From Symptom to Outcome: Defining Clinically Meaningful Patient-Reported Appetite Loss in Non-Small-Cell Lung Cancer

Appetite loss is a common and distressing symptom in non-small-cell lung cancer (NSCLC), driven by both treatment side effects and disease progression. It often leads to unintended weight loss and cancer cachexia, significantly impairing patients' quality of life and survival. Yet, appetite loss remains under-recognized in oncology care, with no standard assessment tools or universal management guidelines. In this study, we developed a predictive model to identify clinically meaningful thresholds of appetite loss that were associated with significant weight reduction and decreased survival. We aim to highlight the clinical consequences of appetite loss and advocate for more patient-centred treatment strategies that address this often overlooked but impactful symptom in cancer care.

We analysed longitudinal patient-reported appetite scores, measured by the Lung Cancer Symptom Scale (LCSS), and body weight data from 476 NSCLC patients receiving supportive care and recovering from prior chemoradiotherapy (recovering cohort). A mechanism-based population modelling approach was used to predict the impact of appetite changes on body weight, accounting for significant data variability. Model validation was conducted using data from 380 NSCLC patients undergoing docetaxel chemotherapy (chemotherapy cohort). Clinically meaningful appetite loss thresholds were determined based on the model-predicted appetite loss associated with a 3.5-kg body weight loss and significantly worse survival (hazard ratio > 1, p < 0.05).

We found that, according to the LCSS (100-mm visual analogue scale), a 30-mm (90% CI, 28-32) improvement in appetite corresponded to a 3.5-kg weight gain in the recovering cohort, while a 23-mm (90% CI, 17-30) decline correlated with a 3.5-kg weight loss in the chemotherapy cohort. Significant associations were observed between appetite loss trajectories and overall survival (p < 0.001). Clinically meaningful thresholds for appetite loss were identified as 4 mm at 1 month and 11 mm at 3 months, both significantly associated with reduced OS in patients receiving docetaxel chemotherapy (p < 0.05).

We developed a population predictive model to characterize the relationship between patient-reported appetite and body weight, identifying clinically meaningful thresholds for appetite loss. This work highlights the importance of managing appetite loss in oncology care and supports its use as a quantitative endpoint in clinical trials and practice.