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[ESMO2014]Lungscape研究项目进展——ESMO大会主席Stahel教授
作者:RolfA.Stahel 编辑:肿瘤瞭望 时间:2014/10/29 19:19:17 关键字:新辅助治疗 非小细胞肺癌 

ESMO大会主席 Rolf A.Stahel

  Oncology Frontier: Neoadjuvant therapy is always widely discussed for treating early stage non-small cell lung cancer (NSCLC). The interim analysis of the SAKK study was reported at ASCO this year and the final result is anticipated at this meeting. Could you talk about the potential results and their clinical effects?

  《肿瘤瞭望》:新辅助治疗在早期非小细胞肺癌的治疗是近年研究的热点,去年ASCO报道了SAKK16/00 试验的中期结果,今年大家都非常期待该试验的最终结果,您能介绍并分析一下该结果对临床实践的意义吗?

  Dr Stahel: The question that was posed in this study was, is the addition of radiotherapy after chemotherapy and before surgery an advantage for patients as compared to what has been the standard chemotherapy followed by surgery alone. To our surprise, what we found is that the addition of short-term but intensive radiotherapy did not provide a benefit, neither in terms of remission, nor in terms of survival. It shows that three modalities used in this sense are not better than two modalities. The data out there points out that concomitant chemoradiotherapy (chemotherapy at the same time as radiotherapy) would be better than sequential chemoradiotherapy. So one could still ask, whether concomitant chemoradiotherapy followed by surgery would be better than chemotherapy alone. However, we do not think this will ever be studied. It would be a very complex study and there would also be a question of patient selection. Concomitant chemoradiotherapy is quite a bit more toxic and then having that followed by surgery would mean that we doubt this would be feasible.

  Stahel教授:该研究提出的主要问题是:在手术前的化疗后再增加放疗相较于手术前仅采用标准化疗是否存在优势。但令人吃惊的是,我们发现增加短期密集的放射治疗,无论对肿瘤的缓解还是生存期而言都未曾获益。研究证明联用三种治疗方法并不优于联合两种治疗方法。研究的结果同时显示,同步放化疗优于序贯放化疗。因此可能有人会问,同步放化疗后手术是否会优于单独化疗呢。然而,我们认为可能不会有研究探索这个问题,因为这将是个非常复杂的研究,同时也涉及到患者自身的选择问题。同步放化疗所带来的毒性反应相当多,伴随着如此多的毒性反应再进行手术治疗,我们将质疑这一治疗方式的可行性。

  Oncology Frontier: The prevalence and clinical outcomes for patients with MET protein expression in NSCLC patients has attracted some interest. It is known as one of the studies of the European Thoracic Oncology Platform Lungscape Project. Could you introduce the purpose and progress of this project?

  《肿瘤瞭望》:NSCLC患者中MET蛋白表达率及其临床预后最近比较引人注目。其中有一个欧洲胸部肿瘤平台的Lungscape研究项目,您能简单介绍一下该研究项目的目的及进展情况吗?

  Dr Stahel: The Lungscape Project was a project designed by Dr Peters and his colleagues in pathology. The idea was to have tumor tissue from patients with completely resected curative-intent non-small cell lung cancer on one hand. On the other hand, there was up to five years follow-up on those patients. So we would have the tumor and the outcome and it could be determined from certain biomarkers in the tumor what the prevalence would be and the prognostic impact on those patients. We had published the project on ALK. That has been completed. We have published the project comparing the clinical parameters with the surgery. Now the project that is here is looking at MET expression, the prevalence of MET expression and the outcome. This attracted a bit of interest because at the time we designed this study, there was a big hope that a monoclonal antibody by Genentech targeting MET would find its way into clinical use. Now this study has been negative so the MET immunochemistry expression alone will stand but it doesn’t have a therapy to match it. However, this will not be presented here, but we will be looking at MET amplification by FISH assay, and we are collecting this data now and it will be very important because there is a potential treatment, crizotinib. We plan to do all the biomarkers now and look at PD-L1 expression in the tumor, for example, and the series of mutations in regard to outcome.

  Stahel教授:Lungscape项目是由Peters博士及其病理学方面的同事共同设计的,对完整切除获得的非小细胞肺癌患者的肿瘤组织进行研究,一方面达到治疗目的,另一方面则将其用于这些患者的5年随访。因此我们就能获得肿瘤及其预后结果,并且确定某种在肿瘤中高表达的生物标志物及其对预后的影响。

  我们已经完成了ALK的研究项目并公布了其结果,包括相应的手术临床参数比较。目前的研究则着重观察MET的表达、表达率及其预后。这项研究之所以能引起大家的注意是因为我们在设计这项研究时,希望能通过基因技术靶向MET的单克隆抗体,找到发挥作用的方法并将其投入到临床应用中去。目前仅有MET免疫组化表达的理论依据,但没有相匹配的治疗方法。不过,这些发现在本次大会上还不会公布。我们将通过FISH实验继续观察MET的扩增情况,收集相关数据——这一点很重要,因为有潜在治疗药物即克唑替尼。我们目前正计划对所有生物标志物进行筛选,例如观察肿瘤中PD-L1的表达情况以及一系列与预后有关的突变。

  Oncology Frontier: Additionally to this project, there are many other programs such as EORTC’s SPECTA program. What will be the major changes to cancer treatment as these projects progress?

  《肿瘤瞭望》:除了这项研究,还有许多其他的研究项目,例如EORTC’s SPECTA项目,随着这项研究项目的进展,将会对肿瘤的治疗带来哪些重大的改变?

  Dr Stahel: It has to do with the theme of this meeting – precision medicine for cancer care. To acquire the molecular characteristics of the tumor and then to allow a specific approved treatment or a specific experimental treatment directed against this alteration. In many large centers in Europe, there has been an increase in the capacity to do these types of investigations. However, they do it individually. If you want to know what the prevalence of a certain alteration is and what is the impact on the natural history, you need a very much larger database than just one hospital. So the SPECTAlung is a European collaboration with fifteen or more centers where patients donate their tissue and that will be examined using the most modern technology at that institution, the data will be collected centrally, the patient will be followed and there will be clinical study protocols (we call it a master protocol) for that specific alteration. It really is a collaborative project and we strongly believe this is the only way to move because one center can have 300 patients a year which is not enough. We need collaboration.

  Stahel教授:这恰恰反映了本届大会的主题---癌症治疗中的精准医学。我们通过获得肿瘤的分子学特征,然后获取一个经过审批的特定的治疗方法或是针对性的实验性治疗方法。欧洲许多大型医疗研究中心都逐渐有能力开展这些类型的调查研究,然而却只有个别机构真正开展了研究。如果你想了解某一项分子改变的发生率及其对疾病发生史的影响时,你需要的是一个庞大的数据库而非仅仅一家医院的研究资料。因此SPECTA LUNG项目是一个拥有15个甚至更多机构参与的多中心欧洲合作项目,来自不同研究中心的患者捐献其肿瘤组织,我们利用最先进的技术对其进行检测,然后将采集的数据集中起来,患者将得到随访,对特定的分子学改变将有专门的临床研究流程(我们称之为主流程)。这确实是一个合作性的项目,我们坚信这是研究运作的唯一方式,因为一个研究中心每年有300例患者是远远不够的,我们需要团结合作。

  Oncology Frontier: This meeting has broken a lot of records like the number of attendees and submitted abstracts. As the Chairman of the meeting, what would you consider to be the most important highlight or breakthrough from the meeting?

  《肿瘤瞭望》:本届ESMO大会打破了多项纪录,例如参会人数及递交摘要数。作为本届大会的主席,您认为本届大会上最重要的亮点或者说突破性进展是什么?

  Dr Stahel: I have a personal attachment to the meeting because I hear from my colleagues and generally that ESMO is the place to meet. This is an achievement in itself. I can remember twelve years ago at our first meeting and we presented good education. Now, this is a global meeting place and that is good. We have a large contingent of attendees from Asia and the Americas. The highlights of the meeting will be immune therapy. It is such a striking advance that none of us would have believed it. With respect to scientific program highlights, there is so much else happening across all disciplines in lung cancer, breast cancer, colorectal cancer, cervical cancer and so on.

  Stahel教授:我对ESMO大会有一点个人的依恋,因为我从我的同事们那里听说,ESMO为大家提供了一个相聚的地方。这本身就是一个成就。我还记得12年前我们第一次参加大会时的场景,那时候ESMO提供给大家很好的教育机会。但现在,ESMO成为了一个全球性的会议,这点非常好。我们目前拥有一个来自亚洲和美洲的庞大的与会队伍。本届会议的亮点是免疫治疗,这是一个如此惊人的进步,令人难以置信。至于科研亮点,在肺癌、乳腺癌、结直肠癌、宫颈癌等所有学科几乎都有众多惊喜亮点。

 

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