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Chemotherapy and cancer, what are your survival odds?

Chemotherapy and cancer, what are your survival odds?

11/06/2017
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Merogenomics


An interesting and important study recently surfaced last year that was looking at cancer survival rates when treated with standard medical approaches. So how well are we doing? Read on!

Everyone in the world is familiar with cancer. It is hardly possible to journey through life and not encounter a story of someone who knows someone with cancer. We all identify emotionally with it to various degrees, ranging from fear to empathy. So this is a serious and important subject to be analyzed. And in this study, we are looking at the mortality rates within 30 days of breast or lung cancer treatment initiation, so clearly it is indicative that some of the resulting data will point to the heartbreaking reality of a poor success rate under certain circumstances. It is obviously worthwhile to investigate such information so that appropriate improvements can be discovered.

The anticancer therapies that were investigated were referred to as “any cytotoxic chemotherapy (combined chemo-radiotherapy or chemotherapy only), active anticancer therapies such as use of monoclonal antibodies (eg, trastuzumab), and targeted biological treatments such as EGFR tyrosine kinase inhibitors”. So there is a wide spectrum of modern treatment options. Data was collected on 23 000 cases for breast cancer, and nearly 10 000 cases for non-small cell lung cancer, in England in 2014. You may think, hey, this should be big news, and it was, but how it came to be was a surprising story to me!

I thought, it’s odd that these important findings seemed to have stirred up claims that this is more proof that "the establishment" does not want to find a cure for cancer in order to continue making profits. This is how I understood the gist of some of the reactionary articles, although probably twisted to some degree by my emotional interference. You know how that can sneak in and suddenly shape an opinion, so I might be guilty of that as well. Like when you send a text with an embarrassing autocorrect that will lead to much confusion on the receiving end before you can explain yourself! And as luck would have it, it only happens when you send a message to your partner, or your mom, or worse, your mother-in-law! Misunderstandings galore!

This is the opposite of how I understood the data interpretation as presented by the authors. The importance of such scientific data analysis of cancer survival rates should be focused on improving our current clinical solutions at hand, and not to make overarching claims. Indeed, this research revealed a lot of amazing information that I present below.

In fact, the article did not even investigate whether deaths were caused by side-effects from cancer treatment, cancer progression, or any other causes, so using this manuscript as evidence of harm by chemotherapy is mistaken from my perspective. Just because current medicine might not be able to cope with the treatment of certain cancers, it certainly does not indicate that there is no desire to help people. Based on the assessed numbers, there were few treatment centers that were demonstrating worse than average performance. These were notified to review both their clinical practice and also their data management systems, as poor performance numbers could have been due to data mismanagement and not poor clinical care. In the meantime, these outliers were used by some as the evidence of dangers of chemotherapy treatment, completely ignoring the information that the vast majority of the treatment centers of the entire country performed within the national averages or better. Yes, there was one institution in England for lung cancer treatment that was an extreme outlier, with 30-day mortality rates of more than 50%, and this is what was particularly latched onto by the investigators behind these articles. Indeed such institutions should be investigated, but that was an anomaly, in a hospital trust that saw less than 10 patients in that given year! This is not data that support claims that cancer treatments are dangerous and not meant to actually help people, as there were just too few people involved.

If you read bit further into the article, an interesting fact emerges: that the most common cause of mortality within those thirty days is not the cancer itself, or its treatment as believed by some, but by, and I quote: "neutropenic sepsis (infection resulting from low blood neutrophil count, probably the most important cause of [systemic anticancer therapies]-related death)”. Neutropenic sepsis “is highest in the 30 days after [anticancer therapy], peaking at around 11–15 days after treatment". Typically anticancer therapies are 21–28 days, and thus neutropenic sepsis is captured within those 30 days. Hence, the closer reality is that the treating doctors are in fact faced with very difficult choices in striking the right balance between an ideal dose for the patient that can minimize the odds of the neutropenic sepsis as well as the ability to combat cancerous cells. I would not want that responsibility, I would rather leave it to these experts who are dedicating their lives to help people get better, and cancer is a tough battle to wage for them!

Image containg article quote of the most common cancer mortality cause

Studies of the anticancer therapy impact are not common, as they are typically undertaken during the clinical trials of new therapy development. But conducting such research once treatment is available is important because of the larger sample sizes involved. Therefore the importance of this study is emphasized, which is the first of its kind on a national scale. What I found particularly interesting is that the study assessed both curative and palliative treatment models with regards to impact on mortality, as these treatment options are considered the opposite of one another.

So what is the difference between the palliative and curative model of medical care? Let us start with curative care, and what it encompasses.

Curative care, as its name first implies, focuses on the cure of disease, or the reversal of the progress and eradication of illness. It obviously sounds good, but for the context of the publication to be discussed, it should be understood that this is the only goal of curative care. Furthermore, this approach in modern medicine is distinctly analytic and rational, and based upon scientific inquiry, where the focus of analysis is the disease and not necessarily the patient. Scientific data is valued over any other anecdotal information, so that the test results and data obtained are only by the sanctioned methods used. Information that cannot be validated, explained, or that is subjective and not explainable in a scientific manner is typically disregarded, and at times even trivialized, including the personal opinions of the patient. So you can see why such methods, which are needed for the accurate understanding of disease etiology, might stir up serious emotional feelings, even a suggestion of neglect.

Another consequence of such an approach is that patients can be treated according to the specific organ systems being affected by clinical specialists, as if these organs were independent components of the body, without necessarily possessing an understanding of the entire body impact. Many people in alternative medicine bemoan this system of analysis, and perhaps correctly so, which can add to the confusion of understanding the effectiveness of modern cancer treatment. Modern medicine is also embracing such thinking though; the problem being the ability to effectively measure the whole body system impact. So sticking to the current best methods, medical decisions are based on empirical data that help determine what diagnostic tests and therapeutic treatments will be used on a patient. The result with such an approach is that the final outcome is a detailed analysis of the disease process and doesn’t view the patient as a "whole" individual, so that the treatments of patients are directed towards the disease, and not the patient. Thus the focus on personal issues - such as the impact on the quality of life - is not regarded as critical in targeting the disease-related outcomes. What this means is that if different individuals showcase identical symptoms, in theory, they should be treated in an identical way. Perhaps not the best approach, but it is also changing, as technology is evolving to incorporate ever wider and more complex data.

There is one obvious caveat to such an approach in medicine, in that an effective cure is dependent upon an effective diagnosis and the selection of appropriate treatment, neither of which can always be guaranteed. Far from it in fact! Some illnesses modern medicine can tackle with ease, while others can pose great difficulty. Cancer is one such example. And mistakes can and do occur. Diseases that cannot be cured or slowed are termed untreatable or beyond the help of the current state of knowledge.

I am a scientist and a researcher to the core so therefore I am very familiar with these concepts, and am a proponent of the empirical data-based approach. In fact, I frequently will lament that important decisions are often made that impact many lives without necessarily appropriate and thorough scientific investigation prior to those decisions. And such neglect of scientific oversight can be both very costly and very time consuming.

However, one of the major concepts taught to me during my doctorate studies was that one should be completely open-minded to all potential outcomes when testing a hypothesis, and not become emotionally invested regarding a desired outcome. It makes sense because wishful thinking can compromise the strategy behind planned experiments. Of course, in real life this is much harder to achieve, especially in a scientific world that praises and rewards novel positive results over negative results which state that nothing has happened. You have to admit, that is not very exciting! But a negative result is also important and valuable information. It is like the difference between discovering that drinking 15 pints of beer can upset your visual cortex function, or that nothing happens. For those who enjoy drinking beer, the latter would be pretty useful information (alas, that is not the case, so do not try this experiment in brain visual processing disruption). Not to mention that we are all human, and we tend to enjoy when our claims or suspicions are validated. Who doesn't enjoy feeling smug and smart, right?

But the idea of remaining open-minded toward possible outcomes has the additional advantage that all information could be of potential importance, and all information, including anecdotal and personally-provided content can be subject to some scientific analysis. So while I am a huge proponent of scientific investigation, I am a fan of the palliative care approach too, as I understand it.

Image containing article quote about breast and lung cancer mortality rate

So what is palliative care? In essence, palliative care would be the opposite of curative care, where the sick individual is investigated and treated as a whole, including psychological, cultural, and spiritual aspects, so personal well-being overrides the need to treat the disease itself. Instead, the focus is placed on the control of symptoms, the restoration of functional capacity, and the relief of suffering, as well as treatment of the disease, but only if it fits with the personal acceptance of such an approach. The approach tolerates more subjective information, information beyond the limits of current medicine, along with the personal preferences of a patient. So palliative care appears on the opposite side of the spectrum from curative care, and is used in a place where the curative model cannot help an individual; hence these approaches are often presented as mutually exclusive. In fact, the research article discussed in this post defined palliative care in cancer treatment as "to improve the quality of life for patients with advanced incurable cancers for as long as possible by controlling cancer growth and providing symptom relief.” Such an approach might or might not increase survival time.

And the truth is that elements of palliative care are used in conjunction with the curative approach, as circumstances necessitate it, which sounds appealing. One way to demonstrate this is with a simple infographic that is published and distributed by the BC Cancer Agency.

Image with graphic explaining what is palliative care

But in the study, these two approaches were studied separately.

So let me tell you what the study actually revealed, and let’s distill some facts from this fascinating work. After all the drama and what I saw as misinterpretation of the data, the good news is that 30-day mortality rates are low under the curative treatment model (<1% for breast and 3% for lung cancer on a national level in England). While obviously we can wish these events could be eradicated, the lower these numbers are, the better, as longer survival provides a longer window of opportunity to hopefully find the appropriate method of treatment. Not surprisingly, the mortality rate numbers are higher for palliative care (circumstances where the disease is deemed untreatable), and reaching 7% and 10% levels for breast and lung cancers, respectively.

Image of a graph depicting breast and lung caner mortality rates

Adapted from Wallington M et al. 2016. Lancet Oncol. 17(9):1203

Now the nitty-gritty part of the data, and some interesting findings. The 30-day mortality risk increased significantly with age for curative treatment but decreased significantly with palliative intent for either form of cancer (probably because such individuals are less likely to tolerate the side effects of cancer treatment, suggesting that the toxic effects outweigh the beneficial effects). This was exhibited with what is called “odds ratio”.

Odds Ratio is a statistical method used to determine the difference between two groups of people and the chance of experiencing a certain event. It presents the ratio between the odds of an event occurring in one group of people and the odds of that same event occurring in another group of people. In other words, it is a ratio between two probabilities. So the greater the number, the greater the chances are of the event occurring in one group over the other. For example, the chance of lung cancer development in smokers versus non-smokers, or the chance of a broken hip in people walking on freshly polished floors with socks on versus without. Okay, there probably is no such study, but I hope you get the point! And now that I said all this, I will skip providing these numbers because that would be too confusing to juggle so many numbers between all of the different criteria that was assessed! But I invite you to study the cancer survival odds tables provided in the publication. And I just focus on the gist of things!

Image with article quote about the difference between curative and palliative care in cancer survival

So the fact that the mortality rate decreased for palliative care where patients did not undergo chemotherapy is quite interesting information. It indicates that chemotherapy is not the best option for individuals at the end of life, as it does not bring the desired effects, while negatively impacting their quality of life.

Not surprisingly, patients with cancer with worse overall general wellbeing (this is measured by performance status ranging from no symptoms to patients who are completely bed-bound), had a higher 30-day mortality than those who were generally well. But it brings important information into focus that perhaps patients who are in such a state should be assessed more carefully for the best chemotherapy options prior to commencing such treatment now that the technology exist for such measures.

And this brings up another point that was really surprising to me, which was that treatment-naïve patients, i.e. those without any prior treatment, exhibited a significant increase in 30-day mortality risk compared to those who already had undergone at least one treatment. Once again, considering that DNA-sequencing can reveal information related to the most efficacious chemotherapy approach, what would be the impact of applying such technology to patient survival? Authors of the study commented that such individuals should be more carefully monitored for toxic side effects.

Cancer treatment

And here is a fact that at first seems like a shocking reminder of the disparities observed between people belonging to a different economic status. Most economically-deprived individuals with breast cancer exhibited the highest rate of 30-day mortality, while the least-deprived economic class exhibited the smallest and best odds ratio, with a 7-fold difference observed between these two group’s numbers. But before you react with indignation to the inequalities of the world, let me complicate the picture a little. All other financial-status groups of either lung cancer individuals or any of those under palliative care for breast or lung cancer did not show such patterns. So while money can always help to a degree, cancer appears to be more of an equalizer. But what I would really have loved to know is how many of these individuals (of the thousands of people assessed), utilized the benefits of the latest genomics technologies? These are very powerful modern technologies, but they are not cheap to use, especially with the interpretation of the complex results. This is where a financial status could become an influencing factor, as the incorporation of these technologies into clinical care has commenced but will require time to be equitably available throughout the world, and the study did not go into such nuances.

So for all of that drama created on social media regarding this article, I will agree that perhaps there is some truth in cancer not being treated as effectively as it could be, but if so, it is born from the ignorance of knowing how best to utilize all of the available technology, and not by willful neglect. In fact, the industry is making giant investments into understanding cancer using the latest genomic technologies, precisely to help develop better and more efficacious treatments, with as direct a benefit to patients as possible. Clinical studies show that, and perhaps this research presents some evidence for that as well. The observations offered in this study suggest that that 30-day mortality rates might be higher in the general population than as demonstrated by clinical trials. The authors argue that it is precisely because clinical studies seek fitter patients in order to guarantee greater safety by ensuring that older patients, or those with a worse performance status, are not put under undue risk. Such clinical trial patients also tend to receive far more intensive support and follow-up than what is normally provided in a typical hospital setting due to the cost of resources required.

Image of article quote about cancer genome investments

The bottom line is this study is very valuable for many reasons. It is one-of-a-kind in its scope as well as what type of information it has investigated, and considering the type of subject involved, it deserves a great deal of attention. But I feel that it has received recognition for the wrong reasons. At the same time, because of the attention it has received, whether I agree with it or not, it was the reason I found out about this study, and such negative focus must be born out of some genuine concerns. Do we have reasons to be concerned? Yes, perhaps. But not for the reasons where there is a deliberate avoidance of the desire to cure cancer. I see evidence very much to the contrary myself. I talk to the people involved in the pharmaceutical industry, people involved in clinical trials, in the highest ranks of management and under academic oversight. We are talking about a very strict code of ethical oversight. And my experience so far has always been that the people involved are driven by desire to help. Yes, there is money to be made, but money is the reward for smart inventions, and many of these smart inventions have come from the desire to improve human health. And from my own individual experiences in the agricultural industry, also a desire to improve animal and plant health! People often overlook the amount of investment that is taking place into the continual improvement of medicine. Because these studies have to be so rigorously controlled, they are usually superbly expensive, especially if utilizing expensive novel technologies. To me, the concern should be that we do not have enough studies such as these that help to collect valuable data which could pinpoint how best to improve treatment. Treatment based on understanding whom novel technologies should be applied to, which could truly be life-changing.

Image of article quote about the cost of medical procedures

Interestingly enough, my own emotional investment into the power of genome sequencing (after all, it is my job, so I better love what I study, as long as I am impartial to results), ironically can promote the individualization of a curative approach. In the past, people would have been treated in an identical fashion based on their identical symptoms; but now genome sequencing can potentially aid in a deeper understanding of how their care ought to be personalized. For example, the type or quantity of medication used as part of the treatment. But genome sequencing is a serious matter to consider, as it reveals the most personal biological information about an individual as a whole, with all organ systems involved. Personal considerations, like the subjective opinions of a patient, need to be taken into account due to potential emotional impacts. Is it too soon to be excited that genomic technologies could be fostering an even greater merging of both curative and palliative care approaches? You decide and let me know what you think. You already know how I feel!

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This article has been produced by Merogenomics Inc. and edited by Kerri Bryant. Reproduction and reuse of any portion of this content requires Merogenomics Inc. permission and source acknowledgment. It is your responsibility to obtain additional permissions from the third party owners that might be cited by Merogenomics Inc. Merogenomics Inc. disclaims any responsibility for any use you make of content owned by third parties without their permission.

 

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