Objectives: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.Methods: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.Results: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,p= 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,p= 0.004). This finding is confirmed in an independent M1a patient cohort.Conclusions: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.
目的：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，其在具有惰性生物学特征的胸膜播散型（M1a）NSCLC中的作用仍有待阐明。 方法：本研究纳入41例M1a期患者，进行连续ctDNA与癌胚抗原（CEA）监测。通过比较不同ctDNA与CEA水平患者的无进展生存期（PFS）进行评估，并纳入61例M1a患者组成独立队列进行验证。 结果：在诊断时间点，ctDNA与CEA的检出率分别为22%和55%。在发生胸膜转移进展的患者中，仅10例在纵向时间点检测到ctDNA，灵敏度为50%。此外，纵向可检测与未检测到ctDNA患者的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显著改善（风险比：0.22；95%置信区间0.03–1.48，p=0.004）。该发现在独立M1a患者队列中得到验证。 结论：本研究提示，单纯胸膜播散的M1a期NSCLC可能属于"低释放"肿瘤类型，ctDNA的诊断与预后价值有限。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。
Lung Cancer with Isolated Pleural Dissemination as a Potential ctDNA Non-Shedding Tumor Type
肿瘤(癌症)患者之家