Standards of care in mesothelioma treatment

Summary: The UK has the highest incidence of mesothelioma in the world, but services vary across the country partly due to uneven geographical distribution of cases. The Mesothelioma UK-funded national organisational audit has highlighted challenges in accessing diagnostic procedures such as thoracoscopy, as well as identifying examples of best practice, including access to clinical trials and specialist therapeutic procedures. To ensure equitable and optimal patient care, cancer alliances should have established referral pathways to specialist multidisciplinary team (MDT) services for discussion of all mesothelioma patients

Quantitative and textural analysis of magnetization transfer and diffusion images in the early detection of brain metastases

Purpose: The sensitivity of the magnetization transfer ratio (MTR) and apparent diffusion coefficient (ADC) for early detection of brain metastases was investigated in mice and humans. Methods: Mice underwent MRI twice weekly for up to 31 days following intra-cardiac injection of the brain-homing breast cancer cell line MDA-MB231-BR. Patients with small cell lung cancer underwent quarterly MRI for a year. MTR and ADC were measured in regions of metastasis and matched contralateral tissue at the final time-point and in registered regions at earlier time-points. Texture analysis and linear discriminant analysis were performed to detect metastasis-containing slices. Results: Compared with contralateral tissue, mouse metastases had significantly lower MTR and higher ADC at the final time-point. Some lesions were visible at earlier time-points on the MTR and ADC maps: 24% of these were not visible on corresponding T2-weighted images. Texture analysis using the MTR maps showed 100% specificity and 98% sensitivity for metastasis at the final time-point, with 77% sensitivity 2-4 days earlier and 46% 5-8 days earlier. Only 2/16 patients developed metastases, and their penultimate scans were normal. Conclusion: Some brain metastases may be detected earlier on MTR than conventional T2; however, the small gain is unlikely to justify ‘predictive’ MRI.The authors gratefully acknowledge the Cambridge Institute Biological Resources Unit for expert animal care and technical assistance, the Histopathology Core Facility, Drs Joe Frank and Diane Palmieri for providing the cell line, the advice of Dr. Dan Tozer, and the support of Cancer Research UK [grant number C14303/A17197], the Brian Cross Memorial Trust, the Addenbrooke’s Charitable Trust, the University of Cambridge, Hutchison Whampoa Ltd, the Cambridge Experimental Cancer Medicine Centre, and the NIHR Cambridge Biomedical Research Centre.This is the final version of the article. It first appeared from Wiley via https://doi.org/10.1002/mrm.2625

Quantitative and textural analysis of magnetization transfer and diffusion images in the early detection of brain metastases.

PURPOSE: The sensitivity of the magnetization transfer ratio (MTR) and apparent diffusion coefficient (ADC) for early detection of brain metastases was investigated in mice and humans. METHODS: Mice underwent MRI twice weekly for up to 31 d following intracardiac injection of the brain-homing breast cancer cell line MDA-MB231-BR. Patients with small cell lung cancer underwent quarterly MRI for 1 year. MTR and ADC were measured in regions of metastasis and matched contralateral tissue at the final time point and in registered regions at earlier time points. Texture analysis and linear discriminant analysis were performed to detect metastasis-containing slices. RESULTS: Compared with contralateral tissue, mouse metastases had significantly lower MTR and higher ADC at the final time point. Some lesions were visible at earlier time points on the MTR and ADC maps: 24% of these were not visible on corresponding T2 -weighted images. Texture analysis using the MTR maps showed 100% specificity and 98% sensitivity for metastasis at the final time point, with 77% sensitivity 2-4 d earlier and 46% 5-8 d earlier. Only 2 of 16 patients developed metastases, and their penultimate scans were normal. CONCLUSIONS: Some brain metastases may be detected earlier on MTR than conventional T2 ; however, the small gain is unlikely to justify "predictive" MRI. Magn Reson Med 77:1987-1995, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.The authors gratefully acknowledge the Cambridge Institute Biological Resources Unit for expert animal care and technical assistance, the Histopathology Core Facility, Drs Joe Frank and Diane Palmieri for providing the cell line, the advice of Dr. Dan Tozer, and the support of Cancer Research UK [grant number C14303/A17197], the Brian Cross Memorial Trust, the Addenbrooke’s Charitable Trust, the University of Cambridge, Hutchison Whampoa Ltd, the Cambridge Experimental Cancer Medicine Centre, and the NIHR Cambridge Biomedical Research Centre.This is the final version of the article. It first appeared from Wiley via https://doi.org/10.1002/mrm.2625

Genomic analysis of diet composition finds novel loci and associations with health and lifestyle

We conducted genome-wide association studies (GWAS) of relative intake from the macronutrients fat, protein, carbohydrates, and sugar in over 235,000 individuals of European ancestries. We identified 21 unique, approximately independent lead SNPs. Fourteen lead SNPs are uniquely associated with one macronutrient at genome-wide significance (P < 5 × 10−8), while five of the 21 lead SNPs reach suggestive significance (P < 1 × 10−5) for at least one other macronutrient. While the phenotypes are genetically correlated, each phenotype carries a partially unique genetic architecture. Relative protein intake exhibits the strongest relationships with poor health, including positive genetic associations with obesity, type 2 diabetes, and heart disease (rg ≈ 0.15–0.5). In contrast, relative carbohydrate and sugar intake have negative genetic correlations with waist circumference, waist-hip ratio, and neighborhood deprivation (|rg| ≈ 0.1–0.3) and positive genetic correlations with physical activity (rg ≈ 0.1 and 0.2). Relative fat intake has no consistent pattern of genetic correlations with poor health but has a negative genetic correlation with educational attainment (rg ≈−0.1). Although our analyses do not allow us to draw causal conclusions, we find no evidence of negative health consequences associated with relative carbohydrate, sugar, or fat intake. However, our results are consistent with the hypothesis that relative protein intake plays a role in the etiology of metabolic dysfunction

Genomic analysis of diet composition finds novel loci and associations with health and lifestyle

Abstract: We conducted genome-wide association studies (GWAS) of relative intake from the macronutrients fat, protein, carbohydrates, and sugar in over 235,000 individuals of European ancestries. We identified 21 unique, approximately independent lead SNPs. Fourteen lead SNPs are uniquely associated with one macronutrient at genome-wide significance (P < 5 × 10−8), while five of the 21 lead SNPs reach suggestive significance (P < 1 × 10−5) for at least one other macronutrient. While the phenotypes are genetically correlated, each phenotype carries a partially unique genetic architecture. Relative protein intake exhibits the strongest relationships with poor health, including positive genetic associations with obesity, type 2 diabetes, and heart disease (rg ≈ 0.15–0.5). In contrast, relative carbohydrate and sugar intake have negative genetic correlations with waist circumference, waist-hip ratio, and neighborhood deprivation (|rg| ≈ 0.1–0.3) and positive genetic correlations with physical activity (rg ≈ 0.1 and 0.2). Relative fat intake has no consistent pattern of genetic correlations with poor health but has a negative genetic correlation with educational attainment (rg ≈−0.1). Although our analyses do not allow us to draw causal conclusions, we find no evidence of negative health consequences associated with relative carbohydrate, sugar, or fat intake. However, our results are consistent with the hypothesis that relative protein intake plays a role in the etiology of metabolic dysfunction

Impact of organisation and specialist service delivery on lung cancer outcomes.

INTRODUCTION Data from the National Lung Cancer Audit (NLCA) often show variation in outcomes between lung cancer units which are not entirely explained by case mix. We explore the association between the organisation of services and patient outcome. METHODS Details of service provision were collected via an electronic survey in June 2017. An overall organisational score derived from eleven key service factors from national lung cancer commissioning guidance was calculated for each organisation. The results for each hospital were linked to their patient outcome results from the 2015 NLCA cases. Multivariate logistic regression analysis was used to link the organisational score to patient outcomes. RESULTS Lung cancer unit organisational audit scores varied from 0 to 11. Thirty-eight (29%) units had a score of 0-4, 64 (50%) had a score of 5-7 and 27 (21%) had a score of 8-11. Multivariate regression analysis revealed that, compared with an organisational score of 0-4, patients seen at units with a score of 8-11 had higher 1-year survival (adjusted OR (95% CI)=2.30 (1.04 to 5.08), p<0.001), higher curative-intent treatment rate (adjusted OR (95% CI)=1.62 (1.26 to 2.09), p<0.001) and greater likelihood of receiving treatment within 62 days (adjusted OR (95% CI)=1.49 (1.20 to 1.86), p<0.001). CONCLUSION National variation in the provision of services and workforce remain. We provide evidence that adherence to the national lung commissioning guidance has the potential to improve patient outcomes within the current service structure