Prognostic value of baseline and dynamic circulating tumor cell monitoring in advanced lung cancer patients receiving immunotherapy.

Abstract

8532 Background: Circulating tumor cells (CTCs) and PD-L1 expression on CTCs (bPD-L1) are emerging biomarkers for predicting immunotherapy response. This study assessed the prognostic value of baseline and dynamic CTC monitoring in advanced lung cancer patients receiving immune checkpoint inhibitors. Methods: We prospectively enrolled 53 advanced lung cancer patients (stages III-IV) undergoing immune checkpoint therapy from June 2023 to January 2025 at The Fifth Affiliated Hospital of Sun Yat-sen University. Baseline characteristics (age, gender, histology, treatment modality) were recorded. CTCs and bPD-L1 status were assessed at baseline, and treatment responses were evaluated using RECIST 1.1 criteria. Serial blood samples were collected at Day 42 (T1) and subsequent visits (T2, T3, or Tn) for CTC dynamics monitoring. Results: Baseline Characteristics and CTC Detection: Of the 53 patients, 47 (84.6%) were male and 8 (15.4%) were female, with a median age of 63 years (range: 32–89). Histological subtypes included adenocarcinoma (62.6%), squamous cell carcinoma (16.1%), and small cell lung cancer (17.2%). Treatments included PD-1/PD-L1 inhibitors and chemotherapy. At baseline, CTCs were detected in 60.9% of patients, with detection rates varying by histology: adenocarcinoma (59.6%), squamous cell carcinoma (60.7%), and small cell lung cancer (50.0%). PD-L1-positive CTCs (bPD-L1+) were found in 44.8% of patients, with subtype-specific positivity rates of 41.3%, 39.3%, and 40.0%, respectively. Among 53 patients who completed at least two cycles of immunotherapy, the bPD-L1-positive group (n=17) had an ORR of 64.7% and a DCR of 100%, while the bPD-L1-negative group (n=36) had an ORR of 13.9% and a DCR of 83.3% (p<0.001). Multivariate analysis identified bPD-L1 positivity as an independent predictor of ORR (p=0.04). Serial blood samples from 37 patients at Day 42 (T1) showed that all patients with DCR had stable or decreased CTC counts, while all PD patients showed an increase in CTC count. Extended monitoring in 13 patients revealed consistent patterns: CTC counts increased in PD cases and decreased or remained stable in DCR cases, supporting its role in monitoring treatment efficacy. A linear mixed-effects model showed a significant positive association between PD status and elevated CTC counts (β = 0.821, p<0.05), while non-PD showed a trend towards lower CTC counts (β = -0.370, p=0.1). This suggests that CTC counts may serve as a biomarker for disease progression, particularly in identifying PD patients. Conclusions: Baseline and dynamic CTC monitoring, particularly bPD-L1 status, provides strong predictive and prognostic value in advanced lung cancer patients undergoing immunotherapy. These findings suggest CTCs as a non-invasive liquid biopsy for treatment stratification and real-time monitoring of treatment response. Clinical trial information: ChiCTR2400080132 .