Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
Genomics Unit, Keio Cancer Center, Keio University School of Medicine, Tokyo, Japan.
Ann Surg Oncol. 2023 Jun;30(6):3747-3756. doi: 10.1245/s10434-023-13194-z. Epub 2023 Feb 14.
To guide appropriate treatment strategy, an accurate tumor monitoring modality that reflects tumor burden during neoadjuvant treatment is required for esophageal squamous cell carcinoma (ESCC). We aimed to investigate the clinical utility of circulating tumor DNA (ctDNA) in plasma in patients who received neoadjuvant chemotherapy (NAC) followed by esophagectomy.
Longitudinally collected plasma samples for ctDNA combined with genomic DNA from primary lesions were obtained from patients with histologically confirmed ESCC who underwent NAC followed by subtotal esophagectomy. Next-generation sequencing was performed to identify mutations from the plasma and the primary tumor. The relationships between changes in ctDNA and the pathological response and recurrence were assessed in patients with locally advanced ESCC.
In pretreatment samples from 13 patients, multiple concordant mutations in ctDNA and primary tumors were observed in 11 patients (85%), who were classified as ctDNA positive before treatment. The ctDNA positive rate after NAC correlated with the pathological response (responders, 25%; nonresponders, 100%; p = 0.007). The risk of recurrence increased significantly in patients with positive ctDNA after surgery in analysis of 16 patients; the 1-year recurrence-free survival rates were 90 and 0% in ctDNA-negative and ctDNA-positive groups, respectively (p = 0.0008). In two patients with postoperative recurrence, ctDNA was detected approximately 5.5 months earlier than the diagnosis using radiographical imaging.
ctDNA is a promising biomarker for predicting pathological response and postoperative recurrence in ESCC. To demonstrate the external validity, we are currently preparing a multicenter prospective study.
为了指导合适的治疗策略，对于接受新辅助化疗（NAC）后行食管切除术的食管鳞癌（ESCC）患者，需要一种准确的肿瘤监测方法来反映肿瘤负荷。我们旨在研究接受 NAC 后行食管切除术的患者血浆中循环肿瘤 DNA（ctDNA）的临床应用。
收集经组织学证实接受 NAC 后行次全食管切除术的 ESCC 患者的血浆和原发肿瘤的纵向采集的 ctDNA 结合基因组 DNA 样本。对来自血浆和原发肿瘤的突变进行下一代测序。评估局部晚期 ESCC 患者中 ctDNA 变化与病理反应和复发的关系。
在 13 例患者的预处理样本中，11 例（85%）患者的 ctDNA 和原发肿瘤中观察到多个一致的突变，这些患者在治疗前被归类为 ctDNA 阳性。NAC 后的 ctDNA 阳性率与病理反应相关（有反应者为 25%；无反应者为 100%；p=0.007）。在 16 例患者的分析中，手术后 ctDNA 阳性患者的复发风险显著增加；ctDNA 阴性和 ctDNA 阳性组的 1 年无复发生存率分别为 90%和 0%（p=0.0008）。在两名术后复发的患者中，ctDNA 的检测时间比影像学诊断大约早 5.5 个月。
ctDNA 是预测 ESCC 病理反应和术后复发的有前途的生物标志物。为了证明其外部有效性，我们目前正在准备一项多中心前瞻性研究。
