bluuebunny/crossref_metadata_2025 huggingface dataset:
INNV-09. SURGICAL STRATEGIES FOR OLDER PATIENTS WITH GLIOBLASTOMA
Authors: Barak Tanyeri , Hwang Lee , Chen Justin , Jin Lan , Miyagishima Danielle , Yalcin Kanat , Ogilvie Shahiba , Antonios Joseph , Theriault Brianna , Huttner Anita , McGuone Declan , Lifton Nathan , Blondin Nicholas , Corbin Zachary , Zhang Yawei , Gunel Murat , Erson-Omay Zeynep , Fulbright Robert , Tabar Tanyeri , Moliterno-Gunel Jennifer
Published: November 2021

OBJECTIVE

Though image-guided surgery with intraoperative magnetic resonance imaging (IoMRI) is associated with higher extent of resection, we aimed to determine the clinical outcome of its use, compared to other less time-consuming intraoperative ultrasound (IoUS), in this patient population.

METHODS

Clinical data of 221 consecutive patients aged 70 years or older, who underwent surgical resection for GBM with intraoperative ultrasonography (IoUS) alone or combination of IoMRI + IoUS at Yale New Haven Hospital and Memorial Sloan Kettering Cancer Center were retrospectively reviewed. Variables were analyzed, and comparative analyses were performed, including predictors of overall survival.

RESULTS

The addition of IoMRI was not superior to IoUS alone in terms of overall survival (OS) (HR=0.85, 95% CI 0.49-1.47; P= 0.56) or Karnofsky Performance Score (KPS) at 6 weeks postoperatively (OR=0.51, 95% CI 0.22-1.15; P= 0.102). On the contrary, the length of surgery (LOSx) was significantly longer (P< 0.0001) in the IoMRI group. Postoperative complications were significantly less in the IoUS-only group (OR=0.17, 95% CI 0.3-0.46; P=0.002) and in patients who had a preoperative KPS score of 70 or higher (OR=0.092, 95% CI 0.018-0.47; P=0.004). Patients with relatively lower preoperative KPS scores (< 70) showed significant clinical improvement at 6 weeks postoperatively (P=0.0002). Patients with postoperative complications were more likely to have lower KPS scores at 6 weeks postoperatively (OR=0.30, 95% CI 0.10-0.89; P= 0.031), while increased extent of resection was associated with improved KPS scores at 6 weeks postoperatively (OR=2.171, 95% CI 1.22-3.87; P= 0.009).

CONCLUSION

Aggressive management with surgical resection should be considered in older patients with GBM, even those with relatively poor KPS scores. The use of IoMRI in this patient population does not appear to yield any survival benefit over IoUS but instead significantly prolongs the length of surgery, increasing the risk for potential postoperative complications.
INNV-18. EFFECT OF DURATION OF TUMOR TREATING FIELDS THERAPY ON CELLULARITY DISTRIBUTIONS BEYOND T1W MRI CONTRAST ENHANCING MARGIN AT AUTOPSY IN GLIOMA PATIENTS: PRELIMINARY RESULTS
Authors: Bobholz Samuel , Lowman Allison , Brehler Michael , Sherman John , Duenweg Savannah , Kyereme Fitzgerald , Connelly Jennifer , Cochran Elizabeth , Mueller Wade , Banerjee Anjishnu , LaViolette Peter
Published: November 2021

Tumor treating fields (TTFields) are thought to disrupt the cell division process in glioma. This study uses autopsy tissue samples from patients recruited for brain donation to determine whether TTFields treatment duration and usage affects cellularity distributions beyond the gadolinium contrast enhancing region on T1-weighted (T1w) magnetic resonance imaging (MRI). At autopsy, 43 tissue samples from 18 patients who had undergone TTFields treatment (inclusion criteria: >50% compliance and 25-day duration) were collected from brain slices sectioned in-line with slices from the patients’ final MRI prior to death. Nuclei were segmented on the digitized hematoxylin and eosin (HE) stained tissue samples, which were then used to compute cell count across the slides. Tissue was then aligned to the patient’s final MRI scan prior to death using a custom in-house software, where manually defined control points were used to compute a nonlinear transform to warp the tissue to match the MRI. Histogram features including mean, median, 90th percentile, variance, and skewness, were computed from the cellularity distributions within regions outside the traditional tumor margin defined by T1w contrast enhancement for each subject. General linear models were fit to assess the effects of TTFields usage (percent of day) and duration (in days) on each histogram feature, controlling for age, overall survival, and time between TTFields treatment and death, as well as time between MRI acquisition and death. Longer TTFields treatment duration and overall survival was associated with significantly decreased skewness in the non-enhancing cellularity distributions (p< 0.05) while associations with other metrics remained statistically insignificant. These preliminary results in a small patient cohort suggest that TTFields duration may reduce the presence of high cellularity tails in the non-contrast enhancing distributions. Additional research in larger patient populations is warranted to better understand these findings given the number of confounding factors.
INNV-27. AN INNOVATIVE VIRTUAL MULTI-INSTITUTIONAL, MULTIDISCIPLINARY NEURO-ONCOLOGY TUMOR BOARD: THE NIH-NOB EXPERIENCE DURING THE COVID-19 PANDEMIC
Authors: Rogers James , Acquaye Alvina , Ikiddeh-Barnes Ukeme , Benson Kaitlyn , Boris Lisa , Akindona Funto , Frederico Stephen , Jammula Varna , Kim Yeonju , Timmer Michael , Aboud Orwa , Avgeropoulos Nicholas , Burton Eric , Cachia David , Camphausen Kevin , Colman Howard , Dixit Karan , Drappatz Jan , Dunbar Erin , Forsyth Peter , Komlodi-Pasztor Edina , Mandel Jacob , Lee Eudocia Quant , Ranjan Surabhi , Lukas Rimas , Salacz Michael , Smith-Cohn Matthew , Snyder James , Wooley Joseph , Chaudhry Huma , Theeler Brett , Tsien Christina , Smirniotopoulos James , Butman John , Chittiboina Prashant , Heiss John , Zaghloul Kareem , O’Donnell Kayla , Quezado Martha , Aldape Kenneth , Raygada Margarita , Armstrong Terri , Gilbert Mark , Penas-Prado Marta
Published: November 2021

BACKGROUND

The American Academy of Neurology Institute and Society for Neuro-Oncology recommend multidisciplinary tumor board (MTB) meetings as a quality metric in neuro-oncology. With the COVID-19 pandemic resulting in travel restrictions, we expanded our existing MTB by transitioning to a virtual format that maintained our commitment to providing consultation for primary CNS tumor cases. This transition permitted participation by neuro-oncology teams from over 30 Brain Tumor Trials Collaborative (BTTC)/National Cancer Institute-Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) centers across the United States. Here, we describe results from opening our MTB remotely to these teams.

METHODS

We retrospectively reviewed records from remote MTB meetings held between April 2020 and March 2021. To gauge the impact of our MTB on clinical management, we administered a brief survey querying BTTC members.

RESULTS

Twenty-eight providers presented 41 cases during 24 virtual MTB meetings (range: 1-4 cases per meeting). Two cases (5%) were presented only for educational value. Approximately half (54%) of the cases discussed dealt with diagnosis/management of an NCI-CONNECT rare CNS tumor. During MTB discussions of the 39 cases seeking diagnosis/management recommendations, 32% received clinical trial recommendations, 10% were suggested to enroll in the NCI Neuro-Oncology Branch (NOB) Natural History Study (NCT02851706), 17% received a recommendation to obtain central neuropathology review, and 100% received recommendations for further disease management. Most BTTC survey respondents (83%) found these recommendations impactful in the management/treatment of their presented case or generally useful/informative for their clinical practice.

CONCLUSION

We describe the feasibility and utility of an innovative virtual multi-institutional MTB. These novel remote meetings allowed for discussion of complex neuro-oncology cases and recommendations from experts, particularly important for those with rare CNS tumors. Our study’s findings during the COVID-19 pandemic of the value of providing remote access to MTBs should apply post-pandemic.
INNV-34. NEURO NARRATIVES: AN AUTOETHNOGRAPHIC ACCOUNT OF EXPERIENCING RESILIENCE WITH A BRAIN TUMOR
Authors: Costa Christina Naegeli
Published: November 2021

The current research uses autoethnography as a method to share my experience as a brain tumor patient. In this piece, I reference poems from the day of my diagnosis through my surgery, recovery, and following treatment to demonstrate the thematic factors that allowed me to cope and experience positive emotions as an oncology patient. Results included the factors of trust in medical care, utilizing social support, finding meaning and purpose, and self-love and gratitude. The implications of these factors in relation to resilience structures and discourses to better serve other oncology and chronic illness patients are discussed.
INNV-42. ACTIVE VS RECEPTIVE MUSIC LISTENING THERAPY IN BREAST CANCER PATIENTS USING ARMCAN
Authors: Sengupta Soma , Rebola Claudia , Shatz Rhonna , Koehler Abigail , Rothman Yehudit , Mahammedi Abdelkader , Kirschner Michelle
Published: November 2021

Secondary brain tumors and neurocognitive damage from radiation or chemotherapy are often the commonest neuro-oncological problems in cancer. Breast cancer is the most commonly diagnosed cancer in women, with approximately 2 million women diagnosed in 2018.1 The 10-year survival rate for women diagnosed with breast cancer is 78% (World Cancer Research Fund, 2018). Although the 10-year survival rate is high, women who undergo chemotherapy can experience neurocognitive impairment resulting in significant effects of their cognitive functioning.2 Chemo related dysfunction is known as “chemobrain” or “chemofog.” Chemobrain can result in difficulty with attention, daily activities of living, and memory. This impacts people’s livelihoods and affects their general well-being. Current research on the topic of chemobrain in breast cancer survivors is minimal. However, this study aims to reduce the post-chemotherapy outcomes of chemobrain through the use of interactive versus receptive music. “Brain Fog” or chemobrain is the basis of significant neurological morbidities in the breast cancer population. It causes difficulty in people being able to even carry out activities of daily living. We have developed a prototype “ARMCan—a music software application to help breast cancer patients with “brain fog.” We are conducting a pilot feasibility study to beta test this interactive application which will promote executive function recovery in breast cancer patients with chemobrain.
PATH-02. TWO CASES WITH MULTIPLE HYBRID NERVE SHEATH TUMORS WITH ERBB2 MUTATIONS
Authors: Choi Yoon Jae , Perez-Rosendahl Mari
Published: November 2021

Hybrid nerve sheath tumors are new disease entity incorporated in WHO classification of tumors of the central nervous system 2016 version that includes benign peripheral nerve sheath tumors with combined features of more than one conventional type. Ronellenfitsch et al recently reported one case with ERBB2 D769Y mutation with good clinical response to lapatinib in 2020. We report two cases with imaging findings of multiple peripheral nerve sheath tumors with pathology proven hybrid nerve sheath tumors with ERBB2 mutations. Patient 1 has neurofibroma/schwannoma hybrid nerve sheath tumor with ERBB2 D769Y mutation and patient 2 has plexiform neurofibroma/schwannoma hybrid nerve sheath tumor with ERBB2 V777L mutation. Both of our patients have similar clinical features with adult-onset multiple peripheral nerve sheath tumors without other systemic features of neurofibromatosis type1 or vestibular schwannomas or family history. Hybrid nerve sheath tumors are newly recognized disease and more than half of the cases have multiple peripheral nerve sheath tumors, suggestive of tumor syndrome. Patients with multiple peripheral nerve sheath tumors without systemic features of neurofibromatosis type1 or vestibular schwannomas should be screened for genetic/molecular tests including ERBB2 mutation that might provide treatment options for these patients.
PATH-06. DNA METHYLATION PATTERNS AND IMMUNE MICROENVIRONMENT IN CYSTICGBM
Authors: Chen Zhihua , O’Meally Denis , Frankhouser David , Shahmanyan Mari , Tang Biao , Yao Shu , Rockne Russell C
Published: November 2021

As a rare subtype of glioblastomas (GBM), genetic features in cystic GBM (cGBM) are still largely unknown. We have previously identified a series of active T cell subsets and positive cytokines/chemocytokines in the cystic fluid of cGBMs, including IFN-gamma, IL-2, IL-6, IL-8, TNF-alpha, and MIP-1alpha/beta. This study aimed to evaluate the prognosis of cGBM through DNA methylation patterns and immune microenvironment transcriptional signatures. IvyGAP, EGA and fresh samples from a prospective Chinese cohort were collected to investigate genomic signatures, immune microenvironment and survival outcomes in patients with cGBMs. Gd T1-weighted, T2-weighted, T2-Flair, DWI or ADC images were used to classify cGBM. 143 cases with MGMT/IDH record were used to compare survival time and genomic analysis. Among the three cohorts, Kaplan-Meier analysis showed cystic features have benefit to overall survival (OS). Moreover, cyst feature is the forth factor (HR=0.65, [95% CI 0.42, 1.01]) of survival after IDH, MGMT and Stupp therapeutic regimen. Interestingly, in IDH-wild/MGMT-unmethyled subtype, cGBM patients have longer OS vs noncystic GBM (noncGBM) patients (HR = 0.57, [95% CI 0.33, 0.99]). Compared to noncGBM, cGBM patients have hypomethylation state both in whole gene region and cpG islands. Ivygap database showed between cystic and noncystic group, in sub-structures such as CT (cellular tumor region), CTpan (pseudopalisading cells around necrosis) and CTpnz (perinecrotic zone) there are differential gene expressions and different enrichment pathways. GSEA analysis showed within cGBM group, many gene sets associated with immune function activation such as TRL1/2/3/7 and IFN pathways. These results suggest that cysts of GBM may be associated with hypomethylation status an activated immune microenvironment which is associated with longer survival and may define a unique subgroup of GBM with intrinsically different biology and prognosis.
PATH-13. INTRAOPERATIVE EVALUATION OF IDH MUTATION STATUS AND TUMOR INVASION IN GLIOMA
Authors: Brown Hannah , Garcia Diogo , Chen Rong , Jentoft Mark , Middlebrooks Erik , Chaichana Kaisorn , Quinones-Hinojosa Alfredo , Cooks R Graham
Published: November 2021

BACKGROUND

Intraoperative detection of residual tumor and isocitrate dehydrogenase (IDH) mutations can assist in maximizing surgical resection beyond contrast enhancing margins and guide intraoperative surgical decision making for glioma patients. We aimed to evaluate the use of desorption electrospray ionization-mass spectrometry (DESI-MS) for intraoperative assessment of IDH mutations and estimation of tumor cell percentage (TCP).

METHODS

This is a prospective study using intraoperative DESI-MS analysis of freshly obtained tissue samples to evaluate IDH mutations via 2-hydroxyglutarate (2-HG) intensity and TCP via measurement of N-acetylaspartic acid (NAA) intensity and characteristic lipid profiles. These IDH mutation and TCP estimates were subsequently validated by a senior neuropathologist.

RESULTS

A total of 247 biopsies from a 49-patient study were previously collected and analyzed at Indiana University. Assessment of TCP in 203 margin and core biopsies based on NAA intensity yielded sensitivity, specificity, and accuracy values of 91, 76, and 83%, whereas TCP assessment based on characteristic lipid profiles yielded 76, 85, and 81%, respectively. Assessment of IDH mutation status of 71 core biopsies yielded sensitivity, specificity, and accuracy values of 89, 100, and 94%. Further validation of the methodology is being performed in an ongoing collaboration with Mayo Clinic-Jacksonville, where we have collected 178 biopsies from 24 patients. Preliminary results of IDH mutation assessments indicate 100% sensitivity, specificity, and accuracy.

DISCUSSION/CONCLUSION

We present a novel system to allow intraoperative evaluation of IDH status and to guide surgical resection by TCP measurement from tissue biopsies. Prospectively, we propose to modify our DESI-MS system by placing a surgical material (e.g. cottonoid) along the surgical margin and transferring material from the blot to a microscope slide prior to DESI-MS analysis. This will allow the retention of the spatial distribution of diagnostic molecules while analyzing a wall of the surgical cavity without the need for biopsy.
PATH-27. MGMT PROMOTER STATUS IN IDH1/2 MUTANT ANAPLASTIC ASTROCYTOMA PATIENTS ASSESSED BY DNA METHYLATION PROFILING AND QMS-PCR: A REPORT FROM THE EORTC BRAIN TUMOR GROUP
Authors: Tesileanu Mircea , French Pim , Sanson Marc , Brandes Alba Ariela , Wick Wolfgang , Clement Paul , Kros Johan , Gorlia Thierry , Golfinopoulos Vassilis , van den Bent Martin
Published: November 2021

BACKGROUND

Temozolomide efficacy in high-grade glioma is related to MGMTp methylation. We compared the prognostic and predictive effect of MGMTp between DNA methylation profiling (MGMT-STP27 model) and qMS-PCR in IDH1/2mt anaplastic astrocytoma patients.

METHODS

The 2x2 factorial design phase III CATNON trial randomized 751 adult patients with newly diagnosed 1p/19q non-codeleted anaplastic glioma to 59.4Gy radiotherapy, radiotherapy with concurrent temozolomide, radiotherapy with 12 cycles of adjuvant temozolomide, or radiotherapy with concurrent and adjuvant temozolomide. MGMTp methylation status was assessed with the MGMT-STP27 model using 850k EPIC data, and qMS-PCR. IDH1/2 mutation status was determined with next-generation sequencing. OS was measured from randomization date.

RESULTS

We identified 444 IDH1/2mt anaplastic astrocytoma patients. MGMTp was methylated in 365/440 patients (83.0%) with MGMT-STP27 data, and 168/361 patients (46.5%) with qMS-PCR data. The agreement between both modalities is 59.9% (Cohen’s Kappa score 0.229). At database lock, 289 patients with MGMT-STP27 data were alive and 236 patients with qMS-PCR data. The median OS of MGMTp methylated glioma patients was 9.1 yrs [95%CI 7.5-not reached] for the MGMT-STP27 model, and not reached [95%CI 9.1-not reached] for qMS-PCR. For MGMTp unmethylated glioma patients, the median OS was 6.9 yrs [95%CI 6.2-not reached] for the MGMT-STP27 model, and 6.8 yrs [95%CI 6.2-9.7] for qMS-PCR. The HR for OS based on MGMTp methylation was 0.88 [95%CI 0.58-1.31] for the MGMT-STP27 model, and 0.72 [95%CI 0.50-1.03]) for qMS-PCR. The HR for OS after radiotherapy with any temozolomide vs radiotherapy alone for the MGMT-STP27 model was 0.53 [95%CI 0.37-0.78] for MGMTp methylated, and 0.54 [95%CI 0.25-1.18] for MGMTp unmethylated glioma patients; and for MS-PCR was 0.34 [95%CI 0.19-0.61] for MGMTp methylated, and 0.53 [95%CI 0.33-0.85] for MGMTp unmethylated glioma patients.

CONCLUSION

MGMTp methylation, regardless of assay, was neither prognostic nor predictive for outcome to temozolomide in IDH1/2mt anaplastic astrocytoma patients.
PATH-41. POLYMORPHOUS LOW-GRADE NEUROEPITHELIAL TUMOR OF THE YOUNG WITH FGFR3-TACC3 FUSION MIMICKING HIGH-GRADE GLIOMA: CASE REPORT AND SERIES OF HIGH-GRADE CORRELATES
Authors: Golub Danielle , Pan Peter C , Liechty Benjamin , Slocum Cheyanne , Bale Tejus , Pisapia David J , Juthani Rupa
Published: November 2021

BACKGROUND

Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently-described entity that can occasionally histologically and molecularly mimic high-grade glioma. The histologic and molecular features that predict aggressive behavior in FGFR3-TACC3 altered tumors are unclear.

CASES

We present a rare case of an indolent neuroepithelial neoplasm in a 59-year-old female with imaging initially suggestive of high-grade glioma and analyze common molecular features between this case and a series of high-grade gliomas. After total resection, pathology of the case patient revealed predominantly low-grade cytomorphology, abundant microcalcifications, unusual neovascularization, and a low proliferation index. The lesion was diffusely CD34 immunoreactive and harbored both an FGFR3-TACC3 fusion and a TERT promoter mutation. Based on the overall histologic and molecular profile, a diagnosis of PLNTY was favored. The patient was thereafter observed without adjuvant therapy with no evidence of progression at 15-month follow-up. In contrast, a series of eight adult patients with glioblastomas harboring FGFR3-TACC3 fusions and correspondingly aggressive clinical courses are also presented. Common molecular findings included IDH-wildtype status, absence of 1p19q codeletion, and CDKN2A loss. TERT promoter mutations and lack of MGMT promoter methylation were also frequently observed. These patients demonstrated a median 15-month overall survival and a 6-month progression-free survival.

CONCLUSIONS

PLNTY is a rare low-grade entity that can display characteristics of high-grade glioma, particularly in adults. The potential for a unique entity mimicking PLNTY which may act as a precursor lesion for a more malignant phenotype should be considered in cases with FGFR3-TACC3 fusions and other high-grade features.
NIMG-07. BEYOND RANDOM AND NUMERIC LESIONS: DIFFERENT IMAGING PATTERNS OF CENTRAL NERVOUS SYSTEM METASTASIS BASED ON PRIMARY TUMOR LOCATION AND MOLECULAR PROFILE
Authors: Magalhães Júlia , Moreno Raquel , Takahashi Jorge , Lucato Leandro , Silva Carlos
Published: November 2021

The purpose of this exhibit is to discuss different imaging patterns of central nervous system (CNS) metastasis based on their primary cancer site and to review the recent literature of the particularities of CNS metastasis distribution in the era of molecular advancement in oncology. Selected cases extracted from our institutions database will be presented. The cases will be didactically organized to illustrate the most common imaging characteristics and distribution of brain metastasis based on their organ of origin, such as lung, breast, renal, skin, testicle and gastrointestinal tract. (SCHROEDER T. et al., J Neurooncol. 2020). We will also discuss the correlation between tumor imaging findings and genetic profile. We intend to review well-known CNS metastasis imaging patterns, as preferential involvement of the posterior fossa and anatomic watershed areas in cases of lung cancer (TAKANO, K. et al. Neuro-Oncology, 2016) and the rarity of parenchyma metastasis from prostate cancer (HATZOGLOU V. et al, J Neuroimaging. 2014). We will also demonstrate newly described imaging findings in correlation with primary tumors genetic mutations, such as higher incidence of leptomeningeal involvement in triple negative breast cancer and increase in the number of brain lesions in cases of EGFR positive lung cancer. Familiarity with the most prevalent imaging characteristics of central nervous system metastasis helps oncologists and radiologists not to miss out a CNS progression in case of a known tumor, and also helps to direct systemic investigation of a primary tumor when brain metastasis is the initial presentation. The correlation between molecular profile and the most common sites of CNS involvement can help on treatment planning, including brain radiation (Yanagihara TK,et al., Tomography. 2017), and also bring to discussion the mechanisms of tumor dissemination, which can be targets for future treatments.
NIMG-08. A MULTI-CENTER RADIOMICS-BASED MODEL TO DIFFERENTIATE BETWEEN NEUROFIBROMATOSIS TYPE 1-ASSOCIATED PLEXIFORM NEUROFIBROMAS AND MALIGNANT PERIPHERAL NERVE SHEATH TUMORS
Authors: Ly Ina , Liu Tianyu , Cai Wenli , Kwon Daniel , Michaels Olivia , Bredella Miriam , Jordan Justin , Dombi Eva , Widemann Brigitte , Hirbe Angela , Borcherding Dana , Srihari Divya , Melecio-Vázquez Mairim , Chi Ping , Boswell Demetrius , de Blank Peter , Pollard Kai , Pratilas Christine , Salamon Johannes , Mautner Viktor , Mulder Zachary , Steensma Matthew , Lee Shernine , Korf Bruce , Blakeley Jaishri , Plotkin Scott
Published: November 2021

BACKGROUND

Several MRI features are proposed to distinguish between plexiform neurofibromas (PNF) and malignant peripheral nerve sheath tumors (MPNST) in neurofibromatosis type 1 (NF1), including tumor size, margins, and degree of heterogeneity. However, most of these features are descriptive in nature, subject to intra-/interrater variability, and based on small single-institution studies. The goal of this study was to identify radiomic features that can differentiate between NF1-associated PNF and MPNST.

METHODS

31 MPNSTs and 24 PNFs from five centers were segmented on short TI inversion recovery sequences using a semi-automated segmentation software (3DQI). Standard pre-processing was performed, including N4 bias field correction, intensity normalization (using a mean of 120 SI and standard deviation of 80 SI), and resampling to 1 mm3 voxel resolution. 1688 radiomic features were extracted from the tumor region of interest using PyRadiomics, an open-source Python radiomics package. To classify tumors as PNF or MPNST, we implemented the Boruta algorithm and correlation removal for selection of important features. A Random Forest model was built using the top ten selected features. Five-fold cross-validation was performed and repeated 100 times. Model performance was evaluated using the area under the ROC curve (AUC), sensitivity, specificity, accuracy, and confidence intervals.

RESULTS

The top ten features included in the model were five intensity features, two shape features, and three texture features. The model demonstrated an AUC of 0.891 (95% CI 0.882-0.899), sensitivity of 0.744, specificity of 0.847, and accuracy of 0.802 (95% CI 0.792-0.813).

CONCLUSIONS

Our machine learning model demonstrated high performance in classifying tumors as either PNF or MPNST in NF1 individuals. Inclusion of additional tumors for model training and testing on an independent dataset are underway. Ultimately, our model may enable improved differentiation between PNF and MPNST compared to descriptive MRI features, permit early patient risk stratification, and improve patient outcomes.
NIMG-18. [18F]FLUCICLOVINE PET TO DISTINGUISH PSEUDOPROGRESSION FROM TUMOR PROGRESSION IN POST-TREATMENT GLIOBLASTOMA
Authors: Nabavizadeh S Ali , Doot Robert K , Young Anthony J , Bagley Stephen J , Ware Jeffrey B , Schubert Erin , Jr Fraser Henderson , Pantel Austin , Chen H Isaac , Lee John Y K , Desai Arati , O’Rourke Donald M , Nasrallah MacLean , Brem Steven
Published: November 2021

Differentiation of true tumor progression (TP) from pseudoprogression (PsP) is a major unmet need in patients with glioblastoma. [18F]Fluciclovine is a synthetic amino acid PET radiotracer that is FDA-approved in biochemical recurrence in prostate cancer. The study aim was to assess the value of [18F]Fluciclovine PET in differentiation of histologically confirmed (“true”) TP and PsP in post-treatment of glioblastoma. METHODS: 23 patients with glioblastoma with new contrast-enhancing lesions or lesions showing increased enhancement ( > 25% increase) on standard MRI after completion of radiation underwent 60-minutes dynamic [18F]Fluciclovine PET imaging. Patients subsequently underwent resection of enhancing lesion and tumor percentage vs. treatment-related changes were quantified on histopathology. Patients were considered "true” TP if tumor represented ≥ 50% of the resected specimen, mixed TP-PsP if < 50% and > 10%, and PsP if tumor represented ≤ 10%. Summed 30- to 40-minute post-injection PET images were used to measure SUVpeak and SUVmax (g/mL units). RESULTS: 15 patients with “true” TP, 3 with mixed TP-PsP, and 5 with PsP were included. There was a positive correlation between SUVpeak by PET and tumor percentage by histology (Rho= 0.56, p= 0.006). Patients who demonstrated “true” TP had significantly higher SUVpeak compared to patients with histological PsP (4.8±1.6 vs 2.9± 1.0, p= 0.02, AUC= 0.91, n=20). SUVpeak cut-off of 3.3 provided 93% sensitivity, 80% specificity, and 90% accuracy for differentiation of “true” TP from PsP. Patients with “true” TP/mixed TP-PsP also had significantly higher SUVpeak than patients with PsP (4.6±1.5 vs 2.9± 1.0, p= 0.03, AUC= 0.88, n=23). SUVmax and partial volume-corrected SUVpeak and SUVmax exhibited similar performance. CONCLUSION: Our results indicated that [18F]Fluciclovine PET imaging can accurately differentiate “true” TP from PsP. Further studies are required to confirm these promising early results and determine optimal criteria for interpreting [18F]Fluciclovine PET to distinguish PsP from TP.
NIMG-20. DIFFERENTIATION OF TREATMENT-RELATED CHANGES FROM TUMOR PROGRESSION FOLLOWING BRACHYTHERAPY IN PATIENTS WITH WHO II AND III GLIOMAS USING FET PET
Authors: Bauer Elena , Werner Jan , Brunn Anna , Deckert Martina , Ruess Daniel , Ruge Maximilian , Celik Eren , Fink Gereon , Langen Karl-Josef , Galldiks Norbert
Published: November 2021

BACKGROUND

Following brachytherapy, the differentiation of radiation-induced changes (e.g., radiation necrosis) from actual tumor progression using MRI is challenging. To overcome this diagnostic uncertainty, we evaluated the diagnostic value of O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in glioma patients treated with brachytherapy.

MATERIAL AND METHODS

From 2006-2019, we retrospectively identified WHO grade II or III glioma patients (i) treated with brachytherapy using Iodine-125 seeds, (ii) equivocal or progressive MRI findings inside the radiation field, and (iii) additional FET PET imaging for diagnostic evaluation. Static FET PET parameters such as maximum and mean tumor-to-brain ratios (TBR) and dynamic FET PET parameters (i.e., time-to-peak, slope) were obtained. Diagnostic performances were calculated using receiver operating characteristic curve analyses and Fisher’s exact test. Diagnoses were confirmed histologically or clinicoradiologically.

RESULTS

Following brachytherapy, suspect MRI findings occurred after a median time of 33 months (range, 5-111 months). In 10 of 21 patients (WHO grade II, n=5; WHO grade III, n=16), treatment-related changes were diagnosed. The best diagnostic performance for identification of treatment-related changes was obtained using maximum TBRs (threshold < 3.20;accuracy, 86%; sensitivity, 100%; specificity, 73%; P=0.007). Mean TBRs reached an accuracy of 76% (threshold < 2.05; sensitivity, 89%; specificity, 64%; P=0.010). Dynamic PET parameters did not reach statistically significant results.

CONCLUSION

Our data suggest that static FET PET parameters add valuable diagnostic information to diagnose radiation-induced changes in glioma patients treated with brachytherapy.
NIMG-27. REGORAFENIB RESPONSE ASSESSMENT USING FET PET IN PATIENTS WITH PROGRESSIVE GLIOMA
Authors: Werner Jan-Michael , Bauer Elena , Lohmann Philipp , Tscherpel Caroline , Brunn Anna , Deckert Martina , Kabbasch Christoph , Stoffels Gabriele , Fink Gereon , Langen Karl-Josef , Galldiks Norbert
Published: November 2021

BACKGROUND

The REGOMA phase 2 trial showed an encouraging overall survival benefit of the multikinase inhibitor regorafenib in glioblastoma patients at first progression. We used O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET for the early assessment of response to regorafenib in patients with progressive glioma in an advanced disease stage.

METHODS

Thirty patients with progressive glioma were treated according to the REGOMA trial and prospectively followed. FET PET and MRI were performed at baseline and after the second cycle of regorafenib. Static PET parameters such as maximum and mean tumor-to-brain ratios (TBRmax, TBRmean) and metabolic tumor volumes (MTV) were calculated. Threshold values of FET PET parameters to predict a response were established by ROC analyses using an overall survival of ≥ 6 months as reference. The predictive value of FET PET parameters and their changes concerning overall survival was subsequently evaluated using the Kaplan-Meier test. MRI changes were evaluated according to the RANO criteria.

RESULTS

Up to now, 18 of 30 patients (glioblastoma, 83%; age range, 24-71 years) were eligible for data evaluation. The median number of tumor relapses before regorafenib was 2 (range, 1-4). During regorafenib (median cycles, 4; range, 2-9 cycles), CTCAE grade 3 or 4 side effects occurred in 56% and 11%, respectively. The median overall survival was 6 months (range, 3-18 months). After two cycles of regorafenib, a TBRmean reduction of 13% predicted a significantly longer overall survival (12 vs. 6 months; P=0.034). In contrast, MRI changes evaluated according to RANO criteria (i.e., Stable Disease or Partial Response vs. Progressive Disease) were not predictive (11 vs. 8 months; P=0.644).

CONCLUSION

Data suggest that amino acid PET using the tracer FET may be clinically valuable for identifying responders to regorafenib early after treatment initiation.
NIMG-56. USING RADIOMIC FEATURES FROM DAILY MAGNETIC RESONANCE IMAGING TO PREDICT RESPONSE TO RADIATION THERAPY IN GLIOBLASTOMA PATIENTS: A PILOT STUDY
Authors: Cullison Kaylie , Simpson Garrett , Maziero Danilo , Jones Kolton , Stoyanova Radka , Diwanji Tejan , Azzam Gregory , De la Fuente Macarena , Ford John , Mellon Eric
Published: November 2021

A dilemma in treating glioblastoma is that MRI after chemotherapy and radiation therapy (chemoRT) shows areas of presumed tumor growth in up to 50% of patients. These areas can represent true progression (TP), tumor growth with tumors non-responsive to treatment, or pseudoprogression (PP), edema and tumor necrosis with favorable treatment response. On imaging, TP and PP are usually not discernable. Patients in this study undergo six weeks of chemoRT on a combination MRI/RT device, receiving daily MRIs. The goal of this study is to explore the correlation of radiomics features with progression. The tumor lesion and surrounding areas of growth/edema were manually outlined as regions of interest (ROIs) for each daily T2-weighted MRI scan. The ROIs were used to calculate texture features: statistical features based on the gray-level co-occurrence matrix (GLCM), the gray-level zone size matrix (GLZSM), the gray-level run length matrix (GLRLM), and the neighborhood gray-tone difference matrix (NGTDM). Each of these matrix classes describe the probability of spatial relationships of gray levels occurring within the ROI. Daily texture features were averaged per week of treatment for each patient. Patient response was retrospectively defined as no progression (NP), TP, or PP. A Kruskal-Wallis test was performed to identify texture features that correlated most strongly with patient response. Forty texture features were calculated for 12 patients (19 treated, 7 excluded due to no T2 lesion or progression status unknown, 6 NP, 3 TP, 3 PP). There was a trend of more texture features correlating significantly with response in weeks 4-6 of treatment, compared to weeks 1-3. A particular texture feature, GLSZM Small Zone Low Gray-Level Emphasis, showed increasing difference between PP and TP over time, with significant difference during week 6 of treatment (p=0.0495). Future directions include correlating early outcomes with greater numbers of patients and daily multiparametric MRI.
NIMG-61. CLINICAL UTILITY OF SOMATOSTATIN RECEPTOR PET IMAGING BIOMARKERS FOR CHARACTERIZATION OF MENINGIOMA AMONG INCIDENTAL CNS LESIONS
Authors: Ensign Shannon Fortin , Argarwal Muskan , Badawy Mohamed , Halfdanarson Thorvardur , Johnson Derek , Sonbol Mohamad (Bassam) , Kendi Ayse
Published: November 2021

BACKGROUND

Somatostatin receptor (SSTR) PET/CT is utilized with increasing frequency in the clinical treatment of neuroendocrine tumors. Incidental CNS lesions are commonly noted and presumed to be meningiomas, however 68Gallium (Ga-68)-DOTATATE radionuclide use lacks specificity for meningioma identification. Currently there is no established SSTR-based imaging criteria for classification of incidental CNS lesions.

METHODS

We retrospectively analyzed patients across clinical and radiological databases at Mayo Clinic who had undergone both Ga-68-DOTATATE PET/CT and brain MR imaging who had an incidental CNS lesion identified with clinical or radiographic prediction of meningioma. Known meningioma diagnoses prior to imaging were excluded. Imaging indication, semi-quantitative measures, and corresponding clinical history were analyzed to identify metrics impacting both the predictive and descriptive utility of SSTR-based imaging as compared to corresponding MRI prediction in incidental CNS lesions.

RESULTS

Among 59 patients with a CNS lesion identified on both imaging modalities, most scans were performed for a history of neuroendocrine tumor (71%). Cases with concordant lesion type prediction of meningioma between imaging modalities (N = 25) displayed a higher median SUV max and Krenning score on Ga-68-DOTATATE PET compared to cases with concordant prediction of other lesions (N=10) or discordant prediction of meningioma (N=24). Ga-68-DOTATATE was more likely to discordantly predict meningioma as compared to the corresponding patient MRI in cases with lower SUV max values. The addition of Qclear technology was significantly associated with diagnostic clarification in cases of imaging discordant tumor type prediction. Prior cranial radiation or use of a somatostatin mimetic did not affect quantitative radiographic measures in lesion characterization, and MRI-based tumor size was similar across groups.

CONCLUSION

The continued development of SSTR-based imaging biomarker signatures across incidental CNS lesion subtypes will further define the role of this imaging modality in the clinical diagnosis and management of presumed meningiomas.
NIMG-72. QUANTIFYING INTRA-TUMOR MULTI-GENE HETEROGENEITY OF GBM FROM MRI USING A DATA-INCLUSIVE MACHINE LEARNING ALGORITHM
Authors: Wang Lujia , Hu Leland , Hawkins-Daarud Andrea , Singleton Kyle , Sereduk Christopher , Tran Nhan , Swanson Kristin , Li Jing
Published: November 2021

Intra-tumor genetic heterogeneity is an important cause of treatment failure of GBM. Using MRI and image-localized biopsies, it is possible to train machine learning (ML) models to predict regional genetic status. However, biopsy samples are limited, making it difficult to train a robust ML model. We proposed a data-inclusive model called Weakly Supervised Ordinal Support Vector Machines (WSO-SVM) which leverages the vast amount of MRI data outside the sparsely sampled biopsy regions to augment the biopsy samples to improve ML accuracy. Our study included a unique dataset of 104 image-localized biopsies with spatially matched multiparametric MRI from 30 untreated Glioblastoma (GBM) patients. Each biopsy sample went through genetic sequencing analysis and our study focused on two GBM hallmark genes, EGFR and PDGFRA. For each gene, a biopsy sample was labeled as “altered” if the copy number of this gene was amplified or a mutation was found, and “non-altered” otherwise. From the localized region of six MRI contrasts from T1gd, T2w, diffusion and perfusion imaging, over 300 texture features were extracted. To account for biopsy sample location uncertainty, six neighboring regions of the biopsy sample including four neighbors two pixels away from the biopsy location and two neighbors on adjacent slices were also included in model training. WSO-SVM achieved 0.83 accuracy, 0.77 sensitivity, and 0.86 specificity for classifying EGFR; 0.77 accuracy, 0.74 sensitivity, and 0.79 specificity for classifying PDGFRA, based on 10-fold cross validation. Furthermore, using the trained models, we generated regional EGFR and PDGFRA alteration maps for each patient within the enhancing and non-enhancing tumoral areas. On average we found a greater proportion of enhancing tumor with co-alteration than non-enhancing tumor, while this trend was reversed when considering only one altered gene. The ratio of EGFR vs PDGFRA alterations was higher in non-enhancing tumor than enhancing tumor.
NIMG-74. RESPONSE ASSESSMENT AFTER DOSE-ESCALATED RADIOTHERAPY: IMAGING PROTOCOL OF A MULTICENTER PHASE III TRIAL ON INTRAOPERATIVE RADIOTHERAPY IN NEWLY DIAGNOSED GLIOBLASTOMA (INTRAGO-II;ARO2016-1;AG-NRO-03)
Authors: Pope Whitney , Petrecca Kevin , Radbruch Alexander , Giordano Frank ,   INTRAGO Trialists
Published: November 2021

BACKGROUND

Reliable response assessment of irradiated glioblastomas remains challenging. In an attempt to better distinguish post-therapeutic alterations (such as reactive gliosis, pseudoprogression and radionecrosis) from tumor progression, especially after (local) RT dose escalation as performed in the multinational INTRAGO-II trial, we modified the classical RANO criteria and developed a protocol and workflow for uniform assessment of post-irradiation tumor response.

METHODS

INTRAGO-II is a multinational randomized phase III trial (9 nations, 19 centers) that evaluates the benefit of intraoperative radiotherapy (IORT) with 20-30 Gy to the tumor bed after resection of glioblastoma in addition to standard of care (NCT02685605). Within this trial, advanced imaging is mandatory in addition to standard sequences and measurements (such as the sum of the products of perpendicular diameters, SPD). Specifically, the acquisition of dynamic susceptibility contrast (DSC) sequences as well as the calculation of the normalized relative cerebral blood volume (rCBV) is required. All local assessments are subjected to a central neuroradiology read, which is conclusive. The key modifications to RANO are that (i) an ≥25% increase SPD of the target lesions should be associated with a rCBV≥1 of at least one lesion to be considered radiological progression, (ii) new enhancing lesions should become measurable before they can constitute to radiological progression, (iii) rCBV is normalized against normal appearing white matter from the contralateral brain by reference ROI (with a minimal sphere size of 5x5mm) and (iv) confirmatory scans are mandatory for defining progressive disease.

CONCLUSION/SUMMARY

We present an imaging protocol based on updated RANO that accounts for post-irradiation image alterations. Funding: Carl Zeiss Meditec AG, Germany and MedWave Medical Imaging BV; Registered with ClinicalTrials.gov, number NCT02685605.
NCMP-06. THE RISK AND BURDEN OF THROMBOEMBOLIC AND HEMORRHAGIC EVENTS IN PATIENTS WITH MALIGNANT GLIOMA RECEIVING BEVACIZUMAB
Authors: Ou Alexander , Lin Heather , Yuan Ying , Bornstein Charles , Alfaro-Munoz Kristin , Afshar-Kharghan Vahid , Kamiya-Matsuoka Carlos , Majd Nazanin
Published: November 2021

BACKGROUND

Patients with high-grade gliomas (HGG) often receive anti-angiogenic therapy with bevacizumab to slow disease progression and/or palliate neurological symptoms. Bevacizumab has been associated with an increased risk of two major vascular complications: venous thromboembolism (VTE) and intracranial hemorrhage (ICH). We sought to identify clinical, pathologic, and radiographic variables correlated with risk of either event occurring in patients with HGG receiving bevacizumab.

METHODS

We retrospectively identified 94 patients with HGG who received bevacizumab at our center from 2015-2021. Variables included demographics, performance status, IDH, MGMT, vascular risk factors, baseline anti-coagulant/anti-platelet use, concurrent chemotherapy, and presence of macrobleeds on MRI (>1 cm3 susceptibility) at the time of bevacizumab initiation. We conducted competing risk analysis using subdistribution hazard models with death as competing risk for ICH or VTE. The effects of covariates on the incidence of hemorrhage or VTE were evaluated in univariate and multivariate settings.

RESULTS

Of 94 patients, 36 (38.3%) and 27 (28.7%) developed VTE and ICH, respectively. 31 (33%) did not develop either. ICH and VTE events occurred after a mean of 4.46 and 5.94 cycles of bevacizumab, respectively. 20 had baseline anti-platelet/anticoagulant use, and 16 had prior VTEs. Patients with macrobleeds on MRI had a larger HR of developing acute hemorrhage [HR=2.368 (1.112, 5.043), p=0.0254]. Patients older than 50 trended toward larger HR of developing VTE in univariate analysis that approached significance [HR=1.799 (0.889, 3.637), p=0.1023]. Sex, performance status, IDH, MGMT, vascular risk factors, baseline anticoagulant/anti-platelet use and concurrent chemotherapy were not significantly associated with occurrence of VTE.

CONCLUSIONS

The presence of macrobleeds on MRI is associated with increased risk of developing acute ICH while on bevacizumab. Older age at diagnosis of HGG may be associated with an increased risk of VTE in patients receiving bevacizumab. Larger studies are needed to confirm these findings.
NCMP-07. IDH MUTANT GLIOMAS PROMOTE EPILEPTOGENESIS VIA D-2-HYDROXYGLUTARATE DEPENDENT MTOR HYPER-ACTIVATION
Authors: Mortazavi Armin , Fayed Islam , Bachani Muzna , Dowdy Tyrone , Jahanipour Jahandar , Khan Anas , Yang Chungzhang , Maric Dragan , Larion Mioara , Ksendzovsky Alexander , Zaghloul Kareem
Published: November 2021

Uncontrolled seizures in patients with low grade gliomas have a significant impact on quality of life and morbidity, yet the mechanisms through which these tumors cause seizures remain unknown. Albeit there are multiple features that contribute to tumor related epileptogenesis, IDH mutations are determined to be an independent factor, although the pathogenesis remains poorly understood. Here, we hypothesize that the active metabolite D-2-hydroxyglutarate (D-2-HG) produced by the IDH-mutant enzyme leads to metabolic disruptions in surrounding cortical neurons that consequently promote seizures. We use a complementary study of in vitro cortical cultures and electrographically sorted human cortical tissue from patients (n=5) with IDH-mutant gliomas to test this hypothesis. We demonstrate that D-2-HG leads to increased neuronal spiking activity (p< 0.0001) and promotes a distinct metabolic profile in surrounding neurons and upregulation of mTOR signaling (p< 0.0001), which is consistent in human epileptic cortex compared to peritumoral nonepileptic cortex. Furthermore, increases in neuronal activity are induced by mTOR activation and reversed with mTOR inhibition. Together, our data suggest that metabolic disruptions and mTOR signaling upregulation in the surrounding cortex due to D-2-HG may be a driving event for epileptogenesis in patients with IDH-mutant low grade gliomas.
NCMP-17. BEWARE: ALL POSTERIOR FOSSA MASSES IN CHILDREN ARE NOT BRAIN TUMORS
Authors: Issai Vanan Magimairajan , Li Jie , Almiski Muhamad , Bunge Martin , Serletis Demitre , Israels Sara
Published: November 2021

INTRODUCTION

Isolated Myeloid sarcoma (MS) of the central nervous system (CNS-MS) is a very rare presentation of Acute Myeloid Leukemia (AML). A 10-year-old boy with a two-week history of intermittent headaches was referred to the emergency department (ED) by an optometrist for evaluation of bilateral papilledema. Physical examination in the ED confirmed the presence of papilledema with no other abnormal neurologic findings. Emergent MRI of the brain showed an avidly homogeneously enhancing extra-axial dural based mass in the right posterior fossa measuring 4.8 cm (AP) x 3.2 cm (CC) x 4.6cm (T), with significant mass effect and peri-tumoral vasogenic edema. Neuro-surgery consultation was obtained and complete blood count (CBC) was normal except for the presence of 13% blasts with occasional Auer rods seen on the peripheral blood smear. Bone marrow aspirate demonstrated 56% myeloblasts; A diagnosis of AML with CNS-MS (CNS-3c) was made and the initial lumbar puncture (LP) was deferred due to the risk of CNS herniation. Induction chemotherapy was initiated as per protocol. A CT scan done two weeks later showed complete resolution of the intracranial mass.

DISCUSSION

The incidental finding of papilledema, with imaging to investigate the intracranial pathology revealed a large posterior fossa mass in our patient. However, the atypical features of the mass (dural based extra-axial location; extensive infiltration into adjacent structures) and the finding of blasts with Auer rods in peripheral blood helped us to diagnose CNS-MS, and avoided an extensive neurosurgical procedure and a delay in definitive therapy. Our patient had a normal CBC and the review of the peripheral blood film by an experienced Hematologist was very crucial in making a clinical diagnosis of MS.

CONCLUSION

Myeloid sarcomas should be considered in the differential diagnosis of an intracranial mass, particularly when accompanied by abnormal findings in the CBC.