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Illogical?

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Illogical?

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Yes, sure, illogical. We know there's about a 10-20% non-compliance rate for endocrine therapy for breast cancer patients. It would be illogical to think that somehow all the non-compliance was distributed all Maxwell's Demon-like into either 1) the whole breast RT group (trend toward more LR vs IMPORT) or 2) the IMPORT group (trend toward less LR vs whole breast). Almost certainly, thanks to the power of randomization, the non-compliance reached entropy between the groups. Finally, thinking Fisherian, "variations in the style of locoregional therapy will never affect OS in breast cancer."


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Yes, sure, illogical. We know there's about a 10-20% non-compliance rate for endocrine therapy for breast cancer patients. It would be illogical to think that somehow all the non-compliance was distributed all Maxwell's Demon-like into either 1) the whole breast RT group (trend toward more LR vs IMPORT) or 2) the IMPORT group (trend toward less LR vs whole breast). Almost certainly, thanks to the power of randomization, the non-compliance reached entropy between the groups.


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Lol 20% noncompliance rate. Also, define "noncompliance" cause its not just "i missed a pill once last week, but otherwise I did great in the last xx months" versus "I take them every other day, it really helps keep my hot flashes in check. Also, sometimes I just skip a few days."


Bro, where do you practice? I think you made my point for me.

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Lol 20% noncompliance rate. Also, define "noncompliance" cause its not just "i missed a pill once last week, but otherwise I did great in the last xx months" versus "I take them every other day, it really helps keep my hot flashes in check. Also, sometimes I just skip a few days."


Bro, where do you practice? I think you made my point for me.

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Imagine a 50-100% endocrine non-compliance rate for each group in the curves above... does endocrine non-compliance affect LR in terms of breast PTVwhole (recurrence 1.5% @7y) vs breast PTVpartial (recurrence 1.2% @7y)? The higher the non-compliance, one becomes more compelled to assume that the raw number of non-adherers is higher, but still equal, in the two different PTV groups (giving a better potential effect of non-compliance on the LR). And, AT WORST, if Maxwell's Demon did put all the endocrine non-adherers in the IMPORT group, non-adherence had no effect on LR... and/or made LR statistically insignificantly less likely. (EDIT: I should also make the point that if the Demon put all the non-adherers in the whole breast group, non-compliance also likewise had no effect on LR.)
 
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We can quibble, now, over whether hypofx is standard for all breast RT indications. As we all know, it is the standard for many rad oncs elsewhere on the planet:

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It is as plain as the tusks coming out of my mouth that one day in the not distant future insurance companies will place 15 fractions as the upper limit of fractions for all breast cancer RT patients... and 5 fractions some years after that if FAST-Forward nodal substudy is good.
Don't practice like the Brits unless you have to. NHS not a destination for medical tourism.
 
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Don't practice like the Brits unless you have to. NHS not a destination for medical tourism.
And yet, in terms of breast hypofractionation, almost all the good usable data for this comes from the Brits... and was originated by the Brits for sure. The Brits "discovered" the alpha/beta for breast cancer and the normal tissue of the breast/ribs/chest wall and so on. START, IMPORT, FAST-Forward, etc. All the feelings of "it's safe to hypofractionate breast" for tumor control and side effects come from Britain. Like when Gene Wilder told Marty Feldman "Damn your eyes!" and Marty Feldman said "Too late!"... it's too late for us NOT to practice like the Brits. We already are.

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And yet, in terms of breast hypofractionation, almost all the good usable data for this comes from the Brits
All true, and their trials are well done IMO. But the statistical tools are misleading and the motivation is clear. This is the NHS. They are very transparent in their published appendices. In terms of EBM, Brits far far far ahead of us.

It is reasonable and in general cost effective to hypofractionate anything. I would not be going beyond moderate hypofractionation for my wife's whole breast.
 
All true, and their trials are well done IMO. But the statistical tools are misleading and the motivation is clear. This is the NHS. They are very transparent in their published appendices. In terms of EBM, Brits far far far ahead of us.

It is reasonable and in general cost effective to hypofractionate anything. I would not be going beyond moderate hypofractionation for my wife's whole breast.
Guns don't kill people, people kill people. Statistical tools are likewise not misleading!

And given that stage I breast cancer is the most common presentation of breast cancer, I likely would not use any sort of fractionation schedule on my wife's whole breast. Of course, I don't have a wife.
 
Guns don't kill people, people kill people. Statistical tools are likewise not misleading!

And given that stage I breast cancer is the most common presentation of breast cancer, I likely would not use any sort of fractionation schedule on my wife's whole breast. Of course, I don't have a wife.
Telling. (not the wife thing, the omission thing).

Fair regarding the guns analogy. Often there isn't an appropriate gun for the job. Toxicity is tough to study well. Rare bad toxicity is not conducive to p-value type work, and common lower grade toxicity has enormous variance in assessment.
 
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Telling. (not the wife thing, the omission thing).

Fair regarding the guns analogy. Often there isn't an appropriate gun for the job. Toxicity is tough to study well. Rare bad toxicity is not conducive to p-value type work, and common lower grade toxicity has enormous variance in assessment.
I would not omit radiation... I just almost never irradiate whole breast for low risk stage I anymore. (And stage 0 or stage I is the majority of what we all see, natch.)

"Rare bad toxicity is not conducive to p-value type work"...
Have to mention: the most significant p-values in MA20 and EORTC 22922 (p<0.001 ranges eg) were for lung toxicity from ENI... not for improved DFS and certainly not improved OS.
 
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Another spinoff to the breast is the worst conversation!
 
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Coming soon by all insurances and they wouldnt be “wrong”:

Standard non IBC RNI without a needed boost: we will only cover 15

Standard non IBC which requires a standard boost: we will only cover 16

APBI candidate: we will cover 5

Non RNI, not APBI: we will cover 5 WBRT

15Fx for RNI seems fine based on updated data. I felt it was 'too early' as a resident but there aren't really any new safety signals I'm aware of. Glad I don't treat breast...

APBI billed as SBRT for 5Fx? Sounds good to me for appropriate candidates. Win-win. That being said, people that are 'candidates' for APBI are much more than the inclusion criteria for the trials - are there clips? Seroma? % of breast filled by the seroma is too big? Unable to create a safe plan due to anatomy?

27/5 Fx WBRT is worse than 16 in terms of toxicity (buried in the supplement section). I would fight for 16Fx WBRT to be an option compared to 5Fx WBRT the same way I fight for conventional prostate to still be an option compared to mod hypo.

Even at end of residency (like 4-5 years ago) we had early stage breast patients who got denied by the boomer attending wanting to do 25Fx in a large breasted patient
 
Have to mention: the most significant p-values in MA20 and EORTC 22922 (p<0.001 ranges eg) were for lung toxicity from ENI... not for improved DFS and certainly not improved OS.
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.
 
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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.
 
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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.
 
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.

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Anything else we can discuss?
 
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.

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5 years not being long enough for breast is the boomerest RO thing ever
 
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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?
 
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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.
 
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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...
 
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?
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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"
 
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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.
 
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.
 
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I do. No age restriction. That doesn't even make biological sense.

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).
 
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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.
 

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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?
 

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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.
 
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.
 
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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.
 
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.
 
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.
 
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