Main content

Multi-morbidity, one-shot radiotherapy during surgery for early stage breast cancer

David Haslam, chair of NICE, talks to Mark Porter about managing the millions of people on five or more drugs a day. Plus one-shot radiotherapy during surgery for breast cancer.

David Haslam, chair of NICE, discusses with Mark Porter how doctors should treat patients with 'multi-morbidity', the millions of people receiving many different drugs for many different conditions. There's plenty of trial data for starting treatments, but a dearth of evidence for stopping them!

And one-shot radiotherapy during surgery for breast cancer may help 20,000 women in the UK. Rather than daily hospital visits for radiotherapy over 5 weeks, a dose is given straight to the open wound during the operation. It is quicker, cheaper and much more convenient, so why isn't it more widely available?

Available now

28 minutes

Programme Transcript - Inside Health

Downloaded from www.bbc.co.uk/radio4

 THE ATTACHED TRANSCRIPT WAS TYPED FROM A RECORDING AND NOT COPIED FROM AN ORIGINAL SCRIPT.  BECAUSE OF THE RISK OF MISHEARING AND THE DIFFICULTY IN SOME CASES OF IDENTIFYING INDIVIDUAL SPEAKERS, THE BBC CANNOT VOUCH FOR ITS COMPLETE ACCURACY.

 INSIDE HEALTH

Programme 1. - Multi-morbidity, one-shot radiotherapy during surgery for early stage breast cancer

 TX:  05.07.16  2100-2130

 PRESENTER:  MARK PORTER

 PRODUCER:  ERIKA WRIGHT

  

Porter

We’re back and over the next six weeks we’ll be reporting on everything from the latest developments in hip surgery, to how happy accidents have changed the face of modern medicine. As well as answering your queries about health issues that you find confusing.

 Coming up today: Breast cancer, a new, quicker, cheaper and more convenient way of treating the disease which could benefit as many as 20,000 women in the UK every year. But if it’s really that good, why isn’t one-shot-radiotherapy more widely available?

 First, a subject that is very close to our hearts here at Inside Health. Twenty percent of adults in the UK are now on five or more medicines – twice as many as in the mid-nineties.  It is a trend that has been accelerated by the burgeoning number of guidelines and a population that is living longer and developing multiple health issues, all of which have their unique treatment pathway. But how do all these different medicines interact?

 To help doctors optimise care for the millions of people receiving different drugs for different health problems the National Institute for Health and Care Excellence is about to release yet more guidance - only this is a bit different from what has gone before.  Professor David Haslam, Chair of NICE and a driving force behind this latest initiative, explains why.

 Haslam

You only have to go to any hospital or look at the way healthcare’s organised to realise we’ve tended to do stuff in single conditions.  So you go to the hospital, there’s a sign for Respiratory Medicine, Cardiac or whatever but real people have lots of problems simultaneously.  And the same goes for the sort of work NICE has done over the years, producing guidance on the management of individual conditions but the recognition is that we’ve got all these people with lots of conditions.  I spent most of my life as a GP and I can remember one of my patients – you both probably have similar patients – a guy who had diabetes and coronary artery disease and hypertension and hyperlipidaemia and chronic kidney disease and osteoarthritis and macular degeneration and hardly surprisingly depression.  Now that lot all put together makes an individual human being whose care we absolutely have to focus on, not just on the individual bits.

 Porter

But if by focusing on the individual bits what might we be doing wrong then, I mean what are you worried about?

 Haslam

Well the real worry is first of all not focusing on the whole human being, which is what we’re all in healthcare for, so just focusing on the condition, not being absolutely sure what matters to the patient.  And then the worry is are we over treating, if you add together all these conditions and all the possible treatments for them you then end up with an awful lot of drugs that may or may not interact in a helpful way.  But on top of all that the way we organise healthcare, your entire life is going to be spent going to one clinic after another, so we really, really need to bring that altogether.

 Porter

Margaret McCartney, as a GP, I can see you nodding there, this rings a few bells.

 McCartney

I think I’m not just nodding but cheering to hear NICE sort of moving the narrative on towards patients as opposed away from them and into these single diseases.

 Porter

This fragmentation we talk about it being in hospitals but actually it’s happening in general practice now isn’t it.

 McCartney

Oh it is entirely happening in general practice and part of the problem, I think, has been this striving for excellence in some way, striving for excellence in managing certain conditions to standards that we aspire to that are those given to us by a guidelines.  But in many ways, and it sounds counterintuitive, very often I think the best cure is not going to be given by following guidelines to the letter, instead it’s going to be about sitting down with patients and having conversations, not about how do I achieve a blood pressure of this number and that number but how do I achieve the quality of life that I’m really looking for here.

 Porter

Give us some idea of the burden – and David referred to the fact that – a lot of people taking a lot of pills.

 McCartney

Yeah and I think this is – it’s so easy for me to prescribe a tablet or to make a hospital referral, it’ll take me minutes to do that but for a patient they have to keep living with that every single day.  So one paper that’s come out looking at the impact of guidelines in the US found that patients who had six chronic conditions if they were following the guidelines to the letter they’d be taking 18 medications a day, having about six and a half to seven contacts with health professionals of various types per month and spending around 80 hours of their time following the guidelines that have been set down for them to do.  So in many ways these aspirations are really pretty unrealistic, do we really want to be spending all this time, well some people might want to but many other people were wanting to put quality of life first and their quality of life might not involve making the same decisions as the guidelines would have made for them.

 Haslam

And of course NICE in its guidelines, all the individual condition guidelines that we produce, we say the same thing, every single time, which are that the recommendations represent NICE’s view arrived at after looking at the evidence.  But we always say when exercising their judgement professionals are expected to take the guideline into account alongside the individual needs, preference and values of their patient.  Now what’s worried me is seeing people forget that, I get this hunch that sometimes people treat that almost like the terms and conditions on a website, they click past to get to the important stuff like the dose of the drug, that is the important stuff, the important stuff is the individual.

 Porter

But herein lies a problem for me anyway David, I completely agree with you but I can see myself – I mean my nightmare scenario is being in a court somewhere where a QC holds up one of your guidelines, this was produced seven years ago Mark and if you turn to page 32 Dr Porter you’ll see this patient should have been on this, that and the other.

 Haslam

Well Mark when you go to court I’ll be very happy to come and join you and to explain what I’ve just said because I don’t know anybody who disagrees with this, I mean it really is vital.  Indeed the people who invented the whole world of basing your medicine around evidence said this right from the start – we must really work with patients not do medicine to them.

 McCartney

But at the start of evidence based medicine guidelines were simple, they were a page sometimes, you know two and a half pages sometimes and very few of them, whereas now we’ve got huge amounts of guidelines.  And the problem is that guidelines are very often used to judge quality in general practice and there’s a big problem where the guidelines are interpreted by the government or by the GP contract, really I think putting a lot of pressure on general practitioners to encourage patients to have treatments, rather than discussing what’s best for you.  And I think it becomes a bit dehumanising for doctors as well when we are following instructions on a computer screen as opposed to talking to people about what they would and wouldn’t like to do.  So I think there’s huge opportunities here, it should almost be like a rebirth of general practice, back to our core values, and rather than judging quality by the amount of prescribing we’re doing let’s judge quality by how good our decisions are.

 Porter

There’s a lot of pressure in general practice at the moment to try and encourage patients to come forward with one problem at a time and this sort of rather flies in the face of this doesn’t it.

 Haslam

Yeah well I think that’s wrong and I completely understand why doctors, who are incredibly pressurised at the moment, feel the need to do that.  But…

 Porter

They don’t have time to do more would be their reply.

 Haslam

But my personal feeling and again the way I practise was if I felt someone was going to have multiple problems I said can we get them all out the way at the beginning, so I know what I’m dealing with.  Many doctors have tried to discourage patients bringing lists, for instance, it’s often seen as a really bad thing, I think it can be really helpful if it helps to plan the consultation at the start and then you don’t have any more time but you know what you’re dealing with.

 Porter

I think it fair to say that this draft guidance is going to be welcomed by pretty well everybody – patients and doctors.  But let’s get down to some specifics, if we may, and one of the things that caught my eye in the initial press release when this was launched was the first point was to stop treatment of limited benefit, de-prescribing if you like, which is very much on vogue at the moment.  Can you give me an example of the sort of treatments that you were thinking about?

 Haslam

Well there’s one very specific one we focus on which is bisphosphonates, which are a treatment that are used for prevention of osteoporosis and there seems to be absolutely no evidence that taking those for longer than three years is beneficial.

 Porter

But there’s lots of people on them for longer than that.

 Haslam

Yeah sure.  What we also have said very clearly in the guidance is we need an awful lot more research into this.  Hardly surprisingly there’s an awful lot more research about starting treatments than there is about stopping treatments and there’s all sorts of reasons that you can postulate why that might be.  But we need to understand much more about this.  But if feels very clear to most people that if you’ve got, for instance, a very elderly patient you don’t need to start them on a drug that’s designed to prevent them having a heart attack in 10 years’ time.  Now that’s not being ageist, it’s just being sensible.  The other thing, having just mentioned age there, I want to stress this isn’t just an issue of the elderly, multi-morbidity or having multiple health problems is a problem across all age groups and particularly people with say learning disabilities, people with long term mental health problems who have an increased incidence of all sorts of physical health problems as well, it’s bringing these altogether.

 McCartney

And deprivation is a massive problem because deprivation means that you will get your multi-morbidity 10-15 years earlier than you would were you not suffering from the effects of inequality.  So that’s a really big problem as well.  And one of the things I think we really do lack is information about drug interactions, so poly-pharmacy, when people are on more and more medicines.  So between 1995 and 2010 the number of adults taking five or more drugs per day doubled to 20%, so we’re seeing huge amounts of people taking lots and lots of medication, a quarter of people aged over 80 are on 10 or more drugs.  And there’s a real dearth of information about the effects of this, in particular the effects on things like falls, which can kill elderly people, and also the effects on obesity, on hypertension, on low blood pressure conversely and on kidney function.  So there’s big, big uncertainties around this, a real lack of information and we’re really struggling a bit in the dark in terms of what’s good to stop.

 Porter

It might come as quite a surprise David that we know so little about stopping therapy.  We have lots of great guidance about how to initiate drug treatments for particular conditions but very little about when to stop it.

 Haslam

Well a lot of this comes down of course to the fact that as people develop other healthcare conditions and maybe other drugs are added in it’s that combination of drugs which is so often the issue, which then makes you wonder is this combination actually delivering enough benefit.

 Porter

Because the default position, if in doubt, is to continue existing therapy and you hear the term you hear people talking about is people being parked on their medication – that it just gets repeated and repeated and nothing gets changed.  And what you’re pushing for perhaps is a more aggressive review?

 Haslam

No, what – I think particularly what the guidance is pushing for is more research into actually knowing the answer.  The last thing I want is for listeners who are out there on sort of 10 tablets a day to stop them all because that almost certainly will be dangerous.  And of course the importance of pharmacists, I think they could bring a really important role into these sort of reviews, working in partnership with the doctor and the patients.  But I do want researchers – and the guidance is really keen on researchers to do more work into this.

 McCartney

We really are missing an awful lot of evidence, there’s huge gaps in it.  And it would be really great to have better trial data, to be using data from big research databases, data that’s been gathered already in the GP database for example, and actually find out what happens when we stop things.  It’s stopping things, it’s thinking about whether we need to continue things or not, what does the evidence say.  A lot of the time we’re prescribing for someone – a drug – for 15 or 20 or 25 or 30 years now whereas the original trials might have just been for five or 10 years.  And it does put big question marks over what we’re doing when we really should be having smaller question marks at this stage.

 Haslam

And of course the potential different combinations of different medications is almost infinite and particularly in care homes with research which suggested the average person in a care home is on nine different medications and we know very little about the interactions here.  But as well, don’t forget, it’s not just the drug interactions, it’s the sheer hassle of taking all those pills and we’ve all got elderly relatives who have their dosette boxes lined up with the pills they’re taking each time of day, it’s pretty darn impossible to get that right.

 Porter

Professor David Haslam and Dr Margaret McCartney, we must it leave it there. Thank you both very much. The new guidance is expected to be published in September. More details on the Inside Health website.

 

Breast cancer therapy is always evolving, but there has been a consistent theme in surgery over the last 40 years that less can sometimes be more. Prior to starting my career in the eighties the standard treatment for breast cancer was to remove the whole breast – a mastectomy – even for very early cancers. Then researchers discovered that for most women it was just as effective to only remove the lump – a lumpectomy – and then treat the remaining breast with radiotherapy daily for up to five weeks. It transformed breast cancer surgery for all involved.

 And now there is change in the air again, only this time it is the radiotherapy that could get the “less is more” approach. Could a one-off dose of radiotherapy, given directly into the wound at the time of surgery, work as well as five weeks of treatment given to the whole breast? Well, the results of the Targit study - a randomised controlled trial comparing the two over five years– suggests it might.

 Bernstein

My name is Marcel Bernstein.  Four years ago, when I was 69, I discovered that I had breast cancer, early stages, and I was told by the first breast surgeon I saw that I should have a mastectomy.  I reeled out of his office with my husband in a state of shock.  The first thing we said was we need a second opinion.  I heard about Targit and it sounded amazing.  It sounded amazing because I’m a very busy woman – I teach, I’m a journalist, I’m a writer – I didn’t have time to be seriously ill, I didn’t have time for weeks and weeks of radiotherapy, which frightened me.

 Vaidya

My name is Professor Jayant Vaidya.  I’m a professor of surgery and oncology at University College London.  Back in 1990s I did some work in the laboratory in which I found that when I take a mastectomy specimen, and these were women who came to Tata Hospital in Mumbai who had small tumours and originally it has been six weeks of radiation for every day.  So if someone came from outside Bombay from north of India to me, as a senior registrar, I had to tell the patient – you’ve got breast cancer, can you stay in Bombay for six weeks.  If she said yes, I said okay we can preserve your breast because we can do a lumpectomy and give the radiotherapy for six weeks.  But as many of them couldn’t actually stay here because they were daily wage earners, they had to go back to their families, they said okay I can’t stay I’ll have a mastectomy instead.  And they didn’t want to have a mastectomy and many of them had small enough tumours that we could preserve the breast.  And these patients’ mastectomy specimens is what I analysed in the pathology lab.  And I found that these patients have one tumour, they also had other cancers all over the breast, in two-thirds of these patients had other cancers scattered in the breast, logically that would mean that everybody should have a mastectomy but what has been found in clinical trials is that if these patients, who normally have these other cancer spread, are treated with radiation and lumpectomy cancer reoccurs only around the tumour.  So if cancer’s recurring only around the tumour why radiate the whole breast?  That was the question in the paper which was published in 1996.  And I came here to test a hypothesis that giving radiation only around the tumour is as effective as all breast radiation.

 Porter

Was it difficult working on a hypothesis in that you’re playing with fire effectively here, if you get it wrong it can have quite significant consequences?

 Vaidya

Firstly morally our duty was to make sure we don’t jeopardise patients’ outcome.  Giving radiation at the time of surgery we didn’t know whether it was safe or not.  So first we tested it was safe to do.  After we tested it in these patients and we knew it was safe to do in 2000 we said well now is the time to do the trial.  So it went through a standard ethics approval process and we started the randomised trial where we named the procedure called Targit, we called it targeted intraoperative radiotherapy or Targit for short.

 Bernstein

It was explained to me as being a one-stop treatment, that you had your surgery and during the time you were under the anaesthetic you got a big shot of radiotherapy directly into the tumour bed.  So the rest of your body was not affected, you weren’t going to have heart problems, your lungs – all the bits of you with radiotherapy can be affected were in fact untouched.  Also the fact that next day it was over.  And what sounded marvellous to me was that instead of being ill for weeks or months I was going to be better almost immediately.

 Vaidya

At the time of the operation I would remove the lump with some normal tissue around it, then we would assess what the size of the tumour bed, what is left behind, the cavity is, and use the correct size of the applicator that goes in there.  Then we tailor the cavity by putting a very meticulous stitch in this cavity and insert this spherical applicator inside the tumour bed.  Then we switch on the machine for about 20-25 minutes, switch off the machine, take the applicator out and stitch the breast back.  And the patient can go home the same day or the next day.

 Porter

And in terms of time what does it actually add to a typical operation?

 Vaidya

A typical operation it adds probably between half an hour to 45 minutes. 

 Porter

One of the problems that people might think about giving radiotherapy to a fresh wound is that that scar needs to heal and basically you’re giving it x-rays that kill the cells.

 Vaidya

Yes we were worried about it when we started this back in 1998.  We found no evidence absolutely that there was any problem with wound healing.  And in the randomised trial there was no difference in wound healing problems in these three and a half thousand patients.  When you operate there is a wound, where there’s a wound the body tries to heal, when the body tries to heal it stimulates movement of cells.  So the fluid that collects in the wound, we found, actually stimulates cancer cells.  If you collect the fluid from a wound which has had intraoperative radiotherapy it doesn’t stimulate cancer cells.  So we said well maybe that is actually a good thing, it was a good surprise because by that time the trial had already started.  So we found the results were very similar – that if you receive intraoperative radiation at the time of lumpectomy the chance of remaining alive at the end of five years, without a recurrence, is 93.9%.  If you had normal radiation it was 92.5%.

 Porter

Broadly the same.

 Vaidya

Broadly very similar at five years.

 Porter

The Targit trial has attracted a lot of attention from around the world, but the idea that a one shot approach could work as well as conventional radiotherapy remains controversial. Anthony Zeitman is Professor of Radiation Oncology at Harvard Medical School

 Zeitman

Anything that moves us away from lengthy inconvenient treatment, radiation to the heart, can only be a good thing.  But if we’re going to give up something that’s been working very, very well for a long time we have to really kick the tyres and know that what we’re doing is as good as, if not superior.

 Porter

And looking at this trial at this stage my take is that it does appear equivalent to our current gold standard because we don’t know what’s going to happen over the next four to six years do we?

 Zeitman

Absolutely it does appear equivalent but as many oncologists remind us breast cancers often recur five years, 10 years, 15 years down the line.  So many are arguing that yes this is intriguing but it’s not enough yet to overturn what we’re currently doing.  If you just remove a lump – a lump of cancer – from the breast and just follow a lady, don’t give any radiation treatment at all, while the majority of recurrences occur right where the lump was certainly many women have recurrences elsewhere in their breast.  This new device that’s been developed just irradiates the area where the lump was and doesn’t irradiate any other part of the breast.  And many would predict that there will be an increased risk of recurrence when compared with whole breast radiation if you follow these women long enough.  So for many sceptics they don’t quite believe in their hearts that this device is going to be as good as conventional treatment.  But the surgeons are saying, on the other hand, we’ve got a randomised trial, best form of evidence, can’t do better than that.

 Porter

If the surgeons are for this in general then I mean is there some resistance, is that what you’re saying, in the oncologists’ camp?

 Zeitman

Yes there is some resistance, it’s in the oncologists’ camp, because they are – they’re very reluctant to give up on a treatment that’s worked so well for 30 years – whole breast radiation together with a lumpectomy – without convincing solid evidence.  And most believe that the results are premature.  Having said that if these results do mature, in the way they seem to be developing, then I think it will potentially be a game changer.

 Vaidya

Now the interesting thing about radiotherapy is this that if you look at trials of radiation and if you see what effect radiation has compared to no radiation you find that the difference in the local recurrence starts appearing in the first two or three years.  Most of it is over by three years and after five years the difference between the two groups remains the same however many years you follow.

 Porter

So you would hope that although the data’s not that old that actually this trend will continue and the local recurrence rates will remain the same?

 Vaidya

They may increase in both groups in a similar manner.  That is what all previous data has shown. 

 Porter

But local recurrence isn’t the only problem…

 Vaidya

No.

 Porter

…what about secondaries – I mean recurrence occurring elsewhere in the body?

 Vaidya

That has not been any different between these two groups.

 Porter

So that’s exactly the same?

 Vaidya

It’s exactly the same.  Breast cancer deaths in both groups is exactly the same.

 Porter

And what about outcomes in terms of the way that the breast looks, the cosmetic appearance?

 Vaidya

The cosmetic appearance is at least as good and in the first few years it’s better with intraoperative radiation.

 Sexton

My name’s Jenny Sexton and I’m 65 years old.

 Porter

What attracted you to this one shot approach?

 Sexton

I had a lumpectomy the size of a golf ball removed and you would not know with a magnifying glass that I’ve had anything done.  There’s no marks, there’s no burns, there’s no – even the surgical things, so you can’t see.  And in the other sense we live where I would have to do a 100 miles round trip daily for up to five weeks was just not on the cards.

 Porter

Not having to travel this 100 miles every day, which is a hell of a journey for anyone.

 Sexton

Well definitely, I mean great, who would want that?

 Porter

Well some cancer specialists it would seem. In the most part their reluctance is due to an understandable desire to see more proof but could conflicts of interest – both professional and financial – be a factor too?

 Anthony Zeitman:

 Zeitman

This always happens in medicine, I wish it didn’t but it does.  So if you consider a general radiation oncologist’s business, for want of a better term, his practice, his or her practice, maybe a quarter or a third of that is managing women with breast cancer.  So potentially there’s a big loss to their current practice, possibly even to their current income.  Surgeons, of course, stand to gain from this in terms of extending their field of practice and what you might call an economic opportunity.  So there is this little undercurrent that lies beneath the science.  I mean I personally do think that time is going to resolve this.  If this trial will stand up or it won’t.  It is likely that both sides will be winners and ultimately I think the patients will be winners.  I think this device is probably going to be very useful for some women with breast cancer but probably not all.  The oncologists will have to yield those patients to the surgeons.  But I think there’ll still be many women with many kinds of breast cancer who still require what you might call traditional treatment.  So I think evidence will ultimately cause us to draw a truce line somewhere in between where both camps would like it to be.

 Porter

And here in the UK there appears to be another obstacle. Swindon breast surgeon Nathan Coombs was part of the team behind the Targit study.

 Coombs

As a clinician I’ve got a moral responsibility to make sure I do no harm to my patients and that leaves me with a dilemma.  Targit is a treatment that’s certainly as safe, possibly safer, in terms of breast cancer treatment.  Can I actually not offer this treatment to my patients and force them to travel for standard external beam radiotherapy when a newer, as effective and safer treatment is actually available in the UK that is actually not being allowed to be given to our patients on the NHS?

 Porter

Well you say it’s not being allowed…

 Coombs

It’s not being funded.  So if a treatment’s not being funded, if I was to give this treatment, the hospital doesn’t get any money for it, which then means the hospital will be making a loss.  Unfortunately hospitals in the NHS have to operate as a business.  It hasn’t yet had the agreement of funding by NHS England.  As a person who treats people in the smaller semi-rural communities our patients need to travel to local radiotherapy centres to receive their treatment.  We actually did some calculations that if Targit IRT was used widely in the UK the number of miles that would be saved across the UK would be millions.  I can only see an advantage for giving Targit IRT rather than a disadvantage.

 Porter

Because that’s one of the tricky things with the NHS isn’t it, it’s good for patients, it’s good for Swindon Hospital, it’s good for you – you provide a better service – but it probably means it’s bad for somebody else because that business is not going their way and by business I mean the resources, the equipment, the expertise, the staff.

 Coombs

NHS England are being very cautious to make sure that they don’t want to open Pandora’s Box.  If this treatment was widely available there will be an impact of getting these machines available across the country and there will be a small cost implication for those hospitals and also they want to make sure it’s safe.  But what we do know that it is safe and when it is used it is cheaper than giving the standard treatment.

 Porter

We asked NHS England for an update on the situation and was sent this statement:

 Statement from NHS England

We are committed to broadening access to innovative and effective radiotherapy services as a key part of implementing the Cancer Strategy, which seeks to save an extra 30,000 lives by 2020.

 We have assessed intraoperative radiotherapy for early breast cancer previously, and await further evidence on its effectiveness and advantages over other forms of radiotherapy before reviewing our position.

 

 Whatever the final decision intraoperative radiotherapy will never be suitable for every woman but it is thought that as many as 20,000 could benefit from it every year in the UK if it were to be fully adopted by the NHS. As ever, more details on our website.

  Just time to tell you about next week’s programme which includes the latest developments in diagnosing asthma, and a radical new approach to treating the common skin complaint acne rosacea.  Join me then to find out more.

Broadcasts

Podcast