• Dr Virginia Wolstenholme

Health

Q&A: Virginia Wolstenholme

Dr Virginia Wolstenholme, consultant oncologist, on advances in treatments for malignant melanoma

Interview: Viel Richardson
Image: Orlando Gili

What is melanoma?
It is a form of skin cancer. It is often detected by finding melanoma cells in a mole. It is related to UV damage to the skin.

When do patients come to you?
Usually when the malignant melanoma cells have spread to other parts of the body. By then, the patient’s condition is usually quite advanced. This normally means that they will need treatment such as chemotherapy, immunotherapy or radiotherapy. Areas of the body where we most commonly see the cells are the lungs, liver and brain. At this stage it’s very serious, but we do have treatments that we can use to help control the disease.

Have treatments changed much during your time in the field?
There have been some really dramatic changes over the past five years or so, in terms of what we understand about melanoma and how we treat it. For the previous 30 years there had been no real development and we were using chemotherapy drugs which had very poor response and success rates. But we have recently been able to find out more about the cancer cells and mutations in their genetics.

Such as what?
There is, for example, something called the BRAF genetic mutation. We have found that 50 to 60 per cent of patients who develop melanomas have this mutation in their cancer cells. Having this information enables us to treat patients in a different way. It has allowed us to give patients highly targeted new drugs which attack the cancer while minimising side effects. This is hugely important, because there are several different treatment options for cancer, and finding the right one for the patient quickly is key.

Several clinical trials have shown treatments based on BRAF information give excellent results in comparison to previous treatments. The patients’ responses were far superior, as were the overall survival rates. It has completely altered the way in which we now approach treating melanomas.

How do the modern cancer drugs work?
There are a variety of drugs, one of which involves a type of cell in the body called a T-lymphocyte (T-cell) which helps fight infection and control diseases such as cancer. One of the drugs that we use works by enabling the T-cell to fight the disease for longer than it normally would.

How do the side effects compare to the old treatments?
Unfortunately it does not eliminate them. Because these drugs affect the immune system, there are different side effects that can be related to them—things like inflammation in different parts of the body, such as the bowels or liver, and these will have their associated symptoms. We tell patients the things they need to look out for and to contact us straight away if they see any of them. But the benefits of the treatments far outweigh these issues. Nowadays we are able to manage the side-effects such as nausea very effectively.

Dr Virginia Wolstenholme

I believe you were involved in clinical trials for some of these treatments.
I was involved in the first international studies to use this type of drug, which was very exciting.  When we began to see how well patients were responding and the dramatic impact on their diseases, it was exhilarating. It made me feel that we were accomplishing something that was going to make a real difference to people’s lives. There were patients who were looking at living for several years as opposed to a prognosis of less than 12 months, which they would have had with the previous treatments. It was the beginning of a real change in the way we treat melanomas.

What is it like working in these trials?
For the patients it’s great because it means they have a chance to get new and potentially improved treatments, and for the doctors it’s good to get experience with new drugs, see their efficacy and understand their side effects. There are very strict controls through the process, and your contact with each patient is higher because a high level of data needs to be recorded. It was a lot of extra work but I really enjoyed it.

The data was presented to the medical community several years ago and the approach is now in widespread use, but the data is still being studied, so we are continuing to learn new things.

It’s a familiar word, but what exactly is chemotherapy?
Chemotherapy involves administering drugs either by tablets or intravenously, that are designed to kill cancer cells. Different drugs have different modes of action in terms of how they kill the cells. Normally the patient will have these as an outpatient. But melanoma nowadays is very rarely treated with chemotherapy because we have all these other treatments as well. Techniques such as immunotherapy and radiotherapy have become increasingly important in treating melanoma over the last couple of years.

What is immunotherapy?
The drugs I mentioned earlier are a type of immunotherapy—it is where we use drugs to help the patient’s own immune system destroy the cancer cells. It is a good approach because we are working with the patient’s system instead of having to suppress it.

What is radiotherapy?
Radiotherapy is x-ray treatment. It works by using x-rays to damage the DNA in cancer cells. It’s designed to stop the cell replicating. Historically it has not been commonly used as melanoma treatment. But over the years we have developed ways to give it more accurately and safely, which allows us to give higher, more effective radiation dosages without affecting the healthy tissue around the tumour. This is a treatment that does not require surgery so it’s great for people for whom general anaesthetic may be a risk.

What improvements would you like to see in the field?
I would like us to get better at predicting which treatment a patient will respond to, so we can get it to them more quickly. There are also drug resistant tumours and I would like us to gain a better understanding of them. We know, for example, that people with the BRAF mutation can develop resistance to the drugs, but we also know that by using a combination of a BRAF inhibitor and another drug called a MEK inhibitor, we can overcome this resistance. I would like to see more improvements like this coming through.

Where do you see melanoma treatment in five years’ time?
One of the things that is really very exciting at the moment is the way we are beginning to combine immunotherapy and radiotherapy treatments for individual cases, which we think will produce better results. Also, new immunotherapy drugs are evolving and getting better—it is an area of the field that I find incredibly exciting.