Rhodin Kristen E, O'Connor Margaret H, Therien Aaron, Hollander Shayna, Geron Viviana, Nair Uma, Rakestraw Emily, Salama April K, Shah Riddhishkumar, Tyler Douglas S, Beasley Georgia M
Department of Surgery, Duke University, Durham, NC, USA.
Department of Medicine, Duke University, Durham, NC, USA.
Ann Surg Oncol. 2025 Mar 27. doi: 10.1245/s10434-025-17194-z.
Adjuvant therapies reduce recurrence in patients with clinical stage IIB/IIC/III melanoma; however, better risk stratification and patient selection are needed. Circulating tumor DNA (ctDNA) as a marker of micrometastatic residual disease is being explored for such purposes in other malignancies. We aimed to explore the feasibility of serial ctDNA monitoring in patients with stage II/III melanoma, as well as the association of ctDNA elevation with disease burden and outcomes.
A single-institution prospective study was conducted on patients with clinical stage IIB/IIC/III melanoma. Primary tumor was sent to Natera for generation of a tumor-informed mPCR-NGS assay (Signatera™). Peripheral blood was collected for analysis at pre-specified timepoints. Patients were stratified by ctDNA elevations both pre- and postoperatively to compare tumor characteristics and recurrence-free survival (RFS).
Overall, 30 patients were enrolled. The median Breslow depth was 4.4 mm and 70% were ulcerated. Signatera™ assays were successfully created for all 30 patients. Median follow-up from the time of surgery was 16 months and 13 patients recurred with median RFS of 19 months. Eight of these 13 patients (62%) had detectable ctDNA levels predating their clinical or radiographic recurrence. Elevated ctDNA at the first post-operative timepoint was associated with worse RFS.
ctDNA monitoring is feasible for patients with high-risk cutaneous melanoma. Our findings suggest that detectable ctDNA post-operatively may be associated with worse outcomes. Elevations during surveillance may predict subsequent clinical recurrence; however, the role of ctDNA in adjuvant therapy decision-making and surveillance is not yet ready for broad application.
辅助治疗可降低临床IIB/IIC/III期黑色素瘤患者的复发率；然而，仍需要更好的风险分层和患者选择方法。循环肿瘤DNA（ctDNA）作为微转移残留疾病的标志物，正在其他恶性肿瘤中用于此类目的的探索。我们旨在探讨对II/III期黑色素瘤患者进行连续ctDNA监测的可行性，以及ctDNA升高与疾病负担和预后的关系。
对临床IIB/IIC/III期黑色素瘤患者进行了一项单机构前瞻性研究。将原发性肿瘤送至Natera公司，以生成肿瘤知情的多重PCR-下一代测序分析（Signatera™）。在预定时间点采集外周血进行分析。根据术前和术后ctDNA升高情况对患者进行分层，以比较肿瘤特征和无复发生存期（RFS）。
总共招募了30名患者。Breslow深度中位数为4.4mm，70%的患者有溃疡。为所有30名患者成功创建了Signatera™分析。从手术时起的中位随访时间为16个月，13名患者复发，中位RFS为19个月。这13名患者中有8名（62%）在临床或影像学复发之前ctDNA水平可检测到。术后第一个时间点ctDNA升高与较差的RFS相关。
ctDNA监测对于高危皮肤黑色素瘤患者是可行的。我们的研究结果表明，术后可检测到的ctDNA可能与较差的预后相关。监测期间的升高可能预示随后的临床复发；然而，ctDNA在辅助治疗决策和监测中的作用尚未准备好广泛应用。
