Department of General Surgery, Rostock University Medical Center, Rostock, Germany.
Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Medical Center Schleswig- Holstein, Kiel, Germany.
J Cancer Res Clin Oncol. 2024 Sep 22;150(9):428. doi: 10.1007/s00432-024-05944-7.
Liquid biopsy is a minimally invasive procedure investigating tumor mutations.
In our retrospective study, we investigated whether molecular therapy monitoring of patients receiving neoadjuvant radio(chemo)therapy on a daily routine is possible in 17 patients with locally advanced rectal cancer. Six patients received short-course radiotherapy (5 × 5 Gy) with subsequent surgery, six patients were treated according RAPIDO protocol with short-course radiotherapy followed by chemotherapy (FOLFOX4) and subsequent surgery and five patients received conventional neoadjuvant radiochemotherapy with 5-FU followed by surgery. Response was assessed by Dworak. Liquid biopsies were taken before and immediately after neoadjuvant radiotherapy to isolate and ultradeeply sequence cell free DNA with a panel of 127 genes. Somatic mutations were determined bioinformatically by comparison with normal DNA from leukocytes to distinguish them from germline variants or aging mutations.
In 12 patients (71%) at least one somatic mutation was detected. In 8/12 patients a decrease and in 4/12 an increase or mixed response in ctDNA was seen. Statistical correlation between ctDNA analysis and clinical response could not be seen.
ctDNA is responding to neoadjuvant therapy and liquid biopsy is easily integrated into a daily routine. As part of translational research this protocol leaves room for further investigations.
液体活检是一种微创程序，可检测肿瘤突变。
在我们的回顾性研究中，我们调查了在 17 例局部晚期直肠癌患者中，每天是否可以对接受新辅助放化疗的患者进行分子治疗监测。6 例患者接受短程放疗（5×5 Gy），随后进行手术；6 例患者根据 RAPIDO 方案接受短程放疗后化疗（FOLFOX4），然后进行手术；5 例患者接受常规新辅助放化疗（5-FU），然后进行手术。反应通过 Dworak 评估。在新辅助放疗前和放疗后立即采集液体活检样本，用 127 个基因的panel 分离和超深度测序游离 DNA。通过与白细胞的正常 DNA 进行比较，对体细胞突变进行生物信息学分析，将其与种系变异或衰老突变区分开来。
在 12 例患者（71%）中至少检测到一个体细胞突变。在 8/12 例患者中，ctDNA 检测到下降，在 4/12 例患者中检测到增加或混合反应。ctDNA 分析与临床反应之间没有统计学相关性。
ctDNA 对新辅助治疗有反应，液体活检很容易融入日常实践。作为转化研究的一部分，该方案为进一步的研究留下了空间。
