Institution
University of Turin
Education•Turin, Piemonte, Italy•
About: University of Turin is a education organization based out in Turin, Piemonte, Italy. It is known for research contribution in the topics: Population & Cancer. The organization has 29607 authors who have published 77952 publications receiving 2480900 citations. The organization is also known as: Universita degli Studi di Torino & Università degli Studi di Torino.
Topics: Population, Cancer, Medicine, Transplantation, Context (language use)
Papers published on a yearly basis
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TL;DR: The combination of trastuzumab and lapatinib is active and well tolerated in treatment-refractory patients with HER2-positive metastatic colorectal cancer.
Abstract: Summary Background We previously found that dual HER2 blockade with trastuzumab and lapatinib led to inhibition of tumour growth in patient-derived xenografts of HER2 -amplified metastatic colorectal cancer. In this study, we aimed to assess the antitumour activity of trastuzumab and lapatinib in patients with HER2-positive colorectal cancer. Methods HERACLES was a proof-of-concept, multicentre, open-label, phase 2 trial done at four Italian academic cancer centres. We enrolled adult patients with KRAS exon 2 (codons 12 and 13) wild-type and HER2-positive metastatic colorectal cancer refractory to standard of care (including cetuximab or panitumumab), an Eastern Cooperative Oncology Group performance status of 0 or 1, and at least one measurable lesion. We defined HER2 positivity in tumour samples by use of immunohistochemistry and fluorescence in-situ hybridisation in accordance with our previously validated colorectal cancer-specific diagnostic criteria. Eligible patients received intravenous trastuzumab at 4 mg/kg loading dose followed by 2 mg/kg once per week, and oral lapatinib at 1000 mg per day until evidence of disease progression. The primary endpoint was the proportion of patients achieving an objective response (defined as complete response or partial response), which was assessed by independent central review in the intention-to-treat population. This trial is registered with EudraCT, number 2012-002128-33. Findings Between Aug 27, 2012, and May 15, 2015, we screened 914 patients with KRAS exon 2 (codons 12 and 13) wild-type metastatic colorectal cancer and identified 48 (5%) patients with HER2-positive tumours, although two died before enrolment. Of these patients, 27 were eligible for the trial. All were evaluable for response. At the time of data cutoff on Oct 15, 2015, with a median follow-up of 94 weeks (IQR 51–127), eight (30%, 95% CI 14–50) of 27 patients had achieved an objective response, with one patient (4%, 95% CI −3 to 11) achieving a complete response, and seven (26%, 95% CI 9–43) achieving partial responses; 12 (44%, 95% CI 25–63) patients had stable disease. Six (22%) of 27 patients had grade 3 adverse events, which consisted of fatigue in four patients, skin rash in one patient, and increased bilirubin concentration in one patient. No grade 4 or 5 adverse events were reported. We detected no drug-related serious adverse events. Interpretation The combination of trastuzumab and lapatinib is active and well tolerated in treatment-refractory patients with HER2-positive metastatic colorectal cancer. Funding Associazione Italiana Ricerca Cancro (AIRC), Fondazione Oncologia Niguarda Onlus, and Roche.
707 citations
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University of Amsterdam1, University College London2, Sheba Medical Center3, National and Kapodistrian University of Athens4, Paris Descartes University5, Lille University of Science and Technology6, Centre Hospitalier Regional et Universitaire de Lille7, University of Turin8, Maastricht University9, French Institute of Health and Medical Research10, Seconda Università degli Studi di Napoli11, Charles University in Prague12, Odense University Hospital13, University Medical Center Groningen14, University Medical Center15, Freeman Hospital16, University of Padua17
TL;DR: A revised definition of dilated cardiomyopathy (DCM) is proposed in an attempt to bridge the gap between recent understanding of the disease spectrum and its clinical presentation in relatives, which is key for early diagnosis and the institution of potential preventative measures.
Abstract: In this paper the Working Group on Myocardial and Pericardial Disease proposes a revised definition of dilated cardiomyopathy (DCM) in an attempt to bridge the gap between our recent understanding of the disease spectrum and its clinical presentation in relatives, which is key for early diagnosis and the institution of potential preventative measures. We also provide practical hints to identify subsets of the DCM syndrome where aetiology directed management has great clinical relevance.
707 citations
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TL;DR: Dietary habits may promote steatohepatitis directly by modulating hepatic triglyceride accumulation and antioxidant activity as well as indirectly by affecting insulin sensitivity and postprandial triglyceride metabolism.
703 citations
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TL;DR: Limiting tidal volume to 6 ml/kg predicted body weight and plateau pressure to 30 cm H(2)O may not be sufficient in patients characterized by a larger nonaerated compartment.
Abstract: Rationale: Tidal volume and plateau pressure limitation decreases mortality in acute respiratory distress syndrome. Computed tomography demonstrated a small, normally aerated compartment on the top of poorly aerated and nonaerated compartments that may be hyperinflated by tidal inflation.Objectives: We hypothesized that despite tidal volume and plateau pressure limitation, patients with a larger nonaerated compartment are exposed to tidal hyperinflation of the normally aerated compartment.Measurements and Main Results: Pulmonary computed tomography at end-expiration and end-inspiration was obtained in 30 patients ventilated with a low tidal volume (6 ml/kg predicted body weight). Cluster analysis identified 20 patients in whom tidal inflation occurred largely in the normally aerated compartment (69.9 ± 6.9%; “more protected”), and 10 patients in whom tidal inflation occurred largely within the hyperinflated compartments (63.0 ± 12.7%; “less protected”). The nonaerated compartment was smaller and the norma...
702 citations
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Katholieke Universiteit Leuven1, Ottawa Hospital Research Institute2, University of Turin3, University of Bern4, Cliniques Universitaires Saint-Luc5, Bristol-Myers Squibb6, University of Melbourne7, Peter MacCallum Cancer Centre8, University of Sydney9, Flinders University10, Catholic University of Leuven11
TL;DR: In this paper, the authors studied the association between KRAS mutation status (p.G13D vs other KRAS mutations) and response and survival in a pooled data set of 579 patients with metastatic colorectal cancer treated with cetuximab between 2001 and 2008.
Abstract: Context Patients with metastatic colorectal cancer who have KRAS codon 12- or KRAS codon 13-mutated tumors are presently excluded from treatment with the anti-epidermal growth factor receptor monoclonal antibody cetuximab. Objective To test the hypothesis that KRAS codon 13 mutations are associated with a better outcome after treatment with cetuximab than observed with other KRAS mutations. Design, Setting, and Patients We studied the association between KRAS mutation status (p.G13D vs other KRAS mutations) and response and survival in a pooled data set of 579 patients with chemotherapy-refractory colorectal cancer treated with cetuximab between 2001 and 2008. Patients were included in the CO. 17, BOND, MABEL, EMR202600, EVEREST, BABEL, or SALVAGE clinical trials or received off-study treatment. Univariate and multivariate analyses, adjusting for possible prognostic factors and data set, were performed. The effect of the different mutations was studied in vitro by constructing isogenic cell lines with wild-type KRAS, p.G12V, or p.G13D mutant alleles and treating them with cetuximab. Main Outcome Measures The main efficacy end point was overall survival. Secondary efficacy end points were response rate and progression-free survival. Results In comparison with patients with other KRAS-mutated tumors, patients with p.G13D-mutated tumors (n=32) treated with cetuximab had longer overall survival (median, 7.6 [95% confidence interval {CI}, 5.7-20.5] months vs 5.7 [95% CI, 4.9-6.8] months; adjusted hazard ratio [HR], 0.50; 95% CI, 0.31-0.81; P=.005) and longer progression-free survival (median, 4.0 [95% CI, 1.9-6.2] months vs 1.9 [95% CI, 1.8-2.8] months; adjusted HR, 0.51; 95% CI, 0.32-0.81; P=.004). There was a significant interaction between KRAS mutation status (p.G13D vs other KRAS mutations) and overall survival benefit with cetuximab treatment (adjusted HR, 0.30; 95% CI, 0.14-0.67; P=.003). In vitro and mouse model analysis showed that although p.G12V-mutated colorectal cells were insensitive to cetuximab, p.G13D-mutated cells were sensitive, as were KRAS wild-type cells. Conclusions In this analysis, use of cetuximab was associated with longer overall and progression-free survival among patients with chemotherapy-refractory colorectal cancer with p.G13D-mutated tumors than with other KRAS-mutated tumors. Evaluation of cetuximab therapy in these tumors in prospective randomized trials may be warranted. JAMA. 2010; 304(16): 1812-1820
702 citations
Authors
Showing all 30045 results
Name | H-index | Papers | Citations |
---|---|---|---|
Michael Grätzel | 248 | 1423 | 303599 |
Lewis C. Cantley | 196 | 748 | 169037 |
Kenneth C. Anderson | 178 | 1138 | 126072 |
Elio Riboli | 158 | 1136 | 110499 |
Giacomo Bruno | 158 | 1687 | 124368 |
Silvia Franceschi | 155 | 1340 | 112504 |
Thomas E. Starzl | 150 | 1625 | 91704 |
Paolo Boffetta | 148 | 1455 | 93876 |
Marco Costa | 146 | 1458 | 105096 |
Pier Paolo Pandolfi | 146 | 529 | 88334 |
Andrew Ivanov | 142 | 1812 | 97390 |
Chiara Mariotti | 141 | 1426 | 98157 |
Tomas Ganz | 141 | 480 | 73316 |
Jean-Pierre Changeux | 138 | 672 | 76462 |
Dong-Chul Son | 138 | 1370 | 98686 |