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Karin JC Sanders,1 Juliette HRJ Degens,1 Anne-Marie C Dingemans,2 Annemie MWJ Schols1 1Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands; 2Department of Respiratory Medicine, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands Background: Computed tomography (CT) is increasingly used in clinical research for single-slice assessment of muscle mass to correlate with clinical outcome and evaluate treatment efficacy. The third lumbar level (L3) is considered as reference for muscle, but chest scans generally do not reach beyond the first lumbar level (L1). This study investigates if pectoralis muscle and L1 are appropriate alternatives for L3. Methods: CT scans of 115 stage IV non-small cell lung cancer patients were analyzed before and during tumor therapy. Skeletal muscle assessed at pectoralis and L1 muscle was compared to L3 at baseline. Furthermore, the prognostic significance of changes in muscle mass determined at different locations was investigated. Results: Pearson’s correlation coefficient between skeletal muscle at L3 and L1 was stronger (r=0.90, P

Background: Brown adipose tissue (BAT) has been primarily researched as a potential target for mitigating obesity. However, the physiological significance of BAT in relation to cachexia remains poorly understood. The objective of this study was to investigate the putative contribution of BAT on different components of energy metabolism in emphysematous chronic obstructive pulmonary disease (COPD) patients., Methods: Twenty COPD patients (mean ± SD age 62 ± 6, 50% female, median [range] BMI 22.4 [15.1-32.5] kg/m 2 and 85% low FFMI) were studied. Basal metabolic rate (BMR) was assessed by ventilated hood, total daily energy expenditure (TDEE) by doubly labelled water and physical activity by triaxial accelerometry. BMR was adjusted for fat-free mass (FFM) as assessed by deuterium dilution. Analysis of BAT and WAT was conducted in a subset of ten patients and six age-matched, gender-matched and BMI-matched healthy controls. BAT glucose uptake was assessed by means of cold-stimulated integrated [18F]FDG positron-emission tomography and magnetic resonance imaging. WAT was collected from subcutaneous abdominal biopsies to analyse metabolic and inflammatory gene expression levels. Lung function was assessed by spirometry and body plethysmography and systemic inflammation by high sensitivity C-reactive protein., Results: Mean TDEE was 2209 ± 394 kcal/day, and mean BMR was 1449 ± 214 kcal/day corresponding to 120% of predicted. FFM-adjusted BMR did not correlate with lung function or C-reactive protein. Upon cooling, energy expenditure increased, resulting in a non-shivering thermogenesis of (median [range]) 20.1% [3.3-41.3] in patients and controls. Mean BAT glucose uptake was comparable between COPD and controls (1.5 [0.1-6.2] vs. 1.1 [0.7-3.9]). In addition, no correlation was found between BMR adjusted for FFM and BAT activity or between cold-induced non-shivering energy expenditure and BAT activity. Gene expression levels of the brown adipocyte or beige markers were also comparable between the groups. No (serious) adverse events were reported., Conclusions: Although COPD patients were hypermetabolic at rest, no correlation was found between BMR or TDEE and BAT activity. Furthermore, both BAT activity and gene expression levels of the brown adipocyte or beige markers were comparable between COPD patients and controls., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: Assessment of handgrip strength and fat-free mass provides quick and objective information on muscle performance and mass that might complement subjective World Health Organization Performance Status (WHO PS). We investigated to what extent the presence of pre-treatment handgrip weakness and low fat-free mass index (FFMI) provides additional prognostic information on top of well-established prognostic factors (including WHO PS) in non-small cell lung cancer (NSCLC) patients selected for curative-intent (chemo)radiation., Methods: Prospectively, patients with early and locally advanced NSCLC (stages I-III) treated with (chemo)radiation were enrolled. Handgrip weakness and low FFMI, derived from bioelectrical impedance analysis, were defined using normative values and were correlated with overall survival (OS)., Results: We included 936 patients (age 68 ± 10 years; 64% male; 19% stage I, 9% stage II, and 72% stage III disease; 26% handgrip weakness; 27% low FFMI). In patients with good performance status (WHO PS 0 or 1), handgrip weakness and low FFMI were significant prognostic factors for OS, after adjustment for age, gender, disease stage, and co-morbidities. The combined presence of handgrip weakness and low FFMI was a strong prognostic factor for OS when compared with patients with normal handgrip strength and FFMI (hazard ratio: 1.79, 95% confidence interval: 1.34-2.40, P < 0.0001). In patients with impaired performance status (WHO PS ≥ 2, 19% of sample), handgrip weakness and low FFMI were not related to OS., Conclusions: In early and locally advanced NSCLC patients treated with curative-intent (chemo)radiation who have good WHO PS, patients with combined handgrip weakness and low FFMI have the worst prognosis., (© 2020 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: Muscle depletion negatively impacts treatment efficacy and survival rates in cancer. Prevention and timely treatment of muscle loss require prediction of patients at risk. We aimed to investigate the potential of skeletal muscle radiomic features to predict future muscle loss., Methods: A total of 116 patients with stage IV non-small cell lung cancer included in a randomised controlled trial (NCT01171170) studying the effect of nitroglycerin added to paclitaxel-carboplatin-bevacizumab were enrolled. In this post hoc analysis, muscle cross-sectional area and radiomic features were extracted from computed tomography images obtained before initiation of chemotherapy and shortly after administration of the second cycle. For internal cross-validation, the cohort was randomly split in a training set and validation set 100 times. We used least absolute shrinkage and selection operator method to select features that were most significantly associated with muscle loss and an area under the curve (AUC) for model performance., Results: Sixty-nine patients (59%) exhibited loss of skeletal muscle. One hundred ninety-three features were used to construct a prediction model for muscle loss. The average AUC was 0.49 (95% confidence interval [CI]: 0.36, 0.62). Differences in intensity and texture radiomic features over time were seen between patients with and without muscle loss., Conclusions: The present study shows that skeletal muscle radiomics did not predict future muscle loss during chemotherapy in non-small cell lung cancer. Differences in radiomic features over time might reflect myosteatosis. Future imaging analysis combined with muscle tissue analysis in patients and in experimental models is needed to unravel the biological processes linked to the radiomic features., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: We aimed to investigate the influence of both hypothyroidism and thyroid-stimulating hormone (TSH) suppression on vascular inflammation, as assessed with 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/computed tomography (CT)., Methods: Ten thyroid carcinoma patients underwent an 18 F-FDG PET/CT during post-thyroidectomy hypothyroidism and during thyrotropin (TSH) suppression after 131 I (radioiodine) ablation therapy. We analysed the 18 F-FDG uptake in the carotids, aortic arch, ascending, descending, and abdominal aorta to investigate the effects of thyroid hormone status on arterial inflammation. Target-to-background ratios (TBRs) corrected for blood pool activity were established for all arterial territories. Results were further compared to euthyroid historic control subjects., Results: In general, there was a trend towards higher vascular TBRs during TSH suppression than during hypothyroidism (TBR max all vessels = 1.6 and 1.8, respectively, p = 0.058), suggesting a higher degree of arterial inflammation. In concurrence with this, we found increased C-reactive protein (CRP) levels after levothyroxine treatment (CRP = 2.9 mg/l and 4.8 mg/l, p = 0.005). An exploratory comparison with euthyroid controls showed significant higher TBRs during TSH suppression for the carotids, aortic arch, thoracic descending aorta, and when all vascular territories were combined (TBR max p = 0.013, p = 0.016, p = 0.030 and p = 0.018 respectively)., Conclusions: Arterial inflammation is increased during TSH suppression. This finding sheds new light on the underlying mechanism of the suspected increased risk of cardiovascular disease in patients with TSH suppression.

Objectives: To evaluate the relationship between early changes in muscle and adipose tissue during chemotherapy and overall survival (OS) in stage IV non-small cell lung cancer (NSCLC)., Materials and Methods: In this post-hoc analysis of the first line NVALT12 trial (NCT01171170) in stage IV NSCLC, skeletal muscle (SM), radiation attenuation (RA), subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were assessed at the third lumbar level on CT-images obtained before initiation of chemotherapy and shortly after administration of the second cycle. The contribution of changes in different body compartments to overall survival was assessed., Results: CT scans of 111 patients were included. Analysis of body composition changes between the baseline and the follow-up scan, revealed that overall SM cross sectional area (CSA), radiation attenuation and SAT CSA decreased respectively by -1.2 ± 2.9 cm 2 /m 2 (p < 0.001), -0.7 ± 3.3 HU (p = 0.026) and -1.9 ± 8.7 cm 2 /m 2 (p = 0.026), while no significant changes in VAT tissue were observed. Longitudinally, median OS was significantly shorter among patients losing SM compared to patients with preserved SM (9.4 versus 14.2 months; HR 1.9, 95% CI: 1.23, 2.79, p = 0.003). Multivariate analyses showed that proportional loss of muscle mass was associated with poor OS (HR 0.949, 95% CI: 0.915, 0.985, p = 0.006) independent from important clinical prognostic factors including WHO-PS, gender, age and Charlson comorbidity index., Conclusion: Early loss of SM during first line chemotherapy is a poor prognostic factor in stage IV NSCLC patients. Future studies have to reveal whether early supportive intervention guided by initial CT muscle response to chemotherapy can influence the wasting process and related mortality risk., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)

Muscle wasting frequently occurs in severe emphysema. Improving respiratory mechanics by bronchoscopic lung volume reduction using endobronchial valves (EBV) might prevent further loss or even increase in muscle mass. CT-derived skeletal muscle mass gain was observed in 39/49 patients 6 months after EBV. Multiple linear regression showed that gain in muscle (β=2.4; 95% CI 0.2 to 4.6; p=0.036) and intramuscular fat (β=3.1; 95% CI 0.2 to 5.9; p=0.035) is associated with improved 6 min walk distance independent of the change in residual volume. Skeletal muscle remodelling associates with improved exercise capacity after EBV, independent of hyperinflation reduction. TRIAL REGISTRATION NUMBER: Clinical trial registered with the Dutch trial register www.trialregister.nl (NTR2876), Results., Competing Interests: Competing interests: KJCS has nothing to disclose. KK reports non-financial support from ZonMW, The Hague, NL (government granting agency), during the conduct of the study; grants, personal fees, non-financial support and other from PneumRx/BTG, CA, USA, grants, personal fees, non-financial support and other from PulmonX, CA, USA, outside the submitted work. LEGWV has nothing to disclose. D-JS reports grants, personal fees, non-financial support and other from PulmonX Inc., CA, USA, outside the submitted work. AMWJS has nothing to disclose., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

The clinical manifestations of chronic obstructive pulmonary disease (COPD) reflect an aggregate of multiple pulmonary and extrapulmonary processes. It is increasingly clear that full assessment of these processes is essential to characterize disease burden and to tailor therapy. Medical imaging has advanced such that it is now possible to obtain in vivo insight in the presence and severity of lung disease-associated features. In this review, we have assembled data from multiple disciplines of medical imaging research to review the role of imaging in characterization of COPD. Topics include imaging of the lungs, body composition, and extrapulmonary tissue metabolism. The primary focus is on imaging modalities that are widely available in clinical care settings and that potentially contribute to describing COPD heterogeneity and enhance our insight in underlying pathophysiological processes and their structural and functional effects.