Extrapolating from Z11

[deleted4401]

So, a few of the breast surgeons we work with (both fellowship trained) have changed their practice. We've had 3 cases of patients treated with upfront mastectomy and sentinel lymph node biopsies. In these cases the patients had big T2 tumors and then would have 1 or 2 positive sentinel lymph nodes. Knowing our take on PMRT, based on the size of tumor and other factors, they'd presume we would offer PMRT (and in all these cases we would have). So, they end up omitting the dissection, the patient is sent for chemo, and then to us.

So, this is clearly not recommended by NCCN, nor is it standard of care for anyone. However, there is some logic to it. 1) Other than the breast surgery, the treatment is the same as Z11 and the burden of disease is similar. 2) Radiation works to treat microscopic axillary disease, as seen in B04 and the French axillary RT vs dissection trial. 3) If the patient is going to get PMRT anyway, the risk of lymphedema will be lower with SLN bx + RT compared to ALND + RT.

I've discussed with my partners and mentors, and we all agree that it isn't the right way to go about things. Is anyone else seeing this change in practice? Other than the obvious fact of it not being studied, does anyone have any good clinical reasoning to not do it? The problem with wrapping my head around it is that if these patients were included on Z11 and received comprehensive RT, I think they would have done fine. But, I just hate going off protocol so drastically.

-S

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[napoleondynamite]

I saw this trend as well in Philly with our breast surgeons. On a philosophical level, I kind of think it makes sense. In B04 pts were cN+ even and still did just as good without ALND.

I guess one question I have is whether this should affect the timing of RT vs chemo at all? In the sequencing studies, there was no difference, but pts had ALND.

 

[OTN]

I really think it's a step in the right direction, even though I agree it's getting a bit ahead of the data.

However, do we even have any good data that suggests a benefit to axillary dissection? Taking Z11, MA.20 and B04 all into account, I don't have any problem with trying to sterilize the axilla with radiation therapy.

 

[medgator]

Seems ok as long it's known that these pts will be getting RT afterwards (Big caveat that some med oncs/surgeons seem to forget when trying to extrapolate from that trial).

 

[Palex80]

My problem with having to "sterilize" the axilla, without having a proper axilla pathological staging is:
What do I do with the paraclavicular (or even internal mammary) nodes?

Do I use some nomogramm to decide if I have to treat or should I treat them always (at least the paraclavicular nodes)?
The German radiation therapy guidelines for breast cancer for example, state that if you decide to treat the axilla, then you should treat the paraclavicular nodes too.

I get the feeling, that we may end up seeing more pneumonitis than we did in the past couple of years and especially in younger left-sided patients and I hate having to treat lots of heart due to tangents designed to cover the axilla too.

It will probably still be less toxicity than it was 30 years ago, when people were treating 2D extensively, but people didn't have CT scans and DVHs back then, deomonstrating exactly how much healthy lung/heart tissue they were treating...


The whole problem is being further escalated due to the MA.20-data, that were presented as an abstract so far.
http://www.asco.org/ASCOv2/Meetings/Abstracts?vmview=abst_detail_view&confID=102&abstractID=79126

 

[deleted4401]

MA.20 really confuses me. Those patients all had full dissections and intermediate risk for recurrence, and the RT still provided a benefit, even in high risk T2N0 patients and that is just data that needs to be reported ASAP.

Yeah, if we have node positive patients that are having CW RT, the NCCN recommends that SCV/apex be treated, and says to consider IMN. I think most US docs would treat the former but not the latter. They don't have recommendations yet regarding what to do in the situation I mentioned above.

 

[Palex80]

Yeah, if we have node positive patients that are having CW RT, the NCCN recommends that SCV/apex be treated, and says to consider IMN. I think most US docs would treat the former but not the latter. They don't have recommendations yet regarding what to do in the situation I mentioned above.

I understand that NCCN recommends SCV/apex, but in Europe, most of us treat the chest wall only for patients with less than 3 involved axillary nodes in the postmastectomy setting (or at least we will be treating only the chest wall, until mature MA.20 data are available and extrapolated to post-mastectomy patients ).
RT to SCV/apex is usually reserved for patients with more than 3 positive nodes or other "high-risk features" like ECE or big cranially located primaries, etc.


The problem im my opinion are the "borderline" patients.
If you had a pT2 (2.5 cm) pN1 (1/18) cM0 G2 R0 who was treated with a mastectomy (for whatever reason), most European radiation oncologsts would treat that patient with post mastectomy RT for the chest wall only.
However, if the surgeons decided to ommit axillary staging you get a
pT2 (2.5 cm) pN1 (1/2) cM0 G2 R0 presented. The chest wall will be treated because of the positive node, but now I am faced with the question if I have to treat the paraclavicular fossa and the whole axilla.

The difference in terms of potential acute and long term toxicity through such an approach for the same patient are big. Lymphedema shouldn't be much of an issue, since the patient actually was spared from extensive axillary resection. But what about pneumonitis, fibrosis, coronary heart disease and (last but not least) the higher risk of secondary malignancies through larger volume irradiation (which may grow even larger, based on the fact that some people may opt to use IMRT to spare the heart/lungs?)?

I am

 

[medgator]

MA.20 really confuses me. Those patients all had full dissections and intermediate risk for recurrence, and the RT still provided a benefit, even in high risk T2N0 patients and that is just data that needs to be reported ASAP.

Yeah, if we have node positive patients that are having CW RT, the NCCN recommends that SCV/apex be treated, and says to consider IMN. I think most US docs would treat the former but not the latter. They don't have recommendations yet regarding what to do in the situation I mentioned above.

A lot of people I think just treat IMNs if they are involved/positive on a PET or CT, myself included.

 

[seper]

I have faced same situation and it worries me.
When a patient has a large primary tumor and 2/2 removed nodes are involved, probability of residual disease in axilla is close to 100%.
Despite NSABP B-04 data, I have very serious doubts that 50.4 Gy to the axilla is equivalent to full dissection.

 

[deleted4401]

Hmm... What about French trial for cN0 patients randomized to ALND vs RT? Very little difference in outcomes at 15 years, only difference was isolated axillary recurrence was 2% higher in RT arm. http://www.ncbi.nlm.nih.gov/pubmed/14701770?dopt=Abstract

Then, I came across another trial. It's a subset (>60, cN0, eligible for Tam). Randomized to dissection vs. observation. If they received RT, it was breast and did not include axilla. No difference in outcome, better QOL without dissection. http://www.ncbi.nlm.nih.gov/pubmed/16344321?dopt=Abstract

Finally, in CALGB 9343 (70 years and up, T1N0, ER+, randomized to RT vs no RT), these patients weren't to have any axillary staging (no SLN biopsy or dissection).

So, enough circumstantial data out there to make it a viable treatment option - (i.e. substitute axillary RT for dissection in undissected patients OR omitting axillary therapy completely in selected patients, typically older and receptor positive), but then you have MA.20 that nearly shows a survival benefit with just the additional of regional nodal treatment. It's very contradictory, and that's why it's tough when surgeons go off path to really understand what the patient outcomes will be, with or without treatment.

S

 

[seper]

Simul, these data that you are quoting apply only to low risk patients. Large T2 breast Ca with 2 metastatic LN is a different disease.

 

[deleted4401]

You're right, I sort of just glossed over the point you were trying to make. Sorry!

It's hard comparing b/c if your patient had SLN bx, they were cN0 and they would have been on B04 and maybe the other one, but not CALGB, depending on what "large" is, since they did not do SLN. But, if you're patient was cN+ and didn't get dissection, yeah that's a big problem.

S