Kalil Jennifer A, Krzywon Lucyna, Petrillo Stephanie K, Tsamchoe Migmar, Zlotnik Oran, Lazaris Anthoula, Metrakos Peter
Department of Surgery, Royal Victoria Hospital - McGill University Health Center, Montréal, QC, Canada.
Research Institute, McGill University Health Center, Montréal, QC, Canada.
Front Oncol. 2024 Oct 8;14:1418696. doi: 10.3389/fonc.2024.1418696. eCollection 2024.
Approximately 50% of patients diagnosed with colorectal cancer develop colorectal cancer liver metastases (CRLM). Although curative intent liver resection provides 5-year survival of 40-50%, up to 70% of patients develop recurrence of CRLM. Detection of minimal residual disease (MRD) is essential for timely, optimized treatment. This study evaluated the feasibility and utility of using circulating tumor DNA (ctDNA) to identify MRD and predict disease recurrence.
Patients with CRLM that underwent liver resection and had known KRAS or PIK3CA mutations were retrospectively identified. Serial blood samples were collected every 3 months following surgery for disease surveillance. ctDNA was isolated from the samples and analyzed with digital PCR (dPCR).
KRAS and PIK3CA mutations were identified by dPCR in 29 patients over 115 timepoints. In patients with detectable ctDNA at time of liver resection, 81% (13/16) developed disease recurrence, while 46% (6/13) of the patients with undetectable ctDNA recurred (p=0.064). Presence of ctDNA was detected in 27.6% (8/29) of the initial postoperative samples. Radiologic recurrence was later diagnosed in 100% (8/8) of these patients, while 52% (11/21) who had undetectable ctDNA postoperatively recurred (p=0.026). Detectable ctDNA postoperatively was associated with a shorter disease-free survival (DFS) of 9 months vs 13 months in patients who had undetectable ctDNA (HR 2.95, 95% CI 1.16-7.49; p=0.02).
Liquid biopsy using dPCR can identify low levels of ctDNA, enabling early detection of disease recurrence. Additionally, the presence of ctDNA postoperatively was predictive of recurrence. This study corroborates current literature and provides rational for moving toward a clinical trial using ctDNA and dPCR to detect MRD after CRLM resection.
约50%被诊断为结直肠癌的患者会发生结直肠癌肝转移（CRLM）。尽管根治性肝切除可使5年生存率达到40%-50%，但高达70%的患者会出现CRLM复发。检测微小残留病（MRD）对于及时、优化治疗至关重要。本研究评估了使用循环肿瘤DNA（ctDNA）来识别MRD并预测疾病复发的可行性和实用性。
回顾性纳入接受肝切除且已知存在KRAS或PIK3CA突变的CRLM患者。术后每3个月采集系列血样进行疾病监测。从样本中分离ctDNA并采用数字PCR（dPCR）进行分析。
在115个时间点对29例患者进行dPCR检测，发现了KRAS和PIK3CA突变。肝切除时ctDNA可检测到的患者中，81%（13/16）出现疾病复发，而ctDNA不可检测的患者中46%（6/13）复发（p=0.064）。术后初始样本中27.6%（8/29）检测到ctDNA存在。这些患者中100%（8/8）随后被诊断为影像学复发，而术后ctDNA不可检测的患者中有52%（11/21）复发（p=0.026）。术后ctDNA可检测到与无病生存期（DFS）较短相关，ctDNA不可检测的患者DFS为13个月，而前者为9个月（风险比2.95，95%置信区间1.16-7.49；p=0.02）。
采用dPCR的液体活检可识别低水平的ctDNA，从而实现疾病复发的早期检测。此外，术后ctDNA的存在可预测复发。本研究证实了现有文献，并为开展使用ctDNA和dPCR检测CRLM切除术后MRD的临床试验提供了依据。
