Gastrointestinal Cancer Center, Linz, Austria; Department of Surgery, Ordensklinikum Linz, Austria; Johannes Kepler University Linz, Medical Faculty, Linz, Austria.
Department of Diagnostic and Interventional Radiology, Ordensklinikum Linz, Austria.
Eur J Surg Oncol. 2022 May;48(5):1046-1053. doi: 10.1016/j.ejso.2021.11.138. Epub 2021 Dec 1.
Circulating tumor DNA (ctDNA) represents a promising tool for diagnosis, prognosis and treatment monitoring of several malignancies. Its association with tumor burden in pancreatic ductal cancer (PDAC), especially in localized disease, is not fully explored yet. We aimed to investigate the association of pretherapeutic ctDNA levels in localized and metastatic PDAC with tumor volume and clinical outcomes.
Liquid biopsy for ctDNA detection was prospectively obtained from patients with localized or disseminated PDAC prior to either resection or systemic treatment. Detection rates and levels of ctDNA (digital droplet PCR) were correlated to tumor volume, relapse rate and survival.
60 patients with localized and 47 patients with metastatic PDAC were included. ctDNA was detected in 10% of localized and 57.4% of metastasized PDAC samples. In localized disease, ctDNA detection significantly correlated with the numbers of involved locoregional lymph nodes (p = 0.030). Primary tumor volume did not correlate with ctDNA levels in neither localized (p = 0.573) nor metastasized disease (p = 0.878). In disseminated disease, ctDNA levels correlated with total tumor volume (p = 0.026) and especially with liver metastases volume (p = 0.004), but not with other metastases. Detection of pretherapeutic ctDNA was associated with shorter DFS in localized (3.3 vs. 18.1 months, p = 0.000), whereas ctDNA levels were associated with worse survival in metastatic PDAC (5.7 vs. 7.8 months, p = 0.036).
ctDNA positivity indicates major nodal involvement or even presence of undetected distant metastases associated with early recurrence in localized PDAC. Moreover, it predicts worse clinical outcome in both localized and metastatic disease.
循环肿瘤 DNA（ctDNA）是一种很有前途的工具，可用于诊断、预后和监测多种恶性肿瘤的治疗效果。但其与胰腺导管癌（PDAC）的肿瘤负荷之间的关系，尤其是在局限性疾病中，尚未得到充分探讨。我们旨在研究局限性和转移性 PDAC 患者的治疗前 ctDNA 水平与肿瘤体积和临床结局之间的关系。
前瞻性地从接受局部或全身性治疗的局限性或转移性 PDAC 患者中获取液体活检以检测 ctDNA。检测 ctDNA（数字液滴 PCR）的检出率和水平与肿瘤体积、复发率和生存率相关。
纳入了 60 例局限性和 47 例转移性 PDAC 患者。局限性和转移性 PDAC 样本中 ctDNA 的检出率分别为 10%和 57.4%。在局限性疾病中，ctDNA 的检出与局部区域淋巴结受累的数量显著相关（p=0.030）。原发性肿瘤体积与局限性（p=0.573）和转移性（p=0.878）疾病中的 ctDNA 水平均无相关性。在转移性疾病中，ctDNA 水平与总肿瘤体积相关（p=0.026），特别是与肝转移体积相关（p=0.004），但与其他转移无关。治疗前 ctDNA 的检出与局限性 PDAC 的无病生存期较短相关（3.3 个月与 18.1 个月，p=0.000），而 ctDNA 水平与转移性 PDAC 的总生存期较差相关（5.7 个月与 7.8 个月，p=0.036）。
ctDNA 阳性提示局部 PDAC 中存在主要淋巴结受累，甚至存在未检测到的远处转移，与早期复发相关。此外，它预示着局限性和转移性疾病的临床结局更差。
