APBI and the question of surgical margins

[Palex80]

I have been discussing this with a few colleagues: "Why do APBI guidelines suggest not to perform APBI in patients with rather close margins?"

I understand that the APBI trials were designed that way, but is there any biologic rationale to recommend WBRT over APBI for a rather close margin? I am not talking about "tumor-touching-ink", but the usual margins we often see in daily practice, like 2-3 mm.

Mandatory margins in the Florence trial were 5mm and in the IMPORT Low trial 2mm.
Florence trial included a 10 Gy in the WBRT-arm, Import-Low did not.

Thoughts?

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[Sheldor]

Will be curious what other think, to me it makes absolutely no sense. Why would you switch from APBI (Which has 1.5-2cm margin anyway) to WHOLE BREAST RADIATION because the margin was 2mm not 5mm. Honestly, to me I think it again shows one of the big problems with our field that we can't collectively use our reason and say, "Hmm, maybe the answer for a local problem isn't treating a non-existant problem way far away." Nope, time to do another decade long randomized trial this time comparing outcomes between 1mm margin and 5 mm margin.

End rant. Anyway, I offer it to people with any margins except positive.

 

[RSAOaky]

Probably not biological. We’re treating microscopic disease with a bioequivalent dose. Even if you make the argument that close margins is a surrogate for underrepresented disease, which in theory could increase the volume of microscopic disease being treated, which statistically could lead to a higher rate of recurrence, it doesn’t make sense to do whole breast instead of partial because you’re still going to give the bioequivalent dose of radiation, just to a larger area.

The only logical reason in my mind is if you think having a closer margin increases the chance of some undetected microscopic disease in the vicinity of the tumor bed that you could marginally miss with a partial breast technique. This is less of an issue with import low.

At the end of the day, it’s trial design. If you’re designing a partial breast trial to show equivalence, you’re selecting the lowest risk patients you can. The flip side to that is “we don’t know if 2mm is just as good for LIVI as 5mm.”

I also was not aware that the guidelines for LIVI were 5mm on surgical bed. I’ve just been using the APBI guidelines. I don’t know about you guys, but most of my surgeons aren’t doing 5mm margins these days. May be a reason to increase the CTV margin a smidge.

 

[BobbyHeenan]

Will be curious what other think, to me it makes absolutely no sense. Why would you switch from APBI (Which has 1.5-2cm margin anyway) to WHOLE BREAST RADIATION because the margin was 2mm not 5mm. Honestly, to me I think it again shows one of the big problems with our field that we can't collectively use our reason and say, "Hmm, maybe the answer for a local problem isn't treating a non-existant problem way far away." Nope, time to do another decade long randomized trial this time comparing outcomes between 1mm margin and 5 mm margin.

End rant. Anyway, I offer it to people with any margins except positive.

ABS guidelines and breast surgeon society guidelines agree with you as far as I can remember...negative margin then apbi fine.

 

[deleted1111261]

No tumor on ink for IDC

I was thinking same for dcis, but let’s complicate and say 2mm, because <2mm I’d recommend re-excision (not necessarily WBI).

People definitely pick and choose .. they use the Florence dosing, but restrict it to those that meet suitable criteria from ASTRO. Which is fine, but the ASTRO guidelines are hooey. None of their groups correlate with anything.

 

[TheWallnerus]

Mandatory margins in the Florence trial were 5mm and in the IMPORT Low trial 2mm.
Florence trial included a 10 Gy in the WBRT-arm, Import-Low did not.

Thoughts?

And thus the standard for 26/5 APBI in the entire United Kingdom is 2mm or greater margins.

But the rationale I see is: put yourself in shoes of Dr Surgeon. Dr Surgeon can generally “see” the tumor and Dr Surgeon doesn’t “play cute” and attempts to take a good margin in every lumpectomy case because Dr Surgeon knows this factor is important. Whenever pathology comes back in the report with a 1mm margin or sub-mm margin, Dr Surgeon is always surprised. “Huh, didn’t expect that.” So a close margin obtained at the hands of someone who always tries to avoid a close margin could have implications for a larger tumor size or multifocality or multicentricity.

Just playing devil’s advocate. Remember cancer may not grow as a perfect sphere…

 

[Ray D. Ayshun]

And thus the standard for 26/5 APBI in the entire United Kingdom is 2mm or greater margins.

But the rationale I see is: put yourself in shoes of Dr Surgeon. Dr Surgeon can generally “see” the tumor and Dr Surgeon doesn’t “play cute” and attempts to take a good margin in every lumpectomy case because Dr Surgeon knows this factor is important. Whenever pathology comes back in the report with a 1mm margin or sub-mm margin, Dr Surgeon is always surprised. “Huh, didn’t expect that.” So a close margin obtained at the hands of someone who always tries to avoid a close margin could have implications for a larger tumor size or multifocality or multicentricity.

Just playing devil’s advocate. Remember cancer may not grow as a perfect sphere…

26/5?

 

[TheWallnerus]

26/5?

The UK APBI standard. The RCR has outlined why this won’t be trial-tested and doesn’t need to be. That rationale actually dovetails with the margin discussion here.

 

[taserlaser]

The UK APBI standard. The RCR has outlined why this won’t be trial-tested and doesn’t need to be. That rationale actually dovetails with the margin discussion here.

I agree fully with the RCR here, 26Gy APBI it really should be considered standard. We do logical leaps in other tumor sites, but of course this is breast…

My Centre is opening another APBI vs WBRT trial, RAPID2. Which is fine, whatever. 26 Gy APBI vs 26 Gy WBRT. I personally would have rather seen 26 vs 30 APBI perhaps. Protocol allows for 1mm margins iirc. Something something poor representation of high grade, LVI on apbi trials, yada yada. Pros and cons of harmonized group practice 🫠

 

[TheWallnerus]

My Centre is opening another APBI vs WBRT trial, RAPID2. Which is fine, whatever.

"Which is fine, whatever." Ha. I feel the sarcasm. Some people know best; many people think UK people are not those people.

 

[OTN]

"Which is fine, whatever." Ha. I feel the sarcasm. Some people know best; many people think UK people are not those people.

Data shows, on a population basis, across all measured cancer sites, survival in the UK is ~10% less than that in the US.

This is not debated - in fact, the NHS is trying to figure out how to improve their survival to get closer to the US, but without spending the money. No luck yet.

 

[theradiator]

"Which is fine, whatever." Ha. I feel the sarcasm. Some people know best; many people think UK people are not those people.

You know what, screw NICE. I will start listening to them when US medical oncologists adopt NICE guidelines for systemic therapy.

 

[medgator]

You know what, screw NICE. I will start listening to them when US medical oncologists adopt NICE guidelines for systemic therapy.

Nice doesn't even approve a lot of their therapies to begin with, historically. Bingo

 

[TheWallnerus]

Data shows, on a population basis, across all measured cancer sites, survival in the UK is ~10% less than that in the US.

This is not debated - in fact, the NHS is trying to figure out how to improve their survival to get closer to the US, but without spending the money. No luck yet.

And yet, 15 years ago, breast radiotherapy practice US vs UK was wildly divergent. Now it’s very similar; as we know, the UK didn’t change.

 

[Fpg1245]

And yet, 15 years ago, breast radiotherapy practice US vs UK was wildly divergent. Now it’s very similar; as we know, the UK didn’t change.

They don’t have dedicated radiotherapy physicians again probably to save money. In The UK and honestly they aren’t all that interested in developing the modality Therefore it’s just an extra thing that clinical oncologists don’t want to be bothered with. And it’s expensive when they can just treat people with drugs they get on massive discount due to the way they negotiate for drugs.

The fact that we adopted this here has to do more with the the fact that academic rad onc has metastasized into all aspects of community practice with the academic rad oncs dictating all treatments

If there’s one thing I’ve learned coming from an academic program, it’s that those attendings have nothing but contempt for any type of clinical responsibility.

 

[medgator]

They don’t have dedicated radiotherapy physicians again probably to save money. In The UK and honestly they aren’t all that interested in developing the modality Therefore it’s just an extra thing that clinical oncologists don’t want to be bothered with. And it’s expensive when they can just treat people with drugs they get on massive discount due to the way they negotiate for drugs.

The fact that we adopted this here has to do more with the the fact that academic rad onc has metastasized into all aspects of community practice with the academic rad oncs dictating all treatments

If there’s one thing I’ve learned coming from an academic program, it’s that those attendings have nothing but contempt for any type of clinical responsibility.

💯

 

[deleted1111261]

Take your fish and chips and shove it!

 

[communitydoc13]

I have been discussing this with a few colleagues: "Why do APBI guidelines suggest not to perform APBI in patients with rather close margins?"

I understand that the APBI trials were designed that way, but is there any biologic rationale to recommend WBRT over APBI for a rather close margin? I am not talking about "tumor-touching-ink", but the usual margins we often see in daily practice, like 2-3 mm.

Mandatory margins in the Florence trial were 5mm and in the IMPORT Low trial 2mm.
Florence trial included a 10 Gy in the WBRT-arm, Import-Low did not.

Thoughts?

I think it has to do with how non-inferiority trials are run and then how we apply the lessons from those trials.

In general, non-inferiority trials are looking at scenarios where outcomes are very, very good and asking, "Can we do less?"

The trialists will pick a scenario where non-inferiority is likely. Widely negative margins, favorable pathologic features etc. Non-inferiority of course never means non-inferiority but just statistically very little inferiority. If your local failure without XRT is sitting at 5-10%, pretty much any technique can be shown to be statistically non-inferior within a given trial design.

I think most data indicated that a positive margin is associated with a roughly 2x risk of local recurrence in breast CA. So they leave these out. There might actually be enough recurrence signal to indicate "inferiority" if they included these patients within the trial.

So the trial is run to succeed but excludes clinical scenarios where the new technique might be appropriate.

 

[TheWallnerus]

I think it has to do with how non-inferiority trials are run and then how we apply the lessons from those trials.

In general, non-inferiority trials are looking at scenarios where outcomes are very, very good and asking, "Can we do less?"

The trialists will pick a scenario where non-inferiority is likely. Widely negative margins, favorable pathologic features etc. Non-inferiority of course never means non-inferiority but just statistically very little inferiority. If your local failure without XRT is sitting at 5-10%, pretty much any technique can be shown to be statistically non-inferior within a given trial design.

I think most data indicated that a positive margin is associated with a roughly 2x risk of local recurrence in breast CA. So they leave these out. There might actually be enough recurrence signal to indicate "inferiority" if they included these patients within the trial.

So the trial is run to succeed but excludes clinical scenarios where the new technique might be appropriate.

That said, as I recall, trials like IMPORT as they were going along started tossing in more ER negative and grade 3 patients because the number of events were so low.

I misspoke above. The standard in the UK for APBI is 1mm margin or greater (even though IMPORT limit was 2mm as stated). They did this “pragmatically” according to them. Pragmatism in breast cancer is good.

 

[communitydoc13]

Pragmatism in breast cancer is good.

It is good. Just not terribly concordant with "clinical evidence".

What do they say about the "tyranny of the phase III randomized trial".

 

[deleted1111261]

I just don't get how treating the whole breast for a close margin changes anything.

 

[communitydoc13]

I just don't get how treating the whole breast for a close margin changes anything.

Maybe the margins mean something about the disease. More infiltrative, more prone to multifocality. If margins only reflected surgical skill, then sure, I get that there should be no benefit to whole breast (although there would likely be some benefit to dose escalation).

 

[Palex80]

Data shows, on a population basis, across all measured cancer sites, survival in the UK is ~10% less than that in the US.

All easily explainable.

Typical british teenagers:

Typical US teenagers:

I am getting kicked after this post...

 

[OTN]

All easily explainable.

Typical british teenagers:
View attachment 361645

Typical US teenagers:
View attachment 361647


I am getting kicked after this post...

HPV-mediated cancers are easier to treat than those caused by alcohol or tobacco, so I'll buy it

 

[evilbooyaa]

"Which is fine, whatever." Ha. I feel the sarcasm. Some people know best; many people think UK people are not those people.

A health system that is already hemorrhaging money, massively underfunded, and short on staff/centers to be able to accomodate the mass of patients that require treatment, to the point that there are waiting lists for cancer treatment, perversely incentivizes getting a patient IN and a patient OUT ASAP to maximize cost/benefit (not for the patient, but for the system), that uses clinical oncologists who do both systemic and radiation therapy (and thus radiation therapy is considered more of a necessary nuisance rather than something that can actually be optimized).


That health system wants to use 5 fraction for near everything in the most common diagnosis requiring radiation in the absence of data?

I'm shocked. Shocked, I say.

Anyways, APBI for no tumor in ink should be fine. If I was a Chirag Shah academic breast type, I'd do it all the time. Given APBI when I became an attending was already looked at with extreme side eye, I stuck with ASTRO suitable. Could go with ABS suitable.

 

[medgator]

All easily explainable.

Typical british teenagers:
View attachment 361645

Typical US teenagers:
View attachment 361647


I am getting kicked after this post...

Uh no

Young people are having less casual sex and spending more time scrolling on social media

A new study adds to evidence that financial uncertainty and social media are changing the sexual landscape for young adults.

www.insider.com

 

[Bequerel]

A health system that is already hemorrhaging money, massively underfunded, and short on staff/centers to be able to accomodate the mass of patients that require treatment, to the point that there are waiting lists for cancer treatment, perversely incentivizes getting a patient IN and a patient OUT ASAP to maximize cost/benefit (not for the patient, but for the system), that uses clinical oncologists who do both systemic and radiation therapy (and thus radiation therapy is considered more of a necessary nuisance rather than something that can actually be optimized).


That health system wants to use 5 fraction for near everything in the most common diagnosis requiring radiation in the absence of data?

I'm shocked. Shocked, I say.

Anyways, APBI for no tumor in ink should be fine. If I was a Chirag Shah academic breast type, I'd do it all the time. Given APBI when I became an attending was already looked at with extreme side eye, I stuck with ASTRO suitable. Could go with ABS suitable.

Academic breast is like saying academic palliation. It’s only as difficult as you want to make it. Common sense is paramount. I treat more breast patients a year as a generalist than any of my “academic breast” attendings ever did. Just 10 years ago, I remember these same “academic breast” attending arguing against hypofracfionation for Dcis. APBI for low risk small tumors with no tumor on ink is fine. After DEBRA trial completed and published, we might not even have an opportunity to even see these patients.

 

[HolySmokes]

Academic breast is like saying academic palliation. It’s only as difficult as you want to make it. Common sense is paramount. I treat more breast patients a year as a generalist than any of my “academic breast” attendings ever did. Just 10 years ago, I remember these same “academic breast” attending arguing against hypofracfionation for Dcis. APBI for low risk small tumors with no tumor on ink is fine. After DEBRA trial completed and published, we might not even have an opportunity to even see these patients.

Couldn't agree more. Chirah doesn't use close margins as a reason to forgo APBI, so I feel perfectly comfortable doing the same.

We have the DEBRA trial open at my site and I've talked enough patients out of it by offering 5fx APBI upfront that I think the med onc has stopped even trying to accrue.