bluuebunny/crossref_metadata_2025 huggingface dataset:
NCMP-17. MISMATCH REPAIR MUTATIONS AND THE CENTRAL NERVOUS SYSTEM: A CASE SERIES OF GERMLINE MUTATIONS AND CNS MALIGNANCY
Authors: Ruiz Amber , Graber Jerome
Published: December 2020

Our understanding of genetic predispositions for malignancy is continually evolving. One family of germline mutations well described in the literature is that of the DNA mismatch repair mechanism (MMR). Lynch syndrome (LS) is due to a loss of function mutation of several MMR genes- MSH2, MLH1, MSH6, and PMS2. Germline MMR mutations lead to microsatellite instability and loss of genomic integrity resulting in an increased risk for various cancers (colorectal, genitourinary, etc). LS may be as common as 1 in 400 people and some MMR mutations have been associated with gliomas. There is a paucity of information regarding frequency of glioma subtypes as well as tumor genetic and molecular characteristics which have important clinical implications. We describe a case series of 6 individuals with germline MMR mutations and brain tumors. Those with MSH2 and PMS2 mutations (n=3) developed glioblastomas at a mean age at diagnosis of 48 years. These tumors expressed MGMT hyper-methylation and high tumor mutational burden. Only one had IDH-1 mutation. Those with MLH1 mutations (n=3), did not develop gliomas. This raises the question of differential glioma subtype development based on MMR gene. It also highlights the possibility of Lynch-associated gliomas having more favorable treatment response due to MGMT methylation and potential response to immunotherapy based on high tumor mutational burden. Though the sample size is small, there appears to be a preponderance of women compared to men (5:1 respectively). Larger studies are needed to verify CNS involvement in germline MMR mutations. In doing so, we hope to identify factors that may influence clinical management and lead to a better understanding of treatment response and disease prognosis.
NCOG-15. PREGNANCY AND GLIOMA
Authors: Rodriguez Andrew , Ruff Michael
Published: December 2020

Improvements in treatments and prognosis in glioma patients has led patients the opportunity for pregnancy despite their diagnosis. In this retrospective case series of 13 patients evaluated at Mayo Clinic, we identified patients who were pregnant at or after glioma diagnosis from 1998-2019. Clinical information was obtained through the electronic medical record. Tumor grade, treatments, peripartum complications, and pediatric outcomes were analyzed. Median follow-up for pregnant patients was 13.5 years (range, 0-24). Of the 13 patients, 2 patients received temozolomide and radiation during pregnancy for glioblastoma and had no peripartum complications. Median survival time in these patients after further treatments was 23.5 months (range, 23.3-23.8). Two children from these pregnancies had no fetal malformations or pediatric developmental delays with median follow-up of 8.8 years (range, 4.7-12.8). Three patients received radiation during pregnancy for high grade gliomas and had no fetal malformations or peripartum complications. Eight patients had one or multiple pregnancies with median 2 (range, 1-3) children at or after diagnosis with 14 children total. Eleven of the 14 children had no fetal malformations or peripartum complications and were conceived without reproductive assistive technologies. Two children, who were identical twins, were born with a placental malformation but otherwise had normal pediatric development. One child was born pre-term and had long-term developmental delays.
NCOG-52. TUMOR TREATING FIELDS IN MENINGIOMA
Authors: Mawrin Christian
Published: December 2020

BACKGROUND

High-grade meningioma are aggressive intracranial tumors and currently only limited treatment options exist. Therefore, there is a need for further studies in search of new therapies. Tumor Treating TTFields (TTFields) therapy serves as an effective treatment against glioblastoma (GBM). Phase 3 clinical trials investigate the use of TTFields in other intracranial tumors, i.e. brain metastases of the non-small cell lung cancer. We here provide an overview of the currently available data regarding the use of TTFields in meningioma.

MATERIALS AND METHODS

We performed a literature search using the term “Tumor treating fields” “NovoTTF”, “TTFields” and “Optune” in combination with “Meningioma”. A brief overview of TTFields in meningioma is provided here.

RESULTS

In vitro studies using patient-derived anaplastic grade III meningioma cell lines showed that TTFields treatment at a frequency of 200 kHz causes a significant reduction of cell proliferation and clonogenicity as well as altering cell morphology. In a case report of a 44-year-old woman suffering from a right anterior temporal tumor as well as a distant right parietal extra-axial convexity meningioma TTFields and Temozolomide treatment was initiated. Brain MRI scans 8, 16 and 20 weeks later showed a reduction in the meningioma tumor size of 42%, 58% & 60%, respectively. Currently, two ongoing trials test the efficacy and safety of the use of TTFields in meningioma patients: a phase II single arm trial (n=27), investigating the combination of TTFields and Bevacizumab in recurrent or progressive meningioma (NCT02847559); and a pilot trial, investigating the effects of TTFields as monotherapy on recurrent atypical and anaplastic meningioma (NCT01892397).

CONCLUSIONS

First data indicate that TTFields might be an option in future high-grade meningioma treatment. Clinical trials need to show safety and efficacy for the TTFields treatment in meningioma patients.
NCOG-61. A CASE OF LONG TERM SURVIVOR OF DISSEMINATED AND RELAPSED GERMINOMA. EIGHTEEN YEARS OF FOLLOW UP
Authors: Fujimaki Takamitsu , Matsuno Akira
Published: December 2020

Germinomas will respond to first-line treatment in general, but prognoses of disseminated and/or relapsed disease are sometimes poor and detailed course of those patients are not well documented. Here we report one of such cases. PATIENT: A 35-year-old man (at the time of abstract submission) initially had polyuria at the age of 15 and anorexia at 16. At the age of 17, MRI showed neurohypophyseal and disseminated tumor along lateral ventricular walls. He was diagnosed to have germinoma by partial resection of the tumor. ICE (Ifosfamide, Cisplatin, Etoposide) chemotherapy was given followed by 24 Gy whole ventricular irradiation. The tumor was well controlled for 22 months. However despite maintenance ICE chemotherapy, the tumor relapsed along the ventricular walls. With simultaneous BEP (Bleomycin, Etoposide, Cisplatin) chemotherapy and 40 Gy whole neuroaxis irradiation, all the tumor disappeared and he remains in complete remission now. He is receiving hormone replacement therapy. Eight years after the initial surgery, an MRI showed cavernous angioma in the cerebellum and the number has been increasing in follow-up scans. Asymptomatic minor bleeding occurred 14 and 15 years after the initial surgery. On MRA, no vasculopathy on major vessels has been identified. His wife gave birth to his first child through infertility treatment, when he was 34. He finished graduate school to obtain master degree and working as a company employee. CONCLUSION: Germinoma is a disease that can cause long-term survival even after recurrence. However, complications may occur and multimodality approaches are needed for the survivors.
NCOG-67. QUANTIFYING THE UTILITY OF A MULTIDISCIPLINARY NEURO-ONCOLOGY TUMOR BOARD
Authors: Khalafallah Adham , Jimenez Adrian , Romo Carlos , Kamson David , Kleinberg Lawrence , Weingart Jon , Brem Henry , Grossman Stuart , Mukherjee Debraj
Published: December 2020

BACKGROUND

There is limited research attempting to measure the efficacy of tumor boards (MDTBs) in the treatment of patients with tumors affecting the nervous system.

OBJECTIVE

The objective of the present study was to quantify the utility of a MDTB in providing alternative diagnostic interpretations and treatment plans for this patient population.

METHODS

A prospective study of patient cases discussed at four hospitals’ MDTBs between July and November 2019 was performed. Demographic data, diagnoses, treatment plans, and eligibility for clinical trials were recorded, among other variables.

RESULTS

A total of 176 patient cases met eligibility criteria. The majority of patients (53%) were male with a mean age of 52 years. The most frequent diagnosis was glioblastoma (32.4%). Among the evaluable cases, MDTBs led to 38 (21.6%) changes in image interpretation and 103 (58.2%) changes in patient management. Additionally, patients whose cases were discussed at MDTBs had significantly shorter referral times compared to patients whose cases were not discussed (p= 0.024).

CONCLUSION

MDTB discussions led to a significant number of diagnostic and treatment plan changes as well as shortened referral times, highlighting the potential clinical impact of multidisciplinary care for patients with nervous system tumors.
NCOG-69. SEX DIFFERENCES IN GLIOBLASTOMA PATIENT SURVIVAL AS A FUNCTION OF EXTENT OF SURGICAL RESECTION AND CYCLES OF ADJUVANT TEMOZOLOMIDE DURING STANDARD-OF-CARE REGIMENS
Authors: Lorence Julia , Bencomo Tomas , White Haylye , Rickertsen Cassandra , Massey Susan , Singleton Kyle , Hawkins-Daarud Andrea , Johnston Sandra , Porter Alyx , Mrugala Maciej , Bendok Bernard , Hu Leland , Rubin Joshua , Swanson Kristin
Published: December 2020

OBJECTIVE

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults, with males more commonly affected than females(1.6:1). Despite advancements in treatments, prognosis is dismal with a median overall survival of 15 months. Our aim was to investigate sex as a variable in GBM patient survival after receiving incremental levels of standard-of-care treatment regimens – different extents of surgical resection and different numbers of cycles of adjuvant temozolomide chemotherapy.

METHODS

Drawing from our extensive multi-institutional brain tumor repository, we investigated GBM subjects with overall survival (OS), extent of resection (EOR), number of temozolomide (TMZ) cycles, and sex data (n=620, males: n=387, females: n=233). Cox proportional hazard ratios were computed to investigate the multivariable predictive value of the patient variables with OS. Patients were then divided into groups based on their sex, EOR (either biopsy, subtotal resection (STR) or gross total resection (GTR)), and TMZ cycles (I: < 6 cycles, II: 7-11 cycles and III: >12 cycles).

RESULTS

We observed that STR was beneficial for females (HR=0.52; CI=0.33-0.83; p-value=0.013), while for males the benefit was not detected (HR=0.73; CI=0.46-1.15; p-value=0.173) for STR but was detectable for GTR (HR=0.58, CI=0.37-0.90; p-value=0.014). Females receiving 7-11 cycles of TMZ showed a survival benefit (HR=0.52; CI=0.12-0.53; p-value=0.048) while males in the same group did not (HR=0.74; CI=0.46-1.19; p-value=0.21), in comparison to those in group I of TMZ cycles. No sex differences were identified in patients receiving < =6 cycles or >=12 cycles.

CONCLUSION

Together, our results contribute to the growing literature that sex differences exist in GBM patients, even in response to standard-of-care therapies. This should be accounted for when designing clinical trials for GBM so that we may advance our pursuit to deliver personalized medicine.
NIMG-09. PREDICTING OVERALL SURVIVAL OF GLIOBLASTOMA PATIENTS ON MULTI-INSTITUTIONAL HISTOPATHOLOGY STAINED SLIDES USING DEEP LEARNING AND POPULATION-BASED NORMALIZATION
Authors: Hao Jie , Agraz Jose , Grenko Caleb , Park Ji Won , Viaene Angela , Nasrallah Maclean , Kim Dokyoon , Bakas Spyridon
Published: December 2020

MOTIVATION

Glioblastoma is the most common and aggressive adult brain tumor. Clinical histopathologic evaluation is essential for tumor classification, which according to the World Health Organization is associated with prognostic information. Accurate prediction of patient overall survival (OS) from clinical routine baseline histopathology whole slide images (WSI) using advanced computational methods, while considering variations in the staining process, could contribute to clinical decision-making and patient management optimization.

METHODS

We utilize The Cancer Genome Atlas glioblastoma (TCGA-GBM) collection, comprising multi-institutional hematoxylin and eosin (H&E) stained frozen top-section WSI, genomic, and clinical data from 121 subjects. Data are randomly split into training (80%), validation (10%), and testing (10%) sets, while proportionally keeping the ratio of censored patients. We propose a novel deep learning algorithm to identify survival-discriminative histopathological patterns in a WSI, through feature maps, and quantitatively integrate them with gene expression and clinical data to predict patient OS. The concordance index (C-index) is used to quantify the predictive OS performance. Variations in slide staining are assessed through a novel population-based stain normalization approach, informed of glioblastoma distinct histologic sub-regions and their appearance from 509 H&E stained slides with corresponding anatomical annotations from the Ivy Glioblastoma Atlas Project (IvyGAP).

RESULTS

C-index was equal to 0.797, 0.713, and 0.703 for the training, validation, and testing data, respectively, prior to stain normalization. Following normalization, staining variations in H&E and ‘E’ gained significant improvements in IvyGAP (pWilcoxon< 0.01) and TCGA-GBM (pWilcoxon< 0.0001) data, respectively. These improvements contributed to further optimizing the C-index to 0.871, 0.777, and 0.780 for the training, validation, and testing data, respectively.

CONCLUSIONS

Appropriate normalization and integrative deep learning yield accurate OS prediction of glioblastoma patients through H&E slides, generalizable in multi-institutional data, potentially contributing to patient stratification in clinical trials. Our computationally-identified survival-discriminative histopathological patterns can contribute in further understanding glioblastoma.
NIMG-25. TRANSFERRIN RECEPTOR 1 TARGETED PET/CT AND NIFR PROBES FOR IMAGING GLIOBLASTOMA MOUSE MODELS
Authors: Ni Xiang-Rong , Zhao Yi-Ying , Cai Hai-Ping , Yu Zhi-Hui , Wang Jing , Chen Fu-Rong , Yu Yan-Jiao , Feng Guo-Kai , chen Zhong-ping
Published: December 2020

OBJECTIVE

A new imaging technology that indiscriminately detects intracranial glioblastoma (GBM) can help neurosurgeons remove tumor mass completely. Transferrin receptors (TfR 1) have been widely investigated as a diagnostic and therapeutic target in GBM. A TfR 1-targeted peptide, CRTIGPSVC (CRT) can accumulate at high levels in GBM tissues. In our study, taking the advantage of CRT, we synthesized two molecular imaging probes for imaging GBM precisely. One is a PET/CT probe 18F-NOTA-CRT, and the other is a near-infrared fluorescent (NIFR) probe Cy5-CRT.

METHODS

We initially confirmed the overexpression of TfR 1 in most of GBM and the tumor-specific homing ability of 18F-NOTA-CRT and Cy5-CRT in orthotopic U87 GBM (TfR 1 overexpression) mouse models. We then examined the feasibility of Cy5-CRT for specially identifying the GBM tissue margin in the intracranial U87 xenografts in vivo and ex vivo. Next, we compared Cy5-CRT with the clinically used fluorescein sodium in identifying tumor margins. Finally, we used Cy5-CRT to carry out a fluorescence-guided operation on a orthotopic U87 mouse model.

RESULTS

Both 18F-NOTA-CRT and Cy5-CRT probes specifically accumulated in U87 GBM xenografts with TfR 1 overexpression, but not in U373 GBM xenografts with very low TfR 1 expression. Cy5-CRT detected the intracranial tumor burden with exceptional contrast, enabling fluorescence-guided GBM resection under NIFR live imaging conditions. Importantly, Cy5-CRT recognized the GBM tissue margin more clearly than fluorescein sodium.

CONCLUSIONS

Our probes were capable of thoroughly detecting GBM tissue in vivo imaging. For translational applications, we may screen patients before surgery by PET/CT imaging with 18F-NOTA-CRT to identify gliomas with TfR 1 overexpression. As for fluorescence-guided surgery, the TfR 1-targeted optical probe Cy5-CRT specifically differentiates tumor tissues from normal brain with high sensitivity, indicating its potential application for the precise surgical removal of GBM. Keywords: Transferrin receptor 1; PET/CT; near-infrared fluorescence imaging; glioblastoma, fluorescence-guided surgery
NIMG-35. IMPROVING CETCS MICRONEEDLE VISIBILITY IN A MAGNETIC RESONANCE IMAGING ENVIRONMENT
Authors: Morales Brianna , Mehta Jason , Rylander Christopher
Published: December 2020

INTRODUCTION

Annually, there are less than 20,000 cases of glioblastoma reported in the United States. This malignant tumor type has a survival rate of 5.6% and patient survival is approximately 14 months. The current standard of treatment is tumor resection, an attempt to remove the tumor; followed by, chemotherapy and radiation treatment. A newer form of treatment is convection-enhanced delivery (CED). Dr. Chris Rylander’s lab developed a novel method of CED, known as the convection-enhanced thermo-therapy catheter system (CETCS). The implementation of CETCS will be in an MRI environment, which calls for a need to improve the contrast of the needles against the native brain tissue. Increased contrast of the needles could improve remote control of the needles, and delivery of the drug.

METHODS

We evaluated several groups: (1) Control (water and air), (2) Nanomaterials in Polyimide Resin (Iron oxide nanoparticles and gadolinium oxide nanoparticles, some were contained in a polyetheretherketone tubing), and (3) Stainless Steel Wire (SS 316L). We cast needle groups into a 0.6% (w/w) Agarose phantom. Then, images were acquired with a 3T Siemens MRI and a 20-channel head coil in a series of 30 slices through the axial face of the phantom to the proximal face of the cube. Width analysis was conducted using Syngo FastView to determine the size of the artifacts in the MR images.

RESULTS

All modifications had a higher contrast than the controls, and the two largest artifacts measured were the SS 316L (4.9 ± 0.3 mm) and the iron oxide nanoparticles in the polyimide resin (3.5 ± 0.1 mm). An additional observation was the non-uniform shape of the two groups with the large artifacts.

DISCUSSION

Future iterations of these modifications need to be adjusted based on the desired artifact size, currently set to be at least 2 mm in diameter.
NIMG-56. THE RARE CASE OF PRIMARY DURAL BASED MARGINAL ZONE B-CELL LYMPHOMA CAMOUFLAGING AS MILD FOCAL DURA THICKNESS AND PACYMENINGEAL ENHANCEMENT
Authors: Hrachova Maya , Perez-Rosendahl Mari , Kong Xiao-Tang
Published: December 2020

INTRODUCTION

Primary Dural Based Marginal Zone B-Cell Lymphoma (MZBCL) is a subtype of PCNSL with an incidence rate ranging from 0.6 to 3% of all brain tumors. MZBCL typically presents as an extra-axial mass resembling meningioma. Here we report an unusual case of MZBCL with initial radiographic findings of mild nonspecific thickening tentorium and pachymeningeal enhancement surrounding 7th and 8th cranial nerves.

CASE REPORT

A 58-year old woman with clinical history of CMV infection, polyclonal gammopathy and unruptured left ICA aneurysm post coil embolization who presented for an evaluation of mild thickening and enhancement of the left tentorium cerebelli and 7th/8th nerve root complex. Differential considerations included inflammatory/autoimmune conditions (idiopathic hypertrophic pachymeningitis, neurosarcoidosis, Tolosa-Hunt syndrome), infections, structural lesion, benign or malignant neoplasm. Serum studies were normal. Multiple CSF studies were negative. Flow cytometry showed no malignant cells with few small lymphocytes. She was followed with the imaging surveillance for nine months until further increased thickening of dura on MRI. She underwent cerebellar dural biopsy that was consistent with MZBCL composed mainly of small CD20+ B-cells and negative MYD88. PET scan showed no systemic involvement. Bone biopsy revealed no evidence of lymphoma. The focal leptomeningeal enhancement improved significantly after she received four doses of systemic rituximab treatments.

DISCUSSION

Our case highlights the importance of surveillance and brain biopsy in cases of mild focal dura/pachymeningeal thickness and enhancement if no conclusive diagnosis has been established, as it might be one of the rare tumors such as MZBLC.
NIMG-64. DISTINCT IMAGING PATTERNS OF PSEUDOPROGRESSION IN GLIOMA PATIENTS FOLLOWING PROTON VERSUS PHOTON RADIATION THERAPY
Authors: Graber Jerome , Ritterbusch Reed , Halasz Lia
Published: December 2020

PURPOSE

Radiologic Assessment in Neuro-Oncology (RANO) criteria define pseudoprogression (Ps) after photon radiation for gliomas, as occurring less than twelve weeks from radiation, within the high dose radiation field. However, some patients receiving proton manifest lesions that appear subjectively different from photon Ps based on timing and location (more than six months from radiation and deeper to the prior tumor), which would be called tumor progression by RANO. We retrospectively reviewed MRI changes after proton or photon radiation for gliomas. We propose criteria to characterize proton pseudoprogression (ProPs) distinct from photon pseudoprogression or tumor progression.

METHODS

Post-treatment MRIs of patients with gliomas were reviewed, along with clinical and pathological data. 77 proton patients were reviewed for the presence of ProPs, and 64 photon patients were reviewed for imaging changes. Data collected included the location, timing, and morphology of the lesions, tumor type, chemotherapy, and clinical symptoms.

RESULTS

16 (21%) of the patients who received protons had imaging changes unique to protons, at a mean of 14.6 months after radiation. We established the following criteria to characterize ProPs: not immediately in or adjacent to the resection cavity; ~ 2cm opposite from target beam entry; can resolve without treatment; subjectively multifocal, patchy, small (< 1cm). None of the photon patients had lesions that met our criteria for ProPs (p< 0.001).

CONCLUSION

Patients who receive protons can have a unique subtype of pseudoprogression (Ps), which we refer to as proton pseudoprogression (or ProPs). These lesions could be mistaken for tumor progression, but typically resolve spontaneously. ProPs can possibly be explained by the increased relative biological effectiveness of protons and beam angle selection which may deposit at ~2cm deep to the target. Recognizing these lesions can prevent unnecessary treatment for mistaken tumor progression, especially in the context of clinical trials that include proton.
NIMG-66. AI-BASED PROGNOSTIC IMAGING BIOMARKERS FOR PRECISION NEUROONCOLOGY AND THE RESPOND CONSORTIUM
Authors: Davatzikos Christos , Badve Chaitra , Kazerooni Anahita Fathi , Bashyam Vishnu , Bakas Spyridon , Colen Rivka , Mahajan Abhishek , Balaña Carmen , Capellades Jaume , Puig Josep , Jain Rajan , Sloan Andrew E , Marcus Daniel S , Choi Yoon Seong , Lee Seung-Koo , Chang Jong Hee , Poisson Laila M , Griffith Brent , Dicker Adam P , Flanders Adam E , Booth Thomas C , Rathore Saima , Akbari Hamed , Sako Chiharu , Bilello Michel , Shukla Gaurav , Brem Steven , Lustig Robert , Mohan Suyash , Nasrallah MacLean , O’Rourke Donald M , Bagley Stephen , Barnholtz-Sloan Jill S
Published: December 2020

AI-based methods have shown great promise in a variety of biomedical research fields, including neurooncologic imaging. For example, machine learning methods have offered informative predictions of overall survival (OS) and progression-free survival (PFS), differentiation between pseudoprogression (PsP) and progressive disease (PD), and estimation of mutational status from imaging data. Despite their promise, AI, and especially the emerging deep learning (DL) methods, are challenged by several factors, including imaging heterogeneity across scanners and lack of sufficiently large and diverse training datasets, which limits their reproducibility and general acceptance. These challenges prompted the development of the ReSPOND (Radiomics Signatures for PrecisiON Diagnostics) consortium on glioblastoma, a growing effort to bring together a community of researchers sharing imaging, demographic, clinical and (currently) limited molecular data in order to address the following aims: 1) pool and harmonize data across diverse hospitals and patient populations worldwide; 2) derive robust and generalizable AI models for prediction of (initially) OS, PFS, PsP vs. PD, and recurrence; 3) test these predictive models across multiple sites. In its first phase, ReSPOND aims to pool together approximately 3,000MRI scans (from 10institutions plus TCIA), along with demographics, KPS, and (for a subset) MGMT/IDH1 status. We present initial results testing the generalization of a previously trained model of OS on 505Penn datasets to 2independent cohorts from Case Western Reserve University and University Hospitals (N=44), and Penn (N=67). The results indicate good generalization, with correlation coefficients between OS/predicted-OS between 0.25 to 0.5, depending on variable availability, which is comparable to cross-validated accuracy previously obtained from the training set itself (N=505). Additional preliminary studies evaluating prediction of future recurrence from baseline pre-operative scans in de novo patients (Penn model applied to CWR) indicated potential for guiding targeted dose escalation and supra-total resection (excellent predictions in 6/12 patients, modest in 1/12, and poor in 5/12).
PATH-38. METASTATIC MENINGIOMA CAUSING CHRONIC RESPIRATORY FAILURE
Authors: Wallace Dhiren , Wallace Gerald , Fenwick Nichols , Vender John , Sood Ambika , Mattox Samantha , Sharma Suash
Published: December 2020

Meningiomas are the most common primary intracranial tumor accounting for almost 37% of all CNS tumors. Malignant meningiomas are uncommon, accounting for 0.5% of all meningiomas. Malignant meningioma that is metastatic outside the cranium/skull is even rarer, with only a few case reports. Metastases to the lung and abdomen have been reported and thought to travel via venous drainage. WHO Grading suggest that Grade III meningiomas have the greatest potential to metastasize extra-cranially. We present the case for the 47-year-old Senegalese American man with biopsy proven Grade II meningioma metastatic to his lungs with resultant hypercapnic respiratory failure.
QOLP-04. PILOT STUDY OF A VIDEOCONFERENCE-BASED PSYCHOLOGICAL INTERVENTION FOR FAMILY CAREGIVERS OF PATIENTS WITH MALIGNANT GLIOMAS
Authors: Forst Deborah , Mesa Michelle , Kaslow-Zieve Emilia , El-Jawahri Areej , Greer Joseph , Sereno Isabella , Corveleyn Amy , Anand Maya , Landay Sophia , Horenstein Arielle , Temel Jennifer , Jacobs Jamie
Published: December 2020

BACKGROUND

Caregivers of patients with malignant gliomas experience substantial anxiety symptoms while caring for someone with progressive neurological decline. Yet, interventions to reduce psychological distress and improve quality of life (QoL) in this caregiver population are lacking.

METHODS

We conducted an open pilot study evaluating feasibility and acceptability of a cognitive behavioral therapy-based intervention for caregivers of patients with malignant gliomas with clinically significant anxiety (Generalized Anxiety Disorder [GAD-7] score ≥ 5). Caregivers participated in six videoconference sessions with a mental health provider. We defined the intervention as feasible if ≥ 70% of eligible caregivers enrolled and ≥ 70% of those enrolled completed ≥ 50% of sessions. We evaluated intervention acceptability in semi-structured interviews. Caregivers completed baseline and post-intervention surveys assessing anxiety and depression symptoms (Hospital Anxiety and Depression Scale), QoL (Caregiver Oncology Quality of Life Questionnaire), caregiving burden (Caregiver Reaction Assessment), self-efficacy (Lewis Cancer Self-Efficacy Scale), and perceived coping skills (Measure of Current Status-Part A). We explored post-intervention changes using paired t-tests.

RESULTS

We obtained consent from 70.0% (21/30) of caregivers approached, of which 66.7% (14/21) had clinically significant anxiety and thus were eligible to participate (mean age=55.7 years, 64.3% female). Among enrolled caregivers, 71.4% (10/14) completed ≥ 50% of sessions. In semi-structured interviews, all participants found the intervention helpful and valued the ability to participate remotely via videoconference. Among caregivers who completed at least one session, 80.0% (8/10) completed all assessments and were included in analyses. Post-intervention, caregivers reported reduced anxiety symptoms (P=.02) and improved QoL (P=.03) and coping skills (P=.001). We found no significant change in depression, caregiving burden, or self-efficacy.

CONCLUSION

Our videoconference-based intervention is feasible and acceptable to caregivers. Participants reported significant improvements in anxiety symptoms, quality of life, and coping skills post-intervention, supporting further investigation of the intervention in a randomized controlled trial.
QOLP-24. ENGAGING PATIENTS AND CAREGIVERS TO IMPROVE THE IMPORTANCE AND QUALITY OF SUPPORTIVE CARE RESEARCH IN NEURO-ONCOLOGY
Authors: Peters Katherine , Randazzo Dina , Johnson Margaret , Kim Jung-Young , Patel Mallika , Affronti Mary
Published: December 2020

BACKGROUND

From the time of diagnosis to end of life, patients with primary brain tumors experience challenges to maintain quality of life. While traditional research focuses on clinical trials that involve directly treating cancer, we have designed a specific research committee at our institution that promotes supportive care research to improve patients’ and caregivers’ quality of life. Past research has shown that issues key to patients and caregivers often differ from what researchers and providers might appreciate as important. Incorporating input from brain tumor patients and caregivers is vital to direct the most relevant and necessary supportive care research.

METHODS

As part of an IRB-approved quality improvement project, we sought the opinions of our supportive care research committee about what are the essential quality of life issues for brain tumor patients and caregivers. We polled our committee before and after a session with patients and caregivers discussing factors relevant to their quality of life. After this patient/caregiver intervention, we used a group discussion and note comparison technique to distill down key elements to advance supportive care research for this population.

RESULTS

Engagement of the committee included members that were neuro-oncology providers, biostatisticians, and data/regulatory/clinical trial staff. Before the intervention, common themes about key issues for patients and caregivers were comfort, pain management, counteracting side effects, cognitive issues, and financial toxicity. While similar themes emerged after the patient/caregiver intervention, the committee gleaned that aspects of communicating outcomes and support of caregivers were consistently mentioned from the discussion session with patients and caregivers.

CONCLUSIONS

Opinions of brain tumor patients and caregivers are crucial in driving future direction and relevance of supportive care research in neuro-oncology. Our supportive care research committee will continue to engage patients and caregivers and are planning interventions to improve communication and support for caregivers.
QOLP-30. FEAR OF CANCER RECURRENCE IN PRIMARY BRAIN TUMOR PATIENTS: DO DISEASE-RELATED CHARACTERISTICS MATTER?
Authors: Braun Sarah , Aslanzadeh Farah , Thacker Leroy , Loughan Ashlee
Published: December 2020

BACKGROUND/PURPOSE

Fear of cancer recurrence (FCR) is associated with disease-related variables including cancer stage and time since diagnosis in non-CNS cancer patients. However, no studies have investigated these relationships in primary brain tumor patients (PBT), with most research on FCR excluding this population purposefully. Given that a diagnosis of PBT is diverse in terms of prognosis, treatment, and disease trajectory, FCR in neuro-oncology may be different from other cancer populations and warrants investigation.

METHODS

PBT patients receiving care at an NCI-designated cancer center completed the FCR-7, a validated questionnaire assessing FCR. Disease-related variables, including tumor grade, tumor hemisphere, and time since diagnosis were obtained via medical records and investigated as correlates of FCR using t-test, non-parametric Kruskal-Wallis test, and Pearson correlation, respectively.

RESULTS

Eighty PBT patients (58% female; M age=50.83, range=20-86) agreed to participate. Average patient FCR7 was 17.15 (SD=8.93). The 60th percentile of patient FCR7 was 17.00 and the 90th percentile was 31.90. There was no difference in FCR between low and high tumor grades (p = 0.50). There was no difference in FCR between left, right, and bilateral tumor hemispheres (p = 0.67). Similarly, time since diagnosis was unrelated to FCR (p = 0.54).

CONCLUSION

Inconsistent with findings in non-CNS cancer, FCR was not related to disease-related variables in PBT patients. Given the certainty of tumor recurrence in this population, FCR may be a more robust experience in PBT patients, such that disease characteristics do not buffer this cancer-specific distress. These results emphasize the need for inclusion of PBT in psycho-oncology research, particularly investigations of psychotherapy targeting FCR across disease-related variables such as tumor grade, tumor hemisphere, and time since diagnosis. The lack of generalizability of non-CNS cancer findings and the further exclusion of this population will prevent efforts to provide patient-centered end-of-life care within neuro-oncology.
RADT-02. CLINICAL OUTCOMES OF BREAST BRAIN METASTASES BY SUBTYPE FOLLOWING LINAC BASED STEREOTACTIC RADIATION
Authors: Thawani Chetna , Mills Matthew , Figura Nicholas , Sarangkasiri Siriporn , Washington Iman , Robinson Timothy , Diaz Roberto , Etame Arnold , Vogelbaum Michael , Yu Hsiang-Hsuan , Ahmed Kamran
Published: December 2020

BACKGROUND

Management of breast cancer brain metastases has become an increasing concern due to improved systemic control. Failure patterns in the brain may vary by breast cancer subtype.

OBJECTIVE

In this study, we sought to distinguish our institutional clinical outcomes following stereotactic radiation by breast cancer subtype.

METHODS

A total of 180 breast cancer patients treated over 279 stereotactic sessions to 646 brain metastases were identified from our LINAC based stereotactic radiation institutional registry. Patients were treated between August 2004 and May 2019. Outcomes including distant brain metastases control (DC) as well as overall survival (OS) following stereotactic radiation were assessed from review of the clinical chart and radiologic examinations.

RESULTS

The median age of patients was 55 (range: 28-86 years). Subtypes in order of decreasing frequency were hormone receptor (HR)+ (n=64; 36%), HR+/HER2+ (n=47; 26%), triple negative (TN) (n=43; 24%), and HR-/HER2+ (n=26; 14%). TN patients had the shortest interval from systemic metastases to brain metastases diagnosis; HR-/HER2 + 16 months, HR+ 13.3 months, HR+/HER2 + 11 months, and TN 1.4 months (p=0.02). Median follow-up from brain metastases diagnosis was 21.2 months (range: 0.9-135.4 months). Twenty-four month Kaplan-Meier (KM) DC rates varied by subtype and were 49% (HR+/HER2+), 38% (HR+), 33% (HR-/HER2+) and 21% (TN) (p=0.0004), respectively. Similar differences were noted in OS with 24 month KM rates of 58% (HR+/HER2+), 51% (HR-/HER2+), 27% (HR+), and 14% (TN), p< 0.0001. A total of 26 patients (14%) were noted to undergo leptomeningeal disease (LMD) progression. No differences were noted by subtype and LMD progression (p=0.88).

CONCLUSIONS

In our institutional series of breast cancer brain metastases treated with stereotactic radiation, significant differences were noted in clinical outcomes by breast cancer subtype. HR+/HER2+ patients had the best DC and OS rates while outcomes were poorest for TN patients.
RADT-19. EFFECTS OF RADIATION DOSE-RATE AND TUMOR CHARACTERISTICS ON LOCAL CONTROL AND TOXICITY AFTER RADIOSURGERY FOR ACOUSTIC NEUROMAS
Authors: Josef Villafuerte Conrad , Gentili Fred , Shultz David , Berlin Alejandro , Heaton Robert , van Prooijen Monique , Cusimano Michael , Schwartz Michael , Zadeh Gelareh , Payne David , Tsang Derek
Published: December 2020

INTRODUCTION

The effect of stereotactic radiosurgery (SRS) dose-rate on tumor control for acoustic neuroma (AN, or vestibular schwannoma) is unclear.

METHODS

This was a retrospective study of all patients treated for AN with frame-based cobalt-60 SRS at the Toronto Western Hospital between 2005-2019. Dose rates on the day of SRS were calculated from the calibration dose-rate while accounting for the cobalt-60 half-life of 5.2713 years. Local failure was defined as continued tumor growth >36 months post-SRS, tumor resection for LF, or use of any repeat SRS for LF. Cumulative incidence of LF was reported after accounting for competing risks of death, on a per-lesion basis. Comparisons of actuarial LF were made using Gray’s test. Multivariable analysis of LF was performed using a proportional hazards model.

RESULTS

A total of 607 patients were treated for 617 acoustic neuromas. Median follow-up was 5.0 years. 158 tumors (26%) were cystic. 71 tumors (12%) had previous resection. Nine patients received 10-11 Gy due to large tumor size; all remaining patients received 12 Gy to approximately the 50% isodose line. Median dose rate was 2.4 Gy/min (range, 1.3-3.7). There was no association between dose rate and LF (≥ 2.4 Gy/min vs. < 2.4 Gy/min, 6.07% vs. 6.12% at 5-year follow-up, p = 0.75). The adjusted local failure-specific hazard ratio (HR) for dose rate (per Gy/min) was 1.2 (95% CI 0.69-2.1, p = 0.52). Patients with previous surgery had higher LF, with a HR of 3.6 (95% CI 1.7-7.8, p = 0.0012), after adjusting for presence of cysts (HR 0.27, p = 0.034) and maximum tumor diameter (HR 1.055 per cm, p = 0.071).

CONCLUSIONS

In a large cohort of patients with acoustic neuromas, radiosurgery dose-rate was not associated with tumor control. Previous resection was a strong risk factor for local failure after SRS.
RADT-41. ASSESSING THE ROLE OF ADJUVANT RADIATION THERAPY AND RISK FACTORS FOR RECURRENCE FOLLOWING GROSS TOTAL RESECTION OF ATYPICAL MENINGIOMAS
Authors: Harrison Farber S , So Veronica , Mooney Michael , Cole Tyler , Przybylowski Colin , Rogers Leland , Sanai Nader
Published: December 2020

While meningiomas are commonly benign brain tumors, as many as 30% may be classified as atypical, or WHO Grade 2. Patients are at risk of recurrence following resection and often are prescribed adjuvant radiation therapy (RT)-although most data on this treatment is retrospective and has shown mixed RESULTS: In this study we assessed the influence of adjuvant RT following gross total resection (GTR) in patients with newly diagnosed atypical meningiomas at our institution and sought to determine predictors of tumor recurrence. All patients who underwent GTR (Simpson Grade I and II) at their index operation from 1994-2014 were retrospectively reviewed. Patients then either underwent observation or adjuvant RT (Intensity-Modulated Radiation Therapy (IMRT) or stereotactic radiosurgery (SRS)). A total of 145 patients had documented GTR at the time of initial resection, including 88 females (61%) and 57 males (39%), with a mean age of 58 +/- 15.7 years. 118 patients were followed with observation after surgery while 27 (18.6%) patients received adjuvant RT prior to known recurrence (IMRT for 15 patients (55.5%) and SRS in 12 patients (44.4%)). Patients receiving adjuvant RT had significantly larger tumors, as well as a higher incidence of spontaneous necrosis and small cell phenotype on histopathology. Overall 5-year PFS in our cohort was 71.6% (CI 60.6%-84.7%) and was unchanged by adjuvant RT (p = 0.52). 23 patients (15.8%) had a recurrence with a mean follow up of 42.9 months (17.1-53.5 months). Male gender (HR=1.02, p=0.019), tumor size (HR=1.17, p= 0.002) and MIB-1 > 4 (HR=8.50, p=0.04) were associated with increased recurrence risk. There was no association between radiation type (SRS vs. IMRT) and risk of recurrence (p= 0.154). In our patients, adjuvant RT following GTR of atypical meningiomas did not improve PFS. Risk factors for recurrence included male gender, larger tumor size, and MIB-1 > 4.
RADT-46. SYSTEMATIC REVIEW OF RADIOSENSITIZERS FOR MALIGNANT BRAIN TUMORS: POTENTIAL FOR LEARNING FROM PAST FAILURES
Authors: Beg Usman , Snyder Brianna , Madhani Sarosh , Hamidi Nima , Mansouri Alireza
Published: December 2020

INTRODUCTION

Radiation therapy (RT) is the cornerstone of management of malignant CNS tumors but its efficacy is limited in hypoxic tumors. Although numerous radiosensitizer compounds have been developed to enhance the effect of RT, progress has been stagnant. Through this systematic review of the literature on radiosensitizers for malignant CNS tumors, we have sought to provide an overview of radiosensitizers developed to date, summarize their safety and efficacy, and evaluate areas for possible improvement.

METHODS

PUBMED, EMBASE, Cochrane, and Web of Science were searched using terminology pertaining to radiosensitizers for brain tumor RT according to PRISMA guidelines. Publications reporting clinical evidence of non-antineoplastic radiosensitizers with RT for malignant CNS tumors were included. Pre-specified variables were extracted. Outcomes of interest were overall survival, progression-free survival, adverse events, and quality-of-life outcomes.

RESULTS

Forty-eight publications were identified which included 20 unique non-antineoplastic radiosensitizing agents. Only 2/20 agents, fluosol with oxygen, and efaproxiral, showed improvement in outcomes in patients with glioblastoma and brain metastasis, respectively. A larger study was not able to confirm the latter. While molecular similarities between these two agents were not identifiable, the effective mechanism of action allowed them to modulate hypoxia from within blood vessels, without crossing blood-brain barrier. Nine agents required dose modification, change of schedule, or complete discontinuation due to toxicities.

CONCLUSION

Despite decades of research, progress in the field of radiosensitizers for malignant CNS tumors has been limited. Available data demonstrates the lack of progress in identifying effective radiosensitizers for brain tumors. Of the many non-antineoplastic radiosensitizers that have been tested, only two have showed (limited) efficacy by targeting tumor oxygenation. Alternative strategies such as synthetic drug design, based on a mechanism of action that is independent of crossing the blood-brain barrier, may be necessary. Such studies are currently underway.
RTID-01. RADIOSURGERY FOLLOWED BY TUMOR TREATING FIELDS FOR BRAIN METASTASES (1-10) FROM NSCLC IN THE PHASE 3 METIS TRIAL
Authors: Mehta Minesh , Gondi Vinai , Brown Paul , Ahluwalia Manmeet
Published: December 2020

BACKGROUND

Tumor Treating Fields (TTFields) are non-invasive, loco-regional, anti-mitotic treatment modality comprising alternating electric fields. TTFields have demonstrated efficacy in preclinical non-small cell lung cancer (NSCLC) models. TTFields treatment to the brain was safe and extended overall survival in newly-diagnosed glioblastoma. The objective of the METIS study [NCT02831959] is evaluation of the efficacy and safety of TTFields in NSCLC patients with brain metastases.

METHODS

NSCLC patients (N=270) with 1-10 brain metastases were randomized 1:1 to stereotactic radio surgery (SRS) followed by continuous TTFields ((150 kHz, > 18 hours/day) within 7 days of SRS or supportive care. The portable device delivered TTFields to the brain using 4 transducer arrays, while patients received the best standard-of-care for systemic disease. Patients were followed every two months until second intracranial progression. Key inclusion criteria: KPS ≥70, new diagnosis of 1 inoperable or 2–10 supra- and/or infratentorial brain metastases from NSCLC amenable to SRS; and optimal therapy for extracranial disease. Prior WBRT, surgical resection of metastases, or recurrent brain metastases were exclusionary. Primary endpoint was time to 1st intracranial progression. Secondary endpoints included time to neurocognitive failure (HVLT, COWAT and TMT), overall survival, radiological response rate (RANO-BM and RECIST V1.1); quality-of-life; adverse events; time to first/second intracranial progression for patients with 1–4 and 5–10 brain metastases; bi-monthly intracranial progression rate from 2–12 months; and time to second intracranial and distant progression. The sample size (N=270) was calculated using a log-rank test (Lakatos 1988 and 2002) with 80% power at two sided alpha of 0.05 to detect a hazard ratio of 0.57. On September, 2019, an independent Data Monitoring Committee (DMC) reviewed METIS trial data collected to that point. The DMC concluded that no unexpected safety issues had emerged and recommended continuation of the METIS study as planned.
RTID-06. ENHANCING TUMOR TREATING FIELDS THERAPY FOR RECURRENT GLIOBLASTOMA WITH TARGETED AND INDIVIDUALIZED SKULL REMODELING SURGERY. A MULTI-CENTER RANDOMIZED PHASE 2 TRIAL
Authors: Mikic Nikola , Korshøj Anders
Published: December 2020

BACKGROUND

We present an upcoming(Sep. 2020) randomized, comparative, multi-center, investigator-initiated, interventional, phase 2 trial testing the efficacy of a novel therapeutic concept for recurrent glioblastoma(GBM). The intervention combines personalized targeted skull remodeling surgery(SR-surgery) with Tumor Treating Fields(TTFields) and best practice medical oncological therapy. SR-surgery involves strategically placed burr holes to strengthen the electric field in the tumor region. Preclinical studies indicate that SR-surgery provides a marked and focal enhancement(~100%) of TTFields. We recently concluded a phase 1 safety/feasibility study indicating promising clinical efficacy and no clinically significant toxicity related to the intervention. This subsequent randomized, comparative phase 2 trial aims to validate superior efficacy of the treatment.

METHOD

We will utilize a comparative, 1:1 randomized, minimax two-stage phase 2 design with an expected sample size of 70 patients, interim futility analysis at 1-yr follow-up of the first 52 patients and a maximum sample size of 84 patients. Patients will receive either 1)TTFields and best practice medical oncological treatment(control arm) or 2) SR-surgery plus TTFields and best practice medical oncological treatment (interventional arm). Major eligibility criteria include age ≥ 18 years, supratentorial GBM, Karnofsky performance score(KPS) ≥ 70, focal tumor, and lack of uncontrollable epilepsy or significant co-morbidity. The study is designed to detect a 20% increase in the overall survival rate 12 months(OS12) assuming OS12=40% in the control group and OS12= 60% in the intervention group. Secondary endpoints include hazard ratio of overall survival and progression-free survival, objective response rate, QoL, KPS, steroid dose, and toxicity. Patients will be followed for the whole trial period(36 months). The average expected follow-up is 18 months and includes regular assessment of toxicity, response and QoL. Endpoint data will be collected at the end of the trial, occurrence of suspected unexpected serious adverse reactions(SUSARs) or unacceptable serious adverse events(SAEs), withdrawal of consent, or loss-to-follow-up.