Giunta Emilio Francesco, De Falco Vincenzo, Vitiello Pietro Paolo, Guerrera Luigi Pio, Suarato Gabriella, Napolitano Rossella, Perrone Alessandra, Argenziano Giuseppe, Franco Renato, Caraglia Michele, Martinelli Erika, Ciardiello Davide, Ciardiello Fortunato, Napolitano Stefania, Troiani Teresa
Medical Oncology Unit, Department of Precision Medicine, Università degli Studi della Campania "Luigi Vanvitelli", 80131 Naples, Italy.
Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, TO, Italy.
Cancers (Basel). 2022 Jun 21;14(13):3053. doi: 10.3390/cancers14133053.
Liquid biopsy is a potentially useful tool for melanoma patients, also for detecting BRAS/NRAS mutations, even if the tissue analysis remains the current standard.
In this work, we tested ctDNA on plasma samples from 56 BRAF-V600/NRAS mutant stage III/IV melanoma patients using a real-time quantitative PCR (qPCR)-based platform. The study population was divided into two cohorts: the first including 26 patients who had undergone radical resection (resected cohort) and the second including 30 patients who had unresected measurable disease (advanced cohort). Moreover, for 10 patients in the advanced cohort, ctDNA assessment was repeated at specified timepoints after baseline testing. Data were analyzed and correlated to the clinicopathologic characteristics and outcomes.
In the baseline cohort, a higher tissue-plasma concordance was seen in patients with high burden of disease (sum of diameters ≥30 mm, ≥2 metastatic sites, elevated LDH levels); furthermore, monitoring of these patients through ctDNA analysis was informative for therapeutic responses. On the other hand, the low sensitivity of this technique did not allow for clinically valuable prediction of relapses in radically resected stage III/IV patients.
Overall, our data suggest that qPCR-based ctDNA analysis could be informative in a subset of locally advanced and metastatic melanoma patients with specific clinical-radiological characteristics, supporting further investigations in this setting.
液体活检对于黑色素瘤患者而言是一种潜在有用的工具，即便组织分析仍是当前的标准方法，它也可用于检测BRAF/NRAS突变。
在本研究中，我们使用基于实时定量聚合酶链反应（qPCR）的平台，对56例BRAF-V600/NRAS突变的III/IV期黑色素瘤患者的血浆样本进行了循环肿瘤DNA（ctDNA）检测。研究人群分为两个队列：第一个队列包括26例接受根治性切除术的患者（切除队列），第二个队列包括30例有可测量的未切除病灶的患者（晚期队列）。此外，对于晚期队列中的10例患者，在基线检测后的特定时间点重复进行ctDNA评估。对数据进行分析，并与临床病理特征和预后相关联。
在基线队列中，疾病负担较重（直径总和≥30 mm、转移部位≥2个、乳酸脱氢酶水平升高）的患者组织与血浆的一致性更高；此外，通过ctDNA分析对这些患者进行监测有助于了解治疗反应。另一方面，该技术的低敏感性无法对根治性切除的III/IV期患者的复发进行具有临床价值的预测。
总体而言，我们的数据表明，基于qPCR的ctDNA分析对于具有特定临床放射学特征的局部晚期和转移性黑色素瘤患者亚组可能具有参考价值，支持在该领域进行进一步研究。
