直肠癌多模式治疗期间循环miRNA作为生物标志物的表达水平——TiMiSNAR-mirna：TiMiSNAR试验（NCT03962088）的一项子研究
Expression levels of circulating miRNAs as biomarkers during multimodal treatment of rectal cancer - TiMiSNAR-mirna: a substudy of the TiMiSNAR Trial (NCT03962088).
作者信息
Monsellato Igor, Garibaldi Elisabetta, Cassinotti Elisa, Baldari Ludovica, Boni Luigi, Elmore Ugo, Delpini Roberto, Rosati Riccardo, Perinotti Roberto, Alongi Filippo, Bertocchi Elisa, Gori Stefania, Ruffo Giacomo, Pernazza Graziano, Pulighe Fabio, De Nisco Carlo, Morpurgo Emilio, Contardo Tania, Mammano Enzo, Perna Federico, Menegatti Benedetta, Coratti Andrea, Buccianti Piero, Balestri Riccardo, Ceccarelli Cristina, Cavaliere Davide, Solaini Leonardo, Ercolani Giorgio, Traverso Elena, Fusco Vittorio, Torri Valter, Orecchia Sara
机构信息
Department of Surgery, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Via Venezia 16, 15121, Alessandria, Italy.
Department of Radiation Oncology, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy.
出版信息
Trials. 2020 Jul 25;21(1):678. doi: 10.1186/s13063-020-04568-9.
BACKGROUND
Neoadjuvant chemoradiotherapy followed by surgery is the mainstay treatment for locally advanced rectal cancer, leading to significant decrease in tumor size (downsizing) and a shift towards earlier disease stage (downstaging). Extensive histopathological work-up of the tumor specimen after surgery including tumor regression grading and lymph node status helped to visualize individual tumor sensitivity to chemoradiotherapy, retrospectively. As the response to neoadjuvant chemoradiotherapy is heterogeneous, however, valid biomarkers are needed to monitor tumor response. A relevant number of studies aimed to identify molecular markers retrieved from tumor tissue while the relevance of blood-based biomarkers is less stringent assessed. MicroRNAs are currently under investigation to serve as blood-based biomarkers. To date, no screening approach to identify relevant miRNAs as biomarkers in blood of patients with rectal cancer was undertaken. The aim of the study is to investigate the role of circulating miRNAs as biomarkers in those patients included in the TiMiSNAR Trial (NCT03465982). This is a biomolecular substudy of TiMiSNAR Trial (NCT03962088).
METHODS
All included patients in the TiMiSNAR Trial are supposed to undergo blood collection at the time of diagnosis, after neoadjuvant treatment, after 1 month from surgery, and after adjuvant chemotherapy whenever indicated.
DISCUSSION
TiMiSNAR-MIRNA will evaluate the association of variation between preneoadjuvant and postneoadjuvant expression levels of miRNA with pathological complete response. Moreover, the study will evaluate the role of liquid biopsies in the monitoring of treatment, correlate changes in expression levels of miRNA following complete surgical resection with disease-free survival, and evaluate the relation between changes in miRNA during surveillance and tumor relapse.
TRIAL REGISTRATION
Clinicaltrials.gov NCT03962088 . Registered on 23 May 2019.
背景
新辅助放化疗后手术是局部晚期直肠癌的主要治疗方法，可使肿瘤大小显著减小（降期）并使疾病分期提前（降期）。术后对肿瘤标本进行广泛的组织病理学检查，包括肿瘤退缩分级和淋巴结状态，有助于回顾性地了解个体肿瘤对放化疗的敏感性。然而，由于对新辅助放化疗的反应存在异质性，因此需要有效的生物标志物来监测肿瘤反应。许多研究旨在鉴定从肿瘤组织中获取的分子标志物，而对基于血液的生物标志物的相关性评估则不够严格。目前正在研究将微小RNA作为基于血液的生物标志物。迄今为止，尚未开展在直肠癌患者血液中鉴定相关微小RNA作为生物标志物的筛查方法。本研究的目的是调查循环微小RNA在TiMiSNAR试验（NCT03465982）纳入的患者中作为生物标志物的作用。这是TiMiSNAR试验（NCT03962088）的一项生物分子亚研究。
方法
TiMiSNAR试验中所有纳入的患者应在诊断时、新辅助治疗后、术后1个月以及必要时辅助化疗后进行血液采集。
讨论
TiMiSNAR - MIRNA将评估新辅助治疗前后微小RNA表达水平的变化与病理完全缓解之间的关联。此外，该研究将评估液体活检在治疗监测中的作用，将完全手术切除后微小RNA表达水平的变化与无病生存期相关联，并评估监测期间微小RNA变化与肿瘤复发之间的关系。
试验注册
Clinicaltrials.gov NCT03962088。于2019年5月23日注册。
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