tbuckley/cabot-search huggingface dataset:
Impact of chronic hepatitis c virus infection in patients with non-oropharyngeal cancers.
Authors: Georgios Angelidakis, Erich M. Sturgis, Minas P. Economides, Ying Jiang, Harrys A. Torres
Journal: Journal of Clinical Oncology (2018)

e18027 Background: Chronic Hepatitis C virus (HCV) infection has been associated with high prevalence of Head and Neck cancers and increased risk of cancer progression and mortality in patients (pts) with oropharyngeal cancers. However, the impact of HCV infection in pts with non-oropharyngeal cancers (NOPCs) is unknown. Herein we analyze the prevalence, hepatic and oncologic consequences of HCV in pts with NOPCs. Methods: In this retrospective cohort study, pts with NOPCs screened for HCV antibody and seen at MD Anderson (1/2004-12/2015) were reviewed. HCV infection was defined as detectable HCV RNA in serum. Risk of 5-year overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) were compared between HCV-infected and uninfected pts. Cox proportional hazards regression analysis was used to evaluate the effect of HCV infection on cancer outcomes. Results: Of the 42,731 cancer pts screened for HCV, 253 had NOPCs. Among them, 215 had available data and were further analyzed with NOPCs involving oral cavity 94 (44%); larynx 68 (32%); nasopharynx 32 (15%); hypopharynx 18 (8%); and paranasal sinuses/nasal cavity 3 (1%). Reactive HCV antibody was found in 41 (19%) of NOPC pts and most (37/41 or 90%) had confirmed HCV infection. Not all were referred for HCV care (26/41 or 63%) nor underwent cirrhosis work up (29/41 or 71%). Almost one-half (14/29 or 48%) of HCV-infected pts had cirrhosis, 4 (29%) had advanced (decompensated) cirrhosis. When compared to the 178 uninfected pts, the 37 with HCV infection had more laryngeal cancers (49% vs 28%, p< 0.05); higher smoking history (85% vs 63%, p< 0.05); and alcohol use (61% vs 25% p< 0.001). Compared to uninfected pts, those with HCV infection had comparable OS, PFS and DFS; but numerically developed more hepatocellular carcinoma as a second primary malignancy (HCC-SPM) in cirrhotics (5/14 or 36% vs 1/10 or 10%, p= 0.34). Of the 5 infected pts with HCC-SPM, 1 died of HCC with NOPC in remission. Conclusions: Among all NOPCs, HCV seems to be particularly associated with laryngeal cancers. There is little awareness among oncologists of the hepatic consequences of HCV including liver disease progression and HCC-SPM in infected pts with NOPCs.
Use of a multi-drug regimen gemcitabine, 5-fluorouracil, irinotecan, cisplatin bevacizumab, docetaxel and cyclophosphamide (GFIP/BDC) for heavily pretreated epithelial ovarian (EOC), Fallopian tube (FT) and primary peritoneal (PP) cancer.
Authors: Melissa Schwartz, Samantha Cohen, Peter Remsen Dottino, Ann Marie Beddoe
Journal: Journal of Clinical Oncology (2017)

e17073 Background: Despite initial response rates to standard platinum-based chemotherapy for EOC/FT/PP, the majority of patients relapse. The purpose of this study was to describe response and tolerability of GFIP/BDC, a modification of the G-FLIP regimen (Bruckner et al), in patients with persistent or recurrent EOC/FT/PP. Treatment consisted of a 2-day combination of gemcitabine 300mg, 5-fluorouracil 500mg/m2, irinotecan 20-30mg/m2, cisplatin 20mg/m2, bevacizumab 4mg/kg, docetaxel 20mg/m2, and cyclophosphamide 20mg/m2 administered every 14 days. Methods: A retrospective descriptive analysis of 20 patients from a single academic institution who received combination GFIP/BDC therapy from January 1, 2011 to August 31, 2016 for persistent or recurrent EOC/FT/PP. Toxicities were retrospectively graded using CTCAE v4.0. Results: Twenty patients were identified with a median age 57.5 years (range 32-71). 85% of patients were non-Hispanic white, 90% had cancer of high-grade serous histology, and all had a GOG performance status of 0-1. Patients had received a median of 3 prior regimens and 95% were platinum-resistant. Median number of cycles administered was 9 (range 3-48) and patients remained on treatment for a median of 5.1 months (range 1.5-24). Thirteen patients (65%) experienced a clinical response (1 complete, 12 partial) with a median duration of 5 months (range 1.5-20). Eight patients (45%) survived progression free for at least 6 months. Grade 3 adverse events were hematologic (5), constitutional (3), gastrointestinal (3), neurologic (2), and vascular (1). Grade 4 adverse events included severe neutropenia (1) and anaphylaxis (1). Thirteen patients (65%) experienced at least one grade 3/4 adverse event. Patients discontinued treatment due to disease progression 65% (13), toxicity 20% (4), patient preference 10% (2), and one patient (5%) is currently on treatment. Conclusions: Selected EOC/FT/PP patients who have failed multiple lines of conventional cytotoxic treatment may benefit from GFIP/BDC. Toxicity might be a limiting factor for administration.
TCT-361 Heart Team Approach to CAD Management in Patients Undergoing Elective Vascular Surgery Who Have Asymptomatic Ischemia-producing Coronary Stenosis
Authors: Andrejs Erglis, Dainis Krievins, Sanda Jegere, Gustavs Latkovskis, Indulis Kumsars, Karlis Strenge, Kaspars Kisis, Edgars Zellans, Ligita Zvaigzne, Inga Narbute, Christopher Zarins
Journal: Journal of the American College of Cardiology (2018)
Exosomes secreted from mesenchymal NSCLC cells to promote invasiveness and metastatic capability of recipient cells through UCHL1.
Authors: Yoshihisa Shimada, Tetsuya Okano, Paul Yenerall, Kenneth Huffman, Brenda Timmons, Boning Gao, Dhruba Deb, Norihiko Ikeda, John D. Minna
Journal: Journal of Clinical Oncology (2018)

e24008 Background: Cancer-derived exosomes are intracellular signaling organelles that can act to help cancer cells invade neighboring tissues, induce epithelial-mesenchymal transition (EMT) in target cells, and prime metastatic sites for disease spread. Here we show that uptake of mesenchymal non-small cell lung cancer (NSCLC)-derived exosomes mediates phenotypic alterations in both immortalized human bronchial epithelial cells (HBEC) and epithelial NSCLC cells, and how exosome-mediated cellular communication drives EMT programs. Methods: Exosomes isolated from lung mesenchymal NSCLC cell lines (H1299, A549, H2073), an epithelial NSCLC cell line (H1993), and immortalized human bronchial epithelial cells (HBEC-3KT, 30KT) were characterized. We examined the effects of mesenchymal NSCLC-derived exosomes on EMT phenotypic changes of HBECs and H1993 and their influence on metastasis in murine models. Mass spectrometry was performed to identify candidate proteins carried in tumor exosomes that induce phenotypic changes in recipient cells. Results: Mesenchymal NSCLC-derived exosomes transferred functional EMT-related proteins and transcriptional factors (vimentin, ZEB, SNAIL, TWIST) to epithelial cells in amounts sufficient to mediate the phenotypic alterations. Mass spectrometric quantitative expression of exosomes identified that ubiquitin carboxy-terminal hydrolase L1 (UCHL1) was widely shown only in mesenchymal NSCLCs and their exosomes in both protein and RNA expression. The treatment of mesenchymal NSCLC-derived exosomes carried exogenous UCHL1 overexpression in target HBECs. UCHL1 knockdown of mesenchymal NSCLC cells reduced migration and invasion as well as suppressed pulmonary metastases that had been driven by cancer-derived exosomes, which led to the overexpression of UCHL1 in colonized pulmonary tumors. Conclusions: The initiation of EMT process followed by the interplay between tumor cells and the surrounding microenvironment via mesenchymal NSCLC-derived exosomes that carry a selection of EMT factors and UCHL1 is, at least in part, responsible for promoting lung cancer invasion and metastasis.
Bioengineering Organs for Blood Detoxification
Authors: Cécile Legallais, Dooli Kim, Sylvia M. Mihaila, Milos Mihajlovic, Marina Figliuzzi, Barbara Bonandrini, Simona Salerno, Fjodor A. Yousef Yengej, Maarten B. Rookmaaker, Natalia Sanchez Romero, Pilar Sainz‐Arnal, Ulysse Pereira, Mattia Pasqua, Karin G. F. Gerritsen, Marianne C. Verhaar, Andrea Remuzzi, Pedro M. Baptista, Loredana De Bartolo, Rosalinde Masereeuw, Dimitrios Stamatialis
Journal: Advanced Healthcare Materials (2018)

For patients with severe kidney or liver failure the best solution is currently organ transplantation. However, not all patients are eligible for transplantation and due to limited organ availability, most patients are currently treated with therapies using artificial kidney and artificial liver devices. These therapies, despite their relative success in preserving the patients' life, have important limitations since they can only replace part of the natural kidney or liver functions. As blood detoxification (and other functions) in these highly perfused organs is achieved by specialized cells, it seems relevant to review the approaches leading to bioengineered organs fulfilling most of the native organ functions. There, the culture of cells of specific phenotypes on adapted scaffolds that can be perfused takes place. In this review paper, first the functions of kidney and liver organs are briefly described. Then artificial kidney/liver devices, bioartificial kidney devices, and bioartificial liver devices are focused on, as well as biohybrid constructs obtained by decellularization and recellularization of animal organs. For all organs, a thorough overview of the literature is given and the perspectives for their application in the clinic are discussed.
Prognostic factors in pancreatic adenocarcinoma: Data from a high resolution cancer registry (HRCR) of Reggio Emilia province.
Authors: Romano Sassatelli, Tiziana Cassetti, Massimo Vicentini, Lucia Mangone, Claudio Sacchettini, Giuliana Sereni, Paolo Giorgi Rossi, Carmine Pinto
Journal: Journal of Clinical Oncology (2016)

e15728 Background: The aim is to identify key factors influencing prognosis using high resolution variables from a HRCR. Methods: 542 Resident (excluded 8 cases with Death Certificate Only) subjects diagnosed with pancreatic adenocarcinoma between 2008and 2012 were extracted from HRCR and linked with Reggio Emilia diabetes register. Relative excess risks of death is calculated with Cox proportional hazard model, adjusted for age ( ≤ 54, 55-74, 75-84, 85+), gender, period (2008-2010 vs 2011-2012), subsite (head, body, tail and unknown), stage (I, II-III, IV, unknown), resident area (urban, sub-urban and mountain district), Ca19.9 at diagnosis ( < 100 and > 100 previously adjusted for jaundice) and previous diagnosis of diabetes (yes/no). Results: The relative survival at three years was 10%. Risk of death increasing with age. Female have lower risk (HR 0.8 [0.7-1.0]). Survival increased in the most recent period (HR 0.8 [0.7-1.0]). Unknown subsite has worst prognosis compared to those defined (HR 1.2 [1.0-1.6]). Survival decrease only for stage IV (HR 2.2 [1.3-3.7]), while stage II and III have similar survival compared to stage I (HR 0.9 [0.5-1.6]). Mountain show a significantly increased risk (HR 1.62 [1.19-2.20]) and sub-urban area shows a slightly increased risk (HR 1.11 [0.90-1.37]). Subjects with diabetes have a two fold increased risk of death (HR 2.2 [1.6-3.1]). There are no differences in prognosis between different plasmatic levels of CA19.9 (HR 1.1 [0.9-1.5]). Conclusions: The main prognostic factors, age, stage and sex, have been confirmed. Only patients with stage IV have poorer prognosis, while stage II and III do not discriminate patients with shorter survival. A previous diagnosis of diabetes strongly predicts a shorter survival, suggesting that this condition might be an indicator of late cancer symptoms presentation.
Electronic cigarette vapour enhances pneumococcal adherence to airway epithelial cells under abnormal conditions of exposure
Authors: Massimo Caruso, Rosalia Emma, Virginia Fuochi, Pio M. Furneri, Riccardo Polosa
Journal: European Respiratory Journal (2018)

We read with great interest the research article by Miyashita et al. [1], in which the authors showed that e-cigarette aerosol emissions increase platelet-activating factor receptor (PAFR) expression and, consequently, Streptococcus pneumoniae adhesion to human airway epithelial cells. These findings led authors to conclude that e-cigarette use has the potential to increase susceptibility to pneumococcal infection. Unfortunately, the evidence presented in the paper is inadequate to provide much confidence in this conclusion. E-cigarette vapour enhances pneumococcal adherence to airway epithelial cells under "abnormal" conditions of exposure <http://ow.ly/O9J030keaYe>
Outcomes of patients (pts) with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE): Global OPTIMIS final analysis.
Authors: Markus Peck-Radosavljevic, Masatoshi Kudo, Jean-Luc Raoul, Han Chu Lee, Thomas Decaens, Jeong Heo, Shi-Ming Lin, Hong Shan, Yefa Yang, Inga Bayh, Keiko Nakajima, Ann-Lii Cheng
Journal: Journal of Clinical Oncology (2018)

4018 Background: TACE is often used to treat unresectable HCC (uHCC). However, there is no globally accepted consensus on the indication and definition of TACE failure. It is critical to reassess the risk/benefit of continuing TACE after failure as it may delay or prevent pts from receiving subsequent treatments. Methods: OPTIMIS, an international, prospective, observational study, enrolled pts with uHCC for whom a decision to treat with TACE was made at study entry. Practice patterns, safety, subsequent treatments, and outcomes data were collected. TACE ineligibility was defined and consistent with international and regional guidelines. Data were analyzed using descriptive statistical methods. Results: Overall, 1650 pts received TACE; 529 pts (32%) were BCLC stage C, 118 (7%) had extrahepatic spread, and 123 (7%) had portal vein thrombosis. At inclusion visit, 636 pts (39%) received TACE despite being TACE ineligible according to protocol-specified criteria. After first TACE, the proportion of pts with chronic liver function deterioration (worsening in CTCAE grade 30–90 days post TACE) ranged from 11% to 29% across assessed liver parameters. Complete and partial response rates to first TACE (N=1650) were 14% and 26%, respectively, which decreased by second (10% and 16%; n=1002), third (10% and 15%; n=580), and fourth (8% and 17%; n=338) TACE. Progressive disease rate increased by number of TACE procedures: 18%, 21%, 25%, and 27% for first, second, third, and fourth TACE, respectively. In total, only 507 pts (31%) became TACE ineligible during the study. Of those 507 pts, 47 (9%) received sorafenib at the time of TACE ineligibility and 460 (91%) received sorafenib later or not at all. Considerable imbalances between the 2 cohorts were observed; a propensity score analysis is planned to analyze overall survival from TACE ineligibility. Conclusions: These results indicate that real-world TACE use appears to deviate from treatment guidelines. This heterogeneity highlights the need for a globally accepted consensus on the indication and definition of TACE failure. These observations also indicate the importance of monitoring liver function in pts receiving TACE. Clinical trial information: NCT01933945.
Biomarker-driven indication selection in JTX-2011 ICONIC clinical trial.
Authors: Heather Anne Hirsch, Jason Reeves, Tong Zi, Amit Deshpande, Guang Yang, Alexander Needham, Jenny Shu, Arun Khattri, Ryan J. Brisson, Carol Tan, Christopher Harvey, Deborah Law, Jennifer Michaelson, Elizabeth G. Trehu, Sriram Sathyanarayanan, Tanguy Y. Seiwert
Journal: Journal of Clinical Oncology (2017)

11602 Background: ICOS (Inducible T cell CO-Stimulator) is a co-stimulatory molecule expressed primarily on T lymphocytes. Clinical and preclinical data suggest that ICOS mediates anti-CTLA-4 driven anti-tumor responses. JTX-2011 is an ICOS agonist antibody in clinical development in advanced solid tumors (ICONIC trial). JTX-2011 is designed to generate an anti-tumor immune response via stimulation of T effector cells and preferential reduction of intra-tumoral T regulatory cells. Single agent preclinical efficacy correlates with the percentage of ICOS-expressing T cells within the tumor. We report indication selection and patient enrichment strategy for ICONIC using in silico and IHC analysis and assessment of potential predictive biomarkers for JTX-2011 using ex vivo tumor histoculture. Methods: Integrated analysis was performed from the TCGA for ICOS expression in histologic and molecularly defined tumors and immune cell signatures. ICOS expression was analyzed by IHC in a subset of indications based on in silico analysis. ICOS expression on intra-tumoral Tregs and PD-L1 were analyzed in a cohort of 126 head and neck squamous cell carcinomas (HNSCC). Ex vivo histoculture assays of human HNSCC was treated with JTX-2011 and assessed for IFNg gene signature induction. Results: ICOS mRNA expression was analyzed in ~10,000 solid tumors samples across ~30 indications. ICOS expression in key indications was confirmed using IHC. Based on frequency of high ICOS expression, non-small cell lung cancer, HNSCC, triple negative breast carcinoma, gastric cancer, and melanoma were selected as indications for ICONIC. Results were confirmed in clinical samples using multiplex immunofluorescence and ICOS IHC. A wide range of ICOS expression was observed suggesting that identification of an ICOS “high” group may enrich for patients likely to benefit from ICOS agonist therapy. In ex vivo histoculture assays of human HNSCC tumors treated with JTX-2011, ICOS IHC and ICOS RNA gene signatures correlated to response endpoints. Comparison of ICOS and PDL1 expression identified subsets of tumors in multiple indications with high ICOS but low PDL1 expression. Conclusions: These data support prioritization of specific tumor types the ICONIC trial.
Sorafenib administered using a high-dose, pulsatile regimen in patients with advanced solid malignancies: A phase I exposure escalation study.
Authors: Lemonitsa Hillegonda Mammatas, Anthe S. Zandvliet, Maria Rovithi, Richard Honeywell, Eleonora Swart, Godefridus J. Peters, Catharina Wilhelmina Menke, Henk M.W. Verheul
Journal: Journal of Clinical Oncology (2017)

TPS2620 Background: Sorafenib is currently prescribed at a standard fixed dose of 400 mg twice daily in a continuous schedule. Increased exposure to sorafenib is associated with improved outcome. However, further increase in the dose of this continuous schedule is precluded due to toxicity. A high-dose, pulsatile schedule may result in increased sorafenib exposure while maintaining acceptable toxicity and has demonstrated promising preclinical antitumor activity. 1 Sorafenib plasma concentrations present with large interpatient variability. As drug effectivity is largely dependent on AUC exposure, personalized dose titration based on the sorafenib plasma AUC 0-12h of an individual patient seems more suitable than a standard fixed dose. In this phase I trial, a high-dose, weekly schedule of sorafenib is being studied, using exposure escalation cohorts based on a target AUC 0-12h, instead of conventional dose escalation cohorts. Methods: Adult patients are included with locally advanced or metastatic solid tumors for whom no standard therapy exists. High-dose sorafenib is administered once a week. Pharmacokinetic monitoring is performed during the first 3 weeks of treatment in each patient to evaluate if the target plasma sorafenib AUC 0-12h of the cohort is reached and sorafenib dose is adjusted accordingly. Cohorts consist of 3-6 patients per exposure level, starting with target AUC 0-12h 25-50 mg x h/L, analogous to the continuous schedule. The target AUC 0-12h is increased in subsequent cohorts until exposure limiting toxicity occurs. Main objectives are to assess safety and establish the maximum tolerated plasma AUC 0-12h of high-dose, pulsatile sorafenib. At this dose level 10 extra patients will be included. Tumor biopsies are required in all patients of this expansion cohort to study antitumor effects and for direct comparison of plasma and intratumor sorafenib concentrations. Furthermore, a simplified method will be developed for measurement of plasma sorafenib exposure using dried blood spot sampling at 1-2 time points. Nine patients have already been included. Reference: 1 Wang X. et al. J Transl Med 2011;9:220. Clinical trial information: NCT02636426.
A Review of Squamous Cell Vulvar Cancers in Waikato Region, New Zealand.
Authors: Prashanth Hari Dass, Marion Kuper-Hommel
Journal: Journal of Clinical Oncology (2016)

e17032 Background: Squamous cell vulvar cancer management guidelines are scarce. The objectives of the study were to review the patient characteristics and outcomes of vulvar cancers. Methods: Retrospective review of all vulvar cancer cases registered between 1/1/2000 to 31/8/2015. Cases were identified from clinical coding, radiation and medical oncology department databases. Cases were staged using TNM & FIGO classifications. Results: Of the 60 cases, 47 patients with Squamous cell vulvar cancer were reviewed. 13 patients excluded (11 non squamous histological diagnosis & 2 cases diagnosed before 1/1/2000). 81% were of European ethnicity & 19% Maori. Median age was 69 years (57 years for Maori vs 76 years for European). Advanced disease (Stage III & above) was seen in 58% European versus 44% Maori. Vulval pruritis, lump, pain & bleeding were most common symptoms at presentation. 31% had prior lichen sclerosus. 36% reported prior smoking history. Comorbidities include hypertension(44%), obesity(25%), ischemic heart disease(23%), diabetes(19%), & second malignancy excluding skin cancers(19%). 68% had vulvectomy or wide local excision. Inguinal lymph node dissections performed in 56% cases (43% bilateral & 13% unilateral). 6% cases underwent sentinel node procedure. Wound cellulitis (21%) & lymphedema (17%) were the most common acute & late complication respectively. Cases were identified as Stage I(34%), Stage II(11%), stage III(36%), & stage IV(19%). 80% cases received radiotherapy (RT) mean 50Gy. 17% received palliative RT. 23% cases were treated with chemoradiation i.e 15% with 5-Fluororuacil(5-FU), Mitomycin versus 8% with weekly Cisplatin. Grade 3 or higher toxicities was seen in 72% of 5-FU, Mitomycin versus 0% in Cisplatin group. 5 year overall survival(OS) was 73%(Stage I), 40%(Stage II), 44%(Stage III) and 29%(Stage IV). Median follow up was 33months. Conclusions: Vulvar cancers are rare. European patients present at an older age and more advanced disease compared to Maori. Treatment is associated with high morbidity. Co-morbidities & advanced age are potential explanations. Weekly Cisplatin is much better tolerated compared to 5FU, Mitomycin. This series calls for collaboration to generate guidelines to optimise management.