European Multidisciplinary Conference in Thoracic Oncology (EMCTO) 2013

Surgery in mesothelioma

Dr Paul Baas - Netherlands Cancer Institute, Amsterdam

Paul, you’re chairing the section on mesothelioma and this is a very difficult disease but there are a number of modalities and progress has been made. Let’s start with surgery, what’s happening there?

Well we had a very nice session about mesothelioma and we think that there is some progress being made, especially in the field of the surgery. In the old days we all looked at taking out as much as possible, referring your patient to the surgical clinic who was specialised in that, but that was, of course, going along with quite some toxicity. But nowadays we try to select the patients better for a very large intervention – removing the lung, the pleura, diaphragm etc. – and more to the limited resections. So there is now a new name, it’s called MCR, macroscopic complete resection, and it’s the idea that if we are able to ask our surgeon to perform a macroscopic complete resection, 99% of the tumour has been taken out and then, using other modalities, you can try to kill the rest.

And what is the scope, then, for chemotherapy?

The scope for chemotherapy, because it’s not only chemotherapy, is that we have a standard treatment with platinum and an antifolate and when you use that you can maybe give it before the surgical treatment or after the surgical treatment. And if you are still in doubt you can also add radiotherapy.

From the session from your talks here in Lugano, what is current opinion about the mix between surgery and chemotherapy and, indeed, radiotherapy?

At least it’s clear that surgery alone is not an option, you have to combine it with another modality. At this moment what we briefly touched on is that we would like to go for pleurectomy decortication combined with chemotherapy. So you’re trying to open the chest and leave as much of the lung in place as possible, reducing the side effects that the patients can better undergo chemotherapy treatment.

Now does that go under the label of multi-modality treatment or would you extend that even further and add more things?

Yes, I think that’s the way we think it should be – at least two modalities, that’s the minimum. We also like to add radiotherapy but the study so far in unselected patient groups, or limited selected patients groups, they do not yet give the responses that we would like to see. So finding out who is a candidate for a sort of resection combined with chemotherapy and maybe also radiotherapy, that would really be the tri-modality but we still have a few steps to go.

You’re a cancer doctor, you have a patient with mesothelioma, what are the decisions that you now need to take?

First of all you must decide whether he or she is a candidate for multi-modality treatment. So normally the patient must be in good condition and have adequate pulmonary and cardiac function. When they do have, you consider together in your team, together with surgeons, radiation oncologists, pathologists etc., is this a person who is going for the multi-modality approach. You must be sure that there’s a good chance that he or she will survive the whole treatment; so not only operating and then say, “Ah, bad luck, it was too advanced,” you must try to save the patient unnecessary treatments.

And if the patient is not a candidate for multi-modality treatment, what then?

What then? Well we have, of course, a standard but the standard means that we only have a median survival gain of about three months so we would like to do more.

Standard consisting of?

Of cisplatin with an antifolate. So this is the standard, it’s much better than best supportive care only because that makes really a difference of about six months, but we still have after two years of follow-up that 80% of our patients have recurrence of the tumour or even died. So we are now exploring new pathways. So the biology, and this was one of the talks presented by Felley-Bosco, it was very interesting to hear how the biology, molecular biology, is now developing. We are now able to identify some pathways which seem to be very important and also give the possibility to interact and to try to stop certain processes in the cell.

Potentially how could this help patients with poorer performance status?

It might be so that, by giving a treatment, maybe with an oral drug on a regular basis like a daily treatment, it might even improve the quality of life, the performance of the patient and maybe make them suitable for additional treatments. Now I don’t think that if a patient comes in with a very advanced case of mesothelioma that giving a tablet or chemotherapy-like treatment will render him or her ready for surgical resection, that I think will not be, but I think we might be able to make it a more chronic disease with the maintenance of quality of life.

Of course, here at the oncology meeting in Lugano we’ve been hearing a lot about biomarkers, molecules to help direct therapy, druggable targets, do you see any coming up in mesothelioma?

Well we have been examining also quite a lot of biomarkers and it’s still tricky. For every solid tumour it’s still tricky and to date there are only a few really registered and accepted by EMA and FDA. So this is a field of interest. We are looking that especially in the laboratory also to see if, for instance, the vasculature which is very important in mesothelioma, if expression of certain of the receptors, we can measure them but we do not yet know if they will reflect the response to treatment. So that is what is on-going for instance.

So full scale personalisation of therapy based on molecular analysis is not appropriate at the moment for mesothelioma?

Not yet but there are many centres, including my own centre in Amsterdam, where we take samples from the patients’ pleural fluid and we do short-time cultures and we try to expose them to different chemotherapies because we know  that the standard chemotherapy is not always doing its work. So for second line we now try to identify patients who might be very sensitive for a completely different combination of drugs. And in addition we have, for instance, a collaboration with other institutes also like the Sanger Institute in Cambridge, where we are doing sequencing of older material that we have.

Can the molecular information give you insights into which chemotherapy drugs might be better?

I think it will give you a lot of insight in maybe what you should not do. Maybe it’s a more negative approach but it’s just as important because if you have, for instance, an enzyme that will break down your chemotherapy, your antifolate, very quickly then it’s a waste of time to prescribe it to your patient. So what we also want to know are there certain driver mutations that we can target and, on the other hand, is there something that we can find out of our primary cultures or other analysis techniques that we can prevent giving unnecessary treatment?

It’s very satisfying to know that there’s such a range of sophisticated new knowledge emerging about this difficult to treat cancer but what message would you leave doctors with finally?

What I think is very important is that what we also do is to set up together with Zurich, with my colleague Isabelle Opitz, mesoscape from the ETOP. What we want to do in Europe is to collect as much as possible information on the patients that are suffering from mesothelioma. Is their pathology available, what kind of pathology? Can we do, then, on the spot in the local hospital additional tests and make it possible to come with better studies and also to have a better idea of how to proceed for the next future?

Well, Paul, thanks ever so much for coming in. It’s been great to hear this news.

I enjoyed it, thank you.