My last blog post was about alternative medicine in cancer treatment. That piece was about patients who refuse all other treatment, and thankfully that is still a relatively rare occurrence. Usually, patients use alternative medicine alongside their regular treatment. As a result, studying patients who refuse all regular treatment isn't necessarily the most informative thing.Because of this distinction, researchers from Yale decided to have a look at patients who do this, and they published their results this month. It is not encouraging reading.The research showed that if patients used alternative medicine at the same time as conventional medicine, they were twice as likely to die in the 5 years after diagnosis. I will get into the details and the numbers below, but first I want to repeat that statement. If patients used alternative medicine at the same time as conventional medicine, they were twice as likely to die in the 5 years after diagnosis. That is a shocking toll.Before I get into the study itself, I want to briefly explain this result. Essentially, if someone uses alternative medicine, they are more likely to refuse other parts of the treatment. So this terrible loss of life is probably not because a specific alternative medicine was causing a problem, but because the belief in pseudoscience has corroded and undercut the public’s trust in medicine. People believe that their alternative treatment is viable replacement for conventional therapy.This belief has not sprung out of nowhere; an entire industry has been built on the idea that medicine is “toxic”, and that if something is “natural” it is automatically better for you.I know so many people who use alternative medicine, from acupuncture, to supplements, to homeopathy, and they often say “what’s the harm?”. Well, this is the harm. Because of the normalisation of this kind of thinking, patients are making bad medical decisions, and are dying as a result. I will say it again: patients who used alternative medicine at the same time as conventional medicine were twice as likely to die in the 5 years after diagnosis.So what does the science actually tell us? Research from a few years ago showed that if someone uses alternative medicine, they are more likely to skip certain parts of their treatment. However, that study didn’t look at how this impacted their survival. This new paper takes that finding and looked at a larger population of patients to see if the use of alternative medicine alongside conventional treatment had any affect (good or bad) on cancer.Firstly, the authors confirmed that in their population of patients, those who used alternative medicine were far more likely to refuse or skip part of their treatment. This included surgery, radiotherapy, chemotherapy and hormone therapy.For example, 7% of patients who used alternative medicine refused surgery, while only 0.1% of other patients did. 34% of alternative medicine using patients refused part of their chemotherapy, while only 3% of other patients did. In a way, this is understandable: these treatments are hard, and make people feel awful. If you already believe that your side effect free alternative medicine is a viable replacement for your chemo, then skipping a round of chemo doesn’t seem like that big a deal.Just to be clear, interventions like surgery, radiotherapy or chemotherapy are not used because we think they improve survival; they are used because we know it. Huge numbers of clinical trials have been done to figure out what allows patients to live longer, and these treatments do that. And refusing some of these seems to be what is doing the damage in patients taking alternative medicine.There is not much more I can really say about this study, apart from the usual caveats. A lot of patients lie to their doctors about their use of alternative medicine, so that could be a confounding factor. The authors were very strict with their criteria, so as a result, the study was relative small, with only 258 alternative medicine-using patients. That being said, it is the biggest study we have on the topic, and the analysis was very rigorous.What this study really shows is the harm that the “natural” industry is doing. Vaccination rates are falling all around the western world. Species are being wiped out because of the popularity of traditional Chinese medicine. But perhaps most damagingly, a third of the American population regularly use alternative medicine without any evidence that is has any effect, spending nearly $200 billion in the process. With such a huge number of people using it, and with the credulous treatment it receives in Hollywood and other media, it is no wonder that people assume it works. It has been marketed and accepted by a large number of people as a true alternative to medicine, and as a result, people are dying for no reason.This is why it is so important to call out pseudoscience when it comes up. We live in a world where medicine is advancing on a daily basis. We can live longer, healthier lives, but people are increasingly taking that for granted and turning towards pseudoscientific ideas, because they are more "natural". The reality is that the more people who understand that alternative medicine does nothing, the better.
Alternative medicine and cancer survival
I often wonder just how much I annoy people when the topic of alternative medicine (alt med) comes up. In general, if someone says something I don’t agree with, I let it slide. When it comes to alt med, however, I don’t seem to have the same restraint. It’s unfortunate really, as it comes up surprisingly often, and my position comes across as pretty extreme.People ask “What’s the harm?”, and point out that “Even if it doesn’t do anything, people feel better having tried it”. I empathise with this position, but completely disagree. The point I try to make is that if we accept the use of alt med, we legitimize it, making people more likely to choose it over conventional medicine.
The focus of this post is cancer patients who put all their trust in alt med. While it's true that most people use alt med alongside real medicine, the popularity of, and belief in, the alt med movement means that it is inevitable that some people will ignore mainstream medicine in favour of alternatives.Unfortunately this does happen, and it happens regularly enough for us to study it. A few months ago, researchers from Yale published a paper looking into the outcomes for cancer patients who chose alt med over conventional treatment.The authors chose four types of cancer to look at: breast, prostate, lung and bowel. Additionally, they chose patients who had early stage disease, so had a good chance of surviving their cancer.Before I get on to the results of their study, one interesting thing to note is that the researchers show that the patients who rejected conventional treatment were more likely to be younger, healthier, more highly educated, and female. These are the patients who would be expected to have better outcomes than other cancer patients, to survive longer and to have fewer complications. However, that is not what the researchers found.Unsurprisingly, the patients who chose alternative medicine were far more likely to die from their cancer than those who didn’t. In the case of breast cancer, alt med users were nearly 6-times as likely to die. In colorectal cancer they were 5-times as likely. In lung cancer they were twice as likely. To put it simply, choosing alternative medicine above conventional therapy kills cancer patients.So, if 100 women with breast cancer were on conventional therapy, 13 would be expected to be killed by their cancer in the 5 years after diagnosis. If the same women were on alternative medicine instead, 41 of them would be expected to be killed over the same time. It is a damning example of the damage alt med can do.
As always, there are a few caveats with this study. One is that these patients completely rejected conventional therapy. Patients who combined it with conventional therapy were included in the conventional arm, so this study can't say anything about the benefits/damage of that situation.It is also likely that these numbers quoted above are an underestimation. Patients who started using alternative medicine, but switched to conventional therapy (when they realise it was not working) will have been counted in the conventional therapy group, meaning that in reality the use of alt med is probably doing even more damage than described in this paper.This all brings me back to my original point. When people give alt med a sheen of validity by claiming it works, it starts to be seen as a true alternative to our tried and tested treatments. The reality is that it simply isn't. As long as it has some legitimacy, a proportion of the population will use it instead of real medicine, at best wasting money, and at worst seriously damaging their own health. I argue with people about alt med because if I don’t, I feel like I am tacitly agreeing that it has some clinical use, when I know it is not true.To paraphrase an old saying, you know what they call alternative medicine that has been shown to work? MEDICINE. And real medicine saves lives.
How improved cancer screening can make us think we are doing better than we really are
This blog post is a follow on from this post I wrote about cancer survival, and is about some really interesting quirks we encounter when we try to study it. These problems arise when we increase our ability to detect the cancer at earlier stages.
Lead time bias
The first of these is known as lead time bias. Because of better technology, we can now diagnose cancer earlier. So imagine a case where a new screening technique lets us catch a cancer 1 year earlier. The catch is that no matter how early we catch it, in this case the disease is going to progress and ultimately kill the patient.
So before the introduction of this new technology the patient might only survive 1 year after diagnosis, because we are catching it late. After the introduction, we can now catch the disease early, and the patient will survives 2 years after diagnosis.
If we were just looking at the numbers, we might think that we are making significant progress with this disease, because patients are now surviving for 2 years rather than just 1. However, we have done nothing to increase the patient's lifespan. If we hadn’t caught it at all, the patient would have died on the same day.This is known as lead time bias. Because we are catching a disease earlier, it can look like patients are surviving longer, when in fact they are not. It is an easy mistake to make, but a very important bias to consider when we are talking about cancer survival.
Length time bias
The second problem appears when you realize that if we detect a cancer early, it is possible that we are detecting a cancer that might never have progressed at all. It isn't well-known, but there are cancers that never progress to a dangerous level. If we look at autopsies, nearly half of all men have prostate cancer when they die. However, only a small proportion of them actually die from prostate cancer. The rest have the cancer, but it will never progress. So the men are dying with prostate cancer, but not from prostate cancer. Most of these men will never have symptoms, so will never be diagnosed.If a patient has symptoms, then it is quite likely that the cancer will progress if we don't treat it. However, if we use a screening technology and catch the cancer before symptoms appear, then it is possible (likely) that some of those cancers were never going to progress to a dangerous level.For example, before a screening technology is developed, survival from a particular cancer might be quite low, because we don't detect the cancer until symptoms appear. Then we develop the new screening technology, and suddenly we are detecting all the cancers, regardless of whether they have symptoms or not.If we were just looking at the numbers it would look like the incidence of that cancer is increasing (we now detect extra cancers that we wouldn’t have before), but it would also look like we are successfully treating these additional patients. Even though those cancers would never progress, patients would still get (un-needed) chemotherapy, and it would look like the treatment was successful.The result of this is that we would think that the survival is increasing, but in reality, we are just identifying cancers who we wouldn’t have previously.This is just two examples, but understanding this kind of bias helps us realise just how easily we can be fooled into thinking the wrong thing. This lets you look more critically at studies, and hopefully means we are less prone to bias when carrying out these kind of studies.
Disparities in cancer survival
In my last post I published some good news about cancer survival rates, so I thought it was important to highlight a big problem with our recent success against this disease. This issue is flagged up in a study published at the end of January.It addresses the fact that the gains we have made in cancer diagnosis and treatment are very unevenly spread around the world. To analyze this is greater detail, the scientists studied the differences in survival in different countries, and the results are somewhat predictable.If, for example, you are an Australian or American with breast cancer, you have a 90% chance of surviving. If you are Indian however, you only have a 66% chance.If a child is diagnosed with acute lymphoblastic leukaemia in Finland, they have a 95% chance of beating the disease; in Ecuador, the rate is only 50%.So, over the period of this study (2000 to 2014) roughly 200,000 Indian women died from breast cancer who wouldn’t have died if they were living in the US. Almost 1,000 Ecuadorian children died from acute lymphoblastic leukaemia who wouldn’t have if they were in Finland. The same pattern is seen for all cancers, so it is clear that millions are dying from cancer in less developed countries who would not be if they were born somewhere else.This is even more staggering when you realise that this study did not even include countries at the bottom end of the global poverty index. This excluded nearly one third of the global population, as the records and reporting from these areas is just too unreliable to use.It is clear from the numbers that if you are from a less well-off country, you are far more likely to die after being diagnosed with cancer. This isn’t entirely surprising, as the detection and treatment of the disease changes quickly and can prohibitively expensive.Unfortunately, it is also likely get worse in the coming years. Due to a lack of tobacco regulation in poorer countries, lung cancer is set to increase. The WHO has pointed out that smoking still appears to be increasing in Middle Eastern and African regions, and it is known that the tobacco industry has actively been targeting young people in these countries.Additionally, as our treatments for cancer get more sophisticated, they also get more expensive, something I have written about in the past. When combined with less well supported health systems, and other more pressing public health issues, the picture looks bleak for cancer patients in many low- and middle-income countries.Of course, there are plenty of other public health improvements that can be made around the world that would have a bigger impact on people’s lives than providing better access to cancer treatments. Access to clean water, anti-malarial programs, and HIV and TB treatment programs would be far wiser investments than cancer therapeutics. However, as we in cancer research congratulate ourselves on our successes, it is always worth keeping in mind just how unevenly that success is distributed.
Are cancer rates rising?
Cancer is so prevalent in life now that it is easy to think that the rates are skyrocketing. However, the numbers don’t back this up. In actual fact, we are slowly but surely advancing our response to the disease, and recently published data underlines this progress.The publication was the annual report of the American Cancer Society. In that article, they compile all the recent data to see what trends there are in cancer rates and deaths.The report delivers some good news.Although cancer kills more people in the US than anything except heart disease, the incidence of the disease (the percent of the population diagnosed) is stable or declining, and survival is increasing. This is a steady trend we have seen over the last decade, and it looks like it will continue into the future.To be clear, because the population is increasing we are seeing more cancers, so the total number is rising, but the incidence (which is relative to the population) is not changing. For example, if there are 200 cases of cancer in a population of 100,000 (0.2%), that is the same incidence as 20,000 cases in a population of 10 million (0.2%). The number of cases is different (200 compared to 20,000), but the incidence is the same.Also remember that the older you are, the more likely you are to be diagnosed with cancer. And that people are now surviving longer with the disease than ever before. So, when this increased survival is combined with the rising and older population, it is perfectly understandable that we come into contact with more and more people who have had the disease, and thus think that the rate is increasing.What the data actually shows us is that this is not the case. In women, the overall incidence of cancer is neither increasing nor decreasing. While there are drops in colon and lung cancer, there are increases in breast and skin cancers that offset these, so overall, there is no change.In men we have also seen a drop in colon and lung cancers, but also a large decrease in prostate cancer, which means that overall, male incidence of cancer has dropped by around 2%. The decrease in prostate cancer is largely down to changes in how we screen for the disease, so is probably not a true decrease (before we changed the screening we were detecting lots of cancers that would never have progressed. We no longer count them in the numbers). In reality, the male situation is probably like the female situation, and there has been little change in the numbers.When we look at the survival from cancer, the picture is more optimistic. Since 1991, the overall death rate from the disease has decreased by 1.5% per year, which means that in the last 36 years we have seen a decrease of over 26% in cancer deaths. That means that the likelihood of you dying from cancer has drastically decreased.In 1975, 50% of patients were dead after 5 years. By 2012 this had decreased to 34%, and this trend is continuing, with more people surviving for a longer time after being diagnosed with cancer.There have been several major advances in the last few years, and we are yet to see the real benefit of these, so it looks like this trend for increased survival will continue. It is slow progress, but the numbers certainly give us cause to be optimistic!
Ultra-processed foods and cancer
This story was all over the news today:
“Ultra-processed foods may be linked to cancer, says study”The Guardian, 15th Feb. 2018
The news comes from a French study that looked into whether cancer was associated with highly processed foods. As usual, the question is whether the actual results of the study warrant the hysteria currently playing out in the media? (Spoiler: the answer to that is almost always an emphatic NO!)First things first; this is an excellent study, with well carried out data collection and good analysis of the results. The authors looked at 104,980 people, and asked them to fill out a daily survey about their diet. Using that data they compared cancer rates to the people’s self-reported diets.The study found that high consumption of “ultra-processed foods” was associated with a 12% increased risk of cancer. In men, no one cancer type was specifically increased, in older women the foods were associated with an 11% increase in breast cancer.These studies are notoriously difficult to interpret, mainly because, aside from their diet, there are numerous differences between people. In this study for example, the participants who consumed a higher amount of ultra-processed foods were more likely to be smokers, and less likely to be physically active.Clearly, what people eat is only part of a larger lifestyle. People who eat healthily tend to be healthier in other areas of their lives, so it is very difficult to say that a specific dietary choice is actually causing cancer. The authors of this study tried to correct for things like this, but that is extremely difficult to do, something that was acknowledged by the authors in their paper.It is also worth saying that the definition of “ultra-processed” is a hard one to pin down. The definition used in this study was based on a food classification system called NOVA, but this is still not very clearly defined, which means it is difficult to draw any practical conclusions from it. Unfortunately, in the media the term is wielded to mean anything that isn’t “natural”, despite this being wrong. For example, according to the classification used in this study, gluten-free artisanal bread is ultra-processed, as are vegan health shakes, and organic protein bars.While this is a solid piece of research, the public reaction to it is likely to be misplaced. Unfortunately, it is likely to play into the “clean eating” fad, which is largely nonsense. It is now clear that the fashion for “clean eating” has legitimised eating disorders, and may in fact be doing far more harm than good.However, as global consumption of processed food increases, it is very important that we understand their impact on health. This research clearly warrants more study, but these findings alone cannot offer practical advice to consumers. As always, if you have a varied diet and get a bit of exercise, there isn’t much to worry about!
Cancer vaccine breakthrough?
Every once in a while I see a paper that makes me sit up and say “Wow”. They are rare, but when they happen they let us really see the progress that is being made. This week one of those papers was published in the journal Science Translational Medicine.The study built on recent work that is focused on the immune system, and the potential that we can make it attack a cancer (something which doesn’t normally happen). There has already been some excellent results in this field in human trials, but this study took the work in a slightly different direction. The work was carried out in mice, so is still at an early stage, but the a small clinical trial is starting this month, and that will tell us how optimistic we should be.What these scientists have developed is a clever way to activate the immune cells specifically within the tumour by injecting it with a tiny amount of DNA and another compound. When they did this they found that the tumours shrank and disappeared. It gets better though: they tried the same approach in breast cancer, colon cancer, and melanoma, (three very different cancer types) and saw the same effect across the board.
Perhaps the most exciting part of the work was that when they injected one tumour, the immune system attacked all the tumours in that mouse, which means that this is an approach that may work in late stage patients, who are typically very difficult to treat.The technique itself makes use of a trick that is already used in patients: by injecting a tiny amount of DNA into a patient’s cancer, we can improve responses to chemotherapy. It works by making the immune cells in the vicinity express a marker on their surface, which has the effect of priming them for action. The insight that these scientists had, was that by using a second compound to recognize this marker, they could activate the cells to attack the tumour. Because the injection is directly into the cancer, only the immune cells that recognize the tumour are activated. Some of these then leave the original tumour and attack other ones throughout the body.This approach proved to be remarkably effective. In total, the scientists treated 90 animals with the therapy. Eighty seven of those were cured. Additionally, in some of the mice the tumours became resistant and began to grow again, which is typically what happens in human patients. However, if they then injected this new tumour with the therapy, they saw the same shrinking as before, which is extremely encouraging.It was a startlingly successful study, but as I mentioned above, this work was in mice, so we can’t be sure the results will translate to humans. It’s possible that there will be toxicity to humans, or that there will be issues with stimulating the immune system like this, but it is also very possible that we will see some real benefits of this therapy.It’s an exciting time to be in cancer research!
Does a common drug increase stomach cancer risk?
This story was in the papers this week, linking a very commonly used medication with a doubling in stomach cancer risk. A doubling in the risk of anything sounds bad, but what does it mean in reality?
“Acid reflux drug linked to more than doubled risk of stomach cancer”
The scientists, working in London, published a paper linking the use of proton pump inhibitors (PPIs) with cancer. As around 20 million people in the US take these drugs annually, usually to deal with heartburn, it is obviously very important to be aware of any potential harm they are doing. Indeed, several recent reports have emphasised that these drugs are not as safe as their maker’s say, although the levels of side effects is admittedly extremely low.This study found an increased risk of stomach cancer in people taking the drugs. Those on PPIs were 240% more likely to be diagnosed with the disease. However, to understand this properly, you have to realise the difference between relative risk (which this is) and absolute risk.For example, this increase in relative risk of 240% actually means an increase from 0.24% to 0.57% in the chances of an individual patient getting the disease. In other words, the likelihood of you being diagnosed with stomach cancer goes from a low risk to a slightly less low risk. So of the over 60,000 people included in this study, PPI use was associated with an extra 10 cases of stomach cancer. Most people would consider this acceptable for the benefit they get from the drug.While the increased risk for an individual is low, these drugs are among the most commonly prescribed in the world, as I mentioned above. So, for a population this big, a small increase in risk can result in thousands of additional cases of this disease.Extrapolations like this have to be taken with a pinch of salt however, as they are fraught with issues. For one thing, the study only followed people for 9 years, so it’s difficult to say much about a population of people taking the drugs. Most importantly however, these extrapolations make mass generalisations. Not all patients will be long-term users, while some will be on the drug for longer than the 9 years of the study. It is pretty clear however, that PPI use is associated with many additional cases of stomach cancer.It has to be pointed out though that this is a correlation, and we cannot say that the PPIs are causing the increase. I’ve discussed this in the past here, so I won’t go into detail on this.One last thing to mention is that although PPI use has increased dramatically since they were introduced in 1988, the number of stomach cancer cases has decreased by over 25% in the same time, due to other preventative measures we have put in place. This downwards trend is still continuing, so we can expect further drops in the coming years. Absolute risk v relative riskI showed above that even a large increase in risk of stomach cancer doesn’t mean many extra cases, and I have previously discussed the difference between absolute and relative risk in this blog post.Have a look at the diagram below. In both situations you have a 100% increase in relative risk. However, in one case this means your absolute risk goes from 1% to 2%. In the other it goes from 35% to 70%. Understanding this difference lets you be a lot more critical when reading numbers in the media!
Anti-obesity campaigning and stigmatization
Last year Cancer Research UK launched the latest campaign aimed at reducing obesity related cancers. This is an important issue, with obesity now being recognised as the second biggest preventable cause of cancer, behind only smoking. The evidence for this is extremely solid, and it is expected to cause an additional 15,000 deaths in the UK from cancer this year alone. And the numbers are increasing steadily. In the 20 years from 1993 to 2013, the number of people classed as overweight or obese in the UK increased by 6 million.Looking at these numbers it is very easy to make the case that an anti-obesity campaign is a perfectly acceptable, indeed necessary, part of our strategy to tackle cancer. This was the logic behind the CRUK campaign. However, that initiative was badly received by some people, who described it as “fat phobic” and very insensitive. These objections are easy to dismiss, especially when viewed alongside the obesity related cancer statistics. However, rather than immediately rejecting these arguments, it may be worth considering them for a minute.Let’s get a few things clear first.
- Mental health problems are extraordinarily common and are a huge problem for us as a society. For example, it is thought that 25% of the population will experience mental health issues each year, with the OECD estimating an annual cost to the UK economy of £70 – 100 billion (around €80 – 115 billion). Several reputable sources put the cost as even higher than that. As a comparison, the economic cost of cancer is “just” £15.8 billion (around €18 billion), emphasising just how important an issue mental health is.
- Negative body image is associated with mental health problems. Unfortunately it is an extremely complex and under-studied field, so solid numbers are hard to come by, but it is estimated that 22% of adolescents suffering with depression have clinically significant body image concerns. This does not mean that one causes the other, but it is safe to assume that our societal problem with body image is damaging.
So let's get back to cancer. The above information makes it clear that any anti-obesity campaign must balance the benefit of decreased obesity with the potential of further stigmatizing obesity and increasing body image problems. So does the CRUK campaign do this? This is an image of one of the adverts that drew the ire of body positivity campaigners.
The first question that has to be asked is what is the aim of this campaign? Obviously the charity wanted to draw comparisons between obesity and smoking, emphasising how dangerous it is. The success of the campaign relies on the assumption that people are not aware how dangerous obesity is, and on the second assumption that if they are made aware of this, people will lose weight and crucially, keep it off. It appears that the first assumption is at least partially true. While people are aware that obesity is unhealthy, less than 25% of people are aware of the increased cancer risk. CRUK have identified the need to increase awareness, but it must be pointed out that although the cancer risk is underestimated, people are already aware that obesity is dangerous.The second assumption made by CRUK is that fear of cancer will motivate people to lose weight. Scare tactics have been used in many campaigns, including well-known road safety and anti-smoking drives. The clear intention of this ad is to draw parallels with smoking, and therefore elicit the same response from people. However, there is reason to think that in the case of obesity, negative messaging may not work.A study carried out in 2012 by researchers at Yale University found that messages deemed negative or stigmatizing were seen as the least motivating of all messages. People exposed to these messages were significantly less likely to comply with their recommendations. Furthermore, there is significant evidence that making people feel stigmatized or shamed about their excess weight makes them more likely to eat unhealthily and avoid exercise, thus decreasing the effect of any public health campaign (additional published studies about this can be found here, here, here and here).The sole aim of this campaign is to highlight that obesity is linked to cancer. While this may on the surface seem like a sensible idea, unfortunately it is more likely to stigmatize obesity than have any meaningful effect on weight loss. This demonization of obesity is very prevalent, and studies have shown that society makes extremely damaging assumption about obese people, including that they are lazy, weak-willed, unsuccessful, unintelligent, lack self-discipline and have poor willpower. It is a little acknowledged but extremely prevalent form of prejudice. This stigmatization is known to be extremely damaging to mental health, but also to threaten physical health (through patient's complaints being lazily and incorrectly ascribed to their weight), to generate health disparities, and as I mentioned above, to interfere with effectiveness of obesity intervention efforts.It is clear that we need to do something about obesity. It is one of the most important health interventions we can make as a society, but increasing the stigmatization of obese people is not the way to tackle this issue. Positive, empowering messaging, healthy eating education (especially in childhood), advertising bans and facilitation of exercise have all been parts of successful anti-obesity drives in the past. Normally I think that Cancer Research UK are extremely effective in their campaigning. This time however, I think they got it wrong.
Eggs, cancer, and motivated reasoning
The following headline in the The Daily Express caught my attention this week:
“Ovarian cancer - could EGGS be the cause of disease? Vegan charity research REVEALED”Express.co.uk 14th March 2017
The article goes on to explain that a Bristol based charity called Viva! Health has urged consumers not to eat eggs, claiming that one egg a week increases cancer risk by up to 70%. According to their own website, Viva! Health is a science-based health and nutrition charity, and being “science-based” you would expect them to have sufficient evidence to make a claim as eye-catching as the one above. So is this the case?
Viva! Health claim that eggs are linked to ovarian and prostate cancer in two ways. First, the high cholesterol levels promote these cancers; and second, choline in eggs is linked to prostate cancer. They give references to scientific publications as evidence, but these publications show nothing of the sort. The journal article they point to regarding cholesterol explicitly states that any association between egg consumption and ovarian cancer risk is not due to the cholesterol in eggs. A quick look at the literature also shows that if there is any link between egg consumption and breast or prostate cancer, it is tiny. A similar pattern holds true for the link between choline and prostate cancer. The research that Viva! Health use to support their claim actually shows the opposite, that choline from eggs is not associated with cancer. It’s pretty clear, there’s nothing to worry about.It took me roughly six minutes to debunk both of these claims, using the identical publications that Viva! Health used to support their claims, so an obvious question is how a charity that clearly thinks of itself as “science-based” could come to the opposite conclusion to me. There is a well-known phenomenon in psychology called motivated reasoning. It describes a process by which someone who holds a particular belief seeks out information that confirms what they already believe, rather than rationally assessing the evidence.It is a fascinating mental trick that we are all guilty of. We all cling to different beliefs with different strengths. If I was to tell you that plastic bags are more environmentally friendly than cloth bags (unless the cloth bag is used more than 130 times), you are likely to look at the evidence and relatively quickly change your view without a huge amount of argument. On the other hand, if I was to say that immigration is economically bad for a country (or good depending on your point of view), you are far more likely to argue with me and ultimately reject that argument. Although both the plastic v cloth and the immigration arguments are contentious and depend on the studies you look at, the likelihood is that you reacted differently to each.A lot of recent research has started to dissect these distinct types of beliefs. We have normal beliefs that change with additional information, but we also have a set of beliefs that form the core of our identities. These often take the form of religious or political views, and when these beliefs are challenged we don’t take a rational approach. Instead we employ motivated reasoning, dismissing awkward facts and cherry picking the ones that agree with us. Indeed, if one of these core beliefs is challenged, it is likely that the belief will be ultimately strengthened rather than weakened by the challenge, something called the backfire effect.Motivated reasoning is extraordinarily common in pseudoscience. Topics like climate change and vaccine safety have decades of reputable research behind them, but despite this, deniers ignore the body of evidence and scientific consensus, deciding to rely on small bits of circumstantial evidence or simple untruths to “prove” their points. There seems to be very little we can do to convince people who hold these beliefs so tightly. However, the majority of the population doesn’t have beliefs like this at the core of their identity. They may have heard the arguments and be unsure about the topic, but with clear evidence and explanation, most people will make the right decisions. This is exactly why it is so important to talk about science and to educate people in how to recognize false claims.Motivated reasoning may be behind the Viva! Health claim that eggs cause cancer. They are a charity dedicated to promoting veganism, so it is entirely plausible that their beliefs regarding non-vegan foods are central to their identity. Alternatively however, they may just understand that if you link something to cancer (whether it is true or not), you are far more likely to make it into the papers, and have random bloggers talk about you!
Using stem cells to treat cancer
There are many scam artists around nowadays proclaiming the benefits of their particular unproven stem cell therapy, for anything from curing cancer to making paralysed people walk again. It’s not surprising really; stem cells are a pool of cells in every organ that are almost eternally youthful and can regenerate themselves and all other cells in the organ. They sound almost magical. However, last year the FDA (the US Food and Drug Administration) had to move to crack down on these clinics, citing the of lack of evidence that any of them work and a number of serious complications reported following treatment. Complications including patients in Florida dying, a woman developing bone fragments in eyelids following a stem cell facelift, and another developing nasal tissue in her spine after a doctor promised to cure her paralysis with stem cells.It is a field ripe for abuse partly because it is one with so much potential. Stem cells do have fascinating possible applications, and there is a lot of research going in to them at the moment. Unfortunately, most exposure people have with them is in science fiction or alternative medicine. Which is why it was very interesting to see a study published last week that underlined how much real potential this field of research has. The study used mice instead of humans, so is still at an early stage, but is very promising nonetheless.Scientists from North Carolina were studying a deadly form of brain cancer called glioblastoma (GBM), which has extremely poor prognosis for patients diagnosed with it. The work builds on the bizarre finding that these tumours somehow attract stem cells to them. So if you look at a GBM in humans, there are stem cells inside them that shouldn't be there. Scientists had previously used this fact to load some stem cells with chemotherapy and could show that in mice, the stem cells were attracted by the tumour as expected, but they could also release their therapy while they were there. The problem with this is that we have very few stem cells in the brain so finding them and loading them with drugs is very difficult.In this case the scientists overcame that problem by turning skin cells into brain stem cells. They took skin cells from mice into the lab and, because skin cells originally comes from the spinal cord which is technically part of the brain, were able to trick them into reverting back into that state. They could then give these cells their chemo payload and inject them back into the mice. When they did this the stem cells made their way to the brain and reduced tumour size to almost nothing, which is obviously a very impressive response.There are two key advantages of this approach: 1) we have lots of skin stem cells, so they are easy to get; and 2) you can do it with a patient’s own cells, meaning that you wouldn’t have to worry about rejection, which can cause severe complications. This work still has to undergo significant testing to ensure it is safe for humans, but studies so far have been positive. A group in California have carried out a clinical trial which showed that apart from tissue rejection (which isn’t an issue in this case), stem cells can be a remarkably safe form of therapy.This work is still at an early stage, but it is very encouraging. Considering that the average survival time for a patient with GBM is only a year, any new therapeutic avenues are welcome. The stem cell field is one that is on the cusp of large-scale application, and this could be one of the first in an array of new therapies for cancer and many other diseases. At present however, 95% of clinics offering these therapies are charlatans looking to make money off vulnerable people.
Does Nutella cause cancer?
On a recent cycling trip in Canada, I ate an obscene amount of Nutella. It works as a great lunch, and dipping fresh bread in it is a delicious snack. When you are exercising all day every day, a tasty, spreadable, dippable energy source like this is extremely useful. Don’t get me wrong, it is a very unhealthy food, but despite this, I’m a fan.Which is why I was surprised this week to see Ferrero (the makers of Nutella) defending their product against claims that it causes cancer. A quick internet search revealed the problem. As the Tech Times put it: “Nutella Can Cause Cancer, Study Warns”. The Huffington Post ran with: “Stores Are Pulling Nutella After Report Links It To Cancer”, while the Daily Mail asked “Could Nutella give you CANCER?”. So what is this all about, and should you stop eating Nutella?As I’m sure you can guess, the simple answer is no, there is currently little evidence to suggest that you need to avoid Nutella. This panic was based on a study released by the European Food Safety Authority (EFSA) last year which suggested that when palm oil is refined at above 200°C, it releases something called glycidyl fatty acid esters (GE). Previous work has shown that at high levels this chemical can cause cancer in rats. Ferraro do indeed use palm oil in Nutella, so people have made an assumption that it therefore contains GE. However, Ferrero have clearly stated that they do not process their palm oil at 200°C, so no GE is produced in the process. Case closed.But for the sake of argument, lets pretend they do refine their palm oil at 200°C. Would the hypothetical amount of GE in Nutella be a cause for concern? In the EFSA report they quote the levels of GE that cause tumours in 25% of rats (10.2 mg/kg/day in case you are interested). Now obviously we would want to play it safe, and wouldn’t want to consume anywhere near that amount. So for argument’s sake, lets see how much Nutella we would need to eat to get 1/10,000th of that amount (thanks to this article for calculating the numbers). It turns out that the average adult would need to eat nearly 100g of the stuff every day to reach 1/10,000th of the amount that gives rats cancer. That’s over two jars a week, and if you are eating that much Nutella, then cancer is the least of your problems. The same amount of Nutella (800g) contains over 450g of sugar, which is double what your TOTAL sugar intake should be for a week.Simply put, concerns about cancer are a terrible reason to stop eating Nutella. Their use of palm oil has many other problems associated with it, including the devastating environmental impact, but that is another argument. As always, this is a case of poor journalism. The study itself didn’t mention Nutella, and was just focused on the GE. Some simple fact checking would have shown that Nutella does not process their palm oil in a way that produces GE, but there is nothing like a food scare to attract clicks.
Hot drinks and cancer
You may have seen a frankly terrifying headline this week:
“Hot drinks probably cause cancer, warns World Health Organisation”Telegraph, 15th June 2016
Almost every news source carried this story, and the headlines were universally similar to the one above. This story comes from a report by the WHO, which looked at the association between coffee and mate (a South American herbal tea) and various forms of cancer. In short, they found that there was no association between coffee or mate and cancer, but that the temperature of the beverage may be linked to oesophageal cancer. This, of course, is nothing to worry about. The report classifies hot drinks as “probably carcinogenic to humans”, group 2A in their classification. Other items in this category are the act of frying food, working as a hairdresser or barber, red meat, and working night shifts. This categorisation tells us about the hazard of hot drinks, but not about the risk.The words "hazard" and "risk" are regularly used interchangable, so the distinction between them is one that is lost on most people. Hazard is whether something can happen or not. Risk is the likelihood that it will happen. There is a hazard of crashing when you are driving with your eyes open or with your eyes closed. However, the risk is quite different in each of these cases. This report tells us about the cancer hazard of hot drinks, but nothing about the cancer risk, so the fact that hot drinks are on this list isn’t very informative.So what do we know about the risk of hot drinks. Firstly, this applies to drinks consumed at 65°C or above. So if you put milk in your tea or coffee, then you’re ok. Even if you don’t, oesophageal cancer isn’t very common, so even a big increase in risk wouldn’t translate into many more cases (see below for an explanation of this). If you want to do something to decrease your already small chance of getting oesophageal cancer, then consider stopping smoking, stopping drinking, eating more fruit and veg or losing excess bodyweight, all of which are known risk factors.The system of classification used by the WHO is unfortunately ripe for misinterpretation. It is almost impossible to prove a negative, so proving something definitely doesn’t cause cancer is difficult. The WHO has now classified 1,051 different things for their likelyhood of causing cancer. Of those, they have only rated a single one as “probably doesn’t cause cancer”. (For those who are interested, that one thing is Caprolactam, a compound used in the production of nylon).Nearly half of the rest fall into the “not classifiable” category because we just don’t have enough evidence to say either way. This may be because the evidence is inconclusive, or because studies have never been done. In reality, if the WHO analysed whether swivel chairs caused cancer, they would fall into this category rather than the "probably don't cause cancer"one, because we have never needed to study it.So by the WHO system, we can't say that the following don't cause cancer: chlorinated drinking water, caffeine, mobile phones, fluorescent lighting, hair colouring products, magnets or tea. They are in the “not classifiable” category. However, aloe vera, pickled vegetables and dry cleaning are all classified as “possibly cause cancer”. As you can see, this classification causes more confusion in the general public than anything else.When you understand the difference between hazard and risk it becomes far easier to interpret the constant health scare stories in the media. “Mobile phones may cause cancer” is a terrifying headline, until it is put into this context. The increased understanding of risk is a vital tool in the rational toolbox. And because large parts of the media don’t seem to possess this, it is one that we can get a lot of use out of! Absolute risk v relative riskI mentioned above that even a large increase in risk of oesophageal cancer doesn’t mean many extra cases. To understand this you have to understand the difference between relative risk and absolute risk.Have a look at the diagram below. In both situations you have a 100% increase in relative risk. However, in one case this means your absolute risk goes from 1% to 2%. In the other it goes from 35% to 70%.To to bring it back to hot drinks, imagine a crazy situation where they give us a 50% increase in risk for oesophageal cancer. (Just to be clear, there is not a 50% increased risk with hot drinks, I made that number up as an example of a large increase.)The rate of oesophageal cancer is around 15 cases per 100,000 people, so your risk of getting it is 0.015%. A 50% increase in risk means that the rate would rise from 15 to 22.5 cases per 100,000. In this case your risk has now gone from 0.015% to 0.0225%, an increase of 0.0075%.You can see how an enormous increase in your relative risk (50%) can mean only a tiny increase in your absolute risk (0.0075%). So when you hear someone say that x increases your risk of cancer, your first question should be “but what is the risk of me getting that cancer in the first place?”. Once you know that you will have a far better idea whether the rest of the claim needs to be listened to.
Royal College of Physicians recommends e-cigarettes for smokers
A few months ago I wrote here about the rise of e-cigarettes. In that post I pointed out that e-cigarettes are far less harmful than tobacco, and should be marketed as a safer alternative to smoking. There has been an interesting update on this topic today, with the Royal College of Physicians (RCP) recommending that all smokers be offered and encouraged to use e-cigarettes.You can read my previous post for some of background, but put simply, e-cigarettes vaporise nicotine to allow it to be inhaled (hence it being known as “vaping”). This differs from smoking, where tobacco is burned and the smoke inhaled. This accounts for the primary difference between vaping and smoking; tobacco burning creates thousands of chemicals, 10% of which are known to cause cancer. People inhale far fewer chemicals when vaping, making it 95% safer than smoking.The RCP released a report today (April 28th) stating that
"e-cigarettes are likely to be beneficial to UK public health. Smokers can therefore be reassured and encouraged to use them, and the public can be reassured that e-cigarettes are much safer than smoking"
They go on to state that current evidence shows:
- E-cigarettes are not a gateway to smoking.
- E-cigarettes do not result in the normalisation of smoking.
- E-cigarette use is likely to lead to quit attempts that would not otherwise have happened.
- The dangers of long-term e-cigarette are unlikely to exceed 5% of those associated with smoked tobacco products, and may well be substantially lower than this figure.
An excellent Cancer Research UK blog post on this topic points out that this reduced harm of vaping is something we should focus on. They emphasise that a significant number of people may be unable, or simply not want, to give up smoking. For these people, the aim should be to reduce the danger of their habit by encouraging them to use e-cigarettes rather than traditional cigarettes. This harm reduction strategy has worked well in other cases, such as needle exchanges for intravenous drug users.This is what the NHS already recommends, in the form of nicotine replacement therapy. It has been shown, however, that the delivery of nicotine to the brain via vaping is far more similar to smoking than in nicotine replacement therapy. As a result smokers seem to prefer vaping, and e-cigarettes have now replaced nicotine patches and gum as the most popular aid in quitting smoking in the UK.It has been shown that an overwhelming majority of e-cigarette users are ex-smokers, or current smokers who are trying to cut down or quit. Considering the human toll of smoking (270 deaths in the UK every day), it is commendable that the RCP have recommended e-cigarettes to smokers. While there are still problems with vaping (particularly in marketing to children), the advantages for current smokers are undeniable. The use of alternative sources of nicotine is safer, and should be part of any strategy to reduce the harm of tobacco.
Why screening is hard
It’s a simple fact that the most effective thing we can do to cure more cancers is to catch them earlier. If we find bladder cancer at an early stage, the five year survival is 88%; if we catch it at a late stage, when it has started spreading around the body, it drops below 15%. This is why we screen for certain diseases, including breast, bowel and cervical cancer. These large-scale screening programs are the best hope we have for majorly reducing the toll cancer takes on our lives.Screening, however, is hard. The main problem we face is accuracy. An ideal test would flag up 100% of sick people and 0% of healthy people. However, these tests are never perfect. There is always a percentage of sick people who are not flagged up (false negatives) and a percentage of healthy people who are incorrectly labelled as sick (false positives). And these problems can get pretty bad pretty quickly.The following diagram illustrates this issue. It shows the results of a test that is quite accurate (one that has 90% accuracy) applied to a common disease that is present in 1% of the population.
As you can see above, what sounds like a good screening test results in 10 times more false positives than true positives, while it also tests one person as negative while they are actually positive.In a large population, even a small percentage of error translates into a large number of misidentified patients. This can result in a crippling financial burden on the health system, as well as unnecessary worry, stress and pointless treatment for perfectly healthy people.As a result, only extremely accurate tests can be used in the clinic, which is the reason we screen for so few diseases. So how do we get around this? Well, obviously we have to develop more accurate tests, and a lot of effort is currently being invested in this field.Additionally, we can also improve things by being more selective about the people we screen. If a disease is present in 1% of the general population, but present in 5% of people over 65, then we can screen just the over 65s.So using the above the example of a test with 90% accuracy, if the prevalence is 5% instead of 1%, then rather than 10-times more false positives than true positives, there is just over 2-times. If the test were 98% accurate, then we would have far more true positives than false positives. This increased accuracy in a specific population is what we are working towards.
However, while significant research is being carried out in the development of new tests, it is disappointing to note that this is still a small percentage of cancer research funding. According to the National Cancer Research Institute, in 2011 (the most recent year I could find numbers for), research into early detection, diagnosis and prognosis received just 12.6% of cancer research funding.While it is understandable that research into a “cure” is more attractive than research into early diagnosis, the potential benefits of early diagnosis far outstrip that of drug development. Encouragingly, this level of funding is increasing steadily, and rose from 8.1% in 2002 to 12.6% in 2011. If this research can result in more viable screening programs, this will provide a significant clinical benefit to cancer patients.For more information about screening, I’d recommend having a look at the sense about science website, which does a great job of describing not just this problem, but also many others that arise in screening populations for diseases.
Recent advances in cancer therapy
First off, sorry for the lack of writing in the last few weeks; I’ve been in the middle of a job hunt, so my time has been limited by that. In the time I have taken off however, there have been some major news stories about cancer.The week of the 15th February brought some pretty sensational headlines. These were about a trial of a new immunotherapy, which both The Times and the Independent proclaimed “a cure”, and The Guardian labelled as “unprecedented”.Immunotherapy is an extremely promising branch of cancer therapy that has recently been getting a lot of attention. I have previously written about it here, so I won’t go into detail about how exactly it works. Simply put, it involves taking some of a cancer patient’s immune cells, teaching them to recognise the tumour, and then putting them back into the patient. These immune cells can now identify the cancer, attack it, and hopefully clear it from the system.
These results have not been published yet (they were presented at a conference), so we can’t say for sure how reliable they are. We do know however, that the trial had just 36 patients on it, and that it was looking at a cancer we can already treat with a high degree of success (acute lymphoblastic leukaemia (ALL)), so the headlines were far more sensational than the work deserves. That being said, it does appear to be a very encouraging study. However, as I have previously written, claiming something is a “cure” for cancer is likely to be wrong.This treatment appears to be very effective for ALL, and it may eventually become part of the standard therapy for this disease. However, ALL is just one of a large number of different types of cancer. Couple this with the ability of the disease to develop resistance to therapy and it becomes unlikely that this (or any other therapy) will ever be a “cure” for cancer. So while this is certainly an exciting advance, claiming it is a cure is unfortunately incorrect. It may have the potential to cure some patients, but without long term testing, we just don't know if this is the case.This problem of resistance brings me to the second big cancer story that’s been in the news recently. Coincidentally, it is also to do with immunotherapy. In this study, scientists found that a patient’s cancer carry markers that the immune system could be primed to attack, as I described above.However, it has always been assumed that as a tumour develops, it would change and evolve, resulting in some cells that no longer have these markers, and would therefore be resistant to the immune cells taught to target those markers. What is interesting about this study is that the scientists showed that this may not always be the case, and that all of a patient's tumour cells may still carry the markers, meaning they would all be attacked by the immune system. The video below (from CRUK) describes this very nicely.https://www.youtube.com/watch?v=ZPwrvPerxIkThe potential that a patient won't develop resistance to a therapy is one that scientists and doctors can only hope for. If this study holds, and is extended to other cancers, this dream may become a reality for some people. Again, this is a study on very few patients, but it gives us a tantalising glance at a potential weakness in cancer that could be exploited.It is an exciting time to be a cancer researcher!
Why is cancer so hard to treat?
As a cancer scientist, a common question I get is “When are we going to cure cancer?”. It sounds like a simple question, but the truth is pretty complicated.The first thing to point out is that finding a cure for cancer is extremely unlikely. Cancer is an umbrella term for over 200 different diseases (1000s of different diseases if you include sub-types). Although these diseases have many outward similarities (all grow uncontrollably and have the potential to invade and spread), the biological mechanism is different for most cancer types. The simple answer is that we may find cures for various cancers, but each will need their own research and treatment strategies.To understand cancer you have to understand that it is a disease of evolution. Over the past 4 billion years we have evolved from a single celled organism to the dominant mammals on the planet. This process is driven by random alterations and mutations of our DNA. Each of these mutations has the potential to change our genetics. If that change gives an individual an advantage over the rest, then that individual is more likely to survive and to pass the advantage on to his or her offspring. This selective pressure to retain advantageous traits is known as “Natural Selection”.These random changes and mutations can happen every single time a cell divides. Our cells are actually astonishingly efficient at avoiding and correcting mistakes, preventing most events that could result in a tumour. However, trillions of our cells divide every single day, and not all mutations can be caught.Just like in our evolution, if a mutation gives one of your cells an advantage over the other cells, then this cell will survive over the cells around it. For example, if a mutation causes a cell to multiply out of control, it will outgrow those around it and form a tumour. Moreover, tumours can often result from unique combinations of mutations, which will drive their growth in a different ways.If you take a step back and think about that, you can begin to see why a cancer can be so hard to treat. It is a corruption of our own cells, genetically almost identical to healthy ones, similar enough to make it hard to target, different enough to drive the disease. Most drugs we try to use will have difficulty differentiating between cancer and healthy cells, and as a result will cause terrible side effects.To make things even more complicated, as the tumour itself grows it accumulates more and more mutations. Some of these mutations will cause further advantage over other cells within the tumours, and form their own little part of the growth, meaning that the cancer can be made up of many cells that are genetically different.
This brings us back to the idea of natural selection: when we find a drug that works for a tumour, we are applying a selective, evolutionary, pressure. If any of the different cells in the cancer allow it to resist the therapy, then that cell will quickly take over, giving rise to a chemo resistant cancer (pictured).Tackling this problem requires an understanding of the various mutations that are causing the cancer to grow. This understanding allows us to design drugs towards these specific mutations, a process we have already started. If we can then recognise what mutations are present in a specific tumour (using techniques like liquid biopsies, which we have written about before), we can use this new generation of drugs to target all of the different mutations present. This may, for the first time, allow us to design a treatment specifically aimed at stopping resistance arising.Vast resources are now being invested in developing these targeted therapies. There already have been some significant successes. For example, breast cancer, lung cancer and melanoma patients can now get different drugs depending on the mutations present in their tumours. It is unlikely that we find one drug that will cure cancer, but research in this direction will help us to refine treatments and ultimately improve patient survival.
Tracking tumours with blood samples
This week, a couple of new studies (which can be found here and here) showed that we can track changes in a tumour through blood samples alone. To understand the importance of this it is worth knowing that chemotherapy is going through a radical change at the moment.
The last few years have seen the introduction of a new generation of cancer drugs. These are targeted therapies, ones that are targeted not only towards a specific cancer but also towards specific sub-types of that cancer, based on the mutations that they have in their DNA. Not only are these chemotherapies more effective, but they should also cause fewer side effects than ones used in the past. Several of these targeted therapies have proven to give remarkable responses, with tumours melting away better than we could have dreamed.However, as patients have taken these drugs, an unfortunate pattern has emerged: the patients show amazing responses for a few months, but pretty quickly resistance emerges and the tumours regrow, now insensitive to the therapy.In fact, the very specificity of these drugs is actually their Achilles heel. Because they are designed to target a specific mutation in a specific gene, if certain other mutations occur in the same gene, they can result in resistance to the therapy (for an example of this, see below).It is in this background that the studies mentioned above could prove very important. These studies showed that simply by looking at the blood of patients, the scientists could track what mutations were happening in the tumour. This is because cancers shed lots of DNA into the blood stream, and the researchers could detect and analyse this. They showed that they could track the tumour as it developed, looking at what new mutations were arising. In effect, they could predict resistance to a drug before it became apparent in the patient. Not only that, but they could see how the resistance was happening and suggest alternative therapies that may be effective.This is all very good news. Previously, the only way of doing this was to take a biopsy of the tumour itself, a very invasive procedure that carries its own risks, and one that cannot be carried out regularly. With this new method, we will hopefully be able to monitor the tumour much more closely (patients shouldn’t object to giving blood every couple of weeks), and be proactive in treatment, rather than reactive.This method is still too expensive to be made commonly available, but the cost is rapidly decreasing, and it should be accessible in the near future. Additionally, with the move in cancer treatment towards targeted therapy, this will hopefully majorly increase the effectiveness of our new generation of therapies. Example of resistance to a targeted therapyA drug designed for some lung cancers was targeted towards a specific mutation in a pro-growth protein called EGFR. In these cancers, EGFR was stuck in the “on” position as a result of the mutation, which meant it was driving uncontrolled growth. The drug was specifically developed to turn this protein off again, which resulted in it hitting the cancer, and largely leaving other cells unaffected. This therapy worked beautifully in patients for 10 – 14 months, but resistance appeared after that and we were back to square one in our options for treatment. When they looked at the new, resistant tumour, scientists found that the resistant cells had picked up additional mutations in EGFR, activating it in a different way. As a result, the cells were resistant to our targeted therapy.
The cost of a cancer breakthrough
A new combination of drugs marketed by Bristol-Meyer Squibb has been hailed as a breakthrough in cancer treatment. Almost every media outlet carried a story about the results of a trial that were announced at a conference in Chicago yesterday, with the usual hype. The results are quite remarkable. 58% of metastatic melanoma patients treated with this new drug combination saw their tumours shrink, with the tumours stable or shrinking for a median of 11.5 months. This is amazing when you consider that metastatic melanoma was thought to be largely incurable as recently as 5 years ago. The drugs are each a form of immunotherapy. This refers to a therapy that works by making the patient’s own immune system attack the tumour. In this case, the combination targets two separate mechanisms tumours use to avoid the immune system. Firstly, one drug (Ipilimumab) targets CTLA-4, which is made by the tumour to suppress the immune system. The second drug (nivolumab) targets a protein called PD-1, which prevents the immune system from killing the tumour cells, even if it does recognise them as bad.This is quite a significant breakthrough in the treatment of melanoma but it does come at a cost however. The treatment has significant side effects, with over 80% of patients experiencing these. Furthermore, 55% experienced severe side effects, and 36% of patients had to stop treatment as a result.There is also the issue of cost, a problem I have discussed in a previous blog. Ipilimumab has already been approved by NICE at a cost of at least £42,200 per QALY. Nivolumab hasn’t yet been appraised by NICE, so it’s cost per QALY isn’t available, but in the US it is slightly more expensive than Ipilmumab, costing roughly $150,000 dollars per patient per year. As a combination, it is estimated that it will cost patients in the US $295,000 per year. This may well prove a stumbling block for an already creaking NHS. However, as both Merck and Roche have their own versions of these drugs, the hope is that the competition will force the manufacturers to drop their prices. Whether they will or not remains to be seen.Unfortunately, this breakthrough isn’t the cure that some articles say it is. Between cost and side-effects, there will be problems prescribing it to many patients. It is a welcome advance however, and does herald the development of immunotherapy as another arm in our treatment of cancer.Edit (03/06/05): The $295,000 figure comes from adding the list price of the two drugs. Some outlets are reporting that a discount may be applied to that, making the drug considerably cheaper, potentially bringing it closer to $200,000 per patient per year. While this is a significant discount, $200,000 per patient per year is still a staggering cost. To put it in perspective, if every patient with late stage melanoma was given this drug, Bristol-Meyer Squibb would make over $2,000,000,000 per year from it. When you consider that this is from only the late stage patients, with only one type of cancer, you can see why some people have a problem with the pricing of this and other drugs.
Why are some drugs not provided on the NHS?
The decision not to provide a drug on the NHS can have a devastating impact on patients and their families, and often causes a negative public reaction. However, therapies are getting increasingly expensive (particularly cancer therapies) and NHS has a very limited budget. As a result, in spite of the impact on patients and public opinion, 36% of cancer drugs evaluated since the start of 2014 (see pie chart) have been rejected, usually on the basis of cost.Whether a drug is made available or not on the NHS is decided by the National Institute for Health and Care Excellence (NICE). This is an independent body that looks at the efficacy and cost-effectiveness of any new therapies, and makes recommendations based on their findings. In Scotland, there is a separate organisation (the Scottish Medicines Consortium) that makes the decision.The main metric that NICE uses to make these decisions is the Quality Adjusted Life Year (QALY). This takes into account the quantity AND quality of extra life given to the patient by a particular chemotherapy. So if a drug gives a patient an extra year of perfect health, it is given a QALY of 1.0. If the extra year is not in full health, it is given a value below 1 to account for this. For example, if a new treatment allows a patient to live for 2 additional years compared to the old treatment, but only with a quality of life weight of 0.6 (perhaps the patient is in severe pain as a result), then the treatment gives 2 * 0.6 = 1.2 QALYs to the patient.NICE has set guidelines on how much it can pay per QALY gained. That price is around £30,000, but can rise to £50,000 in some rare circumstances. Now compare that figure with the table below showing NICE recommendations on cancer drugs since the start of last year, and you can begin to see why it has had problems with some cancer therapies, with many drugs estimated to cost over the £30,000 threshold.
| Drug | Recommendation | Cost per QALY* | |
| Pixantrone | Optimised¶ | £22,000 | Link |
| Aflibercept1 | Not Recommended | £44,000 | Link |
| Pemetrexed | Not Recommended | £74,500 | Link |
| Afatinib | Recommended | £11,000 | Link |
| Bortezomib2 | Recommended | £17,800 – £39,600 | Link |
| Enzalutamide | Recommended | £22,600 | Link |
| Ipilimumab | Recommended | £28,600 | Link |
| Dabrafenib | Recommended | £11,000 | Link |
| Imatinib | Recommended | £16,700 - £30,000 | Link |
| Sipuleucel-T | Not Recommended | £48,700 - £512,000 | Link |
| Axitinib | Recommended | £33,500 | Link |
| Pomalidomide3 | Not Recommended | £50,000 - £70,000 | Link |
*depending on treatment ¶Recommended for a smaller group than applied for 1Aflibercept in combination with irinotecan and fluorouracil-based therapy 2Bortezomib in combination with dexamethasone, or with dexamethasone and thalidomide 3Pomalidomide in combination with dexamethasoneThis problem has been partially addressed by the creation in 2010 of the Cancer Drugs Fund, which provides funding for treatments that NICE haven’t judged on yet, or has deemed too expensive. This fund is due to finish in March 2016, but for the time being it provides an additional £340 million per year to pay for cancer drugs. The UK government have yet to comment on the long-term prospects of this fund.It must also be pointed out that this is not a problem with cancer drugs specifically. Many other diseases are facing the same problems. The cystic fibrosis drug Ivacaftor, for example, has had the same issues after it was priced as one of the world’s most expensive medicines (between £335,000 and £1,274,000 per QALY). Despite the cost, this drug is being used for a small number of patients in the UK. There was an extremely good article about the ethical concerns the over pricing of this drug in the British Medical Journal last year that I would encourage everyone to read it (available here for those with access, and by e-mailing us via the contact page on this site for those without).This all brings up another issue: are pharmaceutical companies over-charging for their treatments? According to a 2014 report, the cost of developing a new drug is now $2.6 billion (£1.7 billion), and takes over 10 years. The pharmaceutical companies argue that they have to make their drugs expensive in order to recoup their costs, and this is a valid point. This statement is slightly dented however, by the fact that the industry spends more on marketing than on research, a point well made by John Oliver in his show Last Week Tonight (below). Add to this the fact that the pharmaceutical industry makes a higher profit margin than any other industry, and the pricing of these drugs begins to look unreasonable. This issue is beyond the scope of this blog but you can find more information in this excellent BBC article.It is said that we are beginning the era of “personalised medicine”. Each person will receive a specific treatment for their cancer depending on the genetics of their disease. While this will mean more effective treatment of the disease, it also means that fewer patients will be getting any one drug. Cancer drugs will be used on smaller and smaller subgroups of people, which is likely to increase their price, as the cost of drug development is unlikely to drop. This raises difficult questions for an already struggling NHS. In a time of increasing drug prices and increasing cancer incidence, the challenge of funding these therapies will be a pressing issue for years to come.
[embed]https://www.youtube.com/watch?v=YQZ2UeOTO3I[/embed]
