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BRITISH BROADCASTING CORPORATION
RADIO SCIENCE UNIT
CASE NOTES
Programme 1. - The Royal Marsden Hospital
RADIO 4
TUESDAY 10/01/06 2100-2130
PRESENTER:
MARK PORTER
CONTRIBUTORS:
VINCENT KHOO
MARTIN GORE
STAN KAYE
ROS EELES
STEVE JOHNSTON
PRODUCER:
ADRIAN WASHBOURNE
NOT CHECKED AS BROADCAST
PORTER
I'm standing on the steps of the first hospital in the world to be dedicated solely to the study and treatment of cancers. Set back just a stone's throw from London's busy Fulham Road, the Royal Marsden Hospital was founded in 1851 by Dr William Marsden, after he lost his beloved wife Elizabeth to cancer.
MARSDEN QUOTE
Now gentlemen, I want to found a hospital for the treatment of cancer and for the study of the disease for at the present time we know absolutely nothing about it.
PORTER
While the imposing 19th Century frontage of the hospital remains unchanged, when you get inside it's very 21st Century and exactly what you would expect to find in a hospital at the cutting edge of cancer research. And that's why I'm here today. I'll be finding out about recent developments in the treatment of cancer - including IMRT, a promising new type of radiotherapy, and the latest biological agents like the breast cancer drug Herceptin.
The first thing I've noticed about the Marsden is that it has a very different feel from many of the other hospitals I've been in - maybe it's because I know that most of the people coming through these doors either have cancer, or are visiting a friend or relative who does - but the whole atmosphere feels more sympathetic, warmer even friendlier. Something that's not lost on the 40,000 patients that are referred here each year.
BARBARA
There's something about walking into the Royal Marsden Hospital that actually you look more sort of forward to coming, you know you look forward to having the treatment because it's good and you look forward to meeting your friends here.
PORTER
Is it important for you to meet other people who are going through what you're going through?
BARBARA
It's a fundamental part of the healing process I think that you let your feelings and your thoughts and you let them out and you share them with other people. And we've laughed and we've joked and you know we can dispel that sort of fear factor that this disease does have.
PORTER
Professor Martin Gore is the hospital's medical director.
GORE
We treat all cancers here at the Marsden. We divide the administration and management of the hospital up according to different cancer types. So within those units we have all the different specialties - we have surgeons, physicians, people who specialise in radiation oncology and specialist nurses. And these units are dedicated to that particular cancer.
PORTER
Before we talk about cancer the general public do tend to lump all types of cancer under one banner really but within that there's a wide spectrum of disease.
GORE
Yes indeed, cancers of different parts of the body are of course very different and carry different prognosis and require different treatments and within those particular types of cancer there can be huge differences in terms of treatment and outlook, depending on whether the cancer is caught early or caught late after it's spread to other parts of the body.
PORTER
What do those cancers share in common, what's actually going wrong to our cells to make them become cancerous?
GORE
Well cancer really is a disease of DNA, it's a genetic disease, something goes wrong with the programming of individual cells and they grow in an uncontrolled manner.
PORTER
And that abnormal growth leads to the development of invasive tumours that interfere with the host tissue's normal function, and to the shedding of millions of seedling cells into the circulation which can, in turn, grow into secondary tumours in other vital organs and tissues. Medical oncologist Stan Kaye.
KAYE
I think that it's clear that cancer represents a major challenge and it's because of the nature of the disease is that relatively early on in many cancers there has been spread from the initial site. So although surgery can be very effective in removing and curing some cancers we have to deal with the disease essentially in most people as a systemic problem and that's why the treatments need to be systemic, that's why chemotherapy is a key part of the treatment because essentially an effective chemotherapy gets to the cancer cells wherever they are, wherever they happen to have spread to, in the body. That's not to belittle surgery and radiotherapy, which is a very important part of treatment, dealing with a specific cancer in a specific site in the body.
PORTER
Three types of treatment form the backbone of cancer therapy - surgery to cut the tumour out, drugs or chemotherapy to kill or shrink it, and radiotherapy, blasting the tumour with ionising radiation. Although often regarded as the poor relation in cancer treatment, radiotherapy is a very important weapon in the oncologist's armoury and used to help more people than surgery or chemo put together. Oncologist Vincent Khoo.
KHOO
Radiotherapy works by delivering ionising radiation. This radiation goes into the patient's body and actually destroys the cancer cells ability to divide.
PORTER
How do we get around the problem that it's also doing exactly the same things to our normal tissue?
KHOO
That's a very important point because the whole concept of radiotherapy treatment is that it would treat whatever it's directed at. Cancer cells are more susceptible because they divide more quickly. Normal cells have a greater capacity to repair damage which cancer cells don't. But the main aim of radiation treatment is that we direct most of the radiation to the cancer cells.
PORTER
So how do you target that?
KHOO
We do that in a couple of ways. One, is by recreating the internal anatomy of the individual patient, therefore tailoring the treatment to their internal anatomy. Now that is called three dimensional conformal radiotherapy treatment. In the past without CT we didn't have this ability, so that limited the cure rates in the past because we would simply treat a whole region and it would be the normal tissues and their tolerance that limits the dose we can deliver.
PORTER
So now using CT scans you can build up a 3D picture of what the tumour looks like. And of course they're not round are they necessarily or they're not square, they're unique, each tumour's a different shape from the previous one that you've seen.
KHOO
That right, they come in all sizes and they're unique to the individual patient.
WARD ACTUALITY
Mr Drake would you like to come through. My name's Claire. We're just going to lie you down on the bed and just line your marks up. You won't feel anything at all and you're just hear a buzzing noise, which is just the noise the machine makes. So how have you been feeling?
Okay, thank you, okay.
PORTER
Bob Drake has cancer of the prostate and is having radiotherapy today.
DRAKE
The first treatment I started on was Zoladex, which is a hormonal treatment, it's a testosterone suppressant which treat it but not cure it, it would stop it for two, three, four years whatever. And then something more would have to be considered, which I'm now going through which is the radiotherapy.
PORTER
What did you think when they mentioned the words radiotherapy, do you know anything about it?
DRAKE
Not a great deal. I know effectively what it was, I was aware that it could cause sort of collateral damage, if you like, to cells around it, which is why a much more focused, much more targeted system of delivery - I was asked, you know, would I consider it, to which the answer of course was yes. I'm aware that the cancer may be uncurable or incurable but if it can be treated and I will get a longer life then I will grab anything that is offered to me.
WARD ACTUALITY
You're just going to hear us shouting out measurements to one another, it's just so we can get the coordinates of where we need the treatment to be - alright? So here on the left you're point 6 [indistinct word] and I'm point 8.
PORTER
Bob's treatment involves having a 90 second burst of ionising radiation, five days a week, for seven weeks. He is having a new type of treatment called intensity modulated radiotherapy - or IMRT - designed to focus the radiation more accurately on the tumour, sparing surrounding healthy tissues. Vincent Khoo again.
KHOO
What we do is we use the same techniques as conformal radiotherapy treatment but in this instance each field is further sub-divided into a hundred smaller fields, each of those fields have a different intensity and by modifying the intensities we are able to paint dose to the tumour in the area that we want to treat. And in this manner we can also spare dose to areas we don't want to treat, which is the normal tissues.
PORTER
So you'd be using a convergence of how many beams would you use in one of these machines, how many different beams would be coming in to the tumour?
KHOO
Generally in intensity modulated therapy we would use five or more fields but out of that five - each of those five fields would consist of between 10-15 different fields. And the intensities for each of those fields would vary within the single field itself, giving us the flexibility to paint those doses.
PORTER
So where those five fields converge that's where you get the maximum dose but within each of those fields you could very fine tune the picture you're painting to an irregular ball bearing sized tumour or whatever.
KHOO
Very much, we can now treat concave and U shaped tumours, sparing the organs that lie within the concavity of this U shaped target much better than we were able to before in the past.
WARD ACTUALITY
Okay, so we actually operate the machine from outside and all you'll do is just hear and see the machine moving around you and it just makes a series of whirring noises. Alright, so we'll be back about in a minute and a half or so to get you off.
PORTER
Vincent, obviously there are lots of different applications for radiotherapy, but what sort of common cancers can be treated in this way?
KHOO
There are many sub-sites where radiation is used as curative treatment. Amongst them being breast cancer, lymphomas can be cured with radiation treatment. It can be used as a growth restraint mechanism. In fact in some radiation treatments it has completely reversed the rather amputative nature of surgery. For example, in anal cancers the management of anal cancers has been reversed with the use of chemotherapy and radiation treatment and therefore patients are able to maintain their back passage and avoid having an operation that would leave them with a colostomy or a bag and you can imagine the quality of life issues for the individual patient.
PORTER
I am now in a very different part of the Royal Marsden Hospital, and standing in the reception of the chemotherapy unit where day patients come in during the morning to receive their chemo - normally via an intravenous infusion - before heading home again in the afternoon. Peter is on the last of four treatment sessions following recent surgery for cancer of the colon.
PETER
I had eight weeks recuperation where he said don't lift anything. I said, well can I lift a golf club? - no you can't. Then came back for four more sessions and today is the start of the last session.
PORTER
I must say you look remarkably well. What sort of side effects are you getting from this regime that you're on at the moment - you seem to have all your hair, so ...?
PETER
The captain of our golf club said Peter, you've got more hair than I have and I said, well Bert most people have got more hair than you anyway. So I haven't lost any hair. I feel a bit icky sometimes but they give you these tablets to start with like you take two three times a day for two days.
PORTER
And Peter is not the only one who is finding modern chemotherapy regimes are easier to tolerate. Stan Kaye again.
KAYE
The single biggest thing is that vomiting is now not a problem. The treatment for chemotherapy induced vomiting is much, much better than it was. So actually now the problems that are beginning to emerge more in chemotherapy are much more subtle and maybe to do with fatigue. Hair loss is still a problem, although we can potentially protect that with cooling of the scalp.
PORTER
But it is true to say isn't it - and certainly in general practice I see it - the diagnosis of cancer is shocking enough, having a form of cancer, but it's the concept of - the idea that they're going to require chemotherapy that often scares people even more, there is a perception out there that it is a very nasty process to go through and sometimes worse than the disease itself, I mean you hear people say well I've refused all treatment. When you say you will be needing chemotherapy do you find initial resistance from patients?
KAYE
I think people understandably are concerned about what it might imply but what we have to discuss with everybody is what the balance of risk is between the pros and cons and we're very careful not to give chemotherapy or continue chemotherapy when it looks to us as if it's going to do more harm than good. But the important thing that's developed I guess over the past 5 or 10 years is that in more common cancers, like bowel cancer and breast cancer, lung cancer, chemotherapy is increasingly being given as part of the treatment and given to the right patients after the initial surgery it will reduce the chance of that disease coming back and will increase the cure rate when it's given in that context.
PORTER
Genetics is another key area in the battle against cancer. A person's chances of developing the disease are determined by a combination of genetic predisposition, and environmental factors such as diet and lifestyle. Or to put it another way, Mother Nature loads the gun, and the environment pulls the trigger. But which is the most important? Ros Eeles is a consultant in clinical oncology and cancer genetics.
EELES
The message to take away is that about 5-10% of people who have cancer may have developed the disease because they have a genetic predisposition. And having a positive family history, in other words knowing what happened to your ancestors, may be very important. An example would be if you have breast cancer then if you have a family history of breast cancer of two or more cases at very young age, by which we mean 50 years or less at the age of diagnosis, then that may be very important. And if you have such a family history we'd advise you to talk to your general practitioner because there are now guidelines that have just been published by the government to indicate when somebody with a family history should be referred for specialist advice.
PORTER
If they are referred they'll be coming to see somebody like you presumably, then what happens?
EELES
We take a full family history, right out to your grandparents and even further if you do know about it, and indeed there are now databases - you can look on the web for the death certificates of your ancestors and there's a website for this if you need to find more information. So as much information as possible would be very helpful so that we can confirm the family history. And then what we do is we look at the structure of the family and we look for the ages at which people in your family have had cancer and also the types of cancers that they have had. Sometimes different types of cancers clustering together in your family history may be quite important. An example would be if you had a family history of breast cancer and cancer of the ovary, that would be a warning sign to us that we should do further detective work on the family history.
PORTER
You say further detective work, presumably you're looking for certain sets of genes?
EELES
Yes there are two genes at the moment that we can test for, they're called the braca genes or BRCA1 and BRCA2 - at the moment that's the main genetic test that can be done. There are some rarer ones that we can also test, they're extremely rare and the thing that would flag up which genes we should test for is the family history, types of clustering in the family.
PORTER
So if you have a positive strong family history and or you have one of the braca genes, what are the implications for you as a woman?
EELES
If you have an alteration in one of the braca genes - BRCA1 or BRCA2 genes - it's a risk of 80-85% of developing breast cancer but by the age of 80. So if a woman is 35 when she comes to see us that's not her risk at that age, that's the risk over the whole of her lifetime. Her risk is obviously higher than the general population but for example over the next year that woman's risk would be at its highest only about 3%. So it's low over one year but at lifetime there's a higher risk.
PORTER
What could she do or indeed what can you do to reduce that risk other than screening, is screening all that we can offer?
EELES
At the moment screening is one of the things that we can offer to try and find cancers earlier because we know if you find cancers earlier then they're easier to treat and easier to cure. There are studies going on, we have a specialised clinic at the Institute and the Royal Marsden, which is a clinic where we actually follow up individuals with genetic alterations in these genes. We offer targeted screening and there are new prevention programmes coming along, there are new prevention drugs in trial at the moment for people over the age of 40 and we are trying to look at new prevention programmes for people younger than that.
PORTER
A hospital like the Marsden and the Institute here are right at the cutting edge of onco-genetics, you know genes and cancer, how do we know that this sort of information is percolating out through to local breast cancer units throughout the country?
EELES
Well there's a very well established network already of all the cancer genetics clinics over the whole country.
PORTER
So you're pretty confident that this sort of information is now being disseminated right across the UK?
EELES
Very confident. There are two ways of doing this. One is that centres do talk to each other routinely in specialised meetings. The other thing that has happened is there's something called the National Cancer Research Institute, they have an annual meeting, the first meeting was in Birmingham in October, a very successful meeting, lot of cancer specialists in the UK were there and that meeting is planned to continue for the next five years at least annually.
PORTER
And genetic research isn't just focussing on why some people are more at risk of developing the disease than others - it can also be used to identify genetic changes that differentiate cancer cells from normal tissue, which in turn can identify new targets for drugs. Which is exactly what happened with the drug Herceptin - a major breakthrough in the treatment of breast cancer. Steve Johnston is a clinical oncologist with a special interest in the condition.
JOHNSTON
Herceptin represents one of the new so-called targeted therapies that has been developed to specifically block one of the things that we think goes wrong in cancer cells. All of our previous treatments were fairly non-specific - chemotherapy in particular hits just dividing cells and that's why it causes side effects on the body. And through work that was developed 20 years ago we found that about 20% of breast cancers have a particular gene that goes wrong in them that makes a protein called Her 2. And what they've developed is a very specific drug, it's in actual fact an antibody, which is like the normal defences against infection, an antibody to block this. So it has been engineered really from finding out what's gone wrong in the cancer cell to developing a new treatment.
PORTER
You say one in five, is there anything, any particular characteristics about these types of breast cancer?
JOHNSTON
Yeah the tumours that are Her 2 positive we've found are specifically more resistant to conventional chemotherapy treatments, they're faster growing, more aggressive tumours. And that's why we're so excited about the treatments that have come along with Herceptin because these types of cancers have been more difficult to treat in the past, much more likely to return after chemo or hormone treatments. But Herceptin has really revolutionised and changed that.
PORTER
And how does the binding of the antibody to this receptor on the outside of the cancer cell affect the cancer cell, what's it doing to the cancer cell?
JOHNSTON
Well what's gone wrong in the cancer cell is that instead of having one or two copies of this Her 2 on the surface when the gene goes wrong it makes thousands of copies and that really then drives the growth of the cancer cell very fast. And the antibody literally locks on to it, like a lock and key, and stops that receptor signalling and blocks it. Moreover what we've found is that when it blocks it, it then suddenly reverses the resistance to the conventional treatments and makes chemotherapy suddenly work better and we also now think makes conventional hormone treatments work better. So that's why it is not only to be used on its own but to be used in conjunction with our conventional treatments because it makes them work better.
PORTER
And what practical difference is this going to make to the one in five women who have Her 2 receptors on their cancer cells?
JOHNSTON
Well in the advanced breast cancer setting it's already made a practical difference in that it's doubled their chances of the chemotherapy that they're on working and it's controlled the cancer for much longer. In the early breast cancer setting the key thing is that it's halved the risk of cancer coming back over the first few years. And that makes a substantial difference we think on the chances of being alive.
PORTER
Twenty eight year old Emma is one of the small number of those women offered Herceptin early in the disease to reduce the likelihood of recurrence. The drug is currently only licensed for use in advanced breast cancer. Emma carries the Her 2 gene, has had surgery, radiotherapy and conventional chemotherapy, and is now on a year long course of Herceptin.
EMMA
For me it means coming to the hospital once every three weeks. Initially I had a - my heart monitored just to check that everything was running fine. I think one of the side effects they've found is people with proven kind of heart conditions can sometimes have problems whilst on Herceptin, so they wanted to baseline that data around my heart. So I did that before my first Herceptin treatment and then now I come in once every three weeks and the Herceptin goes through on a drip, a bit like my chemo, it takes an hour and a half.
PORTER
Any side effects?
EMMA
No, not that I'm aware of. I do get very tired but I understand that that's a combination of my whole treatment and everything I've been through rather than the Herceptin itself. But no sickness, which is great.
PORTER
This is a slightly thorny issue about Herceptin at the moment of course is that it's technically not available for women in early cancer, how do you think that's going to change over the next six months or so?
JOHNSTON
I think it's going to change quite rapidly because the cancer community - doctors and the patients - have recognised that this is probably the single biggest advance in the treatment of the disease for 30 years. So that has actually encouraged us in discussions we've been having with the Department of Health, with the various health authorities, to actually get this fast-tracked and available quickly.
PORTER
So the lack of licensing is really about red tape rather than any clinical evidence for the drug to be used in early cancer?
JOHNSTON
That's right. And the key reason that that has not been given yet is that the safety data are being critically evaluated. This drug does have side effects and it does have effects on the heart, in some patients. It tends to be those who are older who may have had a certain type of chemotherapy and we need to fully understand that so that some patients aren't put at excess risk. And so there have been what are called exceptional cases and funding has been approved on a case by case basis. Now clearly that creates a degree of inequity which we as doctors and patients want to rapidly see changed, so that this drug is widely available to all.
PORTER
Herceptin is one of the first of a new range of so-called biological cancer drugs that target specific biological processes that differentiate cancer cells from healthy tissue. And the Marsden is at the forefront of international research into such treatments, with many of the hospital's patients involved in trials to evaluate potential breakthroughs. Peter is one of them - he has cancer of the prostate and is more than happy to get involved in a trial, even though the treatment he is receiving is unproven.
PETER
The options that I've been through have a limited effect and a limited life. So I particularly didn't want to sort of go on one thing and then it only lasts for six months and go on something else and that only lasts for a limited period.
PORTER
But one of the problems of being involved in a trial, it's the very reason why they're trialling that drug, is that they don't necessarily know that it's going to be beneficial and they don't necessarily know that it's going to be comparatively well tolerated.
PETER
No that's quite right and I accept that, I'm not going into this blind thinking oh this is the be all and end all of the treatment for my form of prostate cancer. But I would rather go down this route than go into something that has been tried and tested and has a limited time benefit.
PORTER
And what's practically involved in being in a trial, would you notice anything different from any other patients?
PETER
I think we're all doing different things. I'm lucky because the trial that I'm on is not intravenous, so I just have breakfast and have the drug and then just carry on. But it's just the once a week here for all the blood tests and the ECGs and whatever. At the moment, touch wood, I'm not having any side effects.
PORTER
Stan Kaye is the Director of the Drug Development Unit responsible for clinical trials.
KAYE
I think that the message is that this is a very specialist area of cancer treatment and care and we're looking after patients at a very difficult stage with understandable issues, desperate for new treatments. At the same time we have through all the laboratory work very exciting leads into new treatments. So we have to put all this together that takes us forward recognising that we're looking after real people. One of the most interesting avenues is to work not just on the cancer cell itself but on the cells that surround the cancer cell within a whole cancer. What that means is that if you take a piece of cancer it's composed of a number of different cells - it's composed of the cancer cells themselves and it's composed of surrounding cells that actually the cancer cell influences in ways that we don't want. It can start, for instance, to make those cells develop blood vessels. If we could stop that process, if we could stop the development of blood vessels into a cancer, which the cancer cells need, we can stop the whole process.
PORTER
This is because presumably they're so fast growing they need to draw their blood supply from surrounding tissues.
KAYE
The simile that's often given is essentially the motor car if you turn off the gas, the petrol, the car would stop and that's essentially what is antiangiogenic treatments - that's what they're called - do and they're looking really interesting. Indeed the most important new data on these antiangiogenic treatments I've described are in combination with chemotherapy. In bowel cancer, in lung cancer, in breast cancer, we're going to start some work in ovarian cancer, the data demonstrating that you can improve the outcome of chemotherapy by this antiangiogenic approach is quite persuasive.
PORTER
Despite widely publicised breakthroughs like Herceptin, it's very unlikely that we'll ever have a single magic bullet for cancer. Looking back over the last five years you could be forgiven for thinking that progress has been worryingly slow, but take a longer view - over the last 30 years - and it becomes obvious that oncologists have taken major strides forward. And the future looks bright according to breast cancer specialist Steve Johnston.
JOHNSTON
In breast cancer at the moment there are between 20 and 30 new drugs in medium to late stage of development. It may be another four or five years before another big breakthrough is made like Herceptin but the potential is knowing how the cancers work, we've developed the new drugs in conjunction with academic centres, industry, the pharmaceutical companies and these are now entering fairly large scale trials in breast cancer. So there's a lot to be very optimistic about.
ENDS
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