Cancer cachexia is a state of involuntary
weight loss and altered body composition triggered by an underlying
malignancy. We sought to correlate measures of
cachexia with clinical outcomes in aggressive
lymphomas and to identify biological pathways involved in the
cachexia phenotype for possible druggable targets. Radiographic measures of
cachexia were collected in a retrospective cohort of 109 patients with aggressive
B-cell lymphoma and followed for clinical outcome. We found males with
sarcopenia had reduced progression-free survival (5·4 vs. 72·3 months, P < 0·0005) and overall survival (OS; 30·2 months vs. not reached, NR, P = 0·02); males with adipopenia also had decreased OS (21·6 months vs. NR, P = 0·04). A trend for increased OS was observed in female sarcopenics only (32·8 months vs. NR, P = 0·08). Additionally, we analysed a prospective cohort of 14 patients for differences in circulating molecular targets involved in various biological pathways. There was a significant correlation with
cachexia for reduced serum levels of mediators within the
glucose utilization [
insulin -like growth factor (
IGF)-binding protein 6, P = 0·04;
IGF-1, P = 0·02],
inflammation (
lymphotoxin-like inducible
protein that competes with
glycoprotein D for herpesvirus entry on T cells; LIGHT, P = 0·005), and energy intake/expenditure (
leptin, P = 0·004). We conclude that
cachexia in patients with aggressive
lymphomas has sex-specific prognostic utility and correlates with measurable changes in metabolism and immune function.