Unexpected and durable response with regorafenib in a metastatic colorectal cancer patient without KDR mutation: A case report

Regorafenib is an oral multikinase inhibitor and is approved as salvage therapy in the standard treatment of advanced colorectal cancer (CRC). Due to its limited efficacy, toxicity profile, and cost, it is necessary to identify those patients who may have the most benefit from regorafenib. In a previous case report, kinase insert domain receptor (KDR) mutation has been associated with exceptional clinical response (CR) in an elderly patient treated with a low dose of regorafenib; thus, it was hypothesized that it could represent a new predictive marker of drug response

How local stakeholders perceive agroforestry systems: an Italian perspective

This paper reports the results of a study conducted in Italy, within the AGFORWARD (2014–2017) project, aimed at promoting innovative agroforestry practices in Europe. Agroforestry offers a means for maintaining food production whilst addressing some of the negative environmental effects of intensive agriculture. This study aims to elicit the positive and negative points of view and perceptions of local stakeholders in Italy in relation to three types of agroforestry systems. The Participatory Research and Network Development was implemented in three workshops conducted in Sardinia, Umbria, and Veneto regions, and applied adopting a common methodological protocol. Qualitative data were obtained using open discussions with stakeholders on key issues, challenges and innovations. Quantitative data were obtained from stakeholders completing questionnaires during the workshops. A statistical analysis was applied to elicit the differences in stakeholders’ positive and negative perceptions in relation to production, management, environment and socio-economy aspects. Although the participants in the study came from different geographical and socioeconomic contexts with varied educational and cultural backgrounds, the different professional groups (farmers, policy-makers and researchers) and the three workshops generally shared similar perceptions of the benefits and constraints. The effects of agroforestry on production and the environment were generally perceived as positive, whilst those related to management were generally negative. The process of bringing the groups together seemed to be an effective means for identifying the key research gaps that need to be addressed in order to promote the uptake and maintenance of agroforestry

Creating agroforestry innovation and best practice leaflets

A key output of the EU FP7 project AGFORWARD was a series of 46 agroforestry innovation and 10 agroforestry best practice leaflets for European farmers and other stakeholders. This paper describes the process of over 80 people working together to create the leaflets and the overall result

Quality of life, compliance, safety and effectiveness in fit older metastatic colorectal patients with cancer treated in first-line with chemotherapy plus cetuximab: A restrospective analysis from the ObservEr study

Abstract Objectives The influence of age ( KRAS wild type (WT) metastatic colorectal cancer (mCRC). Methods 225 patients of the Observed study (PS 0-1) were retrieved based on age ( Results The two patient groups (141  p  = 0.002), which is likely due to higher proportions of metastatic resection (27.0% vs 8.3%; p  = 0.001) and utilization of second-line therapy in younger group (58.9% vs 42.9%; p  = 0.028). Conclusion The current data suggest that fit older patients with mCRC can be safely treated with a cetuximab-based therapy, as QoL and safety profile do not seem to be affected by age. In addition, age did not impact the choice of chemotherapy to be associated to cetuximab and treatment compliance

A randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in the treatment of patients with metastatic colorectal cancer-OBELICS (Optimization of BEvacizumab scheduLIng within Chemotherapy Scheme).

BACKGROUND: Despite the improvements in diagnosis and treatment, colorectal cancer (CRC) is the second cause of cancer deaths in both sexes. Therefore, research in this field remains of great interest. The approval of bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, in combination with a fluoropyrimidine-based chemotherapy in the treatment of metastatic CRC has changed the oncology practice in this disease. However, the efficacy of bevacizumab-based treatment, has thus far been rather modest. Efforts are ongoing to understand the better way to combine bevacizumab and chemotherapy, and to identify valid predictive biomarkers of benefit to avoid unnecessary and costly therapy to nonresponder patients. The BRANCH study in high-risk locally advanced rectal cancer patients showed that varying bevacizumab schedule may impact on the feasibility and efficacy of chemo-radiotherapy. METHODS/DESIGN: OBELICS is a multicentre, open-label, randomised phase 3 trial comparing in mCRC patients two treatment arms (1:1): standard concomitant administration of bevacizumab with chemotherapy (mFOLFOX/OXXEL regimen) vs experimental sequential bevacizumab given 4 days before chemotherapy, as first or second treatment line. Primary end point is the objective response rate (ORR) measured according to RECIST criteria. A sample size of 230 patients was calculated allowing reliable assessment in all plausible first-second line case-mix conditions, with a 80% statistical power and 2-sided alpha error of 0.05. Secondary endpoints are progression free-survival (PFS), overall survival (OS), toxicity and quality of life. The evaluation of the potential predictive role of several circulating biomarkers (circulating endothelial cells and progenitors, VEGF and VEGF-R SNPs, cytokines, microRNAs, free circulating DNA) as well as the value of the early [(18)F]-Fluorodeoxyglucose positron emission tomography (FDG-PET) response, are the objectives of the traslational project. DISCUSSION: Overall this study could optimize bevacizumab scheduling in combination with chemotherapy in mCRC patients. Moreover, correlative studies could improve the knowledge of the mechanisms by which bevacizumab enhance chemotherapy effect and could identify early predictors of response. EudraCT Number: 2011-004997-27 TRIAL REGISTRATION: ClinicalTrials.gove number, NCT01718873

Agroforestry creates carbon sinks whilst enhancing the environment in agricultural landscapes in Europe

Agroforestry, relative to conventional agriculture, contributes significantly to carbon sequestration, increases a range of regulating ecosystem services, and enhances biodiversity. Using a transdisciplinary approach, we combined scientific and technical knowledge to evaluate nine environmental pressures in terms of ecosystem services in European farmland and assessed the carbon storage potential of suitable agroforestry systems, proposed by regional experts. First, regions with potential environmental pressures were identified with respect to soil health (soil erosion by water and wind, low soil organic carbon), water quality (water pollution by nitrates, salinization by irrigation), areas affected by climate change (rising temperature), and by underprovision in biodiversity (pollination and pest control pressures, loss of soil biodiversity). The maps were overlaid to identify areas where several pressures accumulate. In total, 94.4% of farmlands suffer from at least one environmental pressure, pastures being less affected than arable lands. Regional hotspots were located in north-western France, Denmark, Central Spain, north and south-western Italy, Greece, and eastern Romania. The 10% of the area with the highest number of accumulated pressures were defined as Priority Areas, where the implementation of agroforestry could be particularly effective. In a second step, European agroforestry experts were asked to propose agroforestry practices suitable for the Priority Areas they were familiar with, and identified 64 different systems covering a wide range of practices. These ranged from hedgerows on field boundaries to fast growing coppices or scattered single tree systems. Third, for each proposed system, the carbon storage potential was assessed based on data from the literature and the results were scaled-up to the Priority Areas. As expected, given the wide range of agroforestry practices identified, the carbon sequestration potentials ranged between 0.09 and 7.29 t C ha−1 a−1. Implementing agroforestry on the Priority Areas could lead to a sequestration of 2.1 to 63.9 million t C a−1 (7.78 and 234.85

First-line FOLFIRI and bevacizumab in patients with advanced colorectal cancer prospectively stratified according to serum LDH: Final results of the GISCAD (Italian Group for the Study of Digestive Tract Cancers) CENTRAL (ColorEctalavastiNTRiAlLdh) trial

Background:Previous findings suggested that bevacizumab might be able to improve response rate (RR) in colorectal cancer patients with high lactic dehydrogenase (LDH) basal levels.Methods:We conducted a phase II trial to prospectively ascertain whether bevacizumab in combination with FOLFIRI could have an improved clinical activity in patients with high LDH serum levels. Primary end point of the study was RR; secondary end points were median overall survival and median progression-free survival (mPFS).Results:A total of 81 patients were enrolled. No difference in terms of ORR (39% vs 31% for low vs high LDH level stratum, P=0.78) and mPFS (14.16 vs 10.29 months, HR: 1.07, 95% CI: 0.51-2.24, P=0.83) between the strata was observed, whereas overall survival (OS) was significantly longer for patients with low LDH (24.85 vs 15.14 months, HR: 4.08, 95% CI: 1.14-14.61, P=0.0004). In a not-pre-planned exploratory analysis using different cut-off ranges for LDH, we observed RR up to 70%, with no improvement in progression-free survival or OS.Conclusions:The CENTRAL trial failed to demonstrate that high LDH levels were related to a significantly improved RR in patients receiving first-line FOLFIRI and bevacizumab. The LDH serum levels should then no further be investigated as a predictive factor in this setting

Duration of adjuvant doublet chemotherapy (3 or 6 months) in patients with high-risk stage II colorectal cancer

PURPOSE: As oxaliplatin results in cumulative neurotoxicity, reducing treatment duration without loss of efficacy would benefit patients and healthcare providers. PATIENTS AND METHODS: Four of the six studies in the International Duration of Adjuvant Chemotherapy (IDEA) collaboration included patients with high-risk stage II colon and rectal cancers. Patients were treated (clinician and/or patient choice) with either fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) and randomly assigned to receive 3- or 6-month treatment. The primary end point is disease-free survival (DFS), and noninferiority of 3-month treatment was defined as a hazard ratio (HR) of < 1.2- v 6-month arm. To detect this with 80% power at a one-sided type one error rate of 0.10, a total of 542 DFS events were required. RESULTS: 3,273 eligible patients were randomly assigned to either 3- or 6-month treatment with 62% receiving CAPOX and 38% FOLFOX. There were 553 DFS events. Five-year DFS was 80.7% and 83.9% for 3-month and 6-month treatment, respectively (HR, 1.17; 80% CI, 1.05 to 1.31; P [for noninferiority] .39). This crossed the noninferiority limit of 1.2. As in the IDEA stage III analysis, the duration effect appeared dependent on the chemotherapy regimen although a test of interaction was negative. HR for CAPOX was 1.02 (80% CI, 0.88 to 1.17), and HR for FOLFOX was 1.41 (80% CI, 1.18 to 1.68). CONCLUSION: Although noninferiority has not been demonstrated in the overall population, the convenience, reduced toxicity, and cost of 3-month adjuvant CAPOX suggest it as a potential option for high-risk stage II colon cancer if oxaliplatin-based chemotherapy is suitable. The relative contribution of the factors used to define high-risk stage II disease needs better understanding