Publications by authors named "Timothy J Perren"

Objectives: Better markers of early response to neoadjuvant chemotherapy (NACT) in patients with breast cancer are required to enable the timely identification of non-responders and reduce unnecessary treatment side-effects. Early functional imaging may better predict response to treatment than conventional measures of tumour size. The purpose of this study was to test the hypothesis that the change in tumour blood flow after one cycle of NACT would predict pathological response.

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Bevacizumab is approved as a maintenance treatment in first-line setting in advanced-stage III-IV ovarian cancers, because GOG-0218 and ICON-7 phase III trials demonstrated progression-free survival benefits. However, only the subgroup of patients with high-risk diseases (stage IV, and incompletely resected stage III) derived an overall survival (OS) gain in the ICON-7 trial (4.8 months).

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Objective: Two randomized phase III trials demonstrated the efficacy and safety of combining bevacizumab with front-line carboplatin/paclitaxel for advanced ovarian cancer. The OSCAR (NCT01863693) study assessed the impact of front-line bevacizumab-containing therapy on safety and oncologic outcomes in patients with advanced ovarian cancer in the UK.

Methods: Between May 2013 and April 2015, patients with high-risk stage IIIB-IV advanced ovarian cancer received bevacizumab (7.

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Objective: In the randomized phase 3 ICON7 trial (ISRCTN91273375), adding bevacizumab to chemotherapy for newly diagnosed ovarian cancer significantly improved progression-free survival (PFS; primary endpoint) but not overall survival (OS; secondary endpoint) in the intent-to-treat (ITT) population. We explored treatment effect according to stage and extent of residual disease.

Methods: Patients with stage IIB-IV or high-risk (grade 3/clear-cell) stage I-IIA ovarian cancer were randomized to receive six cycles of carboplatin and paclitaxel either alone or with bevacizumab 7.

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Purpose: To measure the arterial input function (AIF), an essential component of tracer kinetic analysis, in a population of patients using an optimized dynamic contrast-enhanced (DCE) imaging sequence and to estimate inter- and intrapatient variability. From these data, a representative AIF that may be used for realistic simulation studies can be extracted.

Methods: Thirty-nine female patients were imaged on multiple visits before and during a course of neoadjuvant chemotherapy for breast cancer.

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Molecular profiling and functional assessment of signalling pathways of advanced solid tumours are becoming increasingly available. However, their clinical utility in guiding patients' treatment remains unknown. Here, we assessed whether molecular profiling helps physicians in therapeutic decision making by analysing the molecular profiles of 1057 advanced cancer patient samples after failing at least one standard of care treatment using a combination of next-generation sequencing (NGS), immunohistochemistry (IHC) and other specific tests.

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Background: Angiogenesis is a validated clinical target in advanced epithelial ovarian cancer. Cediranib is an oral antiangiogenic vascular endothelial growth factor receptor 1-3 inhibitor that has shown antitumour activity in recurrent ovarian cancer. We assessed efficacy and safety of cediranib in combination with platinum-based chemotherapy and as continued maintenance treatment in patients with first relapse of platinum-sensitive ovarian cancer.

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Background: The ICON7 trial previously reported improved progression-free survival in women with ovarian cancer with the addition of bevacizumab to standard chemotherapy, with the greatest effect in patients at high risk of disease progression. We report the final overall survival results of the trial.

Methods: ICON7 was an international, phase 3, open-label, randomised trial undertaken at 263 centres in 11 countries across Europe, Canada, Australia and New Zealand.

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Ovarian cancer is an important health concern worldwide. The majority of patients present with advanced disease, and despite initial chemosensitivity, most relapse and die from their disease. Better therapeutic options are urgently required.

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Background: Angiogenesis plays a role in the biology of ovarian cancer. We examined the effect of bevacizumab, the vascular endothelial growth factor inhibitor, on survival in women with this disease.

Methods: We randomly assigned women with ovarian cancer to carboplatin (area under the curve, 5 or 6) and paclitaxel (175 mg per square meter of body-surface area), given every 3 weeks for 6 cycles, or to this regimen plus bevacizumab (7.

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Mucinous epithelial ovarian cancers (mEOC) are a relatively rare subset of ovarian cancers. Despite a relatively favourable outcome in early disease, the more frequent advanced presentation is associated with poorer response to platinum/taxane chemotherapies, and poorer survival, compared to serous ovarian cancers. We consider some of the fundamental clinico-pathological and molecular features, and existing clinical trial data regarding mEOC.

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Purpose: This double-blind, randomized, phase III clinical trial evaluated time to progression (TTP) and overall survival in women with metastatic breast cancer (MBC) who received sialyl-TN (STn) keyhole limpet hemocyanin (KLH) vaccine. Secondary endpoints included vaccine safety and immune response.

Experimental Design: The study population consisted of 1,028 women with MBC across 126 centers who had previously received chemotherapy and had had either a complete or a partial response or no disease progression.

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Purpose: To assess the significance of CA-125 regression as a prognostic indicator and predictor of optimal cytoreduction at interval debulking surgery (IDS) in women with ovarian or primary peritoneal carcinoma receiving neoadjuvant chemotherapy (NAC).

Methods: 63 women treated between 2004 and 2007 with neoadjuvant platinum-based chemotherapy followed by IDS were studied retrospectively. Pre-operative CA-125 values were used to calculate a regression coefficient (CA-125r) using exponential regression analysis.

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For many years the primary management of newly diagnosed advanced ovarian cancer has been cytoreductive surgery followed by chemotherapy, and the mainstay of follow-up of treated women has been serial assay of serum CA-125. The findings of 2 recent research protocols have a significant effect on these aspects of management.

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Background: We have conducted a series of four feasibility studies in stage Ic-IV ovarian cancer exploring six sequential first-line schedules with the same entry criteria in a total of 339 patients. Here we present the results of the sixth study, and an analysis of the overall series.

Methods: In this trial patients received 4 cycles of carboplatin AUC 7 every 3 weeks, followed by 4 cycles of concurrent paclitaxel 175 mg/m(2) (day 1) and gemcitabine 1000 mg/m(2) (days 1 and 8) every 3 weeks.

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Background: Combinations of anthracycline, taxane and fluoropyrimidine are highly active in advanced breast cancer (ABC). In a phase II study of epirubicin 50 mg/m(2), docetaxel 75 mg/m(2), and infusional 5-FU 200 mg/m(2)/day, we found dose-limiting neutropenia and frequent central venous catheter complications. An alternative approach has been tested using weekly fractionation of docetaxel, and oral capecitabine.

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Epithelial ovarian cancer (EOC) remains a major source of cancer morbidity and mortality, despite advances in surgical and chemotherapeutic management. The molecular pathways that control angiogenesis have been demonstrated to be key to the pathogenesis of EOC, and have been shown to have prognostic significance. Increased understanding of the pathways and molecules involved in angiogenesis has allowed the identification of a number of targets for antiangiogenic therapies and the development of a variety of antiangiogenic drugs.

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Purpose: To discover and validate serum glycoprotein biomarkers in ovarian cancer using proteomic-based approaches.

Experimental Design: Serum samples from a "discovery set" of 20 patients with ovarian cancer or benign ovarian cysts or healthy volunteers were compared by fluorescence two-dimensional differential in-gel electrophoresis and parallel lectin-based two-dimensional profiling. Validation of a candidate biomarker was carried out with Western blotting and immunoassay (n = 424).

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Background: This study sought to evaluate routine chest radiography following placement of tunneled central lines using combined ultrasound and fluoroscopic guidance.

Materials And Methods: A prospective study of 150 consecutive patients who underwent placement of tunneled central lines in the vascular radiology suite. Ultrasound-guided vein puncture was performed with an 18-gauge needle in each case, and the access site was noted.

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