Hong Huizhao, Zhang Yingqian, Song Mengmeng, Gao Xuan, Tang Wenfang, Li Hongji, Cui Shirong, Dong Song, Wu Yilong, Zhong Wenzhao, Zhang Jiatao
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510000, China.
Geneplus-Beijing Institute, Beijing 102206, China.
Cancers (Basel). 2025 Jul 30;17(15):2525. doi: 10.3390/cancers17152525.
Circulating tumor DNA (ctDNA) has emerged as a reliable prognostic biomarker in both early- and late-stage non-small cell lung cancer (NSCLC) patients. However, its role in NSCLC with pleural dissemination (M1a), a subset of disease with indolent biology, remains to be elucidated. We collected 41 M1a patients with serial ctDNA and CEA monitoring. Progression-free survival (PFS) was assessed between patients with different levels of ctDNA and CEA. An independent cohort of 61 M1a patients was included for validation. At the diagnostic landmark, the detection rates for ctDNA and CEA were 22% and 55%, respectively. Among patients who experienced disease progression with pleural metastases, only ten had detectable ctDNA in longitudinal timepoints, resulting in a sensitivity of 50%. Moreover, there was no significant difference in PFS between patients with longitudinally detectable and undetectable ctDNA (HR: 0.86, 95% CI 0.33-2.23, = 0.76). In contrast, patients with a decreasing CEA trend within 3 months after diagnosis were associated with an improved PFS (HR: 0.22; 95% CI, 0.03-1.48, = 0.004). This finding is confirmed in an independent M1a patient cohort. Together, our findings suggest that M1a NSCLC with isolated pleural dissemination may represent a "non-shedding" tumor type, where ctDNA shows limited diagnostic and prognostic value. Monitoring early changes in CEA could be a more cost-effective predictor of disease progression.
循环肿瘤DNA（ctDNA）已成为早期和晚期非小细胞肺癌（NSCLC）患者可靠的预后生物标志物。然而，其在伴有胸膜播散（M1a）的NSCLC中的作用，这一具有惰性生物学特性的疾病亚组，仍有待阐明。我们收集了41例接受连续ctDNA和癌胚抗原（CEA）监测的M1a患者。对不同ctDNA和CEA水平的患者进行无进展生存期（PFS）评估。纳入了一个由61例M1a患者组成的独立队列进行验证。在诊断节点，ctDNA和CEA的检测率分别为22%和55%。在发生胸膜转移且疾病进展的患者中，只有10例在纵向时间点可检测到ctDNA，敏感性为50%。此外，纵向可检测到ctDNA和未检测到ctDNA的患者之间的PFS无显著差异（风险比：0.86，95%置信区间0.33 - 2.23，P = 0.76）。相比之下，诊断后3个月内CEA呈下降趋势的患者PFS有所改善（风险比：0.22；95%置信区间，0.03 - 1.48，P = 0.004）。这一发现在一个独立的M1a患者队列中得到了证实。总之，我们的研究结果表明，伴有孤立性胸膜播散的M1a NSCLC可能代表一种“不释放”的肿瘤类型，其中ctDNA的诊断和预后价值有限。监测CEA的早期变化可能是更具成本效益的疾病进展预测指标。
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