PBI in N1mi (actual radiation question)

[Ray D. Ayshun]

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We should have a sub-forum where we ask radiation questions... Have a lady with a RUOQ T1N1mi ER/PR+ breast cancer s/p lumpectomy and SLNB with microscopic disease in the SLN. She has lupus with some mild cutaneous manifestations on plaquenil. She doesn't want mastectomy, and have discussed risks. The cavity with margin and level 1/2 could be treated pretty conveniently instead of WBRT, sparing a ton of tissue. Was wondering if this sounds reasonable in this setting.

 

[seper]

So she had a micrometer in one of the sentinel nodes? I would not target axilla at all. It is up to hormones to address micrometastatic disease.

 

[Ray D. Ayshun]

So she had a micrometer in one of the sentinel nodes? I would not target axilla at all. It is up to hormones to address micrometastatic disease.

I've seen/heard arguments in both directions re this, including Dr. Beriwal on the mednet recommending opening tangents up to get 1 and 2.

Could I just as easily argue that doing nothing more to the breast or axilla would be the right approach if we're saying endocrine therapy will address microscopic disease?

 

[evilbooyaa]

Would do WBI with high tangents for N1mi. I think import low PBI including coverage of level 1/2 is not unreasonable given concerns for lupus toxicity but I also think rt toxicity with homogeneous planning in lupus is more dogma fears than truly evidence based.

We don't need another subforum for case discussions, IMO.

Re reviewing import low, 3 percent of patients were pN1 so it's a very small subset but maybe not unreasonable to treat just cavity.

 

[Radonc90]

Agree with seper.

Most med onc ignores the Nmic stuff, the significance of Nmic is questionable anyway.
I'd agree with PBI and endocrine Rx.

 

[Ray D. Ayshun]

The added confounder was lupus on treatment with some minor, not bothersome, skin manifestations. Ignore that and go forward? I'm comfortable with lupus, but less so with skin involvement.

Also, kinda joking about subforum. Making a reference to the fact that all our threads now focus on the suckiness of the leadership and job consequences, as opposed to the practice consequences of the trials created by those same leaders that are so convoluted we can do anything or nothing with equal efficacy. Technically, import low applies to patients with up to 3+ sons given inclusion criteria. Not sure anyone would actually do that in practice though. But, I digress and just derailed my own thread.

 

[scarbrtj]

We should have a sub-forum where we ask radiation questions... Have a lady with a RUOQ T1N1mi ER/PR+ breast cancer s/p lumpectomy and SLNB with microscopic disease in the SLN. She has lupus with some mild cutaneous manifestations on plaquenil. She doesn't want mastectomy, and have discussed risks. The cavity with margin and level 1/2 could be treated pretty conveniently instead of WBRT, sparing a ton of tissue. Was wondering if this sounds reasonable in this setting.

There's an orgy of data that now essentially forms a kind of a "law" in my mind that the biology and behavior of T1N1mi ER/PR+ is EXACTLY the same as N0. If you can make that mental leap, you have the answer to your question. Also, so propitious that she's taking plaquenil and won't have to worry 'bout COVID 😉.

 

[Ray D. Ayshun]

There's an orgy of data that now essentially forms a kind of a "law" in my mind that the biology and behavior of T1N1mi ER/PR+ is EXACTLY the same as N0. If you can make that mental leap, you have the answer to your question. Also, so propitious that she's taking plaquenil and won't have to worry 'bout COVID 😉.

Yep, I've told her she doesn't even have to wear a mask in the clinic.

 

[Ray D. Ayshun]

There's an orgy of data that now essentially forms a kind of a "law" in my mind that the biology and behavior of T1N1mi ER/PR+ is EXACTLY the same as N0. If you can make that mental leap, you have the answer to your question. Also, so propitious that she's taking plaquenil and won't have to worry 'bout COVID 😉.

Also, what's the data, or at least some of the data you're referring to? As much as I believe in data, there is something different to me deep down about Nanything vs N0. Obviously, sampling error can factor into this, but it's a big step biologically to go from local invasion to surviving a journey down a lymph vessel and buying some real estate in a node, even if it's just a double-wide.

 

[StIGMA]

Idea is that the cancer hasn’t transformed / de-differentiated enough to not need breast stroma support. N1mi hasn’t taken up a home in the nodes / isn’t flourishing there — remove the primary (or add hormones) or maybe even sample on a different day while doing nothing — those cells die on their own.

there’s ample trial evidence/ suggestion that more significant unaddressed nodal disease can die off in breast cancer

of course you can’t tell the patient certainties, but there’s good rationale for essentially ignoring forms of nodal disease

 

[RickyScott]

We should have a sub-forum where we ask radiation questions... Have a lady with a RUOQ T1N1mi ER/PR+ breast cancer s/p lumpectomy and SLNB with microscopic disease in the SLN. She has lupus with some mild cutaneous manifestations on plaquenil. She doesn't want mastectomy, and have discussed risks. The cavity with margin and level 1/2 could be treated pretty conveniently instead of WBRT, sparing a ton of tissue. Was wondering if this sounds reasonable in this setting.

I would favor your approach- cavity and low axilla in one field and have done so in similar situations.

 

[communitydoc13]

I think your plan is fine. Also lumpectomy bed alone is fine. For N1mic, there is data indicating a prognostic impact (somewhere between N0 and N1) disease. For understanding of impact of nodal radiation on N1 disease, one can look at long term post-mastectomy data.

http://download.thelancet.com/pdfs/journals/lancet/PIIS0140673614604888.pdf

.

I have never met Beriwal, but he seems incredibly smart and humble online. His PRO paper on standardizing high tangents vs SCLAV is helpful for standardizing clinic practice (we use it), but defaults to high tangents for N1mic. I have a hard time not following Beriwal's recs.

I am convinced that for ER+ (luminal) disease, XRT is impacting late recurrences. These are a big deal and continue almost monotonically after 5 years. I sometimes wonder if late recurrences are underestimated as: 1. It's really hard to detect a local recurrence on exam and 2: competing risks decrease importance of recurrence and vigilance of exam in older patient.

 

[scarbrtj]

Also, what's the data, or at least some of the data you're referring to? As much as I believe in data, there is something different to me deep down about Nanything vs N0. Obviously, sampling error can factor into this, but it's a big step biologically to go from local invasion to surviving a journey down a lymph vessel and buying some real estate in a node, even if it's just a double-wide.

OK. Let me start. Leave it to you to Google this:
1) 10% of DCIS patients are Nanything
2) ~30% of T1N0 patients have a positive bone marrow biopsy

Be careful about using too much logic in breast cancer, it's a honey trap. Fisher showed that the "lymph node journey" story is (for the most part) a false flag.

 

[RickyScott]

OK. Let me start. Leave it to you to Google this:
1) 10% of DCIS patients are Nanything
2) ~30% of T1N0 patients have a positive bone marrow biopsy

Be careful about using too much logic in breast cancer, it's a honey trap. Fisher showed that the "lymph node journey" story is (for the most part) a false flag.

You can make convincing argument for partial breast alone, but in pts on immunosuppressive agent, could be dealing with more aggressive biology which would sway me to cover nodes with partial breast.

 

[Ray D. Ayshun]

OK. Let me start. Leave it to you to Google this:
1) 10% of DCIS patients are Nanything
2) ~30% of T1N0 patients have a positive bone marrow biopsy

Be careful about using too much logic in breast cancer, it's a honey trap. Fisher showed that the "lymph node journey" story is (for the most part) a false flag.

I'd argue that 0% of those dcis patients have only dcis. Kinda like a path report in a n+ patient that says no lvsi. I can't find the 30% reference. I'll grant you the the old nsabp findings, and can't argue with the more recent studies that support them. I will say I feel more justified in being more aggressive with the nodes after considering rickyscott's point.

 

[scarbrtj]

I'd argue that 0% of those dcis patients have only dcis. Kinda like a path report in a n+ patient that says no lvsi. I can't find the 30% reference. I'll grant you the the old nsabp findings, and can't argue with the more recent studies that support them. I will say I feel more justified in being more aggressive with the nodes after considering rickyscott's point.

To each his own 🙂 Your point about 0% N+ rate in "pure DCIS" is not borne out by the data (strange as the data is). And we don't worry about the axilla in DCIS. I am also not sure one *has* to have LVSI to be N+, just like one doesn't HAVE to have LVSI to be subclinically M1; there are many pT1N0 -LVSI patients with undiscovered cancer cells in the marrow e.g. The idea that there is stepwise progression of primary to node to systemic disease, and that the nodes are somehow an intermediate halfway house of sorts, is a persistent illusion in breast cancer. It's not a COMPLETE illusion, but it's much more illusion than reality. AFAIK treatment of the axilla in T1N0, or T1N1, or T1N1mi, whether by completion surgery or irradiation, changes very, very little. We already know it changes ~nothing in outright pN1 (of the many N1 women who got zilch-o radiation at all in Z0011, in violation, I think the axillary recurrence rate was 0-1%). I think we'd all agree it's "proven" not to budge survival. There may be (is) some effect on isolated axillary recurrences; the NNT is about 50. In other words, there's a ~2% chance that if you intervene in the axilla here you will affect LRC.

 

[Palex80]

AFAIK treatment of the axilla in T1N0, or T1N1, or T1N1mi, whether by completion surgery or irradiation, changes very, very little. We already know it changes ~nothing in outright pN1 (of the many N1 women who got zilch-o radiation at all in Z0011, in violation, I think the axillary recurrence rate was 0-1%). I think we'd all agree it's "proven" not to budge survival. There may be (is) some effect on isolated axillary recurrences; the NNT is about 50. In other words, there's a ~2% chance that if you intervene in the axilla here you will affect LRC.

Oh, no!!! We are going to have that argument again!

 

[evilbooyaa]

I believe there is data that N1mi has an effect similar to N1, while isolated tumor cells are more similar to N0.... hence why staging has defined ITC as N0, and micromets are N1.

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The prognostic significance of micrometastases in breast cancer: a SEER population-based analysis - PubMed

Nodal micrometastasis of breast cancer carries a prognosis intermediate to N0 and N1 disease, even after adjusting for tumor- and patient-related factors. Prospective study is warranted and the results of pending trials are highly anticipated. Until then adjuvant therapy trials should consider...

pubmed.ncbi.nlm.nih.gov

If N0 = normal tangents and N1 = 3-field, then N1mi = high tangents seems like a very reasonable middle ground.

 

[scarbrtj]

I believe there is data that N1mi has an effect similar to N1, while isolated tumor cells are more similar to N0.... hence why staging has defined ITC as N0, and micromets are N1.

Error - Cookies Turned Off

onlinelibrary.wiley.com

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onlinelibrary.wiley.com

The prognostic significance of micrometastases in breast cancer: a SEER population-based analysis - PubMed

Nodal micrometastasis of breast cancer carries a prognosis intermediate to N0 and N1 disease, even after adjusting for tumor- and patient-related factors. Prospective study is warranted and the results of pending trials are highly anticipated. Until then adjuvant therapy trials should consider...

pubmed.ncbi.nlm.nih.gov

If N0 = normal tangents and N1 = 3-field, then N1mi = high tangents seems like a very reasonable middle ground.

but how do you pull off high tangents when your intent is PBI.

Oh, no!!! We are going to have that argument again!

There is no guideline that recommends XRT intervention in the axilla in the setting of N1mi, and I think all the guidelines (now) say don't surgerize it. We did a randomized trial in N1mi, and ~90/450 N1mi (and no ALND) patients got no breast/axilla irradiation or just cavity IORT. There was a ~4/450 isolated axillary recurrence rate in the no ALND group (and a ~1/450 rate in the ALND group). Even if we say ALLLLLL the axillary recurrences in the no ALND arm happened in the N=~90 "no axillary RT" subset (which I think is highly unlikely), we are still talking <5% risk of isolated axillary recurrence. Of course in reality it's likely those ~4 recurrences were spread out over the entire ~450 patients and not just the ~90 "no axillary RT" patients.

But also worth noting: what's patient's age, what was the mammaprint etc.

 

[evilbooyaa]

but how do you pull off high tangents when your intent is PBI.

I mean the case described an UOQ tumor. Could contour level 1/2 of axilla and cover that along with cavity if desired with 'mini tangents'. I personally would not be enthusiastic for it, but given the concerns for lupus-with-skin-manifestations and potential risk for toxicity from OP.

 

[Palex80]

There is no guideline that recommends XRT intervention in the axilla in the setting of N1mi, and I think all the guidelines (now) say don't surgerize it. We did a randomized trial in N1mi, and ~90/450 N1mi (and no ALND) patients got no breast/axilla irradiation or just cavity IORT. There was a ~4/450 isolated axillary recurrence rate in the no ALND group (and a ~1/450 rate in the ALND group). Even if we say ALLLLLL the axillary recurrences in the no ALND arm happened in the N=~90 "no axillary RT" subset (which I think is highly unlikely), we are still talking <5% risk of isolated axillary recurrence. Of course in reality it's likely those ~4 recurrences were spread out over the entire ~450 patients and not just the ~90 "no axillary RT" patients.

Have a blast scarb

ECE and Z11. Has anything changed?

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.

forums.studentdoctor.net

 

[scarbrtj]

I mean the case described an UOQ tumor. Could contour level 1/2 of axilla and cover that along with cavity if desired with 'mini tangents'. I personally would not be enthusiastic for it, but given the concerns for lupus-with-skin-manifestations and potential risk for toxicity from OP.

I suppose it's a "middle ground..." but it ~triples, or more, the irradiated volume (vs doing traditional PBI) with an XRT intervention essentially proven not to increase survival.

 

[scarbrtj]

Have a blast scarb

ECE and Z11. Has anything changed?

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.

forums.studentdoctor.net

well as you know breast is very nuanced; N1miECE is TOTALLY different than N1mi 😉

 

[Ray D. Ayshun]

but how do you pull off high tangents when your intent is PBI.


There is no guideline that recommends XRT intervention in the axilla in the setting of N1mi, and I think all the guidelines (now) say don't surgerize it. We did a randomized trial in N1mi, and ~90/450 N1mi (and no ALND) patients got no breast/axilla irradiation or just cavity IORT. There was a ~4/450 isolated axillary recurrence rate in the no ALND group (and a ~1/450 rate in the ALND group). Even if we say ALLLLLL the axillary recurrences in the no ALND arm happened in the N=~90 "no axillary RT" subset (which I think is highly unlikely), we are still talking <5% risk of isolated axillary recurrence. Of course in reality it's likely those ~4 recurrences were spread out over the entire ~450 patients and not just the ~90 "no axillary RT" patients.

But also worth noting: what's patient's age, what was the mammaprint etc.

Based on the stats class I took with Dr Hahn, for every 100 women I treat 300 will not have an axilla only recurrence.

 

[scarbrtj]

Based on the stats class I took with Dr Hahn, for every 100 women I treat 300 will not have an axilla only recurrence.
View attachment 317845

this is actually what I quote too

 

[Ray D. Ayshun]

this is actually what I quote too

Can I make photoshop requests?

My previous two would look good together.

 

[scarbrtj]

Can I make photoshop requests?
View attachment 317847
My previous two would look good together.

I might have to mow his lawn one day... I'd better demur.

 

[RSAOaky]

How old is the patient?

I think a lot of the reservations about treating patients with SLE are at best loosely evidence based. It's such a heterogeneous disease and while there may be some patients who have more toxicity this has not been the case in the handful of patients I have treated. While most of us don't intentionally treat N1mi as N+, a typical tangent does at least partially include the low axilla. High tangents are a good compromise between treating the patient and treating the physician.

I would be hesitant to hypofractionate someone with SLE though I think this is likely more based in lore than reality, and I would be hesitant to offer partial breast treatment to someone with at least some evidence of nodal disease (LVSI alone is cautionary per ASTRO guidelines). The sad reality is that the treatment that is probably the most evidence based would be conventional whole breast treatment. While IMPORT LOW did permit patients with 1-3 nodes but this made up only 4% of the trial. Another possible compromise would be to treat per test arm 1 of IMPORT LOW which was a typical tangent to 36 Gy with a SIB to the partial breast volume to 40 Gy in 15 fractions.

 

[scarbrtj]

How old is the patient?

I think a lot of the reservations about treating patients with SLE are at best loosely evidence based. It's such a heterogeneous disease and while there may be some patients who have more toxicity this has not been the case in the handful of patients I have treated. While most of us don't intentionally treat N1mi as N+, a typical tangent does at least partially include the low axilla. High tangents are a good compromise between treating the patient and treating the physician.

I would be hesitant to hypofractionate someone with SLE though I think this is likely more based in lore than reality, and I would be hesitant to offer partial breast treatment to someone with at least some evidence of nodal disease (LVSI alone is cautionary per ASTRO guidelines). The sad reality is that the treatment that is probably the most evidence based would be conventional whole breast treatment. While IMPORT LOW did permit patients with 1-3 nodes but this made up only 4% of the trial. Another possible compromise would be to treat per test arm 1 of IMPORT LOW which was a typical tangent to 36 Gy with a SIB to the partial breast volume to 40 Gy in 15 fractions.

Age would be pretty key here. 'Cause in a 68yo with lupus with cutaneous manifestations and very favorable biology (ie in this case a very low Mammaprint), I'm going *gasp* to observe a T1N0. And favorable T1N0 is an intellectual inch (maybe two) away from favorable T1N1mi. Aside: I was discussing with a med student today how far we've come in breast cancer recently. Twenty years ago, this lady probably would have had a completion axillary dissection and whole breast to ~50 Gy plus a ~10 Gy (or 16!) cavity boost... and, depending on age, that might've been after ACT chemotherapy! Now we can offer none of that and more or less cogently discuss observation (with anti-E therapy)? Science... it's a helluva thing.

 

[evilbooyaa]

I'd argue that 0% of those dcis patients have only dcis. Kinda like a path report in a n+ patient that says no lvsi. I can't find the 30% reference. I'll grant you the the old nsabp findings, and can't argue with the more recent studies that support them. I will say I feel more justified in being more aggressive with the nodes after considering rickyscott's point.

I was not actively looking for this, but happened to come across it by chance today, and it made me remember the bolded claim scarb has made a few times in this forum:

Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer - PubMed

The presence of occult cytokeratin-positive metastatic cells in bone marrow increases the risk of relapse in patients with stage I, II, or III breast cancer.

pubmed.ncbi.nlm.nih.gov

This is Stage I-III breast Ca compared to non-malignant pts

Results: "Cytokeratin-positive cells were detected in the bone marrow specimens of 2 of the 191 control patients with nonmalignant conditions (1 percent) and 199 of the 552 patients with breast cancer (36 percent). The presence of occult metastatic cells in bone marrow was unrelated to the presence or absence of lymph-node metastasis (P=0.13). After four years of follow-up, the presence of micrometastases in bone marrow was associated with the occurrence of clinically overt distant metastasis and death from cancer-related causes (P<0.001), but not with locoregional relapse (P=0.77). Of 199 patients with occult metastatic cells, 49 died of cancer, whereas of 353 patients without such cells, 22 died of cancer-related causes (P<0.001). Among the 301 women without lymph-node metastases, 14 of the 100 with bone marrow micrometastases died of cancer-related causes, as did 2 of the 201 without bone marrow micrometastases (P<0.001). The presence of occult metastatic cells in bone marrow, as compared with their absence, was an independent prognostic indicator of the risk of death from cancer (relative risk, 4.17; 95 percent confidence interval, 2.51 to 6.94; P<0.001), after adjustment for the use of systemic adjuvant chemotherapy. "

 

[scarbrtj]

I was not actively looking for this, but happened to come across it by chance today, and it made me remember the bolded claim scarb has made a few times in this forum:

Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer - PubMed

The presence of occult cytokeratin-positive metastatic cells in bone marrow increases the risk of relapse in patients with stage I, II, or III breast cancer.

pubmed.ncbi.nlm.nih.gov

This is Stage I-III breast Ca compared to non-malignant pts

Results: "Cytokeratin-positive cells were detected in the bone marrow specimens of 2 of the 191 control patients with nonmalignant conditions (1 percent) and 199 of the 552 patients with breast cancer (36 percent). The presence of occult metastatic cells in bone marrow was unrelated to the presence or absence of lymph-node metastasis (P=0.13). After four years of follow-up, the presence of micrometastases in bone marrow was associated with the occurrence of clinically overt distant metastasis and death from cancer-related causes (P<0.001), but not with locoregional relapse (P=0.77). Of 199 patients with occult metastatic cells, 49 died of cancer, whereas of 353 patients without such cells, 22 died of cancer-related causes (P<0.001). Among the 301 women without lymph-node metastases, 14 of the 100 with bone marrow micrometastases died of cancer-related causes, as did 2 of the 201 without bone marrow micrometastases (P<0.001). The presence of occult metastatic cells in bone marrow, as compared with their absence, was an independent prognostic indicator of the risk of death from cancer (relative risk, 4.17; 95 percent confidence interval, 2.51 to 6.94; P<0.001), after adjustment for the use of systemic adjuvant chemotherapy. "

We all have our own little internal scientific touchstones; this is one for me. If it says anything, it says: resist Halsteadian thinking in breast cancer (btw, Halsteadian thinking dovetails with some "standards of XRT care" nowadays but I digress). Clearly the March of History shows that the notion ~1/3 of "M0" patients (and about one out of four T1N0) are what we might call "M1mi" is forgotten/pooh-poohed. But if we can pooh-pooh (or not even test for) M1mi surely we can pooh-pooh favorable appearing N1mi. And pooh-poohing N1mi is essentially what the prognostic staging system does.