tbuckley/cabot-search huggingface dataset:
GERM-01. RESPONSE RATES TO DIFFERENT RE-INDUCTION CHEMOTHERAPY REGIMENS IN PATIENTS WITH RECURRENT CENTRAL NERVOUS SYSTEM MIXED MALIGNANT GERM CELL TUMORS
Authors: Mohammad H Abu Arja, Joseph R Stanek, Jonathan L Finlay, Mohamed S AbdelBaki
Journal: Neuro-Oncology (2018)

The lack of a standard treatment approach has contributed to poor outcomes of patients with recurrent central nervous system (CNS) mixed malignant germ cell tumors (MMGCT). There are no data in the literature supporting optimal re-induction chemotherapy regimens that should be used for patients with recurrent CNS MMGCT. A literature review was conducted to explore the response rate of patients with recurrent CNS MMGCT to different re-induction chemotherapy regimens by searching PubMed from 1985 through November 2017. Tumors were classified according to Japanese, European, and North American prognostic group classifications determined at initial presentation. Forty-two responses to various re-induction chemotherapy regimens reported in 38 patients were included. Two patients were inevaluable and their responses to re-induction chemotherapy were excluded. Thirty-five responses to various re-induction chemotherapy regimens were evaluable in 33 patients following a first relapse. Six (17%) responses were reported as complete or continuous complete responses, seven (20%) partial responses, two (6%) were stable disease, two (6%) were mixed responses, 18 (51%) were progressive disease. Five of ten patients treated without platinum-based chemotherapy experienced tumor progression. There was a trend towards a higher rate of tumor progression among histological poor prognostic group patients, and amongst patients relapsing within 24 months of initial diagnosis. The response rate of recurrent CNS MMGCT to re-induction chemotherapy may correlate with the initial prognostic grouping of the tumor and the time to relapse. However, further studies are needed to determine the optimal re-induction chemotherapy regimens for patients with recurrent MMGCT.
Randomized trial of irinotecan and cetuximab (IC) versus irinotecan, cetuximab and ramucirumab (ICR) as 2nd line therapy of advanced colorectal cancer (CRC) following oxaliplatin and bevacizumb based therapy: Result of E7208
Authors: H. Hochster, Paul J. Catalano, Peter J. O'Dwyer, Edith P. Mitchell, Deirdre Jill Cohen, Bryan Andrew Faller, Jeremy S. Kortmansky, Sheetal Mehta Kircher, Jill Lacy, Heinz-Josef Lenz, Udit N. Verma, Al Bowen Benson
Journal: Annals of Oncology (2018)

Introduction: While both anti-VEGF(R) and EGFR antibodies have activity in metastatic RAS wild type CRC, the combination of the two appeared to be detrimental when combined with chemotherapy in unselected CRC patients. We undertook this study to determine whether the anti-VEGFR antibody, ramucirumab, improved activity of Irinotecan and Cetuximab as 2nd line therapy in KRASwt CRC patients, who previously received FOLFOX or CAPOX with bevacizumab (bev) first line therapy, and were now progressing.
A Review of Implant Communication Technology in WBAN: Progress and Challenges
Authors: Assefa K. Teshome, Behailu Kibret, Daniel T. H. Lai
Journal: IEEE Reviews in Biomedical Engineering (2018)

Over the past six decades, there has been tremendous progress made in the field of medical implant communications. A comprehensive review of the progress, current state of the art, and future direction is presented in this paper. Implanted medical devices (IMDs) are designed mainly for the purpose of diagnostic, therapeutic, and assistive applications in heathcare, active living, and sports technology. The primary target of IMDs' design revolves around reliable communications, sustainable power sources, and a high degree of miniaturization while maintaining biocompatibility to surrounding tissues adhering to the human safety limits set by appropriate guidelines. The role of the Internet of Things and intelligent data analysis in implant device networks as future research is presented in this paper. Finally, in addition to reviewing the state of the art, a novel intuitive lower bound on implant size is presented.
Abstract 17452: Inadequate HIV Suppression is Associated With Progression of Coronary Stenosis: The Multicenter AIDS Cohort Study (MACS) Longitudinal Coronary CT Angiography Study
Authors: Wendy S Post, Sabina Haberlen, Mallory D Witt, Long Zhang, Lisa P Jacobson, Todd T Brown, Frank J Palella, Lawrence Kingsley, Matthew Budoff
Journal: Circulation (2017)

Introduction: HIV infected (HIV+) persons are surviving longer due to effective antiretroviral therapy (ART). CVD has emerged as a leading cause of non-AIDS related events. The purpose of this stud...
Stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (LAPC)
Authors: M. Vera Merino, C. Niño de Guzmán, D. Angel Schutte, D. Venencia, L. Suarez Villasmil, S. Zunino
Journal: Annals of Oncology (2018)

Introduction: SBRT would allow local control for LAPC with acceptable toxicity in a short time. The purpose of this work is to assess early and late toxicities and clinical response in patients treated with SBRT. Methods: Between October 2013 and February 2018, 48 patients with LAPC, mean age 64 years (39-84y), treated with neoadjuvant, concomitant or adjuvant chemotherapy plus SBRT were retrospectively analyzed. The treatment dose was 25 Gy to 37.3 Gy given in 3 to 5 daily fractions, utilizing volumetric arc therapy, a 6-MV photon beam and Linac Novalis IGRT-ExaTrac accelerator. GTV and OARs were delineated in CT and PET-CT fused images. OARs were contoured according RTOG criteria. The treatment planning was done in Eclipse V15.1. Acute (≤3m) and late (>3 m) toxicities grades were classified according to the CTCAE V.3.0. Results: Of 48 LAPC patients (27 women/21 men), mean follow up 9.41 m (0.23-23.77), 35 (72.91%) received SBRT in pancreatic tumor as primary treatment, 11 (22.92%) were operated first, followed by SBRT; and 2 patients (4.17%) were rescued with SBRT because recurrence after conventional radiotherapy. 33 patients (68.75%) had adenocarcinoma diagnosis, and 15 (31.25%) had no biopsy. Early toxicity (48 pts) G1: asthenia in 7 (14.5%), nausea in 6 (12.5%) and abdominal pain in 9 (18.75%); G2: asthenia in 4 (8.34%), nausea in 1 (2.08%) and vomiting in 1 pt. (2.08%); G3: enteritis in 2 (4.17%), and one of them interrupted SBRT. Fourteen patients (29.17%) did not have any early toxicity. Late toxicities (21 pts) G1: enteritis in 1 (4.77%) and asthenia in 2 (9.52%); G3: abdominal pain in 1 (4.77%) and G4 in 1 pt. (4.77%) who suffered from intestinal perforation because disease progression. Relive of abdominal pain were observed in 23/48 patients after SBRT (47.92%). Kaplan-Meier survival at 12 and 18 months was 46% and 31% respectively. Thirteen live patients kept in good shape PS0-2. Conclusion: Despite of the heterogeneity in dose and fractionation, we suggest that SBRT is a feasible and safe option for patients with pancreatic cancer.
Lipid Peroxidation Drives Gasdermin D-Mediated Pyroptosis in Lethal Polymicrobial Sepsis
Authors: Rui Kang, Ling Zeng, Shan Zhu, Yangchun Xie, Jiao Liu, Qirong Wen, Lizhi Cao, Min Xie, Qitao Ran, Guido Kroemer, Haichao Wang, Timothy R. Billiar, Jianxin Jiang, Daolin Tang
Journal: Cell Host & Microbe (2018)
Near complete response to Pembrolizumab in microsatellite-stable metastatic sebaceous carcinoma
Authors: Evidio Domingo-Musibay, Paari Murugan, Alessio Giubellino, Sandeep Sharma, Daniel Steinberger, Jianling Yuan, Matthew A. Hunt, Emil Lou, Jeffrey S. Miller
Journal: Journal for ImmunoTherapy of Cancer (2018)

Sebaceous carcinoma is an aggressive adnexal skin tumor with a predilection for the eyelids and sebaceous glands of the head and neck.A 73 year-old man presented with confusion and was found to have widely disseminated sebaceous carcinoma with metastases to brain, lungs, liver, bowel, lymph nodes, and bone. Following initial treatment of the brain metastases with surgery he received post-operative radiosurgery. He then began systemic immunotherapy with pembrolizumab. After 6 months, he developed a near complete response to therapy by irRECIST and RECIST v.1.1. The response was associated with circulating CD8+ T cells with central memory (CM) and effector memory (EM) phenotype and mature CD16 + CD57+ NK cells. During treatment the patient developed adrenal insufficiency requiring high-dose systemic corticosteroids and later adrenal replacement therapy. After 12-months of follow-up he showed imaging evidence of progression in liver, mediastinum, and abdominal lymph nodes. Given persistent, strong PD-L1 expression he resumed pembrolizumab therapy and showed radiographic evidence of an ongoing response to therapy.This is the first report describing objective clinical and radiographic responses following immunotherapy for widely metastatic sebaceous carcinoma. The dramatic therapeutic response to pembrolizumab was associated with peripheral blood circulating memory T cells and mature Natural Killer cells after 6 months (24 weeks) of therapy. This report supports prospective clinical trials of anti-PD1 checkpoint blockade for metastatic sebaceous carcinoma.
Laparoscopic hepatectomy versus open hepatectomy for hepatocellular carcinoma in 157 patients: A case controlled study with propensity score matching at two Chinese centres
Authors: Zhi-cheng Deng, Wen-zhu Jiang, Xiao-dong Tang, Shuang-hai Liu, Lei Qin, Hai-xin Qian
Journal: International Journal of Surgery (2018)
Capecitabine, irinotecan, and bevacizumab in patients with previously untreated metastatic colorectal cancer: Experience of the oncology department of the university hospital of Oran, Algeria
Authors: Z. Behourah, A. Bousahba, L. Djellali
Journal: Annals of Oncology (2018)

Introduction: This study aims to investigate the effectiveness of the associated chemotherapy based on capecitabine and irinotecan (CARIPI) with anti-VEGF, the bevacizumab, in terms of progression free survival (PFS), objective response rate (ORR) and overall survival (OS), in a way to evaluate the clinical benefit and tolerance to patients with mCRC in first line. Methods: A prospective observational study was conducted in the Oncology department of the University Hospital of Oran between March 2012 and May 2015. Eligible patients were aged over 18 years, with non-pre-treated mCRC and performance status HWO ≤ 2. Patients were treated with capecitabine 1000 mg/m2 (800mg/m2 for patients over 65 years old) morning and evening during 14 days associated with irinotecan 240mg/m2 and bevacizumab 7.5mg/kg to D1 every three weeks. Stable or responder patients could receive a maintenance treatment by capecitabine-bevacizumab until the progression of the disease. Results: Fifty-two patients with mCRC were included in the study. The ratio-sex was about 2.05 with a mean age of 57.4 ±1.7 years. 84.6% of patients showed a conserved performance status (HWO of 0-1). A total of 395 cycles was administered with an average of 7.6± 0.4 cycles (CI 95%) [3-16]. Twenty-tree patients (44.2%) received a maintenance treatment by capecitabine–bevacizumab with an average of 11.6 ± 2.2 cycles (CI 95%) [3-41]. After median follow up of 40 months (CI 95%: 42-49), the median PFS in intention to treat (ITT) was about 11 months (95% CI: 7.8 to 14.2) with a PFS rate estimated to 12 months of 44.2%. The ORR in ITT was 39.2% (95% CI: 27.5 to 52.2) and the Disease Control Rate (DCR) was 82.3%. The median OS was 20.8 months (95% CI: 16.5 to 25.1) with an OS rate at 2-year of 39.2%. The main grade 3-4 toxicities were represented by diarrhea (26.9%), neutropenia (13.5%), asthenia (7.7%), vomiting (7.7%), hand-food syndrome (5.8%). Toxicity given to bevacizumab was mainly moderate and representing by thromboembolic events (7.7%), blood pressure (32.7%; G3: 1.9%) and hemorrhagic events (G3:1.9%). Dose reductions of capecitabine and irinotecan were required in 36.5% and 28.8% of patients respectively, due to toxicities. Conclusion: CAPIRI–bevacizumab in first line treatment of the mCRC is really efficient with an acceptable tolerance profile after doses adaptation of capecitabine and irinotecan.
Merkel cell polyomavirus is uncommon in New Zealand Merkel cell carcinomas
Authors: B. Woodhouse, T.J. Robb, J.I. Hearn, P.S. Houseman, G. Hayward, R. Miller, A.P. Restall, M. Findlay, B. Lawrence, C.G. Print, K. Parker, C. Blenkiron
Journal: British Journal of Dermatology (2018)

Merkel Cell Carcinoma (MCC) is a rare skin tumour with an incidence of 0.88 per 100,000 people in New Zealand (NZ), one of the highest in the world 1 and almost on par with close neighbours Australia 2 .Current local diagnostic guidelines do not require analysis of the oncogenic Merkel Cell Polyoma Virus (MCPyV), therefore it has never been questioned whether the NZ-MCC MCPyV rate is similar to North American and European studies (40-89%) or indeed lower, as reported in Australian cohorts (18-24%) in which a UV-mediated etiology is dominant 3-5 .To investigate the presence of the MCPyV in NZ-MCCs we established droplet digital PCR (ddPCR, Bio-Rad) assays to amplify viral gene LTA 6 and gene expression of LTA, in parallel with a viral protein immunohistochemistry (IHC) assay using the commercial CM2B4 antibody 4 .Methods for ddPCR and IHC are available from the authors on request.This study collated a cohort of patients diagnosed with MCC between 1998 and 2016 in the Auckland region.We collected 53 formalin fixed paraffin embedded (FFPE) tumours excised from 35 donors; representing 39 primary or locally recurrent skin
LGG-16. LOW GRADE GLIOMA, 16 YEARS SINGLE CENTER EXPERIENCE
Authors: Stanislava Hederová, Andrea Mocná, Kristína Husáková, Emília Kaiserova, Miroslava Makohusová, Salome Jakešová, Boris Rýchly, Alexandra Kolenová
Journal: Neuro-Oncology (2018)

Low grade gliomas (LGG) are the most frequent tumors of the central nervous system in children. Pediatric LGG are a heterogeneous set of tumors. They encompass tumors of astrocytic, oligodendroglial, and mixed glial-neuronal histology, and are classified according to the World Health Organization (WHO). The objective of our study was to analyze the outcome of patients with LGG from the Department of Pediatric Hematology and Oncology in Bratislava, Slovakia treated in period from January 2000 up to December 2015. The cohort consisted of 139 patients with LGG, 83 boys/56 girls. The most common histological type was pilocytic astrocytoma (WHO grade I) in 64 children. Primary surgery was performed in 102 children and 72 from these do not need any further therapy. Forty eight patients received chemotherapy first or other line therapy. Radiotherapy was used 26 times. In our study median follow up was 82,3 months and overall survival for the whole cohort was 97,2%. In pediatric low grade glioma surgery is the mainstay of therapy. Ten year overall survival rates for patients whose tumors are completely resected are 90% or greater. Chemotherapy is reserved for progressive or recurrent tumors. Radiotherapy can also improve OS but is associated with more frequent adverse effects. Recent advent of integrated genomics and NGS has implicated the activation of RAS/RAF/MEK pathway in tumor genesis of LGG. Many of these biological advances are changing treatment paradigma, particularly in low-grade gliomas, where rationale targeted therapies are currently being explored in clinical trials.
TBIO-16. AUTOMATED CELL ENRICHMENT AND DIGITAL CELL SORTING USING DIELECTROPHORETIC ARRAYS FOR ISOLATION OF CIRCULATING TUMOR CELLS IN PEDIATRIC BRAIN TUMOR PATIENTS
Authors: Katherine Barnett, Kaicen Zhu, Guomiao Shen, Jonathan Serrano, David Harter, Jeffrey Wisoff, Amanda Yaun, Shiyang Wang, Sharon Gardner, Matija Snuderl
Journal: Neuro-Oncology (2018)

Liquid biopsy has the potential to revolutionize diagnosis and management of cancer. In brain tumors, detection of cell free tumor DNA (ctDNA) and circulating tumor cells (CTC) is challenging due to low level of the circulating material. We present a novel workflow for detection and capture of CTCs. Peripheral blood was obtained from five pediatric patients with astrocytoma (n=2), ependymoma (n=1), dysembryoplastic neuroepithelial tumor (n=1), and medulloblastoma (n=1) at initial resection (n=3) and relapse (n=2). Samples were enriched using the ClearBridge ClearCell FX1 system and the suspension stained with antibodies against CD56 and CD45. Samples were analyzed using Silicon Biosystems DEPArray to capture single and pooled CTCs. CTCs were identified by CD56 positivity, while leukocytes were positive for CD45 and NK cells double-positive for CD56 and CD45. CTCs were identified in all 5 patient samples. The number of CD56-positive cells isolated from each sample ranged from 1 to 25 (mean 9). The CD56-positive cells were on average 11.8 µm in diameter (range 9.0-15.7 µm), and CD45-positive cells were on average 10.8 µm in diameter (range 8.9-15.9 µm). Single CTCs and CTC pools are amenable to molecular analysis after whole genome amplification. We report a novel integrated workflow for capturing CTCs in pediatric patients with brain tumors. While rare, CTCs circulate in peripheral blood of patients with brain tumors regardless of their grade and are amenable for molecular analysis. This method has the potential to serve as a non-invasive diagnostic and monitoring method for pediatric brain tumors.
Musculoskeletal pain and exercise—challenging existing paradigms and introducing new
Authors: Benjamin E Smith, Paul Hendrick, Marcus Bateman, Sinead Holden, Chris Littlewood, Toby O Smith, Pip Logan
Journal: British Journal of Sports Medicine (2018)

Traditional pain models that describe tissue pathology as a source of nocioceptive input directly linked with pain expression, have been insufficient for assessing and treating musculoskeletal pain.  The need for pain to be avoided or alleviated as much as possible during physical activity has recently been challenged, with a paradigm shift from traditional biomedical models of pain towards a biopsychosocial model of pain.
The aim of the review is to provide an understanding on the potential mechanisms behind exercise, and to build on this into discussing the additional theoretical mechanisms of painful exercises. Central and peripheral pain mechanisms, the immune system and affective aspects of pain are described. This review focuses on these three mechanisms as these systems appear to respond differently to painful stimulus, compared with necessitating pain-free exercises. They are discussed in relation to the biological effect of exercise for people with chronic pain, with a broader overview of possible mechanisms behind the potentially additional beneficial effect of allowing painful exercises for individuals with chronic musculoskeletal pain. 	
This additional mechanistic consideration could be used to help clinicians in the prescription of therapeutic exercise and for researchers to advance knowledge for such a globally burdensome condition.
Plasma genotyping of patients enrolled on the expansion phase I/II trial of X-396 in patients (pts) with ALK+ non-small cell lung cancer (NSCLC).
Authors: Leora Horn, Heather A. Wakelee, Karen L. Reckamp, George R. Blumenschein, Jeffrey R. Infante, Corey Allan Carter, Saiama Naheed Waqar, Joel W. Neal, Jon P Gockerman, Kimberly Harrow, Gary Dukart, Chris Liang, James J. Gibbons, Jennifer Hernandez, Tara Newman-Eerkes, Lee Lim, Christine Marie Lovly
Journal: Journal of Clinical Oncology (2016)

9056 Background: X-396 is a novel, potent anaplastic lymphoma kinase (ALK) small molecule tyrosine kinase inhibitor (TKI) with additional activity against MET, ABL, Axl, EPHA2, LTK, ROS1 and SLK. We report data on ALK TKI-naive and crizotinib (C)-resistant NSCLC pts treated with X-396. Methods: In this multicenter expansion study, pts with ALK+ NSCLC were treated with X-396 225 mg daily on a 28-day schedule. Pts had measurable disease, ECOG PS 0-1, untreated brain metastases (CNS) and leptomeningeal disease were allowed. NGS on plasma samples was performed at baseline and on study and compared with central tissue results (FISH/IHC). All pts were assessed for response to therapy using RECIST 1.1, adverse events (AEs) using CTCAE version 4.03 were recorded. Results: 60 pts (53% female) have been enrolled. Median age 56 (20-79) years, 67% ECOG PS 1. Of 30 ALK+ NSCLC pts evaluable for response; partial response (PR) was achieved in 19 pts (60%) and stable disease (SD) in 2 pts (7%). In the C-naïve pts (n = 8), PRs were observed in 7 pts (88%). In the 12 pts with prior C but no other ALK TKI, 10 pts (83%) achieved PR and 1 (8%) SD. Median duration of response was 24 - 128 wks. In the 8 pts who had received two or more prior ALK TKIs, there was 1 PR, 3 SD (50% DCR) with response duration of 8-32 wks. CNS responses have been observed in both C naïve and C resistant pts. Plasma and tissue genotyping are available on 27 pts (26 ALK + and 1 ALK -) ALK was detected in plasma in 16 pts all had a response to therapy, two pts were tissue +ve and -ve on plasma testing and had PD, 9 plasma samples were inevaluable. Serial sequencing demonstrated a decrease in ALK in pts responding and an increase at the time of progression. The most common drug-related AEs ( ≥ 20% of pt s) included rash (48%), nausea (26%), vomiting (23%), and fatigue (21%). Most AEs were Grade (G) 1-2. The G3 treatment-related AEs were rash (8 pts), fatigue (1 pt), decreased appetite (1 pt), pruritus (1 pt), and face edema (1 pt). Conclusions: X-396 is well-tolerated and induces response in both C-naive and C-resistant ALK+ NSCLC pts, as well as pts with CNS disease. Plasma sequencing may be used to select pts for therapy and monitor for response and development of acquired resistance. Clinical trial information: NCT01625234.
EMBR-06. MULTIMODAL IMMUNOTHERAPY KEEPS LONG-TERM REMISSION AFTER SECOND RELAPSE OF PINEOBLASTOMA IN INFANT
Authors: Stefaan Van Gool, Jennifer Makalowski, Wilfried Stuecker
Journal: Neuro-Oncology (2018)

The prognosis of relapsing pineoblastoma in infants is dismal. We report here on an infant treated for pineoblastoma with partial resection and subsequent chemotherapy at the age of 14 months. At the age of 23 months, a local relapse was diagnosed, treated again with partial resection and adjuvant chemotherapy. Because of progression within 2 months, treatment was switched to craniospinal radiotherapy and second line chemotherapy. Four months later at the end of treatment, the family requested multimodal immunotherapy with the hope to prolong the status of remission. Multimodal immunotherapy vaccination cycles consisted of Newcastle Disease (NDV) infusions together with modulated electrohyperthermia (mEHT) and injection of autologous dendritic cells loaded with NDV/mEHT-induced serum-derived antigenic extracellular vesicles. Two vaccination cycles were administered. Immunomonitoring showed an increase at least of NDV-reacting IFNg-producing T cells upon in vitro stimulation. Maintenance immunotherapy was continued consisting of 3 days NDV/mEHT each 4 weeks. One week after the third NDV/mEHT maintenance cycle, the child developed a clinical picture of encephalitis, which could be cured without sequelae. No infectious agent could be detected. Later-on, the child received one more DC vaccine without NDV/mEHT. Now, 28 months after diagnosis and 19 months after first relapse, the child is still in full remission. The clinical evolution suggests that multimodal immunotherapy might contribute to establish disease control in relapsing pineoblastoma once remission is reached with standard oncologic treatments.