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[evilbooyaa]

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5 x 6 Gy gives a BED of 48 Gy (a/b=10 Gy)
28 x 1.8 Gy gives a BED of 59.5 Gy (a/b=10 Gy)

a/b for anal cancer cells is however perhaps lower than 10 Gy?

Why would anal cancer cells a/b be lower than 10? Squamous cell, concern for fast repopulation, etc. etc. A/b 10 seems appropriate.

IMPORT-LOW…

So hot in quality and evidence

So cold in the heart and mind of the American MD

Nothing wrong with IMPORT-LOW, but nothing wrong with Livi et al. Different strokes for different folks.

 

[evilbooyaa]

Yes. But.. there are caveats littered like a Ukranian Minefield in Bahkrut with regards to that study.
'
Excellent discussion here: Expert Discussion: Hypofractionated Radiation Therapy – Standard for All Indications?

I stand by my original statement (tongue in cheek one was obviously for fun).

Are you arguing against partial breast irradiation? And you think endocrine compliance has something to do with risk of IBTR that would be non-equal between the two groups?

Are you saying you think risk of LR is HIGHER in APBI than it is without APBI in the studied patient cohorts? B/c I, and the data, disagree pretty strongly about that. Just sayin'.

We used to do 3D H&N and 3D prostate when we didn't know any better. Now we do and we don't do that old stuff anymore.

 

[sirspamalot]

I know we don't do old stuff anymore, but it was easier. I was just whining about my workday.

6 year follow up is not the be all end all for breast cancer. LRR risk doesn't dissipate with time in breast. Patients with low risk cancer can get by without radiation. Outcomes of any radiation, including zero, probably would be similar in older low risk patients who take pillz. Well, except for improved cosmesis (p value fo sho).

Regardless, the experts agree that 16 fx is just fine, and as such, I'm willing to roll with it.

Anything else we can discuss?

 

[TheWallnerus]

Have to reply that you may be making my point. 11 vs 2 patients with grade 2 pneumonitis in arms with 900 patients. 1% vs 0%. That p-value should not be lauded and the added risk may be clinically insignificant.

I will dance on the head of a pin and quibble with the pneumonitis rate numbers; can be more like 4% vs 2%. Clinically insignificant? The number needed to harm w/ breast ENI is arguably smaller (about 40) than the number needed to treat for a DFS w/ ENI (about 100)... an inconvenient truth! But I say all that to also say the ~1% vs ~1% local recurrence rates with whole vs partial breast RT in low risk breast cancer, in IMPORT-LOW, must thus be termed clinically insignificant too.

 

[TheWallnerus]

6 year follow up is not the be all end all for breast cancer. LRR risk doesn't dissipate with time in breast

"An argument without merit!" (!)

 

[deleted1111261]

5 years not being long enough for breast is the boomerest RO thing ever

 

[TheWallnerus]

Nothing wrong with IMPORT-LOW, but nothing wrong with Livi et al. Different strokes for different folks.

For those paying attention, or for Anglophiles, or both, IMPORT-LOW is, now, really 26 Gy/5 fx. Which should offer lower toxicity than 30/5.

 

[evilbooyaa]

"An argument without merit!" (!)

How about 5Fx whole breast is more toxic than 15-16Fx whole breast based on the supplemental data that was buried by the UK folks because they're perversely incentivized to limit number of treatments despite the potential downsides, similar to as is seen in prostate cancer?

PS - my standard is 3 weeks for all whole breasts, so ya can't "OK boomer" me!

Two sets of cultists on either side, what are those of in the middle like me and OTN supposed to do?

 

[sirspamalot]

"An argument without merit!" (!)

Slide are cool. References are better. One thing isn't necessarily another. And breast cancer goes way past 10 years if we're talking about high risk 40 year olds.

Cherry picking low risk patients and hollering about marginally improved cosmetic outcomes, ok dokey.

Meanwhile, I like my job. If you're hypo everything, then I would think you do nothing but 5 fraction rectal, 1 fraction bone mets, and whenever possible, no radiation at all where the benefit is so marginal as to be in doubt.

 

[evilbooyaa]

For those paying attention, or for Anglophiles, or both, IMPORT-LOW is, now, really 26 Gy/5 fx. Which should offer lower toxicity than 30/5.

Not unreasonable to do but no clinical data on 26/5 partial breast in terms of 'establishing a standard'. Is it enough dose in the PBI setting compared to the same dose for WBI? We know how sensitive LC rates are to even slight differences in total RT dose across a 5fx regimen...

 

[sirspamalot]

5 years not being long enough for breast is the boomerest RO thing ever

Tell it to your 40 yo high risk patient. LOL who needs any follow up after 5 years, what a waste of time amirite?

 

[deleted1111261]

Tell it to your 40 yo high risk patient.

I do. No age restriction. That doesn't even make biological sense.

 

[sirspamalot]

If you don't understand the difference between a high risk 40yo patient and a 65 yo ER+ low risk patient, its you who is lacking common sense.

 

[TheWallnerus]

How about 5Fx whole breast is more toxic than 15-16Fx whole breast based on the supplemental data that was buried by the UK folks because they're perversely incentivized to limit number of treatments despite the potential downsides, similar to as is seen in prostate cancer?

PS - my standard is 3 weeks for all whole breasts, so ya can't "OK boomer" me!

Two sets of cultists on either side, what are those of in the middle like me and OTN supposed to do?

 

[deleted1111261]

If you don't understand the difference between a high risk 40yo patient and a 65 yo ER+ low risk patient, its you who is lacking common sense.

I am here to learn. Explain please why dose/fraction would change outcomes in 40 vs 65 year old? Data please, as this is "common sense"

 

[Gfunk6]

How about a trial of 26 Gy/5fx partial breast/no hormone vs no RT/hormones vs 5 years of weekly pembrolizumab

@TheWallnerus you will never succeed in life until you start to think like a Med Onc

 

[TheWallnerus]

Not unreasonable to do but no clinical data on 26/5 partial breast in terms of 'establishing a standard'.

At the level of evidence to which I think you're hinting, we will never get that "standard." So we have it now, or we don't. You/we decide!

 

[sirspamalot]

No, you're not hear to learn. You're hear to espouse your one sided holy grail views based on 6 year follow up data without regard to the potential for long term risk to patients who may be at high risk not only for local recurrence but distal failure as well.

 

[deleted1111261]

Slide are cool. References are better. One thing isn't necessarily another. And breast cancer goes way past 10 years if we're talking about high risk 40 year olds.

Cherry picking low risk patients and hollering about marginally improved cosmetic outcomes, ok dokey.

Meanwhile, I like my job. If you're hypo everything, then I would think you do nothing but 5 fraction rectal, 1 fraction bone mets, and whenever possible, no radiation at all where the benefit is so marginal as to be in doubt.

Well
1) 5 Fx rectal in TNT setting has been shown to be worse for LR. So, no. Only shorten if it is the same outcome (cure/toxicity)
2) Single fx bone mets are phenomenal. I do 10-16 Gy in 1 often.
3) Breast omission trials have made me believe even more strongly in the value of 5-16 Fx treatment which reduces the risk of recurrence to almost nil per year.

 

[deleted1111261]

No, you're not hear to learn. You're hear to espouse your one sided holy grail views based on 6 year follow up data without regard to the potential for long term risk to patients who may be at high risk not only for local recurrence but distal failure as well.

Try me! @elementaryschooleconomics @TheWallnerus and @NotMattSpraker have changed my practice.

 

[communitydoc13]

I do. No age restriction. That doesn't even make biological sense.

https://www.nejm.org/doi/full/10.1056/nejmoa1701830

ER+ breast cancer comes back forever. It's almost like looking at 5 year outcomes for prostate cancer.

Age also matters enormously for ER+ breast CA. Utility of genomic studies limited in younger patients for a number of reasons (including menstrual modulation of genomic profiles).

 

[sirspamalot]

As I said above, I'm willing to do 16 fraction regimen because it is what patients are hearing from their medoncs and are willing to accept. No point in belaboring this any further.

 

[evilbooyaa]

So clinicians felt that some aspects of the breast seemed to do worse with 26/5 WBI and patients felt that their breasts were more swollen at 5-YEARS post treatment, with ZERO advantages to the 26/5 arm besides simply 10 treatments.

In a system that is incentivized to reduce treatments (NHS) this is a great win and patients will have to deal with these increased feelings of bother.

In a system that is not incentivized to reduce treatments, why would we put our patients at a higher-risk of LATE toxicity simply to cut some fractions?

I know I compared this to moderately hypofractionated RT for prostate cancer, but this is arguably WORSE since we're talking about PERMANENT late side effects that are worse with the 5fx arm.

People well say "well it doesn't matter" but I imagine it'll matter to them if/when they have a patient needing whole breast RT.
For those who are proponents of 5fx whole breast - you telling female family members to get this if they have early stage BC?

 

[Mandelin Rain]

 

[deleted1111261]

Oh, I wasn't speaking in specifics. I just don't think you need more than 5 years for breast cancer, as every study from 1970s to now has shown that the 5 year results will define the outcome.

I don't do 26/5 for whole breast, ever. Yet.

 

[Mandelin Rain]

If only there was artificially unbiased way of intelligently determining the best volume, dose, and fractionation for breast cancer, then we could all happily starve together.

 

[deleted1111261]

https://www.nejm.org/doi/full/10.1056/nejmoa1701830

ER+ breast cancer comes back forever. It's almost like looking at 5 year outcomes for prostate cancer.

Age also matters enormously for ER+ breast CA. Utility of genomic studies limited in younger patients for a number of reasons (including menstrual modulation of genomic profiles).

So, I hear you, but that is in terms of follow up for recurrence. None of the studies have shown a change after 5 year mark AFTER the treatment.

What I am saying is - if the 5 year results show efficacy and same toxicity, friends, it's not changing at 10 years.

 

[sirspamalot]

Because treatment hasn't changed for breast cancer since the 1970's? So nothing will change?

It must have felt so good to write that sentence, and yet, here we are.

 

[deleted1111261]

Because treatment hasn't changed for breast cancer since the 1970's? So nothing will change?

It must have felt so good to write that sentence, and yet, here we are.

Man comprehension is difficult out there in MO!

Anyway - no - the way breast cancer studies work haven't changed since the 70s. Not one study has shown a difference in the 10 year update. I don't know how else to keep saying this.

 

[TheWallnerus]

Regardless, the experts agree that 16 fx is just fine,

Dude... I am the expert. You are the expert.

 

[sirspamalot]

Man comprehension is difficult out there in MO!

Anyway - no - the way breast cancer studies work haven't changed since the 70s. Not one study has shown a difference in the 10 year update. I don't know how else to keep saying this.

LOL. We are constantly learning new information. There clearly are risks that go beyond 10 years and trial patients aren't community patients. "No differences" eh? Your 'outcome' of low risk patients having few differences in recurrence (local failures) outcome proves the obvious we already knew. What we didn't know was but f'd around and found out was: ultra short course may be acceptable but as noted, may have consequences with regards to side effects. Maybe we already knew that was coming from our old skool APBI trial.

Anyway:

I don't care for the personal attack(s) you're waging and find your holier-than-thou attitude pretty unpleasant. I'll say it again: I suggest we move on.

 

[TheWallnerus]

Not one study has shown a difference in the 10 year update. I don't know how else to keep saying this.

There clearly are risks that go beyond 10 years

One of the nice features of the Kaplan-Meier analysis, which is non-parametric, is that the "risk rate" is assumed to be proportional (and reliably proportional between randomized groups as well) over time... even beyond 10 years. To be more clear, results at <10y are highly predictive of results even with longer follow-up; this will be associated with how "strong" the originally witnessed statistical (in)significance was however.

 

[Mandelin Rain]

You do things a completely reasonable way, that's not my completely reasonable way of doing it?

 

[deleted1111261]

LOL. We are constantly learning new information. There clearly are risks that go beyond 10 years and trial patients aren't community patients. "No differences" eh? Your 'outcome' of low risk patients having few differences in recurrence (local failures) outcome proves the obvious we already knew. What we didn't know was but f'd around and found out was: ultra short course may be acceptable but as noted, may have consequences with regards to side effects. Maybe we already knew that was coming from our old skool APBI trial.

Anyway:

I don't care for the personal attack(s) you're waging and find your holier-than-thou attitude pretty unpleasant. I'll say it again: I suggest we move on.

Not holier than thou and I apologize that it appears that way.

Saying that you need 10 year follow up for breast is just a way to delay the inevitable, inexorable decline of not only indications, but fractions, which unfortunately hurts us all. It seemed okay to do this in the past - to wait for 10 years. But, every single study shows the exact same thing and the 5 year toxicity outcomes, if they are equal in both arms, will be equal at 10 years. If recurrences are lower at 5 years, they will be lower at 10 years.

The 26/5 whole breast data at the 5 year mark - it already shows potential problems with cosmesis. So, I don't use it. If, like the other studies, did not show a problem, then I would use it - like IMPORT or Livi. For me - personally speaking - if a treatment is equal in terms of cure / toxicity, choose the shorter one - because its good for patients and sometimes is lower cost. I have very little concern about the cost at this point because the US health care system is sofa king broken that me choosing a shorter course won't fix the problems. But, people have lives and if they can get back at it quicker, I'm on board. This forum has led me to reconsider conventional for prostate - I would say I have evolved on this point. It has a different time course for the toxicity (earlier) and a different intensity (higher). Not in all patients. So, I understand why people do it.

 

[deleted1111261]

You do things a completely reasonable way, that's not my completely reasonable way of doing it?

It's not what people choose to do, it's the rationale.

Whelan originally came out with 5 year data and basically 0% of America touched it. Then 10 year came out. I presented the data as a PGY5 at our faculty meeting and man people were resisting. The data over the last decade has still not shown optimal uptake of the shorter treatment. I took over for a fella who up to 2021 - 99% received 60.4 in 33 Fx. What are people waiting for? If 5 isn't enough, 10 isn't enough, then what is?

15-16 +/- 4-5 is fine and works were well, but not evidence based (Wallnerus has pointed out that Whelan had no boost; with 6.7% recurrence at 10 years, boost doesn't help much, but most people do it. APBI had 5 year f/u and of course it was ignored. At 10 years, it is still barely making up a few percent of overall breast treatment, even though the toxicity outcomes are stunning.

5 years outcome for escalation / boost even with toxicity is routinely accepted. 5 year outcome for de-escalation for whatever reason needs 10-15-million year follow up.

 

[communitydoc13]

What I am saying is - if the 5 year results show efficacy and same toxicity, friends, it's not changing at 10 years.

I agree with the toxicity part. Timelines to toxicity are pretty well tabulated in the FAST work out of UK actually. Most toxicity evident within 1-2 years. Telangiectasias continue to get worse over time. Breast hardness continues to get worse over time. Shrinkage happens within year I believe (a nice pearl to tell your patients).

Regarding efficacy, there is some danger here. There is a spike in recurrences after cessation of endocrine therapy.

 

[medgator]

If only there was artificially unbiased way of intelligently determining the best volume, dose, and fractionation for breast cancer, then we could all happily starve together.

Something that money-grubbing community guys have been clamoring for for a very long time. Which likely won't happen any time soon

 

[sirspamalot]

protons have entered the chat

 

[Palex80]

Why would anal cancer cells a/b be lower than 10? Squamous cell, concern for fast repopulation, etc. etc. A/b 10 seems appropriate.

I doubt that anal cancer repopulates like H&N cancer. Think of all the split course regimes we used to wirk with. No reports of tumor regrowth during the pause.
Then think about how anal cancer often slowly regresses after completion of treatment, not like esophageal cancer which can be in CR by the end of treatment sometimes.

 

[deleted1111261]

I agree with the toxicity part. Timelines to toxicity are pretty well tabulated in the FAST work out of UK actually. Most toxicity evident within 1-2 years. Telangiectasias continue to get worse over time. Breast hardness continues to get worse over time. Shrinkage happens within year I believe (a nice pearl to tell your patients).

Regarding efficacy, there is some danger here. There is a spike in recurrences after cessation of endocrine therapy.

I have seen no evidence connecting post ET recurrences linked with dose/fx. Is there something specific you’re referring to?

 

[communitydoc13]

I have seen no evidence connecting post ET recurrences linked with dose/fx. Is there something specific you’re referring to?

Not at all, and I agree with you. I was thinking of XRT omission trials. I’m pretty sure all of our dose regimens are more than enough for the vast majority of patients.

 

[CaesarRO]

It's not what people choose to do, it's the rationale.

Whelan originally came out with 5 year data and basically 0% of America touched it. Then 10 year came out. I presented the data as a PGY5 at our faculty meeting and man people were resisting. The data over the last decade has still not shown optimal uptake of the shorter treatment. I took over for a fella who up to 2021 - 99% received 60.4 in 33 Fx. What are people waiting for? If 5 isn't enough, 10 isn't enough, then what is?

15-16 +/- 4-5 is fine and works were well, but not evidence based (Wallnerus has pointed out that Whelan had no boost; with 6.7% recurrence at 10 years, boost doesn't help much, but most people do it. APBI had 5 year f/u and of course it was ignored. At 10 years, it is still barely making up a few percent of overall breast treatment, even though the toxicity outcomes are stunning.

5 years outcome for escalation / boost even with toxicity is routinely accepted. 5 year outcome for de-escalation for whatever reason needs 10-15-million year follow up.

BIG 3–07/TROG 07.01 did 2x2 for DCIS looking at conventional vs hypo and boost vs no boost. So there's that data for the hypo + boost paradigm. I haven't heard anyone question the benefit of boost purely on a conventional vs hypo basis.

@TheWallnerus Help me with my stats interpretation. From the PRIME II update, they had this gem:

If you generously assume a HR of the benefit of endocrine therapy from baseline of 0.5, then going from no adjuvant to → endocrine, takes you down HR 0.5. If you then stop endocrine therapy and your HR relative to the new 0.5 baseline is 4.66, doesn't that mean your risk is more than double what it would have been if you never started endocrine at all?

Haven't seen anybody discuss this yet, and they don't show the data that they are talking about here. The CI goes below 2, but that's a wide range, and while we talk a lot about poor compliance I haven't seen anything about starting and stopping being worse than never starting at all. Thoughts?

I cannot wait for the modern APBI vs AI trials to report. None of my patients want to take anti-estrogens.

 

[taserlaser]

Whelan is about to open up RAPID2, 26 Gy whole breast vs 26 Gy partial breast.

the original draft protocol mandated a very poor conformity index so that partial breast was not like Florence but more like import low. Sigh. That’s been changed fortunately. There is still quibbling over margins but looks like it will be 2.5 cm = ctv + ptv

one would think we had enough data to walk from 26 Gy whole breast to 26 Gy partial, but alas, some will not be convinced.

 

[deleted1111261]

Whelan is about to open up RAPID2, 26 Gy whole breast vs 26 Gy partial breast.

the original draft protocol mandated a very poor conformity index so that partial breast was not like Florence but more like import low. Sigh. That’s been changed fortunately. There is still quibbling over margins but looks like it will be 2.5 cm = ctv + ptv

one would think we had enough data to walk from 26 Gy whole breast to 26 Gy partial, but alas, some will not be convinced.

Adherence to protocols to the letter is one of the silliest things RadOncs do.

“But Whelan didn’t have DCIS”

Illogical

 

[Fpg1245]

Whelan is about to open up RAPID2, 26 Gy whole breast vs 26 Gy partial breast.

the original draft protocol mandated a very poor conformity index so that partial breast was not like Florence but more like import low. Sigh. That’s been changed fortunately. There is still quibbling over margins but looks like it will be 2.5 cm = ctv + ptv

one would think we had enough data to walk from 26 Gy whole breast to 26 Gy partial, but alas, some will not be convinced.

If people were gonna adopt it, it would have happened already.

 

[OTN]

Whelan is about to open up RAPID2, 26 Gy whole breast vs 26 Gy partial breast.

the original draft protocol mandated a very poor conformity index so that partial breast was not like Florence but more like import low. Sigh. That’s been changed fortunately. There is still quibbling over margins but looks like it will be 2.5 cm = ctv + ptv

one would think we had enough data to walk from 26 Gy whole breast to 26 Gy partial, but alas, some will not be convinced.

Why are they comparing partial breast RT to a known inferior whole breast treatment? Are the academics really just accepting that it's ok that cosmesis in the long-term is harmed so we can offer ten fewer radiation treatments? When did that become ok? Do they tell their patients that's the trade-off?

 

[sirspamalot]

Because if you're in academics, you need something, anything to keep those papers rollin and these are some of the highest profile topics one can hype.

 

[communitydoc13]

Because if you're in academics, you need something, anything to keep those papers rollin and these are some of the highest profile topics one can hype.

Yep. Everyone on this board is already thinking too hard about this. If only we had new drugs to give.

 

[deleted1111261]

Why are they comparing partial breast RT to a known inferior whole breast treatment? Are the academics really just accepting that it's ok that cosmesis in the long-term is harmed so we can offer ten fewer radiation treatments? When did that become ok? Do they tell their patients that's the trade-off?

100%

This is a useless study.

Other than philosophically, what is the hesitation with 30 Gy / 5 APBI - like why drop to 26/5? Use the 30 Gy volume as boost, 26/5 to larger area and use IGRT.

They do so well - data supports this, personal outcomes support this.

 

[Ray D. Ayshun]

Can't we just design a trial and ask ChatGPT what will happen?