循环肿瘤DNA清除率作为接受新辅助免疫检查点抑制剂治疗的实体瘤患者病理完全缓解的预测生物标志物：一项系统评价和荟萃分析
Circulating tumor DNA clearance as a predictive biomarker of pathologic complete response in patients with solid tumors treated with neoadjuvant immune checkpoint inhibitors: a systematic review and meta-analysis.
作者信息
Valenza C, Saldanha E F, Gong Y, De Placido P, Gritsch D, Ortiz H, Trapani D, Conforti F, Cremolini C, Peters S, Mateo J, Subbiah V, Parsons H A, Partridge A H, Curigliano G
机构信息
Harvard Chan School of Public Health, Harvard University, Boston, USA; Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, USA.
Harvard Chan School of Public Health, Harvard University, Boston, USA; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada.
出版信息
Ann Oncol. 2025 Jul;36(7):726-736. doi: 10.1016/j.annonc.2025.03.019. Epub 2025 Apr 3.
BACKGROUND
In patients with solid tumors undergoing neoadjuvant immune checkpoint inhibitor (ICI) therapy, identifying biomarkers to predict pathologic complete response (pCR) preoperatively could enhance treatment modulation. Circulating tumor DNA (ctDNA) clearance is a potential predictor of pCR, though its analytical and clinical validity has yet to be established. This systematic review and meta-analysis aims to assess the role of ctDNA clearance as a predictor of pCR in patients with solid tumors treated with neoadjuvant ICIs.
MATERIALS AND METHODS
A systematic search of PubMed, EMBASE and conference proceedings up to 5 August 2024 was carried out to identify phase Ib, II or III clinical trials investigating ctDNA clearance and pCR in patients with solid tumors and detectable ctDNA, undergoing neoadjuvant therapy with ICIs. Using a bivariate model, we estimated the pooled sensitivity and specificity of ctDNA clearance in predicting pCR, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio, with 95% confidence intervals (CIs).
RESULTS
Thirteen trials involving 380 patients with detectable ctDNA at baseline were included. ctDNA was assessed with a tumor-informed approach in 11 (85%) trials. Overall, 38% of patients achieved pCR and 73% had ctDNA clearance before/at the surgery. Pooled sensitivity was 0.98 (95% CI 0.86-1.00), specificity was 0.53 (95% CI 0.37-0.69), positive likelihood ratio was 2.09 (95% CI 1.48-2.93), negative likelihood ratio was 0.04 (95% CI 0.01-0.26), diagnostic odds ratio was 57.36 (95% CI 8.12-405.12). Significant heterogeneity was observed across studies (I ∼70% for all metrics), indicating considerable variability in the diagnostic performance.
CONCLUSION
The lack of ctDNA clearance may identify patients unlikely to have a pCR. Instead, the confirmatory power of ctDNA clearance is limited by low specificity and high heterogeneity due to the variability of the assays, and warrants further study. Therefore, clinicians should not rely on the use of ctDNA clearance to inform treatment decisions in the neoadjuvant setting.
背景
在接受新辅助免疫检查点抑制剂（ICI）治疗的实体瘤患者中，术前识别预测病理完全缓解（pCR）的生物标志物可加强治疗调整。循环肿瘤DNA（ctDNA）清除是pCR的一个潜在预测指标，但其分析和临床有效性尚未确立。本系统评价和荟萃分析旨在评估ctDNA清除作为新辅助ICI治疗实体瘤患者pCR预测指标的作用。
材料与方法
对截至2024年8月5日的PubMed、EMBASE和会议论文集进行系统检索，以确定研究实体瘤且ctDNA可检测、接受新辅助ICI治疗患者的ctDNA清除和pCR的Ib、II或III期临床试验。使用双变量模型，我们估计了ctDNA清除预测pCR的合并敏感性和特异性、阳性似然比、阴性似然比和诊断比值比，并给出95%置信区间（CI）。
结果
纳入13项试验，共380例基线时ctDNA可检测的患者。11项（85%）试验采用肿瘤知情方法评估ctDNA。总体而言，38%的患者实现了pCR，73%的患者在手术前/手术时实现ctDNA清除。合并敏感性为0.98（95%CI 0.86 - 1.00），特异性为0.53（95%CI 0.37 - 0.69），阳性似然比为2.09（95%CI 1.48 - 2.93），阴性似然比为0.04（95%CI 0.01 - 0.26），诊断比值比为57.36（95%CI 8.12 - 405.12）。各研究间观察到显著异质性（所有指标的I²约为70%），表明诊断性能存在相当大的变异性。
结论
ctDNA未清除可能提示患者不太可能实现pCR。相反，由于检测方法的变异性，ctDNA清除的确认能力受到低特异性和高异质性的限制，需要进一步研究。因此，临床医生不应依赖ctDNA清除情况来指导新辅助治疗中的决策。
Zotero 插件