A need to simplify informed consent documents in cancer clinical trials. A position paper of the ARCAD Group.

Background: In respect of the principle of autonomy and the right of self-determination, obtaining an informed consent of potential participants before their inclusion in a study is a fundamental ethical obligation. The variations in national laws, regulations, and cultures contribute to complex informed consent documents for patients participating in clinical trials. Currently, only few ethics committees seem willing to address the complexity and the length of these documents and to request investigators and sponsors to revise them in a way to make them understandable for potential participants.

How health-related quality of life assessment should be used in advanced colorectal cancer clinical trials.

Traditionally, the efficacy of cancer treatment in patients with advance or metastatic disease in clinical studies has been studied using overall survival and more recently tumor-based end points such as progression-free survival, measurements of response to treatment. However, these seem not to be the relevant clinical end points in current situation if such end points were no validated as surrogate of overall survival to demonstrate the clinical efficacy. Appropriate, meaningful, primary patient-oriented and patient-reported end points that adequately measure the effects of new therapeutic interventions are then crucial for the advancement of clinical research in metastatic colorectal cancer to complement the results of tumor-based end points.

Trends in colorectal cancer mortality in Europe: retrospective analysis of the WHO mortality database.

Objective: To examine changes in colorectal cancer mortality in 34 European countries between 1970 and 2011.

Design: Retrospective trend analysis.

Data Source: World Health Organization mortality database.

Disease-free survival as a surrogate for overall survival in adjuvant trials of gastric cancer: a meta-analysis.

Background: In investigations of the effectiveness of surgery and adjuvant chemotherapy for gastric cancers, overall survival (OS) is considered the gold standard endpoint. However, the disadvantage of using OS as the endpoint is that it requires an extended follow-up period. We sought to investigate whether disease-free survival (DFS) is a valid surrogate for OS in trials of adjuvant chemotherapy for gastric cancer.

Progression-free survival as a surrogate for overall survival in advanced/recurrent gastric cancer trials: a meta-analysis.

The traditional endpoint for assessing efficacy of chemotherapies for advanced/recurrent gastric cancer is overall survival (OS), but OS requires prolonged follow-up. We investigated whether progression-free survival (PFS) is a valid surrogate for OS. Using individual patient data from the GASTRIC meta-analysis, surrogacy of PFS was assessed through the correlation between the endpoints and through the correlation between the treatment effects on the endpoints.

Role of chemotherapy for advanced/recurrent gastric cancer: an individual-patient-data meta-analysis.

We conducted an individual-patient-data meta-analysis of the efficacy of chemotherapy on overall survival (OS) and progression-free survival (PFS) in advanced/recurrent gastric cancer (AGC). Our primary research question was whether the experimental arms of the trials included in the meta-analysis showed a benefit as compared with their corresponding control arms. MEDLINE (up to 2010), Cochrane Central Register of Controlled Trials, National Institutes of Health (NIH) trial registry and proceedings of major oncologic and gastrointestinal cancer meetings were searched.

A phase II randomized study of combined infusional leucovorin sodium and 5- FU versus the leucovorin calcium followed by 5-FU both in combination with irinotecan or oxaliplatin in patients with metastatic colorectal cancer.

Background: Leucovorin Sodium (LV/Na) has a high solubility, and is stable when given with continuous infusion of 5-FU. It could maintain significant plasma concentration of 5, 10-meTHF during the whole 5-FU perfusion with the potential of increasing 5-FU cytotoxicity. We conducted a randomized phase II clinical trial on leucovorin calcium (LV/Ca) and LV/Na in metastatic colorectal cancer patients (mCRC).

Differential diagnosis of adnexal masses: sequential use of the risk of malignancy index and HistoScanning, a novel computer-aided diagnostic tool.

Objective: To assess the value of ovarian Histo-Scanning(™) , a novel computerized technique for interpreting ultrasound data, in combination with the risk of malignancy index (RMI) in improving triage for women with adnexal masses.

Methods: RMI indices were assessed in 199 women enrolled in a prospective study to investigate the use of HistoScanning. Ultrasound scores were obtained by blinded analysis of archived images.

Mathematical models to discriminate between benign and malignant adnexal masses: potential diagnostic improvement using ovarian HistoScanning.

Purpose: Accurate preoperative clinical assessment of adnexal masses can optimize outcomes by ensuring appropriate and timely surgery. This article addresses whether a new technology, ovarian HistoScanning, has an additional diagnostic value in mathematical models developed for the differential diagnosis of adnexal masses.

Patients And Methods: Transvaginal sonography-based morphological variables were obtained through blinded analysis of archived images in 199 women enrolled in a prospective study to assess the performance of ovarian HistoScanning.

A new computer-aided diagnostic tool for non-invasive characterisation of malignant ovarian masses: results of a multicentre validation study.

Objectives: To prospectively assess an innovative computer-aided diagnostic technology that quantifies characteristic features of backscattered ultrasound and theoretically allows transvaginal sonography (TVS) to discriminate benign from malignant adnexal masses.

Methods: Women (n = 264) scheduled for surgical removal of at least one ovary in five centres were included. Preoperative three-dimensional (3D)-TVS was performed and the voxel data were analysed by the new technology.

Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials.

Purpose: Adjuvant systemic chemotherapy administered after surgical resection of colorectal cancer metastases may reduce the risk of recurrence and improve survival, but its benefit has never been demonstrated. Two phase III trials (Fédération Francophone de Cancérologie Digestive [FFCD] Trial 9002 and the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada Clinical Trials Group/Gruppo Italiano di Valutazione Interventi in Oncologia [ENG] trial) used a similar design and showed a trend favoring adjuvant chemotherapy, but both had to close prematurely because of slow accrual, thus lacking the statistical power to demonstrate the predefined difference in survival. We report here a pooled analysis based on individual data from these two trials.

The accuracy of transrectal ultrasonography supplemented with computer-aided ultrasonography for detecting small prostate cancers.

Objective: To determine the extent to which computer-aided ultrasonography of the prostate (HistoScanning, Advanced Medical Diagnostics, Waterloo, Belgium) can identify tumour foci that correspond to a volume of >or=0.50 mL.

Patients And Methods: Between September 2004 and February 2006, 29 men were HistoScanned before scheduled radical prostatectomy.

Cost-effectiveness of cetuximab in combination with irinotecan compared with current care in metastatic colorectal cancer after failure on irinotecan--a Belgian analysis.

This analysis compared the cost-effectiveness in Belgium of cetuximab plus irinotecan with current current care in the treatment of epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer (CRC) that has failed irinotecan-containing therapy. Treatment outcomes and medical resource use data for patients receiving cetuximab plus irinotecan from the BOND study were compared with those from a matched group of patients (current care) (n = 66). Two scenarios were considered in which cetuximab was discontinued either at 6 weeks or at 12 weeks if there was no tumour response at those time points.

Irinotecan combined with infusional 5-fluorouracil/folinic acid or capecitabine plus celecoxib or placebo in the first-line treatment of patients with metastatic colorectal cancer. EORTC study 40015.

Background: The study aimed to demonstrate the noninferiority of capecitabine to 5-fluorouracil (5-FU)/folinic acid (FA), in relation to progression-free survival (PFS) after first-line treatment of metastatic colorectal cancer and the benefit of adding celecoxib (C) to irinotecan/fluoropyrimidine regimens compared with placebo (P).

Patients And Methods: Patients were randomly assigned to receive FOLFIRI: irinotecan (180 mg/m(2) i.v.

Computer-aided ultrasonography (HistoScanning): a novel technology for locating and characterizing prostate cancer.

Objective: To assess the extent to which prostate HistoScanning (PHS), a new ultrasound-based technology that uses computer-aided analysis to quantify tissue disorganization induced by malignant processes, can identify and characterize foci of prostate cancer compared with step-sectioned radical prostatectomy (RP) specimens.

Patients And Methods: Between September 2004 and February 2006, 29 men had PHS before their scheduled RP. A three-dimensional ultrasound raw-data file was acquired, and PHS analysed regions of interest (ROI) corresponding to tissue volumes of approximately 0.

Managing older patients with colorectal cancer.

Colorectal cancer (CRC) is predominantly a disease of older persons, and our population is aging. Physicians and their older patients commonly face the dilemma of whether or not to give/receive systemic chemotherapy for CRC. Evidence supports the safety and efficacy of systemic chemotherapy in fit older patients motivated enough to enroll onto clinical trials.

Long-term survival of patients downstaged by oxaliplatin and 5-fluorouracil combination followed by rescue surgery for unresectable colorectal liver metastases.

Objectives: To evaluate long-term survival of patients resected for primarily unresectable colorectal liver metastases downstaged by systemic chemotherapy.

Methods: Among a group of 82 patients with advanced colorectal cancer, 39 had unresectable liver metastases. After treatment with systemic 3-weekly 5FU/folinic acid/oxaliplatin chemotherapy, the outcome of 11 patients made resectable thanks to chemotherapy was compared to that of 28 patients who were not.

Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer.

Purpose: Oxaliplatin, fluorouracil, and leucovorin are commonly used to treat advanced and resected colorectal cancer. This analysis compares the safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly (FOLFOX4) in patients age younger than and at least 70 years.

Patients And Methods: This retrospective analysis included 3,742 colorectal cancer patients (614 age > or = 70) from four clinical trials testing FOLFOX4 in the adjuvant, first-, and second-line settings.

Colorectal cancer (CRC) screening using sigmoidoscopy followed by colonoscopy: a feasibility and efficacy study on a cancer institute based population.

Background: Advanced distal neoplasia found at sigmoidoscopy could be the marker for more proximal lesions.

Patients And Methods: In the setting of a screening clinic, subjects underwent flexible sigmoidoscopy. If no significant lesion was found, sigmoidoscopy was planned after 5 years.

Correlation between the response to cetuximab alone or in combination with irinotecan and the activated/phosphorylated epidermal growth factor receptor in metastatic colorectal cancer.

Despite staining positive for the epidermal growth factor receptor (EGFR), a significant number of EGFR-expressing colorectal cancers are resistant to cetuximab, a chimeric monoclonal antibody directed against EGFR. Activation of EGFR through the autophosphorylation of its tyrosine residues stimulates different signaling downstream pathways and may reflect the level of receptor utilization by the tumor. This study investigated activated/phosphorylated EGFR (pEGFR) in 23 patients with EGFR-positive metastatic colorectal cancer refractory to irinotecan and treated with cetuximab, alone or in combination with irinotecan.

Clinical Cancer Advances 2005: major research advances in cancer treatment, prevention, and screening--a report from the American Society of Clinical Oncology.

This year, for the first time, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances 2005: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant clinical research presented or published over the past year across all cancer types. ASCO embarked on this project to provide the public, patients, policymakers, and physicians with an accessible summary of the year's most important research advances. While not intended to serve as a comprehensive review, this report provides a year-end snapshot of research that will have the greatest impact on patient care.