Multiplex picodroplet digital PCR to detect KRAS mutations in circulating DNA from the plasma of colorectal cancer patients.

Background: Multiplex digital PCR (dPCR) enables noninvasive and sensitive detection of circulating tumor DNA with performance unachievable by current molecular-detection approaches. Furthermore, picodroplet dPCR facilitates simultaneous screening for multiple mutations from the same sample.

Methods: We investigated the utility of multiplex dPCR to screen for the 7 most common mutations in codons 12 and 13 of the KRAS (Kirsten rat sarcoma viral oncogene homolog) oncogene from plasma samples of patients with metastatic colorectal cancer.

[Cutaneous adverse reactions of EGFR (epidermal growth factor receptor)-inhibitors: therapeutic algorithm of the French PROCUR group].

The epidermal growth factor receptors (EGFR)-inhibitors are frequently responsible for cutaneous adverse drug reactions that may alter the patients' quality of life and hamper the continuation of treatment. We present here the experience of a group of French multidisciplinary experts - the PROCUR group (PRise en charge de la tOxicité CUtanée des anti-EGFR) - created in order to establish a therapeutic algorithm. It was built in three steps under the responsibility of a steering committee: (1) a systematic literature review was performed by a group of three dermatologists and one oncologist; (2) regional meetings evaluated practical aspect of the treatments in France; (3) a final meeting confrontating the practices in France and the evidence-based medicine including the steering committee, the bibliographic group, and oncologists, radiotherapists, dermatologists and hepato-gastroenterologists involved in regional scientific committees, resulted in a therapeutic algorithm, resulting in the collegial writing of this algorithm.

Circulating tumor cells in locally advanced pancreatic adenocarcinoma: the ancillary CirCe 07 study to the LAP 07 trial.

Background: Pancreatic carcinoma is one of the leading causes of cancer-related mortality. At the time of diagnosis, 30% of patients present with a locally advanced pancreatic carcinoma (LAPC). As circulating tumor cells (CTCs) count may be a surrogate of the cancer metastatic abilities, CTC detection rates and prognostic value were studied in a prospective cohort of LAPC patients.

A randomised phase III intergroup trial comparing high-dose infusional 5-fluorouracil with or without folinic acid with standard bolus 5-fluorouracil/folinic acid in the adjuvant treatment of stage III colon cancer: the Pan-European Trial in Adjuvant Colon Cancer 2 study.

Purpose: To investigate whether infusional high-dose 5-flurouracil (HD-FU) provides a significant improvement in recurrence-free survival (RFS) and overall survival (OS) compared with a standard bolus 5-FU regimen (Mayo Clinic) in patients with curatively resectable stage III colon cancer.

Methods: Patients (n=1601) were randomised to receive either the Mayo Clinic regimen or one of the three HD-FU regimens; LV5FU2, the Arbeitsgemeinschaft Internistische Onkologie (AIO) or the Grupo Espaňol para el Tratamiento Digestivos (TTD), the data from which were combined to provide the HD-FU arm for final analysis.

Results: Patients were evenly balanced for age, TMN, tumor grade and vascular and lymphatic invasion.

Taking into account successive treatment lines in the analysis of a colorectal cancer randomised trial.

The FFCD 2000-05 randomised trial included 410 patients with advanced colorectal cancer and compared a sequential arm S treated with 5-fluorouracil and leucovorin (LV5FU2) followed by FOLFOX (LV5FU2+oxaliplatin) and then FOLFIRI (LV5FU2+irinotecan) and a combination arm C that begins directly with FOLFOX followed by FOLFIRI. The first aim of this study was to analyse the prognostic effects on overall survival of disease progression, and of toxicities under first-line therapy. We also studied the benefit of introducing irinotecan in each arm.

Liver angulometry: a simple method to estimate liver volume and ratios.

Objectives: Volumetry is standard method for evaluating the volumes of the right liver (RL), left liver (LL), left lateral segments (LLS), total liver (TL) and future liver remnant (FLR). The aim of this study was to report a simple technique based on measurements of liver angles (angulometry) that can be used to predict liver ratios.

Methods: Fifty computed tomography (CT) scans obtained in subjects with normal liver were studied.

Geriatric factors predict chemotherapy feasibility: ancillary results of FFCD 2001-02 phase III study in first-line chemotherapy for metastatic colorectal cancer in elderly patients.

Purpose: Elderly patients form a heterogeneous population. Evaluation of geriatric factors may help evaluate a patient's health status to better adapt treatment.

Patients And Methods: Elderly patients with previously untreated metastatic colorectal cancer (mCRC) were randomly assigned to receive fluorouracil (FU) -based chemotherapy either alone or in combination with irinotecan (IRI) in the Fédération Francophone de Cancérologie Digestive (FFCD) 2001-02 study.

Infrared imaging as a cancer diagnostic tool: introducing a new concept of spectral barcodes for identifying molecular changes in colon tumors.

Complementary diagnostic methods to conventional histopathology are under scrutiny for various types of cancers for rapid and molecular level diagnostics. In this perspective, a biophotonic approach based on infrared spectral micro-imaging combined with multivariate statistical analysis has been implemented on colon tissues. The ability of infrared imaging to investigate the intrinsic biochemical features of cells and tissues has been exploited to develop a new concept of spectral bar coding.

Impact of FOLFIRINOX compared with gemcitabine on quality of life in patients with metastatic pancreatic cancer: results from the PRODIGE 4/ACCORD 11 randomized trial.

Purpose: To compare the quality of life (QoL) of patients receiving oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) or gemcitabine as first-line chemotherapy and to assess whether pretreatment QoL predicts survival in patients with metastatic pancreatic cancer.

Patients And Methods: Three hundred forty-two patients with performance status 0 or 1 were randomly assigned to receive FOLFIRINOX (oxaliplatin, 85 mg/m(2); irinotecan, 180 mg/m(2); leucovorin, 400 mg/m(2); and fluorouracil, 400 mg/m(2) bolus followed by 2,400 mg/m(2) 46-hour continuous infusion, once every 2 weeks) or gemcitabine 1,000 mg/m(2) weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. QoL was assessed using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire C30 every 2 weeks.

Prognostic factors in patients with non resectable metastatic colorectal cancer in the era of targeted biotherapies: relevance of Köhne's risk classification.

Background: Köhne's prognostic classification has been previously proposed, based on performance status, alkaline phosphatase level, number of metastatic sites and white blood cells count.

Aims: To identify prognostic factors for survival and to assess the validity of Köhne's classification, in the era of targeted biotherapies, in patients treated with chemotherapy for non resectable metastatic colorectal cancer.

Methods: A total of 290 consecutive patients were retrospectively identified in all gastroenterology units of one French county, between 2004 and 2008.

Pancreas cancer-associated polymyositis of the legs regressing after cephalic duodenopancreatectomy: case report and review of the literature.

Context: Inflammatory myopathy, such as polymyositis, has been widely reported as paraneoplastic syndrome associated with various malignancies. However, its association with pancreas adenocarcinoma is very uncommon.

Case Report: A case of a patient with paraneoplastic polymyositis of both legs associated with pancreatic adenocarcinoma is reported here.

The added value of quality of life (QoL) for prognosis of overall survival in patients with palliative hepatocellular carcinoma.

Background & Aims: Several prognostic classifications (PCs) have been developed for use in palliative care in patients with hepatocellular carcinoma (HCC). We have recently suggested that CLIP combined with WHO PS has the greatest discriminative power. We evaluated the prognostic value of quality of life (QoL) data and whether the latter could improve classification of palliative HCC patients.

Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial.

Background: No treatment options are available for patients with metastatic colorectal cancer that progresses after all approved standard therapies, but many patients maintain a good performance status and could be candidates for further therapy. An international phase 3 trial was done to assess the multikinase inhibitor regorafenib in these patients.

Methods: We did this trial at 114 centres in 16 countries.

Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial.

Background: Bevacizumab plus fluoropyrimidine-based chemotherapy is standard treatment for first-line and bevacizumab-naive second-line metastatic colorectal cancer. We assessed continued use of bevacizumab plus standard second-line chemotherapy in patients with metastatic colorectal cancer progressing after standard first-line bevacizumab-based treatment.

Methods: In an open-label, phase 3 study in 220 centres in Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany, the Netherlands, Norway, Portugal, Saudi Arabia, Spain, Sweden, and Switzerland, patients (aged ≥18 years) with unresectable, histologically confirmed metastatic colorectal cancer progressing up to 3 months after discontinuing first-line bevacizumab plus chemotherapy were randomly assigned in a 1:1 ratio to second-line chemotherapy with or without bevacizumab 2·5 mg/kg per week equivalent (either 5 mg/kg every 2 weeks or 7·5 mg/kg every 3 weeks, intravenously).

Infrared spectral imaging as a novel approach for histopathological recognition in colon cancer diagnosis.

Innovative diagnostic methods are the need of the hour that could complement conventional histopathology for cancer diagnosis. In this perspective, we propose a new concept based on spectral histopathology, using IR spectral micro-imaging, directly applied to paraffinized colon tissue array stabilized in an agarose matrix without any chemical pre-treatment. In order to correct spectral interferences from paraffin and agarose, a mathematical procedure is implemented.

Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer.

Purpose: The ACCORD 12 trial investigated the value of two different preoperative chemoradiotherapy (CT-RT) regimens in T3-4 Nx M0 resectable rectal cancer. Clinical results are reported after follow-up of 3 years.

Patients And Methods: Between November 2005 and July 2008, a total of 598 patients were randomly assigned to preoperative CT-RT with CAP45 (45-Gy RT for 5 weeks with concurrent capecitabine) or CAPOX50 (50-Gy RT for 5 weeks with concurrent capecitabine and oxaliplatin).

Impact of primary tumour resection on survival of patients with colorectal cancer and synchronous metastases treated by chemotherapy: results from the multicenter, randomised trial Fédération Francophone de Cancérologie Digestive 9601.

Objective: To assess the impact of primary tumour resection on overall survival (OS) of patients diagnosed with stage IV colorectal cancer (CRC).

Design: Among the 294 patients with non-resectable colorectal metastases enrolled in the Fédération Francophone de Cancérologie Digestive (FFCD) 9601 phase III trial, which compared different first-line single-agent chemotherapy regimens, 216 patients (73%) presented with synchronous metastases at study entry and constituted the present study population. Potential baseline prognostic variables including prior primary tumour resection were assessed by univariate and multivariate Cox analyses.

Outcome of patients with platelet-derived growth factor receptor alpha-mutated gastrointestinal stromal tumors in the tyrosine kinase inhibitor era.

Purpose: Platelet-derived growth factor receptor-alpha (PDGFRA) mutations are found in approximately 5% to 7% of advanced gastrointestinal stromal tumors (GIST). We sought to extensively assess the activity of imatinib in this subgroup.

Experimental Design: We conducted an international survey among GIST referral centers to collect clinical data on patients with advanced PDGFRA-mutant GISTs treated with imatinib for advanced disease.

Is palliative laparoscopic hyperthermic intraperitoneal chemotherapy effective in patients with malignant hemorrhagic ascites?

Malignant hemorrhagic ascites may complicate the terminal evolution of digestive cancers with peritoneal carcinomatosis. It has a bad influence on prognosis and may severely impair patients' quality of life. Palliative laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) has been proposed to treat debilitating malignant ascites.

[News in management of colorectal cancer at JFHOD 2012 meeting].

All aspects of the management of colorectal cancer were presented during the 2012 edition of JFHOD meeting, from screening to new drugs tested in metastatic situation. It was confirmed that an average number of more than 0.8 detected polyps was a quality criteria of screening colonoscopies performed for positive Hemoccult(®).

Management of cutaneous adverse events induced by anti-EGFR (epidermal growth factor receptor): a French interdisciplinary therapeutic algorithm.

Purpose: Cutaneous adverse events induced by epidermal growth factor receptor (EGFR) inhibitors can hamper the patients' quality of life. The aim of our work was to draft an algorithm for the optimised management of this skin toxicity.

Methods: This algorithm was built in three steps under the responsibility of a steering committee.

Induction chemotherapy and dose intensification of the radiation boost in locally advanced anal canal carcinoma: final analysis of the randomized UNICANCER ACCORD 03 trial.

Purpose: Concomitant radiochemotherapy (RCT) is the standard for locally advanced anal canal carcinoma (LAACC). Questions regarding the role of induction chemotherapy (ICT) and a higher radiation dose in LAACC are pending. Our trial was designed to determine whether dose escalation of the radiation boost or two cycles of ICT before concomitant RCT lead to an improvement in colostomy-free survival (CFS).

What is the clinical benefit of preoperative chemoradiotherapy with 5FU/leucovorin for T3-4 rectal cancer in a pooled analysis of EORTC 22921 and FFCD 9203 trials: surrogacy in question?

Background: Two phase III trials of neoadjuvant treatment in T3-4 rectal cancer established that adding chemotherapy (CRT) to radiotherapy (RT) improves pathological complete response (pCR) and local control (LC). We combined trials to assess the clinical benefit of CRT on overall (OS) and progression free survival (PFS) and to explore the surrogacy of pCR and LC.

Patients And Methods: Individual patient data from European Organisation for Research and Treatment of Cancer (EORTC) 22921 (1011 patients) and FFCD 9203 (756 patients) were pooled.

Serum creatine kinase increase in patients treated with tyrosine kinase inhibitors for solid tumors.

Regarding the frequency of muscular complains with the use of tyrosine kinase inhibitors (TKIs), we hypothesize that creatine kinase (CK) elevation may be more frequent than usually reported. We conducted a prospective study on patients treated with TKIs for solid tumors, to assess the incidence of CK increase on treatment. Most of the patients (105/155) had a gastrointestinal stromal tumor.