Episode 3: Large panels in clinical routine? A reality check from two oncologists - Dr. Westphalen & Dr. Winder

Mélanie Moxhet

Dec. 1, 2020

PODCAST_EN

Dr. Westphalen, Comprehensive Cancer Centre (Munich) & Dr. Winder, LFK Feldkirch (Austria) and Swiss Tumour Molecular Institute (Zurich)

Shift in perspective. In this episode of your ONCOmmunity podcast, we will discuss the clinical utility of large panels from the point of view of two oncologists: Dr. Benedikt Westphalen, medical director of precision oncology, medical clinic 3 LMU at the Comprehensive Cancer Centre in Munich, and Dr. Thomas Winder, head of gastroenterology, haematology, oncology and infectiology at the Feldkirch Regional Hospital in Austria and director of the Swiss Tumour Molecular Institute in Zurich.

Comprehensive molecular testing is becoming more and more affordable and available. There are challenges remaining, but both oncologists will come back to cases where extensive genomic tests translated into promising treatment approaches for cancer patients and will consider future changes in the clinical decision-making process.

With the increase of molecular tests, there has also been a desire to be able to discuss these test results in interdisciplinary expert panels. We need cross-sectoral networks for precision oncology so that physicians in private practice and at smaller hospitals can benefit from a wide range of modern, molecular oncology”, they say about the importance of bundling knowledge and harmonizing clinical findings.

Moderator

00:06 Welcome to “ONCOmmunity – the molecular oncology podcast” by OncoDNA. Previously, we discussed the clinical utility of large panels from the perspective of pathology laboratories. Today we would like to shift our perspective to that of the oncologist.

00:23 Our experts today are Dr. Benedikt Westphalen, Oncologist, Medical Director of Precision Oncology, Medical Clinic 3 LMU at the Comprehensive Cancer Centre in Munich, and Dr. Thomas Winder, Head of Gastroenterology, Haematology, Oncology and Infectiology at the Feldkirch Regional Hospital in Austria and Director of the Swiss Tumour Molecular Institute in Zurich, Switzerland. Hello everyone. 

Dr. Benedikt Westphalen

0:53 Yes. Hello and good morning from Munich.

Dr. Thomas Winder

00:56 Good morning from Austria. Glad to be here.

Moderator 

1:00 Gentlemen, comprehensive molecular genomic testing is becoming more and more affordable and available. Do you see this leading to changes in the clinical decision-making process?

Dr. Thomas Winder

01:14 Yes, I think that is a very important point. This testing enables us to detect rare changes and treat patients in a targeted manner. If we look at the BRAF mutation, for example, testing is performed in around two thirds of patients with metastatic colorectal carcinoma. That is low because we have a specific treatable consequence behind it.

01:40 When we talk about rare changes, it is important to pool our knowledge and consolidate it in registries. This allows us to jointly evaluate rare changes and to see the resulting treatment consequences.

01:54 As we do more molecular tests, it will be important in the future to harmonise the reports and discuss the results in molecular tumour boards to consequently give good recommendations to the treating physicians and oncologists.

Dr. Benedikt Westphalen

02:18 Yes, I would absolutely agree based on our experience here in Munich. With the increase in molecular tests, we see a rising desire to discuss such test results in interdisciplinary expert panels. And that’s why we and our colleagues from all medical specialities decided to set up a molecular tumour board and to concentrate specifically on the results of advanced molecular diagnostics and their possible diagnostic and therapeutic consequences. 

Moderator

02:48 Is this the standard procedure today in every hospital, in every area of oncology?

Dr. Benedikt Westphalen

2:58 The increasingly widespread use of advanced molecular diagnostics in cancer therapy is a relatively new development, so it is only in the last few years that we have to deal with the growing quantity of medical reports.

3:10 Accordingly, the larger, specialised cancer centres started to set up these expert committees, namely molecular tumour boards or precision oncology programmes, already a few years ago. It is very resource-intensive, and it requires a lot of dedication and a broader range of experts compared, for example, to a classic gastrointestinal tumour board. It is therefore often reserved to core centres to have the resources to support these molecular tumour boards.

3:41 We got together with the 14 German core centres of the German Cancer Aid organisation and founded a working group that pursues precisely this goal, which Thomas already mentioned, of achieving harmonisation. We were recently able to publish a consensus manuscript in the European Journal of Cancer, with the aim of creating a general framework for how to structure precision oncology and hopefully make it available to all patients in the future.

Dr. Thomas Winder

04:16 I’d like to add that this is possibly a very, very important initiative that we need in relation to molecular oncology. For precision oncology, the core centres must team up to provide a joint offer to the private practices and smaller hospitals, so that oncologists working there can participate, contribute their experience, but also benefit from the network.

Moderator

04:43 You are talking about your colleagues working in more rural locations. What are the challenges to sharing knowledge to these colleagues and what opportunities are there in molecular genomics?

Dr. Thomas Winder

04:57 I believe that in recent years a lot has changed within molecular oncology for our colleagues at local level and in private practices. If we just look at lung cancer, there are now numerous molecular changes that we need to test for, that we need to think about, because they have a specific, treatable consequence. And this is why it is important to provide support and platforms, and I think this is where the molecular tumour board comes in as an essential and important platform to support these colleagues.

Dr. Benedikt Westphalen

05:32 Yes, I also think that it is important to work together towards this increasingly complex and interdisciplinary medicine. That's why our molecular tumour board in Munich is not a closed shop, and we are able to include colleagues from other hospitals or oncological practices, both in person and digitally via virtual molecular tumour boards. It’s often the case that advanced molecular diagnostics are only used at a later stage along a patient’s pathway, and these patients are often not treated at core centres.

06:04 There’s nothing more sad than a potentially treatable molecular alteration being disregarded because it gets overlooked in the heavy everyday workload of a large oncological practice.

6:15 Here we see it as our task not to detach the patient from their environment, but to identify and support new options.

Moderator

06:26 What added value do you see for the treating oncologist and for the patient in choosing a comprehensive genomics test?

Dr. Thomas Winder

6:37 I think that the relevant alterations we look at are rarer and rarer events. It is in only 1% to 5% of the cases where molecular changes occur. And we also make a clonal selection through our therapy. I always use the following example: you all know about antibiotics; at some point you become resistant to an antibiotic and you have to change the therapy, the treatment.

07:04 It is the same in oncology. Our treatment causes resistances. We can identify them and then modify our therapy. And I think that is very, very important.

7:16 Another substantial point is: in situations where we run out of approved therapy options for our patients, we need to carry out a broad molecular characterisation. On the one hand, to offer a selected patient a good off-label use, and on the other hand - and this is very, very important– to include these patients in clinical trials.

Dr. Benedikt Westphalen

07:47 I absolutely agree. And we are facing more and more molecular changes that can no longer be covered with small panels. I would like to mention tumour mutational burden, for which a certain genomic territory has to be analysed in order to be able to detect this biomarker, even if this biomarker is still discussed controversially.

08:08 A second important example in my opinion are complex fusion events such as in NTRK and FGFR, where we need a panel that can capture these events independently of the fusion partner. We can no longer do that with a small panel or even a single gene test. This must be done with a quality-assured, large panel in order to diagnose these highly relevant alterations for our patients and to address them appropriately.

Moderator

08:41 Are such diagnostic tests actually affordable?

Dr. Thomas Winder

8:47 I think it is important to not only see the costs of the tests, but also the potential savings by treating our patients correctly, because drug costs in oncology are increasing enormously. And with these molecular analyses we can specifically select patients for a therapy. We can exclude patients from a therapy where we know in advance that the therapy may not work, and in cases where we know the therapy works, we can selectively apply it at an early stage. And I think this is what should be clearly emphasised here.  

Dr. Benedikt Westphalen

09:26 In this context you should also bear in mind that the costs for advanced molecular diagnostics, even if it costs several thousand euros, are only a fraction of the overall costs for treatment of a patient with an advanced tumour disease.

09:42 The second point to consider: In the course of a cancer disease, biomarker tests are carried out repeatedly, and each individual genetic test also comes with a certain cost. For example, there are reliable socio-economic cost analyses of non-small cell lung cancer that show that it is no longer cheaper to test individual genes, and that a panel provides the relevant information at a more affordable price.

10:09 Furthermore – and this is a point that should also be considered – testing via NGS panels uses less tissue, consequently, you get all the information needed for patient management from a “one-stop shop”.

Moderator

10:30 One of your medical colleagues once said: If I cannot provide therapy, I don’t need diagnostics. So now my question to you is: How can the results of extensive genomic tests actually be translated into promising treatment approaches for patients?

Dr. Thomas Winder

10:50 I think that is an important question. We are very advanced with the technology and can test a lot, but we see that it often fails due to access to the correct medication, especially in therapy-resistant situations.

In Austria this is still pretty good. Here, we can try a therapy attempt for two months, and in the event of a response, the health insurer will assume the costs. It is more difficult in Switzerland because the situation is reversed. There are extensive possibilities for testing, but access to medication is difficult, and the health insurer issues a rating for the corresponding cost reimbursement, and this depends on whether, in a treatment-resistant situation, the patient can be treated off-label or not.

Dr. Benedikt Westphalen

11:46 In addition to the questions around access to therapy, which Thomas has just described very well, I also think that we should consider medicine as a self-learning system: Are there diseases where advanced molecular diagnostics should be used earlier? I am thinking of cholangiocarcinomas, for example.

Personally, I would like all patients to be tested early and comprehensively, but unfortunately that is not yet possible.

12:14 It will be the task of medical professionals who are active in this field of precision oncology, as I would like to call it, to support colleagues in determining where and when testing makes sense so that we do not get into this frustrating situation of testing, testing, testing, almost just for the testing’s sake alone, but it never results in therapeutic consequences.

Moderator

12:41 Thank you both for your insights and explanations.

In the next episode of “ONCOmmunity – the molecular oncology podcast” by OncoDNA, we will discuss the ever-changing landscape of biomarker interpretation and big data in molecular diagnostics. Thank you for listening.