From immunotherapy to mRNA vaccines – the latest science on melanoma treatment explained
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More than 16,000 Australians will be diagnosed with melanoma each year. Most of these will be caught early, and can be cured by surgery.
However, for patients with advanced or metastatic melanoma, which has spread from the skin to other organs, the outlook was bleak until the advent of targeted therapies (that attack specific cancer traits) and immune therapies (that leverage the immune system). Over the past decade, these treatments have seen a significant climb in the number of advanced melanoma patients surviving for at least five years after diagnosis, from less than 10% in 2011 to around 50% in 2021.
While this is great news, there are still many melanoma patients who cannot be treated effectively with current therapies. Researchers have developed two exciting new therapies that are being evaluated in clinical trials for advanced melanoma patients. Both involve the use of immunotherapy at different times and in different ways.
The first results from these trials are now being shared publicly, offering insight into the future of melanoma treatment.
Immunotherapy before surgery
Immunotherapy works by boosting the power of a patient’s immune system to help kill cancer cells. One type of immunotherapy uses something called “immune checkpoint inhibitors”.
Immune cells carry “immune checkpoint” proteins, which control their activity. Cancer cells can interact with these checkpoints to turn off immune cells and hide from the immune system. Immune checkpoint inhibitors block this interaction and help keep the immune system activated to fight the cancer.
Results from an ongoing phase 3 trial using immune checkpoint inhibitors were recently published in the New England Journal of Medicine.
This trial used two types of immune checkpoint inhibitors: nivolumab, which blocks an immune checkpoint called PD-1, and ipilimumab, which blocks CTLA-4.
Some 423 patients (including many from Australia) were enrolled in the trial, and participants were randomly assigned to one of two groups.
The first group had surgery to remove their melanoma, and were then given immunotherapy (nivolumab) to help kill any remaining cancer cells. Giving a systemic (whole body) therapy such as immunotherapy after surgery is a standard way of treating melanoma. The second group received immunotherapy first (nivolumab plus ipilimumab) and then underwent surgery. This is a new approach to treating these cancers.
Based on previous observations, the researchers had predicted that giving patients immunotherapy while the whole tumour was still present would activate the tumour-fighting abilities of the patient’s immune system much better than giving it once the tumour had been removed.
Sure enough, 12 months after starting therapy, 83.7% of patients who received immunotherapy before surgery remained cancer-free, compared to 57.2% in the control group who received immunotherapy after surgery.
Based on these results, Australian of the year Georgina Long – who co-led the trial with Christian Blank from The Netherlands Cancer Institute – has suggested this method of immunotherapy before surgery should be considered a new standard of treatment for higher risk stage 3 melanoma. She also said a similar strategy should be evaluated for other cancers.
The promising results of this phase 3 trial suggest we might see this combination treatment being used in Australian hospitals within the next few years.
mRNA vaccines
Another emerging form of melanoma therapy is the post-surgery combination of a different checkpoint inhibitor (pembrolizumab, which blocks PD-1), with a messenger RNA vaccine (mRNA-4157).
While checkpoint inhibitors like pembrolizumab have been around for more than a decade, mRNA vaccines like mRNA-4157 are a newer phenomenon. You might be familiar with mRNA vaccines though, as the biotechnology companies Pfizer-BioNTech and Moderna released COVID vaccines based on mRNA technology.
mRNA-4157 works basically the same way – the mRNA is injected into the patient and produces antigens, which are small proteins that train the body’s immune system to attack a disease (in this case, cancer, and for COVID, the virus).
However, mRNA-4157 is unique – literally. It’s a type of personalised medicine, where the mRNA is created specifically to match a patient’s cancer. First, the patient’s tumour is genetically sequenced to figure out what antigens will best help the immune system to recognise their cancer. Then a patient-specific version of mRNA-4157 is created that produces those antigens.
The latest results of a three-year, phase 2 clinical trial which combined pembrolizumab and mRNA-4157 were announced this past week. Overall, 2.5 years after starting the trial, 74.8% of patients treated with immunotherapy combined with mRNA-4157 post-surgery remained cancer-free, compared to 55.6% of those treated with immunotherapy alone. These were patients who were suffering from high-risk, late-stage forms of melanoma, who generally have poor outcomes.
It’s worth noting these results have not yet been published in peer-reviewed journals. They’re available as company announcements, and were also presented at some cancer conferences in the United States.
Based on the results of this trial, the combination of pembrolizumab and the vaccine progressed to a phase 3 trial in 2023, with the first patients being enrolled in Australia. But the final results of this trial are not expected until 2029.
It is hoped this mRNA-based anti-cancer vaccine will blaze a trail for vaccines targeting other types of cancer, not just melanoma, particularly in combination with checkpoint inhibitors to help stimulate the immune system.
Despite these ongoing advances in melanoma treatment, the best way to fight cancer is still prevention which, in the case of melanoma, means protecting yourself from UV exposure wherever possible.
Sarah Diepstraten, Senior Research Officer, Blood Cells and Blood Cancer Division, WEHI (Walter and Eliza Hall Institute of Medical Research) and John (Eddie) La Marca, Senior Research Officer, Blood Cells and Blood Cancer, WEHI (Walter and Eliza Hall Institute of Medical Research)
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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What Grief Does To Your Body (And How To Manage It)
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What Grief Does To The Body (And How To Manage It)
In life, we will almost all lose loved ones and suffer bereavement. For most people, this starts with grandparents, eventually moves to parents, and then people our own generation; partners, siblings, close friends. And of course, sometimes and perhaps most devastatingly, we can lose people younger than ourselves.
For something that almost everyone suffers, there is often very little in the way of preparation given beforehand, and afterwards, a condolences card is nice but can’t do a lot for our mental health.
And with mental health, our physical health can go too, if we very understandably neglect it at such a time.
So, how to survive devastating loss, and come out the other side, hopefully thriving? It seems like a tall order indeed.
First, the foundations:
You’re probably familiar with the stages of grief. In their most commonly-presented form, they are:
- Denial
- Anger
- Bargaining
- Depression
- Acceptance
You’ve probably also heard/read that we won’t always go through them in order, and also that grief is deeply personal and proceeds on its own timescale.
It is generally considered healthy to go through them.
What do they look like?
Naturally this can vary a lot from person to person, but examples in the case of bereavement could be:
- Denial: “This surely has not really happened; I’ll carry on as though it hasn’t”
- Anger: “Why didn’t I do xyz differently while I had the chance?!”
- Bargaining: “I will do such-and-such in their honor, and this will be a way of expressing the love I wish I could give them in a way they could receive”
- Depression: “What is the point of me without them? The sooner I join them, the better.”
- Acceptance: “I was so lucky that we had the time together that we did, and enriched each other’s lives while we could”
We can speedrun these or we can get stuck on one for years. We can bounce back and forth. We can think we’re at acceptance, and then a previous stage will hit us like a tonne of bricks.
What if we don’t?
Assuming that our lost loved one was indeed a loved one (as opposed to someone we are merely societally expected to mourn), then failing to process that grief will tend to have a big impact on our life—and health. These health problems can include:
As you can see, three out of five of those can result in death. The other two aren’t great either. So why isn’t this taken more seriously as a matter of health?
Death is, ironically, considered something we “just have to live with”.
But how?
Coping strategies
You’ll note that most of the stages of grief are not enjoyable per se. For this reason, it’s common to try to avoid them—hence denial usually being first.
But, that is like not getting a lump checked out because you don’t want a cancer diagnosis. The emotional reasoning is understandable, but it’s ultimately self-destructive.
First, have a plan. If a death is foreseen, you can even work out this plan together.
But even if that time has now passed, it’s “better late than never” to make a plan for looking after yourself, e.g:
- How you will try to get enough sleep (tricky, but sincerely try)
- How you will remember to eat (and ideally, healthily)
- How you will still get exercise (a walk in the park is fine; see some greenery and get some sunlight)
- How you will avoid self-destructive urges (from indirect, e.g. drinking, to direct, e.g. suicidality)
- How you will keep up with the other things important in your life (work, friends, family)
- How you will actively work to process your grief (e.g. journaling, or perhaps grief counselling)
Some previous articles of ours that may help:
- How To Keep On Keeping On ← this is about looking after general health when motivation is low
- The Mental Health First-Aid You’ll Hopefully Never Need ← this is about managing depression
- How To Stay Alive (When You Really Don’t Want To) ← this is about managing suicidality
- Life After Death? (Your Life; A Loved One’s Death) ← this is about bereavement and romance
If it works, it works
If we are all unique, then any relationship between any two people is uniqueness squared. Little wonder, then, that our grief may be unique too. And it can be complicated further:
- Sometimes we had a complicated relationship with someone
- Sometimes the circumstances of their death were complicated
There is, for that matter, such a thing as “complicated grief”:
Read more: Complicated grief and prolonged grief disorder (Medical News Today)
We also previously reviewed a book on “ambiguous loss”, exploring grieving when we cannot grieve in the normal way because someone is gone and/but/maybe not gone.
For example, if someone is in a long-term coma from which they may never recover, or if they are missing-presumed-dead. Those kinds of situations are complicated too.
Unusual circumstances may call for unusual coping strategies, so how can we discern what is healthy and what isn’t?
The litmus test is: is it enabling you to continue going about your life in a way that allows you to fulfil your internal personal aspirations and external social responsibilities? If so, it’s probably healthy.
Look after yourself. And if you can, tell your loved ones you love them today.
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Astrology, Mental health and the Economics of Well Being
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Ultimately can the mental health system single-handedly address the concerns of inequality and economic access in society?
Around 75 per cent of the Indian population lives in rural areas, but their access to quality mental health care is limited and traditional approaches continue to be in use. The shortage is to such a large extent that there are only 0.7 physicians per 1000 population and only one psychiatrist for every 343,000 Indians. While over the years the mental health sector has seen major developments, like the 2017 mental health care act. This act establishes equal access for all citizens, to avail government-run or funded mental health services in the country. However, it does not bridge the gap in society as the majority of the population remains deeply unaware or unable to access these services.
While the uncertainties of the pandemic brought mental wellbeing to the forefront, the national budget for the sector dropped, making this an issue of human rights. This accessibility to services is further corroborated by the recurring financial expenses of medications and frequent visits to government clinics. The cost of sessions is steep and a single session is not ideal. Spending exorbitant amounts on healthcare is a burden most families can’t afford leading to debt. In the absence of insurance and healthcare schemes and provisions, therapy remains a luxury to many Indians.
Economic struggles are only one of the causes of this discerning gap in the mental health sector. Barriers caused by sexuality, gender, caste and religion also play a major role in mediating people’s perception and access to therapeutic services. The persistent stigma surrounding mental health, especially in India continues to be a hindrance to seeking help. The supernatural inhibitions and disparity in knowledge across communities only create more confusion. The notion that mental well being is an optional expense is popular, even though the country’s population is in a dire state. Data collected in a WHO report found that nearly 15 per cent of Indian adults need active intervention for one or more mental health issues.
The population disregards the very prevalence of such mental disorders and more than often finds it fruitless to receive treatment. Some who are open-minded fail to afford the hiked fees that therapists in urban settings charge, leaving them with no option. While for years Indians attributed the systemic weakness of the mental health system to the people’s attitudes, a 2016 survey showed more than 42% of people have positive attitudes toward mental wellbeing and treatment. While the skeptics remain, these underprivileged sections of society too struggle to gain the accessibility they deserve.
This is where astrology, tarot card reading and other spiritual practices, have created a market for themselves in the well-being industry. The sceptics, and those from poor socio-economic backgrounds resort to these local and easily accessible ways of coping, to instil the faith they so desperately need. Astrology is a layman’s substitute for therapy, or for some even a supplement when they cannot afford extended periods of treatment. Visiting a local astrologer in many ways breeds the self-awareness one would expect from a session in therapy. These practices even hold certain similarities to actual psychotherapy settings, in the way they define, and alleviate aspects of one’s personality and behaviour.
Very often one simply needs an explanation, or an answer to the ‘why’ no matter how scientifically rooted that response truly is. Astrologers impart a level of faith, that things will get better. For those in rural areas, struggling to provide the bare necessities to their family affording therapy is impossible, so their local psychic, astrologer or pandit becomes their anchor during emotional duress. Tarot cards and other practices primarily focus on the future and act as a guide point for how to deal with the things ahead. For a farmer coping with anxiety, access to anti-anxiety medication is strained, and so is therapy. His best bet remains to consult his next-door jyotish about his burdens.
A famous clinician Caroline Hexdall in an interview said that “ Part of the popularity of astrology and tarot today has to do with their universal nature”. With growing technology and the pervasiveness of social media, people can gain easy access to self-care and astrology resources. Apps and web pages provide daily tarot cards, zodiac signs readings and astrological predictions for people, and almost serve the purpose of a therapist. Is reading the lines on our palm, and checking the alignment of the stars enough to cure the mental illness they undergo? Is it a solution or a quick fix as a consequence of an ignorant healthcare system?
Several studies have also shown the deteriorating effects of depending on astrology. Cases of worsening and onset of depression, anxiety and personality disorders are common for those who use astrology as more than just a temporary coping mechanism. It also becomes a source of losing control, as every feeling is attributed to fate and destiny, instilling a sense of helplessness. Ultimately can the mental health system single-handedly address the concerns of inequality and economic access in society?
Maahira Jain is a third-year student at Ashoka University studying Psychology and Media studies. She is a movie buff and is extremely passionate about writing and traveling.
This article is republished from OpenAxis under a Creative Commons license. Read the original article.
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The Four Pillar Plan – by Dr. Rangan Chatterjee
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Dr. Rangan Chatterjee, a medical doctor, felt frustrated with how many doctors in his field focus on treating the symptoms of disease, rather than the cause. Sometimes, of course, treating the symptom is necessary too! But neglecting the cause is a recipe for long-term woes.
What he does differently is take lifestyle as a foundation, and even that, he does differently than many authors on the topic. How so, you may wonder?
Rather than look first at exercise and diet, he starts with “relax”. His rationale is reasonable: diving straight in with marathon training or a whole new diet plan can be unsustainable without this as a foundation to fall back on.
Many sources look first at exercise (because it can be a very simple “prescription”) before diet (often more complex)… but how does one exercise well with the wrong fuel in the tank? So Dr. Chatterjee’s titular “Four Pillars” come in the following order:
- Relax
- Eat
- Move
- Sleep
He also goes for “move” rather than “exercise” as the focus here is more on minimizing time spent sitting, and thus involving a lot of much more frequent gentle activities… rather than intensive training programs and the like.
And as for sleep? Yes, that comes last because—no matter how important it is—the other things are easier to directly control. After all, one can improve conditions for sleep, but one cannot simply choose to sleep better! So with the other three things covered first, good sleep is the fourth and final thing to fall into place.
All in all, this is a great book to cut through the catch-22 problem of lifestyle factors negatively impacting each other.
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The Brain Health Kitchen – by Dr. Annie Fenn
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This is a cookbook built around the MIND diet, which we talked about in our “Four Ways To Upgrade The Mediterranean Diet” article.
As such, it’s a top-tier gold-standard diet to be following for brain health, and having it as a book of recipes makes actually eating this way a lot easier!
The book does talk about the science first before getting to the recipes, so don’t worry, you won’t have to reverse engineer the dietary guidelines from the recipes; everything is explained well.
The recipes (of which there are 100) are diverse enough to be interesting without being so complicated as to be difficult. The ingredients are largely nutritional powerhouses, and most if not all can be found in your nearest reasonable-sized supermarket. Also, the recipes are (as you might reasonably expect), very plant-forward, but not entirely plant-based (as you might have guessed from the salmon on the front cover).
Bottom line: if you’d like to eat more healthily for your brain, but are a little stumped on what to do with the four ingredients you remember are brain-healthy, this book will help expand your horizons—not to mention your culinary repertoire!
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Reishi Mushrooms: Which Benefits Do They Really Have?
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Reishi Mushrooms
Another Monday Research Review, another mushroom! If we keep this up, we’ll have to rename it “Mushroom Monday”.
But, there’s so much room for things to say, and these are fun guys to write about, as we check the science for any spore’ious claims…
Why do people take reishi?
Popular health claims for the reishi mushroom include:
- Immune health
- Cardiovascular health
- Protection against cancer
- Antioxidant qualities
- Reduced fatigue and anxiety
And does the science agree?
Let’s take a look, claim by claim:
Immune health
A lot of research for this has been in vitro (ie, with cell cultures in labs), but promising, for example:
Immunomodulating Effect of Ganoderma lucidum (Lingzhi) and Possible Mechanism
(that is the botanical name for reishi, and the Chinese name for it, by the way)
That’s not to say there are no human studies though; here it was found to boost T-cell production in stressed athletes:
Cardiovascular health
Here we found a stack of evidence for statistically insignificant improvements in assorted measures of cardiovascular health, and some studies where reishi did not outperform placebo.
Because the studies were really not that compelling, instead of taking up room (and your time) with them, we’re going to move onto more compelling, exciting science, such as…
Protection against cancer
There’s a lot of high quality research for this, and a lot of good results. The body of evidence here is so large that even back as far as 2005, the question was no longer “does it work” or even “how does it work”, but rather “we need more clinical studies to find the best doses”. Researchers even added:
❝At present, lingzhi is a health food supplement to support cancer patients, yet the evidence supporting the potential of direct in vivo anticancer effects should not be underestimated.❞
Check it out:
Anticancer effects of Ganoderma lucidum: a review of scientific evidence
Just so you know we’re not kidding about the weight of evidence, let’s drop a few extra sources:
- Ganoderma lucidum: a rational pharmacological approach to surmount cancer
- Ganoderma lucidum as an anti-cancer agent
- Extract from Ganoderma lucidum suppresses cervical cancer cell malignancy
- Ganoderma lucidum spore oil induces apoptosis of breast cancer cells
- Ganoderma lucidum enhances carboplatin chemotherapy effect
- Ganoderma lucidum inhibits prostate cancer cell migration
- Ganoderma lucidum fruiting body extracts inhibit colorectal cancer
- Inhibitory activity of medicinal mushroom Ganoderma lucidum on colorectal cancer
- Ganoderma lucidum (reishi mushroom) for cancer treatment
By the way, we shortened most of those titles for brevity, but almost all of the continued with “by” followed by a one-liner of how it does it.
So it’s not a “mysterious action” thing, it’s a “this is a very potent medicine and we know how it works” thing.
Antioxidant qualities
Here we literally only found studies to say no change was found, one that found a slight increase of antioxidant levels in urine. It’s worth noting that levels of a given thing (or its metabolites, in the case of some things) in urine are often quite unhelpful regards knowing what’s going on in the body, because we get to measure only what the body lost, not what it gained/kept.
So again, let’s press on:
Reduced fatigue and anxiety
Most of the studies for this that we could find pertained to health-related quality of life for cancer patients specifically, so (while they universally give glowing reports of reishi’s benefits to health and happiness of cancer patients), that’s a confounding factor when it comes to isolating its effects on reduction of fatigue and anxiety in people without cancer.
Here’s one that looked at it in the case of reduction of fatigue, anxiety, and other factors, in patients without cancer (but with neurathenia), in which they found it was “significantly superior to placebo with respect to the clinical improvement of symptoms”.
Summary:
- Reishi mushroom’s anti-cancer properties are very, very clear
- There is also good science to back immune health claims
- It also has been found to significantly reduce fatigue and anxiety in unwell patients (we’d love to see more studies on its benefits in otherwise healthy people, though)
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Peanuts vs Pecans – Which is Healthier?
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Our Verdict
When comparing peanuts to pecans, we picked the peanuts.
Why?
Peanuts are an oft-underrated nut!
In terms of macros, peanuts have more than 2.5x the protein and slightly more carbs, while pecans have very slightly more fiber and a lot more fat, of which, mostly healthy monounsaturated and polyunsaturated fats, though it’s worth noting that peanuts’ fats are equally healthy and have a similar general profile, just, less fat per 100g than pecans do. There’s a lot going for both of these very different nuts here, so we’ll call this category a tie.
In the category of vitamins, peanuts have more of vitamins B2, B3, B5, B6, B7, B9, E, and choline, while pecans have more of vitamins C and K (of which they are still not a very good source, but peanuts have none so they can technically claim it for those two vitamins); thus, a clear win for peanuts here, especially as most of its vitamins had very large margins of difference over pecans, and peanuts are a good source of all the vitamins mentioned for them.
When it comes to minerals, peanuts have more calcium, iron, magnesium, phosphorus, potassium, and selenium, while pecans have more manganese and zinc. Another win for peanuts!
Adding up the sections makes for a clear win for peanuts, but by all means enjoy either or both (diversity is good), unless you are allergic, in which case, please don’t!
Want to learn more?
You might like:
Why You Should Diversify Your Nuts
Enjoy!
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