The national comprehensive cancer network distress thermometer as a screening tool for the evaluation of quality of life in uveal melanoma patients.

PURPOSE: To assess quality of life (QoL) status via the National Comprehensive Cancer Network (NCCN) distress thermometer as a psychooncological screening tool in uveal melanoma patients. METHODS: One hundred and six consecutive patients suffering from uveal melanoma completed the distress thermometer between 04/2018 and 12/2018. Practical, emotional, family concerned, spiritual, physical and overall distress levels, distribution of distress and subgroup analyses defining groups of potential high distress levels in need of intervention were assessed. Descriptive statistics, cross-tabulations, chi-square and Fisher's exact test as well as correlation coefficients (Spearman's rho) and receiver operating characteristic (ROC) were used for analysis. RESULTS: Patients with higher T-category had significantly more emotional problems and spiritual concerns (p = 0.046 and p = 0.023, respectively). Female patients accounted for higher rates of physical issues (p = 0.034). Lower best corrected visual acuity (BCVA) was correlated with higher distress levels (p = 0.037). Patients resulting in loss of BCVA of ≥3 lines reported higher distress levels (p = 0.029). A distress threshold of 5 on the basis of ROC analysis showed a corresponding sensitivity of 100% and specificity of 76%. CONCLUSION: The NCCN distress thermometer could be integrated well into our clinical routine and proved to be a rapid, yet sensible screening tool for emotional and physical distress in patients with uveal melanoma. Special attention should be paid to patients with higher T-category and patients resulting in lower levels of BCVA. As in patients with different tumour entities, the established distress threshold of ≥5 proposing intervention proved to be adequate for uveal melanoma patients.

Fenofibrate Inhibits Cytochrome P450 Epoxygenase 2C Activity to Suppress Pathological Ocular Angiogenesis.

Neovascular eye diseases including retinopathy of prematurity, diabetic retinopathy and age-related-macular-degeneration are major causes of blindness. Fenofibrate treatment in type 2 diabetes patients reduces progression of diabetic retinopathy independent of its peroxisome proliferator-activated receptor (PPAR)α agonist lipid lowering effect. The mechanism is unknown. Fenofibrate binds to and inhibits cytochrome P450 epoxygenase (CYP)2C with higher affinity than to PPARα. CYP2C metabolizes ω-3 long-chain polyunsaturated fatty acids (LCPUFAs). While ω-3 LCPUFA products from other metabolizing pathways decrease retinal and choroidal neovascularization, CYP2C products of both ω-3 and ω-6 LCPUFAs promote angiogenesis. We hypothesized that fenofibrate inhibits retinopathy by reducing CYP2C ω-3 LCPUFA (and ω-6 LCPUFA) pro-angiogenic metabolites. Fenofibrate reduced retinal and choroidal neovascularization in PPARα-/-mice and augmented ω-3 LCPUFA protection via CYP2C inhibition. Fenofibrate suppressed retinal and choroidal neovascularization in mice overexpressing human CYP2C8 in endothelial cells and reduced plasma levels of the pro-angiogenic ω-3 LCPUFA CYP2C8 product, 19,20-epoxydocosapentaenoic acid. 19,20-epoxydocosapentaenoic acid reversed fenofibrate-induced suppression of angiogenesis ex vivo and suppression of endothelial cell functions in vitro. In summary fenofibrate suppressed retinal and choroidal neovascularization via CYP2C inhibition as well as by acting as an agonist of PPARα. Fenofibrate augmented the overall protective effects of ω-3 LCPUFAs on neovascular eye diseases.