在淋巴瘤的诊疗领域，传统方法如组织活检虽具重要价值，但其侵入性、不方便反复取样及不能全面反映肿瘤异质性的局限性日益凸显。液体活检作为一种新兴的非侵入性检测技术，正在淋巴瘤的诊疗中展现出巨大的潜力。在近日召开的“中国临床肿瘤学会（CSCO）第八届血液肿瘤学术大会”上，瑞士贝林佐纳肿瘤研究所Davide Rossi教授分享了“液体活检（ctDNA）在恶性淋巴瘤诊断和治疗中的作用”的精彩内容。《肿瘤瞭望-血液时讯》现场特邀Davide Rossi教授接受采访，就该话题做进一步深入分享。

《肿瘤瞭望-血液时讯》液体活检，特别是循环肿瘤DNA（ctDNA），在肿瘤学领域显示出了巨大的潜力。请您谈谈ctDNA分析的最新进展以及它们是如何影响恶性淋巴瘤的诊断和治疗?

Davide Rossi教授：首先，关于液体活检的数据非常令人兴奋，但目前尚不足以直接应用于临床。液体活检在淋巴瘤领域仍处于研究中，目的是生成更多数据，以确定它在患者管理中的实用性。基于目前掌握的信息，我们可以说它可能有效地进行基因识别。比如可以使用液体活检进行基因突变的识别。它可能有助于更好地理解治疗后的PET扫描结果。然而，如何使用这些信息尚不清楚。到目前为止，指南中还没有关于在实践中使用循环肿瘤DNA（ctDNA）的建议。

Oncology Frontier-Hematology Frontier：Liquid biopsy, particularly circulating tumor DNA (ctDNA), has shown promise in the field of oncology. Could you discuss the latest advancements in ctDNA analysis and how they have impacted the diagnosis and treatment of malignant lymphomas?

Professor Davide Rossi：Thank you very much for your question. I have to say first that the data that we have on liquid biopsy are very exciting but not yet ready or sufficient to be transferred readily into the clinic nowadays. So this still remains, in lymphomas, a research assay. But the aim, of course, is to generate more data to really identify where it can be useful for patient management. Based on the information that we have today, We can say that it may effectively profile gene mutations. So if you want to identify a gene mutation, you can do it on liquid biopsy. It may help in interpreting better the results of PET scans after therapy. These are considerations that we know. How to use this information is less clear and so far, there are no recommendations in guidelines to use ctDNA in practice.

《肿瘤瞭望-血液时讯》在您的经验中，液体活检在临床实践中的应用如何改变了恶性淋巴瘤患者的管理？仍然需要解决的一些挑战和限制是什么？

Davide Rossi教授：我认为，在将ctDNA技术应用于淋巴瘤的临床实践之前，我们需要将用于评估该问题的技术标准化和统一化，因为不同的中心采用了许多不同的方法。我们不知道如果在不同中心共享同一样本，结果是否相同。这是一个我们必须要做的努力，以说服社区和临床医生。临床医生可能不太了解技术细节，但我们要让他们相信，我们的检测结果足够好，可以用于患者。因此，标准化和统一化是在社区推广之前的必要步骤。因为ctDNA是一种难以处理的DNA类型，需要仔细设计和测量。

Oncology Frontier-Hematology Frontier: In your experience, how has the integration of liquid biopsy into clinical practice changed the management of patients with malignant lymphomas? What are some of the challenges and limitations that still need to be addressed?

Professor Davide Rossi：I think that before implementing ctDNA technologies for lymphomas in clinical practice, we need to standardize and harmonize the technology we use to assess this matter, because many different centers use many different approaches. And so, I don't know actually whether the results would be the same if we share the same sample across the centers. This is an effort that we have to undertake to convince the community. The clinicians, who may not be so deep into the technicalities, that the results of our assays are good enough to be used in patients. So harmonization and standardization is a missing step before launching this in the community. Because ctDNA, as you were mentioning, is a difficult type of DNA and requires careful assays, a careful design of assays for being detected and measured.

《肿瘤瞭望-血液时讯》展望未来，您认为液体活检在恶性淋巴瘤领域应用的下一个重要步骤是什么？您认为有哪些新兴技术和方法将显著提高我们诊断和治疗这些癌症的能力？

Davide Rossi 教授：对于技术的未来方向，我认为我们正在使用的方法超高深度肿瘤个性化检测（CAPP-Seq），和美国其他中心以及欧洲和中国也在使用的方法，在社区中更为一致。这可能第一步。这不是一个商业检测，而是一个定制的学术诊断方法。我们知道自己在做什么，以及它的表现如何。我们知道它的局限性和优缺点。我认为重要的是要真正了解血液学家社区如何看待ctDNA对患者的价值。正如我之前提到的，在去年卢加诺会议上，社区的感觉是我们还没有准备好在实践或指南中使用这些技术。但讨论仍在进行中，我们期待在明年的卢加诺淋巴瘤会议上看到更多数据，届时看看人们的看法是否会改变。他们可能会被至少建议在每个临床试验中实施这一点，以获取更多信息。

Oncology Frontier-Hematology Frontier：Looking ahead, what do you envision as the next big steps in the application of liquid biopsy in the field of malignant lymphoma? Are there any emerging technologies or approaches that you believe will significantly enhance our ability to diagnose and treat these cancers?

Professor Davide Rossi：For the dialogue diagram for the technology. I think that CAPP-Seq，the method that we use and that other centers in the us in Europe and also in China are using is the one that is more consistent across the community. So this might be a first way to proceed. It is not a commercial essay，is a custom academic diagnostic approach. This is as the value that we know what we are doing and we know how it performs. We know the limitation and the pros and cons. That's the first aspect. I think that is important to really have the feedback from the community of hematologist on where they see the value for patients in ctDNA as I mentioned before，last year during the Lugano conference，the feeling of the community was that we are not ready for these in the practice or in the guidelines. But there is an ongoing discussion and we will see whether with more data next year in the Lugano meeting on lymphomas, the people has changed their mind. They may be redirected to at least suggest to implement this in every clinical trial to get more Information.

专家简介

Davide Rossi 教授

瑞士贝林佐纳肿瘤学研究所（IOR）实验血液学实验室主任

瑞士南部肿瘤研究所（IOSI）血液学部副主任