Background/Objectives: Conventional imaging assesses therapy response in stage IV solid-tumor patients in 8- to 12-week intervals, delaying detection of non-responders. We evaluated a quantitative PCR (qPCR) assay that interrogates size-distributed cell-free DNA (cfDNA) fragments to provide earlier insights into treatment efficacy.Methods: In this prospective study, 128 patients with metastatic lung, breast, or colorectal cancer provided plasma 12–21 days after the first dose of a new systemic regimen. The qPCR targets multi-copy retrotransposon element fragments of greater than 80 bp, greater than 105 bp, and greater than 265 bp, as well as an internal control. A model integrates these quantities into a Progression Score (PS) ranging from 0 to 100; higher values indicate probable disease progression.Results: The PS model yielded an area under (AUC) the receiver-operating-characteristic (ROC) curve of 0.93 for predicting radiographic progression at first imaging. Scores were strongly bimodal: 92% of patients with PS > 90 progressed, whereas 95% with PS < 10 did not. Intermediate scores (10–90) comprised a mixed cohort. Assay performance was unaffected by tumor genomic profile.Conclusions: This cfDNA-based Progression Score (PS) assay enables tumor- and therapy-agnostic, non-invasive monitoring of treatment response as early as two weeks after initiation. By flagging ineffective regimens well before standard imaging, the test can accelerate clinical decision-making, reduce exposure to futile therapy, and potentially improve outcomes in stage IV cancer. Early treatment plan changes may also avoid the high costs of ineffective treatments, prevent downstream toxicity-related hospitalizations, and free up limited imaging and infusion-suite capacity—yielding savings for patients, payers, and healthcare systems.
背景/目的：传统影像学评估IV期实体瘤患者治疗反应通常间隔8至12周，导致对无应答者的识别延迟。本研究评估了一种定量PCR（qPCR）检测方法，通过分析不同大小的游离DNA（cfDNA）片段，为治疗疗效提供更早期的评估依据。 方法：在这项前瞻性研究中，128例转移性肺癌、乳腺癌或结直肠癌患者在接受新系统治疗方案首剂后12-21天提供血浆样本。qPCR检测针对大于80 bp、大于105 bp和大于265 bp的多拷贝逆转录转座子元件片段及内参基因。通过模型将这些定量数据整合为0-100分的进展评分（PS），分值越高提示疾病进展可能性越大。 结果：PS模型预测首次影像学进展的受试者工作特征曲线下面积（AUC）达0.93。评分呈现显著双峰分布：PS > 90的患者中92%发生进展，而PS < 10的患者中95%未进展。中间评分（10-90）患者构成混合队列。检测性能不受肿瘤基因组特征影响。 结论：这种基于cfDNA的进展评分（PS）检测方法可在治疗开始后两周实现与肿瘤类型和治疗方案无关的无创治疗反应监测。通过早于标准影像学发现无效治疗方案，该检测可加速临床决策、减少无效治疗暴露，并可能改善IV期癌症患者的预后。早期治疗方案的调整还能避免无效治疗的高昂费用、预防毒性相关住院事件，并释放有限的影像学和输液资源，从而为患者、支付方和医疗系统节省开支。
肿瘤(癌症)患者之家