Breast boost after complete response to neoadjCT

[scarbrtj]

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The American trial boosted everyone. The Canadian trial boosted no one. The UK trial boost about 50%.

Feel free to boost or not boost whoever you want. Benefit may be minimal, but so is the toxicity. Those 4-5 fractions won't bankrupt the system, especial once bundled.

One exception. Don't "not boost" the lady in the OP. She needs it. Based on a solid footing of randomized data? No.

Tergiversation is a lot more reasonable here IMHO than writing verbs with exclamation points after them. Five extra fractions won't bankrupt the system. But at, let's say, $150/fraction, 5 extra fractions, one extra OTV at $350, ~150,000 hypofx-boostable women per year in the US... "only" an extra $165 million per year in treatments of questionable/unproven benefit. CMS allots about 10 times this amount for rad onc as a whole.

Is the boost in breast hypofx the only boost in modern rad onc where the fraction sizes are typically smaller than the non-boost fractions?

How big should the boost be in partial breast, which I use in many low-risk patients nowadays. The argument evidently is: the boost works no matter the initial dose or fraction size, so it should work in partial breast too. I use the dose they used in the trial: 40/15. I'd consider adding an extra five fractions of 0.4 Gy per fraction, for a total dose of 42.

A good number.

 

[scarbrtj]

The American trial boosted everyone. The Canadian trial boosted no one. The UK trial boost about 50%.

Feel free to boost or not boost whoever you want. Benefit may be minimal, but so is the toxicity. Those 4-5 fractions won't bankrupt the system, especial once bundled.

One exception. Don't "not boost" the lady in the OP. She needs it. Based on a solid footing of randomized data? No.

Rather than go in the weeds with editing my previous post...
In the American trial that boosted everyone, this I presume, I know of no one who is doing 15 times 3.2 Gy to 48 Gy for the cavity. This would not be something I would do of my own volition and seems almost experimental. There was measurable late toxicity from START near these fraction sizes. Again, why flirt with the toxicity when you can't even give a number for the benefit. The benefit from boosting in START was literally 1/∞. Re: the Canadian trial that boosted no one, the first time I saw a publication of "true" breast hypofx was "Whelan-1" where everyone was boosted. In Whelan-2, no one was boosted and the recurrence rates were half or less than that of Whelan-1... without the boost.

 

[Mandelin Rain]

In the worldwide experience of hypofractionated breast cancer treatment, I'd estimate that about 50% of women were boosted about 50% were not. These women were not randomized against each other. There's neither been a spate of reported recurrences without boost, nor even mild toxicity with boost. Common sense and experience with passe' traditionally fractionated radiation (2 Gy v 2.66 Gy, huge difference I know), indicates that a subset of women may benefit from a few more days of radiation colloquially known as boosting. I treat those same women with a boost after 15 or 16 fractions, because my brain tells me it's reasonable to do so and it also tells me that I don't need hard data to justify every decision it makes.

I'll leave it at that though. Desperation to prove the unprovable is unbecoming.

 

[scarbrtj]

I will concur that for the most part this is splitting hairs (insert witty gif/YouTube link etc/distraction/obscure study) as the net effect of a boost as demonstrated by phase 3 randomized trials is typically a small but meaningful local control benefit without discernible survival benefit. However, this benefit is in the order of 10% at 10 years (Impact of pathological characteristics on local relapse after breast-conserving therapy: a subgroup analysis of the EORTC boost versus no boost trial. - PubMed - NCBI) in younger and/or higher grade patients and I am hesitant to omit such therapy in this population.

As such, I will firmly stand by the fact that the net body of evidence favors a local control benefit for boost radiotherapy (see above). Admittedly, there is no smoking gun per se in the setting of pure hypofractionation but your overall argument smacks hollow as we rarely repeat clinical trials after discerning small incremental benefits in other aspects of related treatment (this link, that link, the other link). Additionally, once a therapy becomes standard, it becomes borderline unethical to engage in counterpractice and and as a result a comparative dataset does not exist to prove or disprove your counterpoint, and the foundational trials will likely never be repeated.

We have even confirmed the local control benefit of a boost in lowly DCIS, and they even included hypofractionated studies! (Association of Radiotherapy Boost for Ductal Carcinoma In Situ With Local Control After Whole-Breast Radiotherapy).

Furthermore the available data would suggest that hypofractionated whole breast radiation offers a gentler effect on cosmesis without any negative effect (and typically superior outcomes) on tumor control (insert every hypofractionated study ever) so I have difficulty understanding how the boost becomes such as distasteful thing in this setting.

You mention your continued use of boost in conventional fractionation. Do you continue to use antiquated dosing schedules outside of regional nodal irradiation (which you appear to abhor?). I have not conventionally fractionated a whole breast patient in 5+ years and would not feel right witholding a boost in my higher risk patients. I think your staunch anti boost stance deserves an in depth description of your practice patterns lest you deceive us by sins of omission.

Are we discussing whether God exists or breast boosts help in hypofx; both about as provable.

I don't know about "confirmed" in DCIS. Pretty strong word. Again, lots of non-hypofx data in there, retrospective, etc. (They said the hypofx patients were treated with "13 to 16-Gy fractions" heh heh). Four thousand patients... <1% LC benefit at 5 years, ~3% LC benefit at 15 years. How exciting (Eeyore voice). We'd maybe need to spend a billion dollars to save one DCIS patient's life w/boost in a hundred years. I will never boost a hypofx DCIS patient. You can't make me!

Re: boost being beneficial for invasive, younger, higher grade, patients, etc... I concur. But (there's always a but) in the hypofx studies there has been a remarkably consistent theme: grade and age and other things don't affect the LC patterns within these subsets when dose (Nfx vs Hfx, boost vs no boost) compared. A signal seen in the normofx trials is not being seen in the hypofx trials. Young people had a ~15-20% LR risk in START, but boosting (~50% of patients got it, we don't know who did... theoretically it was simply dealer's choice) wasn't seen to affect this at all. In Whelan-2, where a slightly higher whole breast hypofx dose was given than was given in START, but no one got a boost, merely doing no-boost hypofx significantly dropped the 5y LR risk in young patients from ~7% to ~3%. A boost wouldn't help a ~3% LR risk at 5y very much even though the subset is "high risk." The LR risks in the young seem lower in no-boost/higher*-dose Whelan than sometime-boost/lower*-ish-dose START. Clearly what we "knew" in normofx (what I "knew" in normofx was that boost was a class solution) is not translating/extrapolating into hypofx very convincingly. I don't think this is a failure of or illogicality of radiobiology, a failure on my part to be intelligent, or even conflicting with previous boost data, as much as it is the increasing success of breast cancer therapeutics as the years march forward. As they get more successful, the boost will inevitably become less so. Ongoing validation of the Fisher hypothesis: you can't really affect survival with local control, but things that affect survival affect everything-else (of which local is a part of) control.

But why shouldn't we have a boost trial for hypofx in young patients. That'd be a great trial. Right now the data says boosting makes no difference or is apt not to. Let's disprove that. As can be seen here in this dearth of data, we need science not opinions/extrapolation. If boosting in hypofx can't easily swat away some skepticism by little 'ol me on the little 'ol Internet, boosting's not a fait accompli.

But "borderline unethical." "Smacks hollow." "Antiquated schedules." "Deceive by sins of omission." I'm not criticizing anybody's faith. I'm simply saying here's why it's reasonable to be an atheist.

*-regarding the whole breast dose only

 

[Palex80]

But (there's always a but) in the hypofx studies there has been a remarkably consistent theme: grade and age and other things don't affect the LC patterns within these subsets when dose (Nfx vs Hfx, boost vs no boost) compared. A signal seen in the normofx trials is not being seen in the hypofx trials

This is not completely correct. Noone can say that.

What we know:
1. Boost or no–boost has no impact on LR within the trials. But the use of boost was not randomized, but let to the discretion of the treating physician.
2. Fractionation plays no role on LR risk when taking into account histological factors for increased LR.

We do not know, if boost or no–boost in matched pairs of patients (based on risks for LR) had an impact.
But the trials were never designed to show that.

 

[Pointless]

In the worldwide experience of hypofractionated breast cancer treatment, I'd estimate that about 50% of women were boosted about 50% were not. These women were not randomized against each other. There's neither been a spate of reported recurrences without boost, nor even mild toxicity with boost. Common sense and experience with passe' traditionally fractionated radiation (2 Gy v 2.66 Gy, huge difference I know), indicates that a subset of women may benefit from a few more days of radiation colloquially known as boosting. I treat those same women with a boost after 15 or 16 fractions, because my brain tells me it's reasonable to do so and it also tells me that I don't need hard data to justify every decision it makes.

I'll leave it at that though. Desperation to prove the unprovable is unbecoming.

Agree with all of this. I don't think this issue requires delving too far into the weeds. There is a small local control benefit to boost in selected patients and little additional toxicity. It makes perfect sense to make your decision re: boost or not boost the same way, whether you are conventionally fractionating or hypofracing. Any additional thought given to this matter is a bit of a fool's errand.

 

[xrthopeful]

Well said

 

[scarbrtj]

This is not completely correct. Noone can say that.

What we know:
1. Boost or no–boost has no impact on LR within the trials. But the use of boost was not randomized, but let to the discretion of the treating physician.
2. Fractionation plays no role on LR risk when taking into account histological factors for increased LR.

We do not know, if boost or no–boost in matched pairs of patients (based on risks for LR) had an impact.
But the trials were never designed to show that.

When Whelan-2 (42.5/16 whole breast no boost) came out in 2002, I started hypofractionating all low-risk patients (no grade 3's, all older Stage I ER+/Her2-). I looked at Whelan-1. That schedule (40/16 plus 12.5/5 boost) didn't seem safe to me and the IBTR rate was 11%; with 42.5/16 and no boost, it was ~3%. I remember this all really clearly. I did scour the studies in those days because I was deciding to radically change my practice. The Canadian data was strong and compelling, and I knew the rest of the world (UK for example) hypofractionated breast cancer. So I began doing hypofractionation exactly as in Whelan-2 in 2003: 42.5/16, no boost. It felt very safe. Got a lot of pushback (can you imagine what that SDN discussion would have been like), but one thing that never came up was whether there was a "boost superior" (B.S.) possibility for 42.5/16.

The only reason to do boosting in breast hypofx is because you think the benefit-to-risk ratio is favorable and is thus superior to not doing boost. But until now I haven't really encountered or dove deep into B.S. thinking. Aside from normofx-to-hypofx B.S. extrapolation, where is this B.S. thought pattern coming from; is it START? START is data rich. They boosted thousands of patients in START, and thousands they did not boost. All we know is they boosted people in whom B.S. thinking applied; we don't know what their B.S. criteria were. But they examined the B.S. idea in START; I know because they said so. I also know their post-hoc analyses for individual risk factors (boosting or not, grade, age, etc.) were multivariate analyses. It's certainly what I do when I do post-hoc analysis on a bunch of different variables. It "[attempts] to examine whether a difference persists after 'controlling' for the effect of the covariate that can impact the numerical dependent variable of interest." So I rather send it back to you...

When you say "We do not know, if boost or no–boost in matched pairs of patients (based on risks for LR) had an impact"... how do you know that we don't know? To hold onto a B.S. hypothesis here we have to suppose that of the thousands of patients who got boosted in START, the trialists simply didn't look at the effect of boost/no-boost in the young patients, or high grade patients, and so on. All that data is there... but they just didn't press COMPUTE in their stat spreadsheet to see if it mattered. Or they pressed COMPUTE and they just decided not to share that post-hoc analysis with us. One post-hoc analysis the START trialists have shared though is this: treatment time elongation in hypofractionation is associated with worse local control, with the "extrapolation" being if you sequentially boost: bad.* Better concomitantly boost, if you're boosting, and keep it at ~15 fractions total or less. And you know my next question: will we have more side effects with concomitant boosts at >3Gy per day?

Who knows! But this will clearly allow us all to hold on to our B.S.

* EDIT: One out of three patients have "mild or marked change in photographic breast appearance by 5 years" with UK START regimens? What's going on? I pride myself on great cosmetic outcomes and that seems really high.