scarbrtj

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Either the results have been 1) misinterpreted by people unintelligent, 2) misreported by people untruthful, or 3) are not too good to be true. So roughly there's a 67% chance they're too good to be true :) But I hope they're true. I get a bit of anxiety thinking about if they're true. If REALLY true, then all the curative treatments I've given with my TrueBeam or whatever today were substandard. I hate substandard.* But my center could not easily, if at all, afford a new machine tomorrow.

* I have been recently talking to a friend at a proton center where most of the institution's H&N patients are being sent. First, I was a little surprised that they're doing chemoRT with protons and doing curative HNSCC treatments with protons. Second, I was interested to hear that it seems most people are agreeing the proton HNSCC patients have less side effects. Third, I kind of felt the pang of jealousy with the preceding statement. I want to give treatments with less side effects too!
 

Krukenberg

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Either the results have been 1) misinterpreted by people unintelligent, 2) misreported by people untruthful, or 3) are not too good to be true. So roughly there's a 67% chance they're too good to be true :) But I hope they're true. I get a bit of anxiety thinking about if they're true. If REALLY true, then all the curative treatments I've given with my TrueBeam or whatever today were substandard. I hate substandard.* But my center could not easily, if at all, afford a new machine tomorrow.

* I have been recently talking to a friend at a proton center where most of the institution's H&N patients are being sent. First, I was a little surprised that they're doing chemoRT with protons and doing curative HNSCC treatments with protons. Second, I was interested to hear that it seems most people are agreeing the proton HNSCC patients have less side effects. Third, I kind of felt the pang of jealousy with the preceding statement. I want to give treatments with less side effects too!
Compound this with the fact that cyclotron-based proton beams are, at the moment, the only means to treat non-superficial rumors with FLASH. A radically different linac design is under development currently though that may be able to do IMRT FLASH.
 
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evilbooyaa

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Seems like a cool idea. No idea how it works but I don't really care as long as it does work. Look forward to some human safety results upcoming.

What if we could deliver all the radiation a tumor needed in a single treatment, even in big areas, without having to worry about the side effects?
 
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RollTideRadOnc

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* I have been recently talking to a friend at a proton center where most of the institution's H&N patients are being sent. First, I was a little surprised that they're doing chemoRT with protons and doing curative HNSCC treatments with protons. Second, I was interested to hear that it seems most people are agreeing the proton HNSCC patients have less side effects. Third, I kind of felt the pang of jealousy with the preceding statement. I want to give treatments with less side effects too!
I would be cautious interpreting anecdotal word that protons are better for HNSCC unless there're robust data showing this the case. As far as I know, there are no such prospective or high quality data. Just like everyone "knew" that protons would be better for prostate, the case of protons for HNSCC may also prove to be spurious (which is in no way to cast aspersions on our well meaning colleagues who work with protons). And the financial toxicity for patients is not insignificant.

In my opinion, do you know what's likely better than protons for HN cancer? Appropriate de-escalation.
 

medgator

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In my opinion, do you know what's likely better than protons for HN cancer? Appropriate de-escalation.
Agree, although to be fair, there isn't much "prime time" data there either, at least nothing I'd hang my hat on in community practice.... Outside of maybe being ok with weekly instead of Q3 weeks cisplatin for my p16/hpv+ pts, I'm not doing anything different at this point
 
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thecarbonionangle

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people who routinely treat with protons anecdotally assure you that their prostate and head and neck patients do better than photons. For prostate I have not seen any good data. We will see. With head and neck plans, sometimes they look pretty nice sparing the oral cavity or some specific area, but it is not generally always better, case by case for sure.
 

evilbooyaa

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I would be cautious interpreting anecdotal word that protons are better for HNSCC unless there're robust data showing this the case. As far as I know, there are no such prospective or high quality data. Just like everyone "knew" that protons would be better for prostate, the case of protons for HNSCC may also prove to be spurious (which is in no way to cast aspersions on our well meaning colleagues who work with protons). And the financial toxicity for patients is not insignificant.

In my opinion, do you know what's likely better than protons for HN cancer? Appropriate de-escalation.
That's all in HPV+ Oropharynx (appropriately). There's much more to H&N cancer than HPV+ Oropharynx. I see more H&N (definitive or adjuvant) that is NOT HPV+ OPhx by like a 5:1 ratio.

I don't disagree with your point, just saying. And 1016 was a step back IMO. I'm not doing any dose de-escalation off protocol without a very good, appropriately powered phase III.

In regards to the first point - completely agree. Anecdotes for protons in the current era, given how long it's been around, is absolute non-sense. Show me the money (published data).
 
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OTN

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people who routinely treat with protons anecdotally assure you that their prostate and head and neck patients do better than photons. For prostate I have not seen any good data. We will see. With head and neck plans, sometimes they look pretty nice sparing the oral cavity or some specific area, but it is not generally always better, case by case for sure.
Anecdotal data is not data.
 

xrthopeful

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for head and neck - now that more people are doing IMPT, some of the plans look good for sure on paper, but in terms of the high-moderate dose volume, not that different than a tight VMAT modern plan. Yeah, the 5-10 Gy IDL and such will be there on a photon plan that you don't see on the proton plan. Hard to know if it matters.

for pelvis - just don't think proton will ever help.
 
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evilbooyaa

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well yeah certainly not, that was my point. There's little data. All the plans I see are pretty nice, but data is important
I continue to have concerns that what is shown on a pretty proton plan is not what is actually being delivered due to inherent uncertainties of proton (and other particle) therapy. Otherwise all these dosimetric improvements should have shown some clinical benefit, somewhere, long ago.
 

thecarbonionangle

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I continue to have concerns that what is shown on a pretty proton plan is not what is actually being delivered due to inherent uncertainties of proton (and other particle) therapy. Otherwise all these dosimetric improvements should have shown some clinical benefit, somewhere, long ago.
cautious of particle therapy as well for that reason. Especially in the head and neck there's lots of air in sinuses and open spaces. The uncertainties make it doubtful to me that is what is actually being delivered, although they assure you that is what happening and they have taken all those factors into account when I have asked.

As someone already pointed out, forgot who, the recent carbon ion therapy papers from japan in head and neck have in some cases larger nodal failure rates, also bad toxicities like blindness in some patients. The angle still needs to be worked out.
 

scarbrtj

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for head and neck - now that more people are doing IMPT, some of the plans look good for sure on paper, but in terms of the high-moderate dose volume, not that different than a tight VMAT modern plan. Yeah, the 5-10 Gy IDL and such will be there on a photon plan that you don't see on the proton plan. Hard to know if it matters.

for pelvis - just don't think proton will ever help.
A FLASH DVH and an IMRT DVH can ostensibly look exactly the same, but it's claimed the FLASH DVH correlates with less side effects than the IMRT DVH does. Perhaps this is true in protons too. I think we just don't know--for sure.
Otherwise all these [proton] dosimetric improvements should have shown some clinical benefit, somewhere, long ago.
Amen to that.
 

ramsesthenice

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We will have to wait to see how it pans out but I think there is a fundamental (and theoretical) difference between FLASH and conventional radiotherapy worth mentioning. Preclinically, there is reasonable evidence that normal tissues are, for whatever reason, relatively insensitive to RT delivered using short bursts with an exceedingly high dose rate. Tumors, on the other hand, appear to sustain high levels of oxidative damage. A lot of the classic radiobiologists and redox/metabolism folks are really excited about it and have been for a while. One of the biggest potential advantages of FLASH radiotherapy is that normal tissue avoidance may not be as critical as it is with conventional dose rates.

Again, not ready for prime time. Its way to early to decide its a game changer. If it pans out it could be. Or it could be yet another magic bullet that misses the mark.
 
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evilbooyaa

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A FLASH DVH and an IMRT DVH can ostensibly look exactly the same, but it's claimed the FLASH DVH correlates with less side effects than the IMRT DVH does. Perhaps this is true in protons too. I think we just don't know--for sure.
Right. I'm going to have the same standards for this as I do for protons. Show me clinical toxicity outcome data, ideally in humans. I look forward to it. Could you imagine how awesome this would be for patients? What if chemotherapy wasn't the magic bullet? What if we could just do FLASH radiation to the entire body like taking a picture of somebody with a camera and it selectively killed every cancer cell but not normal tissue? No need for surgery or medical oncology.

Of course, this is unlikely to happen (just like all those medical oncology magic bullets), but it's a cool idea.
 

scarbrtj

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implied :)
What if we could just do FLASH radiation to the entire body like taking a picture of somebody with a camera and it selectively killed every cancer cell but not normal tissue? No need for surgery or medical oncology or 4-year radiation oncology residencies
 
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Gfunk6

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If FLASH really pans out like the preliminary data suggests, it will be hilarious to see people continue to justify proton/carbon/MRILinac when a 25 year old accelerator with an amped up dose-rate can do a better job in fewer fractions with less toxicity.

I went to a FLASH symposium earlier this year and apparently older linacs can be retrofitted to do this.
 
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Lamount

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If FLASH really pans out like the preliminary data suggests, it will be hilarious to see people continue to justify proton/carbon/MRILinac when a 25 year old accelerator with an amped up dose-rate can do a better job in fewer fractions with less toxicity.

I went to a FLASH symposium earlier this year and apparently older linacs can be retrofitted to do this.
Is that with electrons or photons? I heard that this was possible only in electron mode as the dose rate of electrons have to be orders of magnitude higher to account for inefficiency of the bremsstrahlung conversion to X Rays (I.e > 95% electron fluence is lost to heat). Are the older LINACs capable of producing an electron current high enough to support X Ray dose rates > 40 Gy/s?
 

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The other caveat to flash is presumably you’ll still have to modulate the beam to do imrt so you’d either have to do mlc movements faster than the dose rate or do step and shoot imrt with a break to start and stop the beam between each segment. I highly doubt that you could do flash with 2D and avoid all the toxicity you would with imrt. Who knows though
 
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Is that with electrons or photons? I heard that this was possible only in electron mode as the dose rate of electrons have to be orders of magnitude higher to account for inefficiency of the bremsstrahlung conversion to X Rays (I.e > 95% electron fluence is lost to heat).
Yes, that's correct. Older linacs have been converted to FLASH mode in a preclinical animal setting, but this only works with electrons, and it's done basically by removing the metal layer that converts electrons to x-rays (which, as you point out, is incredibly inefficient). I think that even if the linac had a mode that would give you 1000x more power for free, you still couldn't do FLASH with x-rays because the metal would melt before the treatment is finished.

The other caveat to flash is presumably you’ll still have to modulate the beam to do imrt so you’d either have to do mlc movements faster than the dose rate or do step and shoot imrt with a break to start and stop the beam between each segment. I highly doubt that you could do flash with 2D and avoid all the toxicity you would with imrt. Who knows though
This was a question asked to Bill Loo (the clinician leader of a prototype FLASH x-ray platform) this year at AAPM, and his opinion was that you really would want some of both worlds: FLASH capability along with spatial modulation a la IMRT. Obviously we are operating in a data free zone here but if you had to pick and choose one of FLASH and IMRT, I imagine the winner would be disease specific.

Their design for the x-ray FLASH would avoid MLC motion but it sounds like it's in a very early stage (basically a blueprint, with some testing of individual components they want to build).
 

Palex80

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1. We know way too little about the radioniology around FLASH radiotherapy. If the theory upholds in clinical practice it will certainly radically change our entire field. All the Rs of radioniology will become rather obsolete and we will be treating patients with new regimes. IF...

2. Protons can lead to less side effects in some HNSCC treatments. I do not have randomized data to back it up, but I have seen it in practice.
In well lateralized tumors we were treating (mainly adenoid cystic carcinomas of salivary glands) you would notice very little mucositis.
Although the ipsilateral parts of the oral cavity / tongue were receiving dose during RT, there was a very steep dose drop happening at the mid-line and practically no dose getting to the other side of the oral/cavity tongue (which is the whole point of the Bragg peak). With IMRT you would still have 10-20 Gy in parts of the contralateral oral cavity. Interestingly the mucositis near the midline on the treated site was especially limited.

The speculation was that due to the zero dose on the contralateral side, the mucosa was healing faster near the midline through faster growing mucosa on the contralateral side which was "crossing over". It's a bit like where you get a sore in your mouth and it starts healing through healthy tissue growing around the damaged spot and healing the injured part.

This effect seems not to take place during IMRT since these limited doses to the contralateral side are enough to stop proliferation of the mucosa into the damaged parts in the high-dose area.

Do I have data to back this up? Nope. It's merely the observation we made.
 

Palex80

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Yes, that's correct. Older linacs have been converted to FLASH mode in a preclinical animal setting, but this only works with electrons, and it's done basically by removing the metal layer that converts electrons to x-rays (which, as you point out, is incredibly inefficient). I think that even if the linac had a mode that would give you 1000x more power for free, you still couldn't do FLASH with x-rays because the metal would melt before the treatment is finished.
Ever heard of the Bialystok incident?


Scary stuff...

 
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evilbooyaa

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2. Protons can lead to less side effects in some HNSCC treatments. I do not have randomized data to back it up, but I have seen it in practice.
In well lateralized tumors we were treating (mainly adenoid cystic carcinomas of salivary glands) you would notice very little mucositis.
Although the ipsilateral parts of the oral cavity / tongue were receiving dose during RT, there was a very steep dose drop happening at the mid-line and practically no dose getting to the other side of the oral/cavity tongue (which is the whole point of the Bragg peak). With IMRT you would still have 10-20 Gy in parts of the contralateral oral cavity. Interestingly the mucositis near the midline on the treated site was especially limited.

The speculation was that due to the zero dose on the contralateral side, the mucosa was healing faster near the midline through faster growing mucosa on the contralateral side which was "crossing over". It's a bit like where you get a sore in your mouth and it starts healing through healthy tissue growing around the damaged spot and healing the injured part.

This effect seems not to take place during IMRT since these limited doses to the contralateral side are enough to stop proliferation of the mucosa into the damaged parts in the high-dose area.

Do I have data to back this up? Nope. It's merely the observation we made.
I'd even take a retrospective chart review comparing protons to IMRT in head and neck as a starter. If someone can prove protons improve clinical toxicity in a frequently treated site (outside of H&N), that is the easiest slam dunk paper into IJROBP ever.

Hell there was a breast one where toxicity was WORSE with protons and that still got published. Valuable data, albeit with a pro-proton spin in the conclusion. Can you imagine the excitement for actually having better clinical outcomes?

If I worked at a proton center I'd have a medical student cranking out one of these chart reviews once a month for every disease site that was treated with protons. I guess I don't get what's that hard about it. That being said, I'd be looking to publish them regardless of the results, which may go against the wishes of the institution.
 

scarbrtj

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If I worked at a proton center I'd have a medical student cranking out one of these chart reviews once a month for every disease site that was treated with protons.
Kid you not, I know a proton center where they are hiring two FTEs at ~$200K a year to do essentially this.