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.

Circulating tumor DNA (ctDNA) clearance is a potential predictor of pCR, though its analytical and clinical validity has yet to be established.

循环肿瘤DNA（ctDNA）清除是pCR的一个潜在预测因子，尽管其分析和临床有效性尚未得到确立。

This systematic reviewand meta-analysisaims to assess the role of ctDNA clearance as a predictor of pCR in patients with solid tumors treated with neoadjuvant ICIs.

本系统评价和荟萃分析旨在评估循环肿瘤DNA（ctDNA）清除作为新辅助免疫检查点抑制剂（ICIs）治疗的实体瘤患者完全病理缓解（pCR）预测因子的作用。

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.

截至2024年8月5日，对PubMed、EMBASE和会议记录进行了系统检索，以识别研究ctDNA清除和pCR的Ib期、II期或III期临床试验，这些试验涉及接受新辅助ICIs治疗的具有可检测ctDNA的实体瘤患者。

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).

我们使用双变量模型估计了ctDNA清除在预测pCR中的汇总敏感性和特异性、阳性似然比、阴性似然比以及诊断优势比，并给出了95%置信区间(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.

纳入了13项试验，涉及380名基线时ctDNA可检测的患者。在11项（85%）试验中，使用了肿瘤信息的方法来评估ctDNA。

Overall, 38% of patients achieved pCR and 73% had ctDNA clearance before/at the surgery.

总体而言，38%的患者实现了pCR，73%的患者在手术前/手术时ctDNA清除。

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).

汇总敏感性为0.98（95%置信区间0.86-1.00），特异性为0.53（95%置信区间0.37-0.69），阳性似然比为2.09（95%置信区间1.48-2.93），阴性似然比为0.04（95%置信区间0.01-0.26），诊断优势比为57.36（95%置信区间8.12-405.12）。

Significant heterogeneity was observed across studies (I2 ∼70% for all metrics), indicating considerable variability in the diagnostic performance.

研究间观察到显著的异质性（所有指标的I2约为70%），表明诊断性能存在相当大的变异性。

Conclusions

The lack of ctDNA clearance may identify patients unlikely to have a pCR.

ctDNA清除的缺失可能识别出不太可能达到病理完全缓解（pCR）的患者。

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.

然而，ctDNA清除的确认能力受限于检测方法的变异性和高异质性，导致其特异性低，因此需要进一步研究。

Therefore, clinicians should not rely on the use of ctDNA clearance to inform treatment decisions in the neoadjuvant setting.

因此，临床医生不应依赖ctDNA清除来指导新辅助治疗的决策。