循环肿瘤DNA在多种肾恶性肿瘤管理中的应用：从辅助和复发/转移设置的病例系列的见解。

IF 11.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Med Pub Date : 2025-08-19 DOI:10.1016/j.medj.2025.100806

Ridwan Alam, Jeffrey W Fuchs, Niraj K Shenoy

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引用次数: 0

摘要

背景：循环肿瘤DNA （ctDNA）监测为检测分子残留疾病和评估治疗效果提供了一种微创方法。虽然越来越多地用于几种癌症，但其在肾脏恶性肿瘤中的临床应用仍未得到充分探索，主要是由于肾癌中ctDNA的低脱落。方法：我们报告了6例不同肾恶性肿瘤（透明细胞肾细胞癌、乳头状肾细胞癌、易位性肾细胞癌、恶性血管平滑肌脂肪瘤和肾盂鳞状细胞癌）的病例系列，这些肿瘤均采用辅助治疗和复发/转移治疗。所有患者在常规成像的同时，使用Signatera（基于外显子组的）肿瘤检测方法进行连续ctDNA检测。结果：ctDNA结果影响了所有6例患者的临床决策。在辅助治疗中，ctDNA阳性表明分子残留疾病，提示开始治疗，并允许在监测期间监测治疗反应和复发。在复发/转移性疾病中，ctDNA趋势通常先于放射学进展，从而能够进行早期干预或修改治疗。在某些情况下，ctDNA在成像不确定性或因毒性导致的治疗中断期间提供了至关重要的见解。持续的ctDNA清除与有利的癌症特异性结果相关。结论：虽然ctDNA监测在肾癌中的低灵敏度、有限的阴性预测价值和经济负担构成了显著的局限性，但阳性结果可能作为基于图像的监测的高信息辅助，用于监测疾病状态和治疗反应。本病例系列支持并告知ctDNA在肾恶性肿瘤治疗中的未来研究。资助：对这些患者进行ctDNA检测得到了Signatera试剂盒制造商Natera的支持。

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Utility of circulating tumor DNA in management of diverse renal malignancies: Insights from a case series in adjuvant and recurrent/metastatic settings.

Background: Circulating tumor DNA (ctDNA) monitoring offers a minimally invasive method for detecting molecular residual disease and assessing treatment response. While increasingly adopted in several cancers, its clinical utility in renal malignancies remains underexplored, primarily due to low ctDNA shedding in kidney cancers.

Methods: We present a case series of six patients with diverse renal malignancies (clear cell renal cell carcinoma [ccRCC], papillary RCC, translocation RCC, malignant angiomyolipoma, and squamous cell carcinoma of the renal pelvis) managed in both adjuvant and recurrent/metastatic settings. All patients underwent serial ctDNA testing using the Signatera (exome-based) tumor-informed assay alongside conventional imaging.

Findings: ctDNA results influenced clinical decisions in all six cases. In the adjuvant setting, positive ctDNA indicated molecular residual disease, prompted initiation of therapy, and allowed monitoring of treatment response and recurrence during surveillance. In recurrent/metastatic disease, ctDNA trends often preceded radiographic progression, enabling earlier intervention or treatment modification. In some instances, ctDNA provided crucial insights during imaging uncertainty or treatment breaks due to toxicity. Sustained ctDNA clearance was associated with favorable cancer-specific outcomes.

Conclusions: While the lower sensitivity, limited negative predictive value, and financial burden of ctDNA monitoring in kidney cancers constitute significant limitations, a positive result can potentially serve as a highly informative adjunct to imaging-based surveillance for monitoring disease status and treatment response. This case series supports and informs future studies on ctDNA in the management of renal malignancies.

Funding: ctDNA testing for these patients was supported by Natera, the manufacturer of the Signatera assay.

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来源期刊

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

期刊介绍： Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.