Cachexia represents a challenging clinical syndrome with a profound effect on patients with cancer, including reduced physical function, reduced tolerance to anticancer therapy, and reduced survival.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, and a lack of US Food and Drug Administration (FDA)-approved treatments for cachexia.1

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 an interest in developing pharmacologic treatments for muscle loss.2 To date, “most of the work on human body weight regulation has been done in the context of obesity,” explains Vickie E. Baracos, PhD, who served on the international consensus expert panel. 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,” said 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?”

NEW DIAGNOSTIC CRITERION

Cachexia occurs in more than 80% of patients with gastric, pancreatic, and esophageal cancer; 70% of those with head and neck cancer; and approximately 60% of patients with lung, colorectal, and prostate cancer, and it contributes directly to death in 20% of cases.3,4 Cachexia was defined as a body mass index (BMI) of less than 20 kg/m2 and an unintentional weight loss of 5% or more over the past 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 of more than 5% over the past 6 months (in the absence of simple starvation); or BMI of less than 20 kg/m2 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 greater than 2%.1

The pathophysiology of cancer cachexia “is characterized by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism,” the expert panel noted. Patient assessment for classification and clinical management, therefore, should include “anorexia or reduced food intake, catabolic drive, muscle mass and strength, [and] functional and psychosocial impairment.”1

PROGNOSTIC VARIABLES: NOT JUST WEIGHT LOSS

Recently, Baracos and colleagues found that skeletal muscle depletion revealed on CT images predicted poor prognosis in patients with cancer. In their study, the researchers assessed 1,473 consecutive patients with lung or gastrointestinal cancer 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

“High weight loss, low muscle index, and low muscle attenuation were independently prognostic of survival,” the researchers reported. Patients with all three of these poor prognostic variables survived 8.4 months (95% CI, 6.5-10.3), regardless of whether they presented as obese, overweight, normal weight, or underweight; in contrast, patients who had none of these variables survived 28.4 months (95% CI, 24.2-32.6; P<.001).”5

Baracos noted that previous clinical studies examining cachexia included patients with only weeks to live. “The thought now is that this has been too late,” she said. “We are in a position to make sure that we catch it early; the detection of weight loss should be incorporated into routine clinical process so that if anything could be done, it could be done as soon as possible.”

This includes, for example, using the Patient-Generated Subjective Global Assessment (PG-SGA), a nutrition assessment tool, to detect malnutrition so patients with cancer can be triaged for nutrition support.6 In a study of hospitalized patients with cancer, the tool was found to be easy to use, and allowed clinicians to quickly identify and prioritize malnutrition. The patient completes the first four boxes of the PG-SGA, which ask about weight (Box 1), food intake (Box 2), symptoms (Box 3), and activities and function (Box 4). Each response is scored, and the scores are totaled.

The remainder of the one-page form is completed by the clinician and includes scoring the patient’s condition (1 point for cancer) and metabolic stress (eg, fever, duration of fever, and use of corticosteroids); physical examination findings, including fat stores, muscle status, and fluid states; and global assessment (A, well-nourished; B, moderately malnourished or suspected malnutrition; or C, severely malnourished) based on weight, nutrient intake, nutrition impact symptoms, functioning, and physical exam. Each of these sections is scored. The scores from the patient-completed boxes and the clinician-completed boxes are totaled for an overall assessment score.