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微小残留病对肝转移结直肠癌早期复发的影响。

Impact of Minimal Residual Disease on Early Recurrence of Liver Metastatic Colorectal Cancer.

作者信息

Kawashima Mampei, Yamada Takeshi, Miyasaka Toshimitsu, Kanaka Shintaro, Kuriyama Sho, Uehara Kay, Matsuda Akihisa, Ohta Ryo, Sonoda Hiromichi, Taniai Nobuhiko, Yoshida Hiroshi

机构信息

Department of Gastroenterological Surgery, Nippon Medical School, Tokyo, Japan.

出版信息

Cancer Sci. 2025 May;116(5):1366-1374. doi: 10.1111/cas.16442. Epub 2025 Mar 10.

Abstract

For patients with resectable colorectal liver metastases (CRLM), the efficacy of adjuvant chemotherapy remains a subject of debate. Several studies have concluded that postoperative circulating tumor DNA (ctDNA) is a marker of minimal residual disease (MRD) and is a useful prognostic factor in patients with nonmetastatic colorectal cancer. However, few studies have explored its application in cases involving metastases. This was an observational study that included CRLM patients who underwent primary and liver tumor resection. By examining targeted sequencing of 50 genes commonly mutated in CRC, we identified at least one somatic mutation in each patient's metastatic liver tumor. Blood samples were obtained before and 1-month after surgery. Fifty-three patients were included, and recurrence was diagnosed in 39 patients. Of those, 13 patients experienced early relapse. ctDNA was detected in 45 patients before surgery and 11 after. All MRD-positive patients experienced recurrence. Among them, nine had early recurrence. MRD-positive patients had poorer recurrence free survival (RFS, p < 0.0001) and overall survival (OS, p < 0.0005). Nine of 13 patients with early recurrence had MRD; however, two of 40 patients without early recurrence also had MRD (p < 0.0001). Among 42 MRD-negative patients, adjuvant chemotherapy had no impact of RFS (p = 0.84) or OS (p = 0.54). MRD proved valuable in predicting the risk of postoperative recurrence in patients with CRLM, particularly because MRD positivity emerged as a significant risk factor for early recurrence. Furthermore, it appears that adjuvant chemotherapy may not effectively improve the prognosis for MRD-negative patients.

摘要

对于可切除的结直肠癌肝转移(CRLM)患者,辅助化疗的疗效仍是一个有争议的话题。多项研究得出结论,术后循环肿瘤DNA(ctDNA)是微小残留病(MRD)的标志物,并且是无转移结直肠癌患者的一个有用的预后因素。然而,很少有研究探讨其在涉及转移病例中的应用。这是一项观察性研究,纳入了接受原发性和肝肿瘤切除的CRLM患者。通过检测50个在结直肠癌中常见突变基因的靶向测序,我们在每位患者的转移性肝肿瘤中鉴定出至少一个体细胞突变。在手术前和术后1个月采集血样。共纳入53例患者,39例被诊断为复发。其中,13例患者出现早期复发。术前45例患者检测到ctDNA,术后11例检测到。所有MRD阳性患者均复发。其中,9例早期复发。MRD阳性患者的无复发生存期(RFS,p<0.0001)和总生存期(OS,p<0.0005)较差。13例早期复发患者中有9例MRD阳性;然而,40例无早期复发患者中有2例也有MRD(p<0.0001)。在42例MRD阴性患者中,辅助化疗对RFS(p=0.84)或OS(p=0.54)无影响。MRD在预测CRLM患者术后复发风险方面被证明是有价值的,特别是因为MRD阳性是早期复发的一个重要危险因素。此外,辅助化疗似乎可能无法有效改善MRD阴性患者的预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8031/12044645/7c37d953ddf8/CAS-116-1366-g001.jpg

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