FLASH radiotherapy's bold approach to cancer treatment
spectrum.ieee.org
spectrum.ieee.org
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.
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.
I guess it was too good to be true.
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.
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?
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
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)
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.
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?
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.
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?
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.
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.
"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".
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.
"This name makes me uncomfortable. I think I'd rather die of cancer."
> 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.
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.)
No pun intended?
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?
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.
There are so many biological cures on the horizon; they can't arrive fast enough.
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?
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.
Those aren’t superstition, just common sense.
But I don’t remember is whether that experiment became SOP or not.
However that’s the current theory, of a long line of theories that did not pan out.
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.
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.
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.