Department of Oncology, Herlev & Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Department of Oncology, Herlev & Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Ann Oncol. 2018 Mar 1;29(3):610-615. doi: 10.1093/annonc/mdx778.
Treatment of patients with locally advanced rectal cancer (LARC) is based on a combination of chemo-radiotherapy (CRT) and surgery. The rate of distant recurrences remains over 25%. Circulating cell-free DNA (cfDNA) in plasma is a mixture of normal and cancer-specific DNA segments and is a promising biomarker in patients with colorectal cancer. The aim of our study was to investigate plasma cfDNA as a prognostic marker for outcome in patients with LARC treated with neoadjuvant CRT and surgery.
In total, 123 patients with LARC were included in 2 biomarker studies. Patients were treated with neoadjuvant CRT before TME surgery. Fifty-two (42%) of the patients received induction chemotherapy with capecitabine + oxaliplatin. Total cfDNA was measured by direct fluorescent assay in EDTA plasma samples obtained at baseline, after induction chemotherapy, and after CRT. Serial samples 5 years after surgery were collected in 51 patients (41%).
Median follow-up was 55 months. Distant or local recurrence was seen in 30.9% of the patients. Patients with baseline cfDNA levels above the 75th quartile had a higher risk of local or distant recurrence and shorter time to recurrence compared with patients with plasma cfDNA below the 75th percentile (HR = 2.48, 95% CI: 1.3-4.8, P = 0.007). The same applied to disease-free survival (DFS) (HR = 2.43, 95% CI: 1.27-4.7, P = 0.015). In multivariate analysis, a high cfDNA level was significantly associated with time to progression and DFS. During follow-up, the association remained significant regardless of time point for sample analysis.
We have demonstrated an association between a high baseline plasma level of cfDNA and increased risk of recurrence, shorter time to recurrence, and shorter DFS in patients with LARC. Consequently, cfDNA could potentially improve pre- and post-treatment risk assessment and facilitate individualized therapy for patients with LARC.
局部晚期直肠癌（LARC）患者的治疗基于化疗-放疗（CRT）联合手术。远处复发率仍超过 25%。血浆中的游离循环 DNA（cfDNA）是正常和肿瘤特异性 DNA 片段的混合物，是结直肠癌患者有前途的生物标志物。我们的研究目的是探讨 cfDNA 作为接受新辅助 CRT 和手术治疗的 LARC 患者预后的预测标志物。
共有 123 例 LARC 患者纳入 2 项生物标志物研究。患者在 TME 手术前接受新辅助 CRT。52 例（42%）患者接受卡培他滨+奥沙利铂诱导化疗。在基线、诱导化疗后和 CRT 后采集 EDTA 血浆样本，用直接荧光分析法测量总 cfDNA。51 例患者（41%）在手术后 5 年内收集了连续样本。
中位随访时间为 55 个月。30.9%的患者出现远处或局部复发。cfDNA 基线水平高于第 75 百分位数的患者与 cfDNA 低于第 75 百分位数的患者相比，局部或远处复发的风险更高，复发时间更短（HR=2.48，95%CI：1.3-4.8，P=0.007）。无病生存（DFS）也是如此（HR=2.43，95%CI：1.27-4.7，P=0.015）。多变量分析显示，高 cfDNA 水平与进展时间和 DFS 显著相关。在随访期间，无论分析样本的时间点如何，这种关联都是显著的。
我们证明了 LARC 患者基线 cfDNA 水平高与复发风险增加、复发时间缩短和 DFS 缩短相关。因此，cfDNA 可能有助于改善 LARC 患者的治疗前和治疗后风险评估，并促进个体化治疗。
