MRI Tumor Regression Grade and Circulating Tumor DNA as Complementary Tools to Assess Response and Guide Therapy Adaptation in Rectal Cancer
MRI Tumor Regression Grade and Circulating Tumor DNA as Complementary Tools to Assess Response and Guide Therapy Adaptation in Rectal Cancer
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DOI：
10.1158/1078-0432.ccr-19-1996
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发表时间：
2020-01-01
影响因子：
11.5
通讯作者：
Cunningham, David
中科院分区：
文献类型：
--
作者：
Khakoo, Shelize;Carter, Paul David;Cunningham, David
目的：术前放化疗（CRT）的反应各不相同。我们评估是否循环肿瘤DNA（ctDNA）可能是一个早期指标的肿瘤反应或进展，以指导治疗适应直肠cancer.Experimental Design：共243系列血浆样本进行了分析，从47例局部直肠癌接受CRT。使用液滴数字PCR在血浆中追踪多达三种体细胞变体。RECIST和MRI肿瘤消退等级（mrTRG）评价缓解。结果：ctDNA的检出率：治疗前为74%（n = 35/47），CRT中期为21%（n = 10/47），完成CRT后为21%（n = 10/47），术后为13%（n = 3/23）。CRT后ctDNA状态与mrTRG的原发肿瘤缓解相关（P = 0.03）。中位随访时间为26.4个月，完成CRT后可检测到ctDNA的患者的无瘤生存期较短[HR 7.1; 95%置信区间（CI），2.4-21.5; P < 0.001]，CRT前和中期持续可检测到ctDNA的患者（HR 3.8; 95%CI，1.2-11.7; P = 0.02），以及CRT前、中、后（HR 11.5; 95%CI，3.3-40.4; P < 0.001）。在可检测到ctDNA的患者中，CRT中期>= 0.07%或完成CRT后>= 0.13%的丰度分数阈值预测转移，CRT中期的敏感性为100%，特异性为83.3%，CRT完成为66.7%。所有3例可检测到ctDNA的患者术后复发，而20例未检测到ctDNA的患者无复发（P = 0.001）。结论：ctDNA可识别患者在新辅助治疗期间和术后发生转移的风险，并可用于定制治疗。
Purpose: Response to preoperative chemo-radiotherapy (CRT) varies. We assessed whether circulating tumor DNA(ctDNA) might be an early indicator of tumor response or progression to guide therapy adaptation in rectal cancer.Experimental Design: A total of 243 serial plasma samples were analyzed from 47 patients with localized rectal cancer undergoing CRT. Up to three somatic variants were tracked in plasma using droplet digital PCR. RECIST and MRI tumor regression grade (mrTRG) evaluated response. Survival analyses applied Kaplan-Meier method and Cox regression.Results: ctDNA detection rates were: 74% (n = 35/47) pretreatment, 21% (n = 10/47) mid CRT, 21% (n = 10/47) after completing CRT, and 13% (n = 3/23) after surgery. ctDNA status after CRT was associated with primary tumor response by mrTRG (P = 0.03). With a median follow-up of 26.4 months, metastases-free survival was shorter in patients with detectable ctDNA after completing CRT [HR 7.1; 95% confidence interval (CI), 2.4-21.5; P < 0.001], persistently detectable ctDNA pre and mid CRT (HR 3.8; 95% CI, 1.2-11.7; P = 0.02), and pre, mid, and after CRT (HR 11.5; 95% CI, 3.3-40.4; P < 0.001) compared with patients with undetectable or nonpersistent ctDNA. In patients with detectable ctDNA, a fractional abundance threshold of >= 0.07% mid CRT or >= 0.13% after completing CRT predicted for metastases with 100% sensitivity and 83.3% specificity for mid CRT and 66.7% for CRT completion. All 3 patients with detectable ctDNA post-surgery relapsed compared with none of the 20 patients with undetectable ctDNA (P = 0.001).Conclusions: ctDNA identified patients at risk of developing metastases during the neoadjuvant period and post-surgery, and could be used to tailor treatment.