Q&A: Prof Ricky Sharma

Portrait: Orlando Gili

What is radiotherapy?
Radiotherapy is the non-invasive use of high-energy radiation to destroy diseased cells. It comes in a number of forms. Traditional radiotherapy uses photons, which are radio waves; the most sophisticated system for that is the Cyberknife—a robotic system that generates the beam and delivers it extremely precisely.

Another form of radiotherapy is particle therapy. We have been able to use electrons for a while now, but these can only treat the skin, or areas close to the surface. However, next year the UK will get machines capable of using protons, which are heavier than electrons and are able to penetrate much deeper.

A third form is molecular radiotherapy, which uses radio-isotopes such as yttrium-90 (Y-90). Here you inject radioactive material into the specific artery or vein that supplies blood to the tumour. One very effective way of doing this is selective internal radiation therapy (SIRT).

What is SIRT?
It is a treatment that we currently use to accurately target tumours in the liver. The process involves injecting millions of miniscule radioactive balls known as microspheres—too small to be seen without a microscope—into the artery that supplies the liver. The particles are just the right size to lodge in tumour vessels, which are narrower than normal blood vessels, and therefore the number of microspheres builds up around the tumour. This targets the cancer in two ways. Firstly, the radiation they emit—over a short distance—combines to deliver a high dose of radiation to the tumour. Secondly, by blocking the vessels, they cut off the tumour’s blood supply.

Is this a standalone treatment?
Initially it was, but in 2007 I published the results of a small trial with 20 patients where I combined SIRT with chemotherapy in a new type of treatment. The results were so striking that we were able to raise the funding to run a much larger trial, involving cancers in other organs as well as the liver. That trial treated 1,103 patients in 14 countries over 10 years. I presented the results earlier this year.

So, what were the results?
They showed reasons for real optimism. There were subgroups of patients that really seemed to benefit. For example, patients with certain types of colorectal cancer seemed to do better with this combination than the control group. There were signs of some synergies developing, meaning that the techniques combine to create benefits that are greater than the sum of their parts, producing unforeseen benefits. The exciting thing is that we have a great deal of data, which we will continue to interrogate for some time to come.

Can this treatment access tumours that would otherwise be untreatable?
It definitely can. If you take the example of liver metastasis, if there were three or four lesions I would consider targeting them individually with the Cyberknife. With more than that, SIRT is often the only available treatment, as they are too widely spread.

Can combined therapy shrink an inoperable tumour to something that is operable?
Yes, sometimes we do see this. In the large trial, between 16-17% of the patients went on to have what were initially inoperable tumours surgically removed as a result of the therapy. It is incredibly gratifying to see such things happen.

What attracted you to radiation oncology?
It was the experience of treating one particular patient. He was admitted with backache, disturbance of bladder function and compromised bowel function. It turned out he had spinal cord compression from prostate cancer. I remember following his case as the cancer specialists treated him using radiotherapy and was amazed at what they did for him. Within a couple of radiotherapy sessions, he was completely back to normal, with no side-effects. I remember thinking that this was completely different from all the other things I was seeing in medicine. I wanted to learn more about this, so I did a PhD in cancer, really drilling down to DNA level, looking at how cancer DNA differs from our normal DNA.

That seems to have been a very scientific approach?
As well as being a clinician, I have always loved the science side of medicine. The research is fascinating and alongside treating patients I head a laboratory team where we do research into radiotherapy and DNA damage. We know that around 40% of successful cancer cures currently involve radiotherapy, and we are trying to improve that percentage by researching new ways to treat cancers that can’t currently be treated with radiotherapy. Our aim is to try to increase the range of conditions we can treat with this very effective tool.

Can you give us an example of this work?
A good example involves some of our work with immunotherapy. The immune system can be very good at destroying cancer cells. It is triggered into action by detecting cells called antigens—toxins or foreign substances in the bloodstream. However, some cancers—75% of bowel cancers, for example—don’t release enough antigens to trigger the immune response. With radiotherapy, we can very selectively stimulate a small part of a tumour, causing it to express just enough antigens to trigger the immune system into action.

Where do you hope things will be in three or four years?
There are several areas where I would like to see progress. I would like to be using SIRT / chemotherapy combination therapy for a wider variety of cancers, such as kidney or lung cancers. I think this is achievable and would have so much to offer. I would also like to see more use of radiology alongside the emerging field of immunotherapy. This is a really exciting area which has the potential to achieve cures that are beyond us at the moment. One of the reasons that it is so exciting is that we are also developing new forms of radiotherapy that are increasingly powerful.

How is radiotherapy evolving?
In terms of the traditional form of radiotherapy, which uses photons, the evolution will be software-driven, allowing for increasingly precise location of tumours and delivery of the treatment. For particle therapy, a new generation of cyclotron and synchrotron machines will allow us to treat people using protons, carbon ions, helium ions and many other types of particle, each of which which will have increased benefits for treating different cancers. One exciting development will be the ability to remove the body’s immune cells prior to radiotherapy, manipulate them and then reintroduce them to attack the cancer from within.

What do you enjoy most about what you do?
I love being a clinician. The most important thing for me is to be seeing patients and ensuring that each one is getting the right treatment. That is the reason I chose oncology in the first place. There is also an amazing positivity that you find with cancer patients and their relatives that you maybe don’t find in other fields of medicine. But I also love the science, so the ideal thing for me is when a patient asks me a question about the basic science underpinning their treatment. That is a great moment.