Background 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. Patients and methods 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%). Results 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. Conclusion 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.

中文翻译：

---

在局部晚期直肠癌患者术前进行新辅助化学放疗后，循环使用无细胞DNA作为治疗失败的预测指标。

背景技术局部晚期直肠癌（LARC）患者的治疗基于化学放射疗法（CRT）和手术的结合。远处复发率仍超过25％。血浆中循环的无细胞DNA（cfDNA）是正常DNA和特定于癌症的DNA片段的混合物，是结直肠癌患者中有希望的生物标志物。我们研究的目的是研究血浆cfDNA作为新辅助CRT和手术治疗的LARC患者预后的指标。患者和方法总共123例LARC患者被纳入2项生物标志物研究。在TME手术之前，对患者进行了新辅助CRT治疗。52名患者（42％）接受了卡培他滨+奥沙利铂的诱导化疗。通过直接荧光法测定基线时获得的EDTA血浆样品中的总cfDNA，诱导化疗后和CRT后。术后5年收集了51例患者（41％）的系列样本。结果中位随访时间为55个月。在30.9％的患者中发现了远处或局部复发。与血浆cfDNA低于第75个百分位数的患者相比，基线cfDNA高于第75个四分位数的患者发生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） 。这同样适用于无病生存期（DFS）（HR = 2.43，95％CI：1.27-4.7，P = 0.015）。在多变量分析中，高cfDNA水平与疾病进展时间和DFS显着相关。在随访期间，无论样本分析的时间点如何，关联性均保持显着性。结论我们证明了cfDNA的基线血浆高水平与LARC患者复发风险增加，复发时间缩短和DFS缩短之间存在关联。因此，cfDNA可能会改善治疗前和治疗后的风险评估，并促进LARC患者的个体化治疗。