Characterization of pretreatment cachexia through cytokine and nutritional analysis in lung cancer: the Marato cohort

BackgroundCancer-associated cachexia, a frequent complication of solid tumours, is not recorded in cancer registries. Cachexia affects patients diagnosed with non-small cell lung cancer (NSCLC); however, a detailed characterization of nutritional and body composition parameters matched with blood-based, non-invasive markers is lacking. We hypothesized that a systematic characterization of cachectic patients may facilitate the development of interventions aimed to improve clinical outcomes. MethodsWe conducted a prospective study of 51 patients diagnosed with locally advanced unresectable NSCLC who underwent concurrent chemoradiotherapy followed by immunotherapy at the HUB-ICO Comprehensive Cancer Centre from 2022 to 2024. The primary objectives were (1) to determine the prevalence of cachexia according to Fearons criteria and (2) to comprehensively characterize patients before and after completing chemoradiotherapy in terms of nutritional status, metabolic parameters, body composition and circulating cytokine levels. Here, we report the baseline assessment results. ResultsMost patients were male (80%), ever smokers (98%) with a median age of 68 years. All patients completed the planned concurrent chemoradiotherapy regimen, while only 43% initiated durvalumab consolidation therapy. At baseline, 53% of patients met the diagnostic criteria for cachexia. Women were more likely to have cachexia at baseline compared to men, although these differences were not statistically significant. Cachexia was significantly associated with tumor stage (p < 0.001), performance status (p = 0.027), lower skeletal muscle index (p = 9e-4) and total adipose tissue index (p = 0.004), elevated C-Reactive Protein blood levels (p = 0.004), moderate to severe malnutrition (p < 0.001), reduced caloric intake (p = 0.007) and diminished physical strength (p=0.001). Proteomic profiling using the O-link platform revealed significant differences in circulating cytokine levels between cachectic and non-cachectic patients. Cachexia was significantly associated with elevated levels of CCL23, IL-6, IL-11, Oncostatin M (OSM), pentraxin-related protein 3 (PTX3), and agouti-related protein (AGRP), among others, demonstrating varying degrees of correlation with caloric intake. GDF15 was associated with weight loss (p = 0.00014), but not with calorie intake or body composition. ConclusionsThis prospective study reveals that cancer cachexia is highly prevalent in patients with unresectable locally advanced NSCLC. In addition to previously known cytokines, we identified several understudied cytokines, which may contribute to a more comprehensive characterization of the cachexia phenotype and help uncover potential targets for therapeutic interventions.