tbuckley/cabot-search huggingface dataset:
A randomized, double-blind, placebo-controlled, multicenter, multinational, phase II trial immunotherapy with L-BLP25 (tecemotide) in patients with colorectal carcinoma following R0/R1 hepatic metastasectomy.
Authors: Stefan Kasper, Friedrich Overkamp, Markus Hermann Moehler, Frank Kullmann, Hauke Lang, Michael Schoen, Victoria Smith-Machnow, Susanna Hegewisch-Becker, Daniel Seehofer, Wolf Bechstein, Michael Heike, Matthias Voehringer, Volker Heinemann, Richard Greil, Michael Geissler, Florian Lordick, Marc Peeters, Eric Van Cutsem, Peter Robert Galle, Carl Christoph Schimanski
Journal: Journal of Clinical Oncology (2013)

TPS3124^ Background: 15-20% of all patients (pts) diagnosed with colorectal cancer (crc) develop metastases (mets) surgical resection remains the only potentially curative treatment available. Current 5-year survival rate following R0 resection of liver mets lies between 28-39%, recurrence occurs in up to 70% of pts. To date, adjuvant chemotherapy has not significantly improved clinical outcomes. The primary objective of the ongoing LICC trial (L-BLP25 In Colorectal Cancer) is to determine whether L-BLP25, an active MUC1-specific cancer immunotherapy, extends recurrence-free survival (RFS) time over placebo in crc pts following R0/R1 resection of liver mets known to highly express MUC1 glycoprotein. Phase III data from L-BLP25 in NSCLC will be reported at this meeting. Methods: This is a multinational, phase II, multicenter, randomized, double-blind, placebo-controlled trial with a sample size of 159 pts from 20 centers in 3 countries. Pts must have stage IV cr adenocarcinoma limited to liver mets. Following curative-intent complete resection of the primary tumor and of all synchronous/metachronous mets, eligible pts are randomized 2:1 to receive either L-BLP25 or placebo. L-BLP25 arm receives a single dose of 300 mg/m 2 cyclophosphamide (CPA) 3 d before 1st L-BLP25 dose, then primary treatment with sc L-BLP25 930 μg weekly for 8 weeks, followed by sc L-BLP25 930 μg maintenance doses at 6-week (year 1 and 2) and 12-week (year 3) intervals until recurrence. Control arm: CPA is replaced by saline solution and L-BLP25 by placebo. Primary endpoint (PE) is RFS time. Secondary endpoints: Overall survival (OS), safety, tolerance, RFS/OS in MUC-1 positive cancers. Exploratory immune response analyses are planned. Study start was in Q3 2011. 19 centers were initialized and 36 patients recruited, no SUSARs occurred. Study recruitment will end Q3 2013: follow-up until Q3 2017. PE assessment is in Q3 2016. Interim analyses are not planned.No major practical issues were identified during setup and early conduct of the study. Clinical trial information: 2011-000218-20.
Depression and anxiety (DA) in children within one year of a cancer diagnosis.
Authors: Patrick Leavey, Julie N Germann, David Leonard, Thomas Stuenzi, Jane LeVieux, Sunita Stewart
Journal: Journal of Clinical Oncology (2013)

10064 Background: While 10% of children were treated with anti-depressants within 1 year of a cancer diagnosis in a previous study, neither the prevalence nor time course of DA were studied. The American Association of Pediatrics advocates for the use of screening for DA, yet data are lacking regarding timing, frequency, or predictive success of screening in children concurrently receiving therapy for cancer. Methods: We evaluated 87 prospectively diagnosed children at a single institution for DA at 5 time points during the first year of a cancer diagnosis. 55 children completed all screening, 70 missed at most one visit. Starting within 1 month of cancer diagnosis, patients completed the Childhood Depression Inventory (CDI) and the Speilberger State/Trait Anxiety Inventory (STAI) and again at 3, 6, 9, and 12 months. Those patients who scored ≥ 11 on the CDI or ≥ one standard deviation above the mean for age on the STAI were referred for psychiatric consultation the same day. Results: Overall 33 patients (39%) indicated symptoms suggestive of either depression or anxiety during their first year of cancer therapy; n=29 (35%) depression, n=17 (20%) state and n=10 (12%) trait anxiety. Fifty-six consultations resulted in 33 psychiatry diagnoses confirmed in 21 patients (23 depression, 3 anxiety and 7 other). Half of the patients received a diagnosis of DA at least twice over the course of the study, suggesting persistent, significant symptoms. Conclusions: We conclude that screening for DA is effective in children with cancer and that prevalence for symptoms is high. The highest risk for symptoms of DA is within 1 month of diagnosis but during the 1st year of therapy children continue to suffer symptoms of DA highlighting the importance of continued screening. [Table: see text]
EZH2 methyltransferase and JMJD3/UTX demethylases are involved in hepatocytic differentiation and liver cancer cells plasticity
Authors: N. Pediconi, L. Lupacchini, D. Salerno, S. Di Cocco, G. Peruzzi, D. Rotili, A. Mai, M. Levrero, L. Belloni
Journal: Journal of Hepatology (2017)
Phase I dose-escalation study of an oral administration of the pan-histonedeacetylase inhibitor abexinostat combined with a fixed dose of doxorubicin in patients with solid tumors.
Authors: Arnaud Scherpereel, Ahmad Awada, Carlos Alberto Gomez-Roca, Eric Wasielewski, Philippe G. Aftimos, Marie-Capucine Willemin, Thierry Gil, Eleonora De Maio, Elsa Jozefowicz, Ioana Kloos, Alice Dorbon, Frédérique Cantero, Jean-Pierre Delord
Journal: Journal of Clinical Oncology (2014)

2575 Background: Preclinical data indicate that abexinostat enhances sensitivity to DNA-damaging agents, such as doxorubicin, particularly when administered 48h before infusion. A phase I dose-escalation study of abexinostat in combination with doxorubicin was performed in candidate patients to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT), and establish the recommended phase II dose (RP2D). Methods: Abexinostat was given 4 consecutive days weekly, 3 out of 4 weeks, and fixed doxorubicin dose of 25 mg/m2 was administered on day 3 of each weekly abexinostat schedule, for a maximum of 6 cycles. Results: 35 patients were included and treated: 23 in the dose-escalation phase in cohorts receiving abexinostat 30 to 75 mg/m² bid, and 12 in the confirmation phase at the RP2D. In the dose-escalation phase, MTD was 75 mg/m² bid with 3 DLTs 2 grade 4 thrombocytopenia, 1 grade 2 neutropenia >7 days. In the confirmation phase (RP2D 60 mg/m² bid), there were 4 DLTs (33% patients): 2 grade 4 thrombocytopenia, 1 grade 3 fatigue, 1 failure to restart treatment due to prolonged grade 2 neutropenia. Most abexinostat-related adverse events were grade 1 or 2 (79%), with 18% grade 3 and 3% grade 4; they were mostly hematological (51%), gastrointestinal (23%), or general disorders (10%). Preliminary pharmacokinetics of the combination showed no interaction between the two drugs. Preliminary efficacy results on 27 evaluable patients showed 3 partial responses (2 at C4 and 1 at C6) and 12 stable disease with median duration of 2 cycles (range C2-C6) as best response. 13 patients received the combination for at least 4 cycles and 11 patients completed 6 cycles. Conclusions: Combination of abexinostat 60 mg/m² bid 4 consecutive days weekly, 3 out of 4 weeks, with doxorubicin at 25 mg/m2 on the third day of each abexinostat cycle appears to be well tolerated in patients with advanced solid tumors. Preliminary efficacy results were observed at different dose levels. Clinical trial information: ISRCTN55052510.
High sustained virologic response rates in hepatitis C virus genotype 3 patients with and without cirrhosis treated with daclatasvir/sofosbuvir or velpatasvir/sofosbuvir ± ribavirin according to baseline resistance analysis
Authors: J. Vermehren, J. Dietz, K.-H. Peiffer, N. Weiler, V. Mücke, G. Dultz, C. Welsch, S. Zeuzem, T.M. Welzel, C. Sarrazin
Journal: Journal of Hepatology (2017)
Efficacy of therapy against chronic hepatitis C virus genotype 1 infection in HIV-coinfected patients with several interferon-free DAA combinations: real life data from the HEPAVIR-DAA Cohort
Authors: K. Neukam, F. Téllez, L.E. Morano-Amado, A. Rivero-Juárez, E. Nuño-Álvarez, M.J. Ríos, J. Macías, D. Merino, M. Pérez-Pérez, J.A. Pineda
Journal: Journal of Hepatology (2017)
SPX-101 Is a Novel Epithelial Sodium Channel–targeted Therapeutic for Cystic Fibrosis That Restores Mucus Transport
Authors: David W. Scott, Matthew P. Walker, Juliana Sesma, Bryant Wu, Timothy J. Stuhlmiller, Juan R. Sabater, William M. Abraham, Timothy M. Crowder, Dale J. Christensen, Robert Tarran
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: Cystic fibrosis (CF) lung disease is caused by the loss of function of the cystic fibrosis transmembrane conductance regulator (CFTR) combined with hyperactivation of the epithelial sodium channel (ENaC). In the lung, ENaC is responsible for movement of sodium. Hyperactivation of ENaC, which creates an osmotic gradient that pulls fluid out of the airway, contributes to reduced airway hydration, causing mucus dehydration, decreased mucociliary clearance, and recurrent acute bacterial infections. ENaC represents a therapeutic target to treat all patients with CF independent of their underlying CFTR mutation.Objectives: To investigate the in vitro and in vivo efficacy of SPX-101, a peptide mimetic of the natural regulation of ENaC activity by short palate, lung, and nasal epithelial clone 1, known as SPLUNC1.Methods: ENaC internalization by SPX-101 in primary human bronchial epithelial cells from healthy and CF donors was assessed by surface biotinylation and subsequent Western blot analysis. SPX-101's in vivo therapeutic effect was assessed by survival of β-ENaC–transgenic mice, mucus transport in these mice, and mucus transport in a sheep model of CF.Measurements and Main Results: SPX-101 binds selectively to ENaC and promotes internalization of the α-, β-, and γ-subunits. Removing ENaC from the membrane with SPX-101 causes a significant decrease in amiloride-sensitive current. The peptide increases survival of β-ENaC–transgenic mice to greater than 90% with once-daily dosing by inhalation. SPX-101 increased mucus transport in the β-ENaC mouse model as well as the sheep model of CF.Conclusions: These data demonstrate that SPX-101 promotes durable reduction of ENaC membrane concentration, leading to significant improvements in mucus transport.
The real world experience of first generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) in patients with advanced lung cancer: Explorative analysis of big data from national health insurance service of Korea
Authors: B.S. Kwon, J.C. Lee, S. Kim, M.Y. Kim, C.-M. Choi
Journal: Annals of Oncology (2017)
Efficacy of oral Direct Acting Antivirals for the treatment of chronic hepatitis/cirhhosis due to hepatitis C virus infection: the real-life experience of the Sicily Registry
Authors: I. Cacciola, S. Petta, M. Di Stefano, M.R. Cannavò, A. Davì, S. Madonia, V. Calvaruso, L.L. Rocca, F. Di Lorenzo, A. Digiacomo, G. Bertino, A. Licata, F. Benanti, R. Volpes, L. Guarneri, A. Averna, I. Scalisi, C. Iacobello, P. Colletti, F. Cartabellotta, V. Portelli, M. Russello, G. Scifo, G. Squadrito, G. Raimondo, A. Craxì, V. Di Marco
Journal: Journal of Hepatology (2017)
Result of clinical study on feasibility of laparoscopy-assisted D2 distal gastrectomy to treat advanced gastric cancer (COACT_1001).
Authors: Young Woo Kim, Young-Kyu Park, Hong Man Yoon, Byung-Ho Nam, Keun Won Ryu, Young-Joon Lee, Oh Jeong, Ki Young Yoon, Jun Ho Lee, Sang Eog Lee, Wansik Yu, Sang-Ho Jeong, Taebong Kim
Journal: Journal of Clinical Oncology (2013)

4105 Background: Benefit of quality of life made laparoscopic gastric cancer surgery attractive, but there are still concerns about laparoscopic lymph node dissection. The aim of this study was to evaluate a feasibility of laparoscopy-assisted distal gastrectomy (LADG) with D2 lymph node dissection compared with open distal gastrectomy (ODG) for advanced gastric cancer (AGC). Methods: Patients with cT2-T4a and cN0-2 (AJCC 7 th staging system) distal gastric cancer were randomly assigned to LADG or ODG. The primary endpoint was the non-compliance rate of the lymph node dissection defined as rate of cases where there was more than one missing lymph node station according to the guidelines of the Japanese Research Society for Gastric Cancer lymph node grouping. Secondary endpoints were perioperative complications, changes of inflammatory and immunological parameters, postoperative hospital stay, and 3 year disease free survival. This trial was registered at ClinicalTrials.gov as NCT01088204. Results: Between Jun 2010 and Oct 2011,204 patients were randomly allocated and underwent either LADG (n=105) or ODG (n=99). 8 patients were excluded in the intention to treatment analysis because of protocol violation and patient’s withdrawal of permission, and finally 100 patients in LADG and 95 patients in ODG were analyzed. There were no significant differences of overall non-compliance rate of lymph node dissection between LADG and ODG groups; they were respectively 47.0% and 43.2%. (p=0.648). In the subgroup analysis according to the stratified risk groups, non-compliance rate in LADG was significantly higher than ODG (52.0% vs. 25.0%, p=0.043) for clinical stage III but it was not significantly different for stage II (46.2% vs. 48.9%, p=0.788). Intraoperative event rate was not significantly different between groups (LADG;6.0% and ODG;4.2%, p =0.748). Complications rate in early postoperative period up to 1 month was also not different between groups (LADG;17.0 %, ODG;18.8%, p=0.749). Conclusions: LADG was feasible in AGC compared with ODG, especially in clinical stage II in terms of non-compliance rate of D2 lymph node dissection and perioperative complications. Clinical trial information: NCT01088204.
Treatment-stage migration maximizes survival outcomes in patients with hepatocellular carcinoma treated with sorafenib: an observational study
Authors: Clarence Yen, Rohini Sharma, Lorenza Rimassa, Tadaaki Arizumi, Dominik Bettinger, Huay Yee Choo, Tiziana Pressiani, Michela E Burlone, Mario Pirisi, Laura Giordano, Anisa Abdulrahman, Masatoshi Kudo, Robert Thimme, Joong Won Park, David James Pinato
Journal: Journal of Hepatology (2017)
Etiology, time frame and spectrum of decompensation in 6236 patients of cirrhosis liver across Asia: a multinational study from APASL ACLF Research Consortium (AARC)
Authors: A. Choudhury, M.K. Sharma, B.C. Sharma, R. Maiwal, V. Pamecha, R. Moreau, Y.K. Chawla, A. Duseja, M.A. Mahtab, S. Rahman, S.S. Hamid, A.S. Butt, W. Jafri, S.S. Tan, H. Devarbhavi, D. Amarapurkar, Q. Ning, C.E. Eapen, A. Goel, D.J. Kim, H. Ghazinyan, G. Shiha, G.H. Lee, Z. Abbas, D.A. Payawal, A.K. Dokmeci, M.F. Yuen, L.A. Leshmana, A. Sood, A. Chan, G.K. Lau, J.D. Jia, Z. Duan, C. Yu, O. Yokosuka, P.N. Rao, S. Shah, V.G.M. Prasad, M.K. Sahu, A. Shukla, J. Hu, S. Treeprasertsuk, V. Arora, K. Mishra, P. Bhatia, P. Jain, G. Kumar, S.K. Sarin
Journal: Journal of Hepatology (2017)
Brigatinib in crizotinib-refractory ALK+ NSCLC: Updates from the pivotal randomized phase 2 Trial (ALTA)
Authors: M.J. Hochmair, M. Tiseo, K.L. Reckamp, H.L. West, H.J. Groen, C.J. Langer, W. Reichmann, D. Kerstein, D.-W. Kim, D.R. Camidge
Journal: Annals of Oncology (2017)
David Oliver: Reducing acute admissions—a timely reality check
Authors: David Oliver
Journal: BMJ (2017)

In March NHS England published Next Steps on the NHS Five Year Forward View , a mid-term report and road map to 2020 of the plan by its chief executive, Simon Stevens, to sustain the NHS in the face of unprecedented crises in funding, demand, and workforce.1

Reducing urgent care activity and hospital beds have been key themes of England’s 44 sustainability and transformation plans (STPs). These are key vehicles for delivering the strategy Stevens set out in the NHS Five Year Forward View . They’ll now be called not plans but “partnerships.”

I welcome Next Steps ’ …
A Systematic Review of the Clinimetric Properties of the 6-Item Version of the Hamilton Depression Rating Scale (HAM-D&lt;sub&gt;6&lt;/sub&gt;)
Authors: N. Timmerby, J.H. Andersen, S. Søndergaard, S.D. Østergaard, Per Bech
Journal: Psychotherapy and Psychosomatics (2017)

In a study aimed at identifying the items carrying information regarding the global severity of depression, the 6-item Hamilton Depression Rating Scale (HAM-D6) was derived from the original 17-item version of the scale (HAM-D17). Since then, the HAM-D6 has been used in a wide range of clinical studies. We now provide a systematic review of the clinimetric properties of HAM-D6 in comparison with those of HAM-D17 and the Montgomery Asberg Depression Rating Scale (MADRS).We conducted a systematic search of the literature in PubMed, PsycInfo, and EMBASE databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Studies reporting data on the clinimetric validity of the HAM-D6 and either the HAM-D17 or MADRS in non-psychotic unipolar or bipolar depression were included in the synthesis.The search identified 681 unique records, of which 51 articles met the inclusion criteria. According to the published literature, HAM-D6 has proven to be superior to both HAM-D17 and MADRS in terms of scalability (each item contains unique information regarding syndrome severity), transferability (scalability is constant over time and irrespective of sex, age, and depressive subtypes), and responsiveness (sensitivity to change in severity during treatment).According to the published literature, the clinimetric properties of HAM-D6 are superior to those of both the HAM-D17 and MADRS. Since the validity of HAM-D6 has been demonstrated in both research and clinical practice, using the scale more consistently would facilitate translation of results from one setting to the other.
Chronic hepatitis C in children in the Russian Federation: a multicenter study
Authors: G.V. Volynets, T.A. Skvortsova, A.S. Potapov, V.N. Panfilova, N.V. Rogozina, A.V. Nikitin, C. Giaquinto, C. Thorne, A. Turkova
Journal: Journal of Hepatology (2017)
Real-world utilization of the new fixed-dose combination elbasvir/grazoprevir in adult patients with chronic hepatitis C in Canada: Z-PROFILE study
Authors: E. Tam, C. Fraser, J. Tremblay, B. Conway, B. Trottier, A. Ramji, S. Borgia, K. Stewart, J. Trépanier, Y. Chalabi
Journal: Journal of Hepatology (2017)
Acute hemodynamic response to beta-blockers: factors influencing its outcome
Authors: J.I. Fortea, A. Puente, P. Ruiz, M.T. Arias-Loste, S. Alvarez, J. Cabezas, A. Cuadrado, S. Llerena, A. Estébanez, F. Casafont, E. Fabrega, J. Crespo
Journal: Journal of Hepatology (2017)
SARAH: a randomised controlled trial comparing efficacy and safety of selective internal radiation therapy (with yttrium-90 microspheres) and sorafenib in patients with locally advanced hepatocellular carcinoma
Authors: V. Vilgrain, M. Bouattour, A. Sibert, R. Lebtahi, M. Ronot, G.-P. Pageaux, B. Guiu, H. Barraud, C. Silvain, R. Gérolami, F. Oberti, J.L. Raoul, C. Costentin, D. Samuel, A. Dinut, H. Pereira, G. Chatellier, L. Castera
Journal: Journal of Hepatology (2017)
The clinical impact of multiplex ctDNA gene analysis in lung cancer
Authors: S. Geva, T. Twito, A. Dvir, L. Soussan-Gutman, M. Ilouze, L.C. Roisman, E. Dudnik, A. Zer, R.B. Lanman, N. Peled
Journal: Annals of Oncology (2017)
The GLOBE score identifies PBC patients at increased risk of liver transplantation or death in different age-categories over time
Authors: J.C. Goet, W.J. Lammers, A. Floreani, A. Pares, H.L.A. Janssen, G.M. Hirschfield, H.R. Van Buuren, C. Corpechot, P. Invernizzi, K.D. Lindor, M.J. Mayo, P.M. Battezzati, F. Nevens, A.L. Mason, K.V. Kowdley, C.Y. Ponsioen, T. Bruns, G.N. Dalekos, D. Thorburn, X. Verhelst, N.K. Gatselis, P.J. Trivedi, R. Poupon, B.E. Hansen
Journal: Journal of Hepatology (2017)
Bim as a predictive T-cell biomarker for response to anti-PD-1 therapy in metastatic melanoma (MM).
Authors: Roxana Stefania Dronca, Svetomir Markovic, Lisa A. Kottschade, Robert R. McWilliams, Matthew Stephen Block, Wendy Kay Nevala, Michael A Thompson, Haidong Dong
Journal: Journal of Clinical Oncology (2015)

9013 Background: Given the variability in response to novel immunotherapeutic agents such as anti-PD1/PD-L1 therapies and the desire to extend their long-term benefit to more patients (pts), there is an increased need for the development of biomarkers that can help predict treatment outcomes and ensure that these treatments, which may have significant toxicities, are offered to pts more likely to benefit. We evaluated Bim (BCL-2-interacting mediator of cell death) in peripheral blood (PB) tumor-reactive CD11ahighPD-1+CD8+cytotoxic T lymphocytes (CTL) as a marker of the status of PD-1 engagement and T-cell reversibility to identify pts with MM who are more likely to benefit from anti-PD-1. Methods: MM patients treated with Pembrolizumab (pembro) 2 mg/kg every 3 weeks through an Expanded Access Program (EAP) had PB collected at baseline and at radiographic tumor evaluation through a separate biomarker sub-study. Frequencies of Bim+ T cells and Bim median fluorescence intensity (MFI) were measured by flow cytometry in gated CD11ahighPD1+ CD8+T cells. Non-parametric t-test was used to compare baseline Bim and percent change in Bim levels in pts who had a radiographic response (CR/PR/SD) compared to those who had progressive disease (PD) at 12 wks. Results: 29/40 ptsenrolled in the EAP had baseline samples and 14/29 pts had serial samplesavailable. Clinical benefit (CR/PR/SD) was observed in 9/27 evaluable pts at 12 wk; 18/27pts had PD. Two pts discontinued therapy for adrenal insufficiency (attribution to pembro unknown) and were not evaluable. Pts with clinical benefit after 4 cycles had higher frequency of Bim+/PD-1+ CD8 T cells at baseline compared to pts with radiographic PD (mean 60% vs. 49%, P = 0.04). In 9/9 responders who had serial PB samples available, the levels of Bim in PD-1+ CD8 T cells decreased after the first 3 months of treatment, and they increased/did not change in all 5/5 nonresponders with serial samples evaluable (P = 0.003). Conclusions: Measurements of Bim levels in tumor-reactive PD-1+ CD8 T cells may select patients likely to benefit from anti-PD-1 therapy, and provide a new non-invasive way to monitor response to anti-PD-1 blockade in MM. These results are being validated on a larger prospective cohort.