Cancer Cachexia: No Longer Simply Involuntary Weight Loss

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Cancer Cachexia: No Longer Simply Involuntary Weight Loss
Cancer Cachexia: No Longer Simply Involuntary Weight Loss

Cachexia represents a challenging clinical syndrome with a profound effect on patients with cancer. Characterized by “a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism,” cachexia can result in significant weight loss and decrease in skeletal muscle mass, which can then lead to decreased physical function, reduced tolerance to anticancer therapy, and can ultimately lessen survival time.1

Yet, weight loss in patients with cancer often remains undiagnosed and untreated, primarily for two reasons: “in the age of obesity,” the importance of skeletal muscle mass—with or without loss of fat mass—is only now being evaluated,1and lack of U.S. Food and Drug Administration (FDA)-approved treatments for cachexia.

However, recent advances in understanding the biology of muscle wasting have led both to an international consensus on the definition and classification of cancer cachexia and to interest in development of pharmacological treatments for muscle loss.2

To date, “most of the work on human body weight regulation has been done in the context of obesity,” Vickie E. Baracos, PhD, who served on the international consensus expert panel, told ChemotherapyAdvisor.com. She pointed out that for centuries, clinical examinations have included body weight; however, “1 kg of human being is not all the same. We've now understood and acknowledged that we must assess body composition; without body composition, you really don't know anything,” added Dr. Baracos, a professor in palliative care medicine in the Department of Oncology at the University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada. What's more important is, “how much muscle, how much fat, and where is that fat?”

Cachexia occurs in more than 80% of patients with gastric, pancreatic, and esophageal cancer; 70% of those with head and neck cancer; approximately 60% of patients with lung, colorectal, and prostate cancer.3 Estimates indicate that cachexia contributes directly to death in 20% of cases.4 Previously, cachexia was defined as a body mass index (BMI) of less than 20 mg/m2 and/or an unintentional weight loss of 5% or more in the previous 6 months in the setting of underlying disease, such as cancer.3 The expert panel has now agreed that cachexia can develop progressively, from precachexia to cachexia to refractory cachexia, “a spectrum through which not all patients will progress.1

The new diagnostic criterion for cachexia is weight loss 5% or more over the past 6 months (in the absence of simple starvation); or BMI 20 mg/m2 or less and any degree of weight loss greater than 2%; or appendicular skeletal muscle index consistent with sarcopenia (males < 7.26 kg/m2; females < 5.45 kg/m2) and any degree of weight loss over 2%. Patient assessment for classification and clinical management should include “anorexia or reduced food intake, catabolic drive, muscle mass and strength, [and] functional and psychosocial impairment.”1

Recently, Dr. Baracos and colleagues found that skeletal muscle depletion, apparent on computed tomography (CT) images, predicted poor prognosis in patients with cancer. A study of 1,473 consecutive patients with lung or gastrointestinal cancer were assessed at presentation for weight loss history, lumbar skeletal muscle index, and mean muscle attenuation by CT. BMI distribution was obese (17%), overweight (35%), normal weight (36%), and underweight (12%).5

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