What question did this study set out to answer?

This research evaluates circulating tumor cells as predictors of treatment response in neoadjuvant chemoimmunotherapy for lung cancer.

April 30, 2026Open Access

Predictive Value of Circulating Tumor Cells in Neoadjuvant Chemoimmunotherapy for Non‐Small Cell Lung Cancer

Puntos clave

This research evaluates circulating tumor cells as predictors of treatment response in neoadjuvant chemoimmunotherapy for lung cancer.
39 patients with NSCLC received neoadjuvant therapy combining PD-1 inhibitors and chemotherapy.
Preoperative imaging was conducted using RECIST 1.1 and compared with pathological outcomes.
CTCs were isolated and characterized, and RNA-sequencing was done on residual tumor specimens.
The MPR rate was 38.5% and pCR rate was 23.1%.
CK+ CTC burden was identified as a predictor of non-response with AUC=0.757.
Combining CK+ CTC counts with imaging improved predictive accuracy to AUC=0.79.

Resumen

ABSTRACT Background The incorporation of immune checkpoint blockade into preoperative regimens has significantly advanced the clinical management of locally advanced non‐small cell lung cancer (NSCLC). Standard imaging modalities frequently fall short in assessing actual pathological regression. Our research sought to evaluate circulating tumor cells (CTCs) as an adjunct predictive tool, while uncovering the transcriptomic shifts within the tumor microenvironment that facilitate cellular shedding. Methods A prospective cohort of 39 patients with NSCLC received neoadjuvant programmed cell death protein 1 (PD‐1) inhibitors combined with platinum‐doublet chemotherapy. Preoperative radiographic evaluations using RECIST 1.1 were cross‐referenced with final pathological outcomes. Peripheral blood CTCs were enriched and phenotypically characterized via multiparametric immunofluorescence (CK, PD‐L1). Bulk RNA‐sequencing of residual tissue specimens was performed to identify gene signatures associated with CTC dissemination. Results The cohort achieved a major pathologic response (MPR) rate of 38.5%, including a pathological complete response (pCR) rate of 23.1%. Preoperative cytokeratin‐positive (CK+) CTC burden emerged as a potential independent predictor of pathological non‐response (AUC = 0.757), outperforming total CTCs and PD‐L1+ CTCs. Crucially, integrating CK+ CTC counts with standard radiographic imaging improved predictive accuracy for pathological outcomes (AUC = 0.79) compared to imaging alone (AUC = 0.54, p = 0.022). Transcriptomic profiling of the residual tumor microenvironment suggested that CTC dissemination may be associated with enhanced proliferative activity, severe local hypoxia and a broad immunological suppression within local microenvironments. Conclusions Preoperative CTC monitoring may serve as a promising complementary biomarker to conventional radiographic imaging, with the potential to help resolve predictive ambiguities in neoadjuvant chemoimmunotherapy for NSCLC.

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