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>> Tom Treasure, MD, MD, FRCS, FRCP:
Now before it gets underway, and before I forget,
I'm going to acknowledge certain groups
who are fundamental to this work.
And first of all, on this slide, the Institute
of Cancer Research, which is the scientific clinical trial end
and research end of the Royal Marsden Hospital,
and the clinical trials unit at the Royal Brompton Hospital,
who have managed two trials which I'm going to talk about,
both of them funded by Cancer Research UK.
And also I'm going to use data which comes
from the Thames Cancer Registry, which is based within KCL
and is one of the,
is the largest cancer registry in Europe.
Now this is a rather ironic slide.
You can see what it is.
It's the two, two towers, and it's an advert for asbestos
from 1981, by which time the dangers of asbestos in terms
of lung disease
and in particular cancer were already well known,
and in a way, this is a sort of rear guard action,
and they're pointing out that asbestos is throughout the
building, throughout [inaudible] in insulation and pipe lagging
and central heating and everything else.
And already it was becoming known,
although probably not widely known,
that asbestos is the cause
of a particularly nasty cancer called mesothelioma.
Now this picture here is a combination of a CT scan,
an x-ray cut vertically, and a PET scan.
Now the, is there a pointer, or shall I con?
Yeah. Sorry.
I thought I was going to be able to use this [inaudible].
On this side, you can see the rib cage, the vertebrae.
These are the shoulders, the neck, the liver, and so on.
So this is a lung, and this is the lung on the healthy side.
On this side, this bright light is a PET scan,
which shows up an area of high metabolism, which is the cancer,
and you can see it's very extensive, surrounding
and encasing the lung, and that's mesothelioma.
Now this is a complicated slide that I'll take you through,
but it shows the relationship
between asbestos and mesothelioma.
Along the bottom here you can see from 1900
up to predictions going into 2040, 45 and so on.
This line, this yellow line is the amount of asbestos
that people were exposed to in this period through the 1940's
and up to about 1980, and the bars show the imports.
So that is asbestos peaking as a very valuable material
in building declining and being effectively banned
and highly regulated.
Then following, and the lag time is over 40 years,
these green spots are deaths from, male deaths,
and that's the majority from mesothelioma,
and the purple line is the prediction
of how that's likely to be followed.
So we found ourselves 15 years ago seeing that rise and knowing
that we had ahead of us a lot of patients coming
to us with mesothelioma.
Now I was working at Guy's Hospital at the time,
and that serves communities with the highest mesothelioma rates
in Great Britain, and you can see the dark blue areas
around the [inaudible],
which was shipbuilding areas and industrial areas.
The Plymouth and Portsmouth Naval Dock Yards and that area
of London where Guy's Hospital is is the site of the old docks,
commercial docks, but also the naval dock yards
down the midway, and those patients came to us
in increasing numbers.
The question for us as surgeons is what could we do about it.
Can we cure mesothelioma?
Well, attempts have been made by very radical operations
to do this in the 70's, and if you look at this area here,
you can see that this is a very extensive massive disease,
and to clear it, you have to, or the way it was done is
to remove the whole of the lung on this side,
but also the membrane around the heart, which is the pericardium,
the diaphragm, strip off the pleura from the chest wall,
and even then would you really clear it.
Well, initial operations were hazardous.
There were high death rates.
The cancer came back very quickly, but it seemed later
on that if it was combined with chemotherapy,
there were better results, and then adding in radiotherapy,
people began to claim that they were able to get longer survival
and maybe even cure it.
And this was the sort thing we were exposed to at the time.
I would have to tell you there were reservations
about this in Britain.
British surgeons didn't take it up with great enthusiasm,
but elsewhere, it was adopted, and we reached a situation
where there were publications claiming good results.
Our patients wanted to know why we couldn't offer it
and were raising the money to go abroad persuaded by this sort
of highly personalized information.
Well, faced with that dilemma,
we wanted to know what we should do.
And the first task was to seek the evidence, which we did
by formal systematic review,
and that was published in "Lancet" 2004.
It seemed to us that these were all retrospective studies,
relatively small groups of patients selected,
reported by enthusiasts, and in all cases,
the patients had completed their various multi modality
treatments, very often two or three treatments on top
of each other, and we did not believe we could see evidence
that the surgery was effective amongst that selected group
of patients, having notable treatments.
So we argued the case for a trial,
which we published in the PMJ.
Now to cut a very long and arduous story short,
we'll cut to the report of that study, which came out in the
"Lancet" 2011 last year.
Now this is a standard way of displaying survival data
if you're not familiar with it.
There's the passage of time along the bottom, six months,
12 months, 18 months, and then in percentage the proportion
of patients surviving, and this was a quite small study.
There was only 50 patients
in total depicted here in two groups.
So each downward notch is the death of a patient as they go
from all the patients entering down here to 18 months.
Now to go back, what happened prior to this was
that we saw patients who were potential candidates,
not only for the surgery but the radiotherapy and chemotherapy
that had to go with this package to try and match the results
that were being presented to us.
So all the patients had chemotherapy and re-evaluation
and further scans, and at this point, if they were regarded
as candidates for surgery [inaudible],
we then randomly allocated to one of two groups.
So you have two groups there of patients.
One group get the surgery, and the other don't.
Now the important thing is that this red line are the patients
who have the surgery and radiotherapy,
and they do considerably worse and the difference,
which is significant, by having the treatment rather than not.
Also important is that this red line actually when you look
at it is not dissimilar.
In fact, is quite similar to the published results.
The results were not that good,
and within the trial we were getting the same sort of results
as were being promulgated.
The important point was that we had control group of patients
who were randomly allocated to not have that operation,
who actually did better by not having it.
So that study was published last year, and at this point,
it's very important to thank colleagues, particularly
at Guy's but other hospitals around the country.
The trial team at the Marsden
and also the British Thoracic Oncology Group,
which brings together all the cancer specialists who deal
with cancer of the chest, mainly lung cancer, but also this sort
of cancer, who awarded us the lifetime achievement award only
last week, which for us is hugely appreciative
from our own colleagues because this was an extremely
difficult study.
Published in the same year was this book by Lionel Shriver.
Now Lionel Shriver wrote "We Need to Talk About Kevin",
and if you've not read that, heard about it,
or seen the film, you should.
It's fascinating, but she's also written this book,
which is about mesothelioma.
And it's based on truth in that a friend
of hers had mesothelioma, not in the lung but in the abdomen,
but the principles are really very much the same.
And in the same week or so, her husband decides to, and you,
this is no secret, this is all on the [inaudible] blurb
so I won't be spoiling the story for you.
To cash in his lifetime saving from his business
of a million dollars to use it in a more
or less altruistic form of retirement,
and they get the news that she has mesothelioma.
So they spend the next year
with the bank balance being eaten away, and towards the end,
the last consultation with the doctor goes like this,
and her husband says, "So what exactly did we buy?
How much time?"
The doctor says, "Oh, I bet we probably extended her life a
good three months," and I'm sorry, Dr. Goldman,
they were not a good three months.
And the point being made is that the quality of life
for this patient in that last year of her life was not
at all good, and nor is it for many patients
who have complex multi modality treatment.
Now, of course, if they are young and in their teens
or their 20's with lymphoma or leukemia,
and they have a terrible year but live for another 50 years,
it's not a bad deal, but these are older patients,
and we're very concerned about it,
and you might wonder how can a novelist put her finger on it
when the doctors count, well, of course,
novelists make things up, and she happens, I think,
to be right about this one, but they're not always right,
but she did happen to get this one well identified.
So why don't the doctors know?
Well, maybe they're just too close up to it.
They're seeing a group of patients
who they've looked after, and they report the ones
where they completed treatment, things went well,
they send in a report to the literature.
What they don't tell us about and, indeed, probably can't
because the records aren't kept in that way
to be accessed retrospectively,
patients who they thought they might make a start
on this treatment but fell by the wayside
for one reason or another.
The cancer progressed on chemotherapy,
or the patient didn't want it and so on.
So we don't know what happens to those patients.
They certainly never tell us in cohort studies
about all the other patients being considered
by the cancer committees, the tumor boards
who were potentially candidates for this surgery,
and none of them know what the overall burden of the disease is
in the population and how this group of patients fit in
and to what extent the representative.
By now, you'll recognize that this is [inaudible] work field,
and each of these figures is a little clay figure.
They're all the same in that they're made like clay
and molded in the hands of his team and have eyes that look
at you and so on, but they're all different, and that's one
of the problems that [inaudible].
Well, now, moving on from mesothelioma to cancer
of the colon, which is much more common.
Mesothelioma causes a couple of thousand deaths a year;
cancer of the colon 40,000 patients in a year,
and many of you will know patients
that have these common cancers.
The three common ones are lung, breast, and colon.
So the colon, the large bowel, large intestine.
A cancer which develops there is a serious matter.
Miserable time perhaps with constipation and diarrhea
and eventually maybe obstruction.
The cancer may block off the bowel completely.
It may erode into other organs and nasty leakages
and fistulas occur and terrible peritonitis.
So you would want a surgeon to deal with that for you
and overcome that immediate problem.
And highly successful, very specialized surgeons deal
with that, and about half the patients with cancer
of the colon are cured, but in the other half,
the disease comes back, or there are secondary deposits,
particularly in the liver and the lung
which cause further trouble.
Now the question here in this much commoner cancer is does
further, again, the matter of advanced aggressive surgery
to remove the secondary cancer in the lung give any benefit.
Now, so that you can keep up in places completely new word
to you - metastasis is the name
for a secondary deposit of cancer.
and, hence, metastasectomy is the operation to remove it.
You will see that coming up.
Again, we needed to seek the evidence,
and here I should give acknowledgement
to the electronic library here,
which when you're doing this sort
of searching work is just fantastic in being able to look
up the world's literature anywhere I happen to be
in the world pretty well.
Don't have to be at my desk here, but also the roles
in society of medicine because some of the things we need
to look at have been published long time ago and are
in rarely read journals down in the basement.
So acknowledgement to those.
Now, this picture, this tangled web is a citation
network analysis.
And, in fact, [inaudible], [laughs] who's here
in the audience, helped us with this and made this picture.
All around the edge, all those circles with numbers
in them are published papers,
and there's a total of 72 of them.
They are all examples of follow-up studies of removal
of lung metastasis in,
with intent to complete cure of a colon cancer.
The lines between them are citations.
So in any scientific or medical paper, as many of you will know,
that at the end of the paper will be a list of 10, 15, 20,
30 articles, other articles to which the authors refer.
So what you can see here is these are all reporting the same
thing over this period of 1971 to 2007, very similar reports,
and they're all [inaudible] each other.
Sort of a frenzy of mutual citation.
And this is really quite typical of what happens
because there is freedom for the authors to quote what they want
to quote, and they will, of course, quote things
that support their view, but that's on the edge here.
There are these four which are papers who don't agree
with them, but they don't get much of a look in.
Now here's one, for example, and this was written by this man,
Torkel Aberg, in 1980, and he asks is this a fact or fiction.
Because he says it's been assumed in all these papers,
assumed, implied, or claimed that were it not
for the operation, survival would be nil,
and he says, well, is that true.
Would some of these patients have survived?
Is it as extreme as that?
That the ones who survive are cured by it.
Now he's a mainstream surgeon, thoracic,
cardiothoracic surgeon himself.
Worked in [inaudible] and was the secretary for years
of our European association, and he was the president for me.
So I know him very well, and he wrote this a long time ago.
So we took that question, we had a look at it, and this is where,
done by Carl, and particularly by Martin Upley.
Now here, again, you've got one of these graphs,
and purple line is of patients with colorectal cancer
who at the time of presentation have metastases,
and that is their survival and data
from the Thames Cancer Registry.
And there at 60 months or five years is the typical time
when people report survival data -
five years' survival data is a pretty typical number to give
for cancers, and it's 40 percent.
Well, first of all, it isn't 0.
It happens to be ten percent at five years going down to
about five percent later, but, still, this would be a good game
if it were all attributable to the surgery,
but there are a couple of problems with that comparison.
In that network analysis that we did,
we did a formal systematic review of 51 reports
from which we could get data,
three and a half thousand patients, and, overall,
fairly consistent message, but 40 percent survival
at five years, but the patients didn't have their operation
at the same time as the colon cancer.
On average, it was three years later.
So, in fact, that steep declining path of the curve is
to some extent irrelevant in this comparison
because to enter this group of patients
of the 40 percent survival,
they have on average already been free
from dying for three years.
So the bit of the curve that's more relevant is
that flatter bit, but there's a bit more to it than that.
Those purple line patients are ones who had metastases right
at the outset, but most patients who have this surgery looked
as though they were cured at the beginning,
and the metastases come back later.
Now the stages, the blue line that patients
with the least severe invasive cancer at the time of operation
and on down ones that go through the wall of bowel,
ones that are tending to spread out into the tissues,
and only the ones in the purple line already have spread.
So if you now make a comparison, taking a group of patients
which are similar in that respect to the ones
in the series, it looks rather different.
So now you reset to 0, and that's the shape of the curve.
Now they're similar in only two respects.
That there has been an interval before the metastasectomy was
performed, and they have the same sort of mixture of severity
of the primary cancer.
They may be different in many other ways,
but it certainly gives you a very different picture
of the comparison which is implicit in those 72 papers
which I showed you and goes largely unquestioned.
Martin and the, his coworkers doing that with us looked
at two papers for this in the big population of patients,
but at 150, they both have this 40 percent five-year survival.
One from America and the other one from Japan and published
in the time when there was this great flurry of activity
in this form of surgery then through the 1990's.
And for both of them, if you looked at a group of patients
from the Thames Cancer Registry who resembled them at least
in those two respects, quite a lot more are alive
than the nil, which is assumed.
So we have a problem.
How to find out what might have happened
to these selected patients within these studies who appear
to do well if they had not been operated.
Very much as I showed you for mesothelioma
where we've actually done that study.
Now the question is is this survival rate,
are they attributable to surgery?
Did the surgery cause them to be alive, or were there features
of those selected for surgery and selection
for surgery which is the effect?
Now there are two favorable features which we'll able
to get out of those papers.
The number of metastases
and usually the paper will say whether there was just one,
three, eight, many.
Usually one, two, and three, that's the typical sort
of thing, and they will also know the interval, and in study
after study favorable features or fewer metastases
and a longer interval.
Now this is a way of thinking about that,
a formal thought experiment.
And here there are 300 little people of whom 25 are green,
and that would, that's five percent,
and they are saying natural survivors who would come
out of the Thames Cancer Registry and be alive,
and they're scattered in amongst them.
But now we've done a bit of sorting out.
Those down on the bottom have many metastases
and then upwards, single metastases,
and along the other direction,
they go from very short intervals to longer intervals.
This is just made up.
Just a way of talking about it, but that's exactly what you do
because these are the features on which patients are selected
for this form of surgery.
Well, if you then operate on the ones in the top corner,
which is about eight percent, in reality the number
of patients selected are less than that.
They're down around five, four percent.
So this is sort of being generous, but just supposing 10
of those 15 natural survivors are amongst the 25
that you have selected for surgery,
you would get your 40 percent.
So our view of this is
that without doing a randomized trial, we won't know.
That's the cover of a rather nice book, which is for those
who are not, are interested but not experts in medical research,
spells out the issues to do with testing treatment,
and they're a group of doctors that [inaudible] and so
on who've produced this nice book.
On the other side, you see the problems of these.
That the cancers are highly variable.
Cancers don't behave in a consistent way.
Some are extremely [inaudible], and some are very aggressive.
Also the treatments are not consistent.
The treatment sort of responds to the patient or the point
of view of the doctor, and very often in multiple treatments.
And out of all that variation, it's difficult
for an individual doctor to see the signal from the noise,
and that's the argument for having a randomized trial.
And we're, we're [inaudible] started.
It's called the [inaudible] trial,
and that's for pulmonary metastasis [inaudible]
and colorectal cancer, and you can see why we go
for these nifty little algorithms [laughs]
like [inaudible].
But my title had the limit set by nature,
and this is where the phrase comes from.
This is a lovely book given to me some time ago as a present,
and from Arthur Holman, who's a cardiologist in this hospital.
We, maybe somebody even knows him.
Eighteen ninety-six he wrote this.
"Surgery of the heart has probably reached the limit set
by nature to all surgery.
No new method and no new discovery can overcome the
natural difficulties of which it presents."
And it's a favorite quotation, which heart surgeons
and [inaudible] thoracic surgeons put up at the beginning
of their lectures and say [inaudible] see.
See how good we are.
That's what they thought.
I put it up as a little memento [inaudible].
He was wrong.
Very good man, but he was wrong.
I could be just as wrong.
So when I tell you that I think there are limits set
by nature, it may not be true.
Maybe surgeons of the future will be able
to do things like [inaudible].
I don't think so, otherwise I wouldn't be giving you this
lecture, but one always has to have this element of uncertainly
about whether we really know it or presenting this
in the department where there are physicists around,
they fished out this.
Didn't know about this.
Albert Abraham Michelson in 1903, much the same time, said,
"The most important fundamental laws and facts
of physical science have all been discovered,
and these are now so firmly established that the possibility
of their ever being supplemented [inaudible] new discoveries is
exceedingly remote."
I wonder if they know about that in [inaudible], but anyway.
That, so it's not just doctors.
It's other people as well have this impression
that where we are now is the right place to be.
We've got it all sorted out.
What more do we need to know?
So my conclusions for you are that the history
of medicine includes many retreats, and it isn't just
because people find a better treatment.
It's quite often because they realize eventually,
maybe after hundreds of years
that the things they aren't doing are not only not helpful
but actually harmful, and I think the surgery
for mesothelioma, which I've shown you,
fits into that category.
Also, doing more, wanting to be seen
to be active may not be better than doing less.
There are times to just back off and do less.
Very, very hard, and that's hard for patients and for doctors
to face, but with secured knowledge,
you can at least give a firm view
that less is better than more.
And also the questions become more and more complicated.
There are things in medicine which aren't very clear cut.
If you have a cataract,
and a skilled eye surgeon operates on you, you can see.
If you have an extremely arthritic hip,
and a good orthopedic surgeon looks after you, you can walk.
But when you've got diseases of vary, varying progression
and with multiple treatments, it's more difficult to see that.
And just because questions are complicated doesn't mean you
should give that form or sort of make it up as we go along.
We need plain answers, and that's why some
of these trials are actually very simple,
the pragmatic trials.
We'll do this, and we'll do that,
and the decision will be made at random.
So, finally, thanks to many colleagues who've contributed
to these studies, and to many colleagues
who haven't necessarily agreed with me
as I've gone along debating these things,
because the process of arguing to
and fro helps clarify what the real issues are.
So I'm grateful to them, too.
But also to many past, present, and future patients willing
to be treated within trials, and we're grateful to them,
but also I think it's worth noting
that there should be some sense of duty in that
because the good treatments that we give now rely
on patients previously who were willing to go into studies.
To have studies for the future relies on people to willingly go
into studies now, and, of course, they should be protected
by good regulation and good science
and not reckless experimentation,
but without people being in the studies now,
we will not know for the future.
So thank you, very much.
[ Applause ]
>> Thank you very much, Professor Treasure.
I think we have time for a couple of questions
if there are any in the audience.
[ Pause ]
[ Inaudible Audience Response ]
>> There's a microphone coming your way.
>> Tom Treasure, MD, MD, FRCS, FRCP:
There's a microphone coming, yes.
I can hear you, but it's so that the, that it's recorded and -
>> Have you ever done any research as to whether surgery
without chemotherapy and radiotherapy are successful?
>> Tom Treasure, MD, MD, FRCS, FRCP: Oh, oh, yes.
Not personally, but surgery
for cancer was practiced a long time before it was ever combined
with chemotherapy and radiotherapy.
And if you have a cancer which is located in one place,
in my case it's lung cancer, and it's well within the lung,
hasn't yet spread through the blood or the lymphatics,
and you take out that portion of the lung,
you can cure the cancer completely, and that, certainly,
well, for many cases of colon cancer.
Now chemotherapy goes
in the blood stream and goes everywhere.
So it's a means of tackling cancer which is disseminated,
which is quite beyond the reach of a surgeon,
this microscoping and it's everywhere.
Increasingly, the two are put together in combinations,
and those combinations have to be studied in randomized trials,
or you can't see the wood for the trees.
So yes. Isolated surgery has been studied
and known to be effective.
The combinations must be.
Not as often as some of us would like to see
of those combinations being tested properly,
but the straight answer is yes, they have been.
[ Pause ]
[ Background Noise ]
>> Do you think that meat and the consumption
of meat contributes to the acquisition of cancer
because I've noticed that vegetarians when they sort
of get older, they don't seem to get any or as many incidences.
And eating fruit and vegetables isn't just a sort of merry line,
but is, contributes to good health and exercise?
>> Tom Treasure, MD, MD, FRCS, FRCP:
I can't give you a clear answer to that.
The best understanding
of cancers are just as I showed you.
Asbestos and mesothelioma are linked, but so is smoking.
If you could extract the data, you could show the same.
So smoking is clearly pro-cancer.
Now there's a great deal of interest in nourishment,
which foods are favorable.
There seem to be very compelling reasons
to make sure we have adequate vegetables, adequate roughage,
and so on, but I don't think there's a simple cause
and effect, but I don't know.
It's not my area, but it's certainly not a clear one.
>> Certainly, do you think there's, exercise, for instance.
Daily exercise like, certainly, sort of daily exercise
and swimming and all of that sort of thing on a daily basis,
that must help keep the body exempt from such things -
>> Tom Treasure, MD, MD, FRCS, FRCP: Well,
I think it keeps the body fit, but there's no real reason
to think it's [inaudible] in cancer.
I think it's quite important to not be, one of the things
that goes, that I don't like to see
with cancer patients is a sort
of you brought it on yourself attitude.
If you'd only done this, or you'd only done that,
this wouldn't have happened.
I don't think that's very fair.
[laughs] I think you, because I don't think it's even,
it's fair even if they, even
if you don't think they've lived very healthily,
you still look after them.
So it's not an area where I think it's useful
in the care of patients.
>> [Inaudible] I was thinking more
of people conducting their lives to -
>> Tom Treasure, MD, MD, FRCS, FRCP: Oh, I agree.
Yes, yes. Absolutely.
Absolutely.
We should all lead better lives and stay fit.
No, it's not, I don't disagree with the sentiment at all,
but the scientific point is there a proven link,
not that I'm really aware of, and I think I'd know.
>> I think these are probably very wise words to end on,
[laughter] if you agree with me.
Thank you very much, all, for being here today, and joining me
in thanking Professor Treasure again for a great talk.
[ Applause ]