tbuckley/cabot-search huggingface dataset:
CRAN-08. NATIONAL UK GUIDELINES FOR THE INVESTIGATION, TREATMENT AND LONG-TERM FOLLOW-UP OF PAEDIATRIC CRANIOPHARYNGIOMA
Authors: Hoong-Wei Gan, Kristian Aquilina, Paul Morillon, Assunta Albanese, Konstantinos Barkas, Chris Chandler, Yen-Ching Chang, Christina Daousi, Evangelos Drimtzias, Sarah Farndon, Tom Jacques, Marta Korbonits, Adam Kuczynski, Jennifer Limond, Louise Robinson, Ian Simmons, Nick Thomas, Sophie Thomas, Nicola Thorpe, Faraneh Vargha-Khadem, Daniel Warren, Bassel Zebian, Conor Mallucci, Ashley Gamble, Sophie Wilne, Barney Harrison, Helen Spoudeas
Journal: Neuro-Oncology (2018)

Craniopharyngiomas are the commonest suprasellar tumour in childhood. Despite high overall survival, children with craniopharyngiomas are at risk of multiple relapses and long-term tumour- and treatment-related morbidity. We sought to provide, for the first time, a national evidence-based standard for best practice for the assessment, treatment, and follow-up of paediatric craniopharyngiomas. 44 clinical questions were formulated based on a PICO (Population, Intervention, Comparison, Outcome) format by a multidisciplinary Guideline Development Group to guide systematic searches via the Ovid MEDLINE (1946-February 2017) and Cochrane Library (2016, Issue 12) databases, identifying 2023 separate research articles. Publications underwent a three-tier filtering process and 300 were reviewed using the GRADE approach. Where recommendations could not be made, a two-stage international Delphi consensus process was conducted. 35 recommendations were made, largely based on low to very low quality evidence. 30 further recommendations achieved >70% agreement via Delphi consensus. Craniopharyngiomas should be managed in tertiary paediatric centres with sufficient neuro-oncology, neurosurgery, endocrinology, radiology, pathology and neuropsychology experience. At diagnosis, tumours should be graded using the “Paris” grading system and surgical treatment tailored to avoid hypothalamic damage, with adjuvant radiotherapy being offered after incomplete resections. Recommendations on the long-term multidisciplinary follow-up of survivors are also detailed. These Royal College of Paediatrics and Child Health (RCPCH)-endorsed guidelines provide the first evidence-based national recommendations for the management of paediatric craniopharyngioma. Through their implementation, we hope to achieve better consistency in the quality of care of such patients and improve long-term quality of survival.
Usefulness of colonic tattooing using ICG in patients with colorectal tumors
Authors: J. Park, H. Moon, I. Kwon, J. Kim, S. Kang, E. Lee, S. Kim, J. Sung, B. Lee, H. Jeong
Journal: Annals of Oncology (2018)

Introduction: Preoperative endoscopic tattooing assists in finding small-sized lesions on the movable part of the colon, especially in limited operative fields of vision. The aim of this study is to prove that tattooing using indocyanine green (ICG) dye is beneficial in the reduction of operation time, postoperative management, and to prove its usefulness according to stage and type of laparoscopic surgery. Methods: From Jan 2012 to Dec 2016, all patients underwent laparoscopic colonic surgery at Chungnam National University Hospital were retrospectively screened, and 1010 patients with colorectal neoplasms were included in the study. Their lesions were tattooed with ICG the day before operation. The tattooed group (TG) included 114 patients, and the non-tattooed group (NTG) were selected by propensity score matching of subjects based on age, sex, tumor staging, and operation method (n = 228). In total, 342 patients were enrolled. Between the groups, the change in (Δ, preoperative − postoperative) hemoglobin and albumin levels, operation time, hospital stay, oral ingestion period, transfusion, and perioperative complications were compared. To compensate for the difference in the operation time due to lymph node dissection in the advanced stage, Non-lymph node invasion group were classified as early stage and lymph node invasion group as advanced stage. The TG and NTG were compared in early stage and advanced stage.TG and NTG were compared according to surgical method to determine the efficacy of tattooing for different colonic surgical procedures. Data were obtained from surgical and anesthesia records, pathologic reports, and medical charts. Results: Preoperative TG had a shorter operation time (174.76 ± 51.6 vs. 192.63 ± 59.9, p = 0.007), hospital stay (9.55 ± 3.36 vs. 11.42 ± 8.23, p = 0.003), and post-operative oral ingestion period (1.58 ± 0.96 vs. 2.81 ± 1.90, p < 0.001). Δ Hemoglobin (0.78 ± 0.76 vs. 2.2 ± 1.18, p < 0.001) and Δ albumin (0.415 ± 0.44 vs. 1.08 ± 0.39, p < 0.001) showed less blood loss intraoperatively in the TG. On comparison of patients with early and advanced tumor stages, early-stage colon cancer patients had better results for operation time, hospital stay, oral ingestion period, Δ hemoglobin, and Δ albumin than did advanced stage patients. Operation methods affected the results, and laparoscopic anterior resection (LAR) showed similar results. However, for left and right hemicolectomy, both groups showed no difference in operation time or hospital stay. Conclusion: Therefore, preoperative tattooing with ICG is useful for laparoscopic colectomy, especially for non-lymph node invasive colon cancer and LAR.
Rechallenge with oxaliplatin and peripheral neuropathy in colorectal cancer patients
Authors: M. Martínez-Villacampa, S. Besora Tavera, C. Santos Vivas, C. Izquierdo, J. Bruna, R. Velasco
Journal: Annals of Oncology (2018)

Introduction: Oxaliplatin (OXA) is a cornerstone in the treatment of colorectal cancer (CRC). Retreatment with OXA is frequently considered as salvage treatment. OXA-induced neuropathy (OIN) is the most frequent and feared long-term side-effect. Methods: CRC patients receiving at least twice OXA-based chemotherapy lines at our institution between June 2000 and July 2016 were reviewed. The aim of this study was to investigate whether retreatment with OXA increases the risk of developing new or worsening previous neuropathy. OIN was assessed by National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI), Total Neuropathy Score©(TNS) and nerve conduction studies. Results: 106 patients were included in the analysis. Median age at OXA-based retreatment was 61.5 [20-83] years. After the first OXA-based chemotherapy treatment, 60.3% of patients developed OIN, 29.2% and 8.4% grade 2 and grade 3, respectively after a median of 11 [1-17] cycles. After 30 [11-90] months of median to retreatment with a median of 8 [1-14] OXA cycles, 39.6%, 22.6% and 0% of patients developed grade 1, 2 and 3 OIN, respectively. Worsening of previous OIN was observed in one third (31.1%) of all patients. OXA cumulative dose was independently associated with greater risk of worsening OIN (p < 0.001). Non-significant trend towards higher TNSc© scores after retreatment were observed (5 [0-11] vs 6 [3-13], p = 0.083). Conclusion: Retreatment with OXA in CRC patients is a feasible option even in patients who previously developed moderate or severe OIN. One third of patients experienced a worsening of their previous OIN. Neurological monitoring of patient candidates to retreatment with OXA should be considered.
MBCL-37. SECONDARY PRIMARY TUMOR AND SURVIVAL OUTCOME IN MEDULLOBLASTOMA: A SURVEILLANCE, EPIDEMIOLOGY, AND END RESULTS (SEER) ANALYSIS
Authors: Chonnipa Nantavithya, Debra Yeboa, Kaiping Liao, Susan McGovern, David Grosshans, Mary McAleer, Kristina Woodhouse, Soumen Khatua, Murali Chintagumpala, Arnold Paulino
Journal: Neuro-Oncology (2018)

To define factors that increase risk of developing second primary tumor (SPT) and analyze survival outcomes in medulloblastoma patients. Patients with medulloblastoma from 1973-2014 from SEER18 registries were classified according to age, gender, race, year of diagnosis, adjuvant treatment, region and histology. Of 2771 cases, 146 cases developed SPT of which 42 were benign. The overall incidence rate of SPT at 10 and 15 years was 3.1% and 5.0%. On multiple linear regression analysis, female gender (p=0.0077) and earlier year of diagnosis (1973-1994) (p<0.0001) were associated with a higher risk of developing SPT. There was no difference in SPT between patients who received only radiation (RT) and radiation + chemotherapy (RT + CT), 4.0% and 2.9% (10 years) and 4.8% and 6.0% (15 years), (p=0.33). The most common site for SPT include CNS (43.2%), thyroid (12.3%) and reticuloendothelial (10.3%). Patients treated with RT + CT showed better overall survival (OS) after initial medulloblastoma diagnosis compared with RT alone, 66.1% and 55.6% (10 years) and 61.4% and 49.7% (15 years), (p=0.0022). OS after secondary malignant and benign tumor diagnosis was 35.1% and 63.5% (10 years) and 30.1% and 63.5% (15 years) respectively, (p<0.0001). Female gender and diagnosis before 1995 correlated with a higher risk of developing SPT. Patients receiving RT + CT had a better OS without a reduction of SPT when compared to RT alone.
MBCL-26. EFFECTIVE MANAGEMENT OF MEDULLOBLASTOMA WITH 2 D CONVENTIONAL MODALITY IN CURRENT ERA OF MODERN TECHNOLOGY – OUR INSTITUTIONAL EXPERIENCE
Authors: Jigna Bhattacharya, Nalin Goyal, Rakesh Vyas, U Suryanarayan, Ankita Parikh
Journal: Neuro-Oncology (2018)

Medulloblastoma is a common CNS tumour in pediatric age group. Post- operative craniospinal irradiation (CSI) with concurrent and adjuvant chemotherapy is the standard approach of the treatment. In current era, Tomotherapy and Proton therapy are very promising modalities. But these modalities are still less available in developing countries. We have treated 51 patients of medulloblastoma with conventional 2D modality. A total 41 patients are on regular follow-up. 76% (n= 31) patients were pediatric and adolescent age group. All the patients were treated in supine position. We have evaluated 31 patients for treatment feasibility, patient compliance, acute reactions and short-term outcome. Patient compliance was 100%. Five patients (16.1%) had acute reactions in the form of ulcers over tip of tongue and neutropenia and were managed conservatively. Two of the patients (6.4%) developed recurrence within 1 to 2 yrs of treatment. Twenty-five patients (80.6%) are asymptomatic till date. Four patients (12.9%) died within 1 year of primary treatment because of different reasons. With proper planning and management, medulloblastoma can be treated successfully with 2D external beam radiotherapy with promising results and acceptable acute toxicities even at the centres where the modern technologies are not available. Long term follow-up is required for disease free and 5-year overall survival data.
Uptake and impact of vaccinating primary school-age children against influenza: experiences of a live attenuated influenza vaccine programme, England, 2015/16
Authors: Richard G Pebody, Mary A Sinnathamby, Fiona Warburton, Nick Andrews, Nicola L Boddington, Hongxin Zhao, Ivelina Yonova, Joanna Ellis, Elise Tessier, Matthew Donati, Alex J Elliot, Helen E Hughes, Sameera Pathirannehelage, Rachel Byford, Gillian E Smith, Simon de Lusignan, Maria Zambon
Journal: Eurosurveillance (2018)

The 2015/16 influenza season was the third season of the introduction of an intra-nasally administered live attenuated influenza vaccine (LAIV) for children in England. All children aged 2‒6 years were offered LAIV, and in addition, a series of geographically discrete areas piloted vaccinating school-age children 7‒11 years old. Influenza A(H1N1)pdm09 was the dominant circulating strain during 2015/16 followed by influenza B. We measured influenza vaccine uptake and the overall and indirect effect of vaccinating children of primary school -age, by comparing cumulative disease incidence in targeted and non-targeted age groups in vaccine pilot and non-pilot areas in England. Uptake of 57.9% (range: 43.6–72.0) was achieved in the five pilot areas for children aged 5‒11 years. In pilot areas, cumulative emergency department respiratory attendances, influenza-confirmed hospitalisations and intensive care unit admissions were consistently lower, albeit mostly non-significantly, in targeted and non-targeted age groups compared with non-pilot areas. Effect sizes were less for adults and more severe endpoints. Vaccination of healthy primary school-age children with LAIV at moderately high levels continues to be associated with population-level reductions in influenza-related respiratory illness. Further work to evaluate the population-level impact of the programme is required.
QOL-57. AT HOME NEUROCOGNITIVE TESTING IS POSSIBLE IN PEDIATRIC BRAIN TUMOR PATIENTS
Authors: Amy Rosenfeld, Michael Etzl, Annie Gieseking, Amanda Goodman, Dianne Peterson, Thomas Daniels, Adrian Schmebri, Brian Harel
Journal: Neuro-Oncology (2018)

Neurocognitive decline is a major cause of morbidity in pediatric brain tumor patients. Traditionally, testing to monitor this decline has been completed in a clinic setting. It is often difficult to obtain neurocognitive evaluations in clinic, and testing only in clinics limits the frequency of assessments. Cogstate is a brief computerized neurocognitive battery capable of being administered in unsupervised settings. We administered the Cogstate battery to off therapy brain tumor patients at home and in the clinic to evaluate its utility in monitoring cognition at home. Demographic data and QOL questionnaires were collected during the in clinic baseline visit, and the Cogstate battery was also completed. A week later, patients completed testing at home. Twenty-five patients enrolled on study and 19 completed both in clinic and at home assessments. Mean age at diagnosis was 9.8 years, and at study enrollment was 13.0 years. Diagnoses included High Risk Medulloblastoma (n=7), Standard Risk Medulloblastoma (n=1), Ependymoma (n=4), Choroid Plexus Carcinoma (n=1), Ganglioglioma (n=3), Germinoma (n= 1), Nongerminomatous Germ Cell Tumor (n=2), Anaplastic Astrocytoma (n=1), Juvenile Pilocyctic Astrocytoma (n=3), Dysembroplastic Neuroepithelial Tumor (n=1), and Protoplasmic Astrocytoma (n=1). Thirteen patients received chemotherapy and 17 received radiation. All patients successfully completed testing and appeared able to understand the task requirements. No differences were observed between testing done in the clinic and at home. It appears possible to monitor cognition over time on a frequent basis in pediatric brain tumor patients. This has significant implications for clinical trials and clinical medicine.
Molecular determinant of steriospecific response by the human P-glycoprotein to isomers of antipsychotic drug flupentixol
Authors: Debjani Mandal, Saibal Dey
Journal: Cancer Research (2008)

3236   Human P-glycoprotein (ABCB1 or Pgp) is an ATP-dependent efflux pump capable of transporting a large variety of structurally unrelated hydrophobic compounds, which include many anticancer drugs and antimicrobial agents. Apart from its transport substrates, Pgp is also known to interact with a broad spectrum of pharmacological agents with modulatory properties. The mechanism by which Pgp can recognize such a diverse group of chemical compounds is yet to be clearly understood. Interestingly, although Pgp can accommodate a considerable degree of structural diversity in its ligand-binding pocket, a precise mode of molecular recognition is apparent from its ability to discriminate between small structural variations. This is evident from the two diametrically opposite effects generated by the  cis  and  trans  isomers of the antipsychotic drug flupentixol on ATP hydrolysis and substrate binding by Pgp. In this study, using alanine-scanning mutagenesis, we identify residue F770 in TM8 as a key component involved in the sensing mechanism that discriminate the structural difference between the two isomers of flupentixol. Substitution of F770 by an alanine (F770A) dramatically reversed the inhibitory potentials of  trans (E)flupentixol on ATP hydrolysis as well as IAAP binding to stimulatory signals. No change was observed in the nature of modulation by the cis isomer of flupentixol, or by other structurally unrelated modulators like verapamil and cyclosorin A. The effect seems to be specific to F770, since substitutions of other nonsonserved residues in TM8 did not show any significant alteration in modulatory properties of flupentixol. To understand the mechanism, we are changing F770 to other amino acid residues with different physicochemical properties studying their effects on other closely related structural analogs of flupentixol.
Survival analysis of a multicentre, randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in patients with metastatic colorectal cancer (mCRC)
Authors: A. Avallone, G. Nasti, G. Rosati, C. Carlomagno, C. Romano, D. Bilancia, A. De Stefano, L. Silvestro, A. Ottaiano, A. Cassata, F. Bianco, F. Izzo, P. Delrio, E. De Gennaro, R. Casaretti, S. Tafuto, V. Albino, U. Pace, S. Lastoria, C. Gallo, A. Budillon, M. Piccirillo
Journal: Annals of Oncology (2018)

Introduction: Bevacizumab is a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, approved in combination with chemotherapy in the treatment of mCRC. It is proposed that its schedule of administration might be critical and that anticipating bevacizumab to chemotherapy might improve treatment efficacy. Methods: mCRC patients, ≤ 75 years, ECOG PS ≤ 1 were randomized (1:1) to receive standard (S) administration of bevacizumab (5mg/kg d1 Q14) with chemotherapy (mFOLFOX/OXXEL regimen for 12 cycles) vs experimental (E) bevacizumab given 4 days before chemotherapy (same dose), at each cycle. Patients could receive maintenance bevacizumab until disease progression or unacceptable toxicity. Primary end point was the objective response rate (ORR). With 80% power and 2-tailed alpha 0.05, an expected 20% increase in response rate, 230 patients were planned. With 163 events, the study also had 80% power to detect a 0.64 hazard ratio (HR) of progression-free survival (PFS). Analyses were based on intention to treat. Correlative studies on biomarkers and FDG-PET were also planned. Results: From May 2012 to Dec 2015, 230 patients were randomised to E (n = 115) and S (n = 115) arm. Median age was 62 (IQ range 53-68), 79% were PS 0, 93% were not pretreated, 53% had a single metastatic site, 71% had a left primary site; RAS-mutant tumors were less frequent in the S vs E arm (54/108 [47%]vs 71/108 [57%]). ORR was 54% in both arms (p = 0.89). With a median follow-up of 42 months, 209 PFS events and 150 deaths were reported. Median PFS was 10.5 and 11.7 months (HR 0.80, 95% CI: 0.61-1.06; multivariate adjusted p = 0.12) and median OS was 23.8 and 29.1 months (HR 0.70, 95% CI: 0.51-0.97; multivariate adjusted p = 0.03), in the S and E arm, respectively. Rate of patients receiving treatment after progression was similar in the two arms. Conclusion: Although anticipating bevacizumab to chemotherapy does not improve ORR, its association with a significant longer OS suggests that the schedule of administration of bevacizumab in combination with chemotherapy could be critical to improve treatment efficacy in mCRC patients. Supported by the Italian Ministry of Health. CT.gov NCT01718873.
HGG-31. EVALUATE THE ANTI-CANCER OF NOVEL CHELATOR DPC ON GLIOBLASTOMA MULTIFORME CELLS
Authors: Godfrey Chi-Fung Chan
Journal: Neuro-Oncology (2018)

Glioblastoma multiforme has extremely poor prognosis by current therapeutic approaches. We previously showed that a novel synthesized chelator DpC (di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone) has acceptable toxicity profile and is effective in treating neuroblastoma in-vitro and in-vivo (Guo, et al. J Hematol Oncol 2016). We evaluated whether DpC works on glioblastoma cells in vitro. Four glioblastoma cell lines (U87, D54, U373 and U138) were screened for cytotoxic effects of DpC (Des Richardson, USydney) using XTT assay. Then flow cytometry, RT-qPCR were used to map out the mechanisms in U87 cell lines. Transwell migration and invasion assays were used to evaluate the anti-metastatic effects of DpC on U87 cells. DpC suppressed the proliferation of all the 4 glioma cell lines, partly by decreased overall intracellular and labile iron pool. DpC increased intracellular ROS; disrupted mitochondrial membrane potential; decreased thiol groups levels; increased DR4 and DR5 expression; activated caspase 8, 9 & 3 resulting in increasing apoptotic cells populations; and induced G1/S cell cycle arrest. Finally, DpC also suppressed migratory and invasive abilities of U87. DpC induce apoptosis, suppress migration and invasion of glioblastoma cells in-vitro. The in-vivo anti-glioblastoma effect of DpC will be tested by orthotopic model in the future.
Safety and Effectiveness of Nurse-Administered Propofol Sedation in Outpatients Undergoing Gastrointestinal Endoscopy
Authors: Masamichi Sato, Akira Horiuchi, Michio Tamaki, Yasuyuki Ichise, Masashi Kajiyama, Yuta Yamamoto, Naoki Tanaka
Journal: Clinical Gastroenterology and Hepatology (2018)
IMMU-23. CMV pp65 RNA-PULSED DENDRITIC CELL VACCINES FOR PEDIATRIC GLIOBLASTOMA AND MEDULLOBLASTOMA: A PHASE I TRIAL
Authors: Daniel Landi, Eric Thompson, James Herndon, John Sampson, David Ashley
Journal: Neuro-Oncology (2018)

Recurrent medulloblastoma and malignant glioma are lethal tumors that are virtually incurable. The cytomegalovirus (CMV) antigen pp65 is ubiquitously expressed on medulloblastoma and malignant glioma but not on healthy brain, making this an attractive candidate for targeted therapy, including immunotherapy. A recently completed phase I trial at Duke evaluated autologous CMV pp65 RNA-pulsed dendritic cell (DC) vaccines in newly diagnosed adult glioblastoma patients. Vaccines were most effective when given with GM-CSF after tetanus-diphtheria toxoid (Td) site preconditioning, achieving a median overall survival of over 40 months. Additionally, DC migration to lymph nodes emerged as a strong biologic correlate with progression-free survival. We are now evaluating this platform in children as a single-arm phase I trial. Our hypothesis is that pp65 RNA-pulsed autologous DC vaccines will be well-tolerated and lead to significant DC migration and pp65-specific T cell responses in children with recurrent medulloblastoma or malignant glioma. As the primary objective, we will establish the safety and feasibility of vaccinating pediatric patients with recurrent medulloblastoma or malignant glioma using CMV pp65 RNA-pulsed DCs with GM-CSF and Td preconditioning. Our secondary objectives are to 1.) assess the ability of radiolabeled DCs to track to vaccine-draining lymph nodes, and 2.) measure T-cell responses against pp65 before and after DC vaccination. Time to progression is not a primary endpoint in this study but will be accessioned to derive hypotheses that may relate other data derived in this study with progression.
HGG-35. COMBINATIONS OF QUANTITATIVE AND QUALITATIVE MRI FEATURES IDENTIFY PROGNOSTIC AND MOLECULAR SUBGROUPS OF SUPRATENTORIAL PEDIATRIC HIGH-GRADE GLIOMA
Authors: John Lucas, Chih-Yang Hsu, Zhaohua Lu, Jared Becksfort, Christopher Tinkle, Alberto Broniscer, Thomas Merchant, Brent Orr, Suzanne Baker, Zoltan Patay, Scott Hwang
Journal: Neuro-Oncology (2018)

BACKGROUNDTo evaluate the potential of quantitative (radiomic) and qualitative (Visually Accessible Rembrandt Imaging, VASARI) imaging features to distinguish between molecularly defined subgroups in supratentorial pediatric high grade glioma (pHGG) and improve prognostication. METHOD AND