早期结肠癌新辅助治疗中的循环DNA

Circulating DNA in the neoadjuvant setting of early stage colon cancer.

作者信息

Bregni Giacomo, Pretta Andrea, Senti Chiara, Acedo Reina Elena, Vandeputte Caroline, Trevisi Elena, Gkolfakis Paraskevas, Kehagias Pashalina, Deleporte Amélie, Van Laethem Jean-Luc, Vergauwe Philippe, Van den Eynde Marc, Deboever Guido, Janssens Jos, Demolin Gauthier, Holbrechts Stephane, Clausse Marylene, De Grez Thierry, Peeters Marc, D'Hondt Lionel, Geboes Karen, Besse-Hammer Tatiana, Rothé Françoise, Flamen Patrick, Hendlisz Alain, Sclafani Francesco

机构信息

Institut Jules Bordet, Brussels, Belgium.

Erasme Hospital, Brussels, Belgium.

出版信息

Acta Oncol. 2022 Oct;61(10):1223-1229. doi: 10.1080/0284186X.2022.2101023. Epub 2022 Jul 22.

DOI:10.1080/0284186X.2022.2101023

PMID:35866544

Abstract

BACKGROUND

While circulating tumour (ct)DNA is an indicator of minimal residual disease and negative prognostic factor in stage II-III colon cancer, no study has ever analysed the value of this biomarker in colon cancer patients treated with neoadjuvant chemotherapy. We sought to fill this gap by using prospectively collected plasma samples from 80 stage III colon cancer patients, receiving one cycle of neoadjuvant FOLFOX followed by surgery +/- adjuvant FOLFOX in the PePiTA trial.

MATERIAL AND METHODS

Samples were collected at baseline, 2 weeks and surgery. NPY and WIF1 were selected as universal methylation markers for ctDNA, and analysed with ddPCR technology. ROC curves were applied for cut-off points, and outcome measures included 5-year disease-free survival (DFS) and 6-year overall survival (OS).

RESULTS

After a median follow-up of 52.5 months, baseline circulating-free (cf) DNA was an independent prognostic factor for DFS (HR 3.35, 95% CI: 1.15-9.77, = .03), and a trend towards a similar association was observed for relative cfDNA changes between baseline and surgery (HR 2.57, 95% CI: 0.94-7.05, = .07). Among 60 ctDNA assessable patients, 25 (42%) had detectable ctDNA at baseline. While detection of ctDNA at any pre-operative timepoint was not associated with outcome, patients with ctDNA increase (change of the worst trending methylation marker ≥11%, or mean ctDNA change of NPY and WIF1 ≥ 0%) between baseline and surgery showed a trend towards worse 5-year DFS (HR 3.66, 95% CI: 0.81-16.44, = .09).

CONCLUSION

This is the first study of ctDNA in the neoadjuvant setting of early-stage colon cancer. Results are hypothesis-generating and should be confirmed in larger series.

摘要

背景

循环肿瘤（ct）DNA是II-III期结肠癌微小残留病的指标和不良预后因素，但尚无研究分析过该生物标志物在接受新辅助化疗的结肠癌患者中的价值。我们试图通过前瞻性收集80例III期结肠癌患者的血浆样本填补这一空白，这些患者在PePiTA试验中接受了一个周期的新辅助FOLFOX治疗，随后接受手术，部分患者还接受了辅助FOLFOX治疗。

材料与方法

在基线、2周和手术时采集样本。选择NPY和WIF1作为ctDNA的通用甲基化标志物，并用数字滴度PCR技术进行分析。应用ROC曲线确定截断点，结果指标包括5年无病生存期（DFS）和6年总生存期（OS）。

结果

中位随访52.5个月后，基线循环游离（cf）DNA是DFS的独立预后因素（HR 3.35，95%CI：1.15-9.77，P=0.03），并且观察到基线与手术之间相对cfDNA变化有类似关联的趋势（HR 2.57，95%CI：0.94-7.05，P=0.07）。在60例可评估ctDNA的患者中，25例（42%）在基线时可检测到ctDNA。虽然术前任何时间点检测到ctDNA均与预后无关，但基线与手术之间ctDNA增加（最差趋势甲基化标志物变化≥11%，或NPY和WIF1的平均ctDNA变化≥0%）的患者5年DFS有变差的趋势（HR 3.66，95%CI：0.81-16.44，P=0.09）。