Introduction

Both quantitative and molecular changes in ctDNA can hold important information when treating metastatic colorectal cancer (mCRC), but its clinical utility is yet to be established. Before conducting a large-scale randomized trial, it is essential to test feasibility. This study investigates whether ctDNA is feasible for detecting patients who will benefit from treatment with epidermal growth factor receptor inhibitors and the prognostic value of circulating tumor DNA (ctDNA) response.

Materials and methods

Patients with mCRC, who were considered for systemic palliative treatment and were eligible for ctDNA analysis. Mutational testing on cell-free DNA (cfDNA) was done by ddPCR. ctDNA response from baseline to the third treatment cycle was evaluated in patients with detectable ctDNA at baseline. ctDNA maximum response was defined as undetectable ctDNA at the third treatment cycle, ctDNA partial response as any decrease in the ctDNA level, and ctDNA progression as any increase in the ctDNA level.

Results

Forty-nine patients were included. The time to test results for mutational testing on cfDNA was significantly shorter than on tumor tissue (p < .001). Progression-free survival were 11.2 months (reference group), 7.5 months (HR = 10.7, p= .02), and 4.6 months (HR = 11.4, p= .02) in patients with ctDNA maximum response, partial response, and progression, respectively. Overall survival was 31.2 months (reference group), 15.2 months (HR = 4.1, p= .03), and 9.0 months (HR = 2.6, p= .03) in patients with ctDNA maximum response, partial response, and progression, respectively.

Conclusion

Pretreatment mutational testing on cfDNA in daily clinic is feasible and can be applied in randomized clinical trials evaluating the clinical utility of ctDNA. Early dynamics in ctDNA during systemic treatment hold prognostic value.

中文翻译：

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可行性评估在 ctDNA 引导试验设计中的重要性 – OPTIPAL II 研究结果

介绍

在治疗转移性结直肠癌 (mCRC) 时，ctDNA 的定量和分子变化都可以提供重要信息，但其临床实用性尚未确定。在进行大规模随机试验之前，有必要测试可行性。本研究探讨 ctDNA 是否可用于检测将从表皮生长因子受体抑制剂治疗中受益的患者以及循环肿瘤 DNA (ctDNA) 反应的预后价值。

材料和方法

考虑接受全身姑息治疗且符合 ctDNA 分析条件的 mCRC 患者。通过 ddPCR 对游离 DNA (cfDNA) 进行突变测试。在基线时可检测到 ctDNA 的患者中评估了从基线到第三个治疗周期的 ctDNA 反应。ctDNA 最大反应定义为在第三个治疗周期检测不到 ctDNA，ctDNA 部分反应定义为 ctDNA 水平的任何降低，ctDNA 进展定义为 ctDNA 水平的任何增加。

结果

包括四十九名患者。cfDNA 突变检测结果的检测时间明显短于肿瘤组织 ( p < .001)。ctDNA 最大缓解、部分缓解和进展患者的无进展生存期分别为 11.2 个月（参考组）、7.5 个月（HR = 10.7，p = .02）和 4.6 个月（HR = 11.4，p = .02） ， 分别。ctDNA 最大缓解、部分缓解和进展患者的总生存期分别为 31.2 个月（参考组）、15.2 个月（HR = 4.1，p = .03）和 9.0 个月（HR = 2.6，p = .03） 。

结论

在日常临床中对cfDNA进行治疗前突变检测是可行的，并且可以应用于评估ctDNA临床效用的随机临床试验。全身治疗期间 ctDNA 的早期动态具有预后价值。