Institute of Biocomputation and Physics of Complex Systems (BIFI), Joint Units IQFR-CSIC-BIFI, and GBsC-CSIC-BIFI, Universidad de Zaragoza, Zaragoza 50018, Spain; Department of Biochemistry and Molecular and Cell Biology, Universidad de Zaragoza, Zaragoza 50009, Spain; Aragon Institute for Health Research (IIS Aragon), Zaragoza, 50009, Spain; Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain; Fundacion ARAID, Government of Aragon, Zaragoza 50018, Spain.
Institute of Biocomputation and Physics of Complex Systems (BIFI), Joint Units IQFR-CSIC-BIFI, and GBsC-CSIC-BIFI, Universidad de Zaragoza, Zaragoza 50018, Spain.
Biochim Biophys Acta Gen Subj. 2018 Aug;1862(8):1701-1710. doi: 10.1016/j.bbagen.2018.04.020. Epub 2018 Apr 26.
Differential Scanning Calorimetry (DSC) is a technique traditionally used to study thermally induced macromolecular transitions, and it has recently been proposed as a novel approach for diagnosis and monitoring of several diseases. We report a pilot study applying Thermal Liquid Biopsy (TLB, DSC thermograms of plasma samples) as a new clinical approach for diagnostic assessment of melanoma patients.
Multiparametric analysis of DSC thermograms of patient plasma samples collected during treatment and surveillance (63 samples from 10 patients) were compared with clinical and diagnostic imaging assessment to determine the utility of thermograms for diagnostic assessment in melanoma. Nine of the ten patients were stage 2 or 3 melanoma subjects receiving adjuvant therapy after surgical resection of their melanomas. The other patient had unresectable stage 4 melanoma and was treated with immunotherapy. Two reference groups were used: (A) 36 healthy subjects and (B) 13 samples from 8 melanoma patients who had completed successful surgical management of their disease and were determined by continued clinical assessment to have no evidence of disease.
Plasma thermogram analysis applied to melanoma patients generally agrees with clinical evaluation determined by physical assessment or diagnostic imaging (~80% agreement). No false negatives were obtained from DSC thermograms. Importantly, this methodology was able to detect changes in disease status before it was identified clinically.
Thermal Liquid Biopsy could be used in combination with current clinical assessment for the earlier detection of melanoma recurrence and metastasis.
TLB offers advantages over current diagnostic techniques (PET/CT imaging), limited in frequency by radiation burden and expense, in providing a minimally-invasive, low-risk, low-cost clinical test for more frequent personalized patient monitoring to assess recurrence and facilitate clinical decision-making.
差示扫描量热法（DSC）是一种传统上用于研究热诱导大分子转变的技术，最近它被提议作为诊断和监测几种疾病的新方法。我们报告了一项应用热液体活检（TLB，血浆样本的 DSC 热谱图）作为诊断评估黑色素瘤患者的新临床方法的初步研究。
对治疗和监测期间收集的患者血浆样本的 DSC 热谱图进行多参数分析（来自 10 名患者的 63 个样本），并与临床和诊断成像评估进行比较，以确定热谱图对黑色素瘤诊断评估的实用性。十名患者中的九名是 2 期或 3 期黑色素瘤患者，在手术切除黑色素瘤后接受辅助治疗。另一名患者患有不可切除的 4 期黑色素瘤，接受免疫治疗。使用了两个参考组：（A）36 名健康受试者和（B）13 名来自 8 名黑色素瘤患者的样本，这些患者成功完成了疾病的手术治疗，并且通过持续的临床评估确定没有疾病证据。
应用于黑色素瘤患者的血浆热谱图分析通常与通过体格检查或诊断成像确定的临床评估一致（约 80%的一致性）。DSC 热谱图没有得到假阴性结果。重要的是，这种方法能够在临床识别之前检测到疾病状态的变化。
热液体活检可与当前的临床评估结合使用，以更早地发现黑色素瘤复发和转移。
TLB 提供了优于当前诊断技术（PET/CT 成像）的优势，由于辐射负担和费用的限制，其频率有限，为更频繁的个性化患者监测提供了一种微创、低风险、低成本的临床测试，以评估复发并促进临床决策。
