In Reply Indeed, both the etiopathogenesis and management of skeletal muscle loss in patients with head and neck cancer remain complex. The thoughtful letter of Mazzola and colleagues helps bring into focus the questions raised by our study and the insights that may be gleaned from these data. We sincerely appreciate the opportunity to expand this discussion.
The effect of cachexia on survival in the context of multiple malignant conditions is well documented.1 Head and neck cancer is unique among these conditions in that the disease directly involves the aerodigestive tract, leading to dysfunction in deglutition secondary to both local tumor invasion and treatment toxicity. Therefore, although our study identified patients who meet the consensus definition for cachexia, the confounding role of sustained undernutrition could not be excluded. If cachexia is the major contributor to survival-affecting skeletal muscle loss, we would expect to see an effect of muscle loss on survival independent of body mass index, as reported by Martin et al.2 Yet, our data clearly demonstrated collinearity between these variables along with an apparent protective effect of obesity, suggesting a primary role for undernutrition, rather than cachexia, in mediating skeletal muscle loss. The absence of obese patients with skeletal muscle depletion from our study limits the validity of this interpretation, as it is unclear whether it represents this overall patient population or is an artifact of retrospective design and study size. Furthermore, without serum cytokine level data we cannot rule out an inflammatory contribution, which prior research suggests may be indicative of cachexia and necessary for muscle wasting.3