Unit of Oncology, University Hospital of Pisa, Pisa, Italy.
Department of Translational Research and New Technologies in Medicine and Surgery, University Hospital of Pisa, University of Pisa, Pisa, Italy.
JCO Precis Oncol. 2022 Nov;6:e2200244. doi: 10.1200/PO.22.00244.
Prognostic tools to estimate the risk of relapse for patients with liver-limited metastatic colorectal cancer (LL-mCRC) undergoing resection with curative intent are needed. Circulating tumor DNA (ctDNA) as a surrogate of postsurgical minimal residual disease is a promising marker in localized CRC. We explored the role of postoperative ctDNA as a marker of minimal residual disease in patients with radically resected LL-mCRC.
Seventy-six patients with LL-mCRC were retrospectively included. DNA from tumor tissue was sequenced, and one somatic mutation was then assessed by digital droplet polymerase chain reaction in plasma samples collected after surgery to identify the persistence of ctDNA. Relapse-free survival and postresection overall survival were compared between patients with positive vs negative postoperative ctDNA.
ctDNA was found in 39 (51%) of 76 patients with LL-mCRC. At a median follow-up of 77 months, 33 of 39 ctDNA-positive patients and 20 of 37 ctDNA-negative patients experienced disease relapse ( = .008). ctDNA-positive patients reported significantly shorter RFS than ctDNA-negative ones (median RFS 12.7 27.4 months hazard ratio, 2.09, = .008). In the multivariable model including other prognostic covariates, this association was still significant ( = .046) and a trend toward shorter overall survival among ctDNA-positive patients was reported (hazard ratio, 1.65, = .183).
The detection of postsurgical ctDNA is an independent negative prognostic marker and identifies patients at high risk of relapse after liver metastases resection.
对于接受根治性切除术的肝转移结直肠癌（LL-mCRC）患者，需要有预测复发风险的预后工具。循环肿瘤 DNA（ctDNA）作为术后微小残留病的替代标志物，在局部结直肠癌中具有广阔的应用前景。本研究旨在探索术后 ctDNA 作为根治性切除的 LL-mCRC 患者微小残留病标志物的作用。
回顾性纳入 76 例 LL-mCRC 患者。对肿瘤组织的 DNA 进行测序，然后通过术后采集的血浆样本中的数字液滴聚合酶链反应（ddPCR）评估一个体细胞突变，以确定 ctDNA 的持续存在。比较 ctDNA 阳性和阴性患者的无复发生存率（RFS）和术后总生存率（OS）。
在 76 例 LL-mCRC 患者中，39 例（51%）检测到 ctDNA。在中位随访 77 个月时，39 例 ctDNA 阳性患者中有 33 例和 37 例 ctDNA 阴性患者中有 20 例发生疾病复发（ =.008）。ctDNA 阳性患者的 RFS 明显短于 ctDNA 阴性患者（中位 RFS 12.7 27.4 个月，风险比 2.09， =.008）。在纳入其他预后协变量的多变量模型中，这种相关性仍然显著（ =.046），ctDNA 阳性患者的 OS 也呈现缩短趋势（风险比 1.65， =.183）。
术后 ctDNA 的检测是独立的负预后标志物，可识别出肝转移切除术后复发风险较高的患者。
