Analytical Validation of Multiplex Biomarker Assay to Stratify Colorectal Cancer into Molecular Subtypes.

Previously, we classified colorectal cancers (CRCs) into five CRCAssigner (CRCA) subtypes with different prognoses and potential treatment responses, later consolidated into four consensus molecular subtypes (CMS). Here we demonstrate the analytical development and validation of a custom NanoString nCounter platform-based biomarker assay (NanoCRCA) to stratify CRCs into subtypes. To reduce costs, we switched from the standard nCounter protocol to a custom modified protocol.

Feasibility of Capecitabine and Oxaliplatin Combination Chemotherapy Without Central Venous Access Device in Patients With Stage III Colorectal Cancer.

Background: 5-Fluorouracil and leucovorin plus oxaliplatin (FOLFOX) or capecitabine plus oxaliplatin (XELOX) is a standard adjuvant treatment for patients with stage III colon cancer (CC). Capecitabine is an oral fluoropyrimidine, and administration of oxaliplatin does not necessarily require the insertion of a central venous access device (CVAD). We evaluated the feasibility of XELOX without a CVAD as adjuvant treatment in patients with stage III CC.

[Global brain metastases management strategy: a multidisciplinary-based approach].

Brain metastases management has evolved over the last fifteen years and may use varying strategies, including more or less aggressive treatments, sometimes combined, leading to an improvement in patient's survival and quality of life. The therapeutic decision is subject to a multidisciplinary analysis, taking into account established prognostic factors including patient's general condition, extracerebral disease status and clinical and radiological presentation of lesions. In this article, we propose a management strategy based on the state of current knowledge and available therapeutic resources.

Pathological response and safety of two neoadjuvant strategies with bevacizumab in MRI-defined locally advanced T3 resectable rectal cancer: a randomized, noncomparative phase II study.

Background: In T3 rectal cancer (RC), preoperative chemoradiotherapy [5-fluorouracil (5-FU-RT)] reduces local recurrences, but does not affect overall survival. New therapeutic options are still necessary to improve clinical outcomes.

Patients And Methods: This randomized, noncomparative, open-label, multicenter, two arms, phase II study was conducted in MRI-defined locally advanced T3 resectable RC.

Slug controls stem/progenitor cell growth dynamics during mammary gland morphogenesis.

Background: Morphogenesis results from the coordination of distinct cell signaling pathways controlling migration, differentiation, apoptosis, and proliferation, along stem/progenitor cell dynamics. To decipher this puzzle, we focused on epithelial-mesenchymal transition (EMT) "master genes". EMT has emerged as a unifying concept, involving cell-cell adhesion, migration and apoptotic pathways.

A cluster randomized trial to evaluate a health education programme "Living with Sun at School".

Over-exposure to sunlight increases the risk of skin cancers, particularly when exposure occurs during childhood. School teachers can play an active role in providing an education programme that can help prevent this. "Living with the Sun," (LWS) is a sun safety education program for school children based on a handy guide for classroom activities designed to improve children's knowledge, but moreover to positively modify their sun safety attitudes and behaviours.

Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial.

Purpose: After curative resection, the prognosis of gastroesophageal adenocarcinoma is poor. This phase III trial was designed to evaluate the benefit in overall survival (OS) of perioperative fluorouracil plus cisplatin in resectable gastroesophageal adenocarcinoma.

Patients And Methods: Overall, 224 patients with resectable adenocarcinoma of the lower esophagus, gastroesophageal junction (GEJ), or stomach were randomly assigned to either perioperative chemotherapy and surgery (CS group; n = 113) or surgery alone (S group; n = 111).

Quantification and clinical relevance of gene amplification at chromosome 17q12-q21 in human epidermal growth factor receptor 2-amplified breast cancers.

Introduction: Human epidermal growth factor receptor 2 (HER2)-amplified breast cancers represent a tumor subtype with chromosome 17q rearrangements that lead to frequent gene amplifications. The aim of this study was to quantify the amplification of genes located on chromosome 17q and to analyze the relations between the pattern of gene amplifications and the patients' characteristics and survival.

Methods: Patients with HER2-positive breast tumors (HER2 score of 3+ by immunohistochemistry or positive for HER2 amplification by fluorescence in situ hybridization (FISH)) (n = 86) and with HER2-negative breast tumors (n = 40) (negative controls) were included in this study.

A pilot study of gemcitabine in combination with oxaliplatin and vinorelbine in patients with metastatic bladder cancer.

Aim: To assess the safety and to obtain preliminary data on the efficacy of the three-drug combination chemotherapy with gemcitabine, oxaliplatin and vinorelbine in patients with metastatic bladder cancer.

Patients And Methods: Patients with metastatic or locally unresectable advanced bladder cancer who had received either no or one previous systemic chemotherapy regimen were eligible. All patients received intravenous gemcitabine 700 mg/m(2) and vinorelbine 25 mg/m(2) on day 1, then intravenous oxaliplatin 85 mg/m(2) on day 2, every 14 days.

Phase I study of irinotecan and cisplatin in combination with pelvic radiotherapy in the treatment of locally advanced cervical cancer: A GINECO trial.

Purpose: To define the recommended dose of the association of weekly irinotecan (Iri) and cisplatin (CP) with pelvic radiotherapy in Locally Advanced Cervical Cancer.

Patients And Methods: Stage IB2-IV cervix cancer patients were treated with escalating doses of Iri starting from 30 mg/m(2) and a fixed dose of CP at 20 mg/m(2), both weekly concomitantly with a 45-Gy pelvic irradiation.

Results: Fifteen patients entered the study, 6 at level 1 (Iri 30 mg/m(2)), 3 at level 2 (Iri 40 mg/m(2)) and 6 at intermediate dose (Iri 35 mg/m(2)).

[Technical considerations for KRAS testing in colorectal cancer. The pathologist's point of view].

The KRAS status is now a mandatory prerequisite in order to treat metastatic colorectal patients with anti-EGFR (epidermal growth factor receptor) antibodies, such as cetuximab (Erbitux) or panitumumab (Vectibix). KRAS mutations are unambiguously linked to a lack of response to these targeted therapies and to a poor outcome. The optimal determination of the KRAS status should be based on coordination between pathologists and biologists.

Physicochemical stability of oxaliplatin in 5% dextrose injection stored in polyvinyl chloride, polyethylene, and polypropylene infusion bags.

Purpose: The physicochemical stability of extemporaneous dilutions of oxaliplatin in 5% dextrose injection stored in polyvinyl chloride (PVC), polypropylene, and polyethylene infusion bags was studied.

Methods: Oxaliplatin 100 mg/20 mL concentrated solution was diluted in 100 mL of 5% dextrose injection in PVC, polypropylene, and polyethylene infusion bags to produce nominal oxaliplatin concentrations of 0.2 and 1.

A phase III randomised trial of LV5FU2 + irinotecan versus LV5FU2 alone in adjuvant high-risk colon cancer (FNCLCC Accord02/FFCD9802).

Background: This multicenter adjuvant phase III trial evaluated the addition of irinotecan to LV5FU2 in colon cancer patients at high risk of relapse.

Patients And Methods: A total of 400 patients with histologically proven primary colon cancer with postoperative N1 detected by occlusion/perforation or N2 were randomised to: A-LV5FU2 [leucovorin 200 mg/m(2), 2-h infusion, 5-fluorouracil (5-FU) 400 mg/m(2) bolus, 600 mg/m(2) 22-h continuous infusion, days 1 and 2] or B-LV5FU2 + IRI (irinotecan 180 mg/m(2) 90-min infusion day 1 + LV5FU2) fortnightly for 12 cycles. Primary end point was disease-free survival (DFS).

Impact of Fc{gamma}RIIa-Fc{gamma}RIIIa polymorphisms and KRAS mutations on the clinical outcome of patients with metastatic colorectal cancer treated with cetuximab plus irinotecan.

Purpose: The antiepidermal growth factor receptor antibody cetuximab shows activity in irinotecan-refractory metastatic colorectal cancer (mCRC), mainly in wild-type KRAS tumors. Cetuximab may also exert antitumor effects through antibody-dependent cell-mediated cytotoxicity (ADCC) in which antibody Fc portion interacts with Fc receptors (FcgammaRs) expressed by immune cells. ADCC is influenced by FcgammaRIIa-H131R and FcgammaRIIIa-V158F polymorphisms that are clinically relevant in follicular lymphoma and metastatic breast cancer treated with rituximab and trastuzumab, respectively.

Survival and reproductive function of 52 women treated with surgery and bleomycin, etoposide, cisplatin (BEP) chemotherapy for ovarian yolk sac tumor.

Background: Ovarian yolk sac tumor (YST) is a very rare malignancy arising in young women. Chemotherapy has dramatically improved the prognosis. Current treatment consists of surgery followed by bleomycin, etoposide, and cisplatin (BEP) chemotherapy.

A randomized, prospective study using the LPG technique in treating radiation-induced skin fibrosis: clinical and profilometric analysis.

Background/purpose: Cutaneous fibrosis is the quite mandatory sequela after a breast cancer treated by radiotherapy and it induces more or less important functional troubles. The LPG technique is a technique of mechanical massage that allows skin mobilization by folding/unfolding. The aim of this study was to evaluate the changes on irradiated skin before and after LPG treatment by clinical and skin replica analysis.

Randomized trial comparing bleomycin/etoposide/cisplatin with alternating cisplatin/cyclophosphamide/doxorubicin and vinblastine/bleomycin regimens of chemotherapy for patients with intermediate- and poor-risk metastatic nonseminomatous germ cell tumors: Genito-Urinary Group of the French Federation of Cancer Centers Trial T93MP.

Purpose: Two chemotherapy regimens for intermediate- and poor-risk metastatic nonseminomatous germ cell tumors were compared for efficacy and toxicity.

Patients And Methods: From February 1994 to February 2000, 190 patients were randomly assigned between either four cycles of BEP (bleomycin 30 mg d1, d8, d15; etoposide 100 mg/m(2) d1-5; cisplatin 20 mg/m(2) d1-5) or four to six alternating cycles of CISCA/VB (cyclophosphamide 400 mg/m(2) d1-2, doxorubicin 35 mg/m(2) d1-2, cisplatin 100 mg/m(2) d3/vinblastine 2.5 mg/m(2) d1-5, bleomycin 25 mg/m(2) d1-5).

[Interim analyses].

The methodological principles for the planning of interim analyses in a phase III clinical trial are presented in this article. The case for superiority, non-inferiority and futility, and the roles of Data Monitoring Committees are summarized. Several examples are presented to illustrate the methodology and to help investigators by better understanding and planning interim analyses in a phase III clinical trial.

Small cell carcinoma with concomitant adenocarcinoma arising in a Barrett's oesophagus: report of a case with a favourable behaviour.

Most Barrett's oesophagus-associated cancers are adenocarcinomas which occur in a pure form. They are rarely combined with another type of malignancy, such as endocrine tumours. Within the endocrine spectrum, small cell carcinomas (SmCC) usually have a highly aggressive behaviour with a poor prognosis.

Detection of single-nucleotide polymorphisms in cancer-related genes by minisequencing on a microelectronic DNA chip.

The ability to realize simultaneous genotyping of multiple single-nucleotide polymorphisms or mutations is valuable in DNA samples from complex multigenic pathologies such as cancer. In this way, the complexity (number of hybridization units per chip) of the developed MICAM DNA chip, and the orientation of the grafted pyrrole oligonucleotides, make it particularly well adapted to the analysis of single-nucleotide polymorphisms/mutations in multiple potential tumoral markers. The proposed genotyping methodology is based on solid-phase minisequencing, where oligonucleotides are designed to anneal immediately upstream of the polymorphism sites, and labeled dideoxynucleotides are used as substrates for polymerase extension.

[Angiogenesis targeting in renal carcinomas].

Angiogenesis targeting with inhibitors of VEGF receptors is currently modifying in depth the treatment strategy of metastatic clear cell renal carcinoma. Although immunotherapy remains prescribed in selected patients with good prognosis, sunitinib and sorafenib are presently the most active agents in this malignancy. The results available, in terms of response as in terms of progression-free survival, argue in favour of the use of sunitinib in first line.

Tritherapy with fluorouracil/leucovorin, irinotecan and oxaliplatin (FOLFIRINOX): a phase II study in colorectal cancer patients with non-resectable liver metastases.

Purpose: To assess the rate of R(0) resection of liver metastases achieved after chemotherapy with FOLFIRINOX.

Patients And Methods: Patients with histologically proven primary colorectal cancer and bidimensionally measurable liver metastasis, not fully resectable based on technical inability to achieve R(0) resection, but potentially resectable after tumor reduction, were given FOLFIRINOX: oxaliplatin 85 mg/m(2), irinotecan 180 mg/m(2), leucovorin 400 mg/m(2), bolus fluorouracil 400 mg/m(2) and fluorouracil 46-h continuous IV infusion 2,400 mg/m(2), every 2 weeks for a maximum of 12 cycles.

Results: Thirty-four patients were enrolled.

Docetaxel and cisplatin in patients with metastatic androgen independent prostate cancer and circulating neuroendocrine markers.

Purpose: A link between neuroendocrine cell differentiation and resistance to androgen deprivation has been observed in prostate cancer, suggesting the possible efficacy of specific treatments. We assessed the efficacy and toxicity of a chemotherapy regimen combining docetaxel and cisplatin in men with androgen independent prostatic adenocarcinoma and circulating neuroendocrine markers.

Materials And Methods: A total of 41 patients were treated with a combination of 75 mg/m(2) docetaxel and 75 mg/m(2) cisplatin every 3 weeks for a maximum of 6 cycles.

[Chemotherapy for metastatic germ cell tumours of the testis].

The gold standard regimen for metastatic testicular germ cell tumours is a combination of bleomycin, etoposide and cisplatin. The number of cycles is defined by pathology (seminoma or non seminoma) and the prognostic criteria of the international classification (degree of elevation of serum tumour markers and presence or not of non pulmonary visceral metastases). The surgical resection of all residual metastatic masses is mandatory after the normalization of serum tumour markers in non seminoma patients.