Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Quebec City, Canada; Department of Molecular Medicine, Université Laval, Quebec City, Canada.
Oncology Data Science, Oncology R&D, AstraZeneca, Gaithersburg, MD, USA.
Cancer Lett. 2024 Jul 10;594:216984. doi: 10.1016/j.canlet.2024.216984. Epub 2024 May 24.
Circulating tumor DNA (ctDNA) positivity at diagnosis, which is associated with worse outcomes in multiple solid tumors including stage I-III non-small cell lung cancer (NSCLC), may have utility to guide (neo)adjuvant therapy.
In this retrospective study, 260 patients with clinical stage I NSCLC (180 adenocarcinoma, 80 squamous cell carcinoma) were allocated (2:1) to high- and low-risk groups based on relapse versus disease-free status ≤5 years post-surgery. We evaluated the association of preoperative ctDNA detection by a plasma-only targeted methylation-based multi-cancer early detection (MCED) test with NSCLC relapse ≤5 years post-surgery in the overall population, followed by histology-specific subgroup analyses.
Across clinical stage I patients, preoperative ctDNA detection did not associate with relapse within 5 years post-surgery. Sub-analyses confined to lung adenocarcinoma suggested a histology-specific association between ctDNA detection and outcome. In this group, ctDNA positivity tended to associate with relapse within 2 years, suggesting prognostic implications of MCED test positivity may be histology- and time-dependent in stage I NSCLC. Preoperative ctDNA detection was associated with upstaging of clinical stage I to pathological stage II-III NSCLC.
Our findings suggest preoperative ctDNA detection in patients with resectable clinical stage I NSCLC using MCED, a pan-cancer screening test developed for use in an asymptomatic population, has no detectable prognostic value for relapse ≤5 years post-surgery. MCED detection may be associated with early adenocarcinoma relapse and increased pathological upstaging rates in stage I NSCLC. However, given the exploratory nature of these findings, independent validation is required.
在包括 I-III 期非小细胞肺癌（NSCLC）在内的多种实体瘤中，诊断时循环肿瘤 DNA（ctDNA）阳性与预后较差相关，这可能对指导（新）辅助治疗具有作用。
在这项回顾性研究中，根据手术后 5 年内是否复发或无疾病状态，将 260 例临床 I 期 NSCLC（180 例腺癌，80 例鳞状细胞癌）患者分配到高风险和低风险组（2:1）。我们评估了基于血浆的靶向甲基化多癌早期检测（MCED）试验检测术前 ctDNA 与整体人群中手术后 5 年内 NSCLC 复发的相关性，随后进行了组织学特异性亚组分析。
在所有临床 I 期患者中，术前 ctDNA 检测与手术后 5 年内复发无关。对肺腺癌的亚组分析表明，ctDNA 检测与结果之间存在组织学特异性关联。在该组中，ctDNA 阳性倾向于与 2 年内复发相关，表明 MCED 试验阳性的预后意义可能在 I 期 NSCLC 中与组织学和时间相关。术前 ctDNA 检测与临床 I 期 NSCLC 向病理 II-III 期 NSCLC 的分期升级相关。
我们的研究结果表明，使用 MCED 对可切除的临床 I 期 NSCLC 患者进行术前 ctDNA 检测，MCED 是一种针对无症状人群开发的泛癌筛查试验，对手术后 5 年内复发没有可检测的预后价值。MCED 检测可能与早期腺癌复发和 I 期 NSCLC 中病理升级率增加相关。然而，鉴于这些发现的探索性性质，需要独立验证。
