Upfront primary tumour resection and survival in synchronous metastatic colorectal cancer according to primary tumour location and RAS status: Pooled analysis of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD).

Introduction: Retrospective studies and meta-analyses suggest that upfront primary tumour resection (UPTR) confers a survival benefit in patients with asymptomatic unresectable metastatic colorectal cancer (mCRC) undergoing chemotherapy, however a consensus of its role in routine clinical practice in the current era of targeted therapies is lacking. This retrospective study aimed to analyse the survival benefit of UPTR in terms of tumour location and mutational status, in patients with synchronous mCRC receiving chemotherapy and targeted therapy.

Patients And Methods: Survival was analysed in a pooled cohort of synchronous mCRC patients treated with a first-line anti-VEGF or anti-EGFR inhibitor in seven trials of the Spanish TTD group, according to UPTR, tumour-sidedness and mutational profiling.

First-Line Biological Agents Plus Chemotherapy in Older Patients with Metastatic Colorectal Cancer: A Retrospective Pooled Analysis.

Background: Biologicals, in combination with chemotherapy, are recommended as first-line treatment of metastatic colorectal cancer (mCRC); however, evidence guiding the appropriate management of older patients with mCRC is limited.

Objective: This study was undertaken to compare the efficacy and safety outcomes in older versus younger patients with mCRC who received first-line biological therapy.

Methods: This retrospective analysis used pooled data from five trials undertaken by the Spanish Cooperative Group for the Treatment of Digestive Tumours.

FOLFOXIRI plus bevacizumab versus FOLFOX plus bevacizumab for patients with metastatic colorectal cancer and ≥3 circulating tumour cells: the randomised phase III VISNÚ-1 trial.

Purpose: 5-Fluorouracil/leucovorin, oxaliplatin, irinotecan (FOLFOXIRI) plus bevacizumab is more effective than doublets plus bevacizumab as first-line therapy for metastatic colorectal cancer, but is not widely used because of concerns about toxicity and lack of predictive biomarkers. This study was designed to explore the role of circulating tumour cell (CTC) count as a biomarker to select patients for therapy with FOLFOXIRI-bevacizumab.

Patients And Methods: VISNÚ-1 was a multicentre, open-label, randomised, phase III study in patients with previously untreated, unresectable, metastatic colorectal carcinoma and ≥3 CTC/7.

Phase I/II trial of sequential treatment of nab-paclitaxel in combination with gemcitabine followed by modified FOLFOX chemotherapy in patients with untreated metastatic exocrine pancreatic cancer: Phase I results.

Background: Although occasioned through different mechanisms, the potential neurotoxicity and also haematological toxicity of nab-paclitaxel and oxaliplatin-based chemotherapy regimen were studied in this trial, which aimed to determine the maximum-tolerated dose (MTD) and to evaluate safety and efficacy of the combination in a sequential regimen of nab-paclitaxel, gemcitabine (GEM) and modified FOLFOX (mFOLFOX) in untreated patients with metastatic pancreatic ductal adenocarcinoma (PDAC).

Materials And Methods: Treatment consisted of nab-paclitaxel (125/100 mg/m) plus GEM (1000/800 mg/m) on days 1, 8 and 15, followed by mFOLFOX (oxaliplatin [85/75/65 mg/m], 5-FU bolus [400/300/200 mg/m], 5-FU infusion [2400/2000/1600 mg/m]) on day 28, of a 42-day cycle. Patients were enrolled at the highest dose level with a subsequent 3 + 3 dose de-escalation plan.

Association Between Baseline Circulating Tumor Cells, Molecular Tumor Profiling, and Clinical Characteristics in a Large Cohort of Chemo-naïve Metastatic Colorectal Cancer Patients Prospectively Collected.

Background: Clinicopathologic characteristics and prognostic and predictive factors offer valuable guidance when selecting optimal first-line treatment in patients with metastatic colorectal cancer (CRC). The association between baseline circulating tumor cell (bCTC) count, molecular tumor profile, and clinicopathologic features was analyzed in a chemo-naïve metastatic CRC population.

Patients And Methods: A total of 1202 patients from the Spanish VISNÚ-1 (FOLFIRINOX/bevacizumab vs.

A new solitary, interstitial species of Loxosomatidae (Entoprocta) from the coast of Galicia (NW Spain), Loxosoma discoides n. sp.

A new solitary species of Loxosomatidae (Entoprocta), Loxosoma discoides n. sp., is described.

Two new species of spionids from the genera Dispio and Prionospio (Polychaeta: Spionidae) from the Iberian Peninsula with redescription and notes on Prionospio (Minuspio) multibranchiata Berkeley, 1927.

A re-assessment of spionid specimens collected from coasts around the Iberian Peninsula and initially assigned to Dispio uncinata Hartman, 1951 and Prionospio multibranchiata Berkeley, 1927 resulted in the recognition of two new species from the genera Dispio and Prionospio: Dispio glandulosa sp. nov. and Prionospio (Minuspio) sanmartini sp.

Mid-term outcome of severe tricuspid regurgitation: are there any differences according to mechanism and severity?

Aims: Patients with significant tricuspid regurgitation (TR) addressed according the new classification in torrential TR may have different prognosis compared with just severe TR patients. We sought to determine distribution and mechanism of consecutive severe TR patients, in accordance with aetiology and severity by applying the new proposed classification scheme and their long-term outcomes.

Methods And Results: Between January and December 2013, 249 patients with significant TR referred to the cardiac imaging unit (mean age 79.

Randomized, double-blind, phase two study of ruxolitinib plus regorafenib in patients with relapsed/refractory metastatic colorectal cancer.

Background: The Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling pathway plays a key role in the systemic inflammatory response in many cancers, including colorectal cancer (CRC). This study evaluated the addition of ruxolitinib, a potent JAK1/2 inhibitor, to regorafenib in patients with relapsed/refractory metastatic CRC.

Methods: In this two-part, multicenter, phase 2 study, eligible adult patients had metastatic adenocarcinoma of the colon or rectum; an Eastern Cooperative Oncology Group performance status of 0-2; received fluoropyrimidine, oxaliplatin, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor therapy (if no contraindication); and if KRAS wild-type (and no contraindication), an anti-epidermal growth factor receptor therapy; and progressed following the last administration of approved therapy.

New species of Dispio Hartman, 1951 and Streblospio Webster, 1879 (Polychaeta, Spionidae) from the coast of the Iberian Peninsula.

Re-assessment of spionid specimens from Iberian Peninsula initially assigned to Dispio uncinata Hartman, 1951 and Streblospio benedicti Webster, 1879 led to the recognition of two new species from the spionid genera Dispio and Streblospio from coasts around the Iberian Peninsula. Dispio elegans sp. nov.

CISNE: An accurate description of dose-effect and synergism in combination therapies.

The precise determination of dose-effect curves and the combination effect of drugs is of crucial importance in the development of new therapies for the most dreadful diseases. We have found that the current implementations of the theory of Chou et al. are not accurate enough in some circumstances and might lead to erroneous predictions of synergistic or antagonistic behaviour.

A Randomized Phase II Study of Axitinib as Maintenance Therapy After First-line Treatment for Metastatic Colorectal Cancer.

Introduction: The aim of this study was to evaluate the efficacy and safety of maintenance therapy with axitinib versus placebo following induction therapy in patients with metastatic colorectal cancer (mCRC).

Patients And Methods: In this double-blinded, phase II trial, patients with mCRC who had not progressed after 6 to 8 months of first-line chemotherapy were randomized to receive axitinib (5 mg twice a day) (arm A) or placebo (arm B).

Results: Forty-nine patients were included: 25 in arm A and 24 in arm B.

Lauren subtypes of advanced gastric cancer influence survival and response to chemotherapy: real-world data from the AGAMENON National Cancer Registry.

Background: The choice of chemotherapy in HER2-negative gastric cancer is based on centre's preferences and adverse effects profile. No schedule is currently accepted as standard, nor are there any factors to predict response, other than HER2 status. We seek to evaluate whether Lauren type influences the efficacy of various chemotherapies and on patient overall survival (OS).

Recommendations for SIR-Spheres Y-90 resin microspheres in chemotherapy-refractory/intolerant colorectal liver metastases.

A Spanish expert panel reviewed current evidence for the use of SIR-Spheres Y-90 resin microspheres in patients with chemotherapy refractory/intolerant unresectable colorectal liver metastases. Substantial evidence for its efficacy and safety is available from a randomized controlled study, retrospective comparative studies and several single arm studies. Clinical evidence data obtained from more than 1500 patients have led to the inclusion of selective internal radiation therapy in the 2016 ESMO Clinical Guidelines as third-line treatment.

Optimization of Mutational Analysis Confirms Improvement in Patient Selection for Clinical Benefit to Anti-EGFR Treatment in Metastatic Colorectal Cancer.

In metastatic colorectal cancer (mCRC), recent studies have shown the importance to accurately quantify low-abundance mutations of the pathway because anti-EGFR therapy may depend on certain mutation thresholds. We aimed to evaluate the added predictive value of an extended panel testing using two commercial assays and a highly sensitive and quantitative digital PCR (dPCR). Tumor samples from 583 mCRC patients treated with anti-EGFR- ( = 255) or bevacizumab- ( = 328) based therapies from several clinical trials and retrospective series from the TTD/RTICC Spanish network were analyzed by cobas, , and dPCR.

Bevacizumab and temozolomide versus temozolomide alone as neoadjuvant treatment in unresected glioblastoma: the GENOM 009 randomized phase II trial.

We sought to determine the impact of bevacizumab on reduction of tumor size prior to chemoradiotherapy in unresected glioblastoma patients. Patients were randomized 1:1 to receive temozolomide (TMZ arm) or temozolomide plus bevacizumab (TMZ + BEV arm). In both arms, neoadjuvant treatment was temozolomide (85 mg/m(2), days 1-21, two 28-day cycles), concurrent radiation plus temozolomide, and six cycles of adjuvant temozolomide.

Challenges in first line chemotherapy and targeted therapy in advanced gastric cancer.

Chemotherapy prolongs survival in advanced gastric cancer (AGC). The challenges involved in this procedure are providing a framework to aid in determining the best single or combined chemotherapy protocols for targeted agents in front-line therapy for patients in a clinical setting. A review of Phase II-III studies published or referenced in major oncology congress publications from 1970 to 2013 was performed.

Prolonged clinical benefit of everolimus therapy in the management of high-grade pancreatic neuroendocrine carcinoma.

Treatment options for patients with high-grade pancreatic neuroendocrine tumors (pNET) are limited, especially for those with progressive disease and for those who experience treatment failure. Everolimus, an oral inhibitor of mammalian target of rapamycin (mTOR), has been approved for the treatment of patients with low- or intermediate-grade advanced pNET. In the randomized phase III RADIANT-3 study in patients with low- or intermediate-grade advanced pNET, everolimus significantly increased progression-free survival (PFS) and decreased the relative risk for disease progression by 65% over placebo.

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).

Impact of the incorporation of tyrosine kinase inhibitor agents on the treatment of patients with a diagnosis of advanced renal cell carcinoma: study based on experience at the Hospital Universitario Central de Asturias.

Introduction: For nearly the past two decades, cytokines (CKs) have been the only systemic treatment option available for advanced renal cell carcinoma (RCC). In recent years, tyrosine kinase inhibitors (TKIs) have demonstrated clinical activity on this tumour. Our purpose is to describe one centre's experience with the use of CKs and TKIs in the treatment of patients with advanced RCC.