Department of Dermatology, Huntsman Cancer Institute, University of Utah, Salt Lake City.
Department of Surgery, Intermountain Healthcare, Murray.
Melanoma Res. 2023 Jun 1;33(3):184-191. doi: 10.1097/CMR.0000000000000892. Epub 2023 Apr 5.
The objective of this study was to evaluate the feasibility of developing personalized, tumor-informed assays for patients with high-risk resectable melanoma and examine circulating tumor DNA (ctDNA) levels in relation to clinical status. Pilot prospective study of clinical stage IIB/C and resectable stage III melanoma patients. Tumor tissue was used to design bespoke somatic assays for interrogating ctDNA in patients' plasma using a multiplex PCR (mPCR) next-generation sequencing (NGS)-based approach. Plasma samples for ctDNA analysis were collected pre-/post-surgery and during surveillance. Out of 28 patients (mean 65 years, 50% male), 13 (46%) had detectable ctDNA prior to definitive surgery and 96% (27/28) tested ctDNA-negative within 4 weeks post-surgery. Pre-surgical detection of ctDNA was significantly associated with the later-stage ( P = 0.02) and clinically evident stage III disease ( P = 0.007). Twenty patients continue in surveillance with serial ctDNA testing every 3-6 months. With a median follow-up of 443 days, six out of 20 (30%) patients developed detectable ctDNA levels during surveillance. All six of these patients recurred with a mean time to recurrence of 280 days. Detection of ctDNA in surveillance preceded the diagnosis of clinical recurrence in three patients, was detected concurrent with clinical recurrence in two patients and followed clinical recurrence in one patient. One additional patient developed brain metastases without detection of ctDNA during surveillance but had positive pre-surgical ctDNA. Our results demonstrate the feasibility of obtaining a personalized, tumor-informed mPCR NGS-based ctDNA assay for patients with melanoma, particularly in resectable stage III disease.
本研究旨在评估为高风险可切除黑色素瘤患者开发个体化、肿瘤信息相关检测的可行性，并研究循环肿瘤 DNA（ctDNA）水平与临床状态的关系。这是一项 IIB/C 期和可切除 III 期黑色素瘤患者的前瞻性研究。采用定制的体细胞检测方法，利用多重聚合酶链反应（mPCR）下一代测序（NGS）技术，检测患者血浆中的 ctDNA。在术前/术后和监测期间收集 ctDNA 分析的血浆样本。在 28 例患者（平均年龄 65 岁，50%为男性）中，13 例（46%）在确定性手术前可检测到 ctDNA，96%（27/28）在术后 4 周内检测到 ctDNA 阴性。术前检测到 ctDNA 与晚期（P=0.02）和临床上明显的 III 期疾病（P=0.007）显著相关。20 例患者继续接受监测，每 3-6 个月进行一次连续 ctDNA 检测。中位随访 443 天，20 例中有 6 例（30%）在监测期间出现可检测的 ctDNA 水平。这 6 例患者中有 3 例在复发前 3 个月检测到 ctDNA，2 例与临床复发同时检测到 ctDNA，1 例在临床复发后检测到 ctDNA。另有 1 例患者在监测期间未检测到 ctDNA 但发生脑转移，且术前 ctDNA 阳性。我们的结果表明，对于黑色素瘤患者，特别是可切除的 III 期疾病患者，获得个体化、肿瘤信息相关的 mPCR NGS 基于 ctDNA 的检测是可行的。
