Ricotta Riccardo, Verrioli Antonella, Ghezzi Silvia, Porcu Luca, Grothey A, Falcone Alfredo, Van Cutsem Eric, Argilés Guillem, Adenis Antoine, Ychou Marc, Barone Carlo, Bouché Olivier, Peeters Marc, Humblet Yves, Mineur Laurent, Sobrero Alberto F, Hubbard Joleen M, Cremolini Chiara, Prenen Hans, Tabernero Josep, Jarraya Hajer, Mazard Thibault, Deguelte-Lardiere Sophie, Papadimitriou Konstantinos, Van den Eynde Marc, Pastorino Alessandro, Redaelli Daniela, Bencardino Katia, Funaioli Chiara, Amatu Alessio, Carlo-Stella Giulia, Torri Valter, Sartore-Bianchi Andrea, Vanzulli Angelo, Siena Salvatore
Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
Department of Oncology, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
ESMO Open. 2017 Feb 13;1(6):e000111. doi: 10.1136/esmoopen-2016-000111. eCollection 2016.
To identify imaging markers predicting clinical outcomes to regorafenib in metastatic colorectal carcinoma (mCRC).
The RadioCORRECT study is a post hoc analysis of a cohort of patients with mCRC treated within the phase III placebo-controlled CORRECT trial of regorafenib. Baseline and week 8 contrast-enhanced CT were used to assess response by RECIST 1.1, changes in the sum of target lesion diameters (ΔSTL), lung metastases cavitation and liver metastases density. Primary and secondary objectives were to develop ex novo univariable and multivariable models to predict overall survival (OS) and progression-free survival (PFS), respectively.
202 patients were enrolled, 134 (66.3%) treated with regorafenib and 68 (33.7%) with placebo. In the univariate analysis, PFS predictors were lung metastases cavitation at baseline (HR 0.50, 95% CI 0.27 to 0.92, p=0.03) and at week 8 (HR 0.58, 95% CI 0.36 to 0.93, p=0.02). Baseline cavitation (HR 0.23, 95% CI 0.08 to 0.66, p=0.007), RECIST 1.1 (HR 0.23, 95% CI 0.14 to 0.4, p <0.0001) and ΔSTL (HR 1.16, 95% CI 1.06 to 1.27, p=0.002) predicted OS. We found an increase of 9% of diameter as the best threshold for discriminating OS (HR 2.64, 95% CI 1.61 to 4.34, p <0.001). In the multivariate analysis, baseline and week 8 cavitation remained significant PFS predictors. Baseline cavitation, RECIST 1.1 and ΔSTL remained predictors of OS in exploratory multivariable models. Assessment of liver metastases density did not predict clinical outcome.
RECIST 1.1 and ΔSTL predict favourable outcome to regorafenib. In contrast to liver metastases density that failed to be a predictor, lung metastases cavitation represents a novel radiological marker of favourable outcome that deserves consideration.
识别可预测转移性结直肠癌（mCRC）患者接受瑞戈非尼治疗临床结局的影像标志物。
RadioCORRECT研究是对在瑞戈非尼III期安慰剂对照CORRECT试验中接受治疗的mCRC患者队列进行的事后分析。利用基线期和第8周的增强CT，根据实体瘤疗效评价标准（RECIST）1.1评估反应、靶病灶直径总和的变化（ΔSTL）、肺转移灶空洞形成及肝转移灶密度。主要和次要目标分别是建立全新的单变量和多变量模型，以预测总生存期（OS）和无进展生存期（PFS）。
共纳入202例患者，134例（66.3%）接受瑞戈非尼治疗，68例（33.7%）接受安慰剂治疗。单因素分析中，PFS的预测因素为基线期（HR 0.50，95%CI 0.27至0.92，p = 0.03）和第8周（HR 0.58，95%CI 0.36至0.93，p = 0.02）的肺转移灶空洞形成。基线期空洞形成（HR 0.23，95%CI 0.08至0.66，p = 0.007）、RECIST 1.1（HR 0.23，95%CI 0.14至0.4，p <0.0001）和ΔSTL（HR 1.16，95%CI 1.06至1.27，p = 0.002）可预测OS。我们发现直径增加9%是区分OS的最佳阈值（HR 2.64，95%CI 1.61至4.34，p <0.001）。多因素分析中，基线期和第8周的空洞形成仍是PFS的显著预测因素。在探索性多变量模型中，基线期空洞形成、RECIST 1.1和ΔSTL仍是OS的预测因素。肝转移灶密度评估不能预测临床结局。
RECIST 1.1和ΔSTL可预测瑞戈非尼治疗的良好结局。与未能成为预测因素的肝转移灶密度不同，肺转移灶空洞形成是一个值得考虑的、提示良好结局的新影像学标志物。
