tbuckley/cabot-search huggingface dataset:
DIPG-55. PATTERNS OF CEREBROSPINAL FLUID DIVERSION AND SURVIVAL IN CHILDREN WITH DIFFUSE INTRINSIC PONTINE GLIOMA: A REPORT FROM THE INTERNATIONAL DIPG REGISTRY
Authors: Tabitha Cooney, Mariko DeWire-Schottmiller, Adam Lane, Raya Saab, Pratiti Bandopadhayay, Kathleen Dorris, Roger Packer, Lindsey Kilburn, Jane Minturn, Andrew Dodgshun, Sara Parkin, Stewart Goldman, Eric Sandler, Robert Greiner, Nicholas Gottardo, Hetal Dholaria, Scott L Coven, Tim Hassall, Jordan Hansford, Yvan Samson, Sarah Leary, Ute Bartels, Eric Bouffet, Christopher Tinkle, Michelle Monje, Paul G Fisher, David Ziegler, Murali Chintagumpala, Lars Wagner, Carl Koschmann, Elisa Carrasquedo Benito, James Leach, Blaise Jones, Brooklyn Chaney, Katie Black, Anthony Asher, Hailey Bond, Maryam Fouladi, Katherine E Warren
Journal: Neuro-Oncology (2020)

Abstract There is no standard of care for cerebrospinal (CSF) diversion in children with diffuse intrinsic pontine glioma (DIPG), nor understanding of survival impact. We evaluated CSF diversion characteristics in children with DIPG to determine incidence, indications and potential impact on survival. Data was extracted from subjects registered in the International DIPG registry (IDIPGR). IDIPGR team personnel obtained clinical and radiographic data from the registry database and when appropriate, abstracted additional data from individual medical records. Univariable analyses were performed using the Fisher’s exact test or Wilcoxon rank sum test. Survival was estimated using the Kaplan-Meier method. Evaluable patients (n=457) met criteria for DIPG diagnosis by central radiology review. Ninety-two patients (20%) had permanent CSF diversion. Indications for permanent diversion were hydrocephalus (41%), hydrocephalus and clinical symptoms (35%), and clinical symptoms alone (3%). Those with permanent diversion were significantly younger at diagnosis than those without diversion (median 5.3 years vs 6.9 years, p=0.0002), otherwise no significant differences in gender, race, or treatment were found. The progression-free and overall survival of those with permanent CSF diversion compared to those without permanent diversion was 4.5 and 10.9 months vs 6.9 and 11.2 months, respectively (p=0.001, p= 0.4). There was no significant difference in overall survival in patients with or without permanent CSF diversion among a large cohort of DIPG patients. Patients without permanent diversion had significantly prolonged progression free survival compared to those with permanent diversion. The qualitative risks and benefits of permanent CSF diversion need to be further evaluated.
Correspondence on ‘Jan Gösta Waldenström and rheumatology’
Authors: Haralampos M Moutsopoulos
Journal: Annals of the Rheumatic Diseases (2020)

I read with great interest the article ‘Jan Costa Waldenstrom and Rheumatology’ written by the eminent colleague Wollheim.1 In the late seventies, I had the unique privilege and opportunity to meet, exchange clinical and scientific information and discuss with this giant of medicine, during his visit at the clinical centre of the National Institutes of Health (NIH) in Bethesda, Maryland, USA, in the spring of 1978. I would like to share this inimitable experience with the readers of your distinguished journal. The announcement that the renowned Waldenstrom will visit us, spread around the NIH campus, with the speed of the wind. He was supported by the International Fogarty Center to visit the clinical centre of the NIH for a month, as a senior visiting medical scientist. His programme included several meetings with investigators in person, particularly with those working in areas close to his interest ‘γ-globulin abnormalities’ in order to to discuss with them recent findings, the progress of their research and carefully listen to planned experiments. Moreover, he would participate in outpatient and inpatient rounds and deliver a …
Blockade of atrial angiotensin II type 1 receptors: A novel antiarrhythmic strategy to prevent atrial fibrillation?**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Helmut U Klein, Andreas Goette
Journal: Journal of the American College of Cardiology (2003)
CTNI-35. SURVIVAL OUTCOME AND PROGNOSTIC FACTORS IN ANAPLASTIC OLIGODENDROGLIOMA: A SINGLE-INSTITUTION STUDY OF 95 CASES
Authors: Dongwon Shin, Young Hoon Kim
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVE Anaplastic oligodendroglioma (AO) is a rare intracranial malignant neoplasm and its treatment remains challenging. The aim of this study was to evaluate prognostic factors including surgical, radiographic, and histopathologic analyses in AO patients. METHODS We reviewed the electronic records of 95 consecutive patients who underwent surgical procedures and were diagnosed with AO from 1998 to 2018. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Univariate and multivariable analyses included clinical, histopathological, and radiographic prognostic factors. Subgroup analysis was performed in isocitrate dehydrogenase (IDH1/2)-mutant and 1p/19q-codeleted patients. RESULTS The median PFS and OS were 24.7 months and 50.8 months, respectively. The progression-free 1-, 3-, 5-, and 10-year survival were 75.8%, 42.9%, 32.4%, and 16.4%, respectively. Furthermore, the overall 1-, 3-, 5-, and 10-year survival were 98.9%, 76.9%, 42.9%, and 29.7%, respectively. The median PFS and OS of the IDH1/2-mutant and 1p/19q-codeleted patients were 54.2 and 57.8 months, respectively. Age under 60, frontal lobe location, weak enhancement, gross total resection (GTR), lower Ki-67 index, 1p/19q codeletion, and IDH1/2 mutations were associated with a favorable outcome. Among them, IDH1/2 mutation was the only variable related to better PFS and OS in multivariable analysis. GTR was associated with favorable outcomes in the subgroup analysis. CONCLUSIONS IDH1/2 mutation status was the most important prognostic factor in AO patients. Additionally, in the subgroup analysis, GTR showed better prognosis for IDH1/2-mutant and 1p/19q-codeleted patients.
CTNI-75. A PILOT CLINICAL TRIAL OF OROTECAN (VAL-413), A NOVEL ORAL DOSAGE FORMULATION OF IRINOTECAN: IMPLICATIONS FOR PEDIATRIC BRAIN TUMORS
Authors: Dennis Brown, Jeffrey Bacha, Lars Wagner, Markos Leggas, Sarath Kanekal, Lorena Lopez, Neil Sankar
Journal: Neuro-Oncology (2020)

Abstract Tumors of the brain and of the central nervous system (CNS) are the most common solid tumors in children. Intravenous irinotecan hydrochloride (IRN-IV) is approved for the treatment of adult colorectal cancer. IRN-IV is also used off-label in a wide range of treatment regimens for recurrent adult and pediatric tumors including glioblastoma, pediatric glioma and medulloblastoma. Recently, commercially available IRN-IV has been administered orally (IRN-IVPO) in pediatric patients to reduce intravenous administration-related side effects, improve convenience and reduce clinic time and costs. Unfortunately, the poor palatability of this preparation leads to poor compliance, especially in pediatric patients. VAL-413 is novel formulation developed to improve tolerability of oral irinotecan. The current study (NCT04337177) evaluates the safety and pharmacokinetics of VAL-413 administered with temozolomide for treatment of recurrent pediatric solid tumors. METHODS: Up to 20 patients ≥ 1 to ≤ 30 years of age with recurrent pediatric solid tumors will be enrolled. The primary objective is to establish the recommended phase II dose of VAL-413 when given in combination with temozolomide. Secondary objectives include characterization of the pharmacokinetics of VAL-413 vs. IRN-IVPO, evaluating palatability of VAL-413, assessing the toxicity profile of VAL-413 in combination with temozolomide, and assessment of tumor response. Toxicity is evaluated based on CTCAEv5 and tumor response based on RECISTv1.1. An update on the progress of this trial will be presented.
CTNI-21. SCALP SPARING RADIATION WITH CONCURRENT TEMOZOLOMIDE AND TUMOR TREATMENT FIELDS (SPARE) FOR PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Ryan Miller, Andrew Song, Ayesha Ali, Voichita Bar-Ad, Nina Martinez, Jon Glass, David Andrews, Kevin Judy, James Evans, Christopher Farrell, Maria Werner-Wasik, Inna Chervoneva, Michele Ly, Joshua Palmer, Haisong Liu, Wenyin Shi
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Standard of care for glioblastoma includes concurrent chemoradiation and maintenance temozolomide (TMZ) with tumor treatment fields (TTFields). Preclinical studies suggest TTFields and radiotherapy work synergistically. We report our experience evaluating toxicity of scalp-sparing radiation with concurrent TTFields. METHODS This is a single-arm pilot study (clinicaltrials.gov Identifier: NCT03477110). Patients (age≥ 18 years) with KPS≥ 60 with newly diagnosed glioblastoma were eligible. Patients received concurrent scalp-sparing radiation (60 Gy/30 fx), standard TMZ (75 mg/m2 daily), and TTFields. Maintenance therapy included standard TMZ and TTFields continuation. Radiotherapy was delivered through TTFields arrays. Primary endpoint was safety and toxicity of concurrent TTFields with chemoradiation. RESULTS We report the first eighteen patients on trial. Majority were male (66.7%) with median age 59 years (34 to 77). Median KPS was 90 (70–100). Median follow-up was 6.0 months (1.4 to 18.0). Twelve (66.6%) patients had unmethylated MGMT, five (27.8%) were methylated, and one patient’s status was not obtained. Scalp dose constraints were achieved, with mean dose having a median value of 7.4 Gy (4.3–13.2), D20cc median 23.2 Gy (17.7–36.8), and D30cc median 20.3 Gy (14.8–33.4). Only one possible Grade 3 toxicity was observed in a patient who experienced a seizure in month six of the maintenance phase. Skin toxicity (erythema or dermatitis) was limited to Grade 1 (83.3%) or 2 (5.6%) during the concurrent phase and resolved spontaneously or responded to topical medications. Other Grade 1 events included fatigue (47.3%), cognitive impairment (31.6%), pruritis (52.6%), headache (26.3%), dizziness (15.8%), and nausea (26.3%). Other Grade 2 events included fatigue (21.1%) and headache (10.5%). Nine patients (50%) had progression, with median PFS of 7.6 months (2.2–9.6 months). CONCLUSIONS Concurrent TTFields with scalp-sparing chemoradiation is a safe and feasible treatment option with limited toxicity. Future randomized prospective trials are warranted to define therapeutic advantages of concurrent TTFields with chemoradiation.
EPEN-27. <i>CDKN2A</i> DELETION IN SUPRATENTORIAL EPENDYMOMA WITH <i>RELA</i> ALTERATION INDICATES A DISMAL PROGNOSIS – A RETROSPECTIVE ANALYSIS OF THE HIT EPENDYMOMA TRIAL COHORT
Authors: Stephanie T Jünger, Felipe Andreiuolo, Martin Mynarek, Evelyn Dörner, Anja zur Mühlen, Natalia Velez-Char, Katja von Hoff, Stefan Rutkowski, Monika Warmuth-Metz, Rolf-Dieter Kortmann, Beate Timmermann, Andre O von Bueren, Torsten Pietsch
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Since supratentorial RELA-fusion positive ependymomas are considered a biologically distinct disease, we aimed to identify histological and genetic predictors of outcome in a defined cohort of pediatric patients. MATERIALS AND METHODS We analyzed 54 RELA ependymomas in pediatric patients treated according to HIT2000-E protocols. All cases underwent central neuropathological review. Genome-wide copy number alterations were assessed by molecular inversion probe or SNP array. RELA alterations were detected by RT-PCR, sequencing and assessment of nuclear p65-RelA protein. Copy number alteration of the CDKN2A (cyclin dependent kinase inhibitor 2A) locus and concordant p16 protein expression were analyzed. RESULTS Fifty-two tumors were classified as WHO-grade III (96.3%) with high mitotic activity in 39 cases (72.2%), vascular proliferation in 47 (87.0%), necrosis in 43 (79.6%) and clear cell morphology in 19 (35.2%). All tumors harbored RELA alterations. Homo- or heterozygous CDKN2A deletions were detected in 9 (16.7%) and 14 (25.9%) cases, respectively. p16 protein expression was lost in all cases with homozygous deletion. Median follow-up was 5.4 years with 5-years EFS and OS of 74.1% and 92.6%. In Kaplan-Meier analysis high mitotic activity was related to shorter EFS (p=0.016) and clear cell morphology to longer OS (p=0.039); CDKN2A deletion was associated with shorter OS (homozygous deletion, p=0.009; homo-or heterozygous deletion, p=0.034). No correlation between CDKN2A deletion and high mitotic activity was found but with higher age at diagnosis (p=0.001). CONCLUSION Deletion of CDKN2A occurred in 42.6% of supratentorial ependymomas with RELA alteration and represented a genetic predictor of worse overall outcome in pediatric patients.
LINC-34. OPTIC NERVE INFILTRATION: RARE MANIFESTATION OF CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA IN REMISSION
Authors: Ludi Dhyani Rahmartani
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Optic nerve infiltration in acute lymphoblastic leukemia is a rare manifestation. This infiltration may appear months in advance as an isolated sign of extramedullary relapse and considered as one of the significant clinical findings of central nervous system leukemia. AIM: To describe a case of rapidly progressive optic nerve infiltration in a girl with ALL in remission. CASE: A 13-year-old girl in full remission following treatment for B-cell acute lymphoblastic leukemia presented with decreased vision and proptosis on the left eye. She completed the chemotherapy course two years before. On physical examination, we found the optic disc swelling in her left eyes. There were no signs of relapse from the hematological, cerebrospinal fluid analysis, and bone marrow aspiration. The orbital CT found a mass on the left retrobulbar (size 29x48x32 mm), suspected of optic nerve glioma. The mass has grown rapidly in a month, and she lost her left sight. The involved eye was exenterated (60x55x40 mm). The histopathology and immunohistochemistry showed the B-cell acute lymphoblastic lymphoma. Unfortunately, the patient could not come for further follow up due to the COVID-19 large-scale social distancing. Two months later, she came with pallor and pain in all of her body. The bone marrow aspiration showed leukemic relapse and she is undergoing chemotherapy. CONCLUSION Optic nerve infiltration by leukemia requires both diagnostic certainty and urgent management. A routine ophthalmic assessment is recommended in patients with a history of acute lymphoblastic leukemia to diagnose optic nerve involvement due to leukemic infiltration.
MODL-22. DEVELOPING A REAL-TIME PERSONALIZED DRUG TESTING PLATFORM FOR PEDIATRIC CNS CANCERS
Authors: Sandra Laternser, Chiara Cianciolo Cosentino, Justyna M Przystal, Susanne Dettwiler, Elisabeth Jane Rushing, Nicolas U Gerber, Ana Guerreiro Stücklin, Rachna Prasad, Michael Grotzer, Niklaus Krayenbühl, Sabine Müller, Javad Nazarian
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION The relatively small size of biopsied CNS tumors has presented a historical challenge for real-time drug screens. Moreover, in vivo assessment of drug response does not often benefit patients with aggressive gliomas given the relatively long time (&amp;gt;8 months) of tumor engraftment in the classic mouse PDX models. Here, we aimed to develop an innovative real-time in vivo and in vitro drug screening platform capable of analyzing a minimal number (&amp;lt;1E6) of cells obtained at biopsy. METHODS Existing primary cells were used to test 6 different culture platforms. The top platform was selected and used to expand tumor cells obtained of DMG biopsy. Tumor cells were validated using the minION sequencing platform. Single and combination drug (n=7) screens were performed. Effective drugs were further evaluated in zebrafish PDX and non-tumor bearing models to assess efficacy and toxicity, respectively. RESULTS A total of 8 biopsies were obtained. Successful cell expansion was achieved in 6/8 (75%) and a limited drug screen in 3/6 (50%) of cases. Single and combination drug (n=7) assays identified responder and non-responders to candidate drugs. Systemic toxicity of effective drugs was tested in non-tumor bearing zebrafish. Tumor cells were engrafted in zebrafish providing the opportunity for an in vivo screen. The entire process was completed within 21 days on average. CONCLUSIONS A novel platform was developed for rapid in vitro and in vivo drug screens of tumor cells obtained at biopsy. This platform will provide the opportunity to establish personalized therapy for heterogeneous cancers including DMGs.
RADT-42. ADJUVANT RADIATION THERAPY FOR SUBTOTALLY RESECTED CEREBELLAR LIPONEUROCYTOMA
Authors: Shearwood McClelland, Ulysses Gardner, Mitesh Shah, Gordon Watson, Kevin Shiue
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Classified as a benign glioneural tumor, cerebellar liponeurocytoma is a rare disease (fewer than 80 reported cases) and was upgraded from WHO grade I to grade II in 2007 due to its high recurrence rate. The authors report a case of definitive radiation therapy for recurrent subtotally resected cerebellar liponeurocytoma. METHODS An 80-year-old man having undergone seven resections for his left cerebellar liponeurocytoma without adjuvant therapy over the previous decade at outside institutions was referred for radiation therapy two months following his eighth resection, where gross total resection was limited by the lesion proximity to his brainstem resulting in a 2 cm residual left cerebellar lesion. Pathology revealed tumor cells strongly positive for synaptophysin and a Ki-67 labeling index &amp;lt; 1%. Due to the propensity of this disease to recur following resection, his entire resection cavity was treated with external beam radiation therapy (EBRT) to 46 Gy, followed by a 10 Gy boost to his residual disease yielding a total of 56 Gy to the residual disease. RESULTS Reimaging following the initial 46 Gy revealed the residual disease remained amenable (&amp;lt; 3 cm) to stereotactic radiosurgery (SRS), which was delivered via linear accelerator (10 Gy to the 80% isodose line) in a single fraction. Following EBRT + SRS, the patient responded well. At last follow-up, he has demonstrated no evidence of disease progression, brainstem-related morbidity or surgical incision-related morbidity. CONCLUSIONS The first reported case of SRS treatment of cerebellar liponeurocytoma as the culmination of a coordinated definitive plan beginning with EBRT supports the applicability and feasibility of this treatment strategy following subtotal resection. This case indicates that a radiation treatment plan similar to that for central neurocytoma may be an optimal strategy, and suggests that adjuvant radiation therapy following operative resection of this rare disease may be underutilized.
CBIO-02. COMPREHENSIVE ANALYSIS OF MECHANISMS AND MOLECULAR TARGETS FOR BREAST CANCER LEPTOMENINGEAL METASTASIS
Authors: Noriyuki Kijima, Takamune Achiha, Tomoyoshi Nakagawa, Ryuichi Hirayama, Manabu Kinoshita, Naoki Kagawa, Haruhiko Kishima
Journal: Neuro-Oncology (2020)

Abstract Leptomeningeal metastasis from solid cancer is a devastating state for cancer patients. Leptomeningeal metastasis is diagnosed either by cerebrospinal fluid cytology and/or magnetic resonance imaging (MRI). However, it remains unclear as to whether tumor cells attached to leptomeninges are the same from floating tumor cells in cerebrospinal fluid (CSF). In this study, we aim to analyze the differences between tumor cells attached to leptomeninges and floating cells in CSF by xenograft models. We used breast cancer cell line, MDA-MB-231, labelled with green fluorescent protein (GFP) and luciferase. We injected those cells into right lateral ventricle of NOD/Shi-scid IL2Rγ KO mice. When the mice got any signs of tumor, we dissected spinal cord and got CSF from mice. We sorted tumor cells by flow cytometry and extracted RNA from the sorted tumor cells from spinal cord and CSF, respectively. We analyzed transcriptome differences between tumor cells from spinal cord and CSF by RNA sequencing. We found that extracellular matrix related proteins were highly upregulated while cell growth related proteins were downregulated in tumor cells from spinal cord compared with those from CSF. These results suggest that tumor cells attached to leptomeninges have different transcriptome profiles from floating tumor cells in CSF and extracellular matrix related proteins could be therapeutic targets for breast cancer leptomeningeal metastasis.
Nanotheranostic Interface Based on Antibiotic‐Loaded Conducting Polymer Nanoparticles for Real‐Time Monitoring of Bacterial Growth Inhibition
Authors: Hamidreza Enshaei, Anna Puiggalí‐Jou, Luis J. del Valle, Pau Turon, Núria Saperas, Carlos Alemán
Journal: Advanced Healthcare Materials (2020)

Abstract Conducting polymers have been increasingly used as biologically interfacing electrodes for biomedical applications due to their excellent and fast electrochemical response, reversible doping–dedoping characteristics, high stability, easy processability, and biocompatibility. These advantageous properties can be used for the rapid detection and eradication of infections associated to bacterial growth since these are a tremendous burden for individual patients as well as the global healthcare system. Herein, a smart nanotheranostic electroresponsive platform, which consists of chloramphenicol (CAM)‐loaded in poly(3,4‐ethylendioxythiophene) nanoparticles (PEDOT/CAM NPs) for concurrent release of the antibiotic and real‐time monitoring of bacterial growth is presented. PEDOT/CAM NPs, with an antibiotic loading content of 11.9 ± 1.3% w/w, are proved to inhibit the growth of Escherichia coli and Streptococcus sanguinis due to the antibiotic release by cyclic voltammetry. Furthermore, in situ monitoring of bacterial activity is achieved through the electrochemical detection of β ‐nicotinamide adenine dinucleotide, a redox active specie produced by the microbial metabolism that diffuse to the extracellular medium. According to these results, the proposed nanotheranostic platform has great potential for real‐time monitoring of the response of bacteria to the released antibiotic, contributing to the evolution of the personalized medicine.