Lefèvre Anna Cecilie, Kronborg Camilla, Sørensen Brita Singers, Krag Søren Rasmus Palmelund, Serup-Hansen Eva, Spindler Karen-Lise Garm
Experimental Clinical Oncology, Aarhus University Hospital, Denmark.
Department of Oncology, Aarhus University Hospital, Denmark; Danish Centre for Particle Therapy, Denmark.
Radiother Oncol. 2020 Sep;150:211-216. doi: 10.1016/j.radonc.2020.06.045. Epub 2020 Jul 3.
Measuring circulating-free-deoxyribonucleic-acid (cfDNA) has created a new framework for personalized treatment in oncology. The aim of this study was to analyze the relation between cfDNA and risk factors and outcome in squamous cell carcinoma of the anus (SCCA).
Patients treated with radiotherapy for localized SCCA were included in Aarhus, Denmark from 2016 to 2019. Serum samples from baseline, during and after therapy, were measured for the level of cfDNA in copies per mL by a direct fluorescent assay.
Eighty patients were included. Samples were available at baseline (n = 73) mid-therapy (n = 74), end-therapy (n = 67) and one-year follow-up (1Y) (n = 29). P16-positivity was found in 89% (n = 55). The median level of cfDNA was higher for P16 negative tumors (1.48) compared with the P16 positive tumors (0.90, P = 0.04). Data showed a correlation between baseline cfDNA levels and Gross Tumor Volume (R = 0.13, P < 0.01), and increasing levels with increasing T-stage (T1 = 0.80, T2 = 0.94, T3 = 1.11, T4 = 1.3). Higher cfDNA levels were observed in patients with poor performance status (P < 0.01). The cfDNA level decreased from baseline to mid-therapy (0.92-0.78, P < 0.01) and from baseline to 1Y (0.92-0.71, P < 0.01). Baseline levels for patients with treatment failure (n = 8) were above the 25th percentile (p = 0.05) which translates into difference in disease free survival.
Results indicate an association between baseline cfDNA levels and risk factors in SCCA and a low baseline level correlates to lower risk of treatment failure. Findings contribute with new knowledge of the biological role of cfDNA in SCCA and holds potential knowledge for personalized treatment of SCCA.
检测循环游离脱氧核糖核酸（cfDNA）为肿瘤学个性化治疗创造了一个新框架。本研究旨在分析cfDNA与肛管鳞状细胞癌（SCCA）的危险因素及预后之间的关系。
纳入2016年至2019年在丹麦奥胡斯接受局部SCCA放射治疗的患者。通过直接荧光测定法测量基线、治疗期间和治疗后的血清样本中每毫升cfDNA的拷贝数水平。
共纳入80例患者。在基线（n = 73）、治疗中期（n = 74）、治疗结束时（n = 67）和一年随访期（1Y）（n = 29）均有样本。发现89%（n = 55）的患者P16呈阳性。P16阴性肿瘤的cfDNA中位数水平（1.48）高于P16阳性肿瘤（0.90，P = 0.04）。数据显示基线cfDNA水平与肿瘤总体积之间存在相关性（R = 0.13，P < 0.01），且随着T分期增加水平升高（T1 = 0.80，T2 = 0.94，T3 = 1.11，T4 = 1.3）。体能状态差的患者cfDNA水平更高（P < 0.01）。cfDNA水平从基线降至治疗中期（0.92 - 0.78，P < 0.01），从基线降至1Y时（0.92 - 0.71，P < 0.01）。治疗失败患者（n = 8）的基线水平高于第25百分位数（p = 0.05），这转化为无病生存期的差异。
结果表明SCCA中基线cfDNA水平与危险因素之间存在关联，且低基线水平与较低的治疗失败风险相关。这些发现为cfDNA在SCCA中的生物学作用提供了新知识，并为SCCA的个性化治疗提供了潜在的知识。
