triple negative T1-2N0 (sln) Breast Ca in young patients

[Kroll2013]

Dear colleagues,
Is there any available data about the relapse pattern in young patients with early triple negative Breast Ca, T1-2N0 with only sentinel node?
any numbers about axillary/SCV relapse?
Do you think that adjuvant RT to the breast should include low level axilla ? or SCV?

---

Members don't see this ad.

 

[medgator]

Adjuvant chemotherapy and radiotherapy in triple-negative breast carcinoma: a prospective randomized controlled multi-center trial - PubMed

Patients received standard adjuvant chemotherapy plus radiation therapy was more effective than chemotherapy alone in women with triple-negative early-stage breast cancer after mastectomy.

pubmed.ncbi.nlm.nih.gov

Increased risk of locoregional recurrence for women with T1-2N0 triple-negative breast cancer treated with modified radical mastectomy without adjuvant radiation therapy compared with breast-conserving therapy - PubMed

Women with T1-2N0 TNBC treated with MRM without RT have a significant increased risk of LRR compared with those treated with BCT. Prospective studies are warranted to investigate the benefit of adjuvant RT after MRM in TNBC.

pubmed.ncbi.nlm.nih.gov

 

[Palex80]

MA-20 did include T2 N0. about 10% of all patients were T2 N0.
If you have a look at the (vastly underpowered, not pre-specified) subgroup analysis, it appears that patients with pN0 and/or ER/PR negative tumors have benefitted from regional nodal irradiation.

 

[Kroll2013]

Adjuvant chemotherapy and radiotherapy in triple-negative breast carcinoma: a prospective randomized controlled multi-center trial - PubMed

Patients received standard adjuvant chemotherapy plus radiation therapy was more effective than chemotherapy alone in women with triple-negative early-stage breast cancer after mastectomy.

pubmed.ncbi.nlm.nih.gov

Increased risk of locoregional recurrence for women with T1-2N0 triple-negative breast cancer treated with modified radical mastectomy without adjuvant radiation therapy compared with breast-conserving therapy - PubMed

Women with T1-2N0 TNBC treated with MRM without RT have a significant increased risk of LRR compared with those treated with BCT. Prospective studies are warranted to investigate the benefit of adjuvant RT after MRM in TNBC.

pubmed.ncbi.nlm.nih.gov

supposing that these patients were treated with 3D conformal so they received Rt to the low axilla at least, indirectly within the tangential fields.

MA-20 did include T2 N0. about 10% of all patients were T2 N0.
If you have a look at the (vastly underpowered, not pre-specified) subgroup analysis, it appears that patients with pN0 and/or ER/PR negative tumors have benefitted from regional nodal irradiation.

great. ty a lot.
I was asking because i am exceptionally using VMAT for this patient ( huge Breast, low inserted on the Chestwall). So i needed to decide whether to include nodes or not ; if it was with 3D conformal, low axilla would have received at least 70-80% dose unintentionally.

 

[Kroll2013]

wou

MA-20 did include T2 N0. about 10% of all patients were T2 N0.
If you have a look at the (vastly underpowered, not pre-specified) subgroup analysis, it appears that patients with pN0 and/or ER/PR negative tumors have benefitted from regional nodal irradiation.

would you recommend to cover SCV too?

 

[Palex80]

would you recommend to cover SCV too?

I would treat axilla and SCV.

The question is whether to cover IM or not. I would more likely do it, if you are treating the right side or you can spare the heart with adequate techniques when treating the left side (--> deep inspiration breath hold possible?). I would also more likely do it, if it was a central / medial located tumor.

 

[w00tz]

Yes to RNI if T2, high Ki-67, poor response to neoadjuvant chemo, +LVSI
Not sure if prone is an option. Worry about heart and contralateral breast dose in a young patient.

 

[thecarbonionangle]

Make sure you contour LAD and keep V15<10 (good heartncontouring atlases are out there). I don’t like breast IMRT. I bet your heart dose will be higher compared to 3D.

 

[TheWallnerus]

supposing that these patients were treated with 3D conformal so they received Rt to the low axilla at least, indirectly within the tangential fields.

great. ty a lot.
I was asking because i am exceptionally using VMAT for this patient ( huge Breast, low inserted on the Chestwall). So i needed to decide whether to include nodes or not ; if it was with 3D conformal, low axilla would have received at least 70-80% dose unintentionally.

Make sure you contour LAD and keep V15<10 (good heartncontouring atlases are out there). I don’t like breast IMRT. I bet your heart dose will be higher compared to 3D.

The reason to use VMAT will be to try to decrease inhomogeneity. But 115% inhomogeneity w/ 40/15 has same risk of late side effects as 50/25 w/ 110% inhomogeneity (do the math). Tangent-only approaches, w/ or w/o IMRT, usually best. I like breast IMRT a lot, as does most of the planet (I think); the issue is beam angles and how many shine (even just a little) into the heart and lungs. VMAT's got a lot of angles (so to speak) that shine into places fixed beams don't. I don't super-hate VMAT; I can simply, for breast, come up with equally OK plans a lot quicker and simpler without using it.

 

[Palex80]

Breast-VMAT for the win!

 

[fiji128]

Dear colleagues,
Is there any available data about the relapse pattern in young patients with early triple negative Breast Ca, T1-2N0 with only sentinel node?
any numbers about axillary/SCV relapse?
Do you think that adjuvant RT to the breast should include low level axilla ? or SCV?

This is a tough clinical case that I will get from time to time.

The current NCCN guidelines says that for pathologic T1-3 N0 M0 disease after breast conserving surgery and axillary staging to consider regional nodal irradiation in patient with central/medial tumors or tumors >2 with other high-risk features (young age or extensive LVI). I believe this statement is somewhat new in the guidelines and basically comes from the MA 20 and EORTC inclusion criteria/results.

That being said I would always do low axilla at a minimum even with pN0. Not sure I have ever done RNI with pN0 without adverse or very adverse factors present at the primary site. I don't think doing RNI in this scenario is something where there will be any sort of consensus on if you were to survey rad oncs.

 

[TheWallnerus]

View attachment 333348View attachment 333349

Breast-VMAT for the win!

They can look very good. But you're IMNing here Also should help COVID in her left lung if she has it asymptomatically (double smile emoji)

 

[Palex80]

They can look very good. But you're IMNing here Also should help COVID in her left lung if she has it asymptomatically (double smile emoji)

I thought LDRT works well against COVID! Didn't you read all the Emory-papers?

 

[evilbooyaa]

Assuming upfront surgery:
I personally, would not treat RNI in a T1N0 TNBC patient with negative SLN.
I would consider RNI in a T2N0 TNBC patient with negative SLN, but probably skip it.

Assuming neoadjuvant chemotherapy in a cT1-2N0 TNBC patient
I would not treat RNI in a ypT0/isN0 patient.
I would consider RNI in a cT2/ypT1 patient, but probably skip it.
I would consider RNI in a cT1/ypT1 patient (depending on extent of primary tumor response), but would probably skip it.
I would probably treat RNI in a cT2/ypT2 patient. I would cover IMNs if the tumor was medial in location.

I do not blanket apply MA.20/EORTC inclusion criteria to all my patients.

supposing that these patients were treated with 3D conformal so they received Rt to the low axilla at least, indirectly within the tangential fields.

great. ty a lot.
I was asking because i am exceptionally using VMAT for this patient ( huge Breast, low inserted on the Chestwall). So i needed to decide whether to include nodes or not ; if it was with 3D conformal, low axilla would have received at least 70-80% dose unintentionally.

If using VMAT, I would draw out what would be covered in low axilla if you were to treat in 3D and cover that as well.

If separation is your issue, can you mix in higher beam energies for heterogeneity? I really, REALLY hate VMAT for IMRT breast. I routinely see mean heart doses above 3-4 Gy when patients are getting IMRT (even as high as MHD of 10Gy!) and it's just unnecessary. If you want to do IMRT, then do fixed beam angle, sliding window and it'll get you the homogeneity you need. Even say 5-field or mini-arcs can work if necessary.

View attachment 333348View attachment 333349

Breast-VMAT for the win!

What's the MHD on that? Contralateral breast getting 25% of Rx dose less than ideal as well in a young patient as described in OP! I remember previous discussioni on this - I think you would routinely use very small mini arcs to avoid pooching of the V20 line into the lung (which I see all the time when VMAT is used routinely)?

 

[Palex80]

What's the MHD on that? Contralateral breast getting 25% of Rx dose less than ideal as well in a young patient as described in OP! I remember previous discussioni on this - I think you would routinely use very small mini arcs to avoid pooching of the V20 line into the lung (which I see all the time when VMAT is used routinely)?

MHD is 4.5 Gy from the main plan. Boost with 8 x 2 Gy adds another 0.25 Gy.
Indeed, contralateral breast is an issue. You see it's contured, but still the most medial part receives 10+ Gy.

Please, do consider that contours in Europe are generally a bit more "generous" that in the US. I believe many of you would not contour the IM-CTV with such a margin and would accept less dose coverage there.

 

[Krukenberg]

MHD is 4.5 Gy from the main plan. Boost with 8 x 2 Gy adds another 0.25 Gy.
Indeed, contralateral breast is an issue. You see it's contured, but still the most medial part receives 10+ Gy.

Please, do consider that contours in Europe are generally a bit more "generous" that in the US. I believe many of you would not contour the IM-CTV with such a margin and would accept less dose coverage there.

The RADCOMP atlas has IMN volume similar to yours, but don’t know how far that’s diffused into the community

 

[Palex80]

The RADCOMP atlas has IMN volume similar to yours, but don’t know how far that’s diffused into the community

True.

However, it seems that even some protocols like RTOG 1304 call for very tight PTV margins around the IM-CTV. I do not have the full protocol, but here's something I found online. Have a look at the lower left image. That's a 0mm CTV-PTV-margin in the anterior/posterior direction, or am I mistaken?

 

[TheWallnerus]

True.

However, it seems that even some protocols like RTOG 1304 call for very tight PTV margins around the IM-CTV. I do not have the full protocol, but here's something I found online. Have a look at the lower left image. That's a 0mm CTV-PTV-margin in the anterior/posterior direction, or am I mistaken?
View attachment 333411

Looks zero-ish AP/PA, but few mm side-to-side. In other words totally not a "true" PTV per ICRU or per Stroom and Heijmen or per Schallenkamp or who the heck ever. But hey, it's a "margin." Sometimes these protocolists aren't margin purists by any stretch. Because there is such a WIDE variation in margin approaches/definitions/implementation in many sites, diseases, stages, etc., but rather pretty uniform outcomes, it makes you wonder about all the arguing over margins, especially a few mm here or there, that we do.

 

[fiji128]

True.

However, it seems that even some protocols like RTOG 1304 call for very tight PTV margins around the IM-CTV. I do not have the full protocol, but here's something I found online. Have a look at the lower left image. That's a 0mm CTV-PTV-margin in the anterior/posterior direction, or am I mistaken?

I read this a while back. A good article talking about the differences between RTOG and RADCOMP volumes.

"Comparison of Nodal Target Volume Definition in Breast Cancer Radiation Therapy According to RTOG Versus ESTRO Atlases: A Practical Review From the TransAtlantic Radiation Oncology Network (TRONE)"

DEFINE_ME

"In this review, we will discuss and compare the RTOG and ESTRO nodal target volume guidelines and their respective relevance in the context of contemporary data on patterns of locoregional relapse to improve clinical implementation of these target volume delineation guidelines."

 

[Ray D. Ayshun]

How are people treating cT3N0 triple negative breast cancers following neoadjuvant chemo, age >65, breast conservation vs mastectomy? There are arguments to do pretty much anything, as with all breast cancer, but I have a patient on her way to a ypT0/1N0 response, who's weighing both options surgically.

 

[Palex80]

How are people treating cT3N0 triple negative breast cancers following neoadjuvant chemo, age >65, breast conservation vs mastectomy? There are arguments to do pretty much anything, as with all breast cancer, but I have a patient on her way to a ypT0/1N0 response, who's weighing both options surgically.

This is actually surgical terrain, so I rarely see these patients prior to surgery.
Data is lacking on how to incorporate response to neoadjuvant chemotherapy in this special population to guide RT, so we advise for PMRT even if ypT0 in triple negative disease. We wouldn't treat lymphatics though, if cN0 and pN0.
I think BCS+RT is a very good option for this patient, if a good cosmesis is achievable.

There is some SEER-data showing favorable results with BCS+RT vs. mastectomy.

The different outcomes between breast-conserving surgery and mastectomy in triple-negative breast cancer: a population-based study from the SEER 18 database

Breast-conserving surgery (BCS) including radiotherapy (RT) has been demonstrated to provide at least equivalent prognosis to mastectomy in early-stage breast cancer. However, studies on triple-negative breast cancer (TNBC) patients are relatively scarce. ...

www.ncbi.nlm.nih.gov

I know, I know, it's SEER...

 

[Ray D. Ayshun]

This is actually surgical terrain, so I rarely see these patients prior to surgery.
Data is lacking on how to incorporate response to neoadjuvant chemotherapy in this special population to guide RT, so we advise for PMRT even if ypT0 in triple negative disease. We wouldn't treat lymphatics though, if cN0 and pN0.
I think BCS+RT is a very good option for this patient, if a good cosmesis is achievable.

There is some SEER-data showing favorable results with BCS+RT vs. mastectomy.

The different outcomes between breast-conserving surgery and mastectomy in triple-negative breast cancer: a population-based study from the SEER 18 database

Breast-conserving surgery (BCS) including radiotherapy (RT) has been demonstrated to provide at least equivalent prognosis to mastectomy in early-stage breast cancer. However, studies on triple-negative breast cancer (TNBC) patients are relatively scarce. ...

www.ncbi.nlm.nih.gov

I know, I know, it's SEER...

Sure, but nact confounds this approach, such that I'm having trouble deriving the benefit of pmrt for complete or near complete pathologic response. Is there a path response that would prompt rni for you with respect to the primary, presuming negative nodes?

 

[Palex80]

Sure, but nact confounds this approach, such that I'm having trouble deriving the benefit of pmrt for complete or near complete pathologic response. Is there a path response that would prompt rni for you with respect to the primary, presuming negative nodes?

We recommend treating the chest wall in cT3 cN0 triple negative post NACT even if ypT0 pN0.
We would add RNI most of the times if the patient initially had cN+ disease.
There is a gray area there too, which means that if we had a preoperative PET-CT showing a single small node and nothing more and the surgeon took that node out with a targetted axillary dissection post NACT and both the node and the primary showed a pCR, then we may ommit RNI and go for chest wall only. But if more than 1 node preoperatively and of course if not ypN0, we would do RNI.

I am aware than in the US there is long tradition of doing RNI most of the times when doing PMRT. This is also the case in some parts of Europe.
We are less strict for that and try to divide between indication for PMRT and indication for RNI.

 

[Ray D. Ayshun]

We recommend treating the chest wall in cT3 cN0 triple negative post NACT even if ypT0 pN0.
We would add RNI most of the times if the patient initially had cN+ disease.
There is a gray area there too, which means that if we had a preoperative PET-CT showing a single small node and nothing more and the surgeon took that node out with a targetted axillary dissection post NACT and both the node and the primary showed a pCR, then we may ommit RNI and go for chest wall only. But if more than 1 node preoperatively and of course if not ypN0, we would do RNI.

I am aware than in the US there is long tradition of doing RNI most of the times when doing PMRT. This is also the case in some parts of Europe.
We are less strict for that and try to divide between indication for PMRT and indication for RNI.

Right, but I mean, you'd only treat nodes if positive? For instance, ypT1N0 still gets chest wall only? And yes, you are right about PMRT in the US, at least wrt my training, it's all or none.

 

[Palex80]

Right, but I mean, you'd only treat nodes if positive? For instance, ypT1N0 still gets chest wall only? And yes, you are right about PMRT in the US, at least wrt my training, it's all or none.

Indeed, for a cT3 cN0 that after NACT was a ypT1 pN0 we would advise for RT of the chest wall only.

 

[evilbooyaa]

I am aware than in the US there is long tradition of doing RNI most of the times when doing PMRT. This is also the case in some parts of Europe.
We are less strict for that and try to divide between indication for PMRT and indication for RNI.

Bingo.

cT3N0 TNBC I am recommending 3-field PMRT regardless of response. Someone really wants to omit RT, we can talk about it if they had a PCR. Someone had an ax dissection and really wants to avoid lymphedema then I'll skip the 3-field. But most of the time these will be Mastectomy + SLNB after good clinical response to NAC, and those I'll prefer PMRT + RNI. No randomized data in the NAC era of course...

 

[Ray D. Ayshun]

So as not to hijack the other thread, and only kind of hijack this one (though remaining on the topic of breast cancer being the worst), here's some "sort of" data:

https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.e12625

0/29 LRR at 5 years in N0 women with PCR and breast conserving therapy (No RNI), which speaks to Palex's mention of chest wall only RT.

DEFINE_ME

No benefit in pre-chemo stage I or II

DEFINE_ME

0/4 with PCR had LRR when undergiong obs (lol, I know)

Obv the last paper showing 0/4 is laughable, but at the same time there were only 4 with a PCR, which get grouped in with everyone that fits the paper's title, but also might represent the absolute most favorable biology. IOW, there is likely a massive chasm between ypT0 and ypT1 and more of a jumpable ditch between ypT1 and ypT2, perhaps similar to some of our old dose-finding studies. In any case, I'm dumbfounded that there aren't more data about this scenario (cT3N0 -> ypT0N0).

 

[FrostyHammer]

How are people treating cT3N0 triple negative breast cancers following neoadjuvant chemo, age >65, breast conservation vs mastectomy? There are arguments to do pretty much anything, as with all breast cancer, but I have a patient on her way to a ypT0/1N0 response, who's weighing both options surgically.

Honestly, this is a good case to do BCS because I'd definitely lean towards RT regardless of surgery approach, and even though PMRT is controversial, after BCS it's a slam dunk. RNI after BCS is difficult for these cases. If the grade is high and/or ER- it'd make me want to do RNI more. If you're planning PMRT (with RNI) then ask the surgeon to do SLN and not ALND.

In either case, I'm hypofractionating 100%. If you're one of those people who doesn't hypofractionate PMRT, then all the more reason to do BCS.

 

[mheat3]

If you're one of those people

 

[Ray D. Ayshun]

Odds are I'm one of those people, being as it's most people.