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> Currently, the most plausible theory emerging from her team’s research points to metabolism: Healthy and cancerous cells may process reactive oxygen species—unstable oxygen-containing molecules generated during radiation—in very different ways.
Reminds me of this which I (think) was linked here a while ago: https://www.nature.com/articles/s12276-020-0384-2
It really does feel like all these piecemeal cancer treatments are converging on something resembling a cure.
There was also a study that showed that chemotherapy efficacy was enhanced by fasting before treatment.
It seems that when calories are scarce, healthy cells turtle up while cancer cells keep consuming, so fasting reduces absorption rates in healthy tissues and thus collateral damage.
Healthy cells CAN turtle-up, whereas cancer cells engage in unregulated reproduction. Also, some cancer cells can only consume glucose. Which, in a fasted state, would mean that the majority of energy would be in ketones(if the individual were metabolically healthy), starving the cancer cells to death.
Why wouldn’t a strict keto diet not be a cure for those cancers?
Because the cancers cells adapt! (fast reproduction and high mutation rate of the cancerous cells make that process quicker than antibiotics resistance)
the body will actually turn protein into glucose, so the body will never be completely glucose free.
many people try it, but the results are mixed.
Please don't throw around random "a study that showed" about cancer treatments and chemotherapy. If you really think it needs to be shared, share the study and while you're at it, check in with a good oncologist or knowledgeable friend too. In my ~10 years of enduring chemo and other treatments, the amount of garbage you have to wade through from "well meaning" anecdata like "wheat grass" or "smoke huge bongloads" or "don't eat sugar" makes an already horrible process worse.
And yes I checked this with my onc at MSK. Dietary glucose in particular -- if you cut out enough sugar to starve cancer cells you would be doing lots of damage elsewhere as well.
There is this review that havent found any effects: https://www.mdpi.com/2072-6643/15/12/2666 Note that they excluded 274 out of 283 studies, considering only 9. It's in mdpi which is not great.So, the jury is still out I guess
The jury is not out -- it's an unconfirmed hunch that, as the study you link notes, risks harming patients who are having trouble keeping down food as it is.
This is just keto and fasting fans pushing their obsession on cancer patients. Same for marijuanauts -- anti-nausea drugs have long outperformed cannibinoids but you still have stoner friends offering you spliffs (ok, save them for later)
People eat keto diets all the time. What damage do you think they are doing to themselves?
The damage risked by Keto diets includes nutrient deficiency, liver and kidney problems, constipation, fuzzy thinking and mood swings.
Of these risks it's the potential veering into liver and kidney problems that deserves the closest monitoring.
See: https://www.health.harvard.edu/staying-healthy/should-you-tr...
~ Howard E. LeWine, MD, Chief Medical Editor, Harvard Health Publishing
You’re talking about elimination diets, I’m talking about skipping a meal.
I'm saying that cancer treatments are some of the most scientifically-validated procedures out there, because there's essentially unlimited money to pay for them. They have eliminated or modulated any negative side effect they can, via improved anti-nausea drugs, careful dosing+timing, etc.
Still, you can experience all sorts of discomforts during the tmt. I nearly fainted and got horrible chills when getting oxaliplatin for the first time. You're saying I should have _fasted_ for this?
There was a study that chemotherapy works best in the _morning_. Derek Lowe had an article about this:
D'oh. Forgot to add the link: https://www.science.org/content/blog-post/get-early-start
Did you notice the huge warning at the top of the article? This is garbage science.
No. I read the article when it came out, so I missed the update.
I guess it was too good to be true.
The PubPeer discussion of the original paper is kind of interesting https://pubpeer.com/publications/A32D7989007655CBF8D9DB2A250...
Theryq - why would they go with this name when everyone in the field knows about the Therac-25 radiation overexposure incidents?
Therac-25 is a great case study for software engineers too, recommend reading the Wikipedia article for anyone who hasn't, it's not too long.
> Previous models had hardware interlocks to prevent such faults, but the Therac-25 had removed them, depending instead on software checks for safety.
https://en.wikipedia.org/wiki/Therac-25
Another interesting part of the story is the user element. The issue was most often triggered by fast, experienced technicians who were able to key commands more quickly than Therac engineers anticipated:
> After strenuous work, the physicist and operator were able to reproduce the error 54 message. They determined that speed in editing the data entry was a key factor in producing error 54.
Therac is the first one I list and Knight Capital is the second. It is in fact possible to bankrupt your company by misusing feature toggles.
I learned about Therac at college in the 90s.
Some years later, I interviewed at Knight Capital, just a couple of weeks before their blowup. (Dreadful interview at which I did dreadfully, being asked to write C _over the phone_ by a supremely uninterested engineer. Quite a red flag in retrospect.)
I feel like you should get yourself a merit badge printed for that, sewed onto your laptop bag.
> Quite a red flag in retrospect.
No pun intended?
Sounds like my Amazon interview.
> Therac-25 is a great case study for software engineers too, recommend reading the Wikipedia article for anyone who hasn't, it's not too long.
I re-read the original paper every few months, more frequently if I'm working on Safety-of-Life-Critical equipment. Which, given my day job, means I'm re-reading it every couple of weeks at most.
Keeps you sharp, doesn't it?
The audience of this website is disproportionately aware of the Therac-25 compared to the general public. For the obvious reason, engineering, but also geographically: The Therac-25 being a North American incident that affected Canada and the US. Whereas Theryc is a French company.
While I do agree with your point, as a Swede not even born when the incidents happen I still knew about it, was brought up in a computer science class.
If I have cancer then whether to trust the radiation machine due to the name is certainly a choice I can make, but you get to own your own priorities in that case.
I feel like I have heard about this in a million different management anecdotes in my corporate trainings about management stuff/QA.
> The Therac-25 being a North American incident that affected Canada and the US
CGR who provided the accelerators and basic PDP11-based computing platform were a French company.
> Whereas Theryc is a French company.
I have been a Citroën enthusiast for about 30 years. I love French cars.
I have repaired lots of Valeo electronics modules for vehicles.
I'm not sticking my head in a French fucking particle accelerator.
Saw at the podiatrist that someone named a shoe company Kuru, presumably not after the prison disease affecting gait.
Perhaps after 来る.
Redemption arc.
Literally an arc.
Exactly what I thought as soon as I learned the name.
It's like, man, how to kill a product?
No pun intended.
It could even work? But you put yourself behind such a poorly placed 8 ball when you do these things. Even among researchers, people are a little superstitious about stuff like this. It's always in the back of everyone's mind.
> Even among researchers, people are a little superstitious about stuff like this.
Being superstitious is not common in the medical treatment world, where weird product names are common.
A doctor isn’t going to include the device’s brand name in their decision process for treating a cancer patient.
The Therac-25 case study is noted in the medical world but not to the same extent as in engineering. The case was a tragedy of bad engineering, but the doctors involved in directing the treatments were not at fault for the radiation over exposures.
> It's like, man, how to kill a product?
"This name makes me uncomfortable. I think I'd rather die of cancer."
I doubt any of that is valid. Therac-25 happened 44 years ago, that's a very long time, and many people involved in cancer research today weren't even alive when it happened.
"Theryq" and "Therac" are not quite the same either. The word "therapy" and derivatives of it using "thera" are still used widely across the medical industry.
So I'm not really sure why anyone here is making a big deal about the name of the company being "Theryq".
It’s an s-tier case study for UX research though. Maybe the doctors don’t remember but we do.
First thing that leapt out at me.
Comment was deleted :(
Hey, FLASH finally hit Hacker News! I remember my professors talking about this in graduate school. It's a fairly well-established effect: the tumor selectivity of radiation is much better at ultra-high dose rates. It is still unclear exactly why. But there are a lot of studies about it:
> It is still unclear exactly why
It'll be nice when we figure it out, then we can understand the unintended consequences better.
Not that it should prevent its use or anything; fuck cancer.
Interesting the effect's reason is still unclear.
I was starting to infer there was a better focusing ability so it could start and exit as a broad cone of radiation and keep the peak intensity at the tip of the focal cones at the tumor-tissue, and the short pulse also helped the healthy tissue.
But the way this sounds, it's more like a straight beam delivering similar intensity to healthy and tumor tissue but the biological effect strongly differs between healthy vs tumor tissue?
Yes, the radiation dose under the conventional metric (energy divided by mass) is the same, but the effects on biological systems change. I included a little speculation on the chemistry in my response to a sibling comment.
My guess would be that the radiation doesn't itself care but that tumors have some other characteristic (like multiplying rapidly) that makes them more susceptible to it. Similarly to how you can sometimes attack them with medication that inhibits cell division.
Yeah that's the conventional dose rate effect, not the FLASH effect. The FLASH effect happens on timescales so short that ordinary considerations like the cell cycle or DNA repair mechanisms are inherently ruled out. Instead it might have to do with the type of radical species that form in normal cells versus tumors, possibly related to oxygenation, pH, glycolysis byproducts, etc.
The first interaction of radiation with tissue is usually this:
H2O + ħv >> H2O+ + e- (fugitive)
The radical ion H2O+ is extremely reactive and usually protonates another water molecule immediately:
H2O+ + H2O >> H3O+ + OH*
The hydroxyl radical has a half life of about a nanosecond and will usually be the main "reagent", diffusing until it runs into an organic molecule which will be oxidized and thus degraded. At high enough dose rates, the peak concentration of hydroxyl radicals and more stable radicals like superoxide could be much higher, leading to "nonlinear" effects, i.e. byproducts of multiple radicals interacting with each other or a protein.
One thing I found confusing about the nature article is that it mostly discusses conventional linear accelerator + bremsstrahlung X-ray radiation versus very high dose rate FLASH in the form of electron beams, proton beams, or even carbon ion beams.
Do we know that what the chemical mechanism for damage from charged particle beams is? Is it similar enough to compare directly like this? Are the timescales short enough that charge deposition might matter?
The article is a bit unclear, but we have both a very wide range of X-ray vs charged particle studies, and increasingly of conventional vs FLASH studies with a range of modalities (e.g. the seminal FLASH paper was FLASH electrons vs conventional electrons). FLASH photon vs conventional photons are also increasingly being generated, although they've been more of a pain to generate.
So it's clear there is a temporal FLASH effect, which is not purely a question of radiation type.
That's not to say it's necessarily exactly the same effect - we still don't have a perfect quantitative understanding of the effects of different radiation types even at normal dose rates, let alone when FLASH differences are added into the mix.
For the other readers in this thread, this poster really knows their stuff.
Hopefully, this will turn out better than proton therapy, which held similar promises of improvement. https://pmc.ncbi.nlm.nih.gov/articles/PMC11506991/
It saddens me with a survivor in my family that the primary therapies are still cut, burn, and poison. They are horrific to experience and just slightly better than the disease.
There are so many biological cures on the horizon; they can't arrive fast enough.
What I find really sad is how slowly this science moves. As I read the article, the “a ha!” breakthrough was in the 1990s. Why did it take them 15-20 years to publish anything??? Coming from the tech industry this is mind boggling.
If you thought there was even a chance you were sitting on a realization that could literally “cure cancer” wouldn’t you want to scream it from the rooftops as loud and fast as possible?
every researcher who believes in their idea shouts (to grant organizations) that their thing is the best. but gathering actual data is difficult.
usually research is super inefficient, academia is full of people who are ... true believers. (sometimes only in their own greatness, and that leads to fraud.) which is amazing, but it's not really conductive to figuring out what's the best way to set up a high-throughput process to generate data.
in many cases it would require them to stop most of what they do and let a specialist team build said pipeline for them. (but that runs into cost problems. and that immediately leads us back to the grant organizations allocating resources.)
for example see how many problems the paper from 2014 had: https://pubpeer.com/publications/A32D7989007655CBF8D9DB2A250...
also see how fiendishly difficult it was initially to create transgenic mice embryos: https://www.astralcodexten.com/i/167092138/prerequisites-dex...
and just an anecdote, I have a friend who worked at a brain research group (they implanted electrodes into rodents, put them into mazes, and then see whether they dream about the maze) and ... it was cool, but IMHO that public money was mostly wasted.
What is the intensity at the focal point versus areas surrounding it?
I recall someone was analyzing the refractive index of various tissues in order to tighten the target area for multi beam radiation therapy. Particularly for brain cancers. By hitting from multiple angles the dosage in surrounding tissues is lower, and by calculating how the head lenses the beam you reduce the high dose area in the middle, like a 3d Venn diagram.
But I don’t remember is whether that experiment became SOP or not.
Won't the effective index of all materials be basically 1 for the high energy electrons involved here?
Seems not in this case. But I believe the use case was deep brain tumors, like the hippocampus, where any beam alignment problems could be life altering.
The sidebar mentions heavier particles having a pronounced Bragg Peak[0] and also existing approaches like multi-beam targeting. The FLASH effect in the article is yet another tool to limit the surrounding damage.
Does this have to do with cell division?
Cellular metabolism from the look of it. Cellular division and metabolism are linked but not synonymous.
However that’s the current theory, of a long line of theories that did not pan out.
Sounds a little too close, in both name and concept, to Therac for my comfort.
How superstitious are you? Do you avoid black cats and ladders?
When corporate arrogance is involved we called it Bayesian inference not superstition.
I avoid any strange animal and walking under ladders.
Those aren’t superstition, just common sense.
I wouldn’t call a ship “Titanic”.
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I generally don't trust cancer-communication if it's juiced up like this incredible headline. There has been huge amounts of progress. We don't need silicon valley idiots starting to make proclamations. It's doing fine without your mediocrity.
(they're French, not Silicon Valley)
The major issue isn't the speed of delivery, and the cancer.
The key question is how do you spare normal tissue, and how do you prove the normal tissue is spared in the long term. Current answer is: You break it apart into multiple sessions, the anti-thesis of FLASH.
Source: my wife is a radiation oncologist.
from the article (pay attention to the part in italics):
FLASH radiotherapy flips the conventional approach on its head, delivering a single dose of ultrahigh-power radiation in a burst that typically lasts less than one-tenth of a second. In study after study, this technique causes significantly less injury to normal tissue than conventional radiation does, without compromising its antitumor effect.
That phrasing isn't perfectly clear, as there's two things at play.
If you're delivering a large dose D all at once, FLASH spares normal tissue compared to conventional rate irradiations, with maintained anti-tumour effect.
But, you can instead deliver your treatment in a number of smaller doses, say n "fractions" of dose d. This also spares normal tissue (1). This latter approach - fractionation - is the way radiotherapy was delivered for most of its history. But at these low doses, FLASH sparing is small to negligible.
So, we have two demands in tension - and its unclear which is actually optimal. Some of the early results in FLASH showed huge sparing, but lots of more recent studies have shown more modest effects which may not be worth giving up benefits of fractionation for(2). And to date I think we have basically no meaningful in-human data to guide this, so there's still a lot of uncertainty.
1 - Fractionation also spares tumours, a bit, but you can offset this by increasing the total dose a bit and still see benefit.
2 - There is a general move to somewhat larger, fewer fractions even in normal radiotherapy, although almost all of these are still below the threshold where FLASH sparing is seen.
Another potential factor at play is the accuracy of delivery. It is generally easier to accurately deliver one quick dose vs daily doses over multiple weeks (due to patient positioning errors, the patient losing weight, soft tissues moving around etc).
Crafted by Rajat
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