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Is the UK falling behind on lung cancer treatment?

Bristol-Myers Squibb developed the questions for this interview, but had no input into the responses or editorial write-up. BMS did check the interview for medical accuracy and compliance with relevant regulations.

Dr Mick Peake, Consultant and Senior Lecturer in Respiratory Medicine for the University Hospitals of Leicester, discusses how the UK compares to Europe in treating lung cancer, the innovations that are improving outcomes and the areas where change and investment is needed.

What is the current outlook for lung cancer patients in the UK? Is it in line with the best countries in Europe, as specified in NHS England’s Cancer Strategy?

“There's no doubt that the UK has been at the bottom of the pile in terms of the one-year survival and five-year survival. The main problem with lung cancer is that by the time they [patients] get to specialist care, the majority of patients have an advanced and, in a sense, incurable disease.

The patients that are at stages 3B and 4 are by far the biggest group, and these all have, essentially, an incurable disease. Some of them, though, will survive a long time. If we look at the very early stages of the disease, stage 1, you'd expect 75 per cent five-year survival - so if you picked up all lung cancers at stage 1, you'd probably increase five-year survival by 75 per cent; whereas if you go back to the mid-2000s, it was about six per cent in Britain. 

The percentage of people, who had stage 1 disease in England in 2014, was only 13 per cent, and only another eight per cent had stage 2. So the rest of them had stage 3 or 4. We don't have contemporaneous data on stage distribution for other parts of the world but we know that if you go back a few years in Scandinavia – particularly in Sweden and Norway – they were getting 18 per cent and 19 per cent stage 1. It’s still not fantastic, but it’s better than the UK.

So we've got a problem with late presentation. The problem I have now in Public Health England is in trying to increase public awareness, primary care awareness, in trying to get people to go to the doctor earlier.”


How can we improve survival rates for lung cancer? 

“The big problem at the moment is that 75 per cent plus have a stage 3 or 4 disease. A small percentage of those are curable with a combination of chemotherapy and radiotherapy. It may be that immunotherapy has a part to play in some of those when they recur. But the big problem with all the industry interests is in the stage 3B and 4, where we're giving essentially palliative chemotherapy.

We've gradually improved the impact of this palliative chemotherapy. For example, when we first looked at the median survival from diagnosis in 1995, it was just under three months. It's now about six to eight months, and in patients that are fit and well and get access to chemotherapy and a targeting agent and possibly immunotherapy, it's getting up to a median survival of 12-18 months.

But the number who get beyond two or three years is still very small. Our recent work on one-year survival by stage for England in 2014 showed that we had made big inroads into stage 1 and 2, and some in stage 3, but we haven't really made much impact on stage 4.”


You’ve worked with lung cancer patients for over 20 years. What have been the main breakthroughs in cancer care during this period?  

“Immunotherapy, for some people, has a remarkable effect. For small numbers, a lot of tumour disappears - sometimes completely, although not very often. When you look at the survival curves, which describe the proportion of patients alive over time, the curves fall; and in almost all clinical trials for advanced disease they eventually reach virtually zero, after two or three years.

What you see with immunotherapy is a plateau, from that declining curve, with around 20 per cent of patients with advanced disease, who have already had chemo and other treatments, living two or three years, and we don't know what the long-term survival of those people is. We know that a small number of them do really well. And we don't really know yet how to define who's going to respond well or not. 

The national lung cancer audit has been feeding back information to clinical teams for more than 20 years to show them how they perform. The biggest gap, in the 90s and early 2000s was in the proportion of people who had an operation. That's the treatment that's going to lead to cure, at the moment. If you can operate on an early-stage disease then you've got a high chance of long-term cure, and over the last 10 years, the number of people getting an operation has more than doubled. Our estimates for the five-year survival of 2013 patients put the five-year survival at 16 per cent.

I was saying earlier that we running at seven to eight per cent five-year survival in the 90s and early 2000s. So we appear to have made a major impact on five-year survival, going up to about 16 per cent. The proportion that are alive at a year has gone up from 22 per cent to about 39 per cent, so we've almost doubled the one-year survival. The bulk of that has been due to better services, better referral to specialists, more early diagnoses, and more people getting an operation. But we're still stuck with this large cohort of people we can't cure. 

The early trials were done with people who had already had one or two lines of chemotherapy and even in that group we were getting 20 per cent of people alive at two years, which is extraordinary. We'd never seen that in people who had advanced disease, who had already had first and sometimes second-line treatment, then going on to have another treatment.

It is a paradigm shift, I think, particularly in second-line or third-line treatments, when they've gone through conventional treatments. It's much less toxic than conventional chemotherapy in the second line context, because by the time people get to second or third-line chemotherapy, they are from a relatively elderly population.

Still, we don't yet know how to identify that 20 per cent. We don't know how long to keep the treatment on for, so you've got people who are doing really well, and two years on - what do you do? Do you stop the drug?”


Are sufficient resources being invested in lung cancer?

“The R&D costs for any new drug now are huge. You're talking about something like a billion dollars to develop an agent like this, with all the research and the safety efficacy. Companies have a relatively short period on the patent. I don't know if the actual production costs are as high.

The situation is that America can spend more, the market in America is hugely bigger, they're not controlled by NICE, and so in a way, the company can just say well, ignore the UK. It's too expensive to get it through, the numbers of patients who will get the drug in the population are small and interference from NICE means that the return on that market, if we reduce it in that market, then we'd have to reduce it in America, because we have to have parity. So they basically set the price based on the American market. But I don't know why they're so expensive to produce. 

The problem with NICE is that the way they assess cancer drugs is based on very old types of research. In the past, they would take chemotherapy A and chemotherapy B in first-line treatment, and they would look at the survival rates in a randomised control trial. And they would work out how much the drug costs, and what the survival benefit is. You've now got a situation where people may be getting three or four lines of treatment, and you can't make an A versus B comparison.

Clearly, this country cannot afford to give every lung cancer patient these drugs. You have to look at the bigger public health issue. I don't think we should just pump hundreds of millions extra into these drugs; you've got to look at the bigger picture. But I think there has to be a sensible and rational basis for how the government and industry come up with whether drugs are made available in England. 

I think we need a much more contemporary way of trying to work out what the health and economic benefits are. The current paradigm doesn't, in my view, fit the nature of these drugs. I think industry has a responsibility to work with the government. In virtually every area of cancer medicine, immunotherapy has the potential to play a part, and possibly a big part, once we identify which patients are going to respond. There needs to be some sort of high-level group, which brings industry, government and academic people together to think about how the UK can afford immunotherapy for the correct individuals.” 


March 2017

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Love a good box set? Then you should watch the Snooker World Championships

The game relies on a steady arm, which relies on a steady nerve. The result is a slow creeping tension needs time and space to be properly enjoyed and endured. 

People are lazy and people are impatient. This has always been so – just ask Moses or his rock – but as illustrated by kindly old Yahweh, in those days they could not simply answer those impulses and stroll on.

Nowadays, that is no longer so. Twitter, YouTube and listicles reflect a desire for complex and involved issues, expansive and nuanced sports – what we might term quality – to be condensed into easily digestible morsels for effort-free enjoyment.

There is, though, one notable exception to this trend: the box set. Pursuing a novelistic, literary sensibility, it credits its audience with the power of sentience and tells riveting stories slowly, unfolding things in whichever manner that it is best for them to unfold.

In the first episode of the first series of The Sopranos, we hear Tony demean his wife Carmela's irritation with him via the phrase “always with the drama”; in the seventh episode of the first series we see his mother do likewise to his father; and in the 21st and final episode of the sixth and final series, his son uses it on Carmela. It is precisely this richness and this care that makes The Sopranos not only the finest TV show ever made, but the finest artefact that contemporary society has to offer. It forces us to think, try and feel.

We have two principal methods of consuming art of this ilk - weekly episode, or week-long binge. The former allows for anticipation and contemplation, worthy pursuits both, but of an entirely different order to the immersion and obsession offered by the latter. Who, when watching the Wire, didn’t find themselves agreeing that trudat, it's time to reup the dishwasher salt, but we’ve run out, ain’t no thing. Losing yourself in another world is rare, likewise excitement at where your mind is going next.

In a sporting context, this can only be achieved via World Championship snooker. Because snooker is a simple, repetitive game, it is absorbing very quickly, its run of play faithfully reflected by the score.

But the Worlds are special. The first round is played over ten frames – as many as the final in the next most prestigious competition – and rather than the usual week, it lasts for 17 magical days, from morning until night. This bestows upon us the opportunity to, figuratively at least, put away our lives and concentrate. Of course, work and family still exist, but only in the context of the snooker and without anything like the same intensity. There is no joy on earth like watching the BBC’s shot of the championship compilation to discover that not only did you see most of them live, but that you have successfully predicted the shortlist.

It is true that people competing at anything provides compelling drama, emotion, pathos and bathos - the Olympics proves this every four years. But there is something uniquely nourishing about longform snooker, which is why it has sustained for decades without significant alteration.

The game relies on a steady arm, which relies on a steady nerve. The result is a slow creeping tension needs time and space to be properly enjoyed and endured. Most frequently, snooker is grouped with darts as a non-athletic sport, instead testing fine motor skills and the ability to calculate angles, velocity and forthcoming shots. However, its tempo and depth is more similar to Test cricket – except snooker trusts so much in its magnificence that it refuses to compromise the values which underpin it.

Alfred Hitchcock once explained that if two people are talking and a bomb explodes without warning, it constitutes surprise; but if two people are talking and all the while a ticking bomb is visible under the table, it constitutes suspense. “In these conditions,” he said, “The same innocuous conversation becomes fascinating because the public is participating in the scene. The audience is longing to warn the characters on the screen: ‘You shouldn't be talking about such trivial matters. There is a bomb beneath you and it is about to explode!’”

Such is snooker. In more or less every break, there will at some point be at least one difficult shot, loss of position or bad contact – and there will always be pressure. Add to that the broken flow of things – time spent waiting for the balls to stop, time spent prowling around the table, time spent sizing up the table, time spent cleaning the white, time spent waiting for a turn – and the ability for things to go wrong is constantly in contemplation.

All the more so in Sheffield’s Crucible Theatre. This venue, in its 40th year of hosting the competition, is elemental to its success. Place is crucial to storytelling, and even the word “Crucible” – whether “a ceramic or metal container in which metals or other substances may be melted or subjected to very high temperatures,” “a situation of severe trial”, or Arthur Miller’s searing play – conjures images of destruction, injustice and nakedness. And the actual Crucible is perhaps the most atmospheric arena in sport - intimate, quiet, and home to a legendarily knowledgeable audience, able to calculate when a player has secured a frame simply by listening to commentary through an earpiece and applauding as soon as the information is communicated to them.

To temper the stress, snooker is also something incredibly comforting. This is partly rooted in its scheduling. Working day and late-night sport is illicit and conspiratorial, while its presence in revision season has entire cohorts committing to “just one more quick frame”, and “just one more quick spliff”. But most powerfully of all, world championship snooker triggers memory and nostalgia, a rare example of something that hasn’t changed, as captivating now as it was in childhood.

This wistfulness is complemented by sensory pleasure of the lushest order. The colours of both baize and balls are the brightest, most engaging iterations imaginable, while the click of cue on ball, the clunk of ball on ball and the clack of ball on pocket is deep and musical; omnipresent and predictable, they combine for a soundtrack that one might play to a baby in the womb, instead of whale music or Megadeth.

Repeating rhythms are also set by the commentators, former players of many years standing. As is natural with extended coverage of repetitive-action games, there are numerous phrases that recur:

“We all love these tactical frames, but the players are so good nowadays that one mistake and your opponent’s in, so here he is, looking to win the frame at one visit ... and it’s there, right in the heart of the pocket for frame and match! But where’s the cue ball going! it really is amazing what can happen in the game of snooker, especially when we’re down to this one-table situation.”

But as omniscient narrators, the same men also provide actual insight, alerting us to options and eventualities of which we would otherwise be ignorant. Snooker is a simple game but geometry and physics are complicated, so an expert eye is required to explain them intelligibly; it is done with a winning combination of levity and sincerity.

The only essential way in which snooker is different is the standard of play. The first round of this year’s draw featured eight past winners, only two of whom have made it to the last four, and there were three second-round games that were plausible finals.

And just as literary fiction is as much about character as plot, so too is snooker. Nothing makes you feel you know someone like studying them over years at moments of elation and desolation, pressure and release, punctuated by TV confessions of guilty pleasures, such as foot massages, and bucket list contents, such as naked bungee jumping.

It is probably true that there are not as many “characters” in the game as once there were, but there are just as many characters, all of whom are part of that tradition. And because players play throughout their adult life, able to establish their personalities, in unforgiving close-up, over a number of years, they need not be bombastic to tell compelling stories, growing and undergoing change in the same way as Dorothea Brooke or Paulie Gualtieri.

Of no one is this more evident that Ding Junhui, runner-up last year and current semi-finalist this; though he is only 30, we have been watching him almost half his life. In 2007, he reached the final of the Masters tournament, in which he faced Ronnie O’Sullivan, the most naturally talented player ever to pick up a cue – TMNTPETPUAC for short. The crowd were, to be charitable, being boisterous, and to be honest, being pricks, and at the same time, O’Sullivan was playing monumentally well. So at the mid-session interval, Ding left the arena in tears and O’Sullivan took his arm in consolation; then when Ding beat O’Sullivan in this year’s quarter-final, he rested his head on O’Sullivan’s shoulder and exchanged words of encouragement for words of respect. It was beautiful, it was particular, and it was snooker.

Currently, Ding trails Mark Selby, the “Jester from Leicester” – a lucky escape, considering other rhyming nouns - in their best of 33 encounter. Given a champion poised to move from defending to dominant, the likelihood is that Ding will remain the best player never to win the game’s biggest prize for another year.

Meanwhile, the other semi-final pits Barry Hawkins, a finalist in 2013, against John Higgins, an undisputed great and three-time champion. Higgins looks likely to progress, and though whoever wins through will be an outsider, both are eminently capable of taking the title. Which is to say that, this weekend, Planet Earth has no entertainment more thrilling, challenging and enriching than events at the Crucible Theatre, Sheffield.

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