Skeletal muscle and visceral adipose radiodensities are pre-surgical, non-invasive markers of aggressive kidney cancer.

INTRODUCTION: Most studies on body composition in kidney cancer have been conducted among patients with metastatic disease. Given that aggressive tumours can adversely impact body composition and even non-metastatic tumours can be aggressive, we evaluated associations between pre-surgical body composition features and tumour pathological features in patients with non-metastatic clear cell renal cell cancer (ccRCC). METHODS: The Resolve Cohort consists of 1239 patients with non-metastatic ccRCC who underwent nephrectomy at Memorial Sloan Kettering Cancer Center between 2000 and 2020. The cross-sectional areas and radiodensities of skeletal muscle, visceral adipose, and subcutaneous adipose tissues were determined from pre-surgical computed tomography (CT) scans at the third lumbar vertebrae using Automatica software. Pearson's correlation coefficients describe inter-relationships among BMI and body composition variables, while odds ratios (OR) and 95% confidence intervals (CI) estimate associations between continuous body composition features (per 1-standard deviation) and advanced stage (Stage III vs. Stages I-II) and high Fuhrman grade (Grades 3-4 vs. 1-2) from multivariable logistic regression models that considered the potential impact of biological sex, contrast enhanced CTs, and early age at onset of ccRCC. RESULTS: The cohort was predominantly male (69%), white (89%), and had a median age of 58. The proportion of patients presenting with advanced stage and high-grade disease were 31% and 51%, respectively. In models that adjusted for demographics and all body composition variables simultaneously, decreasing skeletal muscle radiodensity (i.e., more fat infiltration) but increasing visceral adipose tissue radiodensity (i.e., more lipid depletion) were associated with advanced tumour features. Per 8.4 HU decrease in skeletal muscle radiodensity, the odds of presenting with advanced stage was 1.61 (95% CI: 1.34-1.93). Per 7.22 HU increase in visceral adipose tissue radiodensity, the odds of presenting with advanced stage was 1.45 (95% CI: 1.22-1.74). Skeletal muscle index (i.e., sarcopenia) was not associated with either tumour feature. Similar associations were observed for Fuhrman grade, a more direct marker of tumour aggressiveness. Associations did not differ by sex, contrast use, or age at onset of ccRCC. CONCLUSIONS: Lipid infiltrated skeletal muscle, but lipid depleted visceral adipose tissue were independently associated with advanced tumour features in non-metastatic ccRCC. Findings highlight the importance of evaluating the full range of body composition features simultaneously in multivariable models. Interpreting pre-surgical CTs for body composition for patients may be a novel and non-invasive way to identify patients with aggressive renal tumours, which is clinically relevant as renal biopsies are not routinely performed.

Malnutrition defined by GLIM criteria identifies a higher incidence of malnutrition and is associated with pulmonary complications after oesophagogastric cancer surgery, compared to ICD-10-defined malnutrition.

BACKGROUND & OBJECTIVES: Low muscle mass, measured using computed tomography (CT), is associated with poor surgical outcomes. We aimed to include CT-muscle mass in malnutrition diagnosis using the Global Leadership Initiative on Malnutrition (GLIM) criteria, compare it to the International Classification of Diseases 10th Revision (ICD-10) criteria, and assess the impact on postoperative outcomes after oesophagogastric (OG) cancer surgery. METHODS: One hundred and eight patients who underwent radical OG cancer surgery and had preoperative abdominal CT imaging were included. GLIM and ICD-10 malnutrition data were assessed against complication and survival outcomes. Low CT-muscle mass was determined using predefined cut-points. RESULTS: GLIM-defined malnutrition prevalence was significantly higher than ICD-10-malnutrition (72.2% vs. 40.7%, p < 0.001). Of the 78 patients with GLIM-defined malnutrition, low muscle mass (84.6%) was the predominant phenotypic criterion. GLIM-defined malnutrition was associated with pneumonia (26.9% vs. 6.7%, p = 0.010) and pleural effusions (12.8% vs. 0%, p = 0.029). Postoperative complications did not correlate with ICD-10 malnutrition. Severe GLIM (HR: 2.51, p = 0.014) and ICD-10 (HR: 2.15, p = 0.039) malnutrition were independently associated with poorer 5-year survival. CONCLUSIONS: GLIM criteria appear to identify more malnourished patients and more closely relate to surgical risk than ICD-10 malnutrition, likely due to incorporating objective muscle mass assessment.

Examining the Effect of Time-From-Treatment on Activities of Daily Living Kinematics in Breast Cancer Survivors.

Breast cancer affects one in 8 females with a 5-year survival rate of 89%. Up to 72% of breast cancer survivors have trouble with activities of daily living (ADL) following treatment. Increased time-from-treatment improves some measures of function, yet ADL limitations persist. Therefore, this study assessed the effect of time-from-treatment on upper extremity kinematics during ADLs in breast cancer survivors. Twenty-nine female breast cancer survivors were divided into 2 groups: <1 year (n = 12) and 1-2 years (n = 17) from treatment. Kinematics were collected during 6 ADL tasks, and humerothoracic joint angles were quantified. A 2-way mixed analysis of variance assessed the effects of time-from-treatment and arm on maximum angles for each ADL. Decreased maximum angle existed for breast cancer survivors with increased time-from-treatment during all ADLs. Breast cancer survivors in the 1-2 years group used ∼28° to 32° lower elevation, ∼14° to 28° lower axial rotation, and ∼10° to 14° lower plane of elevation range across tasks. Decreased ranges of arm movement during ADLs with increased time-from-treatment may reflect compensatory movement strategies. Recognizing this shift in strategies and accompanying underlying disease progression can help inform responses to functional performance limitations in breast cancer survivors as delayed effects are present posttreatment.

Associations between Pretreatment Body Composition Features and Clinical Outcomes among Patients with Metastatic Clear Cell Renal Cell Carcinoma Treated with Immune Checkpoint Blockade.

PURPOSE: High body mass index (BMI) may lead to improved immune-checkpoint blockade (ICB) outcomes in metastatic clear cell renal cell carcinoma (mccRCC). However, BMI is a crude body size measure. We investigated BMI and radiographically assessed body composition (BC) parameters association with mccRCC ICB outcomes. EXPERIMENTAL DESIGN: Retrospective study of ICB-treated patients with mccRCC. BMI and BC variables [skeletal muscle index (SMI) and multiple adiposity indexes] were determined using pretreatment CT scans. We examined the associations between BMI and BC variables with ICB outcomes. Therapeutic responses per RECIST v1.1 were determined. We compared whole-transcriptomic patterns with BC variables in a separate cohort of 62 primary tumor samples. RESULTS: 205 patients with mccRCC were included in the cohort (74% were male, 71% were overweight/obese, and 53% were classified as low SMI). High-BMI patients experienced longer overall survival (OS) than normal-weight patients [unadjusted HR, 0.66; 95% confidence interval (CI), 0.45-0.97; P = 0.035]. The only BC variable associated with OS was SMI [unadjusted HR comparing low vs. high SMI 1.65 (95% CI: 1.13-2.43); P = 0.009]. However, this OS association became nonsignificant after adjusting for International Metastatic Renal Cell Carcinoma Database Consortium score and line of therapy. No OS association was seen for adiposity and no BC variable was associated with progression-free survival or radiological responses. Tumors from patients with low SMI displayed increased angiogenic, inflammatory, and myeloid signals. CONCLUSIONS: Our findings highlight the relevance of skeletal muscle in the BMI paradox. Future studies should investigate if addressing low skeletal muscle in metastatic patients treated with ICB can improve survival.

MoveStrong at home: a feasibility study of a model for remote delivery of functional strength and balance training combined with nutrition education for older pre-frail and frail adults.

Exercise and nutrition interventions are often recommended for frailty; however, effective strategies are required for real-world implementation. Our primary aim was to assess the feasibility and acceptability of telephone and virtual delivery of MoveStrong, an 8-week exercise and nutrition program with a 4-week follow-up for older pre-frail and frail adults. A priori criteria for success included: recruitment (≥25/12 weeks), retention at follow-up (≥80%), and adherence to exercise and nutrition sessions (≥70%). We recruited community-dwelling Ontario residents; ≥60 years, ≥1 chronic condition, ≥1 FRAIL scale score. Participants received mailed materials, a personalized exercise program, 11 remote one-on-one training sessions with an exercise physiologist and 3 online dietitian-led nutrition education sessions. We completed exploratory analyses of secondary outcomes including physical function and dietary protein intake. Semi-structured interviews supported program evaluation. In total, 30 participants were enrolled. 28 (93%) participants completed program and follow-up assessments. Adherence to exercise and nutrition sessions (CI) was 84% (77%-91%) and 82% (70%-93%) respectively. At program end and follow-up [mean change (CI)], significant improvements were measured in 30-second chair stand test [3.50 (1.12-5.86), 4.54 (1.94-7.13) chair stands] and dietary protein intake [12.9 (5.7-20.0), 9.2 (0.4-18.1) g]. Overall, participants were satisfied with program delivery. Trial registration number: NCT04663685.

An evaluation of upper limb strength and range of motion of breast cancer survivors immediately following treatment.

BACKGROUND: There is a growing number of breast cancer survivors from improved cancer treatments. However, treatments often impair upper limb function, specifically range of motion and strength, reducing quality of life and function. The primary purpose of this study was to quantify differences in strength and range of motion following treatment. The secondary purpose aimed to measure the activation of each upper limb muscle in the completion of tasks. METHODS: 29 breast cancer survivors were categorized into two groups based on time-since-treatment: 1) up to 1-year post-treatment, and 2) 1 to 2 years post-treatment. Participants completed maximal strength and range of motion tasks. During trials eight muscles were monitored bilaterally. Maximal force output was taken during strength trials, and kinematics were monitored during range of motion trials. A 2 by 2 mixed ANOVA (limb (affected, unaffected) x time-since-treatment) examined interaction and main effects of these factors on task peak force, angle and mean activation. FINDINGS: Time-since-treatment influenced strength (flexion, extension, internal and external rotation) and range of motion (flexion, scapular abduction), wherein the group further from treatment had 11.5-15.5° less range of motion and 27.7-43.6 N less force production. A main effect of time-since-treatment influenced muscular behaviours during both tasks, where activation was higher in the group 1-2 years from treatment. INTERPRETATION: Effects of treatment may manifest in a delayed manner whereby strength and range of motion are reduced in breast cancer survivors to a greater extent in those who are past 1 year of treatment cessation.

Altered features of body composition in older adults with type 2 diabetes and prediabetes compared with matched controls.

BACKGROUND: Ageing is accompanied by muscle loss and fat gain, which may elevate the risk of type 2 diabetes (T2D). However, there is a paucity of data on the distribution of regional lean and fat tissue in older adults with T2D or prediabetes compared with healthy controls. The objective of this study was to compare regional body composition [by dual-energy x-ray absorptiometry (DXA)], muscle and subcutaneous adipose tissue (SAT) thicknesses (by ultrasound), and ultrasound-based muscle texture features in older adults with T2D or prediabetes compared with normoglycaemic controls. METHODS: Eighteen adults > 60 years with T2D or prediabetes (T2D group) were individually matched to normoglycaemic participants [healthy matched (HM) group] for age (±5 years), sex, and body fat (±2.5%). In a single study visit, all participants received a whole-body DXA scan and ultrasound assessment of the abdomen and anterior thigh. At these two landmarks, we used ultrasound to measure muscle and SAT thickness, as well as texture features of the rectus femoris and rectus abdominis. We also conducted an exploratory subanalysis on a subset of participants (n = 14/18 in the T2D group and n = 10/18 in the HM group) who underwent additional assessments including strength testing of the knee extensors (using a Biodex dynamometer), and a fasting blood sample for the measurement of circulating markers of glucose metabolism [glucose, insulin, c-peptide, and the homoeostatic model assessment of insulin resistance (HOMA-IR)]. RESULTS: The T2D group was 72 ± 8 years old (mean ± SD), predominantly male (n = 15/18; 83%), and overweight (BMI: 27.8 ± 4.2 kg/m2 , 33.2 ± 5.3% body fat). DXA-derived upper arm lean mass was 0.4 kg greater (P = 0.034), and leg fat mass was 1.4 kg lower (P = 0.048), in the T2D vs. HM group. Ultrasound-based texture features were distinct between the groups [rectus abdominis blob size: 0.07 ± 0.06 vs. 0.30 ± 0.43 cm2 , P = 0.045; rectus femoris local binary pattern (LBP) entropy: 4.65 ± 0.05 vs. 4.59 ± 0.08 A.U., P = 0.007]. When all participants who underwent additional assessments were pooled (n = 24), we observed that certain ultrasound-based muscle texture features correlated significantly with muscle strength (rectus abdominis histogram skew vs. power during an isokinetic contraction at 60°/s: r = 0.601, P = 0.003) and insulin resistance (rectus femoris LBP entropy vs. HOMA-IR: r = 0.419, P = 0.042). CONCLUSIONS: Our findings suggest a novel body composition phenotype specific to older adults with T2D or prediabetes. We are also the first to report that ultrasound-based texture features correspond with functional outcomes. Future larger scale studies are needed to uncover the mechanisms underpinning these regional body composition differences.

Low-frequency exercise training improves cardiovascular fitness and strength during treatment for breast cancer: a single-arm intervention study.

Aerobic and resistance exercise during and after cancer treatment are important for health-related outcomes, however treatment-specific barriers may inhibit adherence. We explored the effect of lower-frequency exercise training on fitness, body composition, and metabolic markers (i.e. glucose and lipids) in a group of recently diagnosed breast cancer patients. Fifty-two females ≥ 18 years with stage I-IIIB breast cancer were instructed to attend 2 cardiovascular and strength training sessions/week over 12 weeks, but program length was expanded as needed to accommodate missed sessions. Pre- and post-intervention, we measured: (1) cardiovascular fitness, (2) isometric strength, (3) body composition (dual-energy X-ray absorptiometry), and (4) fasting glucose, insulin, c-peptide, and lipids. Pre-intervention, participants were 53 ± 10 years old (mean ± SD) and overweight (BMI: 27.5 ± 5.4 kg m-2, 40.1 ± 6.5% body fat). Forty participants completed the program over a median 20 weeks (range: 13-32 weeks, median frequency: 1.2 sessions/week), over which predicted VO2peak improved by 7% (2.2[0.1-4.4] mL/kg/min) (delta[95% CI]), and strength increased by 7-9% (right arm: 2.3[0.1-4.5] N m; right leg: 7.9[2.1-13.7] N m; left leg: 7.8[1.9-13.7] N m). Body composition and metabolic markers were unchanged. An exercise frequency of 1.2 sessions/week stimulated significant improvements in fitness, and may represent a practical target for patients during active treatment.

Low muscularity increases the risk for post-operative pneumonia and delays recovery from complications after oesophago-gastric cancer resection.

BACKGROUND: Low muscularity is associated with adverse surgical outcomes. We aimed to determine whether low muscularity is associated with an increased risk of post-operative complications and reduced long-term survival after oesophago-gastric cancer surgery. METHODS: Patients who underwent radical oesophago-gastric cancer surgery with preoperative abdominal computed tomography (CT) imaging were included. Low skeletal muscle index (SMI), measured by CT, was determined using pre-defined cut-points. Oncological, surgical, complications and outcome data were obtained from a prospective database. RESULTS: Of 108 patients, 61% (n = 66) had low SMI preoperatively. Patients with low SMI had a higher rate of post-operative pneumonia (30 vs. 7% normal muscularity, P = 0.004). Median length of stay (LOS) was higher in patients with low SMI if they had any complication (19.5 vs. 14 days, P = 0.026) or pneumonia (21 vs. 13 days, P = 0.018). On multivariate analysis, low SMI (OR 3.85, CI 1.10-13.4, P = 0.025), preoperative weight loss (OR 1.13, CI 1.01-1.25, P = 0.027), and smoking (OR 5.08, CI 1.24-20.9, P = 0.024) were independent predictors of having a severe complication. There was no difference in 5-year overall (62% vs. 69%, P = 0.241) and disease-free (11% vs. 21.4%, P = 0.110) survival between low SMI and normal muscle mass groups. CONCLUSION: Low SMI is associated with a significantly increased risk of pneumonia and increased LOS for patients with complications. Assessment of muscle mass may require additional muscle quality, strength, and physical performance measures to enhance preoperative risk assessment.

Myosteatosis predicts higher complications and reduced overall survival following radical oesophageal and gastric cancer surgery.

INTRODUCTION: Low muscle attenuation, as governed by increased intramuscular fat infiltration (myosteatosis), may associate with adverse surgical outcomes. We aimed to determine whether myosteatosis is associated with an increased risk of postoperative complications and reduced long-term survival after oesophago-gastric (OG) cancer surgery. METHODS: Patients who underwent radical OG cancer surgery with preoperative abdominal computed tomography (CT) imaging were included. Myosteatosis was evaluated using previously defined cut-points for low skeletal muscle attenuation measured by CT. Oncological, surgical, complications, and outcome data were obtained from a prospective database. RESULTS: Of 108 patients, 56% (n = 61) had myosteatosis. Patients with myosteatosis were older (69.1 ±â€¯9.1 vs. 62.8 ±â€¯9.8 years, p = 0.001) and had a similar body mass index (BMI) (23.4 ±â€¯5.3 vs. 25.9 ±â€¯6.7 kg/m2, p = 0.766) compared to patients with normal muscle attenuation. Patients with myosteatosis had a higher rate of anastomotic leaks (15% vs. 2%, p = 0.041). On multivariate analysis, myosteatosis was an independent predictor of overall (OR 3.03, 95% CI 1.31-6.99, p = 0.009) and severe complications (OR 4.33, 95% CI 1.26-14.9, p = 0.020). Patients with myosteatosis had reduced 5 year overall (54.1% vs. 83%, p = 0.004) and disease-free (55.2% vs. 87.2%, p = 0.007) survival. CONCLUSION: Myosteatosis is associated with a significantly increased risk of overall and severe complications as well as substantially reduced long-term survival. Assessment of muscle attenuation provides analysis beyond standard anthropometrics and may form part of preoperative physiological staging tools used to improve surgical outcomes.

Assessment of muscle mass using ultrasound with minimal versus maximal pressure compared with computed tomography in critically ill adult patients.

BACKGROUND: Preserved skeletal muscle mass identified using computed tomography (CT) predicts improved outcomes from critical illness; however, CT imaging have few limitations such that it involves a radiation dose and transferring patients out of the intensive care unit. This study aimed to assess in critically ill patients the relationship between muscle mass estimates obtained using minimally invasive ultrasound techniques with both minimal and maximal pressure compared with CT images at the third lumber vertebra level. METHODS: All patients were treated in a single Australian intensive care unit. Eligible patients had paired assessments, within a 72-h window, of muscle mass by ultrasound (quadriceps muscle layer thickness in centimetres, with maximal and minimal pressure) and CT axial cross-sectional area (cm2). Data are presented as mean (standard deviation), median (interquartile range), and frequencies [n (%)]. RESULTS: Thirty-five patients [mean (standard deviation) age = 55 (16) years, median (interquartile range) body mass index = 27 (25-32) kg/m2, and 26 (74%) men] contributed 41 paired measurements. Quadriceps muscle thickness measured using the maximal pressure technique was a strong independent predictor of lumbar muscle cross-sectional area. Within a multivariate mixed linear regression model and adjusting for sex, age, and body mass index, for every 1 cm increase in quadriceps muscle layer thickness, the lumbar muscle cross-sectional area increased by 35 cm2 (95% confidence interval = 11-59 cm2). Similar univariate associations were observed using minimal pressure; however, as per multivariate analysis, there was no strength in this relationship [8 cm2 (95% confidence interval = -5 to 22 cm2)]. CONCLUSION: Ultrasound assessment of the quadriceps muscle using maximal pressure reasonably predicts the skeletal muscle at the third lumbar vertebra level of critically ill patients. However, there is substantial uncertainty within these regression estimates, and this may reduce the current utility of this technique as a minimally invasive surrogate for CT assessment of skeletal muscle mass.

Automated body composition analysis of clinically acquired computed tomography scans using neural networks.

BACKGROUND & AIMS: The quantity and quality of skeletal muscle and adipose tissue is an important prognostic factor for clinical outcomes across several illnesses. Clinically acquired computed tomography (CT) scans are commonly used for quantification of body composition, but manual analysis is laborious and costly. The primary aim of this study was to develop an automated body composition analysis framework using CT scans. METHODS: CT scans of the 3rd lumbar vertebrae from critically ill, liver cirrhosis, pancreatic cancer, and clear cell renal cell carcinoma patients, as well as renal and liver donors, were manually analyzed for body composition. Ninety percent of scans were used for developing and validating a neural network for the automated segmentation of skeletal muscle and adipose tissues. Network accuracy was evaluated with the remaining 10 percent of scans using the Dice similarity coefficient (DSC), which quantifies the overlap (0 = no overlap, 1 = perfect overlap) between human and automated segmentations. RESULTS: Of the 893 patients, 44% were female, with a mean (±SD) age and body mass index of 52.7 (±15.8) years old and 28.0 (±6.1) kg/m2, respectively. In the testing cohort (n = 89), DSC scores indicated excellent agreement between human and network-predicted segmentations for skeletal muscle (0.983 ± 0.013), and intermuscular (0.900 ± 0.034), visceral (0.979 ± 0.019), and subcutaneous (0.986 ± 0.016) adipose tissue. Network segmentation took ~350 milliseconds/scan using modern computing hardware. CONCLUSIONS: Our network displayed excellent ability to analyze diverse body composition phenotypes and clinical cohorts, which will create feasible opportunities to advance our capacity to predict health outcomes in clinical populations.

Profiling Determinants of Resting Energy Expenditure in Colorectal Cancer.

Background: Understanding resting energy expenditure (REE) is important for determining energy requirements; REE might be altered in individuals with cancer. The objective of this study was to characterize determinants of REE in patients with stages II-IV colorectal cancer (CRC).Methods: REE was measured via indirect calorimetry in patients with newly diagnosed CRC. Computerized tomography images from medical records ascertained skeletal muscle and total adipose tissue cross-sectional areas, which were then transformed to lean soft tissue (LST) and fat mass (FM) values (in kg). Linear regression assessed determinants of REE.Results: 86 patients were included (n = 55, 64.0% male; 60 ± 12 years old; median body mass index: 27.6, interquartile range: 24.3-31.2 kg/m2), with most (n = 40) having stage III disease. Age, sex, and weight were significant predictors of REE [R2 = 0.829, standard error of the estimate (SEE): 128 kcal/day, P < 0.001]. Replacing weight with LST and FM yielded a similar model, with age, sex, LST, and FM predictive of REE (R2 = 0.820, SEE: 129 kcal/day, p < 0.001).Conclusion: Age, sex, weight, LST, and FM were the main contributors to REE. Further investigation of REE changes over time and its relationship to total energy expenditure, dietary intake, and clinical outcomes should be explored.

Bioelectrical Impedance Analysis Overestimates Fat-Free Mass in Breast Cancer Patients Undergoing Treatment.

BACKGROUND: Bioelectrical impedance analysis (BIA) is commonly used to assess fat-free mass (FFM) and fat mass (FM) in breast cancer patients. However, because of the prevalence of overweight, obesity and variable hydration status in these patients, assumptions for existing prediction equations developed in healthy adults may be violated, resulting in inaccurate body composition assessment. METHODS: We measured whole-body FFM using single-frequency BIA (50 kHz) and dual-energy x-ray absorptiometry (DXA) in 48 patients undergoing treatment for breast cancer. We applied raw BIA data to 18 previously published FFM prediction equations (FFMBIA ) and compared these estimates to DXA (FFMDXA ; reference method). RESULTS: On average, patients were 52 ± 10 (mean ± SD) years of age and overweight (body mass index: 27.5 ± 5.5 kg/m2 ; body fat by DXA: 40.1% ± 6.6%). Relative to DXA, BIA overestimated FFM by 4.1 ± 3.4 kg (FFMDXA : 42.0 ± 5.9 kg; FFMBIA : 46.1 ± 3.4 kg). Individual equation-generated predictions of FFMBIA ranged from 39.6 ± 6.7 to 52.2 ± 5.6 kg, with 16 equations overestimating and 2 equations underestimating FFMBIA compared with FFMDXA . Based on equivalence testing, no equation-generated estimates were equivalent to DXA. CONCLUSION: Compared with DXA, BIA overestimated FFM in breast cancer patients during treatment. Although several equations performed better than others, none produced values that aligned closely with DXA. Caution should be used when interpreting BIA measurements in this clinical population, and future studies should develop prediction equations specific to breast cancer patients.

Accuracy of Resting Energy Expenditure Predictive Equations in Patients With Cancer.

BACKGROUND: Our purpose was to assess the accuracy of resting energy expenditure (REE) equations in patients with newly diagnosed stage I-IV non-small cell lung, rectal, colon, renal, or pancreatic cancer. METHODS: In this cross-sectional study, REE was measured using indirect calorimetry and compared with 23 equations. Agreement between measured and predicted REE was assessed via paired t-tests, Bland-Altman analysis, and percent of estimations ≤ 10% of measured values. Accuracy was measured among subgroups of body mass index (BMI), stage (I-III vs IV), and cancer type (lung, rectal, and colon) categories. Fat mass (FM) and fat-free mass (FFM) were assessed using dual x-ray absorptiometry. RESULTS: Among 125 patients, most had lung, colon, or rectal cancer (92%, BMI: 27.5 ± 5.6 kg/m2 , age: 61 ± 11 years, REE: 1629 ± 321 kcal/d). Thirteen (56.5%) equations yielded REE values different than measured (P < 0.05). Limits of agreement were wide for all equations, with Mifflin-St. Jeor equation having the smallest limits of agreement, -21.7% to 11.3% (-394 to 203 kcal/d). Equations with FFM were not more accurate except for one equation (Huang with body composition; bias, limits of agreement: -0.3 ± 11.3% vs without body composition: 2.3 ± 10.1%, P < 0.001). Bias in body composition equations was consistently positively correlated with age and frequently negatively correlated with FM. Bias and limits of agreement were similar among subgroups of patients. CONCLUSION: REE cannot be accurately predicted on an individual level, and bias relates to age and FM.

Acute high intensity interval exercise reduces colon cancer cell growth.

KEY POINTS: Physical activity is associated with reduced mortality rates for survivors of colorectal cancer. Acute high intensity interval exercise (HIIE) reduced colon cancer cell number in vitro and promoted increases in inflammatory cytokines immediately following exercise. This acute suppression of colon cancer cell number was transient and not observed at 120 minutes post-acute HIIE. The acute effects of exercise may constitute an important mechanism by which exercise can influence colorectal cancer outcomes. ABSTRACT: Physical activity is associated with significant reductions in colorectal cancer mortality. However, the mechanisms by which exercise mediates this anti-oncogenic effect are not clear. In the present study, colorectal cancer survivors completed acute (n = 10) or chronic (n = 10) exercise regimes. An acute high intensity interval exercise session (HIIE; 4 × 4 min at 85-95% peak heart rate) was completed with serum samples collected at baseline, as well as 0 and 120 min post-exercise. For the 'chronic' intervention, resting serum was sampled before and after 4 weeks (12 sessions) of HIIE. The effect of serum on colon cancer cell growth was evaluated by incubating cells (CaCo-2 and LoVo) for up to 72 h and assessing cell number. Serum obtained immediately following HIIE, but not 120 min post-HIIE, significantly reduced colon cancer cell number. Significant increases in serum interleukin-6 (P = 0.023), interleukin-8 (P = 0.036) and tumour necrosis factor-α (P = 0.003) were found immediately following acute HIIE. At rest, short-term HIIE training did not promote any changes in cellular growth or cytokine concentrations. The acute effects of HIIE and the cytokine flux may be important mediators of reducing colon cancer cell progression. Repetitive exposure to these acute effects may contribute to the relationship between exercise and improved colorectal cancer survival.

Relationships Between Weight Change and Physical and Psychological Distress in Early-Stage Breast Cancer Survivors.

BACKGROUND: Weight gain and unfavorable changes in body composition are common in a growing population of breast cancer survivors, but the etiology of these changes is poorly understood. OBJECTIVE: The aim of this study was to investigate relationships between weight change and symptoms of physical and psychological distress in the first 12 months of completing treatment in women who had completed treatment for breast cancer. METHODS: Physical distress and psychological distress were assessed using the Rotterdam Symptom Checklist, the Distress Thermometer, and the Fatigue Symptom Inventory. RESULTS: Weight change in 28 women since the completion of treatment (mean, 6.4 ± 4.4 months) ranged from -6.0 kg to +5.2 kg (mean, -0.4 ± 3.2), with 6 women gaining and 7 women losing an average of 3.5 ± 1.0 and 5.1 ± 0.8 kg, respectively. Rotterdam mean scores for physical (17.5 ± 9.0) and psychological distress (27.1 ± 16.9) were similar to previous findings for patients with early-stage breast cancer in active treatment and appear to be markedly higher than distress levels previously reported in cancer-free adults. Distress levels, based on the Distress Thermometer, were moderate to severe in 35% of women. Fatigue was common and associated with interference in daily living for some women. Fatigue duration was negatively correlated with weight change (P = -0.46, P < .05). CONCLUSIONS: Symptoms of physical and psychological distress persist for some women in the first year after completing treatment and may associate with weight change. IMPLICATIONS: These findings underscore a need for ongoing assessment and supportive care across the breast cancer trajectory and may guide dietary counseling aimed at promoting healthy body weight and overall health in early survivorship.

Computed tomography-derived assessments of regional muscle volume: Validating their use as predictors of whole body muscle volume in cancer patients.

OBJECTIVE:: Evaluate the accuracy of CT-derived regional skeletal muscle volume (SMV) measurements to predict whole body SMV in patients with melanoma. METHODS:: 148 patients with advanced melanoma who underwent whole body positron emission tomography/CT were studied. Whole body SMV was measured on CT and used as the reference standard. CT-derived regional measures of SMV were obtained in the thorax, abdomen, pelvis, and lower limbs. Models were developed on a discovery cohort (n-98), using linear regression to model whole body SMV as a function of each regional measure, and clinical factors. Predictive performance of the derived models was evaluated in a validation cohort (n = 50) by estimating the explained variation (R2) of each model. RESULTS:: In the discovery cohort, all regional SMV measurements were significantly associated with whole body SMV [ß1 range: 0.673-1.153, all p < 0.001)]. The magnitude of association was greatest for pelvic regional measurements {ß = 1.153, [95% confidence interval (0.989, 1.317)]}. Prediction algorithms incorporating clinical variables and regional SMVs were developed to estimate whole body SMV from regional assessments. Using the validation cohort to predict whole body SMV, the R2 values for the pelvic, abdominal and thoracic regional measurements were 0.89, 0.86, 0.78. CONCLUSION:: Regional measures of SMV are strong predictors of whole body SMV in patients with advanced melanoma. ADVANCES IN KNOWLEDGE:: The first study utilizing whole body imaging as a reference standard validating the use of regional SMVs in cancer patients, including validating the use of regional SMVs outside of traditionally assessed areas.

Screening for low muscularity in colorectal cancer patients: a valid, clinic-friendly approach that predicts mortality.

BACKGROUND: Low skeletal muscle quantified using computed tomography (CT) scans is associated with morbidity and mortality among cancer patients. However, existing methods to assess skeletal muscle from CT are time-consuming, expensive, and require training. Clinic-friendly tools to screen for low skeletal muscle in cancer patients are urgently needed. METHODS: We included 807 scans from non-metastatic colorectal cancer patients. With the digital ruler available in most radiological software, we implemented an abbreviated method to assess skeletal muscle area at the third lumbar vertebra (L3), which consisted of assessing the height and width of the psoas and paraspinal muscles and computing their combined 'linear area' in centimetres squared (cm2 ). A subset of CT scans was assessed twice by two analysts to compute intra-rater and inter-rater reliability. We derived cut-points for 'low' linear area using optimal stratification and then calculated the sensitivity and specificity of these cut-points relative to standard methods (total L3 cross-sectional area assessed with Slice-O-Matic research software). We further evaluated the association of low linear area with death from any cause after colorectal cancer diagnosis in Cox proportional hazards models adjusting for demographics, smoking, body mass index category, and tumour characteristics. RESULTS: The linear area was highly correlated with total cross-sectional area assessed using standard methods [r = 0.92; 95% confidence interval (CI): 0.91, 0.93] overall and within subgroups defined by age, sex, and body mass index group. Intra-rater and inter-rater reliability were equally high (both intra-class correlations = 0.98). Cut-points for low linear area were sensitive (0.75; 95% CI: 0.70, 0.80) and specific (0.77; 95% CI: 0.73, 0.80) for identifying low skeletal muscle relative to the standard of total L3 cross-sectional area. The hazard ratio and 95% CI for death associated with a low linear area were hazard ratio = 1.66; 95% CI: 1.22, 2.25. CONCLUSIONS: Clinic-friendly methods that assess linear area from CT scans are an accurate screening tool to identify low skeletal muscle among non-metastatic colorectal cancer patients. These linear measures are associated with mortality after colorectal cancer, suggesting they could be clinically useful both to improve prognostication and to provide a practical screening tool to identify cancer patients who require nutrition or exercise intervention.

Influence of Contrast Administration on Computed Tomography-Based Analysis of Visceral Adipose and Skeletal Muscle Tissue in Clear Cell Renal Cell Carcinoma.

BACKGROUND: Computed tomography (CT) scans are being utilized to examine the influence of skeletal muscle and visceral adipose quantity and quality on health-related outcomes in clinical populations. However, little is known about the influence of contrast administration on these parameters. METHODS: Precontrast, arterial, and 3-minute postcontrast CT images of 45 patients with clear cell renal cell carcinoma were downloaded from The Cancer Imaging Archive and retrospectively analyzed for visceral adipose cross-sectional area (CSA) and density, and muscle CSA and density at the third lumbar vertebrae. Low muscle CSA index was defined as ≤38.9 cm2 /m2 for women and ≤55.4 cm2 /m2 for men. Low muscle density was defined as <41 Hounsfield units (HU) for body mass index (BMI) <24.9 kg/m2 and <33 HU for BMI ≥25.0 kg/m2 . RESULTS: In both the arterial and 3-minute phases, contrast administration decreased visceral adipose CSA (-20.9 and -20.9 cm2 ; P < .001) and increased visceral adipose density (4.8 and 5.8 HU; P < .001), relative to precontrast images. Muscle CSA index marginally increased in the arterial (0.6 cm2 /m2 ; P = .007) and 3-minute phases (0.8 cm2 /m2 ; P < .001). This likely represents clinically insignificant changes because it does not alter the identification of low muscle CSA (44.4% vs 42.2%; P = 1.00). Skeletal muscle density increased in the arterial (6.4 HU; P < .001) and 3-minute phases (8.7 HU; P < .001), which altered the identification of low muscle density (6.7% vs 31.1%; P < .001). CONCLUSIONS: Future analyses should consider the phase of contrast during CT imaging because it may alter the interpretations of several parameters.