeled as “edema” (ED). Following image co-registration, 693 handcrafted radiomic voxel-based features were extracted from confirmed infiltration (INF) and edema (ED) voxels using a 3D 5x5x5 voxel sliding kernel. Feature selection was performed using the minimum redundancy maximal relevance (MRMR) algorithm, then INF and ED voxel features were used to train two cross-validated binary support vector machine (SVM) models for voxel-wise infiltration prediction: 1) MRF only model and 2) combined MRF and mpMRI model. Following MRMR selection, the combined model included features from T1, T1w, T2w, T1w-Gd, FLAIR, and ADC images. Model performance was evaluated using one withheld subject with multiple known infiltration sites. Balanced test accuracy and receiver operating characteristic (ROC) curve analysis was used to evaluate classification performance.

RESULTS

The MRF only and combined model achieved balanced test accuracies of 77.87% and 73.21% and AUCs of 0.91 and 0.97, respectively.

CONCLUSIONS

This study demonstrates that MRF-based radiomic features can predict GB tumor infiltration with high accuracy and provide complementary value to standard clinical MRI features. Our results indicate the high potential of employing MRF to guide personalized GB treatment strategies.
NIMG-75. REPEATABILITY OF MANUAL SEGMENTATION OF GLIOBLASTOMA ON MRI - QUALITY ASSURANCE FOR A QUANTITATIVE MRI RADIOMICS REPEATABILITY STUDY
Authors: Chan Edward , Martin Philip , Brighi Caterina , Pillay Sugendran , Holloway Lois , Metcalfe Peter , Koh Eng-Siew
Published: November 2022

BACKGROUND

Accurate and repeatable imaging segmentation of glioblastomas is important for effective radiomics modelling of clinical endpoints such as survival and treatment response. Manual and even automated segmentation are prone to variability. The primary objective of this study is to evaluate the repeatability of manually segmented glioblastomas on MRI which will serve as quality assurance for a quantitative MRI radiomics repeatability study.

METHODS

MRI datasets from n=19 patients with recurrent glioblastoma extracted from The Cancer Imaging Archive (RIDER Neuro MRI dataset) comprised of test-retest scans (time-point 1 and 2) acquired on average 2 days apart. The MRI protocol consisted of dynamic contrast-enhanced 3D FLASH using 0.1mmol/kg Magnevist intravenous injection at 3cc/second (TR 3.8ms, TE 1.8ms, 5mm slices, flip angle 25°), contrast-enhanced 3D FLASH (TR 8.6ms, TE 4.1ms, 1mm slices, flip angle 20°) and contrast-enhanced 3D FLAIR (TR 6000ms, TE 353ms, TI 2200ms, 1mm slices, flip angle 180°) on a 1.5T magnet. Contrast enhancing tumour from n=38 MRI scans were manually segmented by a radiologist slice by slice using contrast-enhanced 3D FLASH T1-weighted images on MIM software (v6.9.5). All cases at time-point 1 were contoured before contouring commenced for time-point 2 in the same order. Repeatability and spatial overlap was assessed by Dice similarity coefficient (DSC), Hausdorff distance (HD) and centroid shift.

RESULTS

A comparison of time-point 1 and 2 demonstrated the median DSC for n=19 cases was 0.84 (interquartile range 0.07), mean HD was only 0.1cm and mean centroid shift was 0.2cm.

CONCLUSION

High repeatability and spatial overlap of manually segmented contrast enhancing regions of recurrent glioblastoma were achieved on serial MRI. This substantiates a high level of repeatability which forms a core component of an MRI radiomics platform under development.
NIMG-77. MAGNETIC RESONANCE IMAGING AND AMINO ACID POSITRON EMISSION TOMOGRAPHY IN DIFFERENTIATING TUMOR RECURRENCE FROM RADIATION NECROSIS IN HIGH GRADE GLIOMAS
Authors: Sahu Arpita , Mathew Ronny , Dasgupta Archya , Ashtekar Renuka , Puranik Ameya , Sridhar Epari , Sahay Ayushi , Chatterjee Abhishek , Shetty Prakash , Moiyadi Aliasgar , Gupta Tejpal
Published: November 2022

BACKGROUND AND PURPOSE

Differentiating tumor recurrence (TR) from radiation necrosis (RN) in high grade glioma (HGG) following radiotherapy can be challenging. The ability of conventional magnetic resonance imaging (MRI) to differentiate TR from post-therapeutic effects is often limited. Multiparametric advanced MRI (perfusion) and positron emission tomography (PET) with amino acid tracers, specifically 18F-Fluoroethyl-Tyrosine (FET) can provide relevant additional information on tumor metabolism, which allows for a more accurate diagnosis to differentiate tumor recurrence from radiation necrosis in high grade gliomas.

MATERIALS AND METHODS

Prospective analysis of 62 lesions in 62 patients with HGG who underwent both MRI and FET-PET imaging within three weeks intervals was done independently by a neuroradiologist and nuclear medicine physician. The study was conducted in a tertiary care oncology center between July 2018 and August 2021. Manually segmented regions of interest were placed over the areas of maximum enhancement/suspicion on MRI and FET uptake, which were used to calculate the relative cerebral volume (rCBV) and tumor to background ratios, respectively. Definitive diagnosis (TR versus RN) was made on clinico-radiological follow-up or histopathological report (wherever available).

RESULTS

Out of the 62 lesions that were studied, 46 and 16 had TR and RN, respectively. The sensitivity and specificity for determination of TR in HGG with conventional MRI were 98% and 62.5% respectively, while with FET-PET it was 91% and 87.5% respectively. The PPV , NPV and accuracy for MRI were 88%, 91% , 89% , while for FET-PET it was 95%, 78% and 90% respectively. A combination of MRI and PET parameters (mean target-to-background ratio), demonstrated an increase in diagnostic accuracy to 97%.

CONCLUSION

Cumulative imaging with MRI and FET-PET offers a multiparametric assessment of glioma recurrence that is correlative and complimentary, with higher accuracy and clinical value.
NIMG-79. SPATIALLY MAPPED PREDICTIONS OF EVOLVING TUMOR RESPONSE OF HIGH-GRADE GLIOMA VIA IMAGE-DRIVEN MATHEMATICAL MODELING
Authors: Farhat Maguy , Hormuth David , Langshaw Holly , Bronk Juliana , Curl Brandon , Yadav Divya , Upadhyay Rituraj , Elliot Andrew , Goldman Jodi , Erickson Lily , Talpur Wasif , Lee Maggie , Yankeelov Thomas , Chung Caroline
Published: November 2022

Timely treatment response assessment of high-grade gliomas (HGG), crucial for driving therapeutic decisions, remains a challenge; as HGGs exhibit variable response to treatment within different sub-regions. Current assessment using multi-parametric MRI (mpMRI) depends largely upon follow-up (FU) imaging timepoints for achieving diagnostic certainty, which delays therapeutic interventions. Mathematical modeling (MM) of tumor growth and treatment response can provide spatiotemporal information of HGG evolution in response to treatment, thus allowing for prospective early identification of resilient tumor subregions. AIMS: We aim to initialize and calibrate an image-driven MM framework to forecast HGG response, both at the end of chemoradiotherapy (CRT) and at 3-month FU.

METHODS

In a prospective clinical study, weekly mpMRIs (post-contrast T1, T2 FLAIR, and diffusion) for patients with HGG receiving CRT were used to describe tumor extent and cellularity. This data collected from baseline (pre-CRT) till week 3 (mid-CRT) was used to calibrate a model family to forecast HGG response for each individual patient at week 6 (end CRT) and at 3-month FU.

RESULTS

Error between the forecasted and observed responses was assessed globally using percent error in tumor volume, and at the local level by Pearson correlation coefficient (PCC). In an initial cohort of 11 patients, our MM framework predictions had a percent error in tumor volume of less than 8.6% and at week 6 RT and less than 20% at 3 months FU. The PCCs were 0.84 at week 6 RT and 0.72 at 3 months FU.

CONCLUSIONS

Temporal consistency across this early evaluation of the model predictions show promise of image-driven MM for HGG response forecasting to guide timely personalized assessment and adjustment of treatment.
NIMG-91. DOTATATE PET/MR-GUIDED POSTOPERATIVE MANAGEMENT IN WHO-2 MENINGIOMA: ACTIVE SURVEILLANCE BASED ON PET/MR EVIDENCE OF GROSS TOTAL RESECTION
Authors: Knisely Jonathan , Chang Se Jung , Kim Sean H , Haghdel Arsalan , Roytman Michelle , Madera Gabriela , Magge Rajiv , Liechty Benjamin , Stieg Philip , Pannullo Susan , Schwartz Theodore , Cisse Babacar , Brandmaier Andrew , Juthani Rupa , Noch Evan , Fine Howard , Pisapia David , Ramakrishna Rohan , Karakatsanis Nicolas , Osborne Joseph , Lin Eaton , Ivanidze Jana
Published: November 2022

BACKGROUND

MRI, the standard of care (SOC) for meningioma radiotherapy planning, lacks sensitivity for postoperative small volume disease and osseous or parenchymal invasion. BN003 (NCT03180268) randomizes patients with WHO-2 meningiomas and MRI-determined GTR to observation or 60 Gy IMRT to the resection bed. More sensitive and specific imaging biomarkers may improve clinical outcomes in meningioma by limiting unnecessary radiation of normal tissues and improving radiation targeting. [68Ga]-DOTATATE is a PET radiotracer targeting somatostatin receptor 2 (SSTR2), a highly sensitive and specific meningioma biomarker. We developed a dedicated DOTATATE brain PET/MRI protocol allowing meningioma differentiation from post-treatment change, using SUV analysis and Patlak modeling. Our prospective observational trial (NCT04081701) has imaged over 90 patients with meningioma. This IRB-approved study evaluated PFS in patients with WHO-2 tumors and postoperative GTR by [68Ga]-DOTATATE PET/MRI who were managed solely with active surveillance. We hypothesized that the PFS of patients with GTR by PET/MRI managed with active surveillance would be higher than for patients with MRI-determined GTR, using NRG-BN003’s observation arm (randomized trial comparing observation to fractionated radiotherapy) as a reference standard.

METHODS

92 patients with SSTR2-positive brain neoplasms were enrolled between 9/2019 and 5/2022 and imaged according to our previously published protocol. 8 patients met inclusion criteria (WHO-2 meningioma & postoperative PET/MR GTR) and were followed with SOC MRI. Kaplan-Meier survival analysis was performed.

RESULTS

5/8 subjects (62.5%) were women; the mean age was 67 years. MRI follow-up data were available for a mean of 19.75 months (range: 7-38 months). One subject (12.5%) progressed at 21 months; the remainder remain progression-free. Kaplan-Meier analysis demonstrated 3-year PFS to be 80%, which is substantially higher than the reported 3-year PFS of 69% in the literature.

CONCLUSIONS

[68Ga]-DOTATATE PET can improve the specificity of imaging-based assessment of the extent of resection of WHO-2 meningiomas.
NIMG-92. DOTATATE PET/MR-GUIDED POSTOPERATIVE RADIOTHERAPY IN SUBTOTALLY RESECTED WHO-2 MENINGIOMA: EVALUATION OF PROGRESSION-FREE SURVIVAL IN A PROSPECTIVE COHORT
Authors: Knisely Jonathan , Chang Se Jung , Kim Sean H , Haghdel Arsalan , Roytman Michelle , Madera Gabriela , Magge Rajiv , Liechty Benjamin , Pisapia David , Noch Evan , Fine Howard , Pannullo Susan , Juthani Rupa , Ramakrishna Rohan , Schwartz Theodore , Stieg Philip , Cisse Babacar , Brandmaier Andrew , Karakatsanis Nicolas , Osborne Joseph , Lin Eaton , Ivanidze Jana
Published: November 2022

BACKGROUND

Current postoperative management recommendations for meningioma lack Level 1 evidence. NRG-0539 (NCT00895622) treated recurrent WHO-1 and newly diagnosed and completely resected (by postoperative MRI) WHO-2 meningiomas with postoperative fractionated radiotherapy to 54 Gy, but 3 year PFS remained below 60%. MRI, the standard of care (SOC) for meningioma radiotherapy planning, lacks sensitivity for postoperative small volume disease and osseous or parenchymal invasion. More sensitive and specific imaging biomarkers are needed to improve RT guidance and thereby clinical outcomes in meningioma. [68Ga]-DOTATATE is a PET radiotracer targeting somatostatin receptor 2 (SSTR2), a highly sensitive and specific meningioma biomarker. We developed a dedicated DOTATATE brain PET/MRI protocol allowing meningioma differentiation from post-treatment change, using SUV analysis and Patlak modeling. Our prospective observational trial (NCT04081701) has imaged over 90 patients with meningioma. This IRB-approved study evaluated PFS in patients with WHO-2 tumors who did not achieve GTR by [68Ga]-DOTATATE PET/MRI, managed with PET/MR guided RT, hypothesizing that the PFS of patients with STR by PET/MRI managed with PET/MR guided RT would be higher than for comparable patients enrolled on NRG 0539.

METHODS

92 patients with SSTR2-positive brain neoplasms were enrolled between 9/2019 and 5/2022 and imaged according to our previously published protocol. 7 patients met inclusion criteria (WHO-2 meningioma; postoperative PET/MR with residual activity) who underwent PET/MR-guided RT, followed with SOC MRI. Kaplan-Meier survival analysis was performed.

RESULTS

5/7 subjects (71%) were women; the mean age was 50.7 years. MRI follow-up data were available for a mean of 18.7 months (range: 16-24 months). All patients remain progression-free at this time; Kaplan-Meier analysis demonstrated 2-year PFS to be 100%, which is substantially higher than reported PFS in this clinical population using standard-of-care MRI-guided RT.

CONCLUSIONS

[68Ga]-DOTATATE PET/MR-guidance can improve PFS following postoperative RT in subtotally resected WHO-2 meningiomas.
NIMG-95. IMAGING CHARACTERISTICS OF POLYMORPHOUS LOW GRADE NEUROEPITHELIAL TUMOR (PLNTY)
Authors: Gordon Camille , Quintana Javier , Gonzalez-Gomez Ignacio
Published: November 2022

Polymorphous low grade neuroepithelial tumor of the young (PLNTY) was first described in 2017 in the pathology literature based on the unique histologic and molecular characteristics. Most of the patients in the original article presented with seizures linked to a temporal lobe lesion. We report a pediatric patient who presented with seizures found to have a lesion which was consistent with PLNTY on biopsy. We will review the radiology and pathology of this case with a quick review of the characteristic findings of PLNTY.
NIMG-106. WHAT’S BEHIND TSPO PET LABELLING: DIGGING FOR THE HISTOLOGICAL, CELLULAR AND MOLECULAR CORRELATES
Authors: Weidner Lorraine , Lorenz Julia , Dekorsy Franziska , Quach Stefanie , Ruf Victoria , Bartos Laura , Hau Peter , Tonn Joerg-Christian , Bartenstein Peter , von Baumgarten Louisa , Brendel Matthias , Albert Nathalie , Riemenschneider Markus
Published: November 2022

TSPO is frequently upregulated in glioblastoma. Despite its use as an imaging biomarker for PET in glioma, the interpretation is challenging due to the heterogeneity of cell populations that could contribute to the TSPO-PET signal. We therefore dissected TSPO labelling in connection with the underlying histopathological and molecular features in biopsy samples from glioma patients. Comparing regions of high and low TSPO-PET signal in 58 patients, we assessed TSPO protein expression and expression of cell differentiation markers by use of immunohistochemistry on consecutive sections and by multiplex stains. Our results suggest that apart from microglia and macrophages the glial tumor cells relevantly contribute to the overall TSPO signal in glioma patients. To identify hallmarks and GO terms associated with TSPO labelling/expression we next performed RNAseq in 33 patients. Using DESeq2 followed by FUMA and Reactome as well as GSEA with normalized counts, we identified three TSPO-dependent functional clusters, i.e. apoptosis/DNA repair, extracellular matrix organization and immune system. On the DNA level, we analyzed the TSPO promoter by direct bisulfite sequencing suggesting that a loss of TSPO methylation may mechanistically contribute to the TSPO overexpression observed in high-grade gliomas. Exceeding our investigations on glioma biopsies we stained tissue microarrays (130 individuals) for TSPO that cover a broader spectrum of both human brain pathologies (13 different entities) and non-neoplastic tissues (14 different brain regions). We here found a high degree of heterogeneity of TSPO expression between entities and regions. Merging this information with TSPO-PETs from respective patients/brain regions allows to generate a map of TSPO expression in healthy and diseased brain for clinical use. Altogether, our approach of integrating histological, molecular and imaging data will provide unique insights into TSPO-PET enrichment patterns which may help to better understand and to comprehensively describe the clinical relevance of this novel imaging biomarker.
NIMG-110. FIRST CLINICAL EXPERIENCE WITH BELZUTIFAN IN VON HIPPEL-LINDAU DISEASE-ASSOCIATED CNS HEMANGIOBLASTOMA
Authors: Dhawan Andrew , Peereboom David , Stevens Glen
Published: November 2022

The authors present two cases of von Hippel-Lindau (VHL) disease-associated hemangioblastomas in the central nervous system (CNS) treated with the newly-approved HIF-2α inhibitor, belzutifan. The first case is that of a 31-year-old female with confirmed pathogenic germline VHL mutation who presented with multiple hemangioblastomas diagnosed at 25 years of age. The patient was first managed surgically with resection of three posterior fossa hemangioblastomas but re-presented five years later with headaches and paresthesias of the fingers. She was found to have interval progression of an intramedullary cervical lesion that was monitored radiographically, as well as a new cerebellar lesion. A cerebellar lesion was resected, but the cervical hemangioblastoma was not. Four months after surgery, the patient was started on belzutifan, which she tolerated without issue, and a brisk reduction in peri-lesional edema was observed in the cervical spine and remaining intracranial foci after 2 months of treatment. The second patient is a 30-year-old male with familial VHL disease, initially diagnosed after the discovery of a retinal hemangioblastoma at age 10. He was found to have multiple cerebellar hemangioblastomas, treated with resection at age 24 and then with stereotactic radiosurgery (SRS) at age 25, complicated by radiation necrosis. Imaging surveillance revealed disease progression at age 29 for which he was started on belzutifan. Follow-up imaging after three one month cycles revealed a reduction in perilesional edema and reduced lesion mass effect. Both patients tolerated belzutifan well, with only anemia and fatigue. We highlight in this report our initial experience and early imaging findings associated with belzutifan used for VHL disease-associated CNS hemangioblastomas.
NCMP-02. RENAL CELL CARCINOMA WITH METASTASIS TO THE CHOROID PLEXUS
Authors: Kim Emily , Nadeem Danial , Nguyen James , Ammar Hussam
Published: November 2022

BACKGROUND

Intraventricular brain tumors make up only 0.9–4.5% of all cases of metastatic brain cancer.1 Involvement of the choroid plexus (CP) is even rarer with only a handful of documented cases. 2,3 Here we describe a case of bilateral multifocal metastasis to the choroid plexus appearing 10 years after nephrectomy in a male with stage IV renal cell carcinoma (RCC). CASE PRESENTATION: Our patient is a 74-year-old male with stage IV RCC diagnosed in 2006 and treated with radical nephrectomy and immunotherapy in 2011. In 2020, he presented to the emergency department with altered mental status. Brain magnetic resonance imaging (MRI) revealed an enhancing hemorrhagic lesion in the trigone of the right lateral ventricle (LV) and nodular thickening in the center of the right LV and trigone of the left LV, suggestive of metastatic disease. In 2021, the patient developed refractory seizures, and serial MRIs showed disease progression. He underwent several craniotomies with pathology confirming metastatic clear cell carcinoma, consistent with a renal primary. In 2022, the patient again presented with altered mental status. MRI revealed new avidly enhancing subcentimeter solid nodules in the CP of both LVs consistent with metastatic disease. Per the wishes of the family, palliative measures were pursued, and the patient was discharged home.

CONCLUSION

RCC can reappear several years after nephrectomy. 4 Metastatic RCC appears to have a unique propensity to spread to the ventricular system and the CP, which indicates late progression of disease. 1,5,6 While surgery may be viable if tumor burden is low, therapeutic options are limited in the advanced disease stages, as in our patient. Palliative care should be offered early to maximize remaining quality of life.
NCMP-09. IMPACT OF TUMOUR CHARACTERISTICS AND CANCER TREATMENT ON CEREBROVASCULAR MORTALITY AFTER GLIOMA DIAGNOSIS: EVIDENCE FROM A POPULATION-BASED CANCER REGISTRY
Authors: Brennan Paul , Jin Kai , Figueroa Jonine , Sudlow Cathie
Published: November 2022

BACKGROUND

Brain tumour patients have the highest stroke mortality rates among cancer types, but the factors associated with fatal stroke remain unknown. We aimed to examine to what extent brain tumour grade, a marker of biological aggressiveness, tumour size and cancer treatment are associated with cerebrovascular mortality among patients with malignant glioma, the most common and aggressive brain tumour.

METHODS

We conducted a retrospective, observational cohort study using the US National Cancer Institute’s state and regional population-based cancer registries (NCI SEER). We identified adult patients with a diagnosis of malignant glioma (2000 to 2018, Nf72,916). The primary outcome of interest was death from cerebrovascular disease. Cox regression modelling estimated the associations with cerebrovascular mortality of tumour grade, tumour size and treatment (surgery, radiotherapy, chemotherapy), calculating hazard ratios (HR) adjusted for these factors as well as for age, sex, race, marital status and calendar year.

RESULTS

Higher grade (Grade IV vs Grade II: HR=2.47, 95% CI=1.69-3.61, p< 0.001) and larger brain tumours (size 3 to < 6 cm: HR=1.40, 95% CI=1.03 -1.89, p< 0.05; size ≥ 6 cm: HR=1.47, 95% CI=1.02-2.13, p< 0.05 compared to size < 3cm) were associated with increased cerebrovascular mortality. Having cancer treatment was associated with decreased risk (surgery: HR= 0.60, p< 0.001; chemotherapy: HR=0.42, p< 0.001; radiation: HR= 0.69, p< 0.05). However, among patents surviving five years or more from their cancer diagnosis radiotherapy was associated with higher risk of cerebrovascular mortality (HR 2.73, 95% CI 1.49-4.99, p< 0.01).

CONCLUSIONS

More aggressive tumour characteristics are associated with increased cerebrovascular mortality, and treatment was associated with lower risk within 5 years of diagnosis. Radiotherapy increased risk of fatal cerebrovascular outcome five-years after cancer diagnosis. Further research is needed to better understand the long-term cardiovascular consequences of radiation therapy, and whether the consequent risk can be mitigated.
NCMP-17. PLASMA EXCHANGE FOR IMMUNE CHECKPOINT INHIBITOR INDUCED ACUTE DEMYELINATING POLYNEUROPATHY REFRACTORY TO IVIG
Authors: Kolli Avinash , Pina Yolanda , Peguero Edwin , Gatewood Tyra , Mokhtari Sepideh , Verma Neha
Published: November 2022

The use of immune checkpoint inhibitors in the treatment of cancer has gained prominence due to their effectiveness. Unfortunately, neurological immune-related adverse events represent a growing problem in neuro-oncology practice. Many of these cases are rare and their diagnoses and management can be challenging. We present a case of a 69-year-old male with urothelial carcinoma status post left nephrectomy who developed bilateral lower extremity weakness that began following his first dose of Atezolizumab. After three doses, his lower extremity weakness worsened to the point where he could not walk. A NCV study was performed and was consistent with acute demyelinating polyneuropathy. A cervical MRI (Magnetic Resonance Imaging) showed an enhancing lesion at C6-C8. He was treated with three days of intravenous methylprednisolone every six hours for three days followed by three days of 0.4gm/kg IVIG. He regained his ability to walk after IVIG treatment. The enhancing lesion noted on MRI remained. Three weeks after the first IVIG treatment, he declined significantly, redeveloping symptoms where he could not ambulate and required assistance to use the toilet. He had no lower extremity reflexes and had loss of proprioception of his hands. He was scheduled for another IVIG infusion at .4gm/kg followed by a dose of IVIG .6gm/kg the next day, and then four more days of IVIG .25gm/kg. His lower extremity weakness and difficulty walking remained so he was arranged for plasmapheresis x five cycles. His weakness improved, reflexes returned, and he no longer had proprioceptive loss of his hands. A cervical MRI obtained one month after plasma exchange showed resolution of the C6-C8 enhancing lesion. He is now ambulating with a cane. This case highlights the effectiveness of plasma exchange in a case that was refractory to IVIG
NCMP-23. A UNIQUE CASE OF CHOREIFORM DYSKINESIAS IN A PATIENT WITH METASTATIC RENAL CELL CARCINOMA
Authors: Jaffer Ali-Musa , Graves Andrew , Verma Neha , Mokhtari Sepideh , Pina Yolanda
Published: November 2022

BACKGROUND

Dyskinesias in cancer patients present a diagnostic challenge to clinicians. Etiologies can include paraneoplastic syndromes, chemotherapy related side effects, or primary movement disorders. This is a unique case of choreoathetotic dyskinesias in a patient with metastatic renal cell carcinoma while undergoing treatment with cabozantinib in combination with either placebo or the investigational drug CB-839 (telanglenastat) while on the clinical trial MCC 19671.

RESULTS

We present a 69 year old gentleman with a history of metastatic renal cell carcinoma who developed choreoathetotic dyskinesias eleven months after enrolling in a phase 2 blind study MCC 19671. His CSF paraneoplastic panel and MRI brain imaging were unremarkable. His symptoms abated with stopping his clinical trial drug, after which he withdrew from the trial and opted to continue cabozantinib alone. Unfortunately he developed worsening dyskinesias a week after restarting cabozantinib which was then stopped permanently. He was treated with prednisone and plasma exchange with improvement in his symptoms. Unfortunately, he passed away due to progression of disease two months later.

CONCLUSIONS

This case highlights the first case of choreiform dyskinesias most likely associated with CB-839/cabozantinib, since the patient’s symptoms significantly improved upon stopping the medications. The patient could also have had a novel paraneoplastic-associated antibody which has not been discovered yet. As the investigation into novel chemotherapeutic agents for malignancies continues, the incidence of drug related dyskinesias will need to be monitored.
NCOG-06. CASE REPORT: EXTENDED REMISSION OF HER2-POSITIVE BREAST CARCINOMA WITH BRAIN METASTASES AND LEPTOMENINGEAL DISEASE FOLLOWING INTRATHECAL AND SYSTEMIC TRASTUZUMAB
Authors: Gregory Timothy , Loghin Monica
Published: November 2022

Leptomeningeal disease (LMD) in breast cancer carries a poor prognosis with median overall survival (OS) of 3-4 months. Recent series have indicated prolongation of OS up to 10-13 months in HER2-positive breast LMD treated with intrathecal (IT) trastuzumab. Here we present an unprecedented long-term survival with clinical, radiographic, and molecular response for more than 10 years on IT trastuzumab. A 52-year-old woman presented in 12/2011 with newly diagnosed LMD with previously treated brain and systemic metastases. Her initial diagnosis of HER2-positive left intraductal carcinoma in 5/2005 was treated with bilateral mastectomy, adjuvant chemotherapy with doxorubicin and cyclophosphamide followed by paclitaxel and trastuzumab, as well as local RT. She was disease free until 10/2009 when she presented with headache due to two brain metastases involving the vermis and right occipital lobe. She underwent resection and SRS, followed by chemotherapy with capecitabine and lapatinib. In 12/2010 she received further RT to the posterior fossa for recurrent disease and later required gamma knife to a left occipital metastasis. In 8/2011 she developed back pain and cauda equina syndrome. MRI spine revealed LMD from T11- L2. CSF studies showed > 500 protein, 17 WBCs and malignant cells consistent with her breast primary. Both cerebellar metastasis and cells in the spinal fluid showed over-expression and amplification of HER2neu. She completed RT to the lower spine, and in 1/2012 began IT trastuzumab with continuation of capecitabine and lapatinib. There was progressive LMD in 2/2012 prompting escalation of IT trastuzumab dosing and addition of IT topotecan with systemic trastuzumab. In 10/2019, CSF showed rare malignant cells and IT topotecan was switched to cytarabine while continuing IT trastuzumab, now with durable remission ever since. The low LMD burden and aggressive therapeutic approach, including IT trastuzumab, combined with radiation and systemic therapy may explain the exceptional survival.
NCOG-39. DISCOVERY OF CLINICAL AND DEMOGRAPHIC DETERMINANTS OF SYMPTOM BURDEN IN PRIMARY BRAIN TUMOR PATIENTS USING NETWORK ANALYSIS AND UNSUPERVISED CLUSTERING
Authors: Bergsneider Brandon , Vera Elizabeth , Gal Ophir , Christ Alexa , King Amanda , Acquaye Alvina , Choi Anna , Leeper Heather , Mendoza Tito , Boris Lisa , Burton Eric , Lollo Nicole , Panzer Marissa , Penas-Prado Marta , Pillai Valentina , Polskin Lily , Wu Jing , Gilbert Mark , Armstrong Terri , Celiku Orieta
Published: November 2022

BACKGROUND

Precision health approaches to managing symptom burden in primary brain tumor (PBT) patients are imperative to improving patient outcomes and quality of life. Network Analysis (NA) identifies complex symptom co-severity patterns across large patient cohorts. Unsupervised clustering unbiasedly stratifies patients into clinically relevant subgroups based on symptom patterns. This is the first study to use NA and unsupervised clustering to explore PBT patients’ clinical and demographic determinants of symptom burden.

METHODS

Symptom severity data reported using the MDASI-BT from a two-institutional cohort of 1,128 PBT patients was analyzed. Gaussian Graphical Model networks were constructed for the entire cohort and for subgroups identified by unsupervised clustering. Network characteristics were analyzed and compared using permutation-based statistical tests.

RESULTS

NA on the entire cohort revealed that the majority of PBT patients experience symptoms on four core dimensions that drive overall symptom burden: cognitive, physical, focal neurologic, and affective. These dimensions substantially overlap with factor groupings defined during initial construct validation of the MDASI-BT. Fatigue/drowsiness scored the highest in all network centrality measures, indicating a pivotal role in the symptom experience. Unsupervised clustering identified four patient subgroups: PC1 (n = 683), PC2 (n = 244), PC3 (n = 92), and PC4 (n = 109). Moderately accurate networks could be constructed for PC1 and PC2, but not for PC3 and PC4 due to their small size. The PC1 network closely resembles the all-patient network, and these patients have the highest interference scores among the subgroups with fatigue/drowsiness as the primary driver. PC2 represents an older subgroup in which cognitive symptoms drive symptom burden.

CONCLUSIONS

This novel study identified clinically relevant subgroups of patients with unique symptom burdens. With further validation, our approach may inform more personalized and effective symptom management by identifying symptoms to prioritize for targeting in individual patients.
NCOG-48. A PROSPECTIVE LONGITUDINAL NEUROCOGNITIVE OUTCOME STUDY IN PATIENTS TREATED WITH CAR-T-CELL THERAPY AT 6 MONTHS
Authors: Zarrella Giuliana , Lavoie Mitchell , Gardner Melissa , Johnson Patrick , El-Jawahri Areej , Parsons Michael
Published: November 2022

INTRODUCTION

Chimeric Antigen Receptor T-cell (CAR-T) therapy carries risk of significant neurocognitive function (NCF) toxicities. Longer term NCF outcomes have yet to be reported. The goal of the current study was to assess NCF prospectively in patients undergoing CAR-T.

METHODS

Adult patients undergoing CAR-T participated in NCF testing with a cognitive clinical trial battery (CTB) at baseline and 6 months after treatment. Group change on each test and on the composite score (CTBC) was examined with paired t-tests and individual change, defined as +/-1 SD on CTBC, was also reported.

RESULTS

Forty patients (Mage=62.45, 63% male, 97% Non-Hispanic or Latino) completed NCF testing at baseline, and 28 patients completed NCF measures 6 months post-CAR-T (20 complete CTBC, 8 partial CTB, completed virtually). At baseline, 13/40 patients (33%) had significant impairment in NCF (CTBC Z-score < -1.5), and 2/20 (10%) were impaired at follow-up. In the 20 individuals with pre- and 6-month post-CAR-T CTBC scores, there was no significant change (t(19)=-0.926; p=0.366). Examination of each individual test score also showed no changes (immediate memory (t(26)=-0.084; p=0.934), delayed memory (t(26)=-0.207; p=0.837), memory recognition (t (26)=-0.062; p=0.951) executive function (t(18)=-0.447, p=0.660), and verbal fluency (t(27)=-0.035, p=0.972)). Individual analyses of CTBC at follow-up found the number of patients with meaningful decline=1 (5%), improvement=2 (10%), and no change=17 (85%) on CTBC.

CONCLUSION

Although CAR-T can be associated with acute change in NCF, this prospective longitudinal study showed stable cognitive performance 6 months after treatment. To our knowledge, this is the longest prospective longitudinal study of NCF in CAR-T survivors. This study is limited in that some subjects completed NCF testing virtually at follow-up, limiting the sample size for unconfounded comparison of performance. Future work will examine longer term outcomes and subjective cognitive function in CAR-T survivors.
EXTH-05. TOWARD 100% CLINICAL EFFICACY FOR TUMOR-TREATING FIELDS
Authors: Carlson Kristen , Tuszynski Jack
Published: November 2022

In vitro and in animal models of various tumor cell types, empirical data suggest tumor-treating fields (TTFields) can attain 100% efficacy, with two pre-conditions: 1) Delivering sufficient electric field strength to the target tumor cells, and 2) Changing the direction of the imposed electric field such that intra-cellular structures at any angle with respect to the field see the required efficacious field strength. Requirement #2 reflects empirical findings as well as prevailing theories of TTFields’ mechanism of action, which center on mitosis disruption via energy imparted to polarizable intracellular structures aligned with the field. We tried various trial curve-fits to TTFields empirical dose-response curves. Quadratic formulae yield a close fit, resembling well-known radiotherapy linear-quadratic (LQ) curves and suggesting a connection between the mechanisms of the two treatment modalities: F98 (rat glioma): -16.3271x2 - 0.664019x+100 (R2=0.9995); MDA-MB-231 (human breast cancer): -9.64922x2 + 2.96348x + 100 (R2=0.9999); H1299 (human non-small cell lung carcinoma): -12.0515x2 - 1.58272x + 100 (R2=0.9993); B16 (mouse melanoma): -83.8066x2 + 47.4537x + 100 (R2=0.9954). We extrapolate these fits to predict the approximate required field strength seen at the target cells for 100% efficacy: F98: 2.45 V/cm; MDA-MB-231: 3.4 V/cm; H1299: 2.8 V/cm; B16: 1.4 V/cm. Alternatively, the LQ fits may not reflect the extrapolated high amplitude range for which data is lacking. Under two assumptions, 1) intracellular structures are randomly oriented in vivo, and 2) only two changes of TTFields direction are used, as is the current clinical practice, then extrapolating the dose-response curves predicts that infinite field strength is required for 100% efficacy, since some intracellular structures must be oriented at 90 degrees to the imposed field and the cosine of 90 degrees is zero. Adding a third TTFields direction, not necessarily orthogonal to the plane of the other two directions, can solve this problem.