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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No Bad Parts – by Dr. Richard Schwartz
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We’ve previously reviewed Dr. Schwartz’s “You Are The One You’ve Been Waiting For” and whereas that book doesn’t require having read this one, this one would be an excellent place to start, as it focuses on perhaps the most important core issues of IFS therapy.
We all have different aspects that have developed within us for different reasons, and can generally “become as though a different person when…” and some condition that is met. Those are our “parts”, per IFS.
This book makes the case that even the worst of our parts arose for reasons, that they often looked after us when no other part could or would, and at the very least, they tried. Rather than arguing for “so, everything’s just great”, though, Dr. Schwartz talks the reader through making peace with those parts, and then, where appropriate, giving them the retirement they deserve—of if that’s not entirely practical, arranging for them to at least take a seat and wait until called on, rather than causing problems in areas of life to which they are not well-suited.
Throughout, there is a good balance of compassion and no-bullshit, both of which are really necessary in order to make this work.
Bottom line: if there are parts of you you’re not necessarily proud of, this book can help you to put them peacefully to rest.
Click here to check out No Bad Parts, and take care of yours!
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The Science Of Sounds
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We Think You Might Like The Sound Of This…
We’ve written before about the benefits of mindfulness meditation, and how to do it.
We also reviewed a great book on a related topic:
This is Your Brain On Music – by Dr. Daniel Levitin
(yes, that’s the same neuroscientist that we featured as an expert talking about The Five Keys of Aging Healthily)
But what happens when we combine the two?
Mantra meditation & music
Most scientific studies that have been undertaken with regard to meditation tend to focus on mindfulness meditation. It’s easy, effective, and (which makes a difference when it comes to publication bias) is a very safe bet when it comes to funding.
However, today we’re going to look at mantra meditation, which has a lot in common, neurologically speaking, with music. Indeed, when the two were compared separately in a randomized control trial:
❝Daily mantra meditation or classical music listening may be beneficial for cognitive outcomes and quality of life of breast cancer survivors with cancer-related cognitive impairment.
The cognitive benefits appear to be sustained beyond the initial intervention period.❞
One possible reason for some of the similar benefits is the vagus nerve—whether intoning a mantra, or humming along to music, the vibrations can stimulate the vagus nerve, which in turn activates the parasympathetic nervous system, resulting in body-wide relaxation:
The Vagus Nerve (And How You Can Make Use Of It)
How effective is mantra meditation?
According to a large recent narrative review, it depends on your goal:
❝Based on the studies in the four important areas presented, there is no doubt of a strong connection between mantra meditation and human health.
Strong evidence has been found that practicing mantra meditation is effective in relieving stress and in coping with hypertension.
For the other two areas: anxiety and immunity, the evidence is inconclusive or not strong enough to firmly support the claim that the mantra meditation can be used to reduce anxiety or to improve immunity. ❞
Read in full: Scientific Evidence of Health Benefits by Practicing Mantra Meditation: Narrative Review
this is a very interesting read if you do have the time!
How do I practice mantra meditation?
The definition is broad, but the critical criteria are:
- You meditate…
- …using a mantra
Lest that seem flippant: those really are the two key points!
Meditation comes in various forms, and mantra meditation is a form of focussed meditation. While some focussed meditation forms may use a candle or some other focal point, in mantra meditation, the mantra itself provides the focus.
You may be wondering: what should the mantra be?
Classic and well-tested mantras include such simple things as the monosyllabic Sanskrit “Om” or “Ham”. We’re a health science newsletter, so we’ll leave esoteric meanings to other publications as they are beyond our scope, but we will say that these result, most naturally, in the humming sound that we mentioned earlier stimulates the vagus nerve.
But that’s not the only way. Practitioners of religions that have repetitive prayer systems (e.g. anything that uses prayer beads, for example) also provide the basis of focused meditation, using a mantra (in this case, usually a very short oft-repeated prayer phrase).
How long is needed for benefits?
Most studies into mantra meditation have used timed sessions of 15–30 minutes, with 20 minutes being a commonly-used session length, once per day. However…
- Vagus nerve benefits should appear a lot more quickly than that (under 5 minutes) in the case of mantras that cause that vibration we mentioned.
- Repetitive spoken prayers (or similar repeated short phrases, for the irreligious) will generally effect relaxation in whatever period of time it takes for your brain to be fully focused on what you are doing now, instead of what you were thinking about before. If using counting beads, then you probably already know what number works for you.
(again, as a health science publication, we cannot comment on any otherworldly benefits, but the worldly benefits seem reason enough to consider these practices for their potential therapeutic effects)
10almonds tip: for any meditative practice that you want to take approximately a given period of time, we recommend investing in a nice sand timer like this one, as this will not result in a jarring alarm going off!
Like to jazz things up a little?
Enjoy: Meditation That You’ll Actually Enjoy ← Meditation games!
Prefer to keep things to the basics?
Enjoy: No Frills, Evidence-Based Mindfulness ← The simplest scientific approach
Take care!
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The Mind-Gut Connection – by Dr. Emeran Mayer
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We’ve reviewed books about the mind-gut connection before, so what makes this one stand out?
Firstly, it’s a lot more comprehensive than the usual “please, we’re begging you, eat some fiber”.
And yes, of course that’s part of it. Prebiotics, probiotics, reduce fried and processed foods, reduce sugar/alcohol, reduce meat, and again, eat some greenery.
But where this book really comes into its own is looking more thoroughly at the gut microbiota and their function. Dr. Mayer goes well beyond “there are good and bad bacteria” and looks at the relationship each of them have with the body’s many hormones, and especially neurotransmitters like serotonin and dopamine.
He also looks at the two-way connection between brain and gut. Yes, our gut gives us “gut feelings”, but 10% of communication between the brain and gut is in the other direction; he explores what that means for us, too.
Finally, he does give a lot of practical advice, not just dietary but also behavioral, to make the most of our mind-gut connection and make it work for our health, rather than against it.
Bottom line: this is the best book on the brain-gut connection that this reviewer has read so far, and certainly the most useful if you already know about gut-healthy nutrition, and are looking to take your understanding to the next level.
Click here to check out The Mind-Gut Connection, and start making yours work for your benefit!
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Ginger Does A Lot More Than You Think
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Ginger’s benefits go deep!
You are doubtlessly already familiar with what ginger is, so let’s skip right into the science.
The most relevant active compound in the ginger root is called gingerol, and people enjoy it not just for its taste, but also a stack of health reasons, such as:
- For weight loss
- Against nausea
- Against inflammation
- For cardiovascular health
- Against neurodegeneration
Quite a collection! So, what does the science say?
For weight loss
This one’s quite straightforward. It not only helps overall weight loss, but also specifically improves waist-hip ratio, which is a much more important indicator of health than BMI.
Against nausea & pain
Ginger has proven its effectiveness in many high quality clinical trials, against general nausea, post-surgery nausea, chemotherapy-induced nausea, and pregnancy-related nausea.
Source: Ginger on Human Health: A Comprehensive Systematic Review of 109 Randomized Controlled Trials
However! While it very clearly has been shown to be beneficial in the majority of cases, there are some small studies that suggest it may not be safe to take close to the time of giving birth, or in people with a history of pregnancy loss, or unusual vaginal bleeding, or clotting disorders.
See specifically: Ginger for nausea and vomiting of pregnancy
As a side note on the topic of “trouble down there”, ginger has also been found to be as effective as Novafen (a combination drug of acetaminophen (Tylenol), caffeine, and ibuprofen), in the task of relieving menstrual pain:
See: Effect of Ginger and Novafen on menstrual pain: A cross-over trial
Against inflammation & pain
Ginger has well-established anti-inflammatory (and, incidentally, which affects many of the same systems, antioxidant) effects. Let’s take a look at that first:
Read: Effect of Ginger on Inflammatory Diseases
Attentive readers will note that this means that ginger is not merely some nebulous anti-inflammatory agent. Rather, it also specifically helps alleviate delineable inflammatory diseases, ranging from colitis to Crohn’s, arthritis to lupus.
We’ll be honest (we always are!), the benefits in this case are not necessarily life-changing, but they are a statistically significant improvement, and if you are living with one of those conditions, chances are you’ll be glad of even things described in scientific literature as “modestly efficacious”.
What does “modestly efficacious” look like? Here are the numbers from a review of 593 patients’ results in clinical trials (against placebo):
❝Following ginger intake, a statistically significant pain reduction SMD = −0.30 ([95% CI: [(−0.50, −0.09)], P = 0.005]) with a low degree of inconsistency among trials (I2 = 27%), and a statistically significant reduction in disability SMD = −0.22 ([95% CI: ([−0.39, −0.04)]; P = 0.01; I2 = 0%]) were seen, both in favor of ginger.❞
To de-mathify that:
- Ginger reduced pain by 30%
- Ginger reduced disability by 22%
Read the source: Efficacy and safety of ginger in osteoarthritis patients: a meta-analysis of randomized placebo-controlled trials
Because (in part) of the same signalling pathways, it also has benefits against cancer (and you’ll remember, it also reduces the symptoms of chemotherapy).
See for example: Ginger’s Role in Prevention and Treatment of Gastrointestinal Cancer
For cardiovascular health
In this case, its benefits are mostly twofold:
- It significantly reduces triglycerides and LDL cholesterol, while increasing HDL cholesterol
- It significantly reduces fasting blood sugar levels and HbA1c levels (both risk factors for CVD)
Against neurodegeneration
This is in large part because it reduces inflammation, which we discussed earlier.
But, not everything passes the blood-brain barrier, so it’s worth noting when something (like gingerol) does also have an effect on brain health as well as the rest of the body.
You do not want inflammation in your brain; that is Bad™ and strongly associated with Alzheimer’s and Parkinson’s.
As well as reducing neuroinflammation, ginger has other relevant mechanisms too:
❝Its bioactive compounds may improve neurological symptoms and pathological conditions by modulating cell death or cell survival signaling molecules.
The cognitive enhancing effects of ginger might be partly explained via alteration of both the monoamine and the cholinergic systems in various brain areas.
Moreover, ginger decreases the production of inflammatory related factors❞
Check it out in full, as this is quite interesting:
Role of Ginger in the Prevention of Neurodegenerative Diseases
How much to take?
In most studies, doses of 1–3 grams/day were used.
Where to get it?
Your local supermarket, as a first port-of-call. Especially given the dose you want, it may be nicer for you to have a touch of sliced ginger root in your cooking, rather than taking 2–6 capsules per day to get the same dose.
Obviously, this depends on your culinary preferences, and ginger certainly doesn’t go with everything!
If you do want it as a supplement, here is an example product on Amazon, for your convenience.
Enjoy!
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How often should you wash your sheets and towels?
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Everyone seems to have a different opinion when it comes to how often towels and bed sheets should be washed. While many people might wonder whether days or weeks is best, in one survey from the United Kingdom, almost half of single men reported not washing their sheets for up to four months at a time.
It’s fairly clear that four months is too long to leave it, but what is the ideal frequency?
Bed linen and towels are quite different and so should be washed at different intervals. While every week or two will generally suffice for sheets, towels are best washed every few days.
Anyway, who doesn’t love the feeling of a fresh set of sheets or the smell of a newly laundered towel?
Why you should wash towels more often
When you dry yourself, you deposit thousands of skin cells and millions of microbes onto the towel. And because you use your towel to dry yourself after a shower or bath, your towel is regularly damp.
You also deposit a hefty amount of dead skin, microbes, sweat and oils onto your sheets every night. But unless you’re a prolific night sweater, your bedding doesn’t get wet after a night’s sleep.
Towels are also made of a thicker material than sheets and therefore tend to stay damp for longer.
So what is it about the dampness that causes a problem? Wet towels are a breeding ground for bacteria and moulds. Moulds especially love damp environments. Although mould won’t necessarily be visible (you would need significant growth to be able to see it) this can lead to an unpleasant smell.
As well as odours, exposure to these microbes in your towels and sheets can cause asthma, allergic skin irritations, or other skin infections.
People don’t always agree on how often to change the sheets.
http://rawpixel.com/ShutterstockSo what’s the ideal frequency?
For bedding, it really depends on factors such as whether you have a bath or shower just before going to bed, or if you fall into bed after a long, sweaty day and have your shower in the morning. You will need to wash your sheets more regularly in the latter case. As a rule of thumb, once a week or every two weeks should be fine.
Towels should ideally be washed more regularly – perhaps every few days – while your facecloth should be cleaned after every use. Because it gets completely wet, it will be wet for a longer time, and retain more skin cells and microbes.
Wash your towels at a high temperature (for example, 65°C) as that will kill many microbes. If you are conscious of saving energy, you can use a lower temperature and add a cup of vinegar to the wash. The vinegar will kill microbes and prevent bad smells from developing.
Clean your washing machine regularly and dry the fold in the rubber after every wash, as this is another place microbes like to grow.
Smelly towels
What if you regularly wash your towels, but they still smell bad? One of the reasons for this pong could be that you’ve left them in the washing machine too long after the wash. Especially if it was a warm wash cycle, the time they’re warm and damp will allow microbes to happily grow. Under lab conditions the number of these bacteria can double every 30 minutes.
It’s important to hang your towel out to dry after use and not to leave towels in the washing machine after the cycle has finished. If possible, hang your towels and bedding out in the sun. That will dry them quickly and thoroughly and will foster that lovely fresh, clean cotton smell. Using a dryer is a good alternative if the weather is bad, but outdoors in the sun is always better if possible.
Also, even if your towel is going to be washed, don’t throw a wet towel into the laundry basket, as the damp, dirty towel will be an ideal place for microbes to breed. By the time you get to doing your washing, the towel and the other laundry around it may have acquired a bad smell. And it can be difficult to get your towels smelling fresh again.
Towels should be washed more often than sheets.
New Africa/ShutterstockWhat about ‘self-cleaning’ sheets and towels?
Some companies sell “quick-dry” towels or “self-cleaning” towels and bedding. Quick-dry towels are made from synthetic materials that are weaved in a way to allow them to dry quickly. This would help prevent the growth of microbes and the bad smells that develop when towels are damp for long periods of time.
But the notion of self-cleaning products is more complicated. Most of these products contain nanosilver or copper, antibacterial metals that kill micro-organisms. The antibacterial compounds will stop the growth of bacteria and can be useful to limit smells and reduce the frequency with which you need to clean your sheets and towels.
However, they’re not going to remove dirt like oils, skin flakes and sweat. So as much as I would love the idea of sheets and towels that clean themselves, that’s not exactly what happens.
Also, excessive use of antimicrobials such as nanosilver can lead to microbes becoming resistant to them.
Rietie Venter, Associate professor, Clinical and Health Sciences, University of South Australia
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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The Dirt Cure – by Dr. Maya Shetreat-Klein
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As we discussed in our article “Stop Sabotaging Your Gut”, there is indeed merit to living a little dirty, in particular when it comes to what we put in our mouths. Having the space of an entire book rather than a small article, Dr. Shetreat-Klein expands on this in great detail.
The subtitle mentions “growing healthy kids with food straight from the soil”; it’s worth noting that all the information here (with the exception of concerning breastfeeding etc) is equally applicable to adults too—so if it’s your own health you’re focused on rather than that of kids or grandkids, then that’s fine too.
You may be wondering: what more is there to say than “don’t scrub your vegetables as though you’re about to perform surgery with them”?
There’s a lot of background information on what things help or harm our bodies in the first place, most notably via our gut, and as an important extra consideration, the gut-brain axis. Incidentally, the author is a neurologist by professional background.
Then she gets more specific, into “include and exclude” recommendations. In this matter we have one criticism: she does recommend raw milk over pasteurized, and that is, by overwhelming scientific consensus, a terrible idea. Raw milk is an abundant source of pathogens and a breeding ground for even more. There is “living dirty” and there is “living dangerously”, and drinking raw milk is the latter. See also: Pasteurization: What It Does And Doesn’t Do
However, for the most part, the rest of her advice is sound, and there’s even a recipes section too.
The style is something of a polemic throughout, but the extensive venting does not take away from there being a lot of genuine information in here too.
Bottom line: please skip the raw milk, but aside from that, if you’d like to improve your diet to improve your gut and immune health, then this book can help with that.
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