基于自动化电泳检测的循环无细胞 DNA 完整性预测乳腺癌患者新辅助化疗后病理完全缓解的达成。

Plasma Cell-Free DNA Integrity Assessed by Automated Electrophoresis Predicts the Achievement of Pathologic Complete Response to Neoadjuvant Chemotherapy in Patients With Breast Cancer.

机构信息

Department of Internal Medicine, University of Genoa, Genoa, Italy.

IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

出版信息

JCO Precis Oncol. 2022 Feb;6:e2100198. doi: 10.1200/PO.21.00198.

DOI:10.1200/PO.21.00198

PMID:35201850

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8974578/

Abstract

PURPOSE

The study of plasma cell-free DNA integrity (cfDI) has shown potential for providing useful information in neoplastic patients. The aim of this study is to estimate the accuracy of an electrophoresis-based method for cfDI evaluation in the assessment of pathologic complete response (pCR) in patients with breast cancer (BC) undergoing neoadjuvant chemotherapy (NACT).

PATIENTS AND METHODS

Fifty-one patients with BC undergoing anthracycline-/taxane-based NACT were recruited. Plasma samples were collected from each patient at diagnosis (t0), after anthracycline administration (t1), and after NACT completion (t2). The concentration of differently sized cell-free DNA fragments was assessed by automated electrophoresis. cfDI, expressed as cfDI index, was calculated as the ratio of 321-1,000 bp sized fragment concentration to 150-220 bp sized fragment concentration assessed at t2. cfDI index was then used to build an exploratory classifier for BC response to NACT, directly comparing its sensitivity and specificity with magnetic resonance imaging (MRI), through bootstrapped logistic regression.

RESULTS

cfDI index was assessed on 38 plasma samples collected from as many patients at t2, maintaining a 30/70 ratio between pCR and non-pCR patients. cfDI index showed an area under the receiver operating characteristic curve in predicting the achievement of pCR of 81.6, with a cutoff above 2.71 showing sensitivity = 81.8 and specificity = 81.5. The combination of cfDI index and MRI showed, in case of concordance, an area under the receiver operating characteristic curve of 92.6 with a predictive value of complete response of 87.5 and a predictive value of absence of complete response of 94.7.

CONCLUSION

cfDI index measured after NACT completion shows great potential in the assessment of pCR in patients with BC. The evaluation of its use in combination with MRI is strongly warranted in prospective studies.

摘要

目的

浆细胞游离 DNA 完整性（cfDI）的研究显示出在肿瘤患者中提供有用信息的潜力。本研究旨在评估电泳法评估 cfDI 对接受新辅助化疗（NACT）的乳腺癌（BC）患者病理完全缓解（pCR）评估的准确性。

方法

招募了 51 名接受蒽环类药物/紫杉烷类药物 NACT 的 BC 患者。在诊断时（t0）、蒽环类药物给药后（t1）和 NACT 完成后（t2），从每位患者采集血浆样本。通过自动电泳评估不同大小的游离 DNA 片段浓度。cfDI 表示为 cfDI 指数，定义为 t2 时 321-1000bp 大小片段浓度与 150-220bp 大小片段浓度的比值。然后，通过 bootstrap 逻辑回归，使用 cfDI 指数构建了一种用于 NACT 后 BC 反应的探索性分类器，直接比较其对 MRI 的敏感性和特异性。

结果

对 38 名患者的 38 份血浆样本在 t2 时评估了 cfDI 指数，pCR 患者与非 pCR 患者的比例为 30/70。cfDI 指数在预测 pCR 方面的受试者工作特征曲线下面积为 81.6，截断值高于 2.71 时，敏感性为 81.8，特异性为 81.5。cfDI 指数和 MRI 的联合使用，在一致性的情况下，受试者工作特征曲线下面积为 92.6，完全缓解的预测值为 87.5，完全缓解缺失的预测值为 94.7。