Health-related Quality of Life using the EQ-5D-5L:normative utility scores in a Dutch female population

PURPOSE: Normative utility scores represent the health related quality of life of the general population, are of utmost importance in cost-effectiveness studies and should reflect relevant sexes and age groups. The aim of this study was to estimate EQ-5D-5L normative utility scores in a population of Dutch females, stratified by age, and to compare these scores to those of female populations of three other countries. METHODS: Dutch women completed the EQ-5D-5L online between January and July 2020. Mean normative utilities were computed using the Dutch EQ-5D-5L value set, stratified by age, tested for differences using the Kruskall–Wallis test, and compared to normative utility scores of female populations elsewhere. Additionally, to support the use of the Dutch EQ-5D-5L data in other settings, normative utility scores were also calculated by applying the value sets of Germany, United Kingdom and USA. RESULTS: Data of 9037 women were analyzed and the weighted mean utility score was 0.911 (SD 0.155, 95% CI 0.908–0.914). The mean normative utility scores differed between age groups, showing lower scores in older females. Compared to other normative utility scores of female populations, Dutch mean utilities were consistently higher except for age groups 18–24 and 25–34. With the three country-specific value sets, new age-specific mean normative utility scores were provided. CONCLUSION: This study provides mean normative utility scores of a large cohort of Dutch females per age group, which were found to be lower in older age groups. Utility scores calculated with three other value sets were made available. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11136-022-03271-3

Health-related quality of life (HRQoL) after different axillary treatments in women with breast cancer:a 1-year longitudinal cohort study

Purpose: As life expectancy continues to rise, post-treatment health-related quality of life (HRQoL) of breast cancer patients becomes increasingly important. This study examined the one-year longitudinal relation between axillary treatments and physical, psychosocial, and sexual wellbeing and arm symptoms. Methods: Women diagnosed with breast cancer who received different axillary treatments being axilla preserving surgery (APS) with or without axillary radiotherapy or full axillary lymph node dissection (ALND) with or without axillary radiotherapy were included. HRQoL was assessed at baseline, 6- and 12-months postoperatively using the BREAST-Q and the European Organization for Research and Treatment of Cancer QoL Questionnaire Breast Cancer Module (EORTC QLQ-BR23). Mixed regression models were constructed to assess the impact of axillary treatment on HRQoL. HRQoL at baseline was compared to HRQoL at 6- and at 12-months postoperatively. Results: In total, 552 patients were included in the mixed regressions models. Except for ALND with axillary radiotherapy, no significant differences in physical and psychosocial wellbeing were found. Physical wellbeing decreased significantly between baseline and 6- and 12-months postoperatively (p &lt; 0.001, p = 0.035) and psychosocial wellbeing decreased significantly between baseline and 12 months postoperatively (p = 0.028) for ALND with axillary radiotherapy compared to APS alone. Arm symptoms increased significantly between baseline and 6 months and between baseline and 12 months postoperatively for APS with radiotherapy (12.71, 13.73) and for ALND with radiotherapy (13.93, 16.14), with the lowest increase in arm symptoms for ALND without radiotherapy (6.85, 7.66), compared to APS alone (p &lt; 0.05). Conclusion: Physical and psychosocial wellbeing decreased significantly for ALND with radiotherapy compared to APS alone. Shared decision making and expectation management pre-treatment could be strengthened by discussing arm symptoms per axillary treatment with the patient.</p

Mechanism of IL-12 mediated alterations in tumour blood vessel morphology: analysis using whole-tissue mounts

Angiogenesis is a multistep process that is limited and carefully regulated in normal adult tissue, but in tumours this regulation is disrupted and the process remains ‘switched on’ (Hanahan and Folkman, 1996). Ample experimental data support the fact that tumour growth requires access to blood vessels and subsequent expansion of host vessels to provide nutrients for the growing tumour mass (Folkman, 1995a). Furthermore, many studies in a variety of tumour types have reported a correlation between the extent of tumour vasculature and poor prognosis or increased metastases (Weidner et al, 1991; Folkman, 1995b; Weidner and Folkman, 1996). Thus, accurate assessment of the vasculature of tumours could provide valuable information regarding treatment outcomes and the likelihood of metastatic spread to other sites. Angiogenesis can be regulated by a variety of factors. Several cytokines produced by immune cells also have been shown to affect the process of angiogenesis. One of the most noteworthy is interleukin (IL)-12, which is produced by antigen presenting cells (APC), such as macrophages and dendritic cells (DC) in response to bacterial stimuli or other inflammatory cytokines. Thus, IL-12 plays an important role in both the innate and adaptive immune responses (Trinchieri, 1998). Owing to its central role in stimulating immunity, it has been examined for possible therapeutic effects in the treatment of tumours. In addition to its effects on the immune system, IL-12 has also been shown to inhibit angiogenesis (Voest et al, 1995; Sgadari et al, 1996). Despite studies in both experimental models and in patients (reviewed in Trinchieri and Scott, 1999), and clear demonstrations of therapeutic efficacy, relatively little is known about how it alters vessel formation within tumours. In part, this is due to the difficulty in assessing the three-dimensional structure of vessels and other cellular components within the tumour. Assessment of tumour vessels is generally based on immunohistochemistry of tumour sections. Although use of this technique has led to a great deal of important information, these procedures are extremely time consuming and provide only a limited two-dimensional view of the vessels. This makes it very difficult to visualise the structure of the microvasculature and identify differences among different tumour types or changes following treatment regimens. To more easily and accurately visualise vessels within tumours, we developed a whole-tissue mount technique that provides a three-dimensional view of the tumour vasculature relative to other components of the tumour tissue. This technique was first validated by studying vessels from transgenic mice that express green fluorescent protein (GFP) (Wu et al, 2000), and then used to investigate the mechanism by which IL-12 influences the vessel architecture within B16 tumours

Endothelial Stomatal and Fenestral Diaphragms in Normal Vessels and Angiogenesis

Vascular endothelium lines the entire cardiovascular system where performs a series of vital functions including the control of microvascular permeability, coagulation inflammation, vascular tone as well as the formation of new vessels via vasculogenesis and angiogenesis in normal and disease states. Normal endothelium consists of heterogeneous populations of cells differentiated according to the vascular bed and segment of the vascular tree where they occur. One of the cardinal features is the expression of specific subcellular structures such as plasmalemmal vesicles or caveolae, transendothelial channels, vesiculo-vacuolar organelles, endothelial pockets and fenestrae, whose presence define several endothelial morphological types. A less explored observation is the differential expression of such structures in diverse settings of angiogenesis. This review will focus on the latest developments on the components, structure and function of these specific endothelial structures in normal endothelium as well as in diverse settings of angiogenesis

A quantitative analysis of lymphatic vessels in human breast cancer, based on LYVE-1 immunoreactivity

This study was undertaken to determine the highly sensitive method for detecting tumour lymphatic vessels in all the fields of each slide (LV), lymphatic microvessel density (LMVD) and lymphatic vessel invasion (LVI) and to compare them with other prognostic parameters using immunohistochemical staining with polyclonal (PCAB) and monoclonal antibodies (MCAB) to the lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), and the pan-endothelial marker factorVIII in a series of 67 human breast cancers. In all LYVE-1-stained sections, LV (some of which contained red blood cells) were frequently found localised in extralobular stroma, dermis, connective tissue stroma and adjacent to artery and vein, but were rare within the intralobular stroma or the tumour body (3/67 cases) or areas of widespread invasion. In contrast small blood vessels were observed in intra- and extralobular stroma in the factor VIII-stained sections. Quantitation of vessel numbers revealed that LYVE-1/PCAB detected a significantly larger number of LV than either H&E or LYVE-1/MCAB (P<0.0001). LYVE-1/PCAB detected LVI in 25/67 cases (37.3%) and their presence was significantly associated with both lymph node metastasis (χ2=4.698, P=0.0248) and unfavourable overall survival (OS) (P=0.0453), while not relapse- free survival (RFS) (P=0.2948). LMVD had no influence for RFS and OS (P=0.4879, P=0.1463, respectively). Our study demonstrates that immunohistochemistry with LYVE-1/PCAB is a highly sensitive method for detecting tumour LV/LVI in breast cancer and LVI is a useful prognostic indicator for lymphatic tumour dissemination

Mechanism-related circulating proteins as biomarkers for clinical outcome in patients with unresectable hepatocellular carcinoma receiving sunitinib

<p>Abstract</p> <p>Background</p> <p>Several proteins that promote angiogenesis are overexpressed in hepatocellular carcinoma (HCC) and have been implicated in disease pathogenesis. Sunitinib has antiangiogenic activity and is an oral multitargeted inhibitor of vascular endothelial growth factor receptors (VEGFRs)-1, -2, and -3, platelet-derived growth factor receptors (PDGFRs)-α and -β, stem-cell factor receptor (KIT), and other tyrosine kinases. In a phase II study of sunitinib in advanced HCC, we evaluated the plasma pharmacodynamics of five proteins related to the mechanism of action of sunitinib and explored potential correlations with clinical outcome.</p> <p>Methods</p> <p>Patients with advanced HCC received a starting dose of sunitinib 50 mg/day administered orally for 4 weeks on treatment, followed by 2 weeks off treatment. Plasma samples from 37 patients were obtained at baseline and during treatment and were analyzed for vascular endothelial growth factor (VEGF)-A, VEGF-C, soluble VEGFR-2 (sVEGFR-2), soluble VEGFR-3 (sVEGFR-3), and soluble KIT (sKIT).</p> <p>Results</p> <p>At the end of the first sunitinib treatment cycle, plasma VEGF-A levels were significantly increased relative to baseline, while levels of plasma VEGF-C, sVEGFR-2, sVEGFR-3, and sKIT were significantly decreased. Changes from baseline in VEGF-A, sVEGFR-2, and sVEGFR-3, but not VEGF-C or sKIT, were partially or completely reversed during the first 2-week off-treatment period. High levels of VEGF-C at baseline were significantly associated with Response Evaluation Criteria in Solid Tumors (RECIST)-defined disease control, prolonged time to tumor progression (TTP), and prolonged overall survival (OS). Baseline VEGF-C levels were an independent predictor of TTP by multivariate analysis. Changes from baseline in VEGF-A and sKIT at cycle 1 day 14 or cycle 2 day 28, and change in VEGF-C at the end of the first off-treatment period, were significantly associated with both TTP and OS, while change in sVEGFR-2 at cycle 1 day 28 was an independent predictor of OS.</p> <p>Conclusions</p> <p>Baseline plasma VEGF-C levels predicted disease control (based on RECIST) and were positively associated with both TTP and OS in this exploratory analysis, suggesting that this VEGF family member may have utility in predicting clinical outcome in patients with HCC who receive sunitinib.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00247676">NCT00247676</a></p

Tumour vascularization: sprouting angiogenesis and beyond

Tumour angiogenesis is a fast growing domain in tumour biology. Many growth factors and mechanisms have been unravelled. For almost 30 years, the sprouting of new vessels out of existing ones was considered as an exclusive way of tumour vascularisation. However, over the last years several additional mechanisms have been identified. With the discovery of the contribution of intussusceptive angiogenesis, recruitment of endothelial progenitor cells, vessel co-option, vasculogenic mimicry and lymphangiogenesis to tumour growth, anti-tumour targeting strategies will be more complex than initially thought. This review highlights these processes and intervention as a potential application in cancer therapy. It is concluded that future anti-vascular therapies might be most beneficial when based on multimodal anti-angiogenic, anti-vasculogenic mimicry and anti-lymphangiogenic strategies