bluuebunny/crossref_metadata_2025 huggingface dataset:
NIMG-81. EFFECT OF RE-TREATMENT WITH TEMOZOLOMIDE IN GRADE 2/3 IDH MUTANT GLIOMAS AT FIRST PROGRESSION
Authors: Yogendran Lalanthica , Abbas Salma , Scharf Zachary , Patel Sohil , Schiff David
Published: November 2022

BACKGROUND

Patients with WHO grade 2 and 3 IDHmt gliomas commonly receive temozolomide, with or without radiation therapy, as initial therapy. At progression, temozolomide is sometimes reinstated despite a paucity of data on effectiveness.

METHODS

We reviewed imaging outcomes of patients with grade 2/3 IDHmt gliomas re-treated with temozolomide at first progression between 2007 and 2019.

RESULTS

15 subjects included six grade 2 and five grade 3 oligodendrogliomas, one grade 2 and three grade 3 astrocytomas. Median time between completion of first temozolomide course and initiation of re-treatment was 47 months (range, 8-126 months). Best treatment response after first progression by RANO criteria was stable disease in 10 and progressive disease in 5 patients. Median progression free survival with temozolomide re-treatment was 27.4 months (95% CI: [13.8, 41.2 months] and median overall survival 47.8 months (95% CI: [31.5, 125.6 months]). In 14 patients who had pre- and post- first tumor progression rate measurements, the mean rate of tumor growth by bidimensional product was 0.29 cm2/month (95% CI: [0.17, 0.42 cm2/month], p< 0.001) prior to first tumor progression versus 0.47 cm2/month (95 CI: [0.08, 0.85 cm2/month], p=0.021) during re-treatment with monotherapy temozolomide (prior vs after, p=0.371). The volumetric mean rate of tumor growth was 1.12 cc/month (95% CI: [0.31, 1.93 cc/month], p=0.010) prior to first tumor progression versus 1.29 cc/month (95% CI: [0.15, 2.43 cc/month], p=0.030) during temozolomide re-treatment (prior vs. after, p=0.802).

CONCLUSION

Among 15 patients with progressive IDHmt glioma re-treated with temozolomide, there was no radiographic response by RANO criteria nor a decrease in tumor growth rate during the re-treatment period compared to immediate pre-re-treatment period. These findings suggest previously treated, progressive IDHmt gliomas are generally resistant to temozolomide, underscoring the need for novel therapies.
NIMG-87. CHARACTERIZING IMMUNE PROFILES OF PEDIATRIC MEDULLOBLASTOMA AND THEIR RADIOLOGICAL CORRELATES
Authors: Familiar Ariana , Zhao Chao , Kim Meen Chul , Khalili Nastaran , Madhogarhia Rachel , Arif Sherjeel , Bagheri Sina , Anderson Hannah , Haldar Debanjan , Ware Jeffrey B , Vossough Arastoo , Storm Philip B , Resnick Adam C , Kazerooni Anahita Fathi , Nabavizadeh Ali
Published: November 2022

Recent studies have shown preliminary evidence for differentiation of the tumor microenvironment (TME) and immune landscape between molecularly-defined medulloblastoma (MB) subtypes. Identifying radiological correlates of these TME patterns could establish a non-invasive method of immune profile characterization for guiding patient-centered therapies. Here, we examine immune profiles between MB subtypes using data from Open Pediatric Brain Tumor Atlas (OpenPBTA), and their relationship to tumor measurements from pre-operative MRIs. We identified a retrospective cohort of 94 pediatric MB patients with available molecular subtyping and immune profiles (36 cell types) from bulk gene expression data. A random forest analysis was used to classify the four MB subtypes based on immune profiles. Four cell types had high impact on classification performance: plasmacytoid dendritic cells (PDC; 25.8% accuracy decrease when randomized), hematopoietic stem cells (HSC; 21.9%), plasma B cells (20.3%), and cancer associated fibroblasts (18.8%). Pairwise comparisons revealed SHH and WNT tumors had significantly higher numbers of fibroblasts and HSCs compared to Group3/Group4. We also found novel evidence for significantly lower amounts of plasma B cells in the SHH group, and high PDC levels in Group4, followed by Group3, and low PDC in SHH/WNT. Multi-parametric MRI scans for 39 patients were used to segment tumor volumes. Overall tumor volume was significantly correlated with composite stroma scores (R = 0.34, p = 0.036). Additionally, patients with higher volumes of gadolinium contrast-enhancing compared to non-enhancing components had higher immune (R = 0.42, p = 0.009) and microenvironment (summed immune and stromal cell types; R = 0.44, p = 0.006) scores, regardless of their molecular subtype. Together, our results demonstrate: (1) the use of rich immune profiles for differentiating molecular subtypes of MB and their unique TME characterization; and (2) initial evidence for radiological correlates of these profiles based on pre-operative imaging collected through standard practices.
NIMG-96. SPINAL MENINGEAL MASS LESION: A RARE PRESENTATION OF FOLLICULAR LYMPHOMA
Authors: White Jessica , Clarke Michelle , Paludo Jonas , Sener Ugur
Published: November 2022

OBJECTIVE

We aim to describe a case of follicular lymphoma that presented as a durally-based thoracic spine lesion manifested as rapidly progressive back pain and meningismus.

BACKGROUND

Follicular lymphoma is one of the most common forms of non-Hodgkin’s lymphoma; however, it is rare for follicular lymphoma to present as a spinal meningeal mass lesion.

METHODS

This is a case report and review of literature.

RESULTS

A 38-year-old man developed thoracic back pain that progressed over one month with associated severe focal tenderness over his mid to lower thoracic spine. He developed intermittent numbness of the bilateral lower extremities, nuchal rigidity, difficulty sleeping, and night sweats. An MRI of the thoracic spine demonstrated a dorsal intradural, extramedullary enhancing lesion from T6-T9 extending outside the spinal canal. Dural thickening across the entire circumference of the spinal cord was noted. CT-guided biopsy of the thoracic lesion was performed, and pathology was consistent with follicular lymphoma. FDG PET: CT demonstrated no systemic disease. Bone marrow biopsy was negative for malignancy. Symptoms resolved with dexamethasone therapy. He was treated with bendamustine and rituximab with follow up PET: CT two months later demonstrating a complete response.

DISCUSSION

This case illustrates an unusual presentation of follicular lymphoma as a spinal meningeal mass lesion. Though rare, lymphoma should be included in the differential diagnosis of a dural mass lesion. Prompt diagnosis and initiation of treatment can lead to complete response and resolution of symptoms.
NIMG-99. REAL-TIME DELINEATION OF THE CENTRAL SULCUS WITH THE SPATIAL PROFILE OF SSEPS CAPTURED WITH HIGH-DENSITY ECOG GRID
Authors: Priscella Priscella , Prabhu Sujit , Bhavsar Shreyas , Sudhakar Tummala , Ince Nuri
Published: November 2022

OBJECTIVE

Cortical mapping during tumor resection is critical to reducing the risk of neurological complications. While the somatosensory evoked potential (SSEPs) is widely employed to delineate the central sulcus, the evoked response can be misconstrued from the manual peak interpretation. This is due to the poor spatial resolution of the strip electrode as well as a result of edema or tumor infiltration of the overlying cortex. We present a real-time computer-based visualization system that uses recorded SSEPs with a subdural grid to aid in cortical mapping. Method: The neural data during electrical stimulation of the median nerve at 0.6Hz are picked up with a bio-amplifier. The stimulation artifact recorded from the bipolar electromyogram (EMG) is used as the stimulation onset. The ECoG data are assessed online with MATLAB Simulink to process and visualize the SSEPs waveform. The visualization system is programmed to display the SSEP's peak activation as a heat map on a 2D grid and projected onto a screen, showcasing the nature of the cortical activities over the contact surface area in real-time.

RESULTS

SSEPs were recorded from 3 patients during their awake craniotomies. The ECoG grid occupied a large cortical surface where the heatmap delineated the central sulcus. The color-coding of the heatmap revealed the anterior and posterior channels, providing a consistently high separation accuracy in each patient (accuracy = 98%). The map could be viewed at any time point along the SSEP trace without peak interpretation.

CONCLUSION

We believe that this visualization system will aid in the rapid definition of the sensorimotor area during surgical planning to provide additional information during cortical mapping and facilitate interpreting ECoG grid data.
NIMG-102. RAPNO-DEFINED SEGMENTATION AND VOLUMETRIC ASSESSMENT OF PEDIATRIC BRAIN TUMORS ON MULTI-PARAMETRIC MRI SCANS USING DEEP LEARNING; A ROBUST TOOL WITH POTENTIAL APPLICATION IN TUMOR RESPONSE ASSESSMENT
Authors: Kazerooni Anahita Fathi , Madhogarhia Rachel , Arif Sherjeel , Ware Jeffrey B , Bagheri Sina , Haldar Debanjan , Anderson Hannah , Familiar Ariana , Vidal Lorenna , Aboian Mariam , Storm Philip B , Resnick Adam C , Vossough Arastoo , Davatzikos Christos , Nabavizadeh Ali
Published: November 2022

Volumetric measurements of whole tumor and its components on MRI scans, facilitated by automatic segmentation tools, are essential to reduce inter-observer variability in monitoring tumor progression and response assessment for pediatric brain tumors. Here, we present a fully automatic segmentation model based on deep learning that reliably delineates the tumor components recommended by the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group for evaluation of treatment response. Multi-parametric MRI (mpMRI) scans (T1-pre, T1-post, T2, and T2-FLAIR), acquired on multiple MRI scanners with different field strengths and vendors, for a cohort of 218 pediatric patients with a variety of histologically confirmed brain tumor subtypes were collected. The mpMRI scans were co-registered and manually segmented by experienced neuroradiologists in consensus to identify the tumor subregions including the enhancing tumor (ET), non-enhancing tumor (NET), cystic components (CC), and peritumoral edema (ED) regions. A convolutional neural network model based on DeepMedic architecture was trained using mpMRI scans as the inputs for segmentation of the whole tumor and subregions. The trained model showed excellent performance in segmentation of the whole tumor, as suggested by median dice of 0.90/0.85 for validation (n = 44)/independent test (n = 22) sets. ET and non-enhancing components (union of NET, CC, and ED) were segmented with median dice scores of 0.78/0.84 and 0.76/0.74 for validation/test sets, respectively. The automated and manual segmentations demonstrated strong agreement in estimating VASARI (Visually AcceSAble Rembrandt Images) MRI features with Pearson’s correlation coefficient R > 0.75 (p < 0.0001) for ET, NET, CC, and ED components. Our proposed automated segmentation method developed based on MRI scans acquired with different protocols, equipment, and from a variety of brain tumor subtypes, shows potential application for reliable and generalizable volumetric measurements which can be used for treatment response assessment in clinical trials.
NIMG-105. DEUTERIUM METABOLIC IMAGING (DMI) DETECTS A LARGER WARBURG EFFECT IN HIGH-GRADE BRAIN TUMORS AND IN IDH WILD TYPE GLIOMAS
Authors: Kim Lauren , De Feyter Henk , de Graaf Robin , Fulbright Robert , Liu Yanning , Rothman Douglas , Baehring Joachim , Blondin Nicholas , Kim Peter , Omuro Antonio , Chiang Veronica , Moliterno Jennifer , Omay Sacit Bulent , Piepmeier Joseph , Corbin Zachary
Published: November 2022

BACKGROUND

The Warburg Effect (WE) is a metabolic change in which tumors favor glycolysis over oxidative phosphorylation and has been linked to cancer aggressiveness. Mutations in the isocitrate dehydrogenase (IDH) genes in gliomas are associated with improved outcomes. We deployed a magnetic resonance (MR) spectroscopic imaging technique coined Deuterium Metabolic Imaging (DMI) to measure the WE in multiple brain tumor types.

METHODS

Twenty-one patients underwent DMI, acquired on a Bruker 4T MR scanner after oral administration of 0.75g/kg of deuterated glucose. The WE was defined as the ratio of deuterated lactate, representing glycolysis, over deuterated glutamate and glutamine, representing oxidative phosphorylation. We devised an interval scale from 0 to 2 for the WE results. The Wilcoxon rank sum test was performed to detect differences between groups.

RESULTS

The WE measurements for the largest groups, by diagnosis, showed: glioblastoma (n= 9, mean= 1.67); astrocytoma, IDH-mutant, WHO grade 3 (n= 2, mean= 0.25); oligodendroglioma, WHO grade 3 (n= 3, mean= 0.5); low grade glioma, IDH-mutant (n= 2, mean= 0); and meningioma, WHO grade 2 (n= 2, mean= 0). The WE for high-grade tumors (n= 15, mean= 1.27) was significantly different from the WE for low-grade tumors (n= 5, mean= 0), with p= 0.010. The WE for IDH wild type gliomas (n= 9, mean= 1.67) was significantly different from the WE for IDH-mutant gliomas (n= 9, mean= 0.44), with p= 0.007. Analysis is ongoing.

CONCLUSIONS

DMI successfully and non-invasively detects the WE in many types of brain tumors. The WE was larger in high-grade tumors as compared to low-grade tumors, and the WE was larger in IDH wild type gliomas as compared to IDH-mutant gliomas. If validated with future studies, our results suggest that DMI is a useful tool to measure differences in the metabolism of brain tumors with different clinical behaviors.
NIMG-107. THE LANDSCAPE OF BRAIN TUMOR MIMICS IN NEURO-ONCOLOGY PRACTICE
Authors: Yogendran Lalanthica , Kalelioglu Tuba , Donahue Joseph , Ahmed Haroon , Phillips Kester , Calautti Nicole , Lopes Maria-Beatriz , Asthagiri Ashok , Purow Benjamin , Schiff David , Patel Sohil , Fadul Camilo
Published: November 2022

BACKGROUND

Differentiating neoplastic and non-neoplastic brain lesions is essential to make management recommendations and convey prognosis, but the distinction between brain tumors and their mimics in practice may prove challenging. The aim of this study is to provide the incidence of brain tumor mimics in the neuro-oncology setting and describe this patient subset.

METHODS

Retrospective study of adult patients referred to the Division of Neuro-oncology for a presumed diagnosis of brain tumor from January 1, 2005 through December 31, 2017, who later satisfied the diagnosis of a non-neoplastic entity based on neuroimaging, clinical course, and/or histopathology evaluation. We classified tumor mimic entities according to clinical, radiologic, and laboratory characteristics that correlated with the diagnosis.

RESULTS

The incidence of brain tumor mimics was 3.4% (132/3897). The etiologies of the non-neoplastic entities were vascular (35%), inflammatory non-demyelinating (26%), demyelinating (15%), cysts (10%), infectious (9%), and miscellaneous (5%). In our study, 38% of patients underwent biopsy to determine diagnosis, but in 26%, the biopsy was inconclusive.

DISCUSSION

Brain tumor mimics represent a small but important subset of the neuro-oncology referrals. Vascular, inflammatory, and demyelinating etiologies represent two-thirds of cases. Recognizing the clinical, radiologic and laboratory characteristics of such entities may improve resource utilization and prevent unnecessary as well as potentially harmful diagnostic and therapeutic interventions.
NIMG-108. PHYSICAL STRESSES IN BRAIN TUMORS
Authors: Nia Hadi , Kumar Ashwin , Datta Meenal , Siri Saeed , McHugh Jeffrey , Ferraro Gino , Chatterjee Sampurna , Rapalino Otto , Choi Bryan , Nahed Brian , Jain Rakesh
Published: November 2022

Solid stress, distinct from fluid pressure, is a physical force contained in and transmitted by solid components of the brain tumor, including cells and the matrix they produce. Solid stress has been shown to promote tumor progression, and decrease anticancer therapy efficacy. This is especially relevant in brain tumors, as the rigid skull results in these trapped forces, increasing intracranial pressure, and potentially leading to other complications, including neuronal cell death. Here we present a novel method of quantifying these physical stresses in situ in both mice (glioblastoma [U87], brain metastasis [BT474], and ependymoma models) and patients. Briefly, following a craniotomy, mechanical forces that include solid stress are released, which causes the tissue to deform in peaks (areas under compression) and valleys (areas originally under tension). This tissue deformation is imaged via high-resolution ultrasound and analysed via custom MATLAB code to produce an accurate 3D model of the entire mouse brain, including the tumour region. For human samples, a pre-operative MRI is used to generate a detailed 3D model of the human brain. During surgery, the trapped physical stresses results in a bulge of the dura post craniotomy. We use BrainLab to measure the craniotomy induced brain deformation, which is then registered to the pre-operation MRI before being analysed in an identical fashion to the murine models using SolidWorks and Abaqus. We further show that in the brain metastases model, chemotherapy reduces compression stresses by 51%. Further, our technique results in fast processing time (~ 15 minutes), and has the potential to prevent the need for intraoperative MRI based on position simulations. As such, solid stress measurements provide a new class of mechanical biomarkers that can be correlated to clinical outcomes for predictive and prognostic value.
NCMP-12. SECONDARY VERSUS RECURRENT CENTRAL NERVOUS SYSTEM LYMPHOMA - SIMILAR OR DIFFERENT?
Authors: Bazer Danielle , Zabrocka Ewa , Orwitz Matthew , Kowalska Agnieszka
Published: November 2022

BACKGROUND

Although rare, primary central nervous system lymphoma (PCNSL) affects 0.5 per 100,000 individuals. It is estimated that 5% of cases will develop into secondary central nervous system lymphoma (SCNSL) and 2-5% will evolve into recurrent CNS lymphoma (RPCNSL) with the diffuse large B-cell lymphoma (DLBCL) variant of RPCNSL.

METHODS

This is a retrospective study; data obtained via chart review.

RESULTS

We compared 3 patients with RPCNSL to 3 patients with SCNSL. All patients were EBV and HIV negative, DLBCL variant. The average age of diagnosis with the first malignancy with RCNSL was 62.7 years old and age at recurrence was 66.7. With SCNSL, the initial age of diagnosis averaged to 72.7 years old and with secondary presentation at an average age of 76. Initial PCNSL treatments for RPCSNL were steroids, RCHOP with radiation, and DeAngelis Protocol. Initial malignancies for patients with SCNSL were renal cell carcinoma in 2 patients and atypical chronic lymphocytic leukemia variant with 17p deletion. All patients with RPCNSL presented with altered mental status and 2/3 SCNSL patients were altered upon presentation; 1 SCNSL patient was asymptomatic. The lesions within the RPCNSL cohort were all single lesions, localized to the frontal and temporal lobes. Within the SCNSL cohort, 2/3 patients had multiple lesions, whereas 1 patient had single lesions. All of the RPCNSL patients were ultimately on palliative care. SCNSL 2/3 were lost to follow-up and 1/3 elected to proceed with further treatment.

CONCLUSION

Although differing in etiology, there are shared features among SCNSL and RPCNSL. Most relapses are in the central nervous system, a small number of relapses are isolated systemic relapses, and clinical symptoms occur early and vary. Treatment is similar for both, although the prognosis for RPCNSL is very poor.
NCMP-13. TOLERANCE OF HIGH-DOSE METHOTREXATE TREATMENT OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA (PCNSL) PATIENTS WITH RENAL IMPAIRMENT, CASE SERIES AND REVIEW OF LITERATURE
Authors: Zhu Jay-Jiguang , Chinea Luis , Quintero Juan Carlos Rodriguez , Ware Cornelius
Published: November 2022

PCNSL in immune competent patients is a rare extra-nodal non-Hodgkin lymphoma that accounts for 3–4% of newly diagnosed CNS tumors. Treatment consists of high-dose methotrexate (HD-MTX) based polychemotherapy regimen with or without brain radiation. There are few reported cases supporting the use of HD-MTX as a treatment option in such patients with impaired renal function. The objective of this study was to analyze outcomes and tolerance of HD-MTX based chemotherapy regimen (HD-MTX, rituximab and temozolomide, MRT) in patients with PCNSL and renal impairment. We present five patients with median age 63 (range 40 – 67) at diagnosis, with varying degrees of renal impairments, were all treated with and tolerated well of MRT. They are all alive and have been on observation. Cases 2 & 3 had a one functioning kidney and achieved complete responses (CR) without toxicities. Case 1, with history of grade 3 renal insufficiency during his initial HD-MTX and received carboxypeptidase G2 rescue, tolerated re-treatment with MRT at PCNSL recurrence and achieved a partial response (PR) that has been stable for 44 months. Case 4, who had a cadaver-transplanted kidney, was able to get a CR after 8 treatment with MRT. Case 5, with grade 3 chronic kidney disease from type II diabetes mellitus, achieved CR with MRT with slowing down of his MTX clearance. Literature review for reports with PCNSL and renal impairment treated with HD-MTX through March 31, 2022 identified eight cases and their responses and adverse effects summarized. Due to the low number of published cases and limitation of a retrospective analysis, it is impossible to draw a conclusion on the impact of impaired renal function on the tolerance of HD-MTX treatment of PCNSL. However, our findings indicate that a subset of the patients may still benefit from treatment with HD-MTX based chemotherapy.
NCMP-15. A CASE OF SYSTEMIC METASTATIC DIFFUSE LEPTOMENINGEAL GLIONEURAL TUMOR
Authors: Battini Sahithi , Horta Erika , Gokden Murat , Palys Viktoras
Published: November 2022

INTRODUCTION

Diffuse leptomeningeal glioneural tumor (DLGT) is a very rare central nervous tumor that has no standard of care for its treatment. This report illustrates a case of DLGT with a unique presentation and a first description of multiple systemic metastasis. Case: 19 year-old male with personal history of hereditary multiple osteochondromas and recent covid-19 infection who on investigation of headaches, progressive cranio-neuropathies, and right-sided weakness was found to have vasospasms resulting in acute infarcts in multiple vascular areas, and diffuse leptomeningeal enhancement in the thoracic spine and cauda equina. Patient underwent meningeal biopsy, after 2 months of first symptoms, which revealed DLGT per two different neuro-oncology centers. Course of disease was complicated with hydrocephalus needing shunt placement soon after diagnosis. Craniospinal radiation concurrent with temozolomide was started one month from diagnosis. Patient developed pancytopenia and chemotherapy was stop in the first weeks during radiation therapy. Metastatic disease to bone marrow was diagnosed in the second adjuvant temozolomide cycle through biopsy. One week after, on investigation of pleural effusion, lung metastasis were discovered on pleural cytology and thoracic computer tomography. Liquid biopsy showed non-actionable mutations on PIK3CA, BRAF and KRAS. Chemotherapy with carboplatin and vincristine was started with markedly improvement of pancytopenia and pleural effusions leading to cessation of frequent transfusions and auxiliary oxygen. Vincristine dose was decreased due to painful neuropathy and tinnitus. At the end of endovenous chemotherapy, worsening of disease was found with metastasis to muscles of the face and brain parenchyma. Patient was then enrolled in hospice, dying weeks after.

CONCLUSION

DLGT should be considered in the differential diagnosis of vasospasm. DLGT is a primary central nervous system that can metastasize to other organs. Although no standard of care is yet identified, chemotherapy with vincristine and carboplatin can be offered to systemic metastatic disease.
NCMP-21. PEMBROLIZUMAB-ASSOCIATED MYOSITIS, MYASTHENIC CRISIS, AND MYOCARDITIS IN A PATIENT WITH METASTATIC UROTHELIAL CARCINOMA
Authors: Hein Laura , Narayan Anisha , Lia Franco , Barata Pedro , Trevino Christopher
Published: November 2022

Although immune checkpoint inhibitors (ICIs) have improved systemic cancer care, in rare cases, patients develop neuromuscular immune related adverse events (irAEs), which carry high morbidity and mortality. This case study describes an 85-year-old male who developed the triad of myositis, myasthenic crisis, and myocarditis in association with ICI treatment for metastatic urothelial carcinoma (T3N0M1). The patient developed progressive weakness and gait impairment five weeks after initiating treatment with pembrolizumab. Later, he developed reduced ambulation, fatigue, shortness of breath, and orthopnea with concomitant ECG changes. Clinical exam demonstrated dysphagia, ptosis, proximal muscle weakness, fatigable weakness, and areflexia, ultimately resulting in respiratory failure, intubation, and inability to stand. Lab workup revealed elevated creatinine kinase, myoglobin, lactate dehydrogenase, and aldolase, but was notably negative for acetylcholine receptor and muscle specific kinase antibodies. Labs, clinical timeline, and clinical features supported his diagnoses. Interestingly, the cytokine panel demonstrated a high-normal soluble IL-2 receptor alpha which supports autoimmune pathology and elevated IL-10. The patient was treated with pyridostigmine, prednisone, and plasma exchange (PLEX) for 10 exchanges. EMG 10 days into treatment supported evidence of inflammatory myositis. After methylprednisone and PLEX treatment, the patient’s symptoms improved to ambulation with a walker and occasional BiPap support. His metastatic disease remained stable for several weeks while holding pembrolizumab due to toxicity. This case illustrates how early intervention and aggressive treatment for neuromuscular ICI-induced triad can stabilize patients and improve neurologic recovery. Due to the high morbidity and mortality for these irAEs, the authors support increased clinical scrutiny when evaluating these rare conditions and consideration of investigating the acute inflammatory processes. With improved pathophysiologic understanding of these rare conditions, the community can improve outcomes and refine treatments.
NCMP-25. THE EFFECTS OF POLYPHARMACY IN PATIENTS WITH PRIMARY BRAIN TUMORS
Authors: Hyde Allison , Hernandez Juliana
Published: November 2022

Polypharmacy has been described as the use of five or more medications. With the effects of polypharmacy, patients may report difficulty with adherence to therapy, adverse drug-drug interactions, adverse drug-disease interactions, and cost. The development of cancer treatments for brain cancer is accomplished through clinical trials and the unfortunate truth is that most glioblastoma patients will have died in the time it can take to test a new treatment with more than half dying within the first 15 months of diagnosis. Upon completion, participants will be able to describe the effects of polypharmacy in patients with primary brain tumors in the outpatient setting. Additionally, participants will be able to identify the knowledge, skills, and attitudes necessary in the provision of nursing care to the patient with primary brain tumors. A working group comprised of two registered nurses in specialty neuro-oncology was formed. A knowledge, skills, ability framework was used to develop a survey to assess nurses' knowledge, skills, and attitudes regarding the effects of polypharmacy in patients with primary brain tumors. Two nurses were surveyed. Mean scores were calculated and ranked. The nurses reported important knowledge includes understanding of medication adverse and side effects, epidemiology and disease states including tumor histology. Important skills include neurological exam, triage, critical thinking, and patient education. The goal is to investigate the possibility of prioritizing care to include both a balance between treating the disease, use of concomitant medications and their associated adverse events. And in doing so encourage the individual to report an adverse event. In so doing this the patient is provided a wholistic treatment plan tailoring care to the individual. There was a stronger desire to better understand and manage these events.
NCOG-01. CLINICAL DETERMINANTS IMPACTING OVERALL SURVIVAL OF PATIENTS WITH OPERABLE BRAIN METASTASES FROM NON-SMALL CELL LUNG CANCER
Authors: Piffko Andras , Asey Benedikt , Dührsen Lasse , Ristow Inka , Salamon Johannes , Wikman Harriet , Maire Cecile , Lamszus Katrin , Westphal Manfred , Sauvigny Thomas , Mohme Malte
Published: November 2022

The incidence of brain metastases (BM) in non-small cell lung cancer (NSCLC) patients is continuously increasing. The recent improvements of systemic treatment in NSCLC necessitate continuous updates on prognostic subgroups and factors determining overall survival. In order to improve clinical decision-making, we investigated the clinical determinants affecting survival in patients with resectable NSCLC BM. A retrospective analysis was conducted of NSCLC patients with surgically resectable BM treated in our institution between 01/2015 and 12/2020. Relevant clinical factors affecting survival identified by univariate analysis where included in a multivariate logistic regression model. Overall, 264 patients were identified, with a mean age of 62.39 ± 9.98 years at initial diagnosis of NSCLC BM and overall survival (OS) of 23.22 ± 1.71 months. Factors that significantly affected overall survival from time of primary tumor diagnosis included the systemic metastatic load (mean: 45.9 ± 9.7 vs. 58.9 ± 9.4 months, p = 0.021) as well as a number of BM < 2 (mean: 25.5 ± 4.4 vs. 57.4 ± 7.8 months, p = 0.014). When adjusted for survival time after neurosurgical intervention, a significant survival benefit was found in patients < 60 years (32.5 ± 4.3 vs. 28.5 ± 5.2 months, p = 0.036) and patients without any concurrent systemic metastases at time of NSCLC BM diagnosis (mean 32.4 vs. 34.1, p = 0.032). Our data shows that the number of BM (singular/solitary), gender and age, but not localization (infra-/supratentorial), mass-edema index or time to BM occurrence impact overall survival in NSCLC BM patients.Additionally, our study shows that patients in prognostically favorable clinical subgroups have an overall survival, which differs significantly from current statements in literature. The described clinically relevant factors may improve the understanding of the risks and the course of this disease and aid future clinical decision making in tumor boards.
NCOG-05. A BRAIN METASTASES SURVIVAL MODEL USING AN ENSEMBLE TREE APPROACH
Authors: Shumway John , Tan Xianming , Drossopoulos Peter , Torras Marina , File Madison , Joshi Tushar , Ruhashya Ashley , Yanagihara Theodore , Shen Colette
Published: November 2022

PURPOSE/OBJECTIVE(S)

The primary purpose of this study is to determine whether a machine learning approach can estimate survival in patients with brain metastases undergoing stereotactic radiosurgery or fractionated stereotactic radiotherapy (SRS/SRT). The secondary purpose is to identify covariates of importance.

MATERIALS/METHODS

Data were collected for 377 SRS/SRT treatments in 291 patients done between the years 2008-2021. If a patient was treated with more than one course of SRS/SRT within 30 days, they were counted only once. Twenty-five clinically-relevant variables were identified as covariates and the primary outcome of time from brain metastasis diagnoses to death was used to build a random survival forest model. Brain metastasis location was categorized as infratentorial, supratentorial, or both. An 80/20 split was used for training (n = 302) and test (n = 75) sets. Missing data points were imputed using a just-in-time adaptive tree approach. Minimal depth and variable importance (VIMP) approaches were used to identify prognostic factors. Model performance was assessed using time-dependent area under the receiver operating characteristics curve (tAUC).

RESULTS

Median survival time was 16 months. The most important variables according to minimal depth analysis (depth threshold 5.23) were Karnofsky Performance Status (KPS), extracranial status, age, insurance status, metastases volume, histology, number of metastases, and location. Error rate on the test set was 0.38. tAUC was found to increase continuously over time and at 6, 12, 24, and 36 months was 0.56, 0.63, 0.74, and 0.84 respectively.

CONCLUSION

An ensemble tree approach can provide good survival prediction for patients with brain metastases undergoing SRS/SRT. Model performance, as measured by tAUC, increases over time suggesting better predictive capability at longer time intervals. Future directions include collecting more data to increase model performance, comparing to other models, and validating with external data.
NCOG-09. RADIATION INDUCED CEREBRAL VOLUME LOSS AND CEREBROVASCULAR DISEASE RISK IN SURVIVORS OF GRADE 2 AND 3 GLIOMAS
Authors: Gardner Melissa , Winter Sebastian , Dietrich Jorg , Gerstner Elizabeth , Sherman Janet , Shih Helen , Parsons Michael
Published: November 2022

INTRODUCTION

Cranial irradiation with protons (PRT) as compared with photons (PHT) reduces radiation exposure to healthy brain tissue and may mitigate early- and late-delayed complications. Prior work in our group has demonstrated that PRT results in less brain atrophy over 2 years post-treatment as compared with PHT. It is unknown whether individual factors, such as cerebrovascular disease risk (CVDR; known to be important in post-RT brain changes), interacts with treatment type to affect brain volume change.

METHODS

Patients treated with PRT for grade 2 or 3 gliomas were meticulously matched to patients treated with PHT using an eleven-tiered criterion (i.e., age, sex, tumor type, tumor location, laterality, IDH mutation status, 1p19q deletion status, concurrent chemotherapy, adjuvant chemotherapy, total Gy dose, and number of fractions). Brain volume changes were evaluated by measuring changes in ventricular size in the contralesional hemisphere (to reduce impact of tumor-related changes on volumetric measurements). A CVDR score was created, incorporating history of hypertension, hyperlipidemia, smoking, and diabetes. Correlation and multiple regression analyses examined the relationship between CVDR and brain volume loss over 2 years.

RESULTS

Mann-Whitney tests of independence showed no significant differences in CDVR between PHT and PRT treatment groups. Cerebral volume loss correlated significantly with CVDR (r =.404, p =0.02) and treatment type (r=-.366, p =0.036). Age and gender were unrelated to volume loss. A multiple regression analysis that included treatment type (PHT, PRT) and CVDR accounted for 23% of the variance in volume loss, F(2, 32) = 4.383, p < .021.

CONCLUSION

The current study demonstrates that neurotoxicity of radiation therapy is related to both CVDR and radiation treatment type. Longitudinal data, including a larger sample size, are warranted to confirm these preliminary findings. Inclusion of routine neuropsychological outcome data will be critical to understand the functional significance of these results.
NCOG-11. EXTENT OF RESECTION OF CONTRAST-ENHANCING AND NON-ENHANCING TUMOR: DIFFERENT IMPACTS ON SURVIVAL ACCORDING TO TYPES OF ADULT-TYPE DIFFUSE GLIOMAS IN 2021 WHO CLASSIFICATION
Authors: Park Yae Won , Ahn Sung Soo , Kim Eui Hyun , Kim Jinna , Kang Seok-Gu , Chang Jong Hee , Kim Se Hoon , Lee Seung-Koo
Published: November 2022

BACKGROUND

To evaluate the impact of extent of resection (EOR) of contrast-enhancing (CE) and nonenhancing (NE) tumors in the types of adult-type diffuse gliomas according to the 2021 WHO classification.

METHODS

Total 1,196 adult-type diffuse glioma patients diagnosed between 2001 and 2021 from a single institution were enrolled (183 patients with isocitrate dehydrogenase [IDH]-mutant and 1p/19q codeleted oligodendroglioma [herein oligodendroglioma], 211 patients with IDH-mutant astrocytoma, and 802 patients with IDH-wildtype glioblastoma). Analyses were performed within each type to assess predictors of overall survival, including clinical, imaging data, histological grade, O6-methylguanine-methyltransferase (MGMT) promoter methylation status, adjuvant treatment, and EOR of CE and NE tumors. Subgroup analyses were performed in patients with CE tumor.

RESULTS

Among 1,196 patients, 926 (77.4%) patients had CE tumors. In oligodendrogliomas, gross total removal (GTR) of CE tumor was associated with survival (hazard ratio [HR]=0.09, P< 0.001), whereas GTR of NE tumor was not associated with survival (HR=0.41, P=0.088). In 81 (43.3%) oligodendroglioma patients with CE tumor, GTR of CE tumor was the only independent predictor of survival (HR=0.20, P=0.092) in multivariable analysis. GTR of CE and NE tumors was independently associated with better survival in IDH-mutant astrocytoma and IDH-wildtype glioblastoma (all Ps< 0.05).

CONCLUSIONS

GTR of both CE and NE tumors may significantly improve survival within all types of adult-type diffuse gliomas except oligodendrogliomas. In oligodendrogliomas, the EOR of CE tumor may be crucial in survival; aggressive GTR of NE tumor may be unnecessary, whereas GTR of the CE tumor is recommended.
NCOG-13. BEVACIZUMAB IN IDH WILD TYPE ADULT PATIENTS WITH RECURRENT GLIOBLASTOMA: A REAL WORD STUDY IN CHINA
Authors: Cui Run , Guo Chengcheng , Yang Qunying , Mou Yonggao
Published: November 2022

OBJECTIVE

To investigate the efficacy, safety and application mode of bevacizumab in IDH wild-type adult patients with relapsed GBM.

METHODS

The clinical data of IDH wild-type adult patients with recurrent GBM who received bevacizumab monotherapy or combined chemotherapy in Sun Yat-sen University Cancer Center from 2011 to 2020 were retrospectively analyzed. The enrolled patients had recurred for the first time or multiple times after received surgery, radiotherapy and temozolomide. The objective curative effect was evaluated according to the evaluation criteria of response assessment in neuro-oncology(RANO). Kaplan-Meier method was used for survival analysis, Log-Rank test and Cox regression model were used for prognosis analysis. Adverse reactions were evaluated according to CTC 5.0 standard.

RESULTS

81 patients were enrolled, the objective response rate was 62.9%, the disease control rate was 80.2%, the median progression-free survival (PFS) was 4.4 months (95%CI: 4.0-4.8), and the median overall survival (OS) was 7.8 months (95%CI: 6.8-8.8). Univariate analysis showed that the number of recurrences, the dose of bevacizumab, and whether combined with chemotherapy had no effects on OS. Patients with disseminated tumors, KPS score ≥ 60, MGMT promoter methylation, and ki-67 < 30% had prolonged OS. Multivariate analysis showed that KPS score and MGMT promoter status were independent prognostic factors affecting OS. Major adverse events were mostly grade 1 to 2, including: myelosuppression, hypertension, elevated transaminases, nausea/vomiting, and constipation. No grade 4-5 adverse events occurred.

CONCLUSION

Bevacizumab therapy can improve the survival of IDH wild type adult patients with recurrent GBM and was well tolerated. Early or delayed use of bevacizumab after relapse, low-dose or high-dose usage, and whether combined with chemotherapy had no effect on the OS of patients. KPS score and MGMT methylation status were independent prognostic factors affecting OS.
NCOG-14. INTRAOPERATIVE COGNITIVE-LINGUISTIC MAPPING GUIDED BY VISUALIZATION OF GAMMA BAND MODULATION ELECTROCORTICOGRAMS: PROOF OF CONCEPT IN A PATIENT WITH LEFT TEMPORAL AND OCCIPITAL LOW-GRADE ASTROCYTOMA
Authors: Noll Kyle , Asman Priscella , Connelly Katherine , Tasnim Israt , Swamy Chandra , Ene Chibawanye , Sudhakar Tummala , Grasu Roxana , Liu Ho-Ling , Kumar Vinodh , Muir Matthew , Prinsloo Sarah , Michener Hayley , Wefel Jeffrey , Ince Nuri , Prabhu Sujit
Published: November 2022

OBJECTIVE

Determine the feasibility and preliminary utility of a novel approach to intraoperative brain mapping guided by visualization of electrocorticography (ECoG) heat maps.

METHODS

A 39-year-old male with a biopsy-proven left posterior temporal and occipital WHO grade II IDH-mutant astrocytoma underwent awake craniotomy with intraoperative language mapping. Language mapping utilized a dual iPad stimulus presentation system (NeuroMapper) coupled to a portable real-time neural signal processing system capable of both recording cortical activity and delivering direct cortical stimulation in a closed-loop fashion. An ECoG grid (4x8 with 1cm pitch) which covered the majority of the left temporal lobe was used to assess oscillatory cortical activity during administration of language paradigms including object, action, auditory descriptive, and written descriptive naming. ECoG recording and cortical stimulation were synchronized with stimulus presentation via a photosensor attached to the patient-facing tablet. Gamma band modulations in response to language paradigms at each electrode were processed in real-time and visualized as heat maps in MATLAB/Simulink. Following recording and visualization, bipolar direct cortical stimulation from the grid was conducted for each neighboring electrode pair (up to an intensity of 6 mA) during administration of language tasks.

RESULTS

Despite mild fluent aphasia, a large set of reliable baseline stimuli were obtained for the language mapping paradigms. All naming paradigms resulted in strongest heat map activation at electrode 12 located in the anterior to mid superior temporal gyrus. During stimulation, consistent speech arrest was observed across all paradigms when stimulating electrode pair 11-12, indicating good correspondence with ECoG heat map recordings. Additionally, this region corresponded well with posterior language network representation via resting-state fMRI.

CONCLUSION

Intraoperative real-time visualization of task-based ECoG gamma band modulation is feasible and may help identify targets for direct cortical stimulation. If validated, this may improve the efficiency and accuracy of intraoperative language mapping.
NCOG-16. REAL-WORLD ANALYSIS OF OUTCOMES OF PATIENTS RECEIVING BEVACIZUMAB FOR RECURRENT GLIOBLASTOMA
Authors: Chahal Manik , Harrison Rebecca , Mhurchu Elaine Ni , Thiessen Brian
Published: November 2022

Bevacizumab has been publicly funded in British Columbia (BC) since 2011 for treatment of recurrent glioblastoma (rGBM). We performed a retrospective analysis of patients with rGBM treated with bevacizumab to evaluate treatment practices and outcomes. 245 patients with rGBM treated at BC Cancer centers with bevacizumab between January 2011 and December 2019 were reviewed. Patient demographics, tumor characteristics, treatment regimens, and dates and type of radiographic progression and death were collected. Kaplan-Meier method was used to assess overall survival from time of bevacizumab initiation (BevOS), and comparisons were made using the log-rank test. Median OS was 7 months (CI95 = 6.28-7.73) from bevacizumab initiation. 66% of patients on corticosteroids prior to bevacizumab reduced their dose, and performance status was the same or improved in 84% of patients shortly after initiation, suggesting improvement in quality of life. Patients started on bevacizumab < 6 months from chemoradiation (prior to completion of adjuvant temozolomide) had improved BevOS compared to those who started bevacizumab later (p = 0.019), but there was no association between extent of treatment prior to bevacizumab and outcomes (p = 0.417). Additionally, patients who had local progression prior to bevacizumab initiation had improved BevOS compared to those who had distant progression (p = 0.004), suggesting that pseudoprogression may have prompted the therapeutic switch. Furthermore, though there were no differences in baseline characteristics for patients treated at high volume centers vs. low volume centers, patients treated at high volume centers had improved BevOS (p = 0.004), potentially due to differences in expertise between centers or other social determinants of health not captured in baseline demographics. Together, these data highlight the need for optimization of patient selection and bevacizumab administration in high and low volume centers.
NCOG-17. THE CROSS-SECTIONAL AND LONGITUDINAL ASSOCIATION BETWEEN EXECUTIVE FUNCTIONING AND MULTILAYER CENTRALITY OF THE FRONTOPARIETAL NETWORK IN GLIOMA PATIENTS
Authors: van Lingen Marike , Breedt Lucas , Geurts Jeroen , Hillebrand Arjan , Kouwenhoven Mathilde , Kulik Shanna , Reijneveld Jaap , Stam Cornelis , De Hamer Philip Witt , Zimmermann Mona , Santos Fernando , Douw Linda
Published: November 2022

BACKGROUND

Many patients with glioma suffer from poorly understood executive functioning deficits before and/or after tumor resection. In the past decade, it has become increasingly clear that there is a complex interplay between glioma and both local and global functional activity and connectivity. Moreover, multilayer network integration of the frontoparietal network across multiple modalities has recently been found to explain individual differences in executive functioning in healthy subjects.

OBJECTIVE

To test whether multilayer frontoparietal network integration relates to individual differences in executive functioning before and after glioma resection.

METHODS

Patients with glioma (n = 37) underwent neuropsychological tests assessing word fluency, inhibition, and set shifting as components of executive functioning, and resting-state magnetoencephalography at T1 (at diagnosis, before resection) and T2 (1 year after resection). We constructed binary multilayer networks comprising six layers, with each layer representing frequency-specific functional connectivity between source-localized time series of 78 cortical regions. Average frontoparietal network multilayer eigenvector centrality, a measure for network integration, was calculated at both time points. Regression analyses were used to investigate associations with executive functioning.

RESULTS

At T1, lower multilayer integration (p = .017) and having epilepsy (p = .006) associated with poorer set shifting. Decreasing multilayer integration (p = .022) between T1 and T2 and not undergoing chemotherapy at T2 (p = .004) related to deteriorating set shifting. No significant associations were found for word fluency or inhibition.

CONCLUSION

As hypothesized, our results establish multilayer integration of the frontoparietal network as a cross-sectional and longitudinal correlate of executive functioning in glioma patients, further building upon the idea that glioma impacts the whole brain network and general cognitive functioning. However, multilayer integration did not significantly predict postoperative changes in executive functioning, limiting the direct clinical relevance of this measure.