Interview with Professor Tim Meyer of Royal Free Hospital of University College London, UK
Editor's note: The metaphase hepatocellular carcinoma has great heterogeneity, and the prognosis of patients with different treatment schemes is quite different. How to choose the appropriate treatment plan for patients is a problem that needs to be solved urgently. For this reason, we invited Professor Tim Meyer from the Royal Free Hospital of University College London, UK, to introduce the current treatment progress of medium-term liver cancer, and to share exclusively how to carry out patient risk stratification and treatment options. Now the content is arranged into a text for the readers.
iHepatology: The heterogeneity of intermediate stage liver cancer is very different. Specifically, what treatment methods are included? What important progress has been made in recent years?
Dr Meyer: The original BCLC intermediate stage disease was formally classified according to liver confined disease in good performance asymptomatic patients with well preserved liver function, but, in fact, that covers a very wide spectrum of patients and extent of disease with different prognoses. Over the years, there have been various attempts to subdivide the BCLC B categorization in order to direct treatments appropriately. None of them have been universally accepted. However, there is recognition that early BCLC B may be considered for resection rather than transarterial embolization, and at the opposite end of the spectrum, those with more advanced stage BCLC B may be better served by systemic therapy than transarterial treatment.
iHepatology: As mentioned above, there are various treatment methods for medium-term liver cancer. How should we choose appropriate treatment strategies for patients?
Dr Meyer: There are a number of different factors we take into account in looking at the prognosis and appropriate treatment for patients with BCLC B or intermediate stage disease. Probably the most important is the extent of the disease - the size of the tumors, the number of tumors, the level of the alpha-fetoprotein (AFP). All of these will be taken into consideration. For patients with a very high AFP, multi-nodular, bilobar disease, systemic therapy is likely to be chosen, whereas those with small volume, unifocal disease with well-preserved liver function may be considered for resection or embolization or, increasingly, radiotherapy, which is now used more frequently in patients with liver cancer.
iHepatology: With the latest progress of systemic therapy, especially the combination therapy has gradually revealed its edge. For the treatment of intermediate stage liver cancer, the application of neoadjuvant / transformation therapy is rising. What do you think the development direction and Prospect of the treatment of liver cancer in the medium term in the future?
Dr Meyer: Systemic therapy has improved very significantly in the past few years. The response rates are higher and survival is longer, so I think it will be increasingly used in patients with more advanced BCLC B stage disease. And I think there will also be a tendency to move towards systemic therapy early, for example, for patients who have not had a response to two cycles of embolization. Whereas before, embolization would have been reapplied, I think now systemic therapy would be implemented. With regard to the role of systemic therapy as neoadjuvant treatment, I think that is under investigation. There have been a number of small single-arm trials that have been published already, which have shown that it is feasible to do, and that good pathological responses can be achieved, but we don’t have any large prospective randomized trials. I think that is a work in progress.
iHepatology: The exploration of prognosis model and risk stratification of intermediate stage liver cancer has become an urgent problem to be solved in clinic in recent years. Would you please talk about its importance in clinic? What important progress have we made so far?
Dr Meyer: There have been a number of risk stratification models developed in intermediate stage disease. For example, in our institution, we developed something called the HAP score, which is a score based on albumin, bilirubin, alpha-fetoprotein and the size of the largest tumor nodule. That has been shown to correlate very well with survival. However, what has not been shown is whether patients do any better with systemic therapy, so I think it is one thing to break the intermediate stage down into different risk groups, but it is another thing to say that poor risk groups should be treated differently. We haven’t got that data yet.
iHepatology: As for the research of new therapy for liver cancer, we are concerned that you reported a clinical trial on ADP-A2AFP SPEAR T-cells at this conference. Please introduce the main contents and clinical significance of this study to us?
Dr Meyer: During this conference, I will be presenting the results of a clinical trial in which genetically modified T-cell receptors have been used to target alpha-fetoprotein peptide expressed in HLA molecules for patients with high AFP expressions. These are predominantly patients with 肝癌, but also included some without 肝癌. This is a very complicated treatment to apply. One has to have the right HLA subtype. One has to have the right level of alpha-fetoprotein expression. The patients then need to have a leukapheresis harvest of their T-cells, and then the T-cells need to be transduced with a genetically-engineered T-cell receptor and the cells expanded. All of that can take 4-6 weeks. The patients then need to undergo leukodepleting chemotherapy a few days before they have the T-cell infusions, and then they are followed-up for response. It is a very complicated protocol. However, amongst the patients who were treated, there was one patient who achieved a partial response, another patient had a complete response, but overall, we do not feel the efficacy met the required threshold to continue with the current construct. Therefore, there are going to be further developments that are currently being tested in preclinical models.
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