# Bone mineral density as a prognostic marker in patients with non-small cell lung cancer undergoing neoadjuvant chemoimmunotherapy

## TL;DR

This study shows that bone mineral density measured via CT scans can predict survival outcomes in lung cancer patients receiving chemoimmunotherapy.

## Contribution

First study linking CT-derived L1 bone mineral density to disease-free survival in non-small cell lung cancer patients undergoing neoadjuvant chemoimmunotherapy.

## Key findings

- Higher baseline and preoperative L1 bone mineral density correlates with improved disease-free survival.
- Lower bone mineral density after treatment is associated with poorer outcomes.
- Age and treatment response influence the prognostic value of bone mineral density.

## Abstract

Non-small cell lung cancer (NSCLC) is the most common lung cancer, and surgery is the primary curative treatment approach. Recently, neoadjuvant immunotherapy combined with chemotherapy (NICT) has become an important strategy. However, not all patients benefit, underscoring the need for reliable prognostic biomarkers. Bone mineral density (BMD) is associated with the prognosis of various cancers. This study explores the relationship between computed tomography (CT)-derived BMD and prognosis in NSCLC patients treated with NICT.

101 stage IIA-IIIB NSCLC patients undergoing NICT and R0 resection surgery at our institution were included. Chest CT, highly correlated with dual-energy X-ray absorptiometry (DXA), was used to analyze the baseline and preoperative T10, T12, and L1 BMD. We analyzed disease-free survival (DFS) and overall survival (OS) through Kaplan-Meier survival curves, cox regression, and restricted cubic splines (RCS). Major pathologic response (MPR) and pathologic complete response (pCR) were compared through logistic regression. Subgroup analysis and sensitivity analysis were conducted to evaluate the accuracy of the results.

Median DFS was 22.58 months, and 14 patients experienced tumor recurrence or death. A significant decrease in BMD was observed at the T10, T12, and L1 vertebrae following NICT (p < 0.001). Patients with higher baseline and preoperative L1 BMD had significantly improved DFS (p = 0.002, p = 0.002). The prognostic value for BMD was confirmed through RCS analysis and multivariate Cox-regression analysis, as well as sensitivity analysis. Subgroup analysis revealed that the effect of L1 BMD on DFS showed significant interaction in age and MPR groups, suggesting age specific and treatment-response specific differences.

Both baseline and preoperative L1 BMD are valuable, readily available, and independent prognostic biomarkers for DFS in NSCLC patients receiving NICT.

The online version contains supplementary material available at 10.1186/s12957-025-04186-2.

Key Findings

• Baseline and preoperative L1 bone mineral density (BMD) independently predict disease-free survival (DFS) in non-small cell lung cancer (NSCLC) patients receiving neoadjuvant chemoimmunotherapy (NICT).

• Higher L1 BMD correlates with better DFS.

What is known and what is new?

• Known: NICT improves NSCLC outcomes, but response varies. BMD predicts prognosis in other cancers.

• New: First study linking computed tomography (CT)-derived L1 BMD to DFS in NSCLC under NICT. Low baseline and preoperative BMD are associated with poorer DFS; age and MPR influence BMD's prognostic value.

What is the implication, and what should change now?

• Use CT-derived BMD as a prognostic biomarker for personalized NSCLC treatment.

• Implement bone health strategies during NICT to improve outcomes.

• Investigate BMD-immunotherapy mechanisms and develop BMD-based prognostic models.

The online version contains supplementary material available at 10.1186/s12957-025-04186-2.