ECE and Z11. Has anything changed?

[xrthopeful]

It's true that isolated axillary recurrences aren't super duper common, but the data suggests that RNI impacts distant metastasis as well. sterilizing the basin before the disease gets a chance to met out etc.

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[Burt Radnolds]

Evidence seems to suggest a DMFS benefit from IMC radiation beyond the magnitude of reduction of clinically apparent IMC nodal failure. In turn, the same argument could be applied to the axillary nodes, particularly in our current era of less and less nodal dissection. I see the nodal stations as a sort of halfway house for tumor cells before they seed distantly. Perhaps some sort of immunomodulatory effect is at play locally in the nodes suppressing growth.

If you ever think there might be any disease left in the axilla, I would strongly consider radiating it.

 

[scarbrtj]

If you ever think there might be any disease left in the axilla, I would strongly consider radiating it.

There are really two schools of thought here. One, given that there is a high likelihood of disease in all the other nodes (IMNs, sclav) as well as the patient’s bloodstream when there is disease in the axilla, you wouldn’t just irradiate the axilla; you would need RNI and chemo too (). We knew from Veronesi that even when the sentinel node is negative, there’s a 10% chance the axilla is positive. And when there’s a positive SLN, there’s a 25-40% chance another node will be too. So in other words, there’s potentially vast swaths of underirradiated armpits out there in the world.

The other school of thought is incidence of subclinical disease does not straightforwardly correlate to recurrence and death risk in breast cancer.

I would guess, or hope, the ratio of irradiated axillae to suspiciously subclinically positive axillae is not 1:1 these days. Else we are at risk of iatrogenizing (is that a word) more lymphedema as per MA20, more lung problems as per EORTC 22922, more second cancers as per AMAROS. I’m not being a Cassandra; just saying that the magnitude of these problems is in the ballpark of the magnitude of the benefits we are claiming/guessing.

(Hey Palex. What is the number of ISOLATED axillary recurrences (no breast, no distant, no other node site) in MA20. I think about 19 axillary recurrences total, whole study. But I can not figure how many were truly isolated. Would like to see that. Not a biggie one way or another; wish it were easily accessible data. Specifically about 14/900 axillary recurrences with ALND/no RT, and 5/900 axillary recurrences with RT. So there was about a 9/900 improvement in the axilla with some axillary RT in MA20. But how many were ISOLATED, which would be one imprecise marker of what axillary RT might really be doing. My guess is it was about 1-5 out of 900 women. My guess only.)

 

[Palex80]

There is no way to find out how many of them were isolated. "Isolated" is actually a definition of WHEN you look. Perhaps a patient with vastly dissiminated disease began her "metastatic journey" as an isolated axillary recurrence that noone picked up.

Like others have pointed out: It seems that data from MA20 point at a higher DFS-benefit than a locoregional RFS-benefit through RT, thus the hypothesis is that RNI is eliminating cells on their way to become distant metastasis.

 

[scarbrtj]

Fourth, the recurs-only-in -the-axilla patient is a rare, rare, about 1-in-1000 patient.
Says who?
MA20 certainly doesn't.

There is no way to find out how many of them were isolated. "Isolated" is actually a definition of WHEN you look.

The MA.20 did provide data on isolated recurrences (see below); they just neglected, woe betide us, to tease out the axilla in a precise fashion. All they mention is that the axillary recurrence rate (non-isolated) was ~14/900 without axillary-containing RNI, ~5/900 with. The MA.20 ("best argument" for "proving" axillary RNI does anything?), decreased axillary recurrences by 1% (~1.5% to ~0.5%). This has been the biggest reported drop I know of: a whopping 1%. Not doing axillary RNI in EORTC 22922 dropped axillary recurrences 1.9% to 1.3%.

You probably need to treat 20-30 women to spare one from an axillary recurrence in a collective of patients who are not super-low-risk.

NNT=20 implies ~5% absolute reductions in axillary recurrences, which also implies at least an absolute 5% axillary recurrence risk (ie the best we can do is go from 5% to 0%). Not in EORTC, Z0011, MA20 is there reported 5%+ axillary recurrence rates. MA20 patients: not super low-risk cohort. NNT for axillary therapy per MA20: 100, at best.

In fact, a recurrence in the axilla can be actually more difficult to manage than a recurrence to the breast.

Time for anecdotes. This has been written about by Morrow quite a bit (the best salvages are in relatively untreated axillae e.g.); not that difficult, and certainly still rare...​

​

Three [out of 326] patients [after SNB without ALND] developed a regional failure... The second patient was a woman aged 70 years with infiltrating lobular carcinoma who had 2 of 2 SLNs positive for isolated tumor cells and who declined chemotherapy and received adjuvant supine RT at an outside institution. She developed an ipsilateral axillary recurrence at 36 months that was salvaged with cALND. She developed distant metastases at 78 months and, at last follow‐up, was alive with disease 101 months after diagnosis...​

I see the nodal stations as a sort of halfway house for tumor cells before they seed distantly.

Like others have pointed out: It seems that data from MA20 point at a higher DFS-benefit than a locoregional RFS-benefit through RT, thus the hypothesis is that RNI is eliminating cells on their way to become distant metastasis.

Old-school hypotheses not necessarily justified for resurrection in the pantheon of modern thinking based simply on MA20, EORTC? Halstead saw the lymph nodes as way stations, too; thus surgical locoregional therapy was uniformly accepted as therapeutically impactful, for a time. Here we are thinking XRT locoregional therapy is going to be impactful when MA20, EORTC, Z0011 and a lot of other older stuff too is alluding that it is not. I will have to leave "managing the nodes" in breast cancer... knowing which single one of those 20-30 women, or 100-200 women, will be helped, depending on your vantage point... which nodal station to treat/not treat, and when to choose to do so for Stage II/III br CA... to thaumaturgical types.

 

[xrthopeful]

You are totally missing the boat if you are focusing on the axillary recurrence rate from MA.20 and EORTC Poortman trial and not impact on disease free survival, distant metastasis, and breast cancer mortality.

this is like stuff from 2015. it's 2019.

 

[scarbrtj]

You are totally missing the boat if you are focusing on the axillary recurrence rate from MA.20 and EORTC Poortman trial and not impact on disease free survival, distant metastasis, and breast cancer mortality.

this is like stuff from 2015. it's 2019.

Love boats.
"50 year old. Seeing a 1/1 SLN with microscopic ECE for radiation. No discussion of dissection by surgeon. Mammaprint low-risk so no chemo (gulp). Is this someone you just treat without discussing dissection? Just curious of opinions."
She has a 1% or less axillary recurrence rate with or without dissection, with or without irradiating it. Would just treat with tangents.
Cognizant that
1) the actual risk of disease in the axilla/IMNs/sclav >>>1%,
2) the LR relapse risk >>1% (but know LR relapse risk always lower than the likelihood of LR subclinical disease),
3) RNI of any sort here would have no survival benefit, anemically positive benefits re: the other metrics (DFS, BM, BrCa mortality),
4) the statistically most significant between-group differences from RNI in MA.20/EORTC were increased rates of toxicities: lung and lymphedema.

 

[Palex80]

Scarbtj, you are making the point that MA20 provided a 1% improvement in axillary recurrence rates. Agreed.

Now, the vast majority of patients in MA20 had ALND. Yet, radiation therapy to parts of axilla still led to a 1% decrease in axillary recurrence rates.
AFTER ALND!

Is it so hard to believe that patients who DID NOT have ALND, because they were managed by surgeons based on the flawed Z0011-conclusions will benefit more than 1% through axillary RT in terms of axillary recurrence rates if their radiation oncologist does not treat the axilla?

Isn't that logic?

 

[evilbooyaa]

Scarb, you keep talking about MA.20 and trying to equate it to Z11. MA.20 those patients all got ALND. To make any extrapolation of value of SLNB from MA.20 is incorrect. It was a radiation trial, not a surgical trial. Z11 was an (attempted) surgical trial. I say attempted because when indicated people seemed to treat with high tangents or 3-field (up to 50% of all cases) rather than tangents alone.

There is a difference in clinical scenario between SLNB+ 1/1 w/ ECE (as per OP) and SLNB+ 1/1 w/ ECE followed by ALND showing 0-2 additional lymph nodes involved.

 

[scarbrtj]

Now, the vast majority of patients in MA20 had ALND. Yet, radiation therapy to parts of axilla still led to a 1% decrease in axillary recurrence rates.
AFTER ALND!

ALND adds almost nothing (in the big picture) in terms of decreasing axillary recurrences. And irradiating an axilla adds almost nothing on top of that.
a + b ≃ 0 (where a ≃ almost nothing, b ≃ almost nothing)
Define almost nothing: teeny tiny improvements in LR risk with no change in natural history of dz

Is it so hard to believe that patients who DID NOT have ALND, because they were managed by surgeons based on the flawed Z0011-conclusions will benefit more than 1% through axillary RT in terms of axillary recurrence rates if their radiation oncologist does not treat the axilla?

Isn't that logic?

I believe. ALND lowers axillary LR by 1% at most; AxRT by 1% at most, too. Gotta irradiate/surgerize many axillae for the pyrrhic victory of ~2% better LR risk, no OS improvements, and keeping in mind a LR is seldom isolated, usu accompanied by synchronous local and/or distant recurrence.

Scarb, you keep talking about MA.20 and trying to equate it to Z11. MA.20 those patients all got ALND. To make any extrapolation of value of SLNB from MA.20 is incorrect. It was a radiation trial, not a surgical trial

I don't, and obviously. But Z0011 (and much other data) says ALND is not therapeutically meaningful when there is a positive SLN, in certain (and common) scenarios, and both trials have data re: axillary recurrence rates in various scenarios which seems to be the focus of therapeutic attention for some here.

There is a difference in clinical scenario between SLNB+ 1/1 w/ ECE (as per OP) and SLNB+ 1/1 w/ ECE followed by ALND showing 0-2 additional lymph nodes involved.

Why is there a difference. To me this is like saying there is a different cat in Schrodinger's box before you look at it versus after you look at it. It's the same cat. The wave function is collapsed at the time of node positivity or not; getting more node information, "the more nodes we pluck, the better the lady's luck," within certain limits, is superfluous informationally and therapeutically. Gaining information doesn't change "true" prognoses. A substantial portion of women with 1/1 SN+ have undissected/undiscovered positive nodes, i.e. disease left behind in the axilla. The ratio of disease left behind in the axilla to axillary recurrence rates is in the neighborhood of 20-30:1. This is a counterintuitive pill to swallow. All the data is saying your former scenario is a patient at pretty high risk of being in the latter scenario (ie at risk for more nodes positive with ALND), but even then, there are no clinically significant differences in outcomes nor change in natural history by obtaining those two other nodes whether positive or negative. There are many, many caveats to what I'm saying, first off top of my head latter scenario is going to get chemo 99% of the time w/ 3/3 SN+ and initial OP's scenario 1/1 SN+ is not getting chemo. This--chemo or no--will change natural history. Estrogen modulation. HER2 modulation if applicable. Post-tx lifestyle changes. Application of beautiful, hand-crafted axillary/sclav/IMN fields, vs high tangents, vs standard tangents, vs just a sclav field, etc., almost certainly won't. You think this sea change right here is due to waxing/waning/refinements of nodal RT the last 50 years? C'mon now. This... "Is it so hard to believe that patients who DID NOT have ALND... will benefit more than 1% through axillary RT?"... is magical/wishful thinking clearly at the margins of futility. (And I see none of you guys crossing the toxicity or risk/benefit rubicon here.) But hey I haven't seen people argue so much about "the 1%" since the Democrat debates

 

[xrthopeful]

You would have more luck in your arguments if you didn't speak like a carnie magician trying to distract from the point.

RNI improves breast cancer mortality (EORTC) and in MA-20, distant DFS was improved in everyone with RNI, and in ER- patients, there was a significant 11% DFS benefit (p=0.04) and non-significant 7% OS benefit (p=0.05)

Simple. Done.

 

[evilbooyaa]

I guess I just don't get why you are so incredibly hung up on isolated axillary recurrence as your solitary endpoint when we have evidence of DFS improvement....

 

[scarbrtj]

You would have more luck in your arguments if you didn't speak like a carnie magician trying to distract from the point.

RNI improves breast cancer mortality (EORTC) and in MA-20, distant DFS was improved in everyone with RNI, and in ER- patients, there was a significant 11% DFS benefit (p=0.04) and non-significant 7% OS benefit (p=0.05)

Simple. Done.

Ah the point. Offer us your afflatus re: RNI for 1/1 SN+ patients. And 11% DFS sounds like a lot, laudable even (as does 7% survival improvement); I thought it was more like 3-5% DFS improvement per those trials. Woof.

 

[Palex80]

ALND adds almost nothing (in the big picture) in terms of decreasing axillary recurrences. And irradiating an axilla adds almost nothing on top of that.
a + b ≃ 0 (where a ≃ almost nothing, b ≃ almost nothing)
Define almost nothing: teeny tiny improvements in LR risk with no change in natural history of dz

Sorry, but that's totally unlogical. ALND and axillary RT can reduce the risk of axillary recurrences. Every time a surgeon performs a sentinel node dissection he/she resects 1-3 nodes, often it's just one. But we all know that further nodes can be affected. Not resecting or irradiation those left-behind nodes is going to lead to axillary recurrences. It's obvious.

I believe. ALND lowers axillary LR by 1% at most; AxRT by 1% at most, too. Gotta irradiate/surgerize many axillae for the pyrrhic victory of ~2% better LR risk, no OS improvements, and keeping in mind a LR is seldom isolated, usu accompanied by synchronous local and/or distant recurrence.

Absolutely no data, other than the flawed Z0011-trial to back this up.
And bear in mind what Z0011 was designed to show... A non-inferiority defined as less than 5% survival disadvantage without ALND. 5% OS...
By today's standards such a trial would have difficulty passing my ethical committee. They would ask me if I considered a 4% OS-disadvantage as ethical...


Validated nomograms exist for a reason. And when a non-sentinel nomogram demonstrates the risk for further nodes to be considerable, for example >25%, one should irradiate the axilla in the absence of ALND. It's what we do in other disease sites too. Place your cutoff, wherever you wish.

Who would not give this lady RNI? She qualifies for Z0011.
pT2 pN1 (1/1;sn) cM0 G3 L1 ER+ PR+ Her2new - IDC

64% chance for further nodes according to the MSKCC nomogram...

 

[Krukenberg]

Sorry, but that's totally unlogical. ALND and axillary RT can reduce the risk of axillary recurrences. Every time a surgeon performs a sentinel node dissection he/she resects 1-3 nodes, often it's just one. But we all know that further nodes can be affected. Not resecting or irradiation those left-behind nodes is going to lead to axillary recurrences. It's obvious.


Absolutely no data, other than the flawed Z0011-trial to back this up.
And bear in mind what Z0011 was designed to show... A non-inferiority defined as less than 5% survival disadvantage without ALND. 5% OS...
By today's standards such a trial would have difficulty passing my ethical committee. They would ask me if I considered a 4% OS-disadvantage as ethical...


Validated nomograms exist for a reason. And when a non-sentinel nomogram demonstrates the risk for further nodes to be considerable, for example >25%, one should irradiate the axilla in the absence of ALND. It's what we do in other disease sites too. Place your cutoff, wherever you wish.

Who would not give this lady RNI? She qualifies for Z0011.
pT2 pN1 (1/1;sn) cM0 G3 L1 ER+ PR+ Her2new - IDC

64% chance for further nodes according to the MSKCC nomogram...

View attachment 270003

At my institution we’d use high tangents as many did in Z11 and call it a day. If the patient was ER-negative we may consider RNI more.

MA20 was a negative trial. It did not meet its primary outcome, and our view is that the increase in pulmonary and lymphedema complications is greater than the very very low potential benefit of RNI, esp for ER+ patients.

 

[KHE88]

Why is there a difference. To me this is like saying there is a different cat in Schrodinger's box before you look at it versus after you look at it. It's the same cat. The wave function is collapsed at the time of node positivity or not; getting more node information, "the more nodes we pluck, the better the lady's luck," within certain limits, is superfluous informationally and therapeutically. Gaining information doesn't change "true" prognoses. A substantial portion of women with 1/1 SN+ have undissected/undiscovered positive nodes, i.e. disease left behind in the axilla. The ratio of disease left behind in the axilla to axillary recurrence rates is in the neighborhood of 20-30:1. This is a counterintuitive pill to swallow. All the data is saying your former scenario is a patient at pretty high risk of being in the latter scenario (ie at risk for more nodes positive with ALND), but even then, there are no clinically significant differences in outcomes nor change in natural history by obtaining those two other nodes whether positive or negative. There are many, many caveats to what I'm saying, first off top of my head latter scenario is going to get chemo 99% of the time w/ 3/3 SN+ and initial OP's scenario 1/1 SN+ is not getting chemo. This--chemo or no--will change natural history. Estrogen modulation. HER2 modulation if applicable. Post-tx lifestyle changes. Application of beautiful, hand-crafted axillary/sclav/IMN fields, vs high tangents, vs standard tangents, vs just a sclav field, etc., almost certainly won't. You think this sea change right here is due to waxing/waning/refinements of nodal RT the last 50 years? C'mon now. This... "Is it so hard to believe that patients who DID NOT have ALND... will benefit more than 1% through axillary RT?"... is magical/wishful thinking clearly at the margins of futility. (And I see none of you guys crossing the toxicity or risk/benefit rubicon here.) But hey I haven't seen people argue so much about "the 1%" since the Democrat debates

What in the world are you trying to say?
This is getting almost as bad as defending FiF and reverse planned IMRT as the same thing.
You are making so many hypothetical arguments and incorporating in so many confounding variables.

If you wanna make the argument you don't need to do sentinel node biopsies on elderly people because of the percentage of people getting axillary staging on CALGB 9343 (37%) and the number of axillary recurrences there and in prime 2, fine, that's a reasonable way to go. But to omit any axillary RT on a younger person with known axillary disease, especially anything other than a micromet, based off the results of a crappy study and low observed axillary recurrence rates without any good explanation for the mechanism behind the lower recurrence rate nor a complete understanding of what exactly systemic/hormone therapy is doing is insane IMO. I don't want that recurrence walking back into my office.

Toxicity risk/benefit? Remember these women used to get radical mastectomies and full axillary dissections. With a sentinel lymph node biopsy and at least low axillary conformal RT, without some very god data and a rationale/mechanism for not treating a known site of disease, I'll take that toxicity risk of some lymphedema over the risk of an occasional fatal recurrence. Or at the bare minimum have a discussion and give the patient the option.

Agree with the above. Keep it simple. Single positive sentinel node? 3d tangents covering levels 1 and 2.
Triple negative, very young, extensive ece, other risk factors? Full RNI with a low threshold to escalate to full RNI.

And lets not forget AMAROS which was basically the same trial except ignoring the axilla was not an option. You either got ALND or axillary RT. And guess what, the lymphedema rate with RT was low (14%) and half that of ALND. Axillary recurrence was 1% like Z11. But maybe you want to design a trial that actually specifies SLN Bx only vs. axillary RT vs. ALND. See if that first arm recurrence rate comes out NS. Good luck getting that trial off the ground

God I hate Z11.

Just post the castro pic again.

 

[scarbrtj]

Not resecting or irradiation those left-behind nodes is going to lead to axillary recurrences. It's obvious.

non-obvious, based on data. The nomograms are now red herrings. Ergo the reason the "whole world" (not really TBH) has "learned" to let the axilla be. (And when you have an axillary recurrence, it's almost never isolated; you have to make the case that the axilla is a seeding site, versus breast cancer being a "whole host" disease.)

I guess I just don't get why you are so incredibly hung up on isolated axillary recurrence as your solitary endpoint when we have evidence of DFS improvement...

Because that's where the discussion always goes (see @Palex above).

This is getting almost as bad as defending FiF and reverse planned IMRT as the same thing.

based off the results of a crappy study

heh, it is the same thing ... but when a study is crappy you can dismiss it. "Crappy." Poof. The article, data, nomenclature, etc... irrelevant. For Z0011 its level of crap-to-impact ratio is the closest to one for any study, ever, in the history of medicine I suppose. I never realized it but Z0011 is maybe our specialty's Uncle Buck hat.

But maybe you want to design a trial that actually specifies SLN Bx only vs. axillary RT vs. ALND. See if that first arm recurrence rate comes out NS.

What in the world are you trying to say?

I'm trying to say for the routine case, a woman who comes in clinic with T1/2 with SN+, no ALND, whether you do RNI, axillary RT, tangents, refer for ALND and/or do all the other potential RT maneuvers after, none of that moves the needle for natural history (helps about 1 in 50-100 on LRR risk) nor does it have clinically meaningful outcomes on the axilla. Do whatever you want; doing more does little to nothing except adds in slightly increased risks of side effects depending on how much more you do. For your hypothetical trial, some real world locoregional relapse numbers from some previous trials:
SLN vs ALND: ~0.3% vs 1%, 10y ~17% vs ~19%
ALND vs axillary RT: ~1% vs ~1%, 10y ~4% vs 4%
...what I'm trying to say is that the data is all a mish-mash of very low single digit numbers allowing no clear winner to be declared; the only thing clear is that the axilla is a very rare site of recurrence, and as @Palex points out, the SN nomograms are 100% useless in predicting anything re: clinical outcomes (hence my point that the ratio of axillary involvement to axillary recurrence is about 20 to 30 to one) and have no utility in making clinical decisions nowadays. See @Krukenberg's answer which is indubitably the right answer. Except maybe the high tangents
EDIT

But to omit any axillary RT on a younger person with known axillary disease, especially anything other than a micromet, based off the results of a crappy study and low observed axillary recurrence rates without any good explanation for the mechanism behind the lower recurrence rate nor a complete understanding of what exactly systemic/hormone therapy is doing is insane IMO. I don't want that recurrence walking back into my office.

Ironically, at least this would give me pause, you would maybe see more contralateral breast cancers walking into your office with ipsilateral axillary RT than you would be preventing ipsilateral axillary RT recurrences. This woman just walked in my office; br CA in 1997, now with rectal CA. Every recurrence that walks into your office is a survivor, but not every survivor is a recurrence. That's day 1 doctoring to all and I ain't tellin' you nothin' new. But more and more the survivors way outnumber the isolated LR recurrences nowadays. RNI, or axillary RT, or IM/SC RT, or ALND, or combos thereof, for SN+ patients that are early stage, good-to-reasonable biology, put more or as many survivors w/ problems in the clinic than they keep recurrences out of the clinic thereby casting a pall over dogmatic viewpoints such as doing/not doing something is "insane" or "obvious."

 

[Mandelin Rain]

Rate of finding a positive non-sentinel lymph node on completion dissection in the setting of a positive SLNBx is 38%.

Honest question. If the genomic test determines the need for chemo and literally nothing ever needs to be done for any subclinical disease in the axilla, at what point do we abandon SLNBx? Why haven't we already? (yes, I know there's a trial)

 

[scarbrtj]

Rate of finding a positive non-sentinel lymph node on completion dissection in the setting of a positive SLNBx is 38%.

Honest question. If the genomic test determines the need for chemo and literally nothing ever needs to be done for any subclinical disease in the axilla, at what point do we abandon SLNBx? Why haven't we already? (yes, I know there's a trial)

It's that ~38% that's the reason for all the agita in this thread; 38% rates (10% to 64% @Palex) of "unharvested" disease in sites with <1% risks of isolated recurrences. That's partly what made this study so groundbreaking.

Re: your hypothetical, it would be a possibility/not unthinkable. Needs lots of testing. But subclinical disease is often everywhere in a woman with a positive SN. Her rate of IMN sublcinical disease maybe 20-40%, sclav disease 10+%, CTCs in bloodstream 25%, 1-5% in opposite breast/nodes. Even in the woman with a negative SN, there's a 10% chance that on ALND you'd find a positive node! You might imagine there's a 50% rate probability of not-100%-coveredcompletely untouched-by-the-rad-onc subclinical disease in the average breast cancer patient.

 

[Palex80]

If the rate of subclinical undetectable disease is that high in pN1 patients and irradiating the axilla is futile anyway, as scarbtj proposes, I wonder why do we even bother irradiating the breast? Just call it a day. The patient is pN1, it's futile. No need to treat any more.

 

[scarbrtj]

If the rate of subclinical undetectable disease is that high in pN1 patients and irradiating the axilla is futile anyway, as scarbtj proposes, I wonder why do we even bother irradiating the breast? Just call it a day. The patient is pN1, it's futile. No need to treat any more.

Ha well I'm not some lone wackadoo saying it's futile; there's quite a few who think so too. (And yes, surprise, I do it select cases.) But breast irradiation and chest wall irradiation for pN1 patients have very proven benefits for OS, benefits much more robustly demonstrable than axillary RT e.g. And the vast majority of pN1 patients are getting systemic tx, estrogen modulation, etc. Or even exercise because they made lifestyle changes after their diagnosis; exercise does way more for breast cancer survival than RNI does. The most common cause of death after breast CA diagnosis is not breast cancer, it's heart disease.* Some RNI or axillary RT has essentially been proven, IMHO, not to make this difference (the difference between br Ca-related and cardiac-related mortality) more pronounced. Radiation has been pushed to the limit of its OS-improving ability in breast cancer. I say again:

* I'm casting zero aspersions on RT cardiac effects

 

[Pointless]

This evolved into a very nice discussion outlining the controversies regarding nodal irradiation in breast cancer. To summarize, most on this board would give edit: HIGH tangents for the OP's patient (myself included) and we have one dissenter. There does not appear to be a correct answer. We can probably let the thread die now

 

[scarbrtj]

Well said. Epilogue of epilogues, "correct answers" are as hard to pin down as the Nature Boy was in his day. But there are beliefs, and there are findings retrospective and prospective. If anything clashes with a belief, one must be willing to throw out the belief. Belief versus belief is always a push; no correct answers there. This right here was a belief, untested. This right here was a consequence of that belief. Irradiating almost a quarter of a woman's body is more tied to beliefs than it is findings. Breast cancer is a big umbrella encompassing a wide variety of heterogenously behaving diseases. RNI may make survival and recurrences worse for up to a quarter of br CA patients (see below; table modified for ALTTO). More "correct answers" are truly needed; only that will change beliefs.

 

[xrthopeful]

This evolved into a very nice discussion outlining the controversies regarding nodal irradiation in breast cancer. To summarize, most on this board would give low tangents for the OP's patient (myself included) and we have one dissenter. There does not appear to be a correct answer. We can probably let the thread die now

This was a typo correct - most said NOT to do low tangents, including you.

 

[evilbooyaa]

This evolved into a very nice discussion outlining the controversies regarding nodal irradiation in breast cancer. To summarize, most on this board would give low tangents for the OP's patient (myself included) and we have one dissenter. There does not appear to be a correct answer. We can probably let the thread die now

Would not count Palex as a 'sole' dissenter on this. I know me, as well as multiple others would treat with high tangents and/or full 3-field. I agree that 'convincing' one side they are 'wrong' is unlikely as there isn't a phase III trial comparing these techniques.

All I can say for those who are doing standard tangents alone - hope none of your patients recur in the Axilla or SCV.

 

[xrthopeful]

Based on his previous posts, he was arguing to treat the axilla, so I'm fairly certain he was saying that scarbrtj is the lone dissenter in wanting to do normal tangents alone

 

[Pointless]

This was a typo correct - most said NOT to do low tangents, including you.

Man, that was an epic fail. Yes, I meant high tangents. Most would give high tangents covering the low axilla is what I meant to say.

 

[scarbrtj]

Based on his previous posts, he was arguing to treat the axilla, so I'm fairly certain he was saying that scarbrtj is the lone dissenter in wanting to do normal tangents alone

I thought Palex was lone dissenter with RNI.
I'd do tangents only. Don't know about "high." Better talk to Sampson 'bout that. In my experience, one guy's high tangents are like another guy's medium tangents. Not super well standardized from an EBM perspective IMHO. The amount of data that differing tangent height does anything is... not high.

 

[scarbrtj]

Would not count Palex as a 'sole' dissenter on this. I know me, as well as multiple others would treat with high tangents and/or full 3-field. I agree that 'convincing' one side they are 'wrong' is unlikely as there isn't a phase III trial comparing these techniques.

All I can say for those who are doing standard tangents alone - hope none of your patients recur in the Axilla or SCV.

In the history of radiation oncology have high vs low tangents been associated with increased axillary recurrences. In Z0011 not only was it not, lack of RT at all was not. In the EORTC trial the axilla was not specifically irradiated; and not doing so decreased axillary recurrences by about a half percent. About 15 years ago I saw a sclav recurrence in a woman treated years before I got out of residency. I still have yet to encounter an isolated axillary recurrence. The thing is, I can fondly recall leaving residency and thinking the technicalities and nuances of axillary RT (“PABs”... yikes) were quite vital. The IMNs have higher rates of subclinical disease across all stages than sclav, including in Stage I. (And all Stage I patients nowadays have ~10% chance of being pN1 if the routine ALND were brought back.) Yet the IMN kind of gets left out, at least here. OP’s patient has a 20-40% chance of positive IMN node. High tangent, or low tangent, for her is theoretically deck chair rearranging on the Titanic. Fortunately data gives solace the theory is wrong. Hope none of (.y.)our patients recur in the IMNs.*

*EDIT: you know you've passed breast oral boards once you make it to the question about how to handle an IMN recurrence. AFAIK, there is no oral board question about how to handle an axillary recurrence; so perhaps at least in oral board land IMN recurrences are 100% more common than sclav or axillary recurrences IDK, I've been away from that for a while...

 

[Pointless]

*EDIT: you know you've passed breast oral boards once you make it to the question about how to handle an IMN recurrence. AFAIK, there is no oral board question about how to handle an axillary recurrence; so perhaps at least in oral board land IMN recurrences are 100% more common than sclav or axillary recurrences IDK, I've been away from that for a while...

LOL, I literally had that case as my last one in the breast section of my oral boards. I must have blacked out, because I can't recall for the life of me what my answer was.

 

[scarbrtj]

LOL, I literally had that case as my last one in the breast section of my oral boards. I must have blacked out, because I can't recall for the life of me what my answer was.

Good. Recalls are illegal.

 

[Palex80]

In the history of radiation oncology have high vs low tangents been associated with increased axillary recurrences. In Z0011 not only was it not, lack of RT at all was not. In the EORTC trial the axilla was not specifically irradiated; and not doing so decreased axillary recurrences by about a half percent. About 15 years ago I saw a sclav recurrence in a woman treated years before I got out of residency. I still have yet to encounter an isolated axillary recurrence. The thing is, I can fondly recall leaving residency and thinking the technicalities and nuances of axillary RT (“PABs”... yikes) were quite vital. The IMNs have higher rates of subclinical disease across all stages than sclav, including in Stage I. (And all Stage I patients nowadays have ~10% chance of being pN1 if the routine ALND were brought back.) Yet the IMN kind of gets left out, at least here. OP’s patient has a 20-40% chance of positive IMN node. High tangent, or low tangent, for her is theoretically deck chair rearranging on the Titanic. Fortunately data gives solace the theory is wrong. Hope none of (.y.)our patients recur in the IMNs.*

*EDIT: you know you've passed breast oral boards once you make it to the question about how to handle an IMN recurrence. AFAIK, there is no oral board question about how to handle an axillary recurrence; so perhaps at least in oral board land IMN recurrences are 100% more common than sclav or axillary recurrences IDK, I've been away from that for a while...

I have seen axillary recurrences, quite a few actually. All in patients who did not have their axilla irradiated.

 

[scarbrtj]

When I was a kid a friend was telling me a story about how his dad raced home from work on his bike, in 5 minutes, to stop someone from kidnapping his sister. He was trying to make the point that his dad had a fast bike. In telling the story I realized he was describing the dad traveling between two points separated by about 50 miles, in L.A, in the afternoon on a weekday. "If you travel 50 miles in 5 minutes, that means 300 miles in 30 minutes and 600 miles in one hour. I don't think your dad has a bike that will go 600 miles in one hour in L.A. rush hour traffic." We stayed friends, but I stayed skeptical about his stories.

In the two studies we've been harping on, in one the axilla was irradiated and it saved 10 out of 1000 women (1% decrease) from an axillary recurrence; in the other study, the axilla wasn't specifically irradiated and not irradiating the axilla saved 6 out of 1000 women (0.6% decrease) from an axillary recurrence. This is a "gap" of 4 in 1000 women "hurt" by axillary non-irradiation. Use other studies/other data, slice it any way you want. You'll arrive at roughly similar numbers. Now we must also believe a few more things:
1) You must be the "catcher of the gap" for all axillary recurrences in your area. When you say "quite a few actually" this could be anywhere from 3 to 333; is it 10? If it's ten, this implies you have seen thousands upon thousands of breast cancer patients in your career. (I see about 100 a year.) Not impossible, but, it also implies that...
2) When any woman in the local geographic region has an axillary recurrence, she must come see you. (Supposedly I can predict your region by your RNI proclivities.) You are an axillary irradiator. (You should also be seeing axillary recurrences in the women whose axillae you irradiate; about half or third as much... story for another time.) But somehow you are also seeing axillary recurrences in women not irradiated? So you're getting outside axillary recurrence consults, or are women self-referring to you?
3) You aren't telling about the pattern of the recurrence, which is important. Isolated? Co-recurrent with local disease? With distant disease? Are the recurrences still alive? I specified "isolated" axillary recurrence; because there must be some element of the Halsted theory (and some incidence of isolated nodal failure) that can appertain to axillary irradiation to make it effective. It's the core of any argument for RNI.
4) We also don't know the number of women who didn't get their axilla irradiated who didn't have a recurrence who didn't see you. The numerator is as important as the denominator. If you really are the guy who gets to see all the axillary recurrences in which you played no part, it may skew your worldview. And our view of your worldview.
5) If irradiating the axilla and nodes helps--

All I can say for those who are doing standard tangents alone - hope none of your patients recur in the Axilla or SCV.

I have seen axillary recurrences, quite a few actually. All in patients who did not have their axilla irradiated.

--no one tells the stories about who it hurts. Which is a real oversight. Per the two studies we've mentioned, doing RNI hurts about as many (or half as many) with a detectable toxicity as it helps. If you're doing a lot of RNI--extending it to all 1/1 SN+ patients e.g.--you're also causing increasing toxicity from that. In theory seeing as much toxicity in your own patient population as outside axillary recurrence consults from the heretical non-axillary-irradiators. If irradiating an axilla causes an excess 33 out of 1000 (75/681 vs 57/744, a ~3.3% increase) contralateral breast cancers, but only gives a 4/1000, or 6/1000, or 10/1000, improvement in axillary recurrences as suggested above, why irradiate an axilla? You are literally doing more harm than good. Who knows why that is. ALTTO also showed, depending on biology, RNI makes any recurrence more likely, distant recurrence significantly more likely.

To this day, there are no 600 mph bikes.

 

[KHE88]

To this day, there are no 600 mph bikes.

No, but we're getting close. It's a pretty linear and constant progression. We should be breaking the sound barrier with bikes by 2030 or so. Which is hilariously sooner than we will have a clear answer on the seemingly simple problem of whether to ignore known cancer cells in the axilla or not.

I think you are putting too much faith in sketchy data that goes against common sense. If we were killing people with axillary radiation, then you might have a point. But a little risk of lymphedema compared to a rare but very serious recurrence? I'm with evilbooya, I don't want to see that recurrence, EVER. Doc, you mean to tell me the surgeon found out my early stage breast cancer had spread under my arm and you didn't radiate it and now I finished my tamoxifen and the cancer has come back there and spread to my bones? Well, actually ma'am, let me tell you about this awesome study called Z-11...

And FWIW, you keep harping on IMNs. I don't know about you older guys, but everyone I know training now is trained to always treat IMNs when treating RNI. Full stop. Never give a SCV field without treating IM chain. Easy peasy with breath hold and every once in a while requiring an electron patch. I'm sure there is some place out there that is not teaching residents to always include IMNs in RNI, but most are. For an inner quadrant tumor with a positive SLN, I think it is totally reasonable to include the IMNs without a SCV field, but I would still treat low axilla.

Sentinel lymph node positive in someone not meeting criteria for prime 2 is always getting "high tangents" in my book at a minimum. You wanna play with fire be my guest but I would go through one hell of an informed consent process and document with extensive literature citation.

 

[xrthopeful]

Yeah I think most people in training now are routinely including the IM nodes when doing RNI now and like he said with the use of respiratory gating, the DVH looks pretty good.

 

[Palex80]

In the two studies we've been harping on, in one the axilla was irradiated and it saved 10 out of 1000 women (1% decrease) from an axillary recurrence; in the other study, the axilla wasn't specifically irradiated and not irradiating the axilla saved 6 out of 1000 women (0.6% decrease) from an axillary recurrence. This is a "gap" of 4 in 1000 women "hurt" by axillary non-irradiation. Use other studies/other data, slice it any way you want. You'll arrive at roughly similar numbers. Now we must also believe a few more things:
1) You must be the "catcher of the gap" for all axillary recurrences in your area. When you say "quite a few actually" this could be anywhere from 3 to 333; is it 10? If it's ten, this implies you have seen thousands upon thousands of breast cancer patients in your career. (I see about 100 a year.) Not impossible, but, it also implies that...

I have certainly seen 10. Probably I see at least one per year.

The rates are certainly higher in patients with risk factors and without ALND.

 

[scarbrtj]

But a little risk of lymphedema compared to a rare but very serious recurrence?

A "little" risk. Also a "little" risk of lung fibrosis; 3% risk of lung toxicity. A little risk here and a little risk there...
And regarding recurrences, they're not "very serious" although we can (and do!) quibble over semantics. As Morrow has pointed out, it seems a lot better outcome for the non-RNI patients at time of LRR just perhaps for the reason that they are more easily re-irradiated vs patients who got full axillary or RNI RT. I would much prefer re-irradiating a non-RT'd axilla vs one previously irradiated. And we all can admit even irradiated axillae have recurrences.

Sentinel lymph node positive in someone not meeting criteria for prime 2 is always getting "high tangents" in my book at a minimum. You wanna play with fire be my guest but I would go through one hell of an informed consent process and document with extensive literature citation.

A "hell" of an informed consent process? "Play with fire?" Can we get serious now. Extensive literature citation on high tangents? Is that, like, even possible? (No. Of course not.) High tangent patients get axillary recurrences at the exact same rate as low tangent patients. We can't even agree on what a high vs low tangent is, nor if the axillary nodes are fully/"properly" covered in either case. However, there's data not irradiating the axilla lowers axillary recurrence rates. One had better hellaciously consent both high and low tangent patients.

Doc, you mean to tell me the surgeon found out my early stage breast cancer had spread under my arm and you didn't radiate it and now I finished my tamoxifen and the cancer has come back there and spread to my bones?

Vignette which shows the futility of axillary irradiation and the irrational fears of RNI believers: a woman 5+ years out from LR therapy who has synchronous axillary and distant recurrence. A woman who per the data has perhaps a solidly 0% risk of axillary recurrence without axillary RT. You're talking about what, a 1-in-100,000 event? A 1-in-1,000,000 event? "Axillary RT would have saved her!" Uh OK. My data's no good here. Your bike graph and logic are unassailable

 

[Palex80]

A "little" risk. Also a "little" risk of lung fibrosis; 3% risk of lung toxicity. A little risk here and a little risk there...

Which probably resulted from IM–RT using old techniques. No increased pneumonitis with axillary RT in AMAROS.

Sorry, but I think you are trolling scarbtj.

 

[scarbrtj]

Which probably resulted from IM–RT using old techniques. No increased pneumonitis with axillary RT in AMAROS.

Sorry, but I think you are trolling scarbtj.

Not trolling. Is there ANY data that new IMN-RT techniques give significantly less lung fibrosis risk than "old" techniques? @KHE88 mentioned the electron patch above for IM coverage. Intensity modulated electrons? And yes, all AMAROS showed was significantly more contralateral breast cancers with ipsilateral axillary RT.

 

[KHE88]

A "hell" of an informed consent process? "Play with fire?" Can we get serious now. Extensive literature citation on high tangents? Is that, like, even possible? (No. Of course not.) High tangent patients get axillary recurrences at the exact same rate as low tangent patients. We can't even agree on what a high vs low tangent is, nor if the axillary nodes are fully/"properly" covered in either case. However, there's data not irradiating the axilla lowers axillary recurrence rates. One had better hellaciously consent both high and low tangent patients.

Kinda funny you're picking on me for my use of language, but...

"High tangent patients get axillary recurrences at the exact same rate as low tangent patients."

There's no way you could possibly know that. Show me the PRT with long term follow-up that evaluated 3D tangent or IMRT whole breast only vs. 3D tangent or IMRT whole breast + levels 1-2. Because I never learned about that and think I must have a serious gap in my education!

Also, in the table you linked, there were 1.9% axillary recurrences without nodal RT and 1.3% with RT. But you claimed that axillary recurrences in the no-axillary-RT group were lower. Huh? Even if that were true, would you trust that result? What's your explanation -- that RT kills cancer everywhere in the body except in the axilla where it causes it to grow? Some sort of paradox like the inverse dose rate effect? Maybe alunimum anti-persperirants are interacting and causing secondary axillary primaries? I mean, what?

But I will agree with you that "high tangents" and "low tangents" are stupid terms.

A high tangent typically means just take your normal tangent field covering the whole breast and open up the superior border (just making your tangent field taller). If you do that, you are going to miss some axilla. But I don't think that's what most people who refer to "high tangents" do. Instead they contour out a 3D volume of the axilla they want to treat and have their dosimetrist put on some tangent fields and use their fancy "psuedo-IMRT" to cover it all uniformly. In regards to what "high tangents" meant on Z-11 analysis, who knows. Maybe some covered all of I-II. Maybe/probably some sliced off a portion of it.

 

[gmsquid]

The classic 2D definition of high tangents was the field is within 2 cm of the humeral head and you rotate the collimator to get the low axilla.

 

[xrthopeful]

As Morrow has pointed out, it seems a lot better outcome for the non-RNI patients at time of LRR just perhaps for the reason that they are more easily re-irradiated vs patients who got full axillary or RNI RT. I would much prefer re-irradiating a non-RT'd axilla vs one previously irradiated. And we all can admit even irradiated axillae have recurrences.

This is some of the most backwards logic I've seen from you, and at this point I also have to think you are trolling.


Anyways all of this discussion is quite useless because scarbtj is willfully ignoring the data showing the impact of RNI on overall outcomes including distant mets, DFS, BCM, and suggestion of OS trend in ER negative patients.

 

[KHE88]

This is some of the most backwards logic I've seen from you, and at this point I also have to think you are trolling.


Anyways all of this discussion is quite useless because scarbtj is willfully ignoring the data showing the impact of RNI on overall outcomes including distant mets, DFS, BCM, and suggestion of OS trend in ER negative patients.

Exactly. The logic is that RT to the node-positive axilla doesn't do anything, so omit it give some hormone treatment, and say your prayers.
But if you get a recurrence in the axilla, then suddenly RT does something? Why not just cut it out again and give some more hormone treatment?

This all seems like a lot of hand waving.
The mechanism of RT on tumor killing is not black magic. Ask any current PGY-4 or PGY-5 and they'll tell you exactly in excruciating detail every little last step of the RT-induced DNA damage response and RT-induced signalling pathways.

But who knows maybe we'll see better axillary control with hypofrac RNI. What with that low alpha/beta and all (speaking of black magic and hand waving...).

 

[scarbrtj]

"High tangent patients get axillary recurrences at the exact same rate as low tangent patients."

There's no way you could possibly know that.

I know it per Z0011, the Z0011 followup confirmatory studies, and a HUGE sea of data with varying RT approaches none of which moved the axillary recurrence needle. Now we can argue axillary RT itself decreases axillary recurrences by a percent (the most ever), or no axillary RT decreases axillary recurrences (EORTC 22922). Or maybe axillary RT makes recurrences worse (ALTTO). But as far as axillary RT technique? High or low tangents? For the scant amount of data about that, for a rare problem like axillary recurrences, there is data it makes no difference.
Put it this way: there is some data it makes no difference. There is zero data that it makes a difference.

Also, in the table you linked, there were 1.9% axillary recurrences without nodal RT and 1.3% with RT. But you claimed that axillary recurrences in the no-axillary-RT group were lower. Huh? Even if that were true, would you trust that result?

The table is from EORTC 22922, an RNI study of IM/SC. According to the trialists, "A total of 7.4% of the patients in the control group and 8.3% of the patients in the nodal-irradiation group underwent axillary irradiation." Thus, the large majority of patients did not get axillary RT in either arm. And as mentioned (endlessly by me at this point), not doing axillary RT decreased axillary recurrences by 0.6%.

I don't trust/mistrust results per se. I merely quote them. You seem to mistrust some of the results of Z0011, thereby negating the whole study. Would you do the same (mistrust its results, thus negating the study) for EORTC 22922?

The classic 2D definition of high tangents was the field is within 2 cm of the humeral head and you rotate the collimator to get the low axilla.

Here's where we need more data. Would be good to know axillary recurrences w/fields >2 cm away from humeral head. Or within 1-2 cm of humeral head. Or 0-1 cm from humeral head. And correlate all this with amount of collimator rotation used. And then not only get LRR risks from these technical factors, need DM rates and OS survivals too. Only then can we settle this debate. #sarcasm

This is some of the most backwards logic I've seen from you, and at this point I also have to think you are trolling.

I'm not trying to be backwards. Honestly. I'm just trying to point out what's been reported.
In a retrospective analysis of 20,000 women across Stage I-III, 200 had axillary recurrence.
And among these 200 recurrences, there was an association with "improved overall survival... [and] no initial axillary radiation (P<.001)..."
The strongest factor associated with improved OS among this 200 patient cohort culled from 20,000?
The use of no axillary RT upfront.
This means there is an inconvenient truth:
Upfront axillary RT has been more strongly associated with worse survival, or no improved survival, in the breast literature. It has never been associated with improved survival.

This all seems like a lot of hand waving.

First thing we can agree on.

Anyways all of this discussion is quite useless because scarbtj is willfully ignoring the data showing the impact of RNI on overall outcomes including distant mets, DFS, BCM, and suggestion of OS trend in ER negative patients.

Totally misstates what I have said ("Both MA20 and the EORTC show RNI lowers regional recurrences... in the neighborhood of needing to provide RNI to around 50 women to prevent one regional recurrence; and all that sans survival benefits") and what I've been trying to say.

 

[KHE88]

The table is from EORTC 22922, an RNI study of IM/SC. According to the trialists, "A total of 7.4% of the patients in the control group and 8.3% of the patients in the nodal-irradiation group underwent axillary irradiation." Thus, the large majority of patients did not get axillary RT in either arm. And as mentioned (endlessly by me at this point), not doing axillary RT decreased axillary recurrences by 0.6%.

I'm going to give you the benefit of the doubt here as you are really digging into the data to try and draw a paradoxical conclusion, apparently, that radiating the axilla increases the chances that the cancer will come back there.

https://www.nejm.org/na101/home/literatum/publisher/mms/journals/content/nejm/2015/nejm_2015.373.issue-4/nejmoa1415369/20150717/images/img_xlarge/nejmoa1415369_t2.jpeg

So what am I missing here?
Where are you drawing the conclusion that forgoing axillary RT raised axillary recurrence rates by 0.6%?

Because from your table that you posted, patients who received RNI had improved, not worsened, axillary control by 0.6%
Is that the 0.6% number you are referring to?

Because as you pointed out, not everybody in the RNI received dedicated axillary RT. The only ones who got axillary radiation were the ones who had adverse features after dissection, which again is another confounder.

From the paper,

"Eligibility criteria included unilateral histologically confirmed breast adenocarcinoma of stage I, II, or III with a centrally or medially located primary tumor, irrespective of axillary involvement, or an externally located tumor with axillary involvement. Eligible patients had undergone mastectomy or breast-conserving surgery and axillary dissection. During the last years of the trial, patients were eligible if they had undergone a sentinel-node
biopsy followed by an axillary dissection in the case of a positive node."

"Since the regional nodes are functionally interconnected, it was decided to include the medial supraclavicular nodes, thereby in fact randomizing
between complete nodal treatment (axillary surgery and irradiation of nondissected nodes) and axillary surgery alone. Therefore, we cannot determine
whether internal mammary irradiation or medial supraclavicular irradiation contributed more to the outcome."

This was one of the major limitations of the study that I am aware of. The study is commonly used to support the radiation of IMNs in medial and central tumors (although axillary node positive with tumors in any location were also included). But in the author's own words they admit this is not a valid conclusion to draw as multiple fields were irradiated.

So where is that 0.6% axillary recurrence detriment from axillary RT coming from? Because the tabled you linked shows a 0.6% improvement, not detriment, with nodal radiation, and it doesn't break down the nodal radiation by site. So it can't be that 0.6%, right?

Genuinely confused.

 

[scarbrtj]

So where is that 0.6% axillary recurrence detriment from axillary RT coming from? Because the tabled you linked shows a 0.6% improvement, not detriment, with nodal radiation, and it doesn't break down the nodal radiation by site. So it can't be that 0.6%, right?

Genuinely confused.

Second thing we can agree on. If you look back at what I've said, I've drawn zero conclusions save for the fact that axillary RT does nothing clinically important which is beneficial. When I said "not doing axillary RT decreased axillary recurrences by 0.6%" I was saying it tongue-in-cheek. Because a conclusion from a 0.6% difference about anything from a trial of ~4000 patients would be pretty... bad. If I were to say irradiating the axilla increases recurrences for certain biology, it's not a conclusion; it's merely repeating the data. A data association. (And yes, e.g., ER- was associated with better OS from RNI in the EORTC trial... a trial which excluded directed axillary RT.) No cause/effect, in the strict sense of the word, implied. One can associate zero cause/effects with axillary RT except increased lymphedema (historical data, P<0.05) and higher second cancer risk (AMAROS 10y, p<0.05). One can make no real cause/effect statements re: the axilla from MA20 or the EORTC. All I can say is what the studies found. And, again, MA20 showed a 1.5% axillary recurrence without axillary RT, 0.5% with. And the EORTC reported 1.9% axillary recurrence with nodal-sans-axillary RT, 1.3% axillary recurrence with nodal-sans-axillary RT. Why do I say sans axillary? Because the EORTC said "A total of 7.4% of the patients in the control group and 8.3% of the patients in the nodal-irradiation group underwent axillary irradiation." So a site-by-site breakdown would be meaningless/fruitless. There was a difference of 11 axillary recurrences in this EORTC trial of ~4000 patients where the axilla was rarely irradiated (yes, it was dissected, but it was dissected in both RNI and non-RNI groups). I didn't even imply cause/effect when I associated initial-treatment upfront axillary RT with worse survival: merely said it's associated for the roughly 20,000 patients initially examined. And even there with a p<0.001 for worse survival with axillary RT, absolute numbers are quite small.

Back to your "playing with fire" warning. To me, all this is not playing with fire. It's playing with stupid minutiae. I'm seducible by stupid minutiae but not when it brings along heightened toxicity risks which are equal or greater in magnitude to the benefits of the stupid minutiae.

 

[Palex80]

Not trolling. Is there ANY data that new IMN-RT techniques give significantly less lung fibrosis risk than "old" techniques? @KHE88 mentioned the electron patch above for IM coverage. Intensity modulated electrons? And yes, all AMAROS showed was significantly more contralateral breast cancers with ipsilateral axillary RT.

No, but the point is that we are talking about axillary RT not internal mammary RT.

 

[Pointless]

 

[Palex80]

The table is from EORTC 22922, an RNI study of IM/SC. According to the trialists, "A total of 7.4% of the patients in the control group and 8.3% of the patients in the nodal-irradiation group underwent axillary irradiation." Thus, the large majority of patients did not get axillary RT in either arm. And as mentioned (endlessly by me at this point), not doing axillary RT decreased axillary recurrences by 0.6%.

I truly think you ARE trolling...

EORTC 22922 randomized patients to IM/SC-RT or not.
A small proportion of the patients had axillary RT, evenly distributed between both arms.

There were 1.3% axillary recurrences with IM/SC-RT, while in the control group that rate was 1.9%.

All you can say is that irradiation of the IM/SC DECREASED axillary recurrence rates by 0.6%. That's it.

You can draw ZERO conclusions on the role of axillary RT here.

My personal interpretation is that irradiating the SC probably delivered dose to the higher levels of the axilla, thus eliminating disease there. Not all of us place the border at the same level when delivering SC-RT. And even if it was a trial with a protocol describing treatment techniques and field borders, things happen and dose may have been delivered to the axilla when targetting the SC, according to technique.


Trying to draw conclusions on axillary recurrence rates from trials where (almost) all patients received ALND and then went on to receive regional RT or not and then trying to "project" these recurrences rates to the current setting of "sentinel-node-biopsy --> positive node --> what to do?" is not trivial. Certainly the axillary recurrence rates in high-risk patients, who were truly underrepresented in Z0011 and are now managedwith sentinel-node-biopsy without any further treatment of the axilla are higher. The nomograms clearly point out that these women have a chance of 30+% of further nodes in case of ALND. There is no way that not treating that subclinical disease has no impact on the further course of the disease. If it was that case, we wouldn't / shouldn't be doing post-BCS-RT for subclinical disease either.

 

[medgator]

Yeah I think most people in training now are routinely including the IM nodes when doing RNI now and like he said with the use of respiratory gating, the DVH looks pretty good.

I don't push it on left sided patients, personally, esp if we are talking low nodal burden in a pt with a lateral tumor