AI-Derived CT Body Composition in Advanced Non-Small Cell Lung Cancer: A Multicohort Study

Abstract

The relationship between body composition (BC) and cancer outcomes is complex and incompletely understood. Previous research in non-small cell lung cancer (NSCLC) has been limited to small single-institution studies, which have yielded inconsistent results. We conducted a comprehensive multicohort analysis to evaluate the impact of BC on overall survival (OS) in advanced NSCLC treated with systemic therapy. The analysis included data from the phase I/II CP1108 study (NSCLC Durvalumab cohort) and the chemotherapy arm of the phase III MYSTIC trial. We also analyzed data from Dana-Farber Cancer Institute (DFCI) cohorts receiving immunotherapy alone or in combination with chemotherapy. Baseline and follow-up (FU) CT scans were collected and analyzed using deep neural networks for automatic L3 slice selection and body compartment segmentation (skeletal muscle [SM], subcutaneous adipose tissue [SAT], and visceral adipose tissue [VAT]). We compared OS based on baseline BC measures or their change at the first FU scan. The impact of sarcopenia at baseline was evaluated in association with the delta metrics. A total of 1865 NSCLC patients were analyzed, of which 222 were treated on CP1108, 257 were treated on MYSTIC, 870 received IO monotherapy at DFCI (DFCI-IO), and 516 received chemoimmunotherapy at DFCI (DFCI-CIO). The median ages were 65, 63, 66, and 65, respectively. A loss in SM mass >5%, as indicated by a change in L3 SM area, was significantly associated with poorer OS across all patient groups (median [months]: 5 vs. 19; p<0.001 for CP1108, 11 vs. 14; p = 0.03 for MYSTIC, 11 vs. 17; p<0.001 for DFCI-IO, and 12 vs. 22; p<0.001 for DFCI-CIO). This effect was driven by male patients, with a non-significant association (p>0.5) among female patients in the MYSTIC and DFCI-CIO cohorts. An increase in SAT density >5%, as quantified by the average CT attenuation in HU of the SAT compartment, was significantly linked to poorer OS in three patient groups (median [months]: 4 vs. 19; p<0.001 for CP1108, 10 vs. 17; p<0.001 for DFCI-IO, and 12 vs. 20; p = 0.003 for DFCI-CIO). This was primarily observed among female patients, with a non-significant association (p>0.5) among male patients in the DFCI-CIO cohort. On subgroup analysis, loss in SM mass had an impact on OS in patients with baseline sarcopenia (median [months] 5 vs. 22; p<0.001 for CP1108, 5 vs. 12; p = 0.03 for MYSTIC, 11 vs. 17; p<0.001 for DFCI IO, and 9 vs. 17; p = 0.003 for DFCI-CIO). Conversely, no association was observed between change in SM mass and OS in patients without sarcopenia at baseline in the MYSTIC and DFCI-IO cohorts. Sarcopenia and loss in SM mass during systemic therapy for NSCLC are markers of poor outcome, especially in male patients. SAT density changes are also strongly associated with prognosis, particularly in female patients. Automated CT-derived BC measurements should be considered along with other risk factors in determining lung cancer prognosis and ability to tolerate oncologic treatments.