micromets axillary radiation

[dellort and 57 others]

Hi All,

I'm an M3 currently on an RO elective. I saw the following case and there was looked like there was some disagreement over it at the tumor board.

50 y.o female, (edit: right sided) ILC, initial lumpectomy attempted with sentinel lymph node dissection, 2.5 cm tumor (ER/PR +, grade II, prosigna score intermediate- high risk of recurrence) removed, but positive margins, 0.8mm micromets found in sentinel node. 4 rounds of neoadjuvant tc chemo before mastectomy for clear margins.

It seemed like the breast surgeon didn't want to do an axillary dissection and pushed for axillary radiation instead. One of the ROs at the board said that they felt axillary radiation wouldn't improve survival in the setting of micromets in a single sentinel node, but others mentioned that there is some data for axillary radiation improving survival and recurrence. It seems like the majority also agreed with whole breast external radiation, but one of the conservative ROs (might have been an MO not sure) seemed to not agree.

I know axillary dissection and radiation are equivalent in terms of recurrence risk, with lower rates of lymphedema in radiation (have heard it mentioned in passing by a previous surgical onc preceptor that axillary radiation could cause high rates of radiation induced brachial plexopathy), but I haven't had any teaching on whether either would have value in micromets like this case. I was wondering how some of the attendings on this board would approach the axillary radiation/ dissection issue (and whether they would perform whole breast rads on a mastectomy pt like this). I just remember being taught during preclerkship that you usually dont need rad post mastectomy. I did a quick lit search in clinic today, but it looked like there wasn't a strong consensus regarding this- of course there's a good chance I didn't dig deep enough. Thanks!

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[BobbyHeenan]

The issue here that makes it controversial in my mind is that some people for just 1 micromet in an otherwise negative margin mastectomy and in a dissected axilla (ie one micromet, all other nodes negative) wouldn't recommend any post mastectomy radiation.

In brief, post mastectomy radiation indications were classically tumor > 5cm, + margin, or > 4 lymph nodes positive. Then a meta analysis (though with mostly older chemo) about 5 years ago suggested big benefit still for radiation for 1-3 nodes positive, so NCCN then said "strongly consider" post mastectomy XRT for 1-3 positive nodes...though newer reports now past 1-2 years are suggesting with more modern chemo that 1-3 node benefit may not be as big as we thought (especially for ER+ lower grade tumors).

It may be done in Europe some, but in the US we would rarely give axillary only adjuvant radiation - we usually treat both the chest wall and axilla/supraclav if we're going to treat.

So in this case you will get some people saying to complete the dissection and hope for no further nodes and then no adjuvant XRT at all and others will say to use radiation to treat the axilla.

I'm not sure anyone knows the best/most data driven answer here. I agree that axillary XRT is unlikely to provide survival benefit.

If this patient had multiple sentinel nodes removed I would probably push for observation. If just one node and SLNB positive at our breast tumor board I suspect surg onc would take for dissection without planned XRT after.

 

[evilbooyaa]

Agree with Heenan, he has explained the data well as to the rationale. The rub is, your patient no longer falls into any well-published series of data given how weird stuff has gone (lumpectomy w/ + margins and micro met, followed by mastectomy but no ALND, now asking about RT). The holy grail of favoring post-mastectomy RT (PMRT) in 1-3 LNs is 1) an old meta-analysis that 2) wasn't in the era of neoadjuvant chemotherapy and 3) wasn't in the era of SLNB alone.

Here's the general thought process:

Lumpectomy + SLNB with micromet by itself (no positive margin) is somewhat controversial from what I've seen. Some people do whole breast, some do 3-field including supraclav, but the reasonable (to me) compromise is to do high tangents, where you cover whole breast + axilla level 1 and 2. The patient getting an oncotype and presence or absence of chemotherapy can make people lean one way or the other.

With the positive margin and subsequent mastectomy, the resulting issue is that not doing a ALND means you don't really know what else is or might have been in the axilla. Neoadjuvant chemo complicates the matter further. Some ROs believe that a cleared axilla (ALND) with one micromet out of 7, or 10, or 10+, or whatever people's cut-offs are, is reasonable evidence to show there isn't sufficient risk of disease in the further lymph nodes, and thus wouldn't radiate the axilla.

To me, in a post-mastectomy case similar this one, if you're not radiating the axilla/SCV, then you don't need to radiate the chest wall either (btw, just as a med student tip - whole breast radiation is done after lumpectomy. Post-mastectomy radiation you want to use the term 'chest wall', as there isn't [or at least shouldn't be] any residual breast tissue left).

However, if the decision is made to radiate the lymph nodes, I would certainly radiate the chest wall. Despite whatever the benefits of post-mastectomy RT are, the greatest likelihood of the cancer coming back remains at the chest wall.

If the surgeon is adamantly against an ALND in this scenario, I would do comprehensive PMRT (chest wall, entirety of axilla, and SCV. +/- IMC depending primarily on initial location of tumor and ability to meet lung constraints).

 

[thaddeus]

My understanding is that axillary failure rates are vanishingly low for patients with N1mi who don't receive radiation, even for those only undergoing SLNB:

Axillary Micrometastases and Isolated Tumor Cells Are Not an Indication for Post-mastectomy Radiotherapy in Stage 1 and 2 Breast Cancer. - PubMed - NCBI

NCCN is pretty clear that no further axillary surgery is required after N1mi is found, regardless of whether radiation is planned:

Further arguing against axillary dissection here is the fact that she has already received neoadjuvant chemo. We are supposed to make RT recommendations based on pretreatment extent of disease, so even if it were negative we don't know that there wasn't disease in additional nodes upfront, so I don't see how this changes the treatment recommendation.

In the absence of additional risk factors concerning for LRR (e.g. LVI) I think its reasonable to just observe, but if treatment is offered, I would advocate for CW+axilla only, not including the SCV and IMNs. If she had gotten a negative margin on her initial lumpectomy I think everybody would agree to just treat with high tangents per Z11; I don't see how assessment of her nodal risk changes to include these areas just because the surgeon screwed up her margins.

 

[evilbooyaa]

N1mi to me is treated as N1, otherwise they wouldn't call it N1mi. I think treating CW + Axilla only is reasonable, but I very rarely see or use high tangents in a non-lumpectomy case.

I know axillary dissection and radiation are equivalent in terms of recurrence risk, with lower rates of lymphedema in radiation (have heard it mentioned in passing by a previous surgical onc preceptor that axillary radiation could cause high rates of radiation induced brachial plexopathy),

Also, as an aside, wanted to let OP know that this is essentially not true with currently used fractionation schemes and treatment planning systems. There is some concern about the potential for slightly higher rates of radiation induced brachial plexopathy in the upcoming trials doing hypofractionated radiation to the brachial plexus as well, although that seems unlikely to be something to actually worry about given the European data.

Regardless, your surg onc preceptor is/was blatantly incorrect, and does a disservice to him/herself and the field of oncology by saying crap like that in front of medical students, things that are blatantly incorrect about another specialty.

 

[Gfunk6]

Granted this is a mastectomy case but surprised no one mentioned the AMAROS trial (https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70460-7/abstract?code=lancet-site)

If patient has a positive sentinel LN, radiation to axilla does as good a job as surgical dissection without the enhanced, persistent risk for lymphedema.

 

[dellort and 57 others]

The issue here that makes it controversial in my mind is that some people for just 1 micromet in an otherwise negative margin mastectomy and in a dissected axilla (ie one micromet, all other nodes negative) wouldn't recommend any post mastectomy radiation.

In brief, post mastectomy radiation indications were classically tumor > 5cm, + margin, or > 4 lymph nodes positive. Then a meta analysis (though with mostly older chemo) about 5 years ago suggested big benefit still for radiation for 1-3 nodes positive, so NCCN then said "strongly consider" post mastectomy XRT for 1-3 positive nodes...though newer reports now past 1-2 years are suggesting with more modern chemo that 1-3 node benefit may not be as big as we thought (especially for ER+ lower grade tumors).

It may be done in Europe some, but in the US we would rarely give axillary only adjuvant radiation - we usually treat both the chest wall and axilla/supraclav if we're going to treat.

So in this case you will get some people saying to complete the dissection and hope for no further nodes and then no adjuvant XRT at all and others will say to use radiation to treat the axilla.

I'm not sure anyone knows the best/most data driven answer here. I agree that axillary XRT is unlikely to provide survival benefit.

If this patient had multiple sentinel nodes removed I would probably push for observation. If just one node and SLNB positive at our breast tumor board I suspect surg onc would take for dissection without planned XRT after.

Thanks for the response! Just to make sure I'm understanding you correctly, even in this patient where only a single SLN biopsy was performed, it would be safe to not give radiation and just monitor? Or did you mean that it would be safe to monitor as long as more than the single SLN was removed? In this patient, would there by any benefit to giving just chest wall radiation in isolation (assuming no surgical dissection performed)? You mentioned a pt with a single positive SLN would be taken for surgical dissection, would that still apply to micrometastatic disease? I'm sorry for all the questions, I thought this case might be a good learning opportunity so I'm trying to take in whatever I can

 

[medgator]

Granted this is a mastectomy case but surprised no one mentioned the AMAROS trial (https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70460-7/abstract?code=lancet-site)

If patient has a positive sentinel LN, radiation to axilla does as good a job as surgical dissection without the enhanced, persistent risk for lymphedema.

With the associated effects of xrt including remote but real risk of second malignancy, something to consider in a 50 year old.

If pt hadn't seen neoadjuvant chemo, I don't think it's unreasonable to consider completion dissection followed by chemo followed by observation if nothing else was positive.

The argument for xrt here is persistent nodal disease after chemo.

 

[evilbooyaa]

Granted this is a mastectomy case but surprised no one mentioned the AMAROS trial (https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70460-7/abstract?code=lancet-site)

If patient has a positive sentinel LN, radiation to axilla does as good a job as surgical dissection without the enhanced, persistent risk for lymphedema.

Sure, AMAROS is the only trial that at least had some percentage of mastectomy patients (albeit a small percentage).

However, the question from thaddeus seems to be whether to radiate at all or not. In a post-mastectomy patient with + SLNB for N1mi without completion ALND, I'm radiating nearly 100% of the time, despite what that cited retrospective series may say. High tangents is reasonable IMO.

Thanks for the response! Just to make sure I'm understanding you correctly, even in this patient where only a single SLN biopsy was performed, it would be safe to not give radiation and just monitor? Or did you mean that it would be safe to monitor as long as more than the single SLN was removed? In this patient, would there by any benefit to giving just chest wall radiation in isolation (assuming no surgical dissection performed)? You mentioned a pt with a single positive SLN would be taken for surgical dissection, would that still apply to micrometastatic disease? I'm sorry for all the questions, I thought this case might be a good learning opportunity so I'm trying to take in whatever I can

1st bolded - Controversial IMO. I believe no, but you have a retrospective series of 141 patients with N1mi saying it's OK to. In a world where we have good randomized data (breast cancer) I'm not enthusiastic doing stuff outside of SOC not on protocol.
2nd bolded - Some make an argument saying that if you have more than a certain number of lymph nodes (number is dependent on the person) with only one LN+ (either macro or micromets) then they would feel comfortable omitting radiation.
3rd bolded - Not really. The chest wall isn't a driver for PMRT in this patient. Your primary goal if you're doing RT is to cover the axilla.
4th bolded - IMO, yes, if the surgeon/patient wants to avoid radiation for whatever reason. If surgeon/patient are OK with radiation, then they'd get radiation instead of ALND.

Good questions to ask. None of them have 100% answers in my opinion.

 

[scarbrtj]

1) Recurrence rate in the "untreated" (argue this amongst yourselves that axilla was untreated in an ACOSOG arm) SLN+ axilla is about 1% at 10 years for T1/T2 patients... surgery, no surgery, beam, no beam... these are moot points... your axillary therapeutic interventions will change nothing. You have to operate upon or irradiate maybe 100-200 patients in this clinical scenario to prevent just one recurrence.
2) Furthermore, chemo that this patient received is known to downstage the axilla in about 1/3 patients; at least, that's the ratio I have in my head.
3) PMRT improves survival in 1-3 node positive BrCA (level 1 evidence), but surely this benefit occurs on a spectrum, and a micromet positive PMRT patient will get only a teeny benefit from PMRT, IMHO.

 

[scarbrtj]

3rd bolded - Not really. The chest wall isn't a driver for PMRT in this patient. Your primary goal if you're doing RT is to cover the axilla.

I'm interested why you'd say this. The axilla has a less than 1% chance of recurrence here; chest wall recurrence risk is going to be multiples higher, right?

 

[thaddeus]

To the OP, thanks for bringing this case. Obviously lots of controversy here, with valid arguments on both sides. I think as a medical student presumably considering a career in rad onc, this back and forth is also educational for you to see what gets us all hot and bothered in the rad onc world. If diving into the weeds of the literature and debating subgroup analyses, inclusion criteria, p-values and selection biases tickles your fancy, then rad onc is a great field for you. If this strikes you as a pointless intellectual exercise, other fields may be a better fit.

 

[Ray D. Ayshun]

i feel like the plan for this patient shouldve been worked out prior to the tc. Patient input important as well given the controversy. as its right-sided, it doesnt seem unreasonable to treat the cw and low axilla as a middle ground bt nft and comprehensive pmrt. Also, i wonder if there was any residual disease seen in the specimen. YpT0, inasmuch as thats a thing in this case could also give some idea of recurrence risk.

 

[dellort and 57 others]

Thanks to everyone for contributing their thoughts!

Agree with Heenan, he has explained the data well as to the rationale. The rub is, your patient no longer falls into any well-published series of data given how weird stuff has gone (lumpectomy w/ + margins and micro met, followed by mastectomy but no ALND, now asking about RT). The holy grail of favoring post-mastectomy RT (PMRT) in 1-3 LNs is 1) an old meta-analysis that 2) wasn't in the era of neoadjuvant chemotherapy and 3) wasn't in the era of SLNB alone.

Here's the general thought process:

Lumpectomy + SLNB with micromet by itself (no positive margin) is somewhat controversial from what I've seen. Some people do whole breast, some do 3-field including supraclav, but the reasonable (to me) compromise is to do high tangents, where you cover whole breast + axilla level 1 and 2. The patient getting an oncotype and presence or absence of chemotherapy can make people lean one way or the other.

With the positive margin and subsequent mastectomy, the resulting issue is that not doing a ALND means you don't really know what else is or might have been in the axilla. Neoadjuvant chemo complicates the matter further. Some ROs believe that a cleared axilla (ALND) with one micromet out of 7, or 10, or 10+, or whatever people's cut-offs are, is reasonable evidence to show there isn't sufficient risk of disease in the further lymph nodes, and thus wouldn't radiate the axilla.

To me, in a post-mastectomy case similar this one, if you're not radiating the axilla/SCV, then you don't need to radiate the chest wall either (btw, just as a med student tip - whole breast radiation is done after lumpectomy. Post-mastectomy radiation you want to use the term 'chest wall', as there isn't [or at least shouldn't be] any residual breast tissue left).

However, if the decision is made to radiate the lymph nodes, I would certainly radiate the chest wall. Despite whatever the benefits of post-mastectomy RT are, the greatest likelihood of the cancer coming back remains at the chest wall.

If the surgeon is adamantly against an ALND in this scenario, I would do comprehensive PMRT (chest wall, entirety of axilla, and SCV. +/- IMC depending primarily on initial location of tumor and ability to meet lung constraints).

evilbooya: thank you for breaking down your approach and for the tip regarding terminology. Aren't there a few studies which outlined risk of further lymph node involvement based off tumour size in the SLN? I may be mistaken but I remember the risk of further lymph node involvement as being very low (low single figure %) for a micromet of this size. If this is the case would you actually need surgical dissection in order to determine risk of further axillary disease, or would it be a fairly safe assumption that no further mets would be found- especially in the context of neoadjuvant chemo?

I also echo scarbrtj in that I'm confused as to why you wouldn't still radiate the chest wall if you decide not to do the axilla. Wouldn't chest wall radiation still have benefits in terms of local recurrence?

Also, as an aside, wanted to let OP know that this is essentially not true with currently used fractionation schemes and treatment planning systems. There is some concern about the potential for slightly higher rates of radiation induced brachial plexopathy in the upcoming trials doing hypofractionated radiation to the brachial plexus as well, although that seems unlikely to be something to actually worry about given the European data.

Regardless, your surg onc preceptor is/was blatantly incorrect, and does a disservice to him/herself and the field of oncology by saying crap like that in front of medical students, things that are blatantly incorrect about another specialty.

That's good to know! Looking at some of the older brachial plexopathy studies it looks like there was still a fairly high incidence of new onset BP 20-30 years post radiation. With that in mind, are you ever really concerned about inducing it when radiating the axilla, especially with the new shift towards hypofractionation?

 

[dellort and 57 others]

My understanding is that axillary failure rates are vanishingly low for patients with N1mi who don't receive radiation, even for those only undergoing SLNB:


NCCN is pretty clear that no further axillary surgery is required after N1mi is found, regardless of whether radiation is planned:

View attachment 233952

Further arguing against axillary dissection here is the fact that she has already received neoadjuvant chemo. We are supposed to make RT recommendations based on pretreatment extent of disease, so even if it were negative we don't know that there wasn't disease in additional nodes upfront, so I don't see how this changes the treatment recommendation.

In the absence of additional risk factors concerning for LRR (e.g. LVI) I think its reasonable to just observe, but if treatment is offered, I would advocate for CW+axilla only, not including the SCV and IMNs. If she had gotten a negative margin on her initial lumpectomy I think everybody would agree to just treat with high tangents per Z11; I don't see how assessment of her nodal risk changes to include these areas just because the surgeon screwed up her margins.

To the OP, thanks for bringing this case. Obviously lots of controversy here, with valid arguments on both sides. I think as a medical student presumably considering a career in rad onc, this back and forth is also educational for you to see what gets us all hot and bothered in the rad onc world. If diving into the weeds of the literature and debating subgroup analyses, inclusion criteria, p-values and selection biases tickles your fancy, then rad onc is a great field for you. If this strikes you as a pointless intellectual exercise, other fields may be a better fit.

Thanks for that study! This has been a great discussion, I've greatly enjoyed reading over everyone's thoughts. This is actually one of the things I really enjoy about the field- it's so research driven, and when there isn't any research there's at least measured discourse. I asked this question above as well, but I was wondering if you personally would do CW only and not the axilla. From what I was taught in pre-clerkship it sounded like the primary indication for PMRT was nodal involvement, which is technically present in this case- I'm just not sure how micromets change planning in terms of isolated CW radiation. As PMRT is primarily indicated with nodal involvement, is the spirit of performing it almost purely for the purpose of axillary control with regional breast control secondary to that?

 

[dellort and 57 others]

With the associated effects of xrt including remote but real risk of second malignancy, something to consider in a 50 year old.

If pt hadn't seen neoadjuvant chemo, I don't think it's unreasonable to consider completion dissection followed by chemo followed by observation if nothing else was positive.

The argument for xrt here is persistent nodal disease after chemo.

So in this case would you personally have avoided giving any RT given that she has had neoadj chemo? Or would you still want surgical dissection to determine nodal disease status?

 

[dellort and 57 others]

1) Recurrence rate in the "untreated" (argue this amongst yourselves that axilla was untreated in an ACOSOG arm) surgery, no surgery, beam, no beam... these are moot points... your axillary therapeutic interventions will change nothing. You have to operate upon or irradiate maybe 100-200 patients in this clinical scenario to prevent just one recurrence.
2) Furthermore, chemo that this patient received is known to downstage the axilla in about 1/3 patients; at least, that's the ratio I have in my head.
3) but surely this benefit occurs on a spectrum, and a micromet positive PMRT patient will get only a teeny benefit from PMRT, IMHO.

Thank you for the links! I've previously seen the second study you linked and it makes sense to treat patients along a spectum instead of treating node involvement as categorical. Pardon my ignorance, but do you know if this treating/ stratifying along a spectum applies to other aspects of BC treatment? For example, for size staging, does a 2cm primary represent a tipping point in terms of tumour burden, increasing risk drastically, or is risk for a 1.9cm fairly continuous with that of a 2cm tumour? I've heard that there's a push to change 2a staged patients to 1B, so maybe that wasn't the best example, but hopefully you get the gist of my message

 

[dellort and 57 others]

i feel like the plan for this patient shouldve been worked out prior to the tc. Patient input important as well given the controversy. as its right-sided, it doesnt seem unreasonable to treat the cw and low axilla as a middle ground bt nft and comprehensive pmrt. Also, i wonder if there was any residual disease seen in the specimen. YpT0, inasmuch as thats a thing in this case could also give some idea of recurrence risk.

I agree, it felt strange that a consensus regarding treatment wasn't reached. I'm at an away site for this elective and at my home institution the breast tumour group always reaches a consensus regarding treatment prior to initiation of further therapy. From what I understand, the breast surgeon was the first point of contact and didn't feel the need to present this case as she felt it was cut and dry. When margins came back positive they weren't able to fit the patient in until about 8 weeks post op due to OR constraints so decided to move on to neoadj chemo instead of waiting. Not sure how typical this is..

 

[thaddeus]

Thanks for that study! This has been a great discussion, I've greatly enjoyed reading over everyone's thoughts. This is actually one of the things I really enjoy about the field- it's so research driven, and when there isn't any research there's at least measured discourse. I asked this question above as well, but I was wondering if you personally would do CW only and not the axilla. From what I was taught in pre-clerkship it sounded like the primary indication for PMRT was nodal involvement, which is technically present in this case- I'm just not sure how micromets change planning in terms of isolated CW radiation. As PMRT is primarily indicated with nodal involvement, is the spirit of performing it almost purely for the purpose of axillary control with regional breast control secondary to that?

To answer your question, I would personally feel comfortable omitting radiation altogether unless the patient has additional pathologic features concerning for LRR. However, I think for any patient for 1-3 positive nodes being evaluated for PMRT, it is important to have a balanced discussion with the patient, and would offer radiation if they wanted aggressive therapy and understood the potential long-term toxicities (which do NOT include brachial plexopathy at 50 Gy BTW). If I did treat, I would target CW and low axilla (levels I and II), and omit SCV and IMN nodes. It is very rare that we would treat CW only without targeting any axillary lymph nodes. The only scenarios I can think of are T3N0 after ALND, and a positive margin in a node negative patient. Conversely, if we treat the axilla we always treat the CW. Even in patients for whom the primary indication for PMRT is nodal disease, the CW is the most likely site of recurrence, as scarbrtg mentioned above.

 

[evilbooyaa]

I'm interested why you'd say this. The axilla has a less than 1% chance of recurrence here; chest wall recurrence risk is going to be multiples higher, right?

It is, but if the patient didn't have a N1mi disease we wouldn't even be talking about doing radiation in this scenario, right?. A pT2N0 with positive margin who gets re-resected after neoadjuvant chemo with a mastectomy? 0 indication for PMRT in that case. The N1mi is what is currently driving the discussion regarding potential for PMRT. As I said previously, you wouldn't cover nodes alone, as patient's highest risk continues to be of recurrence at CW.

And it's definitely not 1% man in a post mastectomy patient not getting RT. Z11 had essentially 100% of patients who got some form of axillary radiation, even if they didn't get "high tangents" or a SCV field. Given that it's a lumpectomy trial, and that even regular whole breast fields cover the vast majority of level I and part of level II depending on anatomy. I would certainly not estimate this patient's risk of regional recurrence to only be 1%, otherwise I wouldn't offer her RT. Her risk is 1% if she had a lumpectomy with N1mi disease on SLNB and got whole breast radiation (or high tangents, or a SCV field).

 

[Ray D. Ayshun]

I wonder, for those who would tend to offer treatment in this case, if your decision would change if the patient were 70, or more interestingly, if it were left-sided in a 50 yo.

 

[MDACCRules]

Where are you getting that information? Tangents don't cover as much as you think. Here's another study. And another one. Same seen in PMRT/Reconstructed.

It is, but if the patient didn't have a N1mi disease we wouldn't even be talking about doing radiation in this scenario, right?. A pT2N0 with positive margin who gets re-resected after neoadjuvant chemo with a mastectomy? 0 indication for PMRT in that case. The N1mi is what is currently driving the discussion regarding potential for PMRT. As I said previously, you wouldn't cover nodes alone, as patient's highest risk continues to be of recurrence at CW.

And it's definitely not 1% man in a post mastectomy patient not getting RT. Z11 had essentially 100% of patients who got some form of axillary radiation, even if they didn't get "high tangents" or a SCV field. Given that it's a lumpectomy trial, and that even regular whole breast fields cover the vast majority of level I and part of level II depending on anatomy. I would certainly not estimate this patient's risk of regional recurrence to only be 1%, otherwise I wouldn't offer her RT. Her risk is 1% if she had a lumpectomy with N1mi disease on SLNB and got whole breast radiation (or high tangents, or a SCV field).

 

[scarbrtj]

Z11 had essentially 100% of patients who got some form of axillary radiation, even if they didn't get "high tangents" or a SCV field.

I don't know 'bout that. I'm going to lower your "essentially 100%" to "essentially half, perhaps." At the end of the day, this issue is so hazy, I prefer not to glean any meaningful information whatsoever about therapeutic addressment of the axilla from Z0011.

 

[scarbrtj]

To Dellort, a med student and non- rad onc... this is not a radiation case. It is definitely not an idée fixe axillary radiation therapy case. If one had to choose (a silly choice admittedly) to irradiate CW or axilla here, I can make a good argument outcome would be more affected by CW XRT because its recurrence risk is as high as 10% in node-neg T2 disease (whilst again the axilla has maybe a 1% recurrence risk here). In general, think of the axilla as a giver of prognostic information and not an outright driver of disease or outcome. Involvement of the axilla lets us know if a patient needs CW XRT, or chemo, etc. At best, don't get "worked up" about the axilla. There may be something to regional nodal RT in breast CA, but in terms of evidence IMHO...

{The axilla is not an isolated site of recurrence in intermediate risk breast cancer} >>> {PMRT in various forms improves survival in intermediate risk breast cancer} > {treating the axilla with local therapies affects survival in intermediate risk breast cancer}

The former 2 affect my day to day decision making far more than the latter.

 

[MDACCRules]

This is correct.

To Dellort, a med student and non- rad onc... this is not a radiation case. It is definitely not an idée fixe axillary radiation therapy case. If one had to choose (a silly choice admittedly) to irradiate CW or axilla here, I can make a good argument outcome would be more affected by CW XRT because its recurrence risk is as high as 10% in node-neg T2 disease (whilst again the axilla has maybe a 1% recurrence risk here). In general, think of the axilla as a giver of prognostic information and not an outright driver of disease or outcome. Involvement of the axilla lets us know if a patient needs CW XRT, or chemo, etc. At best, don't get "worked up" about the axilla. There may be something to regional nodal RT in breast CA, but in terms of evidence IMHO...

{The axilla is not an isolated site of recurrence in intermediate risk breast cancer} >>> {PMRT in various forms improves survival in intermediate risk breast cancer} > {treating the axilla with local therapies affects survival in intermediate risk breast cancer}

The former 2 affect my day to day decision making far more than the latter.

 

[evilbooyaa]

I don't know 'bout that. I'm going to lower your "essentially 100%" to "essentially half, perhaps." At the end of the day, this issue is so hazy, I prefer not to glean any meaningful information whatsoever about therapeutic addressment of the axilla from Z0011.

Let me start off by saying that by 'axillary radiation' I meant, at minimum, incidental coverage of level I through the use of regular tangents (I realize I wasn't clear in regards to that) - I'll get to MDACC's points lower down. To be clear, I'm not stating that I'd expect all of level II is covered with standard tangents.

The quoted paper:
228 patient records available
43 got SCV field
185 got tangent only, 142 of which were evaluable for tangent height (meaning 43 not evaluable)
66 ALND patients, 33 of which got high tangents
76 SLNB patients, 40 of which got high tangents

33+40+43 / (228 - 43) = 116/185 = 62.7% - Fair enough, likely ~2/3rd, 3/5ths, whatever you'd like, of patients got some form of dedicated axillary coverage if you extrapolate these numbers to the whole trial.

Per MDACC rules first paper, even in the patients who didn't get high tangents, 50% of level 1 is covered in regular tangents with 90% of prescription dose. That seems lower than what I see on my plans, but fair enough, good to see published data on it, thanks for the education. Second paper states that 38% of regular tangent plans covered ALL of level I and II, which is higher than what I'd expect. The korean paper does show lower numbers (29% getting 95% of prescription dose , although I'm not overtly familiar with the Danish contouring guidelines and how those would be different from the RTOG ones we use.

But scarbrtj and MDACCrules points are well taken. My (updated) counter argument is that nearly 2/3rd of patients treated on Z11 received dedicated axillary radiation. Even in patients getting tangential beam alone, data suggests somewhere from 30% to 50% of level I gets near prescription dose (90%+). Some data says nearly 40% of patients have complete coverage of level I and II. And in this overall combined group, the risk of axillary recurrence is 1%. Hopefully that sounds reasonable to the both of you.

Do I think that a patient getting mastectomy and NO radiation whatsoever also has an axillary recurrence risk of 1%? Absolutely not. I think it is significantly higher than that. Not higher than risk of CW recurrence, FWIW.

 

[scarbrtj]

33+40+43 / (228 - 43) = 116/185 = 62.7% - Fair enough, likely ~2/3rd, 3/5ths, whatever you'd like, of patients got some form of dedicated axillary coverage if you extrapolate these numbers to the whole trial.

This is a garbage in-garbage out trial to try and make XRT pontifications.
891 patients in trial... "Information on RT administered to patients enrolled onto Z0011 was collected in case report forms completed by enrolling providers approximately 18 months after enrollment..." Marvelous. Of these 891, they received 605 reports. Of the 605, they had 228 reports reliable enough to figure out what the hell anybody did RT-wise ("...detailed RT records were only available for approximately one third of patients known to have received RT"). And of the 228, only 138 got planned using 3D so caution I think is still in order re: guessing how much axilla was TRULY covered. Furthermore, of the 605 reports they had, 65 patients evidently didn't receive RT at all.

I hate discussing any radiation-related stuff re: Z0011 mostly because I can't make any radiation-related cogent argument one way or the other. I think it's just better to say axillary recurrences are REALLY low for T2N+ patients.
1) But this patient was just micromet positive; axillary recurrences very low (<1%) even when "no radiation [is] given to the axilla"
2) And this patient received chemo which "treats" the axilla

Do I think that a patient getting mastectomy and NO radiation whatsoever also has an axillary recurrence risk of 1%? Absolutely not.

3) So, funny enough, I think this patient with T2 ER+ nodal micrometastatic disease getting adjuvant chemo (and an un-dissected, un-irradiated axilla) absolutely does have a ~1% axillary recurrence risk.

 

[MDACCRules]

Axillary recurrences are rare and rarely affect clinical outcome.

In his typical way of using 800 words when 80 will do, scarbrtj is saying the chest wall is still the likeliest recurrence site. If your concern is that the undissected axilla is harboring more disease, then you should be still be directing your attention to the chest wall, because that is the issue.

60/20/20 is an easy to remember recurrence pattern (chest wall, superclav, Ax/IMN). So, if you predict a 15-20% chance of recurrence overall (a 'rule of thumb' threshold for PMRT), that means probably no more than 1-2% risk of recurrence in axilla. Additional radiation won't help much, as we saw in MA.20 with all that extra RT reducing locoregional recurrences from 2.5% to 0.5%. Mastectomy + no RT is probably a lot closer to 1-2% than you think. It's just math.

Very few patients benefit from axillary radiation, and many suffer from it.

 

[scarbrtj]

In his typical way of using 800 words when 80 will do

ahem...

 

[Palex80]

I generally utilize the nomograms of the MSKCC and MD Anderson CC for decisions like this.
They give you quite a good estimate of how likely it is more more nodes are present.
Breast Cancer Nomogram to Predict Additional Positive Non-SLN, without Neoadjuvant Chemotherapy - MD Anderson Cancer Center
Breast Cancer Nomogram: Breast Additional Non SLN Metastases | Memorial Sloan Kettering Cancer Center

I tried putting in the data you provided and came up with a risk for additional metastatic nodes in the range of 20-30% with both nomograms. That's not an awful lot but it's also not insignificant.

I do not think that the benefit from nodal RT will be low. Even if the 60/20/20 rule applies and you are looking at a 15-20% recurrence risk at all without any RT, this translates into 6-8% chance of nodal recurrence, if you ommit the lymphatics.
Chest wall recurrences are the most common ones but in my experience many of the chest wall recurrences can be a) early detected b) salvaged with repeat surgery + RT + systemic treatment. Nodal recurrences on the other hand are often detected late and generally cannot be well salvaged.
This is why I would opt to treat the lymphatics, since 6-8% is too much in my humble opinion. This is a right-sided case meaning no additional exposure of the heart to RT if you include the lymphatics and if the patient does not have lymphedema post surgery, chances are she wont develop any after RT either.

Some of you may argue that we are only talking about the axilla RT here and not the supraclavicular fossa and that the benefit from the additional axillary RT will be half of the 6-8%, but:
Treating the supraclavicular fossa "automatically" in PMRT is a relict of the past, when all patients with PMRT for a field covering the supraclavicular fossa. However all those patients also had a complete axillary surgical clearance. Thus the practice of the past cannot be extrapolated in todays practice. Today's axillary undissected patients who only get an SLNB probably have a higher risk for an axillary recurrence than a recurrence in the supraclavicular fossa. Do I have data for that? No, I don't. But if you look closely in the MA20-data, when some patients did not receive complete axillary clearance, you will see that most recurrences were not the in the supraclavicular fossa or the internal mammary chain but rather in the level II of the axilla (which was targetted when treating the supraclavicular fossa in MA20).
What I am trying to say: If you are going to treat this patient with, then your "escalation strategy" in terms of volumes to treat should be CW only --> CW + axilla --> CW + axilla + supraclavicular fossa --> CW + axilla + supraclavicular fossa + internal mammary chain.
But that' s just my personal opinion.

If you are wondering if I treat the supraclavicular fossa in all patients who get PMRT, then my answer is no.
For example a pT3 (let's say 6cm primary in the lower quadrants) pN0 (sn) patient who has had mastectomy would only get CW-RT at my institution. Now this probably opens up a new discussion if we should treat pN0 with PMRT, which I believe is not common in the US. We do it in Europe for select patients, mainly based on the Danish data.

 

[scarbrtj]

I tried putting in the data you provided and came up with a risk for additional metastatic nodes in the range of 20-30% with both nomograms. That's not an awful lot but it's also not insignificant. I do not think that the benefit from nodal RT will be low. Even if the 60/20/20 rule applies and you are looking at a 15-20% recurrence risk at all without any RT, this translates into 6-8% chance of nodal recurrence, if you ommit the lymphatics.

I too looked at the nomograms.org site (and look at it often; I'm a fan), and I believe that data very strongly. I also believe the Z0011 data, and all additional data, showing axillary relapses are MUCH lower than 6-8% risk you "hypothesize" here.
It's a poser, isn't it? Axillary involvement rates are high whilst axillary relapses are much less common. You hypothesize that perhaps 1 out of 3 involved axillas relapse ("...range of 20-30% with both nomograms"... 60/20/20, "6-8% chance of nodal recurrence"), but again, if we go by data instead of hypothesis, the ratio is more like 1 out of 20 involved axillas relapse. Perhaps the answer is abscopalism seen in some breast cancers, or the additional systemic therapies (anti-estrogens, cytotoxic chemo, imunotx, etc.)... I'm hypothesizing here, too. But it is not a hypothesis that this patient is expected to have a ~1% axillary recurrence rate. TBH, the nomograms.org data is ~100% unhelpful to determine/predict axillary recurrence rates. It's apples and oranges.

 

[Palex80]

I too looked at the nomograms.org site (and look at it often; I'm a fan), and I believe that data very strongly. I also believe the Z0011 data, and all additional data, showing axillary relapses are MUCH lower than 6-8% risk you "hypothesize" here.
It's a poser, isn't it? Axillary involvement rates are high whilst axillary relapses are much less common. You hypothesize that perhaps 1 out of 3 involved axillas relapse ("...range of 20-30% with both nomograms"... 60/20/20, "6-8% chance of nodal recurrence"), but again, if we go by data instead of hypothesis, the ratio is more like 1 out of 20 involved axillas relapse. Perhaps the answer is abscopalism seen in some breast cancers, or the additional systemic therapies (anti-estrogens, cytotoxic chemo, imunotx, etc.)... I'm hypothesizing here, too. But it is not a hypothesis that this patient is expected to have a ~1% axillary recurrence rate. TBH, the nomograms.org data is ~100% unhelpful to determine/predict axillary recurrence rates. It's apples and oranges.

Well perhaps it's more the fact, that we never actually LOOK where the initial recurrence happened when we diagnose metastatic disease. Perhaps it's a bit like MA20; quite a high benefit in terms of metastatic free survival with additional radiotherapy with not such a benefit in locoregional control?