Oncology Frontier: Can you give us an overview and outline some of the highlights of the ESMO conference this year?

　　《肿瘤瞭望》：请您回顾和概述一下本次ESMO会议中淋巴瘤领域的亮点。

　　Dr Dreyling: The annual meeting of ESMO has taken off. This year we have more than 20000 people in attendance. ESMO itself， as an association， has over 10000 members. So this is really a growing meeting point to exchange new data. Some of the new data on lymphoma is generating some intense discussion concerning the end of chemotherapy for lymphoma. That was the subject of a symposium and the challenge was made， are we still building on chemotherapy? It probably needs to stay that way for the aggressive lymphomas but for the indolent lymphoma， including CLL， I think we are moving ahead to more defined targeted molecular approaches.

　　Dreyling教授：本次ESMO年会已经落下帷幕，今年我们有超过20 000名的参会者，作为一个学会，ESMO拥有超过10000名的会员，最新的研究数据正是在这一迅速成长的盛会中交流着。淋巴瘤领域的一些最新研究数据引发了关于是否于淋巴瘤治疗中停止化疗的热烈讨论。这是其中一个研讨会的主题，也向我们提出了挑战：“我们的治疗还应该继续依赖化疗吗？”我认为对于侵袭性淋巴瘤，我们或许需要继续依靠化疗，但对于惰性淋巴瘤，包括慢性淋巴细胞白血病，我们应该更为积极地使用靶向药物。

　　Oncology Frontier: For follicular lymphoma， which is generally considered an incurable disease， new agents including PI3 kinase inhibitors and Bruton’s tyrosine kinase inhibitors have shown promising effects in the treatment of refractory relapsed follicular lymphoma. Are there indications that this could well become a curable condition?

　　《肿瘤瞭望》：传统认为滤泡性淋巴瘤是无法治愈的疾病，但是新的药物，如PI3K激酶抑制剂和Bruotn酪氨酸酶抑制剂显示出对难治性复发性滤泡性淋巴瘤的显著疗效，这些研究结果是否意味着滤泡性淋巴瘤未来将转变为一类可治愈的疾病？

　　Dr Dreyling: Yes， its incurable， but I always explain to my patients that it is a chronic disease. Like diabetes， you can’t cure it， but if the disease becomes inactive， you are able to push it back. We have an incredible choice of different agents and the new kids on the block are the B-cell receptor pathway inhibitors. The most prominent ones are ibrutinib and idelalisib. Idelalisib as a PI3K inhibitor is currently registered for double-refractory follicular lymphoma. These are the cases where our standard approaches may be antibodies or alkylating agents. So we now have additional tools to overcome the disease and I think it is the art of the treatment of follicular lymphoma to be able to pick the best of all of the opportunities for the individual patient.

　　Dreyling教授：是的，这个疾病目前无法治愈的，但是我常向患者解释，这是一种慢性疾病。就好比糖尿病，你无法治愈它，但是如果它不再活跃，你就可以战胜它。我们有很多可供选择的药物，以及这些新近的抑制B细胞受体通路的阻断剂。其中效果最明显的的是依鲁替尼和idelalisib。idelalisib是一种PI3K激酶抑制剂，目前已注册用于治疗双抵抗性滤泡性淋巴瘤。对于这些例子，我们既往的标准治疗是使用抗体或烷化剂。因此，我们有了新的武器来对付这种疾病，我认为这是一项治疗滤泡性淋巴瘤的艺术，为患者们选择最好的治疗手段。

　　Oncology Frontier: Rituximab maintenance therapy was recommended because it can prolong the progression-free survival in follicular lymphoma. Are there any clinical trials showing benefit for this treatment for overall survival?

　　《肿瘤瞭望》：利妥昔单抗的维持治疗先被推荐使用，因为它能够延长滤泡性淋巴瘤患者的无进展生存期。有没有临床研究显示该药物有助于延长患者的总生存期呢？

　　Dr Dreyling: There is a meta-analysis of all the randomized trials we have performed so far. That is clearly showing some benefit on overall survival in relapsed disease. In the first-line， the jury is still out. In fact， we have conflicting data. We have the data from the so-called PRIMA trial with 1200 patients indicating a clear-cut benefit on progression-free survival and it is a major benefit that is also clinically relevant. On the other hand， US colleagues performed a study in the “watch and wait” patients who we normally don’t treat， and they again compared ongoing maintenance with rechallenge if the disease is progressing. In this trial， there is no major difference， even for PFS. So what is the message for clinical practice? We still recommend rituximab maintenance after conventional chemotherapy. If you start with rituximab monotherapy for whatever reason， I would discourage it and only recommend a short maintenance following the Ghielmini data.

　　Dreyling教授：有一项荟萃分析综合了目前已进行的所有随机临床试验。它清楚地显示该药对复发性疾病的总生存有益，但对于一线治疗尚无定论。事实上，我们的数据仍具争议。一项名为PRIMA的临床试验纳入了1200例患者，结果明确显示对无进展生存时间有益，并且和临床结局息息相关。然而，另一方面，美国研究人员在我们一般不予治疗的“观望”（watch and wait）患者中开展了一项研究，同样比较了维持治疗和进展时再治疗的情况，结果却没有明显差别，甚至无进展生存时间也无差异。这些研究数据传递给临床实践的信息是什么呢？我们仍然推荐在传统化疗后使用利妥昔单抗维持治疗。我不鼓励在一开始就使用利妥昔单抗单药治疗，不管是因为什么原因，并且根据Ghielmini的研究数据，我只推荐短期维持。

　　Oncology Frontier: Simplified MIPI (mantle cell lymphoma international prognostic index) can predict prognosis of mantle cell lymphoma (MCL). Do you think we can do individual therapy according to simplified MIPI?

　　《肿瘤瞭望》：简化的套细胞淋巴瘤国际预后指数可以预测套细胞淋巴瘤的预后。您认为我们可以根据该简化的MIPI进行个体化治疗吗？

　　Dr Dreyling: It’s a very important question. Mantle cell lymphoma is a confusing disease because it is just in between aggressive and indolent lymphoma. In fact， some of these cases are indolent and others are rather aggressive. It is an art to pick the optimized treatment for the individual patient. MIPI is a huge help， although it is fair to say that it is biased by age. The vast majority of elderly patients are at high risk whereas the low-risk patients are mostly younger patients. What do we apply in our daily clinic? We definitely apply lactate dehydrogenase (LDH) which is extremely important. We do apply Ki-67. Cases above 30% have a much more aggressive clinical course and should be treated like that. Finally， clinical presentation is important as we see some CLL-like features which resemble CLL and are also more indolent.

　　Dreyling教授：这是一个非常重要的问题。套细胞淋巴瘤是一种分类尚模糊的疾病，介于侵袭性和惰性淋巴瘤之间。事实上，某些病例显示出惰性，而另一些病例则更偏向于侵袭性，因此为患者选择最佳治疗方案是门艺术。虽然MIPI存在年龄的偏差，但它仍能提供巨大的帮助。绝大部分的老年患者具有高风险，而大部分年轻患者则相对低风险。我们怎样将它运用到每日的临床实践呢？我们会毫不犹豫地使用最重要的乳酸脱氢酶（LDH），同时还会使用Ki-67，当其数值大于30%时患者常有更具侵袭性的临床表现，应据此治疗。当然临床表现也很重要，我们看见过一些病例呈现慢性淋巴细胞白血病样的特点，类似于慢性淋巴细胞白血病，也更为惰性。

　　Oncology Frontier: Some research has shown the value of PET/CT to judge response assessment. What do you think of PET/CT’s role in evaluating response to treatment?

　　《肿瘤瞭望》：一些研究显示了用PET/CT进行疗效评估的价值。您怎样看待PET/CT在疗效评价中的作用？

　　Dr Dreyling: It really depends on the kind of lymphoma subtype we are talking about. For Hodgkin’s and aggressive lymphoma， we absolutely agree that this is where PET/CT should be performed and that is also reflected in an international consensus， the updated Cheson criteria just published this year in JCO. For indolent lymphoma， we do know that it has some prognostic roles specifically in follicular lymphoma whereas it is not very helpful in mantle cell lymphoma and CLL. So it really depends on the individual lymphoma subtype. I think it is fair to say that outside of clinical studies so far， it does not have therapeutic implications for indolent lymphoma. Now as this field is very complicated， we have all these different lymphoma subtypes， I would like to refer to the update of the ESMO lymphoma guidelines. They are now available in a nicely formatted pocket guide and for those who are more up-to-date， you can download it as an app. This is of incredible help in daily clinic if you really aim for the best possible treatment for your individual patient.

　　Dreyling教授：这取决于我们所讨论的淋巴瘤分型。对于霍奇金淋巴瘤和侵袭性淋巴瘤而言，我们确信PET/CT应该用于疗效评估，而且对这一观点已达成国际共识，今年《临床肿瘤学杂志》上也更新了Cheson疗效评估标准（Cheson criteria）。对于惰性淋巴瘤而言，特别是滤泡性淋巴瘤，PET/CT有一定的预测价值，但其对于套细胞淋巴瘤和慢性淋巴细胞白血病的价值却不明显。因此，PET/CT的评估价值要以具体淋巴瘤分型而定。可以说至今尚无任何临床试验之外的研究，显示出它在惰性淋巴瘤治疗中的应用价值。鉴于这个领域极为复杂，而且我们有这么多不同类别的淋巴瘤分型，我更愿意遵循ESMO更新的诊疗指南。目前已经出版了小巧精美的口袋指南，如果你紧跟时代潮流，还可以下载相应的手机应用程序。如果你真的希望为患者提供最佳的治疗方案，它将提供巨大的帮助。