PMRT case: Dose? Lymphatics or not?

[Palex80]

So here's an interesting case:

45 year old, premenopausal female with 2,4 cm pT4b (skin infiltration) pN1mi (1/2; sn) cM0 G2 micropapillary multicentric breast cancer, ablated with clear margins. The patient also had peritumoral extensive DCIS (>6cm), which has been also resected but with positive margins both in the cranial and the caudal margin.


How would you treat her?


Option 1:
Chest wall RT with something like 56 Gy.
I don't think you can go much higher, since the positive margins are rather hard to exactly localize and distributed over the chest wall in 2 directions. I am not very comfortable with giving 60 Gy over the entire chest wall.

Option 2:
Chest wall + Lymphatics (axilla/paraclavicular) up to around 46-50 Gy, then boost chest wall to 56 Gy.
Micropapillary cancer tends to spread early to nodals and I am not very comfortable with omitting nodal irradiation in a pN1mic (1/2;sn) patient.
The data on sentinel-lymph node for this kind of tumor with a lot of negativ prognostic factors is simply not there IMHO.


On the other hand if the surgeons had managed to clear out the DCIS completely, there could have been people who would have ommited PMRT.


Tough choice. What would you do?

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[Palex80]

Couple of things:
1. Is she going to get an ALND? I know the ACOSOG study but at my institution she would probably get an ALND to give you a better idea about the node status.

Nope. The surgeons declined it, when we asked. The microscopic involvement does not bother them. They would have done ALND, if it was a macroscopic metastasis. I know, I know... Let's just say they are "advice-resistant".

2. Even if she didn't have positive margins, with a 2.4 cm tumor + 6 cm DCIS in a 45 year old with T4 disease I would have offered PMRT to the chest wall. I dont know of many who wouldn't have offered this patient PMRT even without positive margins.

I would have too.
But there are certainly some colleagues who wouldn't have, pointing out, that it was just a pT4b because of the skin infiltration (which was quite focal, I forgot to mention that; not a major ulceration) and saying that only 1 lymph node was involved (and only microscopically).

As for your options, I would chose CW + LN. Im not sure if there is data to support adding the LN with N1mi (1/2) but in the absence of an ALND and node positive I would think to offer her regional + CW.

Me too.



Any idea what dose you would give?

 

[Cancerdancer]

Option 2. Chest wall + SC + PAB. The skin infiltration drives the stage, and trumps everything else. The DCIS has no bearing on the recommendation (i.e. I can't imagine not giving PMRT if it had been all cleared) except to perhaps warrant a slight dose escalation for positive margin areas, as you argue. Pts with skin invasion were included in the PMRT trials showing OS benefit, which all treated the LNs (though I'd skip the IMs), and I'm not aware of any data showing that nodes can/should be omitted in stage IIIb pts, regardless of the SLN results. Being node positive just makes the decision easier, IMO.

 

[seper]

I'd still argue that + DCIS margin is important (relapse rates up to 20% in WBRT studies), and boots the scar/bed to as high as possible dose (? 66 Gy).

 

[deleted4401]

Agree with Dancer's plan and reasoning.
As discussed before, boost in chest wall setting is controversial, but if any way to target, then why not? She's young and may get some benefit.
46 Gy to SCV/Level I-III, 50 to CW, 60 to areas of pos margin if possible to localize.
Not upset at all about not completing dissection - 1 node has already bought her chemo, regional RT that includes level I-III will take care of it.
S

 

[Ursus Martimus]

Not enough information and to make decisions without teasing out the details scares me. First, is the patient really T4b? Someone has to review the path to see what is meant by involvement or infiltarion of the skin.

Classifying Tumors with Dermal Involvement
If there are tumor cells in the dermis without skin ulceration, peau d’orange, edema, or satellite nodules, what is the stage?

Direct skin invasion by AJCC criteria is defined as full-thickness involvement including the epidermis. If the epidermis is intact with only focal dermal involvement, this is not considered T4 but classified by the size of the primary tumor.

Pathology from a lumpectomy revealed a 2 x 1.5-cm mass extending into the skin up to the superficial dermis, without invasion of the epidermis. Is it a T1c or a T4?

This would be classified as T1c. As described above, if the epidermis is intact with only focal dermal involvement, classification is based on the size of the primary tumor.

SO what is it? If the pt was really T4b without neoadjuvant treatment there was no invasive disease at the margins? Who resects people like that? If you are really in Europe, as the profile says there, I would be afraid to be a European women with breast cancer - yikes. What about receptor status? I think this patient has much potential to be over treated under the current unconfirmed assumptions and at very least, the surgeon screwed up.

 

[Palex80]

The pathologic report says that the epidermis was involved, but it was not a big ulceration, just a focal infiltration of the epidermis.
It was a T4b however per definition.
I understand your point and agree that T4b simply because of focal skin infiltration is not necessarily as "bad" as a "standard" T4.
In other words, I would be more worried about a 5,5 cm pT3, than about a 1,8 cm pT4b, that just happened to lie very superficially and only focally invaded the skin.


As far as neoaadjuvant treatment is considered, it was never brought up as an option apparently. There was no way the surgeons would manage a BCS, since the DCIS was that big. They went for mastectomy immediately. After all, there is no proven benefit for neoadjuvant chemo, if you are going to do a mastectomy anyway.


The problem was, that the DCIS was even bigger than they thought, so they ended up with positive margins. The invasive disease was completely removed.

I don't see why you would "be afraid to be a woman with breast cancer in Europe" or why the "surgeon screwed up". Close/positive margins can happen even with a mastectomy anywhere in the world.

 

[Ursus Martimus]

I think you miss the rationale for neoadj, which is not to convert to lumpectomy. It is to help get negative margins. If you thought someone was T4 up front in the US, surgery upfront is not standard. If the tumor was superficial and dermis was the margin, and given negative margins at surgery, one could make the argument for T2. I am not sure where T3 comes from??? Did you personally view the path? I still have not heard about chemo, do they give that where you are? All I have to say is thank God for American health care.

 

[Ursus Martimus]

I think you miss the rationale for neoadj, which is not to convert to lumpectomy. It is to help get negative margins. If you thought someone was T4 up front in the US, surgery upfront is not standard. If the tumor was superficial and dermis was the margin, and given negative margins at surgery, one could make the argument for T2. I am not sure where T3 comes from??? Did you personally view the path? I still have not heard about chemo, do they give that where you are? All I have to say is thank God for American health care.

 

[Cancerdancer]

I think you miss the rationale for neoadj, which is not to convert to lumpectomy. It is to help get negative margins. If you thought someone was T4 up front in the US, surgery upfront is not standard. If the tumor was superficial and dermis was the margin, and given negative margins at surgery, one could make the argument for T2. I am not sure where T3 comes from??? Did you personally view the path? I still have not heard about chemo, do they give that where you are? All I have to say is thank God for American health care.

Palex just told you that the pathology showed pT4b. They have pathologists in Europe, who are physicians, who read the path. And yes, they give chemo in Europe. BCT in a T4b patient with 6 cm of DCIS via NACT is unwise.

This patient sounds like they were managed appropriately. Only your recent string of comments on this thread are inappropriate.

 

[Ursus Martimus]

As far as neoaadjuvant treatment is considered, it was never brought up as an option apparently. There was no way the surgeons would manage a BCS, since the DCIS was that big. They went for mastectomy immediately. After all, there is no proven benefit for neoadjuvant chemo, if you are going to do a mastectomy anyway.

So I apologize for the tone but there are incorrect things that you can not deny. I suggest looking at NCCN guidelined, I heard they were pretty good. The studies that looked at neoadj vs adj chemo were in pts with T1-3 disease (ie NASBP B18). NOT T4, wrong data to quote. Chemo comes first for T4 disease. Please refer me to appropriate references if I wrong.

As far as what taking the face value of the path report as word of God in light of how significantly it changes the patient's treatment doesn't make you negligent, I do however think it makes you a poor doctor. You may beg to differ but that is how I trained. I liken it to not getting a post lumpectomy mammo after a patient with malignant calcs has a lumpectomy. It's a mater of patient advocacy. Some people are thorough and some rely solely on reports.

 

[Cancerdancer]

Chemo comes first for T4 disease. Please refer me to appropriate references if I wrong.

Yeah, good point. Fortunately these silly Europeans realize the difference between cT4 and pT4. The question was about pT4. Rad oncs who go look at the path themselves, and decide that they would've been able preoperatively to predict the pathology, and throw stones at their surgical and/or European rad onc colleagues, rather than address the issue at hand, don't seem to be doing anyone any favors.

As far as what taking the face value of the path report as word of God in light of how significantly it changes the patient's treatment doesn't make you negligent, I do however think it makes you a poor doctor. You may beg to differ but that is how I trained. I liken it to not getting a post lumpectomy mammo after a patient with malignant calcs has a lumpectomy. It's a mater of patient advocacy. Some people are thorough and some rely solely on reports.

BTW, there is little to no data to suggest post-lumpectomy mammo for invasive disease with calcs has any value, if the margins are negative. Nice paper and review of the relevant literature here: PMID 15170149. Of course, I look forward to your prospective references that guide your practice. As a patient advocate I like to not say "Oh I'm not sure all your cancer is removed" and put them through unnecessary painful tests with unneeded anxiety...

 

[deleted4401]

The current rationale for neoadjuvant therapy in most cases is for allowing for a lumpectomy ... There isn't any other reason to do it - it is not proven to be better in any scenario for other outcomes, but does give you prognostic info, if they get pCR.

In T4b with skin ulceration, you could give chemo first or you can do a mastectomy - it's not unresectable, so the order doesn't matter. You could make the argument that you are definitely going to give RT anyway, so neoadjuvant could at least help you out in seeing if it is responsive to the chemo. I don't see how either approach is better or worse, sounds like a physician/patient preference thing. Even though NCCN says preoperative chemo, they are not making an evidence-based recommendation. Can you point to data that indicates that preoperative treatment is better in any way for this patient? If not, I think as long as you can get an R0 resection, either way is fine.

I don't get how this has anything to do with American vs European medicine. And, although I value the NCCN guidelines, it also is not the word of God.

Jeez, the tone of this was nasty. Palex probably thinks, "Man, American doctors are a--holes."

S

 

[Palex80]

Jeez, the tone of this was nasty. Palex probably thinks, "Man, American doctors are a--holes."
S

Not really. Just UM.

 

[medgator]

The current rationale for neoadjuvant therapy in most cases is for allowing for a lumpectomy ... There isn't any other reason to do it - it is not proven to be better in any scenario for other outcomes, but does give you prognostic info, if they get pCR.

That was the other reason I was thinking of. It gives you more info than adjuvant therapy.

 

[Wallachia]

i'm pretty sure on oral boards for this case if u recommended surgery up front there would be issues

 

[Gfunk6]

i'm pretty sure on oral boards for this case if u recommended surgery up front there would be issues

True, but it has more to do with the examiners' bias than objective reality. There are no randomized trials looking at this scenario. What we do know is that compared to adjuvant chemo in locally advanced breast CA, neo-adjuvant chemo offers no OS benefit.

 

[Palex80]

"Seduction to Induction"

 

[Mandelin Rain]

Yeah, good point. Fortunately these silly Europeans realize the difference between cT4 and pT4. The question was about pT4. Rad oncs who go look at the path themselves, and decide that they would've been able preoperatively to predict the pathology, and throw stones at their surgical and/or European rad onc colleagues, rather than address the issue at hand, don't seem to be doing anyone any favors.

I found this thread to be rather interesting. I am unsure why the attack on our colleagues across the pond, but this post seemed very reasonable. It would be hard to justify recommending neoadjuvant chemotherapy in a patient with clinical T2 disease. The pathologic findings are certainly unfortunate for the patient and prognosis, however, hindsight is always 20/20. The question is how to proceed now. I agree that chest wall and SCV are warranted. The utility of the PAB has always baffled me, particulary in someone with a very low volume of nodal disease. Perhaps I'm overlooking something here...

 

[medgator]

Saw a post-menopausal lady pre-op with focal skin involvement/T4b disease from a unicentric 3 cm ER+/H2N- lesion. She likely had a luminal A type tumor considering the poor response after 3 cycles of AC. Surgeon took her to surgery and did a lumpectomy/quadrantectomy with >0.5 cm margins, epidermal involvement of tumor. My gut instinct is to be worried but I can't find any guidelines to say he was in the wrong for doing it unless the skin involvement was "in the context of inflammatory carcinoma".

I'm thinking daily scar bolus, maybe boost higher? Any thoughts?

 

[Burt Radnolds]

I can see why you are concerned, as I think we are somewhat conditioned to see skin involvement as an indication of more aggressive disease. However, I think background factors in this case matter. Was she undergoing yearly mammos? This sounds like it might have been a slow growing neglected tumor that just happened to be superficial enough to partially erode through the skin. Was there dermal LVSI? High grade? This might just fall into the "big dumb tumor" category. It sounds like the surgery was adequate with what I'm assuming involved excision of the overlying skin. I like the scar bolus idea, but do not feel strongly that more dose is required.

 

[Palex80]

Bolus on the scar is certainly a good idea. I'd do 16 Gy boost.