循环肿瘤DNA的早期动态预测食管癌患者的化疗反应,medRxiv - Gastroenterology

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循环肿瘤DNA的早期动态预测食管癌患者的化疗反应
medRxiv - Gastroenterology Pub Date : 2021-03-05 , DOI: 10.1101/2021.02.25.21251979
Ryosuke Fujisawa , Takeshi Iwaya , Fumitaka Endo , Masashi Idogawa , Noriyuki Sasaki , Hayato Hiraki , Shoichiro Tange , Tomomi Hirano , Yuka Koizumi , Masakazu Abe , Tomoko Takahashi , Mizunori Yaegashi , Yuji Akiyama , Mari Masuda , Akira Sasaki , Fumiaki Takahashi , Yasushi Sasaki , Takashi Tokino , Satoshi S. Nishizuka

目的：我们调查了使用数字PCR（dPCR）测量的早期循环肿瘤DNA（ctDNA）变化是否可以预测食管鳞状细胞癌（ESCC）的晚期化疗反应。 设计：我们比较了42例ESCC化疗期间ctDNA的动力学和肿瘤体积。通过在初始化疗前后ctDNA的变异等位基因频率（VAF）与ctDNA的变异等位基因频率（ctf / pre-ctDNA）与总肿瘤体积（post // pre-volume）之比来评估以后的化疗反应的预测准确性使用接收器工作特性曲线分析进行循环。一线化疗结束时，总的阳性和阴性的客观反应（OR）分别定义为肿瘤总体积减少> 50％或≤50％。 结果：来自42位患者的43个肿瘤的突变筛选显示96个突变。使用70个选定的突变（每位患者1-3个），对38例患者的治疗前dPCR-ctDNA数据提供了丰富的信息。用于预测总OR的后/前体积和后/前ctDNA水平的曲线下面积（AUC）分别为0.85和0.88。后/前ctDNA的最佳截止值为0.13。在90％（18/20）的前/后体积≥50％的患者中，总的OR值可以通过后-/-ctDNA进行高精度预测；ctDNA后/ pre-ctDNA的AUC高于量后/ pre-volume的AUC（分别为0.85和0.76）。ctDNA后/ pre-ctDNA低的患者（n = 18）的总生存率明显高于ctDNA后//-ctDNA前的患者（n = 20； P = 0.03）。 结论： 在化疗的初始周期后，早期的ctDNA变化预示了ESCC患者对治疗的更高反应。

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Early dynamics of circulating tumor DNA predict chemotherapy responses for patients with esophageal cancer

Purpose: We investigated whether early circulating tumor DNA (ctDNA) changes, measured using digital PCR (dPCR), can predict later chemotherapy responses in esophageal squamous cell cancer (ESCC). Design: We compared the dynamics of ctDNA and tumor volumes during chemotherapy in 42 ESCC. The accuracy of predictions of later chemotherapy responses were evaluated by the ratio of the variant allele frequency (VAF) of ctDNA (post-/pre-ctDNA) and the total tumor volume (post-/pre-volume) before and after an initial chemotherapy cycle using a receiver-operating characteristic curve analysis. Total positive and negative objective responses (ORs) were defined as either >50% or ≤50% reductions, respectively, in the total tumor volume at the end of first-line chemotherapy. Results: Mutation screening of 43 tumors from 42 patients revealed 96 mutations. The pretreatment dPCR-ctDNA data were informative in 38 patients, using 70 selected mutations (1-3 per patient). The areas under the curve (AUCs) for the post-/pre-volume and post-/pre-ctDNA levels used in predicting the total OR were 0.85 and 0.88, respectively. The optimal cutoff value of post-/pre-ctDNA was 0.13. In 90% (18/20) of patients with a post-/pre-volume ≥50%, the total OR could be predicted by the post-/pre-ctDNA with high accuracy; the AUC by post-/pre-ctDNA was higher than that by post-/pre-volume (0.85 vs 0.76, respectively). Patients with low post-/pre-ctDNA (n = 18) had a significantly better overall survival rate than those with high post-/pre-ctDNA (n = 20; P = 0.03). Conclusions: Early ctDNA changes after an initial cycle of chemotherapy predict later responses to treatment with high accuracy in ESCC patients.

更新日期：2021-03-05

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