Regorafenib is an oral multikinase inhibitor that has shown antitumor activity in a range of solid tumors. Based on data from phase III clinical trials, regorafenib is indicated for the treatment of adult patients with metastatic colorectal cancer who have previously been treated with, or are not considered candidates for, other available therapies, and in patients with advanced gastrointestinal stromal tumors that cannot be surgically removed and no longer respond to other appropriate treatments. A panel of oncology nurses, research coordinators, and other medical oncology experts, experienced in the care of patients treated with regorafenib, met to discuss the best practice for the management of regorafenib-associated adverse events (AEs). The panel agreed that, in clinical trials and daily practice with regorafenib, AEs are common but mostly manageable. The most common and/or important AEs associated with regorafenib were considered to be hand–foot skin reaction, rash or desquamation, stomatitis, diarrhea, hypertension, liver abnormalities, and fatigue. This manuscript describes the experience and recommendations of the panel for managing these AEs in everyday clinical practice. Appropriate education, monitoring, and management are considered essential for reducing the incidence, duration, and severity of regorafenib-associated AEs.

Augustinus-A Debrock (PI), P Ardies (Coordinator). Imelda ziekenhuis-T Lauwerier (PI), A Delbaere (Coordinator). UZ Brussel-W Vincken (PI), S Hanon (Co-I), D Schuermans, K Van Eeckhoudt (Coordinators). CHU St.-Pierre-V Ninane (PI), M Gabrovska (Co-I), F De Cock, S Carlier (Coordinators).

Elastin degradation is accelerated in chronic obstructive pulmonary disease (COPD) and is partially regulated by Matrix Gla Protein (MGP), via a vitamin K-dependent pathway. The aim was to assess vitamin K status in COPD as well as associations between vitamin K status, elastin degradation, lung function parameters and mortality. A total of 192 COPD patients and 186 age-matched controls were included. In addition to this, 290 COPD patients from a second independent longitudinal cohort were also included. Vitamin K status was assessed by measuring plasma inactive MGP levels and rates of elastin degradation by measuring plasma desmosine levels. Reduced vitamin K status was found in COPD patients compared to smoking controls (p < 0.0005) and controls who had never smoked (p = 0.001). Vitamin K status was inversely associated with desmosine (cohort 1: p = 0.001; cohort 2: p = 0.004). Only few significant associations between vitamin K status and lung function parameters were found. Mortality was higher in COPD patients within the quartile with the lowest vitamin K status compared to those within the other quartiles (hazard ratio 1.85, 95% confidence interval (CI), 1.21–2.83, p = 0.005). In conclusion, we demonstrated reduced vitamin K status in COPD and an inverse association between vitamin K status and elastin degradation rate. Our results therefore suggest a potential role of vitamin K in COPD pathogenesis.

BackgroundBronchiectasis–chronic obstructive pulmonary disease (COPD) overlap presents a possible clinical phenotype of COPD, but it is unclear why it develops in a subset of patients. We hypothesized that sensitization to Aspergillus fumigatus (A fum) is associated with bronchiectasis in COPD and occurs more frequently in vitamin D-deficient patients.MethodsThis observational study investigated sensitization to A fum in an outpatient clinical cohort of 300 COPD patients and 50 (ex-) smoking controls. Total IgE, A fum-specific IgE against the crude extract and against the recombinant antigens and A fum IgG were measured using ImmunoCAP fluoroenzyme immunoassay. Vitamin D was measured by radioimmunoassay, and computed tomography images of the lungs were scored using the modified Reiff score.ResultsSensitization to A fum occurred in 18% of COPD patients compared to 4% of controls (P=0.0110). In all, 31 COPD patients (10%) were sensitized to the crude extract and 24 patients (8%) had only IgE against recombinant antigens. A fum IgG levels were significantly higher in the COPD group (P=0.0473). Within COPD, A fum-sensitized patients were more often male (P=0.0293) and more often had bronchiectasis (P=0.0297). Pseudomonas aeruginosa and Serratia marcescens were more prevalent in historical sputum samples of A fum-sensitized COPD patients compared to A fum-non-sensitized COPD patients (P=0.0436). Vitamin D levels were comparable (P=0.2057). Multivariate analysis demonstrated that sensitization to recombinant f1 or f3 had a 2.8-fold increased risk for bronchiectasis (P=0.0030).ConclusionThese results highlight a potential role for sensitization to A fum in COPD-related bronchiectasis.

Background Despite hospitalization for exacerbation being a high-risk event for morbidity and mortality, there is little consensus globally regarding the assessment and management of hospitalised exacerbations of COPD. We aimed to establish a consensus list of symptoms, physiological measures, clinical scores, patient questionnaires and investigations to be obtained at time of hospitalised COPD exacerbation and follow-up. Methods A modified Delphi online survey with pre-defined consensus of importance, feasibility and frequency of measures at hospitalisation and follow-up of a COPD exacerbation was undertaken. Findings A total of 25 COPD experts from 18 countries contributed to all 3 rounds of the survey. Experts agreed that a detailed history and examination were needed. Experts also agreed on which treatments are needed and how soon these should be delivered. Experts recommended that a full blood count, renal function, C-reactive protein and cardiac blood biomarkers (BNP and troponin) should be measured within 4 hours of admission and that the modified Medical Research Council dyspnoea scale (mMRC) and COPD assessment test (CAT) should be performed at time of exacerbation and follow-up. Experts encouraged COPD clinicians to strongly consider discussing palliative care, if indicated, at time of hospitalisation. Interpretation This Europe-wide consensus document is the first attempt to standardise the assessment and care of patients hospitalised for COPD exacerbations. This should be regarded as the starting point to build knowledge and evidence on patients hospitalised for COPD exacerbations.