Cancer cachexia in the era of obesity

Skeletal muscle depletion, independent of body mass index, predicts survival in patients with cancer

It has been known for a long time that involuntary weight loss is prognostic for reduced survival in patients with cancer. What has not been clear is which tissue type might have been lost. Previous research by Vickie Baracos, PhD and colleagues of the Palliative Care Medicine, Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada, showed that sarcopenia (severe muscle depletion) is independently prognostic for poor survival in obese patients with cancer. Her team has now extended these findings to reveal that muscle depletion and low muscle attenuation are poor prognostic factors, regardless of overall body weight. The researchers published novel findings in the Journal of Clinical Oncology. They have been presented in part previously at the Cancer Cachexia: Molecular Mechanisms and Therapeutic Approaches Conference in Boston, USA in September 2012.

The patients in this study were assessed at presentation for weight loss history, lumbar skeletal muscle index, and mean muscle attenuation by computed tomography (CT). The study researchers analysed CT images to quantify the amount of muscle and adipose tissue. In particular, CT imaging allowed them to identify two muscle characteristics: extreme depletion of skeletal muscle and reduced radiation attenuation of muscle.

Body mass index (BMI) distribution was: 17% obese, 35% overweight, 36% normal weight, and 12% underweight. Patients in all BMI categories varied widely in weight loss, muscle index, and muscle attenuation. Thresholds defining associations between these three variables and survival were determined using optimal stratification. High weight loss, low muscle index, and low muscle attenuation were independently prognostic of survival. Patients who possessed all three of these poor prognostic variables survived 8.4 months, regardless of whether they presented as obese, overweight, normal weight, or underweight, in contrast to patients who had none of these features, who survived 28.4 months (p < 0.001).

The present study that assessed nearly 1,500 patients, showed that obese patients with weight loss, sarcopenia and low muscle attenuation had a significantly worse survival, which was in direct contrast to the survival of obese patients without these variables. The researchers concluded that CT images reveal otherwise occult muscle depletion. Patients with cancer who are cachexic by the conventional criterion (involuntary weight loss) and by two additional criteria (muscle depletion and low muscle attenuation) share a poor prognosis, regardless of overall body weight.

According to Dr Baracos confluence of epidemic obesity and epidemic muscle wasting is best description of what they have seen in this study. Dr Lisa Martinaff and Dr Laura Birdsellaff contributed equally to this work as first authors. The study was supported by the Canadian Institutes of Health Research.

Baracos's team plans to move their latest research forward. They will first evaluate therapeutic interventions to prevent or reverse muscle wasting, which include muscle-specific anabolic agents and nutrients essential for the retention or gain of muscle mass. Their analysis, as well as a series of related works, suggests that patients with severe depletion of skeletal muscle may be unusually sensitive to developing serious chemotherapy-related toxicities. The study team evaluates approaches to chemotherapy dosing that will be consistent with the reduced tolerance of these individuals.

The findings and perspective from this study are covered in the news and views section of Nature Reviews Clinical Oncology, as advance online publication, published online on 9 April 2013. The full news and views article you can read through the ESMO Scientific Journals Access programme.