Cleveland Clinic Foundation, Digestive Diseases and Surgery Institute, Department of Hepato-pancreato-biliary & Liver Transplant Surgery, Cleveland, OH.
Cleveland Clinic Foundation, Taussig Cancer Institute, Department of Hematology and Oncology, Cleveland, OH.
JCO Clin Cancer Inform. 2023 Sep;7:e2300111. doi: 10.1200/CCI.23.00111.
Liver metastases occur in about 50% of colorectal cancer cases and drive patient outcomes. Circulating tumor DNA (ctDNA) is emerging as a diagnostic, surveillance, and tumor mutational information tool.
Patients with colorectal cancer liver metastasis (CCLM) seen in a multidisciplinary liver tumor clinic from January to August 2022 received ctDNA testing on each visit. ctDNA was obtained using the Guardant360 platform. Tumor mutational burden (TMB) is defined as the number of identified mutations per megabase of genome analyzed.
Fifty-two patients had available ctDNA, with 34 (65%) tested preoperatively and 18 (35%) postoperatively; nine patients had sequential pre- and postoperative testing. The median time to test result was 12 days (IQR, 10-13.5). There were a greater number of somatic mutations identified preoperatively (n = 29 n = 11) and a greater genomic heterogeneity ( = .0069). The mean TMB score was 12.77 in those without pathologic response to cytotoxic therapy and 6.0 in those with pathologic response ( = .10). All nine patients with sequential testing were positive preoperatively, compared with just three (33.3%) postoperatively ( = .0090). Positive postoperative ctDNA was associated with the increased likelihood of disease recurrence after resection (57%) versus negative ctDNA (0%, = .0419).
Routine ctDNA screening in patients with CCLM is logistically feasible. Liver resection and/or transplant may be associated with clearance of detectable ctDNA and a reduction in TMB or genomic heterogeneity. Persistence of ctDNA alterations postresection appears predictive of disease recurrence. Further studies are necessary to confirm these findings, and longitudinal ctDNA testing is needed to monitor changing tumor biology.
大约 50%的结直肠癌病例会发生肝转移，并影响患者的预后。循环肿瘤 DNA（ctDNA）正成为一种诊断、监测和肿瘤突变信息工具。
2022 年 1 月至 8 月，在多学科肝脏肿瘤诊所就诊的结直肠癌肝转移（CCLM）患者在每次就诊时都接受了 ctDNA 检测。ctDNA 是使用 Guardant360 平台获得的。肿瘤突变负担（TMB）定义为每分析百万碱基基因组中鉴定出的突变数量。
52 名患者有可用的 ctDNA，其中 34 名（65%）在术前进行了检测，18 名（35%）在术后进行了检测；9 名患者进行了术前和术后的连续检测。获得检测结果的中位时间为 12 天（IQR，10-13.5）。术前检测到的体细胞突变数量较多（n=29，n=11），基因组异质性较大（ =.0069）。无细胞毒性治疗病理反应的患者 TMB 评分平均为 12.77，有病理反应的患者为 6.0（ =.10）。所有 9 名连续检测的患者术前均为阳性，而术后仅 3 名（33.3%）为阳性（ =.0090）。术后 ctDNA 阳性与切除后疾病复发的可能性增加相关（57%），而 ctDNA 阴性（0%）则无相关性（ =.0419）。
在 CCLM 患者中进行常规 ctDNA 筛查在操作上是可行的。肝切除术和/或肝移植可能与清除可检测的 ctDNA 以及降低 TMB 或基因组异质性有关。切除后 ctDNA 持续存在似乎可预测疾病复发。需要进一步的研究来证实这些发现，并且需要进行纵向 ctDNA 检测来监测肿瘤生物学的变化。
