Le Cesne Axel, Van Glabbeke Martine, Verweij Jaap, Casali Paolo G, Findlay Michael, Reichardt Peter, Issels Rolf, Judson Ian, Schoffski Patrick, Leyvraz Serge, Bui Binh, Hogendoorn Pancras C W, Sciot Raf, Blay Jean-Yves
Department of Medicine, Institut Gustave Roussy, Villejuif, France.
J Clin Oncol. 2009 Aug 20;27(24):3969-74. doi: 10.1200/JCO.2008.21.3330. Epub 2009 Jul 20.
From February 2001 to February 2002, 946 patients with advanced GI stromal tumors (GISTs) treated with imatinib were included in a controlled EORTC/ISG/AGITG (European Organisation for Research and Treatment of Cancer/Italian Sarcoma Group/Australasian Gastro-Intestinal Trials Group) trial. This analysis investigates whether the response classification assessed by RECIST (Response Evaluation Criteria in Solid Tumors), predicts for time to progression (TTP) and overall survival (OS).
Per protocol, the first three disease assessments were done at 2, 4, and 6 months. For the purpose of the analysis (landmark method), disease response was subclassified in six categories: partial response (PR; > 30% size reduction), minor response (MR; 10% to 30% reduction), no change (NC) as either NC- (0% to 10% reduction) or NC+ (0% to 20% size increase), progressive disease (PD; > 20% increase/new lesions), and subjective PD (clinical progression).
A total of 906 patients had measurable disease at entry. At all measurement time points, complete response (CR), PR, and MR resulted in similar TTP and OS; this was also true for NC- and NC+, and for PD and subjective PD. Patients were subsequently classified as responders (CR/PR/MR), NC (NC+/NC-), or PD. This three-class response categorization was found to be highly predictive of further progression or survival for the first two measurement points. After 6 months of imatinib, responders (CR/PR/MR) had the same survival prognosis as patients classified as NC.
RECIST perfectly enables early discrimination between patients who benefited long term from imatinib and those who did not. After 6 months of imatinib, if the patient is not experiencing PD, the pattern of radiologic response by tumor size criteria has no prognostic value for further outcome. Imatinib needs to be continued as long as there is no progression according to RECIST.
2001年2月至2002年2月，946例接受伊马替尼治疗的晚期胃肠道间质瘤（GIST）患者被纳入一项由欧洲癌症研究与治疗组织（EORTC）/意大利肉瘤组（ISG）/澳大利亚胃肠道试验组（AGITG）开展的对照试验。本分析旨在研究实体瘤疗效评价标准（RECIST）评估的反应分类是否能预测疾病进展时间（TTP）和总生存期（OS）。
按照方案，前三次疾病评估在第2、4和6个月进行。为了进行分析（标志性方法），疾病反应被细分为六类：部分缓解（PR；肿瘤大小缩小>30%）、轻微缓解（MR；缩小10%至30%）、无变化（NC），分为NC-（缩小0%至10%）或NC+（增大0%至20%）、疾病进展（PD；增大>20%/出现新病灶）以及主观PD（临床进展）。
共有906例患者在入组时具有可测量病灶。在所有测量时间点，完全缓解（CR）、PR和MR的TTP和OS相似；NC-和NC+、PD和主观PD的情况也是如此。随后患者被分类为缓解者（CR/PR/MR）、NC（NC+/NC-）或PD。发现这种三类反应分类对于前两个测量点的进一步进展或生存具有高度预测性。伊马替尼治疗6个月后，缓解者（CR/PR/MR）与被分类为NC的患者具有相同的生存预后。
RECIST能够很好地早期区分长期从伊马替尼治疗中获益的患者和未获益的患者。伊马替尼治疗6个月后，如果患者未出现PD，根据肿瘤大小标准的放射学反应模式对进一步预后没有预后价值。只要根据RECIST没有进展，就需要继续使用伊马替尼。
