Cross sectional imaging of truncal and quadriceps muscles relates to different functional outcomes in cancer

Introduction: Following the consensus definition of cancer cachexia, more studies are using CT scan analysis of truncal muscles as a marker of muscle wasting. However, how CT-derived body composition relates to function, strength and power in patients with cancer is largely unknown. Aims: We aimed to describe the relationship between CT truncal (L3) skeletal muscle index (SMI) and MRI quadriceps cross sectional area with lower limb strength, power and measures of complex function. Methods: Patients undergoing assessment for potentially curative surgery for oesophagogastric or pancreatic cancer were recruited from the regional upper gastrointestinal (UGI) or hepatopancreaticobiliary (HPB) multi-disciplinary team meetings. Maximum Isometric Knee Extensor Strength (IKES) and Maximum Leg Extensor Power (Nottingham Power Rig) (LEP) were used as measures of lower limb performance. Both Sit to Stand (STS) and Timed Up and Go (TUG) were used as measures of global complex muscle function. Muscle SMI was measured from routine CT scans at the level of the third lumbar vertebrae (L3) and MRI scan was used for the assessment of quadriceps muscles. Linear regression analysis was performed for CT SMI or MRI quadriceps as a predictor of each measure of performance. Results: Forty-four patients underwent assessment. Height and weight were significantly related to function in terms of quadriceps power, while only weight was associated with strength (P < 0.001). CT SMI was not related to measures of quadriceps strength or power but had significant association with more complex functional measures (P = 0.006, R2 = 0.234 and 0.0019, R2 = 0.175 for STS and TUG respectively). In comparison, both gross and fat-subtracted measures of quadriceps muscle mass from MRI were significantly correlated with quadriceps strength and power (P < 0.001), but did not show any significant association with complex functional measures. Conclusion: CT SMI and MRI quadriceps have been shown to reflect different aspects of functional ability with CT SMI being a marker of global muscle function and MRI quadriceps being specific to quadriceps power and strength. This should therefore be considered when choosing outcome measures for trials or definitions of muscle mass and function

Pathophysiology of cancer cachexia: much more than host–tumour interaction?

Cancer cachexia is a syndrome of progressive nutritional depletion which causes significant morbidity and mortality in cancer patients. One of the main pathogenetic mechanisms underlying cancer cachexia is a complex interaction between the host and the tumour. Tumour cells interact with host cells within the tumour mass resulting in the production of catabolic mediators which degrade host tissue. In addition, the host may mount an aberrant metabolic response to the tumour. However, in recent years, it has also been understood that patient factors, including age and levels of physical activity, and the specific mechanics of protein metabolism in cancer patients may also have a significant impact. In this review article, we not only summarise previous knowledge surrounding host-tumour interaction, but we also discuss these broader concepts in the pathogenesis of cancer cachexia. Clinicians should consider such concepts in the design of an effective multimodal therapy for cachexia

Suppression of Skeletal Muscle Turnover in Cancer Cachexia: Evidence from the Transcriptome in Sequential Human Muscle Biopsies

Purpose: The mechanisms underlying muscle wasting in patients with cancer remain poorly understood, and consequently there remains an unmet clinical need for new biomarkers and treatment strategies.Experimental Design: Microarrays were used to examine the transcriptome in single biopsies from healthy controls (n ¼ 6) and in paired biopsies [pre-resection baseline (weight-loss 7%) and 8 month postresection follow-up (disease-free/weight-stable for previous 2 months)] from quadriceps muscle of patients with upper gastrointestinal cancer (UGIC; n ¼ 12).Results: Before surgery, 1,868 genes were regulated compared with follow-up (false discovery rate, 6%). Ontology analysis showed that regulated genes belonged to both anabolic and catabolic biologic processes with overwhelming downregulation in baseline samples.Noliterature-derived genes from preclinical cancer cachexia models showed higher expression in baseline muscle. Comparison with healthy control muscle (n¼6) revealed that despite differences in the transcriptome at baseline (941 genes regulated), the muscle of patients at follow-up was similar to control muscle (2 genes regulated). Physical activity (step count per day) did not differ between the baseline and follow-up periods (P ¼ 0.9), indicating that gene expression differences reflected the removal of the cancer rather than altered physical activity levels. Comparative gene expression analysis using exercise training signatures supported this interpretation.Conclusions: Metabolic and protein turnover–related pathways are suppressed in weight-losing patients with UGIC whereas removal of the cancer appears to facilitate a return to a healthy state, independent of changes in the level of physical activity

Physical Activity Monitoring: A Responsive and Meaningful Patient-Centered Outcome for Surgery, Chemotherapy, or Radiotherapy?

Context: In surgical and clinical oncology, there is a growing need for patient-centered outcomes that are responsive, meaningful, and fit for purpose. <p/>Objectives: The aim of this study was to validate physical activity (PA) monitoring as a responsive outcome measure at different stages of disease and treatment, by verifying correlations between PA, performance score, and quality of life (QoL). <p/>Methods: Daily life PA of 162 cancer patients, monitored by a device that records time sitting/lying, time standing, time walking, number of steps taken, and walking cadence, was compared with 20 healthy volunteers. In a subgroup of patients, functional status and QoL were assessed using the World Health Organization/Eastern Cooperative Oncology Group and the Karnofsky Performance Status scores and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) questionnaire. <p/>Results: The PA of patients with resectable gastrointestinal cancer did not differ significantly from controls. In contrast, patients with advanced cancer took 45% fewer steps and spent an extra 2.8 hours/day lying/sitting (P = 0.001). Patients undergoing neoadjuvant chemotherapy and surgery (5–6 weeks after operation) experienced a similar reduction in PA. There were significant correlations between PA and the physical and role domains as well as fatigue subscale of the EORTC QLQ-C30 scale. <p/>Conclusion: Objective PA scores correlate significantly with disease stage, functional status, and QoL of patients with cancer. Therefore, activity monitoring can make meaningful objective estimates of patient function in response to cancer and its treatment and may provide surrogate outcomes of QoL