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British Journal of Cancer

Francesco Bertolini
Immune checkpoint inhibitors have shown unprecedented clinical activity in a variety of cancer types, but only in a fraction of patients. Promising in vivo synergies have been demonstrated between checkpoint inhibitors and other drugs and/or chemotherapy or radiotherapy, and effective models are now needed to select the best combinatorial regimen and disease setting.
December 11, 2018: British Journal of Cancer
Vera Gorbunova, J Thaddeus Beck, Ralf-Dieter Hofheinz, Pilar Garcia-Alfonso, Marina Nechaeva, Antonio Cubillo Gracian, Laszlo Mangel, Elena Elez Fernandez, Dustin A Deming, Ramesh K Ramanathan, Alison H Torres, Danielle Sullivan, Yan Luo, Jordan D Berlin
BACKGROUND: Metastatic colorectal cancer (mCRC) has low survival rates. We assessed if addition of veliparib, concurrent to FOLFIRI, improves survival in patients with previously untreated mCRC. METHODS: This study compared veliparib (200 mg BID for 7 days of each 14-day cycle) to placebo, each with FOLFIRI. Bevacizumab was allowed in both arms. The primary endpoint was progression-free survival (PFS). RESULTS: Patients were randomised to receive veliparib (n = 65) or placebo (n = 65) in combination with FOLFIRI...
December 11, 2018: British Journal of Cancer
Marco Durante
No abstract text is available yet for this article.
December 11, 2018: British Journal of Cancer
Kelly L Singel, Kassondra S Grzankowski, A N M Nazmul H Khan, Melissa J Grimm, Anthony C D'Auria, Kayla Morrell, Kevin H Eng, Bonnie Hylander, Paul C Mayor, Tiffany R Emmons, Nikolett Lénárt, Rebeka Fekete, Zsuzsanna Környei, Uma Muthukrishnan, Jonathan D Gilthorpe, Constantin F Urban, Kiyoshi Itagaki, Carl J Hauser, Cynthia Leifer, Kirsten B Moysich, Kunle Odunsi, Ádám Dénes, Brahm H Segal
BACKGROUND: Advanced cancer causes necrosis and releases damage-associated molecular patterns (DAMPs). Mitochondrial DAMPs activate neutrophils, including generation of neutrophil extracellular traps (NETs), which are injurious, thrombogenic, and implicated in metastasis. We hypothesised that extracellular mitochondrial DNA (mtDNA) in ascites from patients with epithelial ovarian cancer (EOC) would correlate with worse outcomes. METHODS: Banked ascites supernatants from patients with newly diagnosed advanced EOC were analysed for mtDNA, neutrophil elastase, and activation of healthy donor neutrophils and platelets...
December 6, 2018: British Journal of Cancer
Katharina Kriegsmann, Mark Kriegsmann, Martin Cremer, Michael Schmitt, Peter Dreger, Hartmut Goldschmidt, Carsten Müller-Tidow, Michael Hundemer
Despite the arrival of novel therapies, multiple myeloma (MM) remains incurable and new treatment options are needed. Chimeric antigen receptor (CAR) T cells are genetically modified T cells that express a CAR directed against specific tumour antigens. CAR T cells are able to kill target tumour cells and may result in long-lasting immune responses in vivo. The rapid development of CAR technologies has led to clinical trials in haematological cancers including MM, and CAR T cells might evolve into a standard treatment in the next few years...
December 6, 2018: British Journal of Cancer
Florence T H Wu, Ping Xu, Annabelle Chow, Shan Man, Janna Krüger, Kabir A Khan, Marta Paez-Ribes, Elizabeth Pham, Robert S Kerbel
BACKGROUND: There are phase 3 clinical trials underway evaluating anti-PD-L1 antibodies as adjuvant (postoperative) monotherapies for resectable renal cell carcinoma (RCC) and triple-negative breast cancer (TNBC); in combination with antiangiogenic VEGF/VEGFR2 inhibitors (e.g., bevacizumab and sunitinib) for metastatic RCC; and in combination with chemotherapeutics as neoadjuvant (preoperative) therapies for resectable TNBC. METHODS: This study investigated these and similar clinically relevant drug combinations in highly translational preclinical models of micro- and macro-metastatic disease that spontaneously develop after surgical resection of primary kidney or breast tumours derived from orthotopic implantation of murine cancer cell lines (RENCAluc or EMT-6/CDDP, respectively)...
November 30, 2018: British Journal of Cancer
Fotios Loupakis, Herbert I Hurwitz, Leonard Saltz, Dirk Arnold, Axel Grothey, Quynh Lan Nguyen, Stuart Osborne, Jonathan Talbot, Stefanie Srock, Heinz-Josef Lenz
BACKGROUND: Two first-line (1L) bevacizumab trials showed the prognostic value of primary tumour location in metastatic colorectal cancer (mCRC). In this retrospective subgroup analysis, further analysis of the predictive effect of bevacizumab is presented. METHODS: Patients with sidedness information from two randomised phase III studies of bevacizumab + chemotherapy (CT) vs CT as 1L mCRC treatment were analysed retrospectively. RESULTS: Sidedness was determined in 1590 (27% right and 73% left) of 2214 patients...
November 29, 2018: British Journal of Cancer
Jun Tian, Fatmah Al Raffa, Meiou Dai, Alaa Moamer, Baharak Khadang, Ibrahim Y Hachim, Khldoun Bakdounes, Suhad Ali, Bertrand Jean-Claude, Jean-Jacques Lebrun
BACKGROUND: Patients with triple negative breast cancer (TNBC) exhibit poor prognosis and are at high risk of tumour relapse, due to the resistance to chemotherapy. These aggressive phenotypes are in part attributed to the presence of breast cancer stem cells (BCSCs). Therefore, targeting BCSCs is a priority to overcoming chemotherapy failure in TNBCs. METHODS: We generated paclitaxel (pac)-resistant TNBC cells which displayed higher sphere forming potential and percentage of BCSC subpopulations compared to the parental cells...
November 28, 2018: British Journal of Cancer
Duncan C Gilbert, Katie Wakeham, Ruth E Langley, Claire L Vale
BACKGROUND: High-risk human papilloma viruses (HPV) are a causative agent of anogenital and oropharyngeal cancers. Patients treated for a preinvasive or invasive HPV-associated cancer may be at increased risk of a second such malignancy. METHODS: We performed a systematic review and random effects meta-analysis to estimate the risk of HPV-associated cancer after prior diagnosis. Studies reporting second cancers at anogenital and oropharyngeal sites after prior diagnoses (preinvasive/invasive HPV-associated cancer) were identified...
November 28, 2018: British Journal of Cancer
Sumei Wang, Donald M O'Rourke, Sanjeev Chawla, Gaurav Verma, MacLean P Nasrallah, Jennifer J D Morrissette, Gabriela Plesa, Carl H June, Steven Brem, Eileen Maloney, Arati Desai, Ronald L Wolf, Harish Poptani, Suyash Mohan
EGFRvIII targeted chimeric antigen receptor T (CAR-T) cell therapy has recently been reported for treating glioblastomas (GBMs); however, physiology-based MRI parameters have not been evaluated in this setting. Ten patients underwent multiparametric MRI at baseline, 1, 2 and 3 months after CAR-T therapy. Logistic regression model derived progression probabilities (PP) using imaging parameters were used to assess treatment response. Four lesions from "early surgery" group demonstrated high PP at baseline suggestive of progression, which was confirmed histologically...
November 27, 2018: British Journal of Cancer
Lorenzo Dutto, Amar Ahmad, Katerina Urbanova, Christian Wagner, Andreas Schuette, Mustafa Addali, John D Kelly, Ashwin Shridhar, Senthil Nathan, Timothy P Briggs, Joern H Witt, Gregory Shaw
BACKGROUND: Active surveillance is recommended for insignificant prostate cancer (PCa). Tools exist to identify suitable candidates using clinical variables. We aimed to develop and validate a novel risk score (NRS) predicting which patients are harbouring insignificant PCa. METHODS: We used prospectively collected data from 8040 consecutive unscreened patients who underwent radical prostatectomy between 2006 and 2016. Of these, data from 2799 patients with Gleason 3 + 3 on biopsy were used to develop a multivariate model predicting the presence of insignificant PC at radical prostatectomy (ERSPC updated definition3 : Gleason 3 + 3 only, index tumour volume < 1...
November 27, 2018: British Journal of Cancer
Tiziana Triulzi, Viola Regondi, Loris De Cecco, Maria Rosa Cappelletti, Martina Di Modica, Biagio Paolini, Pier Luigi Lollini, Serena Di Cosimo, Lucia Sfondrini, Daniele Generali, Elda Tagliabue
BACKGROUND: Optimising the selection of HER2-targeted regimens by identifying subsets of HER2-positive breast cancer (BC) patients who need more or less therapy remains challenging. We analysed BC samples before and after treatment with 1 cycle of trastuzumab according to the response to trastuzumab. METHODS: Gene expression profiles of pre- and post-treatment tumour samples from 17 HER2-positive BC patients were analysed on the Illumina platform. Tumour-associated immune pathways and blood counts were analysed with regard to the response to trastuzumab...
November 27, 2018: British Journal of Cancer
Jesús García-Foncillas, Josep Tabernero, Elena Élez, Enrique Aranda, Manuel Benavides, Carlos Camps, Eloisa Jantus-Lewintre, Rafael López, Laura Muinelo-Romay, Clara Montagut, Antonio Antón, Guillermo López, Eduardo Díaz-Rubio, Federico Rojo, Ana Vivancos
BACKGROUND: Liquid biopsy offers a minimally invasive alternative to tissue-based evaluation of mutational status in cancer. The goal of the present study was to evaluate the aggregate performance of OncoBEAM RAS mutation analysis in plasma of colorectal cancer (CRC) patients at 10 hospital laboratories in Spain where this technology is routinely implemented. METHODS: Circulating cell-free DNA from plasma was examined for RAS mutations using the OncoBEAM platform at each hospital laboratory...
November 23, 2018: British Journal of Cancer
Linnéa Schmidt, Mia Møller, Christa Haldrup, Siri H Strand, Søren Vang, Jakob Hedegaard, Søren Høyer, Michael Borre, Torben Ørntoft, Karina Dalsgaard Sørensen
BACKGROUND: The current inability to predict whether a primary prostate cancer (PC) will progress to metastatic disease leads to overtreatment of indolent PCs as well as undertreatment of aggressive PCs. Here, we explored the transcriptional changes associated with metastatic progression of multifocal hormone-naive PC. METHODS: Using total RNA-sequencing, we analysed laser micro-dissected primary PC foci (n = 23), adjacent normal prostate tissue samples (n = 23) and lymph node metastases (n = 9) from ten hormone-naive PC patients...
November 19, 2018: British Journal of Cancer
Felicitas Rataj, Severin J Jacobi, Stefan Stoiber, Florian Asang, Justyna Ogonek, Nicholas Tokarew, Bruno L Cadilha, Erwin van Puijenbroek, Constanze Heise, Peter Duewell, Stefan Endres, Christian Klein, Sebastian Kobold
BACKGROUND: CD16-chimeric antigen receptors (CAR) T cells recognise the Fc-portion of therapeutic antibodies, which can enable the selective targeting of different antigens. Limited evidence exists as to which CD16-CAR design and antibody partner might be most effective. We have hypothesised that the use of high-affinity CD16 variants, with increased Fc-terminus antibody affinity, combined with Fc-engineered antibodies, would provide superior CD16-CAR T cell efficacy. METHODS: CD16-CAR T (wild-type or variants) cells were co-cultured with Panc-1 pancreatic cancer, Raji lymphoma or A375 melanoma cells in the presence or absence of anti-CD20, anti-MCSP, wild-type or the glycoengineered antibody variants...
November 15, 2018: British Journal of Cancer
Felix Preisser, Elio Mazzone, Sebastiano Nazzani, Michele Marchioni, Marco Bandini, Zhe Tian, Fred Saad, Denis Soulières, Shahrokh F Shariat, Francesco Montorsi, Hartwig Huland, Markus Graefen, Derya Tilki, Pierre I Karakiewicz
BACKGROUND: The National Comprehensive Cancer Network (NCCN) guidelines provide recommendations for staging of prostate cancer patients in the objective regarding presence of locoregional lymph node metastases (LNM) and bone metastases. We tested the performance characteristics of these recommendations in a community setting. METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2014), we identified patients with available Gleason, clinical stage and prostatic specific antigen...
November 14, 2018: British Journal of Cancer
Alison M Schram, Leena Gandhi, Monica M Mita, Lars Damstrup, Frank Campana, Manuel Hidalgo, Enrique Grande, David M Hyman, Rebecca S Heist
BACKGROUND: This phase Ib study evaluated the safety, maximum-tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and preliminary efficacy of pimasertib (MSC1936369B), a MEK1/2 inhibitor, in combination with voxtalisib (SAR245409), a pan-PI3K and mTORC1/mTORC2 inhibitor, in patients with advanced solid tumours. METHODS: This study included a dose escalation and expansion in patients with select tumour types and alterations in the MAPK or PI3K pathways. A 3 + 3 design was used to determine MTD...
November 14, 2018: British Journal of Cancer
Eliana Rulli, Francesca Ghilotti, Elena Biagioli, Luca Porcu, Mirko Marabese, Maurizio D'Incalci, Rino Bellocco, Valter Torri
BACKGROUND: The evaluation of the proportional hazards (PH) assumption in survival analysis is an important issue when Hazard Ratio (HR) is chosen as summary measure. The aim is to assess the appropriateness of statistical methods based on the PH assumption in oncological trials. METHODS: We selected 58 randomised controlled trials comparing at least two pharmacological treatments with a time-to-event as primary endpoint in advanced non-small-cell lung cancer. Data from Kaplan-Meier curves were used to calculate the relative hazard at each time point and the Restricted Mean Survival Time (RMST)...
November 13, 2018: British Journal of Cancer
Lap Ah Tse, Xiaona Lin, Wentao Li, Hong Qiu, Chi Kuen Chan, Feng Wang, Ignatius Tak-Sun Yu, Chi Chiu Leung
BACKGROUND: Population-based studies showed an over 50% decrease in lung cancer risk after quitting smoking for 5-6 years, but the beneficial effect in silicotics remains unknown. We aimed to rectify this knowledge gap using a large historical cohort of 3185 Chinese silicotics since 1981 and followed-up till 2014. METHODS: Baseline information on workers' socio-demographics, smoking habits, occupational history, and medical history was collected. Smoking status was reassessed during follow-up...
November 13, 2018: British Journal of Cancer
Vincenzo Mazzaferro, Bassel F El-Rayes, Michele Droz Dit Busset, Christian Cotsoglou, William P Harris, Nevena Damjanov, Gianluca Masi, Lorenza Rimassa, Nicola Personeni, Fadi Braiteh, Vittorina Zagonel, Kyriakos P Papadopoulos, Terence Hall, Yunxia Wang, Brian Schwartz, Julia Kazakin, Sherrie Bhoori, Filippo de Braud, Walid L Shaib
BACKGROUND: Next-generation sequencing has identified actionable genetic aberrations in intrahepatic cholangiocarcinomas (iCCA), including the fibroblast growth factor receptor 2 (FGFR2) fusions. Derazantinib (ARQ 087), an orally bioavailable, multi-kinase inhibitor with potent pan-FGFR activity, has shown preliminary therapeutic activity against FGFR2 fusion-positive iCCA. METHODS: This multicentre, phase 1/2, open-label study enrolled adult patients with unresectable iCCA with FGFR2 fusion, who progressed, were intolerant or not eligible to first-line chemotherapy (NCT01752920)...
November 13, 2018: British Journal of Cancer
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