Body Composition in Advanced Non-Small Cell Lung Cancer Treated With Immunotherapy

Abstract

Importance: The association 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 and yielded promising, albeit heterogeneous, results.

Objectives: To evaluate the association of BC with oncologic outcomes in patients receiving immunotherapy for advanced or metastatic NSCLC.

Design, setting, and participants: This comprehensive multicohort analysis included clinical data from cohorts receiving treatment at the Dana-Farber Brigham Cancer Center (DFBCC) who received immunotherapy given alone or in combination with chemotherapy and prospectively collected data from the phase 1/2 Study 1108 and the chemotherapy arm of the phase 3 MYSTIC trial. Baseline and follow-up computed tomography (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). Outcomes were compared based on baseline BC measures or their change at the first follow-up scan. The data were analyzed between July 2022 and April 2023.

Main outcomes and measures: Hazard ratios (HRs) for the association of BC measurements with overall survival (OS) and progression-free survival (PFS).

Results: A total of 1791 patients (878 women [49%]) with NSCLC were analyzed, of whom 487 (27.2%) received chemoimmunotherapy at DFBCC (DFBCC-CIO), 825 (46.1%) received ICI monotherapy at DFBCC (DFBCC-IO), 222 (12.4%) were treated with durvalumab monotherapy on Study 1108, and 257 (14.3%) were treated with chemotherapy on MYSTIC; median (IQR) ages were 65 (58-74), 66 (57-71), 65 (26-87), and 63 (30-84) years, respectively. A loss in SM mass, as indicated by a change in the L3 SM area, was associated with worse oncologic outcome across patient groups (HR, 0.59 [95% CI, 0.43-0.81] and 0.61 [95% CI, 0.47-0.79] for OS and PFS, respectively, in DFBCC-CIO; HR, 0.74 [95% CI, 0.60-0.91] for OS in DFBCC-IO; HR, 0.46 [95% CI, 0.33-0.64] and 0.47 [95% CI, 0.34-0.64] for OS and PFS, respectively, in Study 1108; HR, 0.76 [95% CI, 0.61-0.96] for PFS in the MYSTIC trial). This association was most prominent among male patients, with a nonsignificant association among female patients in the MYSTIC trial and DFBCC-CIO cohorts on Kaplan-Meier analysis. An increase of more than 5% in SAT density, as quantified by the average CT attenuation in Hounsfield units of the SAT compartment, was associated with poorer OS in 3 patient cohorts (HR, 0.61 [95% CI, 0.43-0.86] for DFBCC-CIO; HR, 0.62 [95% CI, 0.49-0.79] for DFBCC-IO; and HR, 0.56 [95% CI, 0.40-0.77] for Study 1108). The change in SAT density was also associated with PFS for DFBCC-CIO (HR, 0.73; 95% CI, 0.54-0.97). This was primarily observed in female patients on Kaplan-Meier analysis.

Conclusions and relevance: The results of this multicohort study suggest that loss in SM mass during systemic therapy for NSCLC is a marker of poor outcomes, especially in male patients. SAT density changes are also associated with prognosis, particularly in female patients. Automated CT-derived BC measurements should be considered in determining NSCLC prognosis.

Figure 1.. Overview of the Model Implementation and Study Population

A, Model workflow implemented in the study. B, Study population, which consisted of both retrospective Dana-Farber Brigham Cancer Center (DFBCC) cohorts (chemoimmunotherapy [CIO] and immune checkpoint inhibitor monotherapy [IO]) and prospectively collected clinical trial data from Study 1108 and MYSTIC. C, Body composition profiling at baseline and follow-up scan. D, Representative outputs of the model for patients with varying body composition distributions. Yellow represents subcutaneous adipose tissue (SAT), green represents skeletal muscle (SM), and brown represents visceral adipose tissue (VAT). The panels include a representative high SM/low-fat distribution, a representative low SM/high-fat distribution, and a representative high SM/high-fat distribution. D.2 and D.3 also depict individuals with high VAT and high SAT, respectively, illustrating these 2 distinct body composition phenotypes. 2-D indicates 2-dimensional; 3-D, 3-dimensional; CT, computed tomography.

Figure 2.. Cox Proportional Hazard Models for the Association of Various Parameters With Overall Survival (OS) and Progression-Free Survival (PFS) in the Dana-Farber Brigham Cancer Center Chemoimmunotherapy (DFBCC-CIO) Cohort

The hazard ratios (HRs) and their corresponding 95% CIs are displayed for 3 groups of parameters: (1) clinical parameters, which include demographic and clinical characteristics of the patients at baseline; (2) baseline measures, which consist of measurements taken at the beginning of treatment; (3) delta measures, which represent changes in these baseline measures over time. BMI indicates body mass index; ECOG, Eastern Cooperative Oncology Group; PD-L1, programmed cell death ligand 1; SAT, subcutaneous adipose tissue; SM, skeletal muscle; SMa, skeletal muscle area; VAT, visceral adipose tissue.

Figure 3.. Cox Proportional Hazard Models for the Association of Various Parameters With Overall Survival (OS) and Progression-Free Survival (PFS) in the Dana-Farber Brigham Cancer Center Immune Checkpoint Inhibitor Monotherapy (DFBCC-IO) Cohort

The hazard ratios (HRs) and their corresponding 95% CIs are displayed for 3 groups of parameters: (1) clinical parameters, which include demographic and clinical characteristics of the patients at baseline; (2) baseline measures, which consist of measurements taken at the beginning of treatment; and (3) delta measures, which represent changes in these baseline measures over time. BMI indicates body mass index; ECOG, Eastern Cooperative Oncology Group; programmed cell death ligand 1, PD-L1; PD-L1, programmed cell death ligand 1; SAT, subcutaneous adipose tissue; SM, skeletal muscle; SMa, skeletal muscle area; VAT, visceral adipose tissue.

Figure 4.. Cox Proportional Hazard Models for the Association of Various Parameters With Overall Survival (OS) and Progression-Free Survival (PFS) in the Study 1108 cohort

The hazard ratios (HRs) and their corresponding 95% CIs are displayed for three groups of parameters: (1) clinical parameters, which include demographic and clinical characteristics of the patients at baseline; (2) baseline measures, which consist of measurements taken at the beginning of treatment; and (3) delta measures, which represent changes in these baseline measures over time. BMI indicates body mass index; ECOG, Eastern Cooperative Oncology Group; PD-L1, programmed cell death ligand 1; SAT, subcutaneous adipose tissue; SM, skeletal muscle; SMa, skeletal muscle area; VAT, visceral adipose tissue.

Figure 5.. Cox Proportional Hazard Models for the Association of Various Parameters With Overall Survival (OS) and Progression-Free Survival (PFS) in the MYSTIC Cohort

The hazard ratios (HRs) and their corresponding 95% CIs are displayed for 3 groups of parameters: (1) clinical parameters, which include demographic and clinical characteristics of the patients at baseline; (2) baseline measures, which consist of measurements taken at the beginning of treatment; and (3) delta measures, which represent changes in these baseline measures over time. BMI indicates body mass index; ECOG, Eastern Cooperative Oncology Group; PD-L1, programmed cell death ligand 1; SAT, subcutaneous adipose tissue; SM, skeletal muscle; SMa, skeletal muscle area; VAT, visceral adipose tissue.