3488 - Tumor Volume and Skeletal Muscle Coupling in Stage III NSCLC Treated with Definitive Chemoradiation
Presenter(s)
A. Gupta1, D. P. Umesh1, D. K. Bhatia2, I. Ahmad1, K. S. Chufal1, R. Bajpai3, A. Miller4, and M. Gairola1; 1Department of Radiation Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India, 2Rajiv Gandhi Cancer Institute and Research Center, New Delhi, India, 3School of Medicine, Keele University, Staffordshire, United Kingdom, 4Department of Radiation Oncology, Illawarra Cancer Care Centre, Wollongong, Australia
Purpose/Objective(s): To evaluate longitudinal, phase-specific and correlated changes in metabolic tumour burden and skeletal muscle mass after CCRT in stage III NSCLC.
Materials/Methods: This study enrolled 242 patients with stage IIIA–C (AJCC 8th) NSCLC diagnosed between January 2010 and September 2024, who received either upfront CCRT or neoadjuvant chemotherapy (NACT) followed by CCRT. Metabolic tumour volume (MTV) and skeletal muscle index (SMI; L3 muscle area normalised to height) were derived from PET-CT scans acquired during routine care. Joinpoint modelling identified a clinically anchored hinge at +3 months post-radiotherapy to define an acute phase (=3 months post-RT) and a survivorship phase (>3 months post-RT). We then fitted segmented linear mixed-effects models with patient-level random intercepts and pre-/post-hinge slopes, using within–between (Mundlak) decomposition for time-varying covariates. A Bayesian bivariate mixed-effects model with an unstructured patient-level random-effects covariance matrix quantified correlated changes of MTV and SMI.
Results: 221 patients (1011 PET-CT scans) were evaluable for this analysis. MTV declined faster with CCRT than NACT in the acute phase(-36.7%/month vs -21.9%/month; pinteraction<0.001). SMI declined across the cohort (acute phase = -0.18 units/month; chronic phase = -0.05 units/month; both p<0.05). Within-patient MTV increases were associated with acute muscle depletion (-0.22 SMI units per 1-unit increase in MTV log1p; p=0.024).
The Bayesian model identified four clinically significant relationships: higher baseline MTV correlated with flatter acute tumour regression (?=0.51) and steeper acute muscle loss (?=-0.63); acute MTV and acute SMI slopes were inversely correlated (?=-0.39), and; poor acute tumour regression predicted accelerated chronic muscle loss (?=-0.52).Conclusion: Our analysis identified an association between high baseline metabolic tumour burden and suboptimal early metabolic response as risk factors for sustained sarcopenia. Response-adapted cachexia surveillance and early supportive interventions are potential avenues for future research on this issue.