Provincial development of a patient-reported outcome initiative to guide patient care, quality improvement, and research.

The BC Cancer Agency Radiotherapy (RT) program started the Prospective Outcomes and Support Initiative (POSI) at all six centres to utilize patient-reported outcomes for immediate clinical care, quality improvement, and research. Patient-reported outcomes were collected at time of computed tomography simulation via tablet and 2 to 4 weeks post-RT via either tablet or over the phone by a registered nurse. From 2013 to 2016, patients were approached on 20,150 attempts by POSI for patients treated with RT for bone metastases (52%), brain metastases (11%), lung cancer (17%), gynecological cancer (16%), head and neck cancer (2%), and other pilots (2%). The accrual rate for all encounters was 85% (n = 17,101), with the accrual rate varying between the lowest and the highest accruing centre from 78% to 89% ( P < .001) and varying by tumour site ( P < .001). Using the POSI database, we have performed research and quality improvement initiatives that have changed practice.

Comparison of patient-reported outcomes with single versus multiple fraction palliative radiotherapy for bone metastasis in a population-based cohort.

BACKGROUND: Despite randomized control trials showing equivalent efficacy between single-fraction (SF) and multiple-fraction (MF) radiation therapy (RT) for bone metastases (BoM), considerable variation in fractionation exists. We compared patient-reported outcomes (PROs) following SF versus MF RT in a population-based cohort. METHODS: PROs were chosen to assess patients' perception of pain, function, and symptom frustration. Total score was the sum of the 3 questions. RESULTS: 968 patients completed pre and post-RT PROs, 35% (335) had complicated BoM. Overall, there were no differences in total score improvement (79% vs. 83%; p=0.13), nor for complicated BoM (77% vs. 84%; p=0.12), SFRT and MFRT respectively. On multivariate analysis no differences in improvement in total score were observed between SFRT and MFRT overall (OR=0.71; 95% CI 0.49-1.02; p=0.06), nor for complicated BoM (OR=0.74; 95% CI 0.39-1.39; p=0.35). In the complicated BoM subset, pain complete response (CR) (19% vs. 33%; p=0.01) and functional improvement occurred more commonly in the MFRT group (69% vs. 81%; p=0.04). CONCLUSION: Improvements in PROs for pain, function and symptom frustration were similar between SFRT and MFRT supporting the use of hypofractionated regimens. Using a simple, 3-question, telephone-based questionnaire to assess response to palliative RT is a feasible strategy to collect PROs.

Intake of grape-derived polyphenols reduces C26 tumor growth by inhibiting angiogenesis and inducing apoptosis.

This study evaluated the in vivo antitumor activity of grape-derived polyphenols. BALB/c mice were subcutaneously implanted with C26 colon carcinoma cells, and 2 d later they received either solvent or red wine polyphenols (RWPs) (100 mg/kg/d, human equivalent dose approximately 500 mg/d) in the drinking water for 25 d. Wistar rats received either solvent or RWPs (100 mg/kg/d, human equivalent dose approximately 1000 mg/d) in the drinking water 1 wk before injection of azoxymethane and were studied 10 wk later. In mice, RWPs inhibited tumor growth by 31%, reduced tumor vascularization and the number of lung metastases, decreased proliferation as indicated by down-regulation of Ki67, cyclin D1, and UHRF1, and increased apoptosis as indicated by TUNEL staining and active caspase-3 levels in tumor cells. RWPs reduced expression of VEGF, matrix metalloproteinase (MMP)-2, MMP-9, and cyclooxygenase-2 and increased expression of tumor suppressor genes p16(INK4A), p53, and p73 in tumor cells. In rats, RWPs reduced by 49% the number of azoxymethane-induced aberrant crypt foci (preneoplastic lesions) in colon. Thus, RWPs effectively reduced the development of colon carcinoma tumors in vivo by blunting tumor vascularization and by inhibiting proliferation and promoting apoptosis of tumor cells subsequent to an up-regulation of tumor suppressor genes.

Endothelium-derived contracting factors mediate the Ang II-induced endothelial dysfunction in the rat aorta: preventive effect of red wine polyphenols.

Angiotensin II (Ang II)-induced hypertension is associated with vascular oxidative stress and an endothelial dysfunction. This study examined the role of reactive oxygen species (ROS) and endothelium-derived contracting factors in Ang II-induced endothelial dysfunction and whether these effects are prevented by red wine polyphenols (RWPs), a rich source of natural antioxidants. Rats were infused with Ang II for 14 days. RWPs were administered in the drinking water 1 week before and during the Ang II infusion. Arterial pressure was measured in conscious rats. Vascular reactivity was assessed in organ chambers and cyclooxygenase-1 (COX-1) and COX-2 expression by Western blot and immunofluorescence analyses. Ang II-induced hypertension was associated with blunted endothelium-dependent relaxations and induction of endothelium-dependent contractions in the presence of nitro-L-arginine in response to acetylcholine (Ach). These effects were not affected by the combination of membrane permeant analogs of superoxide dismutase and catalase but were abolished by the thromboxane A(2) (TP) receptor antagonist GR32191B and the COX-2 inhibitor NS-398. The COX-1 inhibitor SC-560 also prevented contractile responses to Ach. Ang II increased the expression of COX-1 and COX-2 in the aortic wall. RWPs prevented Ang II-induced hypertension, endothelial dysfunction, and upregulation of COX-1 and COX-2. Thus, Ang II-induced endothelial dysfunction cannot be explained by an acute formation of ROS reducing the bioavailability of nitric oxide but rather by COX-dependent formation of contracting factors acting on TP receptors. RWPs are able to prevent the Ang II-induced endothelial dysfunction mostly due to their antioxidant properties.

Red wine polyphenols prevent acceleration of neovascularization by angiotensin II in the ischemic rat hindlimb.

Studies in both animals and humans indicate that angiogenesis is implicated in the development of atherosclerotic lesions. Thus, inhibition of angiogenesis may provide a novel therapeutic approach for the treatment of atherosclerosis. Because epidemiological studies have indicated an inverse relation between red wine intake and coronary disease, we determined the antiangiogenic potential of red wine polyphenols (RWPs) in the ischemic hindlimb model. Neovascularization was accelerated by the chronic infusion of angiotensin II (Ang II; 0.1 mg/kg/day). RWPs (25 mg/kg/day) or vehicle were administrated in the drinking water 7 days before the ligation. After 21 days, Ang II potentiated the ischemia-induced neovascularization in the hindlimb, as assessed by microangiography and measurement of microvessel density. This effect was associated with an increased formation of reactive oxygen species (ROS) and increased expression of hypoxia-inducible factor (HIF)-2alpha, endothelial nitric-oxide synthase (eNOS), and vascular endothelial growth factor (VEGF). RWPs intake significantly prevented the angiogenic process, the formation of ROS and nitrated proteins, and the expression HIF-2alpha, eNOS, and VEGF induced by Ang II. Similar preventive effects were observed with the antioxidant and NADPH oxidase inhibitor apocynin. These findings indicate that RWPs have potent antiangiogenic properties in vivo by preventing the expression of proangiogenic factors, including VEGF and eNOS most likely by inhibiting oxidative stress. Thus, the antiangiogenic properties of red wine polyphenols might contribute to their protective effect against coronary disease.

Angiotensin II induces the vascular expression of VEGF and MMP-2 in vivo: preventive effect of red wine polyphenols.

OBJECTIVE: Previous investigations have indicated that angiotensin II (Ang II)-induced hypertension and endothelial dysfunction are prevented by intake of red wine polyphenols (RWPs). Ang II has also been shown to increase the expression of VEGF and MMP-2, two major pro-inflammatory factors, in vascular diseases. Therefore, the aim of the present study was to determine whether intake of RWPs is able to prevent these effects in rats and, if so, to characterize the underlying mechanism. METHODS: VEGF and endothelial NO synthase (eNOS) expression was assessed by immunofluorescence and Western blotting, MMP-2 activity by zymography, and reactive oxygen species (ROS) formation by dihydroethidine. RESULTS: Ang II increased VEGF expression and MMP-2 activity in the aortic wall. Ang II-induced MMP-2 activation is inhibited by N(G)-nitro-L-arginine and MnTMPyP. Ang II increased the expression of eNOS, the formation of ROS and the nitration of proteins. The stimulatory effects of Ang II on these factors are prevented by RWPs intake. CONCLUSIONS: Infusion of Ang II induced vascular expression of VEGF and peroxynitrite-dependent activation of MMP-2, with both effects being prevented by RWPs intake. Thus, prevention of VEGF and MMP-2 expression might be involved in the protective effect of red wine on coronary heart diseases.