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!
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!
Vitamin supplements: unexpected consequences
Over the last number of years, the vitamin and nutritional supplement market has grown phenomenally. It is estimated to be worth over $36 billion in the US, up from $17 billion in 2000. It is thought that nearly 70% of the US population take some kind of dietary supplement, and there is much said and written about their use. One thing that cannot be debated however, is the lack of evidence that they do any good. A prime example of this comes from a study published recently about vitamin B supplements.
The study looked at vitamin B use and lung cancer. They decided to do this because a previous study had reported an increase in these cancers in people taking vitamins B12 and B9, but that study wasn't designed to look specifically at this, so more work was needed.This study looked at over 77,000 people between the ages of 50 and 76, over a number of years. The results were striking. Vitamin B6 or vitamin B12 use was associated with a doubling in lung cancer risk in men, if taken at above the recommended daily allowance. Since people generally have no idea what the recommended daily allowance is, and the levels of these vitamins can be very high in supplements, there may be many people putting themselves at risk. Indeed, the majority of people taking vitamins unknowingly exceeded the recommended daily allowence.There are a few details that are worth noting. First, the effect was only seen in men and not in women. Second, the association was even stronger in smokers, who are already prone to lung cancer. Third, this effect was present for B6 and B12, but not for people taking B9 (also known as folic acid). Finally, the authors found no beneficial effects of vitamin B supplements in any group.So what does this mean in real terms? Of the 37,049 men in this study, 1966 where found to be taking the highest dose of vitamin B. Of that 1966, 36 were ultimately diagnosed with lung cancer. If they had not been taking vitamin B supplements, this would be expected to be 18 lung cancer diagnoses. That suggests that high vitamin B use was associated with roughly an additional 18 cases of lung cancer. When you consider that this study had over 77,000 people enrolled, 18 additional cases of lung cancer may seem quite small, and these numbers are indeed dwarfed by the additional cases caused by smoking, but it is still significant.As always, I have to point out that this study did not show that vitamin B supplementation caused these extra lung cancers, just that men taking high doses were more likely to get it. As I have previously described, correlation is not the same as causation. However, this was a well carried out study, and the authors controlled for as many variables as they could, making it more believable that the vitamin supplementation is contributing to the cancers.What is clear however, is that vitamin B pills give no benefit on any health outcome. Considering that they may even be doing some harm, it emphasises that we should be cautious when supplementing our diet with unnaturally high levels of vitamins. It is generaly assumed that the more vitamins the better, but as this study points out, that is not the case. A healthy, varied diet more than meets our vitamin needs. Why spend money on supplements if we don't need them?
Is coffee bad for you?
People have an undying love for coffee. Around the world, it’s estimated that 2 billion cups are drank every single day. Lots of people can’t start the morning without one, and there’s now a coffee shop on every corner in every city. 
Considering this popularity, it is perhaps unsurprising that the health benefits/health damaging effects of coffee are never far from the news. This year alone has seen 25 different articles on the Daily Mail Online, detailing why the drink is going to make you live longer or shorter, depending on the article. Of those 25, 14 were extolling the benefits of coffee, while 11 were describing the opposite.On one particularly impressive week the site published six separate articles on the topic, claiming among other things that coffee is nature’s Viagra, that it protects against liver cancer, and that it can cause miscarriage and birth defects. If you were to ask somebody whether coffee was good or bad for them, I sincerely doubt that they would know. So what does the evidence say?Quite a lot actually. There have been many studies on the role that coffee may play in different diseases, which I will get in to below. As is almost always the case however, the first thing to say is that there’s probably no need to change your habits. Whether coffee is good for you or bad for you, the effect seems to be minor. If you love your coffee, there’s no need to cut back. If you’re not a drinker, there’s no need to start.Before I get into the health implications of coffee, it is worth mentioning that aside from the drink itself, people should really think about the way they drink their coffee. It is thought that at least 58 billion paper cups are thrown away each year, made from 32 million trees, and requiring a staggering 100 billion litres of water for their production. It is an extraordinarily wasteful industry, and something as simple as buying a reusable cup can make a significant difference, particularly if it is not made from plastic.
Below I have described what the current literature has to say regarding coffee consumption and various diseases. Ultimately, it is safe to say that for a healthy person with no underlying conditions, normal coffee consumption is probably good for you. The benefit is small in all cases, so it is not something to worry about. As always, there are caveats involved (whether you take sugar in your coffee, whether you drink decaffeinated, how hot it is when you drink it…), but I have tried to answer the major questions below. It is worth pointing out that although an individual coffee drinker is unlikely to see any benefit from their habit, due to the large number of drinkers around the world coffee drinking could potentially have a large impact on the overall health of the population.
Ultimately, it is safe to say that for a healthy person with no underlying conditions, normal coffee consumption is probably good for you.
Q: How much coffee is too much?In general, various safety authorities suggest that 2 – 3 cups of coffee in one sitting is perfectly fine, provided that people don’t drink much more than 6 in a day. For most people, 8 – 10 cups will begin to produce negative side effects, including migraine, anxiety, nervousness, trembling, insomnia and an increased heart rate. These side effects are all caffeine related, and this seems to be the main culprit in the coffee-related problems. Obviously the amount of caffeine differs in different coffee brands and brews, and the numbers above relate to roughly one shot of espresso per cup. There has not been any study confirming or refuting long-term detrimental side effects of regularly drinking more than 6 cups per day (apart from extreme cases when people far exceed this), so we can’t really say either.A: 6 cups seems to be the recommended daily limit for a healthy person, but this is largely precautionary. Q: Does coffee change your risk of dying?The simplest thing we can look at is whether coffee makes you live longer. There have been numerous studies into this, and their results have been mixed. It is pretty clear that coffee doesn’t in general shorten life. Several studies have found no correlation between coffee consumption and longer life, however some have found the opposite. The most recent work I could find suggests that those drinking more than 4 cups a day were at a lower risk of dying, however this was only true in people over 45 years of age. This work was presented at a conference and has yet to be published, so I haven’t been able to have a look at their analysis. However, confusingly, other studies have found that those who drink small amounts of coffee (1 cup a day) get a benefit, but that benefit disappears if you drink more than 4 cups. Some studies claim that women benefit more than men, and others that the benefits depends on what ethnic group is being studied. All in all, the literature is mixed, which is a clear sign that if there is an effect, it is a tiny one. It is interesting to note though, that the scientists who carried out the most recent study found that even people who drank decaffeinated coffee got some of this benefit, meaning that the effect may only partially be as a result of caffeine intake.A: Coffee may extend life in certain circumstances, but if it does, the effect is tiny. Q: Are coffee and cancer associated?As coffee drinking and smoking often went hand in hand in the past, it is difficult to separate the two in studies. What is clear is that the results are mixed. A Japanese study suggested that high coffee consumption (over 5 cups a day) had a protective effect. Another recent analysis suggested that coffee is not associated with the large majority of cancers, with a few exceptions. Coffee seems to have a protective effect against liver cancer, but the size of this effect is debatable. However as most liver cancers are related to either smoking or obesity, there are far bigger interventions that can be made to protect against this cancer. There have been studies showing a slightly reduced incidence of endometrial, skin, gallbladder, oral, and kidney cancer in coffee drinkers, but these studies have yet to be confirmed. Finally, there was a suggestion that coffee drinkers were more prone to prostate cancer, but recent studies have cast doubt on this.A: Coffee seems to have a protective effect against liver cancer, and potentially against several others. Q: Does coffee affect heart health?It was thought for a long time that coffee was associated with cardiovascular diseases, hypertension, and heart failure. This makes intuitive sense; when people have too much coffee, they often feel like their heart is racing. Several studies seemed to show this was the case, however none of the studies were thorough enough to tell for sure. More recent studies have shown that this is not the case, and that coffee has either a neutral or a beneficial effect on heart health. For example, some studies show that coffee is protective against coronary heart disease in women, and reduces the risk of death in patients who have had a heart attack. Other studies show no change or an increase in coronary heart disease risk, so any effect is likely to be small.A: Coffee has a neutral or slightly beneficial effect on heart health. Q: How about the effect of coffee on mental health?The number of studies looking at this is smaller than in the previous paragraphs. However, those that have been done do show that coffee has a slight protective effect on depression risk, although some of those studies were of poor quality. Due to the sleep disturbing effects of excess caffeine, there is reason to think that this may also have a detrimental effect on mental health, but the evidence has not backed this up.A: Coffee seems to have a slight beneficial effect on mental health Q: Does coffee play a role in neurodegenerative diseases like Alzheimer’s and Parkinson’s?Lifelong coffee consumption seems to have a protective effect on the development of Alzheimer’s and Parkinson’s. In both cases the effect was more pronounced in the early stages of the disease, and in the case of Parkinson’s, it the effect was bigger in men than in women.A: Long-term coffee drinking has a slight protective effect in age-related dementia Q: Does coffee protect your liver?It is in liver disease that we see the biggest protective effect of coffee. Liver enzymes tend to be lower in coffee drinkers (which is a good thing). Interestingly, this tends to be more pronounced in patients at the highest risk of liver disease, such as alcoholics. It is also beneficial in non-alcoholic liver disease and other metabolic syndromes. Coffee inhibits the Hepatitis C virus, and drinkers show lower levels of damage in their livers, and as mentioned above, coffee seems to have a protective effect against liver cancer.A: Coffee has a slight but significant protective effect against almost all kinds of liver disease and damage Q: Does coffee affect fertility?There is very little evidence that coffee consumption has a measurable effect on fertility. Several studies have shown a slight decrease in semen quality with high caffeine intake, and others show a very slight increase in the time to pregnancy for caffeine drinkers. This study included energy drink consumption have far higher levels of caffeine than coffee, so the results were probably skewed by that population. Several larger studies have found no correlation between coffee consumption and an increased time to pregnancy.A: Coffee drinking does not decrease fertility. Q: Is coffee safe in pregnancy?Many women avoid caffeine during pregnancy, preferring to err on the side of caution in this case. The WHO recommends limiting caffeine intake during pregnancy to 3 cups or fewer per day, and the evidence supports this conclusion. Studies have shown that high caffeine intake is associated with a slightly higher risk of pregnancy loss and developmental defects. If drinking fewer than 3 cups per day however, there is no evidence of an increase in foetal malformation, neurodevelopmental defects, or miscarriage.A: High coffee consumption may cause issues in pregnancy, but no problems have been seen for those drinking 1 – 2 cups per day.
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.
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.
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.
Should children eat rice cakes?
I’ve seen this story pop up on my newsfeed a few times recently, so I thought I’d have a look and see if there is much to it.It is an article about some new guidelines in Sweden regarding arsenic in rice products. They state that due to high levels of arsenic, some rice products can be harmful to children, and that many of them should be rationed, or even avoided altogether.In case you don’t want to read the rest of this blog post, I’ll give you my take on it first. We are already aware that there are high levels of arsenic in rice products, and the US FDA (Food and Drugs Administration) has been monitoring it for years. Long-term exposure to low levels of arsenic has been associated with various cancers, including those of the kidney, bladder and liver. Some in the press have also reported neurotoxicity in children, but there is little reliable evidence for this in the literature.While the link with cancer may be real, the level and time of exposure required to see such effects would suggest that the Swedish Food Safety Authorities are going overboard with this advice, and the possibility of harm is only in extreme cases. So as always, the key is to exercise moderation in all things.The article reports that the Swedish National Food Agency tested 102 rice products for arsenic levels, and recommended that:
"children should not eat rice or rice products such as rice porridge, rice noodles, or breakfast cereal made of puffed rice, such as Rice Krispies, more than four times a week. And with regards to rice cakes, children should completely avoid these."
This advice is slightly puzzling, as it has been known for a long time that there is inorganic arsenic in much of our food, but particularly in rice products. The US FDA has been monitoring arsenic levels in rice products for the last 25 years. In their most recent tests, they analysed over 1300 products, and found results similar to those in Sweden. However, the FDA did not reach the same conclusions regarding safety, something I will go into more later.Unfortunately there isn’t much advice available as to what constitutes “safe” levels of arsenic in food. There are fairly clear guidelines about arsenic in drinking water, but comparing levels in food to those in water is difficult, so the following should be taken with caution.The World Health Organisation (WHO) recommends a limit of 10ug (10 millionths of a gram) per litre of drinking water. They report that there is some evidence of toxicity if the level is 50 – 100ug per litre, which is 5 – 10 times above their recommended limit. Furthermore, they report that from 10 – 50ug per litre there is a possibility of adverse effects, but that these would be at such a low incidence that they would be difficult to detect.Taking the WHO guidelines as reasonable, small children (aged 5 to 8, who drink around a litre of water per day) can expect to stay healthy ingesting 10ug of arsenic per day from their drinking water. This doesn’t take into account the additional arsenic they get from food. However, let’s go with the WHO and take 10ug per day as the safe dose.Many of the rice products tested contain a significant portion of that. Rice cakes, for example, have 4ug of arsenic, while Rice Krispies have 2.2ug. So if a child was to have rice-based cereal for breakfast, rice for dinner and snack on rice cakes, you can see how they could easily exceed our safe dose.This isn’t a problem if it happens irregularly; however, if a child is getting this dose of arsenic every day, then, using the cautious WHO estimates, there is a small possibility of future problems.As I mentioned above, the US FDA have also been keeping an eye on arsenic in rice products. Their testing has been far more comprehensive than that in Sweden, and their findings have been very similar. However, they do not have the same recommendations as the Swedish National Food Agency. The FDA recommends the following:
"Eat a well-balanced diet. All consumers, including pregnant women, infants and children, are encouraged to eat a well-balanced diet for good nutrition and to minimize potential adverse consequences from consuming an excess of any one food. This advice is consistent with the guidance of the American Academy of Pediatrics, which has long stated that parents should feed their infants and toddlers a variety of foods as part of a well-balanced diet.Consider diversifying infant foods: The FDA recognizes that children routinely eat rice products and that by tradition many infants are fed rice cereal as their first solid food. According to the American Academy of Pediatrics, there is no medical evidence that rice cereal has any advantage over other cereal grains as a first solid food and infants would likely benefit from an array of grain cereals."
In conclusion, it is probably right to say that the levels of arsenic in rice may be a problem for children who eat very large amounts of rice products every day. Feeding children 5 rice cakes per day probably isn't the best idea either. However, recommending an outright ban on rice cakes for children seems very extreme, and un-needed. In moderation, they are a perfectly good snack. Parents have enough to worry about, and if a child is getting a balanced diet, then arsenic should not be another thing on that list.
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.
Can dogs smell cancer?
This week the Guardian reported on the ability of dogs to detect prostate cancer.
Dogs trained to detect prostate cancer with more than 90% accuracy The Guardian - 11/04/2015
Italian scientists published a study this week that showed that two dogs they tested were able to detect prostate cancer with remarkable accuracy. One of the dogs correctly detected all cases of prostate cancer and the other detected 98.6% of cancers. On the other hand, the dogs falsely detected cancer in 1.3% and 2.4% of the negative samples too. Both dogs are German Shepherds that had previously been trained for bomb detection, and while their success as bomb sniffers was not addressed, the paper shows that as prostate cancer sniffers they are pretty amazing.How does this compare?In real terms, what do these numbers mean?Consider the UK male population of roughly 30 million, with 0.15% of them being diagnosed with prostate cancer every year. That is 45,000 men.If we test all 30 million men every year, the more accurate dog will detect almost all of the 45,000 cancers each year. However, as it also detects 1.3% false positives, it will also falsely identify the disease in 390,000 perfectly healthy men (1.3% of 30,000,000).This number of false positives may not sound very impressive, but let’s put it in perspective: the standard lab-test for prostate cancer (PSA test) would detect around 27,000 of the 45,000 cancers, but crucially would detect a whopping 3,900,000 false positives! (The exact numbers for this depends on various variables, but I have used the estimates from here, using 3.0 ng/ml testing). So not only does it falsely detect many more prostate cancers than there really are, but importantly almost half of men that do have the disease walk away undiagnosed.This is still a hypothetical situation as PSA is not used routinely to screen for prostate cancer in the general population, but it does emphasise just how effective these dogs are at detecting this disease. I have included a little explanation of cancer screening below for anyone who is interested.Practicalities of using dogs in the clinicThis isn’t the first time dogs have been suggested as good cancer detectors. There have previously been reports of them detecting lung cancer, breast cancer and bladder cancer (albeit with far less impressive results than this). However, at the moment it is just not viable to introduce dogs to the clinic. A test used for cancer detection has to be reliable, and other studies haven’t proven as successful as this one. Add to that the practicalities of using live animals in the clinic (training, housing, feeding and handlers), and you can begin to see why this is not currently planned.However, if scientists can figure out what it is the dogs are actually detecting (at the moment they have no idea), it may be possible to design a much better lab-test for it which will be far easier to get into the clinic. These “electronic noses” are already in clinical trials for lung cancer, and are showing promising results. Whether these will prove to be cheaper and more effective than dogs remains to be seen, but for the time being it is a very active and interesting area of research. And, let’s be honest, most people are likely to prefer having their urine sniffed by a dog than have a rectal examination, the current standard test for prostate problems… Screening for cancerScreening for a disease means testing an entire group of people for the disease, regardless of whether they show symptoms or not. The NHS in the UK provides a screening service for breast, cervical and bowel cancer. These are tests that people undergo as part of a normal health check-up, once they reach a certain age. These screens aim to flag up any potential problems, so the patients can go for further tests.While we have tests for many other cancers, these are the only three that it is deemed cost effective to screen for. Take the PSA test for prostate cancer, mentioned above. The cost to the NHS to further test the high number of false positives would be immense. On top of that there is the worry and stress experienced by people who test positive wrongly. There has been debate in the medical field as to whether breast cancer screen is worth doing, for the same reason.Obviously it would be very desirable to screen the population for every cancer. The earlier a tumour is caught, the better. However, the tests we have for the large majority of cancers are either not reliable enough, or are too expensive, for screening purposes.
Vaccinating ourselves against cancer
Several news outlets carried a story this week regarding very promising results of cancer vaccines trials. This was a very small trial (on just three patients) who had an aggressive and late-stage skin cancer known as melanoma. In all three patients the cancers stopped growing, and they were alive and well at the time of publication. In spite of the low number of patients, this study provides a tantalising glimpse of a brand new form of cancer therapy.
So how would these vaccines work? The aim is to teach the patient’s own immune system that cancer cells are bad. That way, our own bodies could potentially mount a natural and effective response, free of the side-effects of conventional chemotherapy. Myriam has previously posted a great blog on how the immune system works (which can be found here), so I’ll stick to the basics.Our immune system recognises invaders or abnormal growths by reading what molecules are sticking out from the surface of cells. These molecules are known as antigens. If the immune system recognizes a cell's antigens as being foreign or abnormal, it will mount an immune-response to clear it from our system. The key is to correctly differentiate foreign antigens from normal, and this is the responsibility of a group of “teacher” immune cells which differentiate friend from foe and teach the other immune cells to do the same. These teacher cells include cells known as “dendritic cells”, which were used in this study.However, cancer cells are problematic for these “teacher” cells. Because cancers arise from a cell that was once healthy, they are sometimes not recognised as being abnormal, and as a result the immune system isn’t alerted to the problem.What these scientists did was to analyse the cells in a biopsy of the patient’s tumour to understand what molecules (antigens) are sticking out from the surface of only the cancer cells. The next step was to train the teaching cells (dendritic cells) to see these specific antigens as foreign. These newly-educated dendritic cells were then put back into the patient’s blood, where they could teach other immune cells to attack the tumour. Encouragingly, after the dendritic cells were infused back into the patients, they mounted a massive immune response to the tumour. It remains to be seen whether this presents a long term solution to these people’s cancers, but it is an exciting “proof of principle” study.This is a very promising new therapy for cancer. It has the potential to be very specific to the tumour and hence have very few side effects. Large scale use of such technology is still quite a few years away, but his is a very exciting step along that path.
