Breast is the worstest x5?

[Ray D. Ayshun]

I could honestly say the same. Especially for Aunt Tressie who’s 64 with no insurance and is paying out of pocket. Or for Aunt Bessie who’s 80 and in the nursing home. Or for Aunt Jessie, who after I tell her there’s maybe a one in fifty chance of more breast swelling five years from now but she still decides she wants one instead of three plus weeks of treatment. I’d tell Grandpa Fezzy, who happens to be a rad onc, that his 16 fractions plus a 4 fraction boost are almost certainly more likely to give more late effects than 26/5.

I don’t think we can fully feasibly shame the UK for some kind of fraction saving venality alone regarding all their trials… mostly for the mere fact that IMPORT LOW exists.

We 15 fractioners have to take a stand somewhere. Why aren't you doing 22/4? I bet it's all the same, more or less, as 26/5. I really only need to design a trial that studies lr in a population that would get about the same benefit from a tincture of technitium. Then I can say whatever about toxicity.

Edit: why no uncle Jesse? C'mon. Duke I mean.

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[CurbYourExpectations]

Again, treat the patient how you want. I honestly think either is a swell option and I don't think there is anything really morally wrong with either point. I was just talking about the part I found the most interesting, was how different the patients perceived their toxicities versus what the physicians did, but of course not all patients reported their toxicities. For example the physicians noticed significantly more breast distortion and induration, but the patients seemed to think the opposite (not significantly though).

And my fault for not including receipts for some of the points I was making:
Local recurrence p-value about 0.15 (similar to some of the p values you've highlighted regarding the toxicities)

Locoregional relapse p value 0.08, lower than some you highlighted.

"Breast swollen" not significantly different between patients overall. Sure you can break it down into different subgroups and subjectivities and then do some maths and find a statistically significant toxicity at a single time point. And I'm not saying there isn't a possibility of a slightly higher risk of breast swelling, but you probably won't seem to notice, and neither might the patients. The marked comment was because of how you phrased it in your message, but I think you were mistaken in how you wrote it. There were more "marked" in the 15Fx regimen at 5 years, yeah more moderate in the 5Fx group at 5 years, but the absolute numbers are very low, almost the same as the difference in number of patients that had recurrent cancer.

Sure the increased induration seems real and probably a slightly higher risk of side effects overall in patients getting the 5Fx regimen. But also a possibility of tumor recurrences being higher in the 15Fx regimen in this cohort, unless I'm reading something wrong.

I also think @TheWallnerus makes a good point with the costs and patient age, etc. etc. If you're costing hundreds of patients thousands of dollars and possibly worse tumor control for marginal chances of cosmetic difference, utilitarianism might lean towards the shorter fractionation. Then throw on the possibility that most people are possibly tacking on boosts, you're likely wiping any of that potential decrease in cosmetic toxicity away.

I think it's reasonable to talk with patients about a possibility of increased cosmetic issues, I do and I think most people do, but I think both options are okay, and I don't think the UK are wrong or bad for treating all of their patients with 5Fx, if they even do. Not my place to tell you how to treat a patient, or how not to, lots of ways to treat a breast and provide good.

I think that when/if case based treatments start happening there's a real chance we will see lots of shifting from 15+4 or whatever to 5Fx, not saying anyone here is in that boat, but I wouldn't be surprised if it happens.

 

[TheWallnerus]

I also think @TheWallnerus makes a good point with the costs and patient age, etc. etc. If you're costing hundreds of patients thousands of dollars and possibly worse tumor control for marginal chances of cosmetic difference, utilitarianism might lean towards the shorter fractionation. Then throw on the possibility that most people are possibly tacking on boosts, you're likely wiping any of that potential decrease in cosmetic toxicity away

Why insurance companies haven’t imposed a 5 fraction limit on certain breast cancer presentations at this point is mystifying to me

don't think the UK are wrong or bad for treating all of their patients with 5Fx, if they even do

I also think that when/if case based treatments start happening there's a real chance we will see lots of shifting from 15+4 or whatever to 5Fx, not saying anyone here is in that boat, but I wouldn't be surprised if it happens

ROCR and/or its ilk will immanentize the five fraction eschaton, it is certain

But if you do and you still can't see that there is no scenario where 40/15 is MORE toxic by either physician or patient preference compared to 26/5 , then we really can't continue this conversation in good faith.

I am very very interested what portion of your whole breast you treat strict/straight 40 in 15

 

[thesauce]

The hilarious thing about this thread is how it started, and where the discussion veered to. We started with 10 fx whole breast is terrible and physicians are downplaying side effects of hypofrac. Many posts later people are saying 5 fractions might actually have better side effects and there are memes about physicians overcalling toxicity.

That’s not at all how this started. The dose and fractionation in this example is entirely irrelevant. Replace breast with any hypofrac trial.

The point is you have a major academic center essentially lying about their results for career advancement and institutional prestige.

Then it gets propagated to other centers as a reasonable alternative to the standard. It’s disgusting all around.

 

[evilbooyaa]

I could honestly say the same. Especially for Aunt Tressie who’s 64 with no insurance and is paying out of pocket. Or for Aunt Bessie who’s 80 and in the nursing home. Or for Aunt Jessie, who after I tell her there’s maybe a one in fifty chance of more breast swelling five years from now but she still decides she wants one instead of three plus weeks of treatment. I’d tell Grandpa Fezzy, who happens to be a rad onc, that his 16 fractions plus a 4 fraction boost are almost certainly more likely to give more late effects than 26/5.

I don’t think we can fully feasibly shame the UK for some kind of fraction saving venality alone regarding all their trials… mostly for the mere fact that IMPORT LOW exists.

Again, I think having a discussion with patients about their options of 40/15 vs 26/5 and having a data driven pros/cons discussion is worthwhile. All 3 of your patients would probably pick 26/5 and I think that is very reasonable.

What about the 55yo patient who has insurance who is worried about cosmesis? You telling her 26/5 is the only thing you'll offer?

Picking on statistically insignificant things (LR, marked breast swelling, etc.) and reporting those to patients is not what I would consider 'appropriate'.
Picking statistically significant things (overall more moderate/marked breast swelling at a 5-year time point, even if the absolute % increase is say 3-5%).

Why insurance companies haven’t imposed a 5 fraction limit on certain breast cancer presentations at this point is mystifying to me



I am very very interested what portion of your whole breast you treat strict/straight 40 in 15

1. Because it is more toxic and I would fight a p2p on anyone who wasn't allowing 15-16Fx WBI and report to state insurance commissioner and get patient involved for any Rad Onc who was actually blocking it for one of my patients.

2. Anyone who does not need a boost who needs WBI, I think 40-42.6 in 15-16fx is my preferred (not ONLY) option. Whether someone needs a boost or not is immaterial to fractionation regimen. I've seen 26/5 with a 10-16Gy/5-8Fx boost, others are reportedly doing 26/5 followed by a 5.2Fx boost. Arguing that 40/15 with a boost is more toxic compared to 26/5 without a boost is.... well yeah, obvious, from every boost trial. But what fractionation scheme I pick for a patient does not make them more likely to get a boost. Somebody who is getting 40/15 is not *more likely* to get a boost in my hands than someone getting 26/5 (and if a 26/5'er needs a boost, I would do it the SAME way FAST-FORWARD did, at 2Gy/Fx, NOT at the 5.2Gy/1fx way people are just doing). You've mentioned this a few times as what I imagine to be a 'gotcha' and it's.... just not.

Anyone who is boosting the patient in front of them should be boosting that patient regardless of whether they are getting 40/15 or 26/5.

 

[TheWallnerus]

Anyone who does not need a boost who needs WBI, I think 40-42.6 in 15-16fx is my preferred (not ONLY) option

You know, I think you may disagree, we have kind of backed into a logical corner where 40/15 is bound to have better cosmesis than 42.5/16; the "proven" bad cosmesis of 26/5 should be in the same bucket (↓↓↓) of 42.5/16 (at least versus 40/15), or more so. And again... I'd love to know if you Rx'd any 40/15 (no boost!) in 2024. I, personally, love 40/15, and constantly prescribe it: it has the lowest published 5y LR of any breast regimen I've ever seen, but I don't feel it's superior in any significant fashion to 26/5 and never will feel so. (Full disclosure: I need to keep the lights on and can't go "hog wild" with 26/5... it leads to women having to come in two-thirds less, but it also leads to having two-thirds less daily on-treats!)

The thing is, again, a logical conclusion of your logic (and maybe the data?!) is that 40/15 has the "proven best cosmesis" of any whole breast regimen ever reported in the history of medicine... but no one in America is commonly using it.

27/5 is 69, 76, 85, 100, 124, respectively, if you wanted to know; and this 40/27/26 data probably shows the alpha/beta of normal breast lies in the ~2-3 range, and closer to 2 than 3.

 

[drowsy12]

15 fx is my preferred. No one likes the hanging Monday.

 

[Ray D. Ayshun]

15 fx is my preferred. No one likes the hanging Monday.

I have too much hn chemorads to start any breast patients on Monday.

 

[CurbYourExpectations]

Again, I think having a discussion with patients about their options of 40/15 vs 26/5 and having a data driven pros/cons discussion is worthwhile. All 3 of your patients would probably pick 26/5 and I think that is very reasonable.

What about the 55yo patient who has insurance who is worried about cosmesis? You telling her 26/5 is the only thing you'll offer?

Picking on statistically insignificant things (LR, marked breast swelling, etc.) and reporting those to patients is not what I would consider 'appropriate'.
Picking statistically significant things (overall more moderate/marked breast swelling at a 5-year time point, even if the absolute % increase is say 3-5%).


1. Because it is more toxic and I would fight a p2p on anyone who wasn't allowing 15-16Fx WBI and report to state insurance commissioner and get patient involved for any Rad Onc who was actually blocking it for one of my patients.

2. Anyone who does not need a boost who needs WBI, I think 40-42.6 in 15-16fx is my preferred (not ONLY) option. Whether someone needs a boost or not is immaterial to fractionation regimen. I've seen 26/5 with a 10-16Gy/5-8Fx boost, others are reportedly doing 26/5 followed by a 5.2Fx boost. Arguing that 40/15 with a boost is more toxic compared to 26/5 without a boost is.... well yeah, obvious, from every boost trial. But what fractionation scheme I pick for a patient does not make them more likely to get a boost. Somebody who is getting 40/15 is not *more likely* to get a boost in my hands than someone getting 26/5 (and if a 26/5'er needs a boost, I would do it the SAME way FAST-FORWARD did, at 2Gy/Fx, NOT at the 5.2Gy/1fx way people are just doing). You've mentioned this a few times as what I imagine to be a 'gotcha' and it's.... just not.

Anyone who is boosting the patient in front of them should be boosting that patient regardless of whether they are getting 40/15 or 26/5.

To clarify, I don't do that. I discuss similar tumor control and possibility of increased cosmetic side effects with shorter fractionation. Just don't think there is a single correct answer, was pointing out how similarly the difference in numbers were and that those p values were to some of the things you were circling and maybe a few hundred more patients and that LR would be significant, or maybe if 2 or so more patients recur before their 5 year interval, etc. Most people I know do both forms of treatment and just talk with the patients about the pros and cons and let them decide. I think both are good options.
Long discussion about breast radiation. Did anyones mind change about anything? Nope lol

 

[TheWallnerus]

To clarify, I don't do that. I discuss similar tumor control and possibility of increased cosmetic side effects with shorter fractionation. Just don't think there is a single correct answer, was pointing out how similarly the difference in numbers were and that those p values were to some of the things you were circling and maybe a few hundred more patients and that LR would be significant, or maybe if 2 or so more patients recur before their 5 year interval, etc. Most people I know do both forms of treatment and just talk with the patients about the pros and cons and let them decide. I think both are good options.
Long discussion about breast radiation. Did anyones mind change about anything? Nope lol

People’s minds don’t change sans an insurance company fractionation guideline. Most rad oncs would still be giving whole breast at 1.8 to 2 Gy a day (and prostate for that matter) without insurance company fractionation limits I pessimistically believe.

 

[NotMattSpraker]

To clarify, I don't do that. I discuss similar tumor control and possibility of increased cosmetic side effects with shorter fractionation. Just don't think there is a single correct answer, was pointing out how similarly the difference in numbers were and that those p values were to some of the things you were circling and maybe a few hundred more patients and that LR would be significant, or maybe if 2 or so more patients recur before their 5 year interval, etc. Most people I know do both forms of treatment and just talk with the patients about the pros and cons and let them decide. I think both are good options.
Long discussion about breast radiation. Did anyones mind change about anything? Nope lol

This was awesome discussion, better than I've ever had in real life. I really do appreciate SDN, please keep up the strong work!

Just this week I got a little friendly questioning from my practice about why Im doing so much 5 fraction lately. People pick it. I don't have answer. There are also people that pick 15 fractions, but no one ever brings that up haha

I genuinely think a lot of radiation oncologists have just never looked at the appendix of Fast Forward! Its fascinating and informative.

I think everyone in this thread is reasonable except that idiot that enrolled someone to a trial and left the patient with the impression that there are no risks of increased side effects on a trial.

Some academics in this field are wild.

 

[radoncftw]

This was awesome discussion, better than I've ever had in real life. I really do appreciate SDN, please keep up the strong work!

Just this week I got a little friendly questioning from my practice about why Im doing so much 5 fraction lately. People pick it. I don't have answer. There are also people that pick 15 fractions, but no one ever brings that up haha

I genuinely think a lot of radiation oncologists have just never looked at the appendix of Fast Forward! Its fascinating and informative.

I think everyone in this thread is reasonable except that idiot that enrolled someone to a trial and left the patient with the impression that there are no risks of increased side effects on a trial.

Some academics in this field are wild.

i totally agree

i work in a practice that offers most things except brachy (we do alot for GYN, but not for breast or prostate). We have protons and do SRS routinely.

I try to have a balanced discussion. For prostates for example, I discuss conventional vs. hypo vs. SBRT. I discuss proton vs. IMRT. Patients should be aware of the options available and try to make an informed decision.

 

[CurbYourExpectations]

I was with you until protons for prostate 😛

 

[medgator]

People’s minds don’t change sans an insurance company fractionation guideline. Most rad oncs would still be giving whole breast at 1.8 to 2 Gy a day (and prostate for that matter) without insurance company fractionation limits I pessimistically believe.

Again. Not the same. No role for conventional in breast. Not true in prostate. But yes for all practical purposes your statement is likely correct

 

[radoncftw]

I was with you until protons for prostate 😛

it is an option. i discuss PARTIQOL and am open that there is no clear benefit.
Some people have their mind set set on protons before they even see me

 

[BobbyHeenan]

it is an option. i discuss PARTIQOL and am open that there is no clear benefit.
Some people have their mind set set on protons before they even see me

I find this to be true too in my experience.

...and the reason they have their mind made up is because of rad onc advertising, not data.

But I'm not going to spend 40 minutes convincing a patient why proton isn't better. I think it's equal, so I'm not "protecting" them...but i'm certainly not protecting the community/global cost of our insurance premiums either. Only so many battles to have though.

 

[NotMattSpraker]

it is an option. i discuss PARTIQOL and am open that there is no clear benefit.
Some people have their mind set set on protons before they even see me

With no in-state center, patients have been coming to me pretty skeptical of the advertising they see. Or maybe they are just skeptical of everything haha. They are looking for me to validate that they don't have to travel to get protons. PartiQOL has really been a nice study to help these patients.

 

[BobbyHeenan]

With no in-state center, patients have been coming to me pretty skeptical of the advertising they see. Or maybe they are just skeptical of everything haha. They are looking for me to validate that they don't have to travel to get protons. PartiQOL has really been a nice study to help these patients.

PartiQOL has been great...but when there are protons in your region and "my buddy had protons and did great"....that, combined with advertising and dose cloud pics and shiny beautiful centers.....it's an uphill battle.

 

[evilbooyaa]

People’s minds don’t change sans an insurance company fractionation guideline. Most rad oncs would still be giving whole breast at 1.8 to 2 Gy a day (and prostate for that matter) without insurance company fractionation limits I pessimistically believe.

I can tell you that I will not defend anyone doing Conv Fx WBI. Don't think I've done any asn an attending.

 

[TheWallnerus]

I can tell you that I will not defend anyone doing Conv Fx WBI.

One last thing, as Columbo would say...

FAST Forward gives data that seems to lend strong credence to the alpha/beta model and its use over standardly fractionated and hypofractionated scenarios. So...

Red = worse, pink = a little worse, light green = a little better, green = better
(all compared to 40/15)

It is probable a 45/25 whole breast regimen gives less late effects than 40/15. This regimen was always Jay Harris's preferred whole breast regimen back in the day, and it's how I was trained to deliver whole breast. Jay swore up and down 50/25 had more fibrosis than 45/25, and given what we know about 27/5 versus 26/5, he was probably right. (We will likely never prove it, obviously.)

Hence, don't hate on conventional too much. If we are willing to treat a woman three times as long (40/15 vs 26/5) for ~1-2% less fibrosis risk at 5 years, maybe we could defend a rad onc willing to treat a woman ~twice as long (45/25 vs 40/15) for what could perhaps be even greater than a ~1-2% less fibrosis risk.

And 30/5 PBI will always have more risk of late effects than 40/15 PBI, if we believe FAST Forward... and it appears we/you do believe it...

In fact, if the models are correct (and it looks like they are), 30/5 looks very risky. A doozy!

 

[evilbooyaa]

One last thing, as Columbo would say...

FAST Forward gives data that seems to lend strong credence to the alpha/beta model and its use over standardly fractionated and hypofractionated scenarios. So...

View attachment 402374
Red = worse, pink = a little worse, light green = a little better, green = better
(all compared to 40/15)

It is probable a 45/25 whole breast regimen gives less late effects than 40/15. This regimen was always Jay Harris's preferred whole breast regimen back in the day, and it's how I was trained to deliver whole breast. Jay swore up and down 50/25 had more fibrosis than 45/25, and given what we know about 27/5 versus 26/5, he was probably right. (We will likely never prove it, obviously.)

Hence, don't hate on conventional too much. If we are willing to treat a woman three times as long (40/15 vs 26/5) for ~1-2% less fibrosis risk at 5 years, maybe we could defend a rad onc willing to treat a woman ~twice as long (45/25 vs 40/15) for what could perhaps be even greater than a ~1-2% less fibrosis risk.

And 30/5 PBI will always have more risk of late effects than 40/15 PBI, if we believe FAST Forward... and it appears we/you do believe it...

In fact, if the models are correct (and it looks like they are), 30/5 looks very risky. A doozy!

Much we don't know about how heterogeneous plans are.
Numerically yes 30/5 PBI likely to be more toxic but is it statistically and clinically significant? Who knows.

 

[TheWallnerus]

5Fx WBI QD has worse toxicities even at 26/5 compared to 40/15.

~ EPILOGUE ~

Don't know the p-value for the 10y toxicities; suspect they're NS depending on how grouped. But now may have to say something like "5Fx WBI has worse toxicities at 26/5 compared to 40/15 but better local control." Pick a poison.

Given the 10y FAST FORWARD results, and data that 30/5 might have worse tox than 26/5 (and 27/5 worse tox than 26/5 per FAST FORWARD), again I just don't see how 30/5 makes sense for the lowest of the low risk patients anymore. And 30/5 as a standard PBI regimen or not aside, I also don't see how 5 fraction breast limits for certain patients in certain payor guidelines is not going to happen. (To believe that 26/5 is better LC than 40/15, just have to believe that breast ca α/β≤2.17... which is certainly plausible.)

"The results demonstrate excellent long-term local control, minimal late toxicity, and comparable survival outcomes, supporting a major shift in global radiotherapy practice for early breast cancer."



https://oncodaily.com/insight/fast-forward-trial-286216

 

[RadOncMegatron]

~ EPILOGUE ~

Don't know the p-value for the 10y toxicities; suspect they're NS depending on how grouped. But now may have to say something like "5Fx WBI has worse toxicities at 26/5 compared to 40/15 but better local control." Pick a poison.

Given the 10y FAST FORWARD results, and data that 30/5 might have worse tox than 26/5 (and 27/5 worse tox than 26/5 per FAST FORWARD), again I just don't see how 30/5 makes sense for the lowest of the low risk patients anymore. And 30/5 as a standard PBI regimen or not aside, I also don't see how 5 fraction breast limits for certain patients in certain payor guidelines is not going to happen. (To believe that 26/5 is better LC than 40/15, just have to believe that breast ca α/β≤2.17... which is certainly plausible.)

"The results demonstrate excellent long-term local control, minimal late toxicity, and comparable survival outcomes, supporting a major shift in global radiotherapy practice for early breast cancer."

View attachment 403063
View attachment 403064
FAST-Forward trial 10-year results from ESTRO 2025: Hypofractionated breast radiotherapy for 1 vs 3 weeks - OncoDaily

Awesome. Thanks for the post. Do you guys think the every other day approach matters for 30 Gy / 5 (for less toxicity)? Since the Italian trial compared 30 in 5 with 50 plus boost am I crazy for using it in cases for when i would traditionally boost or is breast just the worst?!?!?!

 

[TheWallnerus]

Awesome. Thanks for the post. Do you guys think the every other day approach matters for 30 Gy / 5 (for less toxicity)? Since the Italian trial compared 30 in 5 with 50 plus boost am I crazy for using it in cases for when i would traditionally boost or is breast just the worst?!?!?!

Two questions

Who is a “needs a boost” patient that also, say, is ok for 5fx PBI; they’re almost mutually exclusive in my mind

Is there any level one data that indicates boost improves outcomes (and/or how much does it add tox wise) for hypofractionated or ultrahypofx; obviously that data exists for normofx. Everyone extrapolates from last century’s normofx data re: when to boost hypofx?

 

[BobbyHeenan]

Not sure what to make of this but it’s a HUGE trial. That’s a lot of patients.

 

[CurbYourExpectations]

The death of 40/15? Many are saying it.

 

[BobbyHeenan]

The death of 40/15? Many are saying it.

I had been doing some 40/15 for some locally advanced cases but honestly I think I’ll pump the brakes for those with stable transportation.

 

[madchemist89]

40/15 will be embraced regardless. Trial results are not relevant. People pushing for 40/15 will spin this, and it will go the way of low risk DCIS and T1, ER+ disease in the 65+ cohort. All negative phase 3 trials, but the desire to omit was so strong that the results were hand waved aside.

 

[communitydoc13]

Not sure what to make of this but it’s a HUGE trial. That’s a lot of patients.

Probably nothing….really, it’s probably nothing. Isn’t OS the same in both arms? We all know the uncertainty associated with designating cause of death, and while the trial size is substantial, the end point in question is rare.

15 more bCa “caused” deaths in one arm of a 2000+ pt trial?

I wouldn’t think too hard about it…unless OS trended with it.

There are lots of peculiarities in even good, large trials. Regarding Fast-forward…does anyone believe that 27 Gy is worse at preventing recurrence than 26 Gy (what’s your prior regarding this)? Yet the recurrence rate is worse for 27 Gy…now this is either random (very likely) or due to a peculiar mechanism (like increased induration in 27 Gy leads to further work up and detection bias).

Regarding toxicity and Fast-Forward? You cannot believe the patient or physician assessed numbers very much, and this has been demonstrated in their own publications (where toxicity assessment across different time points was not very concordant).

The best toxicity data in Fast-Forward is the photographic assessment (buried in the supplemental). Both 26 and 27 Gy with about a 3% risk of marked change vs close to zero for 40 Gy. Could also be rando… but I believe this data point (because of both methodology and my assumptions about fraction size).

 

[Palex80]

Probably nothing….really, it’s probably nothing. Isn’t OS the same in both arms? We all know the uncertainty associated with designating cause of death, and while the trial size is substantial, the end point in question is rare.

15 more bCa “caused” deaths in one arm of a 2000+ pt trial?

I wouldn’t think too hard about it…unless OS trended with it.

SKAGEN Trial 1 at ESTRO 2025: Moderately Hypofractionated RT Safe, But Mortality Signal Warrants Caution - OncoDaily

SKAGEN Trial 1 at ESTRO 2025: Moderately Hypofractionated RT Safe, But Mortality Signal Warrants Caution / cancer, ESTRO, ESTRO 2025, ESTRO25, Meattini Icro,

oncodaily.com

 

[Palex80]

Now, perhaps, just perhaps dear @TheWallnerus, not all breast cancers have the same alpha/beta. And perhaps, treating those with a higher alpha/beta with hypofractionation is not a good idea. Perhaps it's the more aggressive ones?

 

[taserlaser]

Probably nothing….really, it’s probably nothing. Isn’t OS the same in both arms? We all know the uncertainty associated with designating cause of death, and while the trial size is substantial, the end point in question is rare.

15 more bCa “caused” deaths in one arm of a 2000+ pt trial?

I wouldn’t think too hard about it…unless OS trended with it.

There are lots of peculiarities in even good, large trials. Regarding Fast-forward…does anyone believe that 27 Gy is worse at preventing recurrence than 26 Gy (what’s your prior regarding this)? Yet the recurrence rate is worse for 27 Gy…now this is either random (very likely) or due to a peculiar mechanism (like increased induration in 27 Gy leads to further work up and detection bias).

Regarding toxicity and Fast-Forward? You cannot believe the patient or physician assessed numbers very much, and this has been demonstrated in their own publications (where toxicity assessment across different time points was not very concordant).

The best toxicity data in Fast-Forward is the photographic assessment (buried in the supplemental). Both 26 and 27 Gy with about a 3% risk of marked change vs close to zero for 40 Gy. Could also be rando… but I believe this data point (because of both methodology and my assumptions about fraction size).

The higher LR rate with 27 is peculiar, but has been identified in one of the other IMPOrT studies as well; higher dose showing increase local recurrence rates. Spurious, or more fibrosis leading to irregular imaging findings and identifying more LR. Hard to say but it’s on their radar for further inquiry afaik

 

[RadOncMegatron]

Probably nothing….really, it’s probably nothing. Isn’t OS the same in both arms? We all know the uncertainty associated with designating cause of death, and while the trial size is substantial, the end point in question is rare.

15 more bCa “caused” deaths in one arm of a 2000+ pt trial?

I wouldn’t think too hard about it…unless OS trended with it.

There are lots of peculiarities in even good, large trials. Regarding Fast-forward…does anyone believe that 27 Gy is worse at preventing recurrence than 26 Gy (what’s your prior regarding this)? Yet the recurrence rate is worse for 27 Gy…now this is either random (very likely) or due to a peculiar mechanism (like increased induration in 27 Gy leads to further work up and detection bias).

Regarding toxicity and Fast-Forward? You cannot believe the patient or physician assessed numbers very much, and this has been demonstrated in their own publications (where toxicity assessment across different time points was not very concordant).

The best toxicity data in Fast-Forward is the photographic assessment (buried in the supplemental). Both 26 and 27 Gy with about a 3% risk of marked change vs close to zero for 40 Gy. Could also be rando… but I believe this data point (because of both methodology and my assumptions about fraction size).

I agree with the sentiment here. For me the question is if 2 weeks /10 fx of convenience is worth it? I plan to use 50 Gy in 25 for RNI as my standard though wouldn’t fault others for using 40 Gy in 15.