tbuckley/cabot-search huggingface dataset:
BIOM-05. CIRCULATING TUMOR CELLS (CTC) IN CEREBROSPINAL FLUID (CSF) AS A PREDICTOR OF SURVIVAL IN CNS METASTASES
Authors: Maria Diaz, Priya Singh, Ivan Kotchetkov, Anna Skakodub, Anne Reiner, Katherine Panageas, Lakshmi Ramanathan, Elena Pentsova
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND CSF-CTC testing using the CellSearch® platform is a validated diagnostic tool for leptomeningeal metastases (LM) from solid tumors. CSF-CTCs can also be detected in patients with brain metastases (BM), but their significance is unclear. Our objective was to evaluate the utility of CSF-CTC quantification in predicting outcomes in CNS metastases. METHODS We retrospectively reviewed charts of patients with solid tumors who underwent CSF-CTC measurement between 2016–2019 at Memorial Sloan Kettering Cancer Center. Information on neuroaxis imaging, CSF results, systemic cancer status, tumor molecular profile and survival was collected. LM was diagnosed by MRI and/or CSF cytology. Survival analyses were performed using Cox proportional hazards modeling, and CSF-CTC splits associated with survival were identified through recursive partitioning analysis (RPA). RESULTS A total of 407 patients (38% lung primary, 34% breast, 28% other tumor types) were included; of these, 144 had LM and 233 had BM diagnosed before or around the time of CSF tests (97 had both). For a subgroup of 101 patients with LM diagnosed within 30 days of CSF sampling, mean CSF-CTCs were 127.3/3ml, compared to 44.6/3ml in the overall cohort. CSF-CTCs predicted survival in these patients, with optimal cutoff at 61 CSF-CTCs/3ml, above which the risk of death doubled (HR=2.09, 95% CI: 1.13–3.87, p=0.02). For 53 patients with BM diagnosed 1–6 months prior to CSF tests, CSF-CTCs (mean 54.1/3ml) also determined higher risk of death when above the optimal cutoff of 94 (HR=5.15, 95% CI: 2.08–12.78, p=0.004). For both groups, positive/suspicious cytology was associated with higher risk of death as well, but these results were not statistically significant (LM group: HR=1.79, 95% CI: 0.95–3.35, p=0.07; BM group: HR=1.86, 95%CI: 0.82–4.22, p=0.14). CONCLUSION In newly diagnosed LM and BM, quantification of CSF-CTCs predicts survival. CSF-CTC analysis can be used as a prognostic tool in patients with CNS metastases.
RADT-38. ADJUVANT RADIOTHERAPY FOR INTRACRANIAL ATYPICAL AND MALIGNANT MENINGIOMAS IN ADULT PATIENTS
Authors: Ansley Unterberger, Aditya Kondajji, Daniel Kulinich, Courtney Duong, Isaac Yang
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Meningiomas, the most common primary brain tumor, account for more than one third of all primary CNS tumors. High-grade meningiomas, WHO grade II and III, comprise between 16%-24% of total meningiomas and are more aggressive, recur more frequently, and portend a worse prognosis than WHO grade I meningiomas. Adjuvant radiation of high-grade meningiomas, while not uncommon, remains variably described in current literature. To assess our institution’s radiation protocol, we examined our cohort of over 200 high-grade meningiomas. METHODS We queried our hospital’s EHR system for surgically resected meningiomas from January 2013 to December 2019. Of 286 results identified, 24 patients met the inclusion criteria: 1) histologically confirmed WHO grade II or III meningioma, 2) primary resection coupled with adjuvant radiation therapy, and 3) no chemotherapy. Only one WHO grade III meningioma met inclusion criteria. Patients with NF2 were excluded. Patient demographics, radiation dosage, fraction number, and dates of surgery, radiation onset, recurrence, and most recent follow-up were recorded. RESULTS Median age at surgery was 56.2 years (± 11.1, range 37.8 – 81.7), and males comprised 70.8% (n = 17) of the population. Only FSRT or IMRT were employed. The most frequent dosage was 55.8 Gy across 31 fractions with a median time to radiation of 2.7 months (± 3.0, range 1.0 – 12.6). 5 out of 24 patients experienced recurrence, which did not include the WHO III tumor. Median time to recurrence was 3.0 years (± 2.0, range .3 – 5.8). Median follow up was 3.5 years (± 2.2, range .3 – 9.3). CONCLUSIONS A fraction of our population experienced recurrence, regardless of grade II or grade III pathology. FSRT remains a safe and effective adjuvant therapy for high-grade meningioma after surgical resection. Future prospective studies comparing differing radiation modalities should be conducted.
Super enhancers define regulatory subtypes and cell identity in neuroblastoma
Authors: Moritz Gartlgruber, Ashwini Kumar Sharma, Andrés Quintero, Daniel Dreidax, Selina Jansky, Young-Gyu Park, Sina Kreth, Johanna Meder, Daria Doncevic, Paul Saary, Umut H. Toprak, Naveed Ishaque, Elena Afanasyeva, Elisa Wecht, Jan Koster, Rogier Versteeg, Thomas G. P. Grünewald, David T. W. Jones, Stefan M. Pfister, Kai-Oliver Henrich, Johan van Nes, Carl Herrmann, Frank Westermann
Journal: Nature Cancer (2020)
COVD-29. CONTINUATION OF TEMOZOLOMIDE CHEMOTHERAPY IN A GLIOBLASTOMA PATIENT AFTER RESOLUTION OF COVID-19 PNEUMONIA
Authors: Jigisha Thakkar, Michael Teitcher, Douglas Anderson, Kevin Barton, Edward Melain
Journal: Neuro-Oncology (2020)

Abstract We present a case of a 33 year-old patient with glioblastoma (IDH wild type, MGMT unmethylated) who was diagnosed with COVID-19 pneumonia while undergoing chemotherapy. The patient did not have any medical comorbidities. He was clinically asymptomatic following surgery, completed concurrent phase of combined chemotherapy and radiation and was undergoing treatment with adjuvant temozolomide. He had radiographic improvement of the brain tumor (decreased size, contrast enhancement and T2 flair) after three cycles of adjuvant temozolomide. However, after cycle three the patient developed fever and abdominal pain. Evaluation in the emergency room revealed low absolute lymphocyte count (0.7 K/MM3), positive COVID-19 point of care test and CT chest revealed patchy peripheral bibasilar ground glass and consolidative opacities compatible with pulmonary infection, with viral etiology such as COVID. Symptoms resolved after 2 weeks. Due to active infection and leucopenia temozolomide was on hold for 1 month. He was considered cleared of infection after resolution of symptoms. Temozolomide was initiated after resolution of leucopenia. Patient continued to do well after administration of subsequent temozolomide cycles and repeat CT chest after 2 months revealed resolution of consolidation and no new areas of consolidation. Temozolomide was safely administered in this patient without reactivation of COVID-19 infection. He did not have any thrombotic events.
18F-FDG PET/CT for Staging and Response Evaluation in a Rare Case of Childhood Ovarian Primitive Neuroectodermal Tumor
Authors: Punit Sharma, Indranil Ghosh, Enam Murshed Khan
Journal: Clinical Nuclear Medicine (2020)

Primitive neuroectodermal tumor (PNET) is an aggressive small cell malignancy. Apart from the central nervous system, they can arise from peripheral sites as well. Ovarian PNETs are extremely rare neoplasms. We here present a case of childhood ovarian PNET, where 18F-FDG PET/CT was efficiently used for staging and response evaluation.
TAMI-40. TUMOR MICROBIOME AND GLIOBLASTOMA (GBM)
Authors: Shlomit Yust-Katz, Elinor Gigi, Deborah Rosenberg, Andrew A Kanner, Yoseph Laviv, Alexandra Benouaich-Amiel, Tali Siegal, Adva Levi Barda, Ravid Straussman
Journal: Neuro-Oncology (2020)

Abstract Bacteria have been found to play major roles in many physiologic/disease processes including cancer. The presence of bacteria within brain tumors has never been explored. The aim of this study was to examine the microbiome of Glioblastoma. A cohort of 40 glioblastoma samples (FFPE), from two medical centers served for DNA extraction using a specialized extraction protocol that includes a bead beating step to ensure complete bacterial DNA recovery. A set of negative controls was introduced at different steps of the assay to identify and monitor contaminating bacterial DNA. We measured the levels of bacterial DNA in the samples using a RT-qPCR assay, amplifying the bacterial 16S rRNA gene and detected bacterial DNA in over 40% of the samples. To characterize the bacterial taxa that are present in GBM tumors, we applied 16S DNA sequencing on the samples. After implementing a stringent set of filters on the sequencing data, eliminating contaminating signal, we detected a total of 22 bacterial taxa in GBM tumors. To visualize bacteria in GBM tissues and learn about their localization within the tissue we used immunohistochemistry staining with anti-lipopolysaccharide (LPS) and anti-lipoteichoic acid (LTA) antibodies detecting gram negative and gram positive bacteria (correspondingly). Bacteria were also visualized by staining bacterial RNA using a 16S rRNA in situ hybridization assay. Staining of a human GBM tissue microarray (TMA) containing 32 cases of GBM showed that the majority of cases stained positive for LPS and ~40% were positive for 16S rRNA staining. Bacterial LPS and 16S rRNA were localized mainly inside the tumor cells. Our study demonstrates, for the first time, that bacteria or bacterial components are present in human Glioblastoma tumors. We are currently expanding our study cohort in order to better define the bacteria found within glioblastoma samples and assess their possible effects
44P The hematologic toxicities of chemo-immunotherapy compared to chemotherapy alone: A systematic review and meta-analysis
Authors: D. Eiger, E. Agostinetto, R. Caparica, M.A. Franzoi, M. Brandão, L. Buisseret, A. de Caluwé, D. Gimenes, S.D. Simon, N.F. Pondé, E. de Azambuja
Journal: Annals of Oncology (2020)
Real-World Evidence of the Use of Approved Carfilzomib Regimens in Patients Previously Exposed or Refractory to Lenalidomide: Updated Results from a Prospective Observational Study
Authors: Xavier Leleu, Borhane Slama, Renato Zambello, Sorina Nicoleta Badelita, Eirini Katodritou, Jo Caers, Thomas Kühr, Florence Suzan, Abeera Mohammad, Sally Wetten, Evangelos Terpos
Journal: Blood (2020)
Connectivity of Radiotracers to Vasodilators: Is Thallium the Missing Link?⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: Vasken Dilsizian
Journal: JACC. Cardiovascular imaging (2009)
Abstract 15660: Impact of Telemedicine on Pediatric Cardiac Center’s Ambulatory Response to the 2019 Novel Coronavirus Disease (covid-19) Pandemic
Authors: Kristine M Mehrtens, Anita Krishnan, Jeffrey P Moak, Craig A SABLE, Rachel Selekman, Charles I Berul, Ian Hovis, Carole Helmandollar, Tyrone A Pender, Christiana Safo, CARMEN ARROYO, Jeffrey A Becker, Ricardo A Munoz, Ashraf S Harahsheh
Journal: Circulation (2020)

Background: The 2019 novel coronavirus disease (COVID-19) pandemic puts cardiology patients at high risk for worsening of their underlying disease due to a decrease in non-emergent outpatient visits and social distancing concerns. Our aim was to assess the impact of telemedicine on ambulatory cardiology. Our hypothesis was that telemedicine would bridge the drop in ambulatory visits thus allowing surveillance visits to continue. Methods: Retrospective study from 3/2 to 6/12/2020 utilizing an administrative ambulatory database. Weekly telemedicine and in-person visits were extracted from EMR schedules. A telemedicine orientation session and individualized in-service sessions were provided to all cardiology staff by an expert in telemedicine. Logistics of scheduling, consenting, conducting the visit, documenting and billing were reviewed. To maximize physical distancing, in-person visits were relocated to regional outpatient centers. Prior to COVID-19, 37 cardiologists and 2 nurse practitioners conducted an average of 350 ambulatory visits/week. Results: The number of providers conducting telemedicine visits increased from 3 (8%) pre-COVID-19 to 31 (79%) during the pandemic. Compared to pre-COVID average, the median (IQR) weekly total ambulatory visits during the pandemic was 62% (57-90%). During the COVID-19 pandemic, the median frequency of telemedicine visits was 18% (11-32%). (Figure 1) Conclusion: Ambulatory in-person cardiology visits decreased during the COVID-19 pandemic; however telemedicine visits partially compensated for this drop. At the height of stay-at-home orders, cardiology in-person outpatient visits decreased to 25%, but rapidly increased back up to 88% the usual in-person visit volume. Future study is needed to assess the impact on patient outcomes, family satisfaction, cost-effectiveness and revenue of telemedicine visits during the COVID-19 pandemic.
QOLP-01. OUTCOME ASSESSMENT OF MULTIDISCIPLINARY BRAIN TUMOR BOARD MEETING RECOMMENDATIONS FOR BRAIN METASTASIS: IS THERE A GAP?
Authors: Fernando Santos-Pinheiro, Joseph Bovi, Wendy Peltier, Jennifer Connelly, Wade Mueller, Michael Straza, Lindsay Puckett, Marianne Crabb, Julianne Leuck, Nathan Zwagerman, Jonathan Thompson, Christopher Schultz, Jennifer Lindstedt, Kimberly Roller-Voigt, Ariel Nelson, Sarah Bichler, Alexandra Leutenegger, Tracy Erlitz, Carolyn Brausch, Hina Saeed, Dustin Hahn, Fernando Santos-Pinheiro
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Brain metastasis (BM) is the most common form of brain cancer affecting 20-40% of cancer patients. Advancements in cancer therapy has prolonged survival but BM incidence has increased. BM management requires a multidisciplinary approach to individualize care via an ever-growing sum of surgical, radiation, and systemic therapy options. Consensus is achieved by multidisciplinary tumor board meeting (MTBm). Nevertheless, BM diagnosis predicts poor prognosis. Palliative Care (PC) is essential for proper BM management. Yet, formal PC assessment may not be available for MTBm. We evaluated whether MTBm consensus recommendations were followed. RESULTS Our weekly MTBm discussed 157 BM cases during 2019 (median age: 64 years [range 28-91], male/female: 82/75). The most common primary diagnosis was lung (n=49, 31%), breast (n=24, 15%), melanoma (n=16, 10%). The majority was newly diagnosed BM (n=143, 91%). MTBm recommendations were divided into three not-mutually-exclusive categories: surveillance/workup (n=78, 50%), BM-directed treatment (n=101, 64%) and GOC discussion (n=7, 4%). MTBm recommendations were fully followed in 113 cases (72%), partially in 13(8%), and not followed in 25(16%). Of the 38 patients whose recommendations were partially/not followed, the main reason was transition to hospice/death (n=26, 68%). Of the 101 patients recommended treatment, 68% (n=68) fully followed it, yet 31% (n=21) of them died within 3 months; for those living longer than 3 months (n=47, 69%), median KPS at 3 months was 70 (range 30-90). Of the entire cohort (n=157), only 20 (13%) established consistent PC follow-up (&amp;gt;1 outpatient visit) and 69 cases (44%) transitioned to hospice/died within 6 months, 30 of which (43%) still completed surgery (n=6) or radiotherapy (n=24) within this period. CONCLUSION Periodic assessment of MTBm recommendations is relevant for sensible BM management. Balancing treatment while focusing on QoL in a patient population with limited survival is challenging. PC assessment at MTBm could close this gap.
The Cost-Effectiveness of Rosuvastatin Therapy: JUPITER (Justification for the Use of statins in Prevention: An Intervention Trial Evaluating Rosuvastatin)⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Mark Hlatky
Journal: Journal of the American College of Cardiology (2011)
CTNI-45. A PHASE 1B/2 CLINICAL STUDY OF NAPABUCASIN IN COMBINATION WITH TEMOZOLOMIDE FOR ADULT PATIENTS WITH RECURRENT OR PROGRESSED GLIOBLASTOMA MULTIFORME (GBM)
Authors: Andrew Chi, Paula DeRobles, Emma Foos, Matthew Hitron, Warren Mason
Journal: Neuro-Oncology (2020)

Abstract Napabucasin is an orally-administered NQO1–bioactivatable investigational agent hypothesized to affect multiple oncogenic cellular pathways including STAT3. This open-label, multicenter, phase 1b/2 study assessed napabucasin plus temozolomide for recurrent/progressive GBM. Phase 1b objectives were safety/tolerability, recommended phase 2 dose (primary), preliminary antitumor activity, and pharmacokinetics/pharmacodynamics (secondary). Phase 2 objectives were preliminary antitumor activity via 6-month progression-free survival (PFS-6 [20% projected]) (primary); disease control rate; median PFS; objective response rate (ORR); and overall survival (OS) (secondary). Arm A enrolled repeat surgical resection candidates; arm B enrolled patients ineligible for further resection. Patients received napabucasin (oral, 480 mg twice-daily) plus temozolomide (150 mg/m2, days 1–5, 28-day cycles). Arm A closed after 4 patients enrolled to prioritize Arm B enrollment. Arm B data are reported. Arm B enrolled/treated 30 patients (median age=56.5 [range=19–83] years; median napabucasin duration=55.0 [range=1–743] days; previous temozolomide=22 [73.3%] patients); all stopped therapy (radiologic progressive disease [PD], n=20; clinically unacceptable toxicities, n=7; follow-up loss, n=2; clinical PD, n=1). Mean relative dose intensity was 67.2% for napabucasin and 90.9% for temozolomide; 14/30 (46.7%) and 25/30 (83.3%) patients received ≥ 90% intended napabucasin and temozolomide doses, respectively. All patients reported ≥ 1 treatment-emergent adverse event (TEAE, grade ≤4); grade 3 TEAEs (≥ 10% patients) were diarrhea (23.3%, 7/30) and abdominal pain (16.7%, 5/30). One patient reported a grade 4 TEAE (seizure, treatment unrelated). PFS-6 was 28.1% (80% CI=16.8%-40.5%). Median PFS was 1.9 months (95% CI=1.8–3.3), with PFS-12 and PFS-18 both 16.8% (80% CI=7.8%-28.8%). ORR was 10% (95% CI=2.1%-26.5%), with 3 partial responses, 6 stable disease, 14 PD, and 7 patients not evaluated. OS-12 was 28.3%. The napabucasin-plus-temozolomide safety profile was consistent with that anticipated for each agent. Napabucasin (480 mg twice-daily) was associated with grade 3 diarrhea and suboptimal compliance. Antitumor effects were observed per the primary endpoint in this patient population.
BIOM-15. SUBVENTRICULAR ZONE INVOLVEMENT IS ASSOCIATED WITH WORSE OUTCOME IN GLIOMA WHO GRADE II INDEPENDENT OF MOLECULAR MARKERS
Authors: Philipp Karschnia, Jonathan Weller, Jens Blobner, Veit M Stoecklein, Mario M Dorostkar, Kai D Rejeski, Robert Forbrig, Maximilian Niyazi, Louisa von Baumgarten, Jorg Dietrich, Joerg-Christian Tonn, Niklas Thon
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND The subventricular zone represents a niche of adult neural stem cells. Involvement of the subventricular zone is associated with decreased survival in malignant glioma. We aimed to determine whether a similar association applies to low-grade gliomas. METHODS A retrospective institutional database search was performed for patients with glioma WHO grade II according to the 2016 classification. Demographic data, histology and molecular signature, imaging, and therapy were recorded and outcome was analysed for tumors with and without infiltration of the subventricular zone. RESULTS 182 patients with glioma WHO grade II were identified, including 97 oligodendrogliomas and 85 astrocytomas. 78 of 182 patients (43%) presented with subventricular zone involvement. Demographics, histopathology, and molecular signature did not differ between patients with and without subventricular zone involvement. First-line management included surgery, chemotherapy, radiotherapy, brachytherapy, and wait-and-scan approaches. Median follow-up was 43 months. Median time to malignant progression was 122 months; median overall survival was not reached. Subventricular zone involvement was a negative prognostic marker for time to malignant progression (p = 0.002) and overall survival (p = 0.023) in the entire cohort as well as in the subgroup of patients who were managed with wait-and-scan approaches. Among patients in which early therapy was provided, subventricular zone involvement was not prognostic for overall survival but for time to malignant progression. In multivariate analysis, subventricular zone involvement was associated with worse prognosis independent of molecular markers or treatment approaches including use of resection. CONCLUSION Subventricular zone involvement represents a key risk factor for worse outcome in glioma WHO grade II. Early first-line therapy may improve outcome in such patients.
Understanding the role of tissue-specific decellularized spinal cord matrix hydrogel for neural stem/progenitor cell microenvironment reconstruction and spinal cord injury
Authors: Yiwei Xu, Jing Zhou, Cuicui Liu, Sheng Zhang, Fenglin Gao, Wenjing Guo, Xiumin Sun, Chi Zhang, Heying Li, Zilong Rao, Shuai Qiu, Qingtang Zhu, Xiaolin Liu, Xiaodong Guo, Zengwu Shao, Ying Bai, Xiao Zhang, Daping Quan
Journal: Biomaterials (2020)
ATRT-27. COST-EFFECTIVE ASSAYS TO SUBGROUP ATRT IN THE DAILY ROUTINE
Authors: María-Jesús Lobon-Iglesias, Arnault Tauziede-Espariat, Mamy Andrianteranagna, Zhiyan Han, Julien Masliah-Planchon, Franck Bourdeaut
Journal: Neuro-Oncology (2020)

Abstract Three atypical teratoid rhabdoid tumors (ATRT) molecular subgroups with different bio-clinical characteristics have been reported (TYR, SHH and MYC). Molecular subgrouping relies on either methylation profiling (reference methods), or expression profiling. However, the cost-effectiveness of such pangenomic screening is questionable. This work aims to study the reliability of alternative techniques for subgroup classification in the daily routine. Illumina EPIC-arrays were performed on 46 samples. Among those cases, expression profiling were analysed by RNAseq (n=30). We designed a 26-gene panel to assess expression profiling using the Nanostring technology; this was applied to 35 tumors. Immunohistochemistry (IHC) was used for 20 samples; it relied on the expression of MITF, TYR, OTX2 and MYC. We first assessed the concordance between DNA methylation and RNAseq based profilings; then, between RNAseq and Nanostring and, finally, between methylation profiling and Nanostring or IHC, the two rapidest and cheapest tools. The concordance between the two expression-based profiling was 19/21. EPIC-arrays and RNAseq or Nanostring were concordant in 26/30 and 30/35 samples, respectively. The concordance was perfect for methylation-defined MYC subtype. Finally, 17/20 tumor samples were classified in the same subgroup by EPIC-arrays and IHC; the 3/20 misclassified tumors were SHH by methylation but consistently MYC by IHC, Nanostring and RNAseq. There was 90–100% of concordance for TYR subgroup (all techniques). We have designed a gene panel-based expression signature that shows promising concordance with RNAseq and methylation profiling. Nanostring assay and IHC well predict ATRT subgroup classification for MYC and TYR subclass, but less so for methylation-defined SHH ones.