Breast RNI and IMN coverage Discussion.... Again. Breast is the worst x 4?

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Ray D. Ayshun

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New breast is the worst case. Just saw a 39 yo with a BRCA mutation who had what was called a cT2N2 ER+ PR-/HER2- breast cancer. This was in the setting of a biopsied 4.6 cm primary and an MRI with 7 abnormal-appearing axillary nodes, none of which were biopsied. Got neoadjuvant chemo followed by lumpectomy and ax dissection. Final staging was ypT1aN0. Residual primary was 1.5 mm with treatment effect noted. 0/17 nodes with no treatment effect noted. For reference, an abnormal node noted on initial MRI went from 1.7 cm to 1.1 cm on repeat after NACT. Wondering if anyone would do whole breast only, or even just observe (based on age, what we know about CR to NACT and genetic predisposition to cancer). My plan as of now is RNI despite only circumstantial evidence of axillary involvement.

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New breast is the worst case. Just saw a 39 yo with a BRCA mutation who had what was called a cT2N2 ER+ PR-/HER2- breast cancer. This was in the setting of a biopsied 4.6 cm primary and an MRI with 7 abnormal-appearing axillary nodes, none of which were biopsied. Got neoadjuvant chemo followed by lumpectomy and ax dissection. Final staging was ypT1aN0. Residual primary was 1.5 mm with treatment effect noted. 0/17 nodes with no treatment effect noted. For reference, an abnormal node noted on initial MRI went from 1.7 cm to 1.1 cm on repeat after NACT. Wondering if anyone would do whole breast only, or even just observe (based on age, what we know about CR to NACT and genetic predisposition to cancer). My plan as of now is RNI despite only circumstantial evidence of axillary involvement.

Breast only.

Kinda surprised they didn't do bilateral MRM, given the BRCA mutation
 
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Breast only.

Kinda surprised they didn't do bilateral MRM, given the BRCA mutation
Bilateral was original plan, but she changed her mind last minute. Why no concern about up-front nodal involvement? I get the lack of treatment effect in the nodes, but was a big, aggressive primary (Ki67 index like 40-60%) with nodes that seemed to shrink during chemo. Or, on the other hand, are you suggesting she had a CR in the axilla, and given the lack of up-front biopsy, it's okay to err on the side of omission?
 
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Bilateral was original plan, but she changed her mind last minute. Why no concern about up-front nodal involvement? I get the lack of treatment effect in the nodes, but was a big, aggressive primary (Ki67 index like 40-60%) with nodes that seemed to shrink during chemo. Or, on the other hand, are you suggesting she had a CR in the axilla, and given the lack of up-front biopsy, it's okay to err on the side of omission?
Could be the 17 lymph nodes taken out…. I’m always more conservative and treat anything that looks like clinical + nodes but I know with breast, the paradigm is always shifting.
 
New breast is the worst case. Just saw a 39 yo with a BRCA mutation who had what was called a cT2N2 ER+ PR-/HER2- breast cancer. This was in the setting of a biopsied 4.6 cm primary and an MRI with 7 abnormal-appearing axillary nodes, none of which were biopsied. Got neoadjuvant chemo followed by lumpectomy and ax dissection. Final staging was ypT1aN0. Residual primary was 1.5 mm with treatment effect noted. 0/17 nodes with no treatment effect noted. For reference, an abnormal node noted on initial MRI went from 1.7 cm to 1.1 cm on repeat after NACT. Wondering if anyone would do whole breast only, or even just observe (based on age, what we know about CR to NACT and genetic predisposition to cancer). My plan as of now is RNI despite only circumstantial evidence of axillary involvement.
I believe no RNI is the best and most evidence-based decision for this patient (shocker!). Administer 15 fractions of IMRT (most evidence-based, too) whole breast.

2024-04-02 11_13_36-Some Patients With Breast Cancer May Safely Avoid Locoregional Irradiation...png

B-51.1.jpg

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17 LNs resected and none were involved, I don't see any reason to treat with RT
 
New breast is the worst case. Just saw a 39 yo with a BRCA mutation who had what was called a cT2N2 ER+ PR-/HER2- breast cancer. This was in the setting of a biopsied 4.6 cm primary and an MRI with 7 abnormal-appearing axillary nodes, none of which were biopsied. Got neoadjuvant chemo followed by lumpectomy and ax dissection. Final staging was ypT1aN0. Residual primary was 1.5 mm with treatment effect noted. 0/17 nodes with no treatment effect noted. For reference, an abnormal node noted on initial MRI went from 1.7 cm to 1.1 cm on repeat after NACT. Wondering if anyone would do whole breast only, or even just observe (based on age, what we know about CR to NACT and genetic predisposition to cancer). My plan as of now is RNI despite only circumstantial evidence of axillary involvement.

Dr. Gerber's response on themednet is so comprehensive. Of course, it is reasonable to omit RNI here, but this is also the patient with several risk factors for regional recurrence and likely not the most representative patient on the b51 trial. You could defend either approach.

edit: omit RNI not XRT (as per below post)
 

Dr. Gerber's response on themednet is so comprehensive. Of course, it is reasonable to omit RNI here, but this is also the patient with several risk factors for regional recurrence and likely not the most representative patient on the b51 trial. You could defend either approach.

edit: omit RNI not XRT (as per below post)
But if I had to press you for an answer. Which is MORE reasonable. Regional nodal RT, or no RNI, in this case? One one hand we don't have a large randomized trial that ever showed OS benefit for pN+ in general, and now we have data that essentially no oncologic outcome is improved for ypN0.

Just dropping this in for more fuel for discussion fire:

2024-04-02 11_40_09-The Internal Mammary Node Irradiation Debate in Node-Positive Breast Cance...png

2024-04-02 11_40_24-Internal Mammary Node Irradiation Debate_ Case Closed_ Not Yet, and Maybe ...png
 
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Any ideas on how frequently an involved node will show no evidence of alive or dead cancer after NACT?
Why does it matter (especially in this case). You will be traipsing through some very unexplored places data-wise if you try to base any RT decision on this. Btw, what side of the body are we talking in this case... left or right?
 
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Post-lumpectomy RT. Arguably survival improving.
I should have been clearer- I don't see any reason to treat the nodes. I would still tx the breast.
 
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Why does it matter (especially in this case). You will be traipsing through some very unexplored places data-wise if you try to base any RT decision on this. Btw, what side of the body are we talking in this case... left or right?
Left. I don't disagree. This is the worst bc surg/med onc decided to forgo evaluating the axilla with a biopsy. The not mature results of B-51 notwithstanding, RNI is still SOC as far as I can tell for cN+ disease. I'm put in the position of altering the staging prior to NACT despite meeting her 8 months later.
 
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Bilateral was original plan, but she changed her mind last minute. Why no concern about up-front nodal involvement? I get the lack of treatment effect in the nodes, but was a big, aggressive primary (Ki67 index like 40-60%) with nodes that seemed to shrink during chemo. Or, on the other hand, are you suggesting she had a CR in the axilla, and given the lack of up-front biopsy, it's okay to err on the side of omission?

I agree with your original plan, and would err on the side of treatment in this thirty nine year old with luminal B disease whose primary failed to achieve a pCr. I would at least offer it and document as such. The 10 year failure rate in the nodes is 2.4% in this population, however.

I personally would not use 5 year data to drive treatment decisions for a patient with a 50 year life expectancy and hormone positive breast cancer.

There are those who believe that microscopic breast cancer cannot be eradicated with 50 Gy in 25 fractions in the nodes but it can in the breast using 26 Gy in 5 fractions instead.
 
I personally would not use 5 year data to drive treatment decisions for a patient with a 50 year life expectancy and hormone positive breast cancer.
Would you use 10 year data? (NB: the nature of actuarial analyses makes 5y outcomes highly predictive of 10y outcomes for two large randomized group comparisons.) Would seem just as suspicious to do so for anyone with a "50 year life expectancy." So you should be safe from any results from B51 for the rest of your career, even a 20 year update. (wink)

Rachel-breast.jpg


RNI is still SOC as far as I can tell for cN+ disease
You didn't use "a standard" or "the standard," so I don't disagree but...

RNI still means "treat the IMNs, plus other things," to me. And IMNs are VERY CONTROVERSIAL (see above). So to call IMN RT "standard" in a 39yo who's ypN0 and has a left-sided cancer... maybe not "standard." In addition, even the NCCN (just) says "strongly consider RNI" for this case. Thus, rather standard... quite standard... not-so-"standard," period. Especially in light of B51 and experts openly stating "At our institution, we will be omitting regional nodal irradiation in most patients who meet the criteria for [B51]." A standard is an evolving thing, or should be.
 
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But if I had to press you for an answer. Which is MORE reasonable. Regional nodal RT, or no RNI, in this case? One one hand we don't have a large randomized trial that ever showed OS benefit for pN+ in general, and now we have data that essentially no oncologic outcome is improved for ypN0.

Just dropping this in for more fuel for discussion fire:

View attachment 384864

View attachment 384865
Damn you!
 
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Would you use 10 year data? (NB: the nature of actuarial analyses makes 5y outcomes highly predictive of 10y outcomes for two large randomized group comparisons.) Would seem just as suspicious to do so for anyone with a "50 year life expectancy." So you should be safe from any results from B51 for the rest of your career, even a 20 year update. (wink)

I'm confused how one can hold that adjuvant radiation is curative in ER+ breast cancer through a mechanism of complete cell kill of residual microscopic disease but then also hold that 5 year outcome data is conclusive given the natural history of ER+ breast cancer, specifically its propensity to recur decades later.

Among 36 924 women with breast cancer, 20 315 became 10-year disease-free survivors. Of these, 2595 developed late BCR (incidence rate = 15.53 per 1000 person-years, 95% confidence interval = 14.94 to 16.14; cumulative incidence = 16.6%, 95% confidence interval = 15.8% to 17.5%) from year 10 to 32 after primary diagnosis. Tumor size larger than 20 mm, lymph node–positive disease, and estrogen receptor–positive tumors were associated with increased cumulative incidences and hazards for late BCR.

 
I'm confused how one can hold that adjuvant radiation is curative in ER+ breast cancer through a mechanism of complete cell kill of residual microscopic disease but then also hold that 5 year outcome data is conclusive given the natural history of ER+ breast cancer, specifically its propensity to recur decades later.

Among 36 924 women with breast cancer, 20 315 became 10-year disease-free survivors. Of these, 2595 developed late BCR (incidence rate = 15.53 per 1000 person-years, 95% confidence interval = 14.94 to 16.14; cumulative incidence = 16.6%, 95% confidence interval = 15.8% to 17.5%) from year 10 to 32 after primary diagnosis. Tumor size larger than 20 mm, lymph node–positive disease, and estrogen receptor–positive tumors were associated with increased cumulative incidences and hazards for late BCR.

Let me see if I can explain this in a way with which a biostatistician would agree. (Of course I know breast cancer patients recur "late.")

I'm merely saying that under the mathematical principles, and mathematics themselves, of a Kaplan-Meier and logrank/Cox proportional hazard analysis of, say, LRFS between two large ~800 patient groups, if one obtains a p-value of 0.69 (the B-51 DFS ... disease free survival... result in this case), and the curves are going out past 5 years (assume 5y median f/u), once followup is obtained to 10 years (the curves will go out farther that 10y for 10y median followup), it is EXCEEDINGLY unlikely the curves will experience a separation such that the p-value will become p<0.05. (Kaplan-Meier based between-group analysis really is one of those rare cases where past performance is indicative of future results.)

Of course we know that "total event proportions" increase over time in almost any actuarial analysis ("On a long enough timeline the survival rate for everyone drops to zero"); except for local control(!!... because dead people get censored from local control, and thus can never have the event). A null hypothesis under KM/logrank/Cox analysis is that the two groups experience event rates at the same proportion, over time. That null hypothesis was "strongly" non-rejected for DFS in B-51. (Bayesian principles would suggest it will be non-rejected again when you look later with more data.)

1712083952657.png



Look at how these events from MA.20 are increasing at a kind of steady-state from day zero; the rate of early/late recurrences is clearly rather equal (within a single arm... betwixt arms, the null was rejected for DFS, LRFS, and distant DFS). Your concerns/points would have more validity if there was a "sudden run on events" past 5-7 years, as I have hypothetically (hyperbolically) shown with the little blue dashed lines...

1712084916575.png
 
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You are looking at this, admittedly, from a purely statistical viewpoint. The assumption being made here is that changes in the survival curves from late recurrences will occur in a reasonably proportionate manner. I.e., radiation affects early recurrences, but not late recurrences. And that may be. Have we done genetic studies on these late recurrences to confirm that these are truly recurrent cancers and not de novo disease? I don't know the answer to that. But I feel confident in saying that we don't know with certainty the effect of omitting radiation in a 39 year old will be when she is eligible to draw social security.
 
The assumption being made here is that changes in the survival curves from late recurrences will occur in a reasonably proportionate manner. I.e., radiation affects early recurrences, but not late recurrences.
Every evidence based medicine decision you ever made, when you adopted a new standard of care, was hopefully made from a purely statistical viewpoint. Else there'd be chaos. Were radiation to affect early but not late recurrence, the recurrences would not be happening in a proportionate manner (over time) and fundamental assumptions of KM analysis (and logrank etc.) would be violated... and I guess every breast rad onc large randomized trial's publication would have to be retracted!
 
Every evidence based medicine decision you ever made, when you adopted a new standard of care, was hopefully made from a purely statistical viewpoint. Else there'd be chaos.

See the A post mortem thread for relevant examples of this concept.

However.

I found myself wading into the "this is all made up" camp when we started doing backflips foaming at the mouth over a p-value of 0.056.
 
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That's awesome! I was getting really tired of giving 76 Gy in 38 fractions (edit excuse me 73.78 Gy/31) to my young pT1-2pN0-2a breast patients. So happy I can go down to 66/33 now.

lol wtf.
 
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Could I get a gold medal, gift certificate, back pat for being prescient (omniscient?) about this. I was sure @Palex80 would write me ;) ;)

Well I wasn’t prescient tbh

Just internalized the … priors


My outlook on this trial (edit: prospective registry) is that it suggests that B51 is (more likely than not) going to show us that the experimental arm of omitting nodal RT in ypN0 patients is going to do fine. That being said, I'll wait until B51 is released to change my practice rather than relying on 291 patients in a single arm fashion.
Did your practice change ;)
 
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No, I would still treat nodes.

The person who trained me would not enroll TNBC on 1304 fwiw.

The screw up here was failure to confirm cN+ disease by biopsy.
 
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No, I would still treat nodes.

The person who trained me would not enroll TNBC on 1304 fwiw.

The screw up here was failure to confirm cN+ disease by biopsy.
Sure re not confirming pre treatment. There's also evidence that there's a benefit to RNI in patients with up front T2N0 triple negative disease.
 
Would anybody's recs change if the case I mentioned was triple negative?
Would not for me (shocker, again). They have higher rates of conversion to pN0 than ER positive; when triple negatives have very "brisk" responses to NAC it's been shown time and again to predict a favorable natural history that the "triple negative" moniker doesn't predict and that IMN RT surely won't affect. Put another way, triple negative cN+ has a better chance of not needing RNI than ER+/HER2-. (Below, low risk = conversion to ypN0).

1712149811550.png
The screw up here was failure to confirm cN+ disease by biopsy.
NB: these "screw ups" are going to happen more and more as we get farther into the future of breast cancer. But eventually today's screw ups become tomorrow's standards of care (e.g., Z0011).
 
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Would not for me (shocker, again). They have higher rates of conversion to pN0 than ER positive

You are ideologically consistent, and I agree with your logic. The breast in this case did not achieve pCr. Failure of a T2 TNBC to achieve pCr in a 39 yo would spook me enough to probably treat nodes even if they were biopsy-negative. This is a bad cancer that really deserves the kitchen sink thrown at it. I do think we are safe with a 5 fraction "low dose" boost, however. :rofl:
 
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You are ideologically consistent, and I agree with your logic. The breast in this case did not achieve pCr. Failure of a T2 TNBC to achieve pCr in a 39 yo would spook me enough to probably treat nodes even if they were biopsy-negative. This is a bad cancer that really deserves the kitchen sink thrown at it. I do think we are safe with a 5 fraction "low dose" boost, however. :rofl:
Took a while to get to this stage of logic, convert my thinking, etc. They say the definition of a Republican is a Democrat who's been mugged. The breast RNI data has been mugging us rad oncs for a while now. Agree not a pCR in this instance, but the primary shrunk by >99.99% and she was staged as cN+ so we must call her ypN0 (0/17 LNs!). We have to contort to ignore this strongly prognostic information and call this a "bad cancer." Can you guys remind me or show any data that cT1-2pN0 triple negative in the "modern systemic era" has any benefit with RNI. I am asking for this because we can talk about the risks/side effects of RNI (and appear "raw numerically" on par, or greater, than the benefits of RNI on DFS for pN0 e.g.; we know there's likely no OS benefit).
 
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Took a while to get to this stage of logic, convert my thinking, etc. They say the definition of a Republican is a Democrat who's been mugged. The breast RNI data has been mugging us rad oncs for a while now. Agree not a pCR in this instance, but the primary shrunk by >99.99% and she was staged as cN+ so we must call her ypN0 (0/17 LNs!). We have to contort to ignore this strongly prognostic information and call this a "bad cancer." Can you guys remind me or show any data that cT1-2pN0 triple negative in the "modern systemic era" has any benefit with RNI.
I’ll be devil’s advocate even though you can convince me either way. Are you that concerned for lymphedema (in general, not with this patient who is at high risk)? What if she had only 2 nodes taken out? Basically, what is your cut off as to when you would consider RNI in these types of cases.
 
Are you that concerned for lymphedema (in general, not with this patient who is at high risk)? What if she had only 2 nodes taken out?
Lymphedema. Cardiotoxicity (she is left sided, will IMNs be treated?, and she's 39yo, etc). Lung toxicity. The most statistically significant result in MA.20 was for lymphedema and in EORTC 22922 it was pulmonary fibrosis. If she has a BMI of 30 or more her risk of lymphedema will be ~20% or more. That's a number that dwarfs any benefits of RNI in N0 breast cancer, in general, and although lymphedema never killed anyone but breast cancer surely has (but RNI is not OS improving... arguably!), toxicity needs to enter into the calculus I think. (If just 2 nodes taken out, yes, her lymphedema risk would be a lot less.)
Basically, what is your cut off as to when you would consider RNI in these types of cases.
pN+... cN+ alone doesn't seem good enough to apply RNI, especially IMN-containing RNI.
 
Lymphedema. Cardiotoxicity (she is left sided, will IMNs be treated?, and she's 39yo, etc). Lung toxicity. The most statistically significant result in MA.20 was for lymphedema and in EORTC 22922 it was pulmonary fibrosis. If she has a BMI of 30 or more her risk of lymphedema will be ~20% or more. That's a number that dwarfs any benefits of RNI in N0 breast cancer, in general, and although lymphedema never killed anyone but breast cancer surely has (but RNI is not OS improving... arguably!), toxicity needs to enter into the calculus I think. (If just 2 nodes taken out, yes, her lymphedema risk would be a lot less.)

pN+... cN+ alone doesn't seem good enough to apply RNI, especially IMN-containing RNI.
I’m usually able to meet all constraints using VMAT and could even omit nodes if needed to in order to meet constraints. One could also advocate for protons in this situation. Basically, if you’re able to meet every constraint, would it still be an issue or is the evidence to support RNI just not that strong to even consider it for a possibly “higher risk patient” even if we have not been able to determine who those patients are at this point.

Personally, I lean more towards the treatment side just because I think the risk of side effects is not that high vs a possible recurrence (although small). I’m not a strong advocate and like I said before, I can be swayed either way.
 
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I’m usually able to meet all constraints using VMAT and could even omit nodes if needed to in order to meet constraints. One could also advocate for protons in this situation. Basically, if you’re able to meet every constraint, would it still be an issue or is the evidence to support RNI just not that strong to even consider it for a possibly “higher risk patient” even if we have not been able to determine who those patients are at this point.

Personally, I lean more towards the treatment side just because I think the risk of side effects is not that high vs a possible recurrence (although small). I’m not a strong advocate and like I said before, I can be swayed either way.
Even if meeting every constraint, there’s still a toxicity risk from RNI. Meeting constraints is a bare minimum, and I agree we can meet them in ~all cases with IMRT. Protons meet the constraints better than photons I bet, on screen; IRL, we see some pretty concerning toxicity reports re: breast and protons imho (surely, their proton plans “met constraints”).

I just follow NCCN guidelines, but temper those (now) through the lens of B51 as in this case and some of the recent IMN trials.
 
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Lymphedema. Cardiotoxicity (she is left sided, will IMNs be treated?, and she's 39yo, etc). Lung toxicity. The most statistically significant result in MA.20 was for lymphedema and in EORTC 22922 it was pulmonary fibrosis. If she has a BMI of 30 or more her risk of lymphedema will be ~20% or more. That's a number that dwarfs any benefits of RNI in N0 breast cancer, in general, and although lymphedema never killed anyone but breast cancer surely has (but RNI is not OS improving... arguably!), toxicity needs to enter into the calculus I think. (If just 2 nodes taken out, yes, her lymphedema risk would be a lot less.)

pN+... cN+ alone doesn't seem good enough to apply RNI, especially IMN-containing RNI.

I pulled up the protocol, and pulmonary fibrosis in EORTC 22922 was defined as radiographic change noted on Xray- no lung function data was collected. FYI in case anyone was wondering.
 
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I pulled up the protocol, and pulmonary fibrosis in EORTC 22922 was defined as radiographic change noted on Xray- no lung function data was collected. FYI in case anyone was wondering.

Sounds about right for the field of breast radiation oncology.
 
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Regarding the case above, patient was clinically N2 and would therefore not qualify for b51. I would treat breast and undissected nodes.
 
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Regarding the case above, patient was clinically N2 and would therefore not qualify for b51. I would treat breast and undissected nodes.
Clinically N2 inasmuch as the radiologists thought the nodes appeared abnormal. No biopsy to confirm. While they got a little smaller after chemo, there was no evidence of tumor, including dead tumor/immune response, in the nodes.
 
Regarding the case above, patient was clinically N2 and would therefore not qualify for b51. I would treat breast and undissected nodes.

b51 also required node biopsy. I agree with assuming worst case (multiple cN+) if the truth can't be known. But I'm a well-known pessimist.
 
New breast is the worst case. Just saw a 39 yo with a BRCA mutation who had what was called a cT2N2 ER+ PR-/HER2- breast cancer. This was in the setting of a biopsied 4.6 cm primary and an MRI with 7 abnormal-appearing axillary nodes, none of which were biopsied. Got neoadjuvant chemo followed by lumpectomy and ax dissection. Final staging was ypT1aN0. Residual primary was 1.5 mm with treatment effect noted. 0/17 nodes with no treatment effect noted. For reference, an abnormal node noted on initial MRI went from 1.7 cm to 1.1 cm on repeat after NACT. Wondering if anyone would do whole breast only, or even just observe (based on age, what we know about CR to NACT and genetic predisposition to cancer). My plan as of now is RNI despite only circumstantial evidence of axillary involvement.
First off - new breast is the worst discussion means that it needs its own thread. Posts have been moved. Robust discussion pretty quickly...

Going to start by just reading the OP:

By cN2, I presume you mean the nodes were matted? Because nodal count doesn't matter for clinical staging. If NOT matted nodes, than she meets B51 criteria. If she has matted notes, then she is too high of risk to be enrolled on B51 (only enrolled cN1 patients) and thus I would definitely treat breast AND nodes.

Assuming she is actually cN1 (numerous nodes but NOT matted, can't remember a time I've truly seen a patient with matted notes), then she meets enrollment criteria for B51. B51 globally was negative, but showed lower HR in patients with ER+, Her2- disease. I would participate in shared decision making with the patient regarding pros/cons of B51 data in terms of treating WBI alone vs WBI + RNI. Especially with 17 resected (and negative nodes), I would have a hard time strongly pushing for RNI despite patient's young age and BRCA mutation. I would verify on CT sim that the 1.1cm node was removed at time of surgery and not left in place. If still present, would consider biopsy, and if positive, then RNI w/ boost.

I would NOT observe after a lumpectomy. B/L MRMs, sure can observe.

Going through the remaining posts:
Left. I don't disagree. This is the worst bc surg/med onc decided to forgo evaluating the axilla with a biopsy. The not mature results of B-51 notwithstanding, RNI is still SOC as far as I can tell for cN+ disease. I'm put in the position of altering the staging prior to NACT despite meeting her 8 months later.
I think waiting for 10-year data in a trial omitting RT is not unreasonable, but I think it is worth a discussion with the patient and some shared decision making regarding pros and cons of the data, similar to how we do shared decision making to discuss potential omission of WBI in 65-70+ year old women w/ early stage IDC.
Would you use 10 year data? (NB: the nature of actuarial analyses makes 5y outcomes highly predictive of 10y outcomes for two large randomized group comparisons.) Would seem just as suspicious to do so for anyone with a "50 year life expectancy." So you should be safe from any results from B51 for the rest of your career, even a 20 year update. (wink)

View attachment 384867


You didn't use "a standard" or "the standard," so I don't disagree but...

RNI still means "treat the IMNs, plus other things," to me. And IMNs are VERY CONTROVERSIAL (see above). So to call IMN RT "standard" in a 39yo who's ypN0 and has a left-sided cancer... maybe not "standard." In addition, even the NCCN (just) says "strongly consider RNI" for this case. Thus, rather standard... quite standard... not-so-"standard," period. Especially in light of B51 and experts openly stating "At our institution, we will be omitting regional nodal irradiation in most patients who meet the criteria for [B51]." A standard is an evolving thing, or should be.

Comparing Rabinovitch's slide which is a discussion of comparing one RT regimen to another is not an equal comparison to thinking of outcomes between omission of RT vs delivering RT. See PRIME and CALGB for pretty significant differences in numerical risks of recurrence between 5 and 10-year data.

And 'MOST patients who meet criteria' may not include a 39yo w/ BRCA mutation with ER+/Her2- cancer (the MOST likely to benefit from RNI as per 5-year B51 results) double digit visible nodes pre-op (would be pN3 if she went for upfront surgery and this wouldn't even be a discussion then).
Alright fine, whole breast. Boost? ;)

100% yes in my practice.
Did your practice change ;)
In short, yes.
In long: MOST patients with N1 disease s/p NACT showing pN0 do not need RNI. I would advocate against it specifically in TNBC and Her2+ patients.

In a ER+/Her2- patient I would have shared decision making regarding that there may be some relative benefit, but the absolute benefit at 5-years is probably relatively minimal, with the caveat that chances of recurrence in ER+ breast cancer increase all the way up to, if not past 10 years, and we don't know how to interpret previous 10-year data in the neoadjuvant chemotherapy era. So a patient who wanted all maximally potentially beneficial therapy, yeah I'd do RNI. In one who was more of a minimalist, I would think omission to be very reasonable.

Would anybody's recs change if the case I mentioned was triple negative?
Yes. TNBC specifically had worse outcomes WITH RT, likely because they are such a good biology group of patients to respond to systemic therapy (as opposed to those who don't sterilize the nodes).
No, I would still treat nodes.

The person who trained me would not enroll TNBC on 1304 fwiw.

The screw up here was failure to confirm cN+ disease by biopsy.
To continue to do things simply because of "that's how I was trained" and ignore a randomized clinical trial which can, in no terms, suggest that RNI is beneficial to TNBC N1 patients who receive NACT and are ypN0, and suggest that RNI may be actively harmful (like a 39-yo getting IMN RT and CAD risk).... that's something I can't wrap my head around.

You had dogma. Now we have evidence stating that the dogma was wrong. We still gonna follow dogma?

I’m usually able to meet all constraints using VMAT and could even omit nodes if needed to in order to meet constraints. One could also advocate for protons in this situation. Basically, if you’re able to meet every constraint, would it still be an issue or is the evidence to support RNI just not that strong to even consider it for a possibly “higher risk patient” even if we have not been able to determine who those patients are at this point.

Personally, I lean more towards the treatment side just because I think the risk of side effects is not that high vs a possible recurrence (although small). I’m not a strong advocate and like I said before, I can be swayed either way.
Protons to put her at higher risk of rib fracture and worse skin reactions? No thanks. Proper 3D or VMAT, likely w/ DIBH (hoping this 39-yo can tolerate it). Cover IMNs above the level fo the heart given no obvious pre-op involvement.

Regarding the case above, patient was clinically N2 and would therefore not qualify for b51. I would treat breast and undissected nodes.
cN2 by number is NOT a thing. Specifically based on location or matted nodes. If she has matted notes, I agree. One could have 11 nodes suspicious pre-NACT but still could be very easily N1.
 
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First off - new breast is the worst discussion means that it needs its own thread. Posts have been moved. Robust discussion pretty quickly...

Going to start by just reading the OP:

By cN2, I presume you mean the nodes were matted? Because nodal count doesn't matter for clinical staging. If NOT matted nodes, than she meets B51 criteria. If she has matted notes, then she is too high of risk to be enrolled on B51 (only enrolled cN1 patients) and thus I would definitely treat breast AND nodes.

Assuming she is actually cN1 (numerous nodes but NOT matted, can't remember a time I've truly seen a patient with matted notes), then she meets enrollment criteria for B51. B51 globally was negative, but showed lower HR in patients with ER+, Her2- disease. I would participate in shared decision making with the patient regarding pros/cons of B51 data in terms of treating WBI alone vs WBI + RNI. Especially with 17 resected (and negative nodes), I would have a hard time strongly pushing for RNI despite patient's young age and BRCA mutation. I would verify on CT sim that the 1.1cm node was removed at time of surgery and not left in place. If still present, would consider biopsy, and if positive, then RNI w/ boost.

I would NOT observe after a lumpectomy. B/L MRMs, sure can observe.

Going through the remaining posts:

I think waiting for 10-year data in a trial omitting RT is not unreasonable, but I think it is worth a discussion with the patient and some shared decision making regarding pros and cons of the data, similar to how we do shared decision making to discuss potential omission of WBI in 65-70+ year old women w/ early stage IDC.


Comparing Rabinovitch's slide which is a discussion of comparing one RT regimen to another is not an equal comparison to thinking of outcomes between omission of RT vs delivering RT. See PRIME and CALGB for pretty significant differences in numerical risks of recurrence between 5 and 10-year data.

And 'MOST patients who meet criteria' may not include a 39yo w/ BRCA mutation with ER+/Her2- cancer (the MOST likely to benefit from RNI as per 5-year B51 results) double digit visible nodes pre-op (would be pN3 if she went for upfront surgery and this wouldn't even be a discussion then).


100% yes in my practice.

In short, yes.
In long: MOST patients with N1 disease s/p NACT showing pN0 do not need RNI. I would advocate against it specifically in TNBC and Her2+ patients.

In a ER+/Her2- patient I would have shared decision making regarding that there may be some relative benefit, but the absolute benefit at 5-years is probably relatively minimal, with the caveat that chances of recurrence in ER+ breast cancer increase all the way up to, if not past 10 years, and we don't know how to interpret previous 10-year data in the neoadjuvant chemotherapy era. So a patient who wanted all maximally potentially beneficial therapy, yeah I'd do RNI. In one who was more of a minimalist, I would think omission to be very reasonable.


Yes. TNBC specifically had worse outcomes WITH RT, likely because they are such a good biology group of patients to respond to systemic therapy (as opposed to those who don't sterilize the nodes).

To continue to do things simply because of "that's how I was trained" and ignore a randomized clinical trial which can, in no terms, suggest that RNI is beneficial to TNBC N1 patients who receive NACT and are ypN0, and suggest that RNI may be actively harmful (like a 39-yo getting IMN RT and CAD risk).... that's something I can't wrap my head around.

You had dogma. Now we have evidence stating that the dogma was wrong. We still gonna follow dogma?


Protons to put her at higher risk of rib fracture and worse skin reactions? No thanks. Proper 3D or VMAT, likely w/ DIBH (hoping this 39-yo can tolerate it). Cover IMNs above the level fo the heart given no obvious pre-op involvement.


cN2 by number is NOT a thing. Specifically based on location or matted nodes. If she has matted notes, I agree. One could have 11 nodes suspicious pre-NACT but still could be very easily N1.
You're right, and I admittedly, was using cN2 incorrectly, but to some degree using it in the same way we talk about T3 disease in prostate based on MRI. Though number of nodes plays no role in clinical staging, I was using it as such. No evidence of matting, at least per notes, as I'm just now meeting her.
 
To continue to do things simply because of "that's how I was trained" and ignore a randomized clinical trial which can, in no terms, suggest that RNI is beneficial to TNBC N1 patients who receive NACT and are ypN0, and suggest that RNI may be actively harmful (like a 39-yo getting IMN RT and CAD risk).... that's something I can't wrap my head around.
That comment was to simply suggest the widespread disagreement on this topic among "experts." I have deviated in so many ways from the dogma I was trained under a decade ago (I'm sure you can guess the institution that "way" originated from) You can read comments on MedNet from the usual suspects. Would be interesting what they would chime in with here, but I doubt you would get a hard NO from the regular breast commenters there. Not ignoring trial. But also consider the fact that we don't have long term data for patients treated with VMAT and DIBH. The risk of undertreating this patient is distant metastatic disease and early death. The risk of overtreating is a very small increase in cardiac events later in life and still small risk of symptomatic lymphedema. Patient is at least getting the option IMO.
 
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That comment was to simply suggest the widespread disagreement on this topic among "experts." I have deviated in so many ways from the dogma I was trained under a decade ago (I'm sure you can guess the institution that "way" originated from) You can read comments on MedNet from the usual suspects. Would be interesting what they would chime in with here, but I doubt you would get a hard NO from the regular breast commenters there. Not ignoring trial. But also consider the fact that we don't have long term data for patients treated with VMAT and DIBH. The risk of undertreating this patient is distant metastatic disease and early death. The risk of overtreating is a very small increase in cardiac events later in life and still small risk of symptomatic lymphedema. Patient is at least getting the option IMO.
Agree, breast is the last site where there is any concrete evidence to support something over another. I would never bet against anything in breast and anyone who is confident in knowing everything there is to know about the best way to give or not give RT is lying!
 
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B51 protocol states that clinical nodal involvement may be assessed by mri, pet, ct, etc. please see section 5.2.5 of the protocol. Under ineligibility criteria please see section 5.3.4
 
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B51 protocol states that clinical nodal involvement may be assessed by mri, pet, ct, etc. please see section 5.2.5 of the protocol. Under ineligibility criteria please see section 5.3.4
Hmmm. I wonder if this refers only to IMN and infra/supraclav involvement as, in this case, what made her N2 by imaging was, like evil said, conflating clinical and pathologic N-staging.
 
You're right, and I admittedly, was using cN2 incorrectly, but to some degree using it in the same way we talk about T3 disease in prostate based on MRI. Though number of nodes plays no role in clinical staging, I was using it as such. No evidence of matting, at least per notes, as I'm just now meeting her.

As you note, T3 (EPE vs SVI) by MRI on prostate is different than saying 15 nodes involved on MRI and thus > N1 (actually N3 if you're counting nodes).

That comment was to simply suggest the widespread disagreement on this topic among "experts." I have deviated in so many ways from the dogma I was trained under a decade ago (I'm sure you can guess the institution that "way" originated from) You can read comments on MedNet from the usual suspects. Would be interesting what they would chime in with here, but I doubt you would get a hard NO from the regular breast commenters there. Not ignoring trial. But also consider the fact that we don't have long term data for patients treated with VMAT and DIBH. The risk of undertreating this patient is distant metastatic disease and early death. The risk of overtreating is a very small increase in cardiac events later in life and still small risk of symptomatic lymphedema. Patient is at least getting the option IMO.

I hear you and not a knock on you specifically. I just think that, of any patient who might ever benefit from RNI in this clinical situation, suggesting that it's a TNBC patient (and not a ER+/Her2- patient) is actively refuted by the data. Like HR is WORSE with RT. RT to a TNBC cN1 patient --> ypN0 after NAC is actively killing them. HR 2.3, statistically significant, CI does not cross 1, when RT is added. Some would say not to over-interpret forest plot data. I disagree. A p-value that is significant may be fragile, but is not underpowered. Findings may be spurious, but just as spurious as with a larger sample size.
 
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