bluuebunny/crossref_metadata_2025_split huggingface dataset:
INNV-03. A MICROFLUIDIC CULTURE PARADIGM FOR THE EX VIVO MAINTENANCE OF HUMAN GLIOBLASTOMA TISSUE - A NEW GBM MODEL?
Authors: Olubajo Farouk , Achawal Shailendra , Rajaraman Chittoor , O’Reilly Gerry , Greenman John 
Published: November 2019

Abstract
The genetic and molecular variations that exist within Glioblastoma (GBM) determine treatment responses. One way to improve patient outcomes is to optimise treatment(s) pre-clinically by studying each tumour on an individual basis. Presented here are the results of a pilot study on the maintenance of human GBM tissue on a microfluidic platform. The device, fabricated using a photolithographic process, was composed of two layers of glass bonded together to contain a tissue chamber and a network of microchannels. A thin mesh layer was inserted to separate the tissue chamber from the microchannels and prevented blockage of the chip. Over an 18-month period, 33 patients were recruited, and 128 tissue sections were maintained in microfluidic devices for an average of 72 hours (h). Tissue viability as measured by Annexin V and Propidium Iodide staining showed that viability was 61.1 % in tissue maintained on chip after 72 h, compared with 68.9 % for fresh tissue analysed at the commencement of the experiment (P < 0.05). Other biomarkers, including Lactate Dehydrogenase (LDH) release and Trypan Blue assay, supported the viability of the tissue maintained on chip. Histological appearances of the tissue remained unchanged during the maintenance period and immunohistochemical analysis of Ki67 and Caspase 3 also showed no statistically significant differences. Analysis has shown a trend with tumours associated with poorer prognoses (e.g. recurrent tumours and IDH wildtype) displaying higher viability on chip compared to tumours linked with better outcomes (Grade 1–3 gliomas, IDH mutants and primary tumours). This work has demonstrated for the first time that human GBM tissue can be maintained ex vivo within a microfluidic device with viability comparable to fresh tissue samples. The model has the potential to be developed as a new platform for studying the biology of brain tumours, with the aim of facilitating personalised treatments.
INNV-04. IDH MUTATION PREDICTION IN GLIOMA: A MULTIMODAL APPROACH
Authors: Juratli Tareq , Zolal Amir , Stasik Sebastian , Pietzsch Mirko , Eisenhofer Graeme , Linn Jennifer , Schackert Gabriele , Thiede Christian , Krex Dietmar , Werner Annett 
Published: November 2019

Abstract

OBJECTIVE
Non-invasive and accurate diagnostic techniques to detect isocitrate dehydrogenase (IDH) mutant glioma may have great potential in routine clinical practice. With this in mind, we performed a multimodal diagnostic approach to predict the IDH mutation status in newly diagnosed gliomas using: 2-Hydroxyglutarate (2HG) single-voxel spectroscopy (SVS), IDH-mutant cell-free tumor-derived DNA (tDNA) in the CSF, in addition to 2HG (D- and L- forms) concentration measurement in the CSF.

METHODS
2HG MR spectroscopy was obtained in 18 patients with a newly diagnosed IDH-mutant glioma. The IDH1/2 mutation status was determined using next generation sequencing in the glioma tissue and in the CSF-tDNA (n=55). In addition, in a subset of patients (n=15), 2HG concentrations were measured in the CSF using liquid chromatography-tandem mass spectrometry (LCMS). Ratios of D-and L-2HG were used to evaluate differences in 2HG accumulation in tumors.

RESULTS
IDH mutations were correctly predicted using the 2HG spectroscopy with 93.3% sensitivity (17/18, 95% CI, 85.3–100%) and 100% specificity (18/18, 95% CI, 88.6–100%). The IDH mutation in the CSF-tDNA was successfully detected with 100% specificity (95% CI, 87.6–100%) and 73.3% sensitivity (95% CI, 65.6–88.3%). The range of the IDH mutation variant allele frequency (VAF) in the CSF-tDNA was 1.53- 47.9%. 2HG detection in the CSF revealed higher sensitivity (100%) and specificity (100%) in a small subset of patients (n = 7). The D-2HG/L-2HG ratios in IDH-mutant cases varied between 1.2 – 13.8, compared with 0.1 – 0.5 in IDH wild-type gliomas.

CONCLUSION
Our findings suggest that 2HG spectroscopy and 2HG detection in the CSF are two reliable methods in IDH mutation prediction in gliomas. On the other hand, the sensitivity of genomic IDH mutation detection in the CSF-tDNA was lower when compared with 2HG detection. Further studies are needed to complement the findings of our exploratory analysis.
INNV-07. THE KOREAN SOCIETY FOR NEURO-ONCOLOGY (KSNO) GUIDELINE FOR GLIOMAS: VERSION 2019.01
Authors: Zoon Kim Young , Kim Chae-Yong , Hoon Lim Do , Chung Dong-Sup 
Published: November 2019

Abstract

BACKGROUND
There was no practical guideline for the management of patients with central nervous system (CNS) tumor in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, started to prepare a guideline for CNS tumors from February 2018.

METHODS
The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords.

RESULTS
First, for the glioblastoma as WHO Grade IV Gliomas, the maximal safe resection if feasible is recommended. Patients aged ≤ 70 years with good performance should be treated by concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide chemotherapy (Stupp’s protocol) or standard brain radiotherapy alone. However, those with poor performance should be treated by hypofractionated brain radiotherapy (preferred) ± concurrent or adjuvant temozolomide or temozolomide alone (Level III) or supportive treatment. Second, for the WHO Grade III Gliomas, patients with anaplastic astrocytoma, IDH-mutant should be treated by standard brain radiotherapy followed by adjuvant temozolomide chemotherapy, or Stupp’s protocol, or standard brain radiotherapy with neoadjuvant or adjuvant PCV chemotherapy, or Standard brain radiotherapy alone (Level III). However, those anaplastic astrocytoma, IDH-wildtype should be treated by the protocol for glioblastoma. Third, for the WHO Grade II Gliomas, patients with diffuse astrocytoma, IDH-wildtype without molecular feature of glioblastoma should be treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy (Level III), or standard brain radiotherapy alone, or observation. And patients with diffuse astrocytoma IDH-mutant and oligodendroglioma (IDH-mutant and 1p/19q codeletion) should be treated according to the risk factors.

CONCLUSION
The recent KSNO’s guideline recommends that glioma should be treated according to the molecular as well as histological features. However, the practice can be limited by the National Insurance for Health in Korea.
INNV-18. THE AVAILABILITY AND ROLE OF CLINICAL PHARMACISTS IN THE AMBULATORY NEURO-ONCOLOGY SETTING: AN INTERNATIONAL SURVEY
Authors: Patel Mallika , Lipp Eric , Miller Patrick Healy Elizabeth , Herndon James , Peters Katherine 
Published: November 2019

Abstract

BACKGROUND
Outpatient clinics treating neuro-oncology patients are becoming more multidisciplinary. Utilization of all team members is critical for the holistic care of these complex patients. Specifically, the role of a clinical pharmacist in the ambulatory multidisciplinary clinic remains undefined and will likely evolve as more therapeutic options are developed to treat central nervous system malignancies. We queried the Society for Neuro-Oncology (SNO) membership about the availability of a clinical pharmacist in their ambulatory setting and, if present, the role of that clinical pharmacist.

METHODS
In an IRB exempt study, we surveyed the SNO community (targeting primarily clinicians) and analyzed responses to queries about clinical pharmacists in the ambulatory neuro-oncology setting.

RESULTS
Of the 65 SNO members who responded, 52 of these were clinical members. Of these 52 clinical members, the majority were physicians (88.5%, n=46). Of these 46 physicians, most were in academic practices (93.5%, n=43). Over half of the 52 clinical respondents (51.9%, n=27) reported that they saw ≥ 30 primary brain tumor patients a month, thus typifying busy clinical neuro-oncology ambulatory clinics. Despite having busy clinics, only 12 (28.6%) of the 42 providers with access to a clinical pharmacist reported that their clinical pharmacist was solely dedicated to neuro-oncology patients. For the respondents who had access to a clinical pharmacist, only 28 (66.7%) of those pharmacists had direct patient interaction in the clinic. The top three roles of the clinical pharmacist included medication review (81%, n=34), chemotherapy dosing and modifications (73.8%, n=31), and practice guideline development (61.9%, n=26), none of which are associated with direct patient interaction.

CONCLUSIONS
We found that while our surveyed population of SNO clinical members have demanding outpatient neuro-oncology practices, most do not have the support or expertise of dedicated neuro-oncology clinical pharmacists.
INNV-28. MOLECULAR TESTING IN NEURO-ONCOLOGY – ASSESSMENT OF UTILITY AND PRACTICE PATTERNS. A SOCIETY FOR NEURO-ONCOLOGY MEMBERSHIP SURVEY
Authors: Mrugala Maciej , Chang Susan 
Published: November 2019

Abstract

BACKGROUND
Molecular testing (MT) is utilized in neuro-oncology with increasing frequency. Multiple molecular panels are available providing a spectrum of information. We were interested in learning how this information is acquired, what are the practice patterns regarding this type of testing, how are the results utilized in patient care and how prepared neuro-oncologists are to interpret these results.

METHODS
We conducted a survey using the Society for Neuro-Oncology membership database. We developed a set of 13 questions and administered the survey to 2022 members using the online platform.

RESULTS
We received 153 responses (7.5% of membership). 89% percent of responders routinely order MT. Of those who do not order MT on all patients, 50% test younger patients and 57% midline tumors. 83% use MT in recurrent glioma. Other common indications for MT included: metastatic tumors, meningioma, medulloblastoma, ATRT. Majority (60%) use in-house panels, followed by Foundation One (35%), TEMPUS (13%), CARIS (10%) and other panels (23%). For 57% of respondents, the data from MT was somewhat useful and for 41% it was very useful. 78% used the results of MT for clinical decision-making. BRAF, EGFR/ALK, H3K27 mutations were most commonly used for treatment decisions. 50% of respondents have molecular tumor boards at their institutions and a majority of practitioners share the results of MT with their patients (95%). Respondents would like to see SNO-endorsed official guidelines on MT, organized lists of targeted agents available for specific mutations, a database of targetable mutations and clinical trials and more educational programs on the subject.

CONCLUSIONS
Molecular testing is neuro-oncology is commonly done. Many providers rely on the information for clinical decision making where appropriate. In-house and commercial genetic panels are equally used in practice. There continues to be a need for more education on the subject and development of neuro-oncology specific guidelines.
INNV-30. RESPONSE WITH COMBINED DABRAFENIB AND TRAMETINIB AFTER BRAF INHIBITOR FAILURE IN BRAF-MUTATED GLIOBLASTOMA: A CASE REPORT
Authors: Kushnirsky Marina , De la Fuente Macarena I , Feun Lynn 
Published: November 2019

Abstract
Glioblastoma (GBM) carries a poor prognosis despite aggressive multimodality therapy. Oncogenic BRAF mutations are present in < 2% of GBM, along with other glioma types (ganglioglioma, pleomorphic xanthoastrocytoma). Although oral inhibitors of the oncogenic BRAFv600 kinase have demonstrated some efficacy in GBM, several mechanisms mediating resistance to BRAF inhibitors through MAPK reactivation have been described. BRAF inhibitor monotherapy is also associated with an increased risk for hyperproliferative skin lesions. We present a case of a 44-year-old man who initially presented with headaches and seizures and was diagnosed with a left temporal, MGMT unmethylated, BRAF V600E mutant GBM. He underwent gross total resection followed by radiation therapy with concurrent temozolomide, followed by 9 cycles of adjuvant temozolomide. He presented with progression of disease (POD) and subsequently failed treatment with carboplatin after two cycles (first recurrence). He had a repeat resection, and was enrolled in a clinical trial of autologous dendritic cell vaccine and presented with POD after 10 months on this treatment (second recurrence). He was started on another clinical trial of BRAF inhibitor, achieving partial response but developed POD after 7 months on this therapy (third recurrence). He was started on BRAF inhibitor dabrafenib and MEK inhibitor trametinib (D+T), achieving complete response. At the time of this report, 8 months after initiating treatment, the patient remains clinically stable with MRI showing CR. To our knowledge, this is the first report of clinical and radiographic response to combined D+T after BRAF inhibitor failure in BRAF-mutated glioblastoma. Several ongoing trials (NCT01677741, NCT01748149, NCT02124772, NCT02684058, NCT02285439), will elucidate the precise role of these drugs as single agent and in combination in pediatric and adult brain tumors.
INNV-31. ACCELERATING NEURO-ONCOLOGY RESEARCH AND IMPROVING PATIENT CARE THROUGH A ROBUST DATA FOUNDATION
Authors: Alfaro-Munoz Kristin , Hallatt Gemma , ravi Vinod , Futreal Andrew , Sookprasong Jamie , Yu Emily , Lari Bryan , Jin Jeff , DeGroot John 
Published: November 2019

Abstract

BACKGROUND
MD Anderson (MDA) strives to maximize learning from the > 44,000 patients seen annually. This has historically been challenging due to the diverse, often unstructured, and siloed nature of patient data. In 2018, MDA partnered with Palantir Technologies to integrate disparate clinical and research data sources into a single cloud-based platform enabling both technical and non-technical users to directly access and analyze data.

METHODS
IT experts, Palantir engineers and end users collaborated to integrate 150 deidentified datasets from the existing data warehouse, Natural Language Processing pipelines, molecular reports, public data and manually curated data, representing data from > 1.5 million patients. Data integration was tested by answering 12 retrospective queries, of which 5 were specific to neuro-oncology cohorts.

RESULTS
All 12 queries were resolved and within the neuro-oncology department we found the cohort identification process to be accelerated with users able to create reports backed by live data, with clear visibility into inputs, analysis and history. In addition, templates were created of common statistical workflows, empowering non-technical users to perform analyses (e.g. KM curve; Volcano plot). Secure access controls enabled increased collaboration between neuro-oncology and other departments.

CONCLUSIONS
This work highlights the value of a data foundation and unlocks the potential for new studies, fueling scientific discovery within neuro-oncology and across the institution. To extend the impact we are piloting a combination of (1) Purposeful structured data capture at the time of care, (2) Use of logic to suggest commonly uncaptured but critical patient events such as progression, and (3) Auditing functionality to allow users to manually fill in gaps and correct data in a transparent manner. Upon completion, we anticipate the ability to increase our research throughput and scope.
INNV-43. IMPROVING POST OPERATIVE FOLLOW-UP AND TIME TO ADJUVANT TREATMENT FOR HIGH GRADE GLIOMA
Authors: Catalino Michael , Zeitouni Daniel , Henretty Sonja , Zhu Anqi , Khagi Simon 
Published: November 2019

Abstract

BACKGROUND
High grade glioma patients are prone to lapses in treatment due to the complexities related to coordination of care, the timing of adjuvant treatment, and insurance barriers. The purpose of this study was to determine the impact of an institutional multidisciplinary protocol on transitions of care after surgery for high grade gliomas between 2015 and 2018.

METHODS
A retrospective cohort study was conducted using CPT codes for enrolled glioma patients between 2015–2018 with unplanned surgery. Historical controls were compared to the intervention group which began enrollment in November 2016. We used time-to-event analysis to compare time to neuro-oncology follow up and time to adjuvant treatment (radiation and/or chemotherapy). The effect of discharge disposition and insurance status was also assessed. The study incorporated an ad hoc analysis of survival outcomes.

RESULTS
The intervention and control groups had similar baseline characteristics. The intervention was associated with more patients following up with neuro-oncology within 2 weeks (51.1% in intervention group compared to 30.0% in control group), more patients starting radiation within 30 days (43.6% and 25.0%, respectively) and more patients starting chemotherapy within 30 days (59.0% and 35.0%, respectively). Time-to-event analysis revealed that the intervention trended toward earlier initiation of chemotherapy (p=0.076). Only 16.7% of patients discharge to a skilled nursing facility were able to initiate chemotherapy at the 30-day mark. Time-to-event analysis revealed that insurance status was significantly associated with initiating chemotherapy at the 30-day mark (p=0.023). Survival analysis is planned and will be reported in a future manuscript.

CONCLUSION
A multidisciplinary approach to capturing patients after surgery decreases time to follow up with neuro-oncology and initiation of adjuvant treatment. Timely follow up is associated with insurance status, discharge disposition, and multidisciplinary discussions between the treatment team and ancillary staff. Survival outcomes are being assessed and will be reported.
MNGI-02. FEATURES OF TUMOR TEXTURE INFLUENCE SURGERY AND OUTCOME IN INTRACRANIAL MENINGIOMA
Authors: Sauvigny Thomas , Ricklefs Franz , Hoffmann Lena , Schwarz Raphael , Burkhardt Till , Westphal Manfred , Ole Schmidt Nils 
Published: November 2019

Abstract

OBJECTIVE
Texture-related factors such as consistency, vascularity and adherence vary considerably in meningioma and are thought to be linked with surgical resectability and morbidity. However, data analyzing the true impact of meningioma texture on the surgical management is sparse.

METHODS
Patients with intracranial meningioma treated between 08/2014-04/2018 were prospectively collected for demographics and surgical treatment with related morbidity and extend of resection (EOR). Tumor characteristics were reported by the surgeon using a standardized questionnaire including items such as tumor rigidity, homogeneity, vascularization and adherence to surrounding neurovascular structure and analyzed for their impact on EOR and neurological outcome using multivariate regression analyses.

RESULTS
296 patients (214 female (72.3%) with intracranial meningiomas were included with a mean age of 60.4 years. 23% of patients had a transient and 6.1% permanent neurological deficits and three patients (1.1%) died. The occurrence of a neurological deficit was associated with duration of surgery (p = 0.013) and tumor adherence to neurovascular structures (p = 0.014). Similar associations were observed in subgroup analyses of different tumor localizations (e.g. convexity and skull base). With regard to EOR, the tumor adherence (p < 0.001) and recurrent surgery (p = 0.001) were found as independent predictors for subtotal resection. Noteworthy, the tumor rigidity had no significant impact on the morbidity or EOR.

CONCLUSION
Our analysis supports the notion that tumor texture has an impact on the surgical management of meningioma and provides sound data that tumor adherence is a significant factor influencing neurological outcome and EOR. In contrast, the influence of tumor rigidity has less impact than previously thought. Preoperative prediction of tumor texture is therefore required for optimized risk assessment.
MNGI-13. DYNAMIC IMAGING OF MENINGIOMA WITH 3’-DEOXY-3’-[18F]-FLUOROTHYMIDINE USING POSITRON EMISSION TOMOGRAPHY: A POSSIBLE PREDICTOR OF TUMOR GROWTH
Authors: Bashir Asma , Bitsch Vestergaard Mark , Marner Lisbeth , Larsen Vibeke A , Ziebell Morten , Fugleholm Kåre , Law Ian 
Published: November 2019

Abstract

BACKGROUND
Positron emission tomography (PET) with 3’-deoxy-3’-[18F]-fluorothymidine (18F-FLT) provides a non-invasive assessment of in vivo tumor proliferation that could be useful for predicting growth potential in meningiomas. We aimed to study static and dynamic 18F-FLT PET metrics prospectively to assess metabolic activity of meningioma, and their associations to potential tumor growth on subsequent MRI scans.

METHODS
Between April 2017 and December 2018, 44 patients harboring MRI-suspected (n = 37) and histologically-verified residual meningiomas (n = 7) underwent a 60-minute dynamic 18F-FLT PET prior to imaging surveillance. Maximum and mean standardized uptake values (SUVmax, SUVmean) with/without normalisation to blood radioactivity obtained from a 40-60-minute static PET image and a 60-minute venous blood sampling were calculated. Total volume of distribution (VT) was estimated by kinetic modeling using a two-tissue reversible compartmental model with a fractional blood volume and metabolite-corrected image-derived input function. Tumor growth rate was calculated by volumetric analysis of subsequent MRI scans.

RESULTS
At the time of this writing, a total of 53 follow-up MRI scans from 33 patients were available for review, with a median follow-up time of 11 months (range, 4–22.5 months). Tumor growth/progression was observed in 12 cases with a monthly median growth rate of 0.10 cm3 (range, 0.03–3.41 cm3). All 18F-FLT metrics were significantly higher in patients with radiological progression compared to patients with stable findings with maximum tumor-to-blood-ratio (TBRmax) as the most promising imaging biomarker (4.9 ± 1.4 vs. 3.4 ± 1.0, P = .003; Mann-Whitney) and the strongest predictor for tumor progression (hazard ratio, 3.125; 95% confidence interval, 1.390–7.028; P = .006; univariate binary logistic regression). Age, gender, previous residual remnant(s) and initial tumor volume (median, 3.1 cm3; range, 0.2–55.3 cm3) had no influence.

CONCLUSION
18F-FLT PET imaging could be a valuable tool in designing a patient-tailored surveillance strategy for patients with asymptomatic meningiomas.