tbuckley/cabot-search huggingface dataset:
HGG-28. INTEGRATIVE ANALYSES OF MRI PARAMETERS, METABOLOMICS AND HYPOXIC BIOMARKERS ARE SHOWING PREDICTIVE CORRELATION WITH PATIENT CHARACTERISTICS AND OUTCOME
Authors: Natacha Entz-Werle, Agathe Chammas, Elisa Ruhland, Consuelo Sebastia, Flaviu Gabor, Aurelie Durand, Eric Guerin, Stephane Kremer, Izzie Jacques Namer, Monique Dontenwill
Journal: Neuro-Oncology (2018)

Gliomas are the most common type of pediatric brain tumors. Most of them are low grades, but one third are high grade gliomas (pHGG) with a significant impact on patients' median survival, which is averaging 1 year depending on mutational background. Despite the progress in their molecular knowledge, we need to understand their development and rapid progression with new approaches, like novel imaging analyses, as well as metabolomics, associated to hypoxic biomarkers. For this purpose, preoperative MRI examinations were retrospectively studied for quantitative parameters (diffusion and perfusion metrics) in 23 patients (10 DIPGs, 10 thalamic or hemispheric pHGG and 3 gliomatosis cerebri). Metabolomic analyses and protein expression of HIF1 and HIF2 were also assessed in the corresponded fresh-frozen and paraffin-embedded samples. Statistical correlations were performed using Khi2 tests and Kaplan-Meier analyses. Among those 23 patients, 9 were overexpressing HIF1 and 3 HIF2, 6 were having both overexpressions. Two patients were not expressing HIF1 and HIF2 either. The ADC values (mean of (0.998 ± 0.22)×10(-3) mm(2)/s) were obtained for all patients, whereas we could only assessed DCE-MRI evaluation in 14 patients. A correlation with a worst patient outcome was observed in the group with higher ADC values (p<0.01). A significant association between HIF2 overexpression, lipolytic metabolism and the higher values of ADC (p<0.05) was assessed, whereas, in the tumors overexpressing HIF1, a correlation with glutaminolysis and ADC values was identified (p<0.04). Our findings suggest that ADC parameter might be predictive of specific hypoxic biomarkers in those malignant brain tumors.
Bariatric Surgery and Hypertension—Reply
Authors: Edward H. Livingston
Journal: JAMA (2018)

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EAPH-05. MOLECULAR PROFILING AND IDENTIFICATION OF TARGETED THERAPIES FOR CHILDREN AND YOUNG ADULTS WITH PRIMARY CENTRAL NERVOUS SYSTEM TUMOURS IN THE UNITED KINGDOM
Authors: Ajla Wasti, Fernando Carceller, Sally George, Eleni Koutroumanidou, Elisa Izquierdo, Pilar Guerra, Magdalena Zarowiecki, James Campbell, Bissan Al-Lazikani, Lynley Marshall, Chris Jones, Matthew Clarke, Karen Powell, Tracey Crowe, Tony Rogers, Julia Chisholm, Sucheta Vaidya, Henry Mandeville, Frank Saran, Bassel Zebian, Samantha Hettige, Safa Al-Sarraj, Leslie Bridges, Tom Jacques, Darren Hargrave, Andy Pearson, Brian Walker, David Gonzalez de Castro, Michael Hubank, Louis Chesler
Journal: Neuro-Oncology (2018)

BACKGROUND. Molecular alterations: point mutations, amplifications and deletions give cells the ability to bypass therapeutic approaches. Molecular profiling facilitates access to personalised strategies to treat patients harbouring such alterations. METHODS. A Next Generation Sequencing (NGS) panel comprising 78 genes (version1) or 92 genes (version2) has been piloted in the UK since March 2016, using formalin-fixed paraffin embedded tissue of children and young adults with solid tumours, including central nervous system (CNS) tumours. RESULTS. Of 156 cases profiled, patients with primary CNS tumours constituted the largest subset (59 patients; 38%). Main diagnoses included high grade astrocytoma (22 patients; 37%), ependymoma (8 patients; 14%) and medulloblastoma (8 patients 14%). In 66% of sequenced samples the panel detected at least one genetic alteration and a total of 54 distinct genetic alterations were uncovered; most frequently in TP53 (16; 14%), H3F3A (8; 7%) and ATRX (7; 6%). In 2 cases (3%), identification of therapeutic targets (BRAF mutations) led to treatment with a combination of BRAF and MEK inhibitors via compassionate access programmes in young adults who had exhausted standard treatment options and were beyond the age eligibility cut-off for enrolment in the ongoing paediatric BRAF/MEK inhibitor studies. CONCLUSIONS. Molecular profiling is increasingly being integrated into standard of care for patients with CNS tumours. However, the finding of truly actionable mutations with available targeted therapies remains limited in clinical practice. More efficient approaches to implement personalised medicine strategies for CNS tumour patients are still needed as is currently illustrated by initiatives such as ESMART (NCT02813135).
MBCL-08. MOLECULAR CHARACTERIZATION OF NODULAR DESMOPLASTIC MEDULLOBLASTOMAS IN YOUNG CHILDREN TREATED ON ACNS1221. A REPORT FROM THE CHILDREN ONCOLOGY GROUP
Authors: Lucie Lafay-Cousin, Giles Robinson, Vasilisa Rudneva, Paul Northcott, Catherine Billups, Arzu Onar-Thomas, Cynthia Hawkins, Charles Eberhart, Craig Horbinski, Linda Heier, Mark Souweidane, Douglas Strother, Maryam Fouladi, Eric Bouffet, Amar Gajjar
Journal: Neuro-Oncology (2018)

ACNS1221 was a single-arm multicenter trial of conventional chemotherapy for children < 4y with localized nodular desmoplastic medulloblastoma and medulloblastoma with extensive nodularity(ND/MBEN), based on a modified HIT SKK 2000 regimen excluding intraventricular methotrexate. The trial prematurely closed for an excess of relapses. Here we provide the final analysis of the clinical and molecular characterization of the cohort. Tumor samples were prospectively collected to describe the molecular profile of ND/MBEN. DNA methylation was performed using Infinium MethylationEPIC BeadChip and profiled on DKFZ molecularneuropathology2.0 classifier. DNA copy-number variants were inferred from DNA methylation arrays using Conumee. Methylation profiles were added to a founder cohort of 87 infant SHH-MB and analyzed by t-distributed stochastic neighbor embedding (t-SNE) to delineate SHH-I and SHH-II subtypes. The cohort included 26 patients(19 ND and 7 MBEN) diagnosed at a median age of 19.7 months. All tumors clustered within the SHH group and separated into 2 subtypes: SHH-I(42%) and SHH-II(58%). SHH-I patients were significantly older than SHH-II patients (p=0.009). Most MBEN were SHH-II(86%) but no significant association was found between histology and subgrouping(p=0.18). Chromosome 2 gain was exclusively described in SHH-I. Eight relapses occurred in SHH-I and 4 in SHH-II (median time of 9.8 months). The 2y PFS for SHH-I and SHH-II was respectively 27.3%(+/-13.4%) and 73.3%(+/-13.4%) (p=0.034). Age <12 mos, MBEN histology and female sex were associated with better PFS. With the ACNS1221 cohort, we prospectively validated the existence of 2 SHH subgroups in young children and the worse outcome of SHH-I subgroup.
Genetic subtyping of breast implant–associated anaplastic large cell lymphoma
Authors: Naoki Oishi, Garry S. Brody, Rhett P. Ketterling, David S. Viswanatha, Rong He, Surendra Dasari, Ming Mai, Hailey K. Benson, Christopher A. Sattler, Rebecca L. Boddicker, Ellen D. McPhail, N. Nora Bennani, Christin A. Harless, Kuldeep Singh, Mark W. Clemens, L. Jeffrey Medeiros, Roberto N. Miranda, Andrew L. Feldman
Journal: Blood (2018)
Identification of Nocardia species from clinical isolates using MALDI-TOF mass spectrometry
Authors: M. Marín, A. Ruiz, C. Iglesias, L. Quiroga, E. Cercenado, P. Martín-Rabadán, Emilio Bouza, Belén Rodríguez-Sánchez
Journal: Clinical Microbiology and Infection (2018)
LGG-58. A PHASE II TRIAL OF POLY-ICLC IN THE MANAGEMENT OF RECURRENT OR PROGRESSIVE PEDIATRIC LOW GRADE GLIOMAS (NCT01188096): PRELIMINARY ANALYSIS
Authors: Dolly Aguilera, Tobey MacDonald, John Crawford, Nadja Kadom, Anna Janss, Claire Mazewski, Robert Craig Castellino, Rachael Gray, Minya Pu, Erin Connelly, Andres Salazar, Donald L Durden
Journal: Neuro-Oncology (2018)

Low dose Poly-ICLC (Polyinosinic-Polycytidylic acid stabilized with polylysine and carboxymethylcellulose) has a direct immune enhancing action independent of interferon, including increased antibody response to antigen, and NK cell, T-cell, macrophage and cytokine activation. We conducted an immunotherapy trial to evaluate the effect of Poly-ICLC in the children with recurrent or progressive low grade gliomas. Criteria for enrollment: progression by MRI and or visual deterioration. Patients received Poly-ICLC 20mcg/kg/dose IM injection twice a week for up to 24 months. 23 patients enrolled, 22 evaluable. Ages 2-20 years. Ten females and 13 males Location: suprasellar (11), spine (1), disseminated (4), others (7). Six patients with NF-1. Pathology: JPA (11), pilomyxoid (5), no pathology (3), Diffuse Astrocytoma, ganglioglioma, Glioneuronal tumor, LGG NOS (1 each). Follow-up range 3 to 58 months. Responses: 43% stable disease, 17% (4/23) partial responses- 3 with NF-1. Visual fields and acuity improved in 33% of patients with NF-1. Two JPA patients that have completed 24 months of therapy: one non-NF with SD and PFS 58 months, one NF-1, PR, PFS for 28 months. Most common toxicities included: fevers, discomfort at the injection site, Grade 1 neutropenia, lymphocytopenia, hypophosphatemia, ALT elevation. One case of grade 4 intratumoral hemorrhage, required medical management alone. No patient required transfusion or admission for fever and neutropenia. No reports of neuropathy. Poly-ICLC is well tolerated, minimal toxicity, radiographic and clinical responses were demonstrated in patients with LGG. Larger clinical trials with Poly-ICLC are being designed.
NSRG-14. SAFETY AND EFFICACY OF GAMMA KNIFE RADIOSURGERY FOR PEDIATRIC BRAIN TUMORS
Authors: Ashley S Plant, Jody Pathare, Darcy Engelhart, Venita Williams, Ivan Kirov, William G Loudon
Journal: Neuro-Oncology (2018)

Radiation therapy (RT) remains a standard of care adjuvant therapy for the treatment of many pediatric brain tumors. However, standard external beam RT is associated with effects on neurocognitive abilities, endocrine function, and the development of secondary malignancies. Since 2002, we have treated 160 pediatric (<18yo) brain tumor patients (median age = 12yrs, age range 2-18yrs) with gamma knife (GK) stereotactic radiosurgery after maximal surgical resection. Tumor types included low grade glioma, ependymoma, medulloblastoma, and metastatic neuroblastoma. Some patients with malignant or metastatic tumors were treated after failing conventional fractionated radiation and/or chemotherapy. GK patients were treated with single, outpatient sessions and those >10yrs generally required only conscious sedation for frame placement. No patients required post-GK admission and there were no reported acute toxicities or long term complications including radiation necrosis or development of secondary malignancy over a median follow-up of 8yrs (range 1-17yrs). The physics employed by GK stereotactic radiosurgery offers potential for significantly decreasing exposure of healthy brain to ionizing radiation, and, therefore, may offer significant safety benefits for pediatric patients with localized brain tumors. The outcomes of GK for pediatric brain tumors are favourable in our experience. In an accompanying abstract, we present outcome data of 23 patients treated with GK for grade I-II astrocytomas. Over the past 16yrs, we have found GK SRS to be effective, well tolerated, and safe in the pediatric population.
Recovery technique using a double scope to rescue failed primary endoscopic ligation
Authors: Yosuke Minoda, Keishi Komori, Ryoko Naruo, Tsutomu Iwasa, Haruei Ogino, Eikichi Ihara, Yoshihiro Ogawa
Journal: Endoscopy (2018)

It is important to address the ideal management of artificial large-sized ulcers or perforations, especially those related to endoscopic submucosal dissection (ESD). A few techniques have been described [1] [2] [3] [4] [5]. However, highly advanced endoscopic skills are usually required to achieve complete closure of the defects using standard hemoclips. In contrast, closure using an endoscopic ligation device (ELD) combined with hemoclips allows closure to be achieved relatively easily [1] [2] [3]. However, we sometimes encounter difficulty when using a combination of endoloop and hemoclips. We therefore propose a recovery technique for cases in which endoloop closure fails ([Video 1]).
Is the PEG-G-CSF useful as the prevention for the severe neutropenia in metastatic colorectal cancer patients treated with FOLFOXIRI plus bevacizumab?
Authors: H. Osumi, E. Shinozaki, T. Wakatsuki, M. Suenaga, T. Ichimura, M. Ogura, Y. Ota, I. Nakayama, D. Takahari, K. Chin, K. Yamaguchi
Journal: Annals of Oncology (2018)

Introduction: FOLFOXIRI plus bevacizumab (Bev) significantly improved both the progression free survival (PFS) and the overall survival (OS) of patients with metastatic colorectal cancer (mCRC). However, as the frequency of grade 3/4 neutropenia is very high, we often require the dose adjustment in the clinical practice. The Polyethylene glycol conjugated granulocyte colony-stimulating factor (PEG- G-CSF), which is characterized by an increased circulating half-life, has the potential to shorten the duration and severity of neutropenia. However, there is a few evidences to evaluate the efficacy of the PEG-G-CSF for the neutropenia in mCRC. This study aimed to evaluate treatment outcomes, safety and the efficacy of the PEG-G-CSF for neutropenia in mCRC patients treated with FOLFOXIRI plus Bev. Methods: We retrospectively analyzed mCRC patients who received FOLFOXIRI plus Bev between December 2015 and December 2017 at the Cancer Institute Hospital. Bev was given as a 5 mg/kg intravenous dose. FOLFOXIRI consisted of a 165 mg/m2 intravenous infusion of irinotecan for 60 min, followed by an 85 mg/m2 intravenous infusion of oxaliplatin given concurrently with 200 mg/m2 leucovorin for 120 min, followed by a 3200 mg/m2 continuous infusion of fluorouracil for 48 h. We evaluated the overall response rate (ORR) according to the RESICT ver 1.1, PFS, OS, adverse events by CTCAE ver 4.0 and the efficacy of the PEG-G-CSF for the neutropenia. PFS and OS were estimated using the Kaplan-Meier method and compared using the log-rank test. Results: A total of 26 patients (13 male, 13 female) with a median age of 53.5 (27-74) were included. The median follow up time of the study was 24.2 months. Among all the patients, 18 patients (69.2%) had the ECOG PS of 0. 8 of 26 patients (30.8%) had right-sided primary tumor location. 23 of 26 patients (88.5%) had the RAS mutant tumor. UGT1A1 status were wild type (26.9%), *6 (23.0%), *28(7.7%), Unknown (42.4%), respectively. The ORR rate was 65.3%, the median PFS was 9.6 months (7.2–16.9), and the median OS was 24.2 months (13.6–NA). Grade 3/4 neutropenia occurred in 53.8% of patients and the febrile neutropenia occurred in 7.7%. The PEG-G-CSF was used in 76.9% of patients. In the patients who used the prophylactic PEG-G-CSF (n = 9), 7 of 9 patients (77.7%) didn't require the dose adjustment. In the patients who used PEG-G-CSF after grade 3/4 neutropenia (n = 11), no one experienced grade 3/4 neutropenia again. 2 of 26 patients (7.2%) required the dose adjustment due to non hematologic adverse events. Conclusion: The PEG-G-CSF is useful to prevent a severe neutropenia and to keep dose intensity in mCRC patients treated with FOLFOXIRI plus Bev.
LGG-54. ORAL VINORELBINE IN PROGRESSIVE UNRESECTABLE LOW-GRADE GLIOMA: EXPERIENCE OF A SINGLE INSTITUTION
Authors: Andrea Cappellano, Cynthia M Silveira, Milena RS Oliveira, Sergio Cavalheiro, Patricia Dastoli, Maria Teresa S Alves, Gregorio Pereira, Frederico A Silva, Daniela Barbosa, Nasjla, Saba da Silva
Journal: Neuro-Oncology (2018)

The management of progressive unresectable low-grade glioma (PULGG) remains controversial. Some series suggests that chemotherapy may delay or even avoid radiotherapy and/or surgery in a proportion of children. Within this context we performed initially an institutional protocol with .8IV vinorelbine, a semi-synthetic vinca alkaloid that shown activity against PULGG. The objective of this study is to evaluate the response as long as the tolerability of oral vinorelbine in patients with diagnosis of optic pathway glioma (OPG). PATIENTS AND Since 2013, 16 patients with recurrent (n=4) and newly-diagnosed (n=12) OPG have been treat with oral vinorelbine in a dose of 90 mg/m2 days 0, 8 and 22 for 18 cycles. Response criteria used a combination of magnetic resonance imaging, physical and visual evaluation. Mean age 8.6 years (4.8-17.9). Three children with neurofibromatosis type 1. Eleven patients had neurosurgical intervention revealing grade I (n=9) and grade II astrocytoma (n=2). Eleven patients were assessable after 4/8 cycles of vinorelbine with 2 objective response (OR), 7 stable disease (SD) and 2 progressive disease (PD), one died after surgery and 1 alive in different protocol. After 18 cycles, seven patients were assessable to date for response with 2 OR, 5 SD. The most important toxicity was gastrointestinal observed in 12 patients- six of them withdraw treatment. None of the patients showed neurotoxicity. The preliminary results suggest that oral vinorelbine may show some activity in PULGG. However, gastrointestinal toxicity should be considered.
Safety of gemcitabine plus nab-paclitaxel in advanced pancreatic cancer patients presenting with hyperbilirubinemia secondary to bile duct obstruction
Authors: M. Sasaki, H. Imaoka, M. Kan, Y. Suzuki, G. Kimura, K. Umemoto, K. Watanabe, H. Takahashi, Y. Hashimoto, I. Ohno, S. Mitsunaga, M. Ikeda
Journal: Annals of Oncology (2018)

Introduction: The MPACT study demonstrated a significant survival benefit of gemcitabine plus nab-paclitaxel (GN) as compared to gemcitabine alone, however, patients with abnormal elevation of the serum total bilirubin (Tbil) levels were excluded from the study. Patients with advanced pancreatic cancer (APC) often present with extrahepatic bile duct obstruction, which can result in elevated Tbil levels. Normalization of Tbil by biliary drainage can take weeks, so safety data to support treatment initiation in patients with elevated Tbil levels are desirable. Therefore, we attempted to evaluate the safety of GN, in terms of the risk of hematological toxicity in APC patients presenting with hyperbilirubinemia secondary to bile duct obstruction. Methods: Data of a total of 351 patients with APC who were treated with GN as first-line treatment at our department between Dec. 2014 and Dec. 2017 were reviewed retrospectively. Patients who underwent biliary drainage before the initiation of GN and received no initial dose reduction were included, while patients with irreversible hyperbilirubinemia due to liver metastasis were excluded. The patients were divided into two groups according to the Tbil levels at the initiation of GN: the normal bilirubin group (NB-G group; Tbil ≦1.5 mg/dL) and hyperbilirubinemia group (HB-G group; Tbil >1.5 mg/dL). The incidence of severe hematotoxicity during the first cycle of treatment was compared between the two groups. The p-values < 0.05 were considered statistically significant and all p-values were two sided. Results: A total of 78 patients, including 59 from the NB-G group and 19 from the HB-G group were included in this analysis. The patient characteristics (NB-G vs. HB-G groups) were as follows: median age, 66 vs. 69; ECOG-PS 0-1/2, 56/3 vs. 19/0; male/female, 28/31 vs. 9/10; UICC-TNM stage III/IV, 22/37 vs. 8/11; primary site head/body-tail, 56/3 vs. 19/0; biliary intervention with plastic stent/metallic stent/surgical bypass, 12/45/2 vs. 3/16/0; median pretreatment Tbil, 0.72 mg/dL (0.22-1.49) vs. 1.8 mg/dL (1.51-2.76). During the first cycle of treatment, severe hematologic adverse events (grade 3/4 neutropenia and/or grade 3/4 thrombocytopenia) occurred in a total of 31 patients and febrile neutropenia in a total of 7 patients. There were no significant differences in the incidence of severe hematological adverse events between the two groups (22 in the NB-G group and 9 in the HB-G group; p = 0.59). Conclusion: The safety of GN, in terms of the risk of hematological toxicity was similar between the NB-G and HB-G groups in this study. For APC patients presenting with hyperbilirubinemia secondary to bile duct obstruction, it might be safe to initiate GN without dose reduction if a suitable procedure for biliary drainage is undertaken prior to the initiation of the treatment.
HGG-39. EFFECT OF TUMOR TREATING FIELDS IN CHILDREN WITH RECURRENT OR PROGRESSIVE HIGH-GRADE GLIOMA AND EPENDYMOMA (PEDIATRIC BRAIN TUMOR CONSORTIUM PBTC048)
Authors: Stewart Goldman
Journal: Neuro-Oncology (2018)

Prognosis is poor in recurrent or progressive pediatric CNS tumors. Children with high-grade gliomas (HGG) after progression cannot be cured; reported median survival is <1-2 years. Overall survival (OS) of pediatric recurrent/progressive ependymoma is also poor. Tumor Treating Fields (TTFields) is an approved anti-mitotic cancer therapy for newly diagnosed and recurrent (supratentorial) glioblastoma (GB). A phase 3 trial in adults with newly-diagnosed GB showed significantly improved event-free (EFS) and OS in patients receiving TTFields plus temozolomide. A phase 3 trial recurrent GB of TTFields monotherapy versus physician’s choice chemotherapy in adults demonstrated comparable OS and improved quality-of-life (QoL). This multicenter trial [NCT03033992] will examine the feasibility and toxicity of TTFields in children (5-21 years) with supratentorial HGG and ependymoma. Secondary objectives include: response rate, EFS, compliance and QoL. The Optune device will be worn ≥18 hours/day for at least 23/28 days of cycle one. Patients will have brain MRIs with/without contrast prior to therapy, after cycles 2, 4, 6, 9, then every 3 cycles thereafter until progression or treatment completion. Treatment may continue up to 26 cycles based on observed benefit/safety. A sample size of 20 patients is planned with an interim analysis after the first 11 patients. Kaplan-Meier estimates of EFS for eligible patients will be provided separately for HGG and ependymoma cohorts. Rates of confirmed sustained objective responses (CR+PR) during treatment will be estimated. All PROMIS and Neuro-QoL scores will be reported using T-score matrix (mean=50; SD=10). The accrual rate is 1.5-2.5 patients/month with a 2-year follow-up.