编者按：2023年欧洲肿瘤内科学会亚洲年会（ESMO ASIA 2023）于12月1～3日在新加坡举行，会议覆盖各瘤种前沿学术进展，汇聚众多肿瘤学国际专家学者。来自德国图宾根皮肤癌中心的Teresa M.Amaral教授在会上针对“高风险Ⅱ期黑色素瘤的辅助治疗：我们还需要前哨淋巴结活检吗？（Adjuvant treatment in high-risk stage II melanoma:Do we still need SLNB?）”话题发表了精彩演讲，《肿瘤瞭望》有幸在现场采访了Amaral教授，请她进一步分享对该问题的看法，介绍黑色素瘤生物标志物研究进展，并对年轻学者如何开展临床试验给出建议。

 

Teresa M.Amaral教授：实际上，这也是我们刚才在我发言的环节中进行的讨论之一。目前，在没有前哨淋巴结活检（SLNB）信息的情况下，我们无法进行辅助治疗，或者至少在没有SLNB的情况下，无法为ⅡB和ⅡC期患者提供治疗，因为现有研究就是这样进行的。我认为我们从SLNB中获得的信息可能还不够，或者说这不是我们决定Ⅱ期患者治疗方案所需的信息。我们需要的可能是如何从SLNB中获得更多信息，并将精力更多地集中在原发肿瘤的特征上。我们正在进行一些前瞻性研究，看看能否提供更多预后信息。对于风险较高的患者，也许我们应该考虑对其进行辅助治疗。

 

因此，目前我们仍然需要SLNB提供的信息，以便首先根据AJCC第8版对患者进行正确分期。其次，至少在ⅡB和ⅡC期黑色素瘤中，已获批准的治疗方法都是基于具备SLNB信息患者的试验。

 

Oncology Frontier:What do you think about the need for sentinel lymph node biopsy(SLNB)for the adjuvant treatment in patients with high-risk stage II melanoma?

 

Dr.Teresa M.Amaral:Yes.So thank you very much for the question.This was actually one of the discussions that we had just now on the session that I was presenting.And currently actually we cannot do adjuvant treatment without information of the sentinel lymph node biopsy(SLNB)or at least you cannot provide treatment for stageⅡB and stageⅡC patients without the SLNB because this was how the studies were performed.In the end，I think probably the information that we get from the SLNB is not enough or maybe it’s not the information that we need to decide the treatment of the patients in stageⅡ.And probably what we need is the way to move forward with from the SLNB and more concentrate our efforts on the primary tumor characteristics.And there are some essays that are being tested prospectively to see if we can provide more prognostic information.And then for the patients that have a higher risk，maybe we should consider to give them adjuvant treatment.

 

So currently，we still need this information from the SLNB for correctly staging the patients according to the AJCC classification of version 8 at first.And second，the treatments that are approved，at least in stage two b and stage two c are based on trials that included patients that had information on the SLNB.

 

Teresa M.Amaral教授：生物标志物不仅适用于黑色素瘤，也适用于其他实体肿瘤。生物标志物可分为两种不同类型，第一种是预后生物标志物，第二种是预测生物标志物。根据你所在的科室，有些生物标志物可能比其他生物标志物对治疗决策更重要。你刚才提到的生物标志物（CP-GEP模型）实际上具有预后价值，这意味着我们可以据此来定义风险组别，即复发高风险患者和复发低风险患者。这对患者的随访，甚至是治疗类型都有影响。

 

在晚期，主要是Ⅳ期，拥有预后生物标志物很重要，但拥有预测生物标志物也很重要，这些生物标志物可以告诉你哪些患者将从全身治疗中获益。因为原则上，这些患者将进行全身治疗。这两种生物标志物都有很多研究在进行。区分这两种生物标志物非常重要。但归根结底，对于晚期患者，我们所缺乏的主要是预测性生物标志物，因为我们知道这些患者的预后如何，但我们不知道哪些患者会对我们所能提供的全身治疗产生反应。

 

因此，我认为全身治疗的发展需要转向更好地识别和更好地定义将从治疗中获益的患者，因为无论如何我们都会为患者提供全身治疗。而问题在于，我们不知道哪些患者获益最大。因此，我们确实需要进行更专门的研究，尤其是我刚刚提到的晚期领域的研究。

 

Oncology Frontier:Your primary research focus is on biomarkers for advanced or early stage melanoma(e.g.，your article published this year on the use of CP-GEP model to identify patients with stage I/II melanoma at high risk of recurrence)，could you please introduce the progress of biomarkers research in melanoma?

 

Dr.Teresa M.Amaral:The biomarkers not only for melanoma，but in other tumor entities.Biomarkers could be divided in two different types.The first is the prognostic biomarker and the second is the predicted biomarker.And depending on the setting that you are working，there are some that might be a little bit more important for treatment decisions than the others.The biomarkers that you just mentioned(CP-GEP model)，it actually has a prognostic value，which means that we can define risk groups based on the outcome of this essay，patients that have a high risk and patients that have a low risk of recurrence.And this has implications in terms of the follow up of the patients that you are going to do.And even in terms of the type of treatment that you can provide.

 

In the advanced setting，mostly in stage four，it’s important to have prognostic biomarkers，but it’s also important to have predicted biomarkers that can tell you which patients will benefit from systemic treatment.Because in principle，you are going to treat these patients with systemic treatment.There are a lot of investigation that is going on in both settings.And it is important to distinguish these two biomarkers.But in the end，for the advanced setting，what we are lacking，it’s mostly predicted biomarkers because we know what is the prognostic of these patients，but we don’t know which patients will respond to the systemic treatment that is that we can offer.

 

So I think the advances in systemic treatment need to be moved to better identifying and better defining the patients that will benefit from the systemic treatment，because this will be offered anyhow.And the issue is that we don’t know which patients will benefit the most.So there we really need to have a more dedicated investigation，especially as I said，in the advanced setting.

 

Teresa M.Amaral教授：如果你刚刚开始肿瘤临床试验工作，你可能不会参与临床试验的设计工作。但如果你想做一项研究者发起的临床试验（IIT），那么就应该从你想解决的问题入手。通常来说，IIT是试图解决临床相关问题的试验，这些问题在日常临床实践中对患者很重要，但很可能不会被药企采纳，因为这可能不会产生大量的利润。因此，你的临床问题可能会在此情况下解决。

 

对于那些正在启动这类临床试验或正在进行临床研究调查的学者，我的建议是从一个简单的问题开始，并尝试回答这个问题。随着时间的推移，它还会涉及到其他试验设计，但最重要的部分，或者说最能改变你临床试验工作方式的部分，实际上就是从解决一个简单问题的试验或研究开始，一个对日常实践非常重要的实际问题。随着时间的推移和投入的增加，你将能够参与临床试验的设计。但那时你已经掌握了基础知识，也做了功课。因此，你有可能在更高级别的临床试验中取得更大的成功。

 

Oncology Frontier:At the conference，you also participated in the session"How to set up in clinical trials".What advice do you have for young scholars who are just starting clinical trials in oncology in terms of designing clinical trials?

 

Dr.Teresa M.Amaral:If you are just starting，you probably will not be involved in the designing of clinical trials.But if you are trying to do an Investigator-Initiated Trial(IIT)，you should start with the question that you want to address.And normally these IITs are trials that will try to address question that is clinical relevant issues that are important for your patients in your daily practice，but most likely will not be picked up by the pharmaceutical industry because it probably will not generate a lot of profit.So your clinical question will be addressed in this setting.

 

My advice for those scholars who are initiating these clinical trials or who are looking into clinical investigations is exactly to start with a simple question and try to answer this question.And over time it can be involve other trial designs，but the most important part or the part that will change the way you work in clinical trials the most，is actually starting with the trial or a study that addresses a simple question，a practical question that is important for the daily practice.And with time and investment，you will be able to move into designing clinical trials.But you already have the basics and you already did get your homework.So chances are that will be more successful in more advanced clinical trials.

 

专家简介

 

Teresa M.Amaral

德国图宾根皮肤癌中心

Teresa M.Amaral教授的主要研究重点是晚期黑色素瘤全身治疗的预测性生物标志物以及早期黑色素瘤的预后和预测性生物标志物。她从2021年起担任图宾根皮肤癌中心转化研究负责人，致力于推动对皮肤癌的了解和治疗。2022年1月，她被任命为图宾根皮肤癌临床试验中心负责人，负责监督多项Ⅰ-Ⅲ期研究，包括研究者发起的临床试验。自2023年1月起，她担任ESMO领导力发展委员会主席，并兼任ESMO理事会成员。