bluuebunny/crossref_metadata_2025_split huggingface dataset:
IMMU-43. ZIKA VIRUS TO TREAT GLIOMA: TURNING COLD TUMORS HOT
Authors: Mazzoccoli Luciano , Nair Sharmila , Jash Arijita , Govero Jennifer , Hu Tong , Shresta Sujan , Shi Pei-Yong , Rich Jeremy , Diamond Michael , Chheda Milan 
Published: December 2020

Abstract
GBM is a hallmark example of an immunotherapy-resistant tumor. Previously, we discovered that Zika virus (ZIKV) has a natural honing capacity to specifically kill GBM stem cells (GSCs). Using two syngeneic glioma models, GL261 and CT2A, we found that in vivo intratumoral ZIKV treatment reduces tumor size and extends median survival far beyond that expected for its anti-GSC effects; additionally, approximately 50% of mice were long-term survivors. We now report that ZIKV treatment is associated with an increase in tumor-specific CD8+ T cells and activated myeloid cells expressing MHC-II and NOS2. Treatment with CD8-depleting antibody abrogates the survival advantage conferred by ZIKV, demonstrating that CD8+ T cells are required for ZIKV efficacy. Remarkably, ZIKV treatment also confers protection against tumor re-challenge 1.5 years after the original treatment, and this too is dependent on CD8+ T cells. Lastly, in a bilateral tumor implantation model, intratumoral ZIKV treatment of one tumor increases overall survival, suggesting ZIKV is efficacious because it generates a global anti-tumor response. Building on the observation that ZIKV treatment increases CD8+ T cells in the tumor bed, we combined ZIKV with α-PD1 immunotherapy. We found survival was dramatically increased compared to either treatment alone. Finally, to improve safety of potential ZIKV treatment for patients, we generated an immune-sensitized virus. This strain remains efficacious as a single agent and in combination with immunotherapy in vivo. Overall, our results suggest ZIKV treatment addresses two key problems in our current treatment of GBM: it specifically targets highly resistant GSC and initiates a potent anti-tumor immune response against the remaining tumor. Our work reveals the mechanistic basis of ZIKV efficacy and demonstrates the potential for ZIKV as a therapy for GBM.
IMMU-52. IMMUNE EFFECTOR CELL ASSOCIATED NEUROTOXICITY (ICANS) AMONG PEDIATRIC AND AYA PATIENTS: MD ANDERSON CANCER CENTER EXPERIENCE
Authors: Brown Brandon , Mahadeo Kris , Khazal Sajad , Petropoulos Demetrios , Tewari Priti , Slopis John , Tambaro Paolo , Sadighi Zsila 
Published: December 2020

Abstract

INTRODUCTION
Immune effector cell associated neurotoxicity (ICANS) and cytokine release syndrome (CRS) are potentially life-threatening complications associated with immune effector cell (IEC) therapies. We characterize ICANS in pediatric and adult young adolescent (AYA) patients receiving IEC therapy at our institution.

METHODS
We reviewed clinical characteristics and severity (based on ASTCT Consensus Criteria) in pediatric and AYA patients who received IEC products from 2018–2019 at MDACC.

RESULTS
Nine patients, median age 15.5 (range: 3–25) years received chimeric antigen receptor (CART) IEC therapy. Four (44%) developed ICANS within median of 8 (range: 3–27) days of CAR T cell infusion and median 6 (range: 2–7) days after CRS. Primary diagnoses were pre-B cell acute lymphoblastic leukemia (8) and mediastinal large B-cell lymphoma (1). Median CRS and ICANS severity grade was 2 (range 1–4). Symptoms included altered mental status (AMS) (5), seizure (1), aphasia (2), impaired ability to write a standard sentence (4). Neuroimaging did not correlate to ICANS symptoms or severity. EEG was performed in 3 and 1 had background slowing correlating with aphasia. CSF was obtained in two revealing lymphocytosis. All received prophylactic anti-epileptic medication and tocilizumab for concomitant CRS. Three received steroids.

CONCLUSION
ICANS may present in almost half of pediatric patients within one week of receiving CART products associated with CRS. CAR-T trafficking into the CSF may explain pleocytosis in the CSF. Prospective studies may clarify. Impaired ability to write a standard sentence and the Cornell Assessment of Pediatric Delirium (CAPD) may be early indicators of ICANS in pediatric/AYA patients.
INNV-06. SECOND GENERATION BRAF/MEK INHIBITION IN ANAPLASTIC PLEOMORPHIC XANTHROASTROCYTOMA
Authors: Stocksdale Brian , Liao Yaping Joyce , Coffey Gwen , Nagpal Seema 
Published: December 2020

Abstract

BACKGROUND
Up to 65% of anaplastic pleomorphic xanthoastrocytomas (A-PXA) harbor the BRAFV600E oncogene. Trials and case series have demonstrated that BRAF-mutant gliomas, including A-PXAs, can be responsive to the first generation BRAF inhibitors dabrafenib and vemurafenib, with an ORR ranging from 26–43%. The second generation BRAF/MEK inhibitor combination encorafenib/binimetinib improves systemic outcome in melanoma patients, has better tolerability, and may have better intracranial activity compared to first generation drugs.

METHOD
We review the three patients with BRAFV600E A-PXA treated with encorafenib/binimetinib in our practice.

RESULTS
Two patients were diagnosed with A-PXA in 2014 and one in 2013. The presence of BRAFV600E was confirmed by molecular testing. All patients have received prior surgery, chemotherapy, and radiation and were at a recurrence when BRAF/MEK inhibition was initiated. One patient had CR after 2 months on treatment and remains in CR at 1-year. One patient, who is also receiving bevacizumab, has a PR, with continued clinical and imaging improvement at 6 months. Our third patient had a PR at 2 months and remains on therapy, currently 3 months post-initiation. All 3 patients report improvement in symptoms. The patient who has been on treatment for 1 year experienced rapid onset bilateral multifocal sub-retinal fluid collections followed by rapid resolution, without intervention, within days of starting treatment. This patient has also had mild decrease in EF over time. We will present continued follow up.

CONCLUSIONS
Encorafenib/binimetinib appears feasible, with 3 of out 3 patients with BRAFV600E A-PXA demonstrating radiographic response; 2 of these patients have durable responses. We stress the importance of a clear lab, cardiac, ophthalmologic, and dermatologic monitoring regimen as side effects can be rapid and severe. Prospective studies with encorafenib/binimetinib in BRAF-mutant primary CNS tumors are underway, and we eagerly anticipate their RESULTS:
INNV-07. THE ROLE OF BIOPSY IN MOLECULAR DIAGNOSIS OF DIFFUSE INTRINSIC PONTINE GLIOMA PATIENTS
Authors: Epelbaum Julia , Krystal Julie , Atlas Mark , Schneider Steven , Mittler Mark , Rodgers Shaun 
Published: December 2020

Abstract

INTRODUCTION
Diffuse intrinsic pontine glioma (DIPG) is an aggressive and fatal pediatric brain tumor. Due to its difficult anatomic location and infiltrative nature, DIPGs are not surgically resectable and more than 90% of children die within two years of diagnosis. Historically, standard of care has consisted of clinical and radiological diagnosis followed by palliative radiation for symptomatic relief. Although tumor biopsy is not necessary for diagnosis, there is debate as to whether the procedure provides benefits that outweighs its risk. Recent studies have proposed that biopsy-driven molecular characterization of these tumors can inform prognosis and identify potential treatment targets that could lead to clinical breakthroughs.

METHODS
This study was a retrospective chart review of 26 patients treated for a DIPG diagnosis between July 1998 and July 2019 at Cohen Children’s Medical Center. We compared outcomes of biopsied vs. non-biopsied DIPG patients through quantitative data analyzing the number and types of treatment given. We analyzed post-surgical data regarding safety of DIPG biopsies which were performed by optical stereotactic needle biopsy or robot-assisted stereotactic biopsy procedures.

RESULTS
There were no permanent biopsy complications in any patient and biopsy did not delay treatment as average hospital stay was 1.5 days. All biopsies collected sufficient material for next generation sequencing analysis and revealed targetable mutations for available clinical trial therapies. 67% of patients were subsequently enrolled in clinical trials, 75% of which required biopsy results for enrollment. MGMT promoter methylation assay results in all tested DIPG biopsy cases indicated resistance to temozolomide, the most common treatment agent given to non-biopsied patients.

CONCLUSION
Biopsy of DIPG tumors is a safe and accurate procedure that does not delay treatment and identifies molecular targets for individualized therapy. The role of biopsy in DIPG patients allows for molecular characterization of DIPG tumors which informs and increases treatment options.
INNV-08. COMPARATIVE STUDY OF THE CANCER TREATMENT POTENTIAL EFFECT OF TUMOR-TREATING FIELDS AND COLD ATMOSPHERIC PLASMA
Authors: Yao Xiaoliang , Goldstein Isaac , Lin Li , Sherman Jonathan , Keidar Michael 
Published: December 2020

Abstract

INTRODUCTION
Cold Atmospheric Plasma (CAP) is ionized gas close to room temperature that generates reactive oxygen and nitrogen species, an electromagnetic field (EMF) and UV, which are selectively cytotoxic to cancer cells. Tumor Treating Fields (TTFields) is an FDA approved cancer treatment that utilizes “low intensity” and “intermediate frequency” alternating electric fields to produce an inhibitory effect on cancerous cells.

OBJECTIVES
In this study, we directly compared CAP and TTFields treatments using U87 glioblastoma tumor cells. We aimed to assess the relative merits of both technologies as potential approaches for brain cancer treatment.

METHODS
In this in vitro study, the cells were treated with either CAP or TTFields at room temperature. In both cases in order the optimize the treatment parameters, the energy we applied was varied for both methods by changing the power and time of the treatment. The resulting cell viability changes were measured 72 hours after treatment.

RESULTS
The results revealed that increased energy resulted in decreased cell viability of U87 glioblastoma tumor cells with both CAP and TTFields treatment. The rate of U87 glioblastoma tumor cell viability under CAP treatment was 80% of the original viability after using 4.8J of energy, compared with 15,752J of energy with TTFields treatment. Additionally, the CAP displayed significantly greater time-efficiency as compared to TTFields. For instance, the most effective TTFields treatment took 4 hours, while the CAP treatment displayed a comparable effect on tumor cell viability with a treatment time of 30 seconds.

CONCLUSIONS
This preliminary in vitro study indicates that CAP treatment is potentially a more favorable effective method of brain cancer therapy. This data indicates that CAP is significantly more energy-efficient and requires significantly less treatment time than TTFields. Future research looks to compare the 2 treatments in an intracranial mouse xenograft model.
INNV-10. EFFECTS OF TTFIELDS USAGE AND DURATION OF USAGE ON CELLULARITY AND Ki67 DISTRIBUTIONS AT AUTOPSY
Authors: Bobholz Samuel , Lowman Allison , Connelly Jennifer , Cochran Elizabeth , Mueller Wade , McGarry Sean , Brehler Michael , LaViolette Peter 
Published: December 2020

Abstract
This study used autopsy tissue samples taken from patients with glioblastoma who had undergone Tumor-Treating Fields (TTFields) therapy to examine the effects of treatment usage and duration on cellular and mitotic activity distributions. We hypothesized that treatment duration and percent compliance would be associated with a change in cellularity. Three tissue samples were collected from 10 patients with glioblastoma at autopsy. These samples were specifically collected in regions that demonstrated clear contrast enhancement on the patients’ last clinical imaging, in order to capture regions of suspected active tumor. Samples were stained with both hematoxylin and eosin (HE) and Ki67 immuno-histochemistry (IHC) and digitized at 40X resolution using a digital microscope. A color deconvolution algorithm was used to separate stains, which allowed nuclei segmentation. Number of cells and percent of Ki67 positive cells were computed across 100x100 superpixels. Spearman’s correlations were used to examine the association between TTFields usage (measured as a percent) and duration of use (in days) and signatures of active tumor proliferation, measured as median cellularity and proportion of Ki67 positive cells across each patients’ three samples. Trending negative associations with median cellularity were observed for both TTFields usage (R=-0.60, p=0.065) and duration (R=-0.61,p=0.063). The magnitude of the treatment duration effect increased when controlling for time between diagnosis and death, despite a p-value drop due to the lost statistical degree of freedom (R=-0.62, p=0.073). No significant effects were observed for Ki67 positive staining. These results generally suggest a possible effect of TTFields therapy duration, where longer treatments and increased compliance lead to lower tumor proliferation. However, these results should be interpreted with caution, as larger, more statistically powerful studies will be better suited to assess the generalizability of the preliminary trends seen in these RESULTS:
INNV-12. A SINGLE-INSTITUTION RETROSPECTIVE REVIEW OF PATIENTS WITH CNS TUMORS WHO INITIATED A KETOGENIC DIET
Authors: Amaral Lauren , Welborn Amelia , Lockshon Laura , Gresham Gillian , Panhans Cristina , Rudnick Jeremy , Irwin Scott , Freedland Stephen , Hu Jethro 
Published: December 2020

Abstract

BACKGROUND
Many patients with CNS tumors express interest in initiating a ketogenic diet (KD). Following a discussion with the physician regarding the limited clinical evidence of KD for CNS tumors, interested patients were referred for evaluation by an oncology-certified dietitian.

METHODS
We performed a single institution retrospective chart review of patients with CNS tumors on a KD. Demographics, clinical characteristics, and diet information were extracted from patient charts. Descriptive statistics were conducted to summarize patterns of adherence to KD across patient characteristics.

RESULTS
From May 2016 to May 2018, 40 patients expressed interest in KD; 24 initiated it. M:F = 18:6, median age 46 (range 27–62). Diagnoses: 18 glioblastoma, 1 anaplastic astrocytoma, 2 grade 2 astrocytoma, 1 grade 2 oligodendroglioma, 1 spinal grade 2 astrocytoma, 1 chordoma. 18 tumors with methylated MGMT, 8 with mutant IDH1. At diet initiation, median KPS 80 (range 70–100); median BMI 25.6 (20.8–39). Median days on diet = 190 days; interquartile range 126–673 days; range 24–1479 days. Diet composition: 15 patients on 3:1 diet (grams fat: grams protein + carbs), 7 patients on 2:1, 2 patients on 1:1. 14 patients monitored blood ketone levels. 11 patients stopped KD: 5 for restrictiveness of diet (median 158 days, range 60–239); 1 for decreased KPS (673 days); 1 for excessive weight loss (108 days); 2 for disease progression (24 and 217 days); 2 lost to follow-up (109 and 125 days). In this small sample, no statistically significant associations between time on diet and age / gender / BMI / KPS / diet composition. However, trend toward longer adherence to diet in females, age &lt; 50, 2:1 diet.

CONCLUSION
It is feasible for patients with CNS tumors to adopt KD. Results from prospective studies are needed to assess effects on QOL, neurocognition, performance status, and survival.
INNV-14. UTILIZATION OF A PATIENT FAMILY ADVISORY COUNCIL TO ADVANCE PATIENT-CENTERED CARE OF BRAIN TUMOR PATIENTS
Authors: Pawloski Jacob , Scarpace Lisa , Gay Nestelynn , Fadel Hassan , Hunt Rachel , Haider Sameah , Robin Adam , Snyder James , Walbert Tobias , Kalkanis Steven , Lee Ian 
Published: December 2020

Abstract

INTRODUCTION
Developing and advancing patient-centered care within neuro-oncology is an essential element of any tertiary brain tumor center. Patient-centered care of neuro-oncology patients requires a holistic approach that integrates oncologic treatment with social and psychological support.

OBJECTIVE
The aim of this study is to evaluate how a Patient Family Advisory Council can be created within an existing brain tumor center and utilized to improve patient-centered care.

METHODS
Current patients and caregivers were recruited by brain tumor staff to participate in monthly meetings. All participants underwent screening and training by our Patient Education Research Center team. Discussions focused on current and future brain tumor center initiatives, and participants were encouraged to give feedback from the patient perspective. New ideas to improve the patient experience were solicited.

RESULTS
A total of 15 participants (female = 57%) were recruited, including 10 with grade 3 or higher brain tumors. Monthly meetings, in-person or virtual, were held for two years. Utilizing participant feedback, the group updated our 80-page patient handbook that contained a variety of patient-caregiver focused resources. Participants also provided feedback on other brain tumor center initiatives such as development of a magnet featuring key phone numbers, an easily accessible website URL for emergencies, and numerous updates to the external website. Additional discussions involved development of neuro-oncology care pathways as we move to a stand-alone cancer center facility and initiation of OncoSTAT and palliative services in this population.

CONCLUSION
Brain tumor patients require a comprehensive oncologic treatment team as well as a wide variety of support services. A Patient Family Advisory Council is an effective method of advancing patient-centered care and a step toward improving the neuro-oncology patient experience.
INNV-16. CLINICAL APPLICABILITY OF INDIVIDUALIZED DRUG RESPONSE PROFILING UTILIZING EX-VIVO TISSUE-DERIVED 3D CELL CULTURE ASSAYS IN HIGH-GRADE GLIOMA: A SINGLE INSTITUTION CASE SERIES USING 3D-PREDICT RESULTS
Authors: Lipinski Lindsay , Abad Ajay , Mechtler Laszlo , Fabiano Andrew , Smith Ashley , DesRochers Teresa , Gevaert Matthew , Vibat Cecile Rose , Fenstermaker Robert 
Published: December 2020

Abstract
Recurrent high-grade glioma is a challenging disease process, without consensus on effective second-line therapy options. Individualized, patient-specific, biologically-based data is desirable in driving therapeutic decision-making. Patients with recurrent high-grade glioma and planned surgical re-resection at our institution were prospectively enrolled into the 3D-PREDICT study. Tissue was collected at the time of surgery for ex vivo 3D cell culture assays comprising a panel of agents commonly used for high-grade glioma, including chemotherapies and targeted therapies used in other solid cancers. In all cases, therapeutic agent selection was guided by the neuro-oncologist’s clinical judgement, factoring the patient’s age, performance status, comorbidities, toxicities/side effect profile of potential agents, and drug accessibility, plus ex-vivo drug response RESULTS: We present 3 cases in which the selection of agents was influenced by the tissue-derived 3D cell culture results; treatment led to clinical response observed in terms of progression free survival, quality of life, and pharmacologic tolerability. In Case 1, a patient with recurrent anaplastic astrocytoma was treated with a BRAF inhibitor for 12 months with excellent tolerability and no radiographic progression. Case 2 demonstrates the use of combination bevacizumab and irinotecan after disease progression subsequent to standard treatment. This patient had local radiographic control for 7 months, tolerating the regimen well. In Case 3, an individual with recurrent glioblastoma was treated with combination carboplatin and etoposide based on assay response prediction to both agents; treatment has been tolerated well with radiographic stability at 6 months while maintaining good performance status. This case series represents our institutional experience of utilizing patient-specific, ex-vivo tissue-derived cell drug response profiling to guide choice of therapy for recurrent high-grade glioma patients. Using individualized, tumor-specific drug sensitivity data to guide these decisions is representative of the ongoing paradigm shift into the realm of individualized medicine to improve outcomes in cancer patients.
INNV-18. RECURRENT SHH MEDULLOBLASTOMA EXTRANEURAL METASTASES TO THE BONE MARROW WITHOUT CNS INVOLVEMENT
Authors: Clifton Brad , Anderson Mark 
Published: December 2020

Abstract
Medulloblastoma is the most common primary brain tumor in children, but is rare in adults. Because of the scarcity of adult medulloblastoma cases, treatment guidelines in the adult population are not well established, especially regarding surveillance and treatment of recurrent disease. A 47-year-old African American male presented with one month of progressive unsteady gait and dizziness. Imaging revealed a posterior fossa mass and the patient underwent gross total resection. Histology confirmed medulloblastoma and molecular subtyping revealed Sonic Hedgehog (Shh) pathway activation. No metastases were found at the time of diagnosis, and the patient received adjuvant craniospinal radiation therapy. Three years later the patient developed low back pain with severe sciatica affecting his gait and pancytopenia. Imaging revealed diffuse osseous disease without CNS recurrence and bone marrow biopsy confirmed recurrent medulloblastoma. The patient subsequently began reduced chemotherapy consisting of cisplatin and etoposide because of his severe pancytopenia. Due to a lack of response after 4 cycles, the SMO antagonist vismodegib was added. Follow-up imaging revealed improvement/stability of osseous disease, lab work demonstrated resolution of pancytopenia, and repeat bone marrow was without malignancy. Vismodegib was continued as maintenance therapy. Six months after completion of cisplatin/etoposide, follow-up imaging revealed progression of metastatic disease. Shh activated medulloblastomas have demonstrated responses to SMO inhibition. However, these responses are often transient secondary to rapid development of resistance, but may have a role to play in patients who have bone marrow involvement that limits use of cytotoxic therapy or bone marrow transplant. Due to poor survival outcomes associated with bone marrow metastases, aggressive screening for bone marrow metastases at diagnosis and in surveillance should be considered.