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肿瘤内水平预测食管鳞癌新辅助化疗的治疗反应。

Intratumoral Levels Predict Therapeutic Response to Neoadjuvant Chemotherapy in Esophageal Squamous Cell Carcinoma.

机构信息

Center for Gastrointestinal Research, Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute, Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas.

Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, California.

出版信息

Clin Cancer Res. 2019 Oct 15;25(20):6170-6179. doi: 10.1158/1078-0432.CCR-19-0318. Epub 2019 Jul 29.

Abstract

PURPOSE

Emerging evidence indicates that gut microbiome plays a crucial role in the cancer pathogenesis. Although () is associated with poor prognosis in multiple cancers, its clinical significance in predicting response to chemotherapy in patients with esophageal squamous cell carcinoma (ESCC) remains unclear.

EXPERIMENTAL DESIGN

The levels were quantified by qPCR assays in tumor tissues from 551 patients with ESCC from two independent cohorts, including 101 patients who received neoadjuvant chemotherapy prior to curative resection. Associations between burden and recurrence-free survival (RFS), as well with chemotherapeutic response were evaluated using response evaluation criteria in solid tumors (RECISTs), primary tumor metabolic response defined by maximum standardized uptake value (SUV) changes in positron emission tomography-CT (PET/CT), and pathologic tumor regression grade (TRG).

RESULTS

High burden of in patients with ESCC associated with poor RFS in both training [log-rank = 0.02; HR = 1.61; = 0.03] and validation cohorts (log-rank = 0.003; HR = 1.96; = 0.004). Importantly, patients with ESCC with high levels of displayed poor chemotherapeutic response for all three evaluation methods: RECIST ( = 0.04), SUV change in PET/CT ( = 0.0004), and TRG ( = 0.003).

CONCLUSIONS

We conclude that high levels of intratumoral have a prognostic significance for predicting poor RFS in patients with ESCC. More importantly, our data indicates that higher burden correlates with poor response to neoadjuvant chemotherapy, suggesting the possibility that an antibiotic intervention against this bacterium may significantly improve therapeutic response in patients with ESCC.

摘要

目的

越来越多的证据表明,肠道微生物群在癌症发病机制中起着至关重要的作用。虽然()与多种癌症的不良预后相关,但它在预测接受新辅助化疗的食管鳞癌(ESCC)患者对化疗反应的临床意义尚不清楚。

实验设计

通过 qPCR 检测 551 例 ESCC 患者肿瘤组织中的水平,其中包括 101 例接受根治性切除术前新辅助化疗的患者。使用实体瘤反应评价标准(RECIST)、正电子发射断层扫描-CT(PET/CT)中最大标准化摄取值(SUV)变化定义的原发肿瘤代谢反应以及病理肿瘤消退分级(TRG),评估 负担与无复发生存(RFS)之间的关联,以及与化疗反应的关联。

结果

ESCC 患者中 负担高与培训[对数秩检验(log-rank)= 0.02;HR = 1.61;= 0.03]和验证队列(log-rank = 0.003;HR = 1.96;= 0.004)的 RFS 差相关。重要的是,ESCC 患者中具有高水平的()对所有三种评估方法(RECIST = 0.04)、PET/CT 中的 SUV 变化(= 0.0004)和 TRG(= 0.003)均显示出较差的化疗反应。

结论

我们得出结论,肿瘤内高水平的()对预测 ESCC 患者 RFS 不良具有预后意义。更重要的是,我们的数据表明,较高的()负担与新辅助化疗反应不良相关,这表明针对该细菌的抗生素干预可能显著改善 ESCC 患者的治疗反应。

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