Body Composition and Blood-Based Prognostic Markers in Immunotherapy-Treated Metastatic Non-Small Cell Lung Cancer

Metastatic non-small cell lung cancer (mNSCLC) is among the leading causes of cancer-related mortality worldwide. Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have improved survival outcomes, yet responses remain heterogeneous. Prognostic biomarkers such as sarcopenia and systemic inflammation-metabolism indices may help optimize patient selection.

This retrospective, single-center cohort study will analyze 115 adult patients with mNSCLC treated with ICIs at Ankara Etlik City Hospital between November 2022 and December 2024. Sarcopenia will be assessed from computed tomography (CT) imaging at the L3 vertebral level by calculating skeletal muscle index (SMI = skeletal muscle area [cm²] / height² [m²]). Patients will be classified as sarcopenic if SMI ≤52.4 cm²/m² for men or ≤38.5 cm²/m² for women. Both baseline and 3-month CT scans will be analyzed to assess dynamic changes (ΔSMI).

The CRP-TyG Index (CTI) will be calculated as:

TyG = ln [triglycerides (mg/dL) × fasting glucose (mg/dL) / 2] CTI = 0.412 × ln [CRP (mg/L)] + TyG Patients will be categorized into low- and high-risk groups using the published cut-off of 4.78.

The primary endpoint is objective response rate (ORR, RECIST v1.1). Secondary endpoints include 12-month progression-free survival (PFS), overall survival (OS), treatment duration, adverse events (graded by CTCAE v5.0), and sarcopenia dynamics. Associations between CTI and sarcopenia will also be explored. Statistical analyses include multivariable logistic regression for ORR and Cox proportional hazards models for PFS/OS, adjusting for age, sex, and ECOG status.

This study aims to integrate radiological (sarcopenia), biochemical (CRP, triglycerides, glucose), and clinical outcomes to determine whether sarcopenia and CTI can serve as practical prognostic markers for immunotherapy in real-world mNSCLC patients.

Inclusion criteria

• Age ≥18 years.
• Histologically confirmed diagnosis of metastatic non-small cell lung cancer (mNSCLC).
• Received at least one cycle of immune checkpoint inhibitor (PD-1 or PD-L1 inhibitor) as part of routine clinical care.
• Availability of baseline CT imaging (within 4 weeks before treatment initiation) and follow-up CT imaging at approximately 3 months.
• Availability of baseline laboratory data including C-reactive protein (CRP), triglycerides, and fasting glucose.
• Adequate clinical records for evaluation of treatment response and survival outcomes.

Exclusion criteria

• Age <18 years.
• Patients without immunotherapy treatment.
• Incomplete or missing CT imaging or laboratory data required for sarcopenia or CTI assessment.
• Patients lost to follow-up before first radiological evaluation.
• Prior malignancy within 5 years (except adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix).