PET-CTs and Breast Cancer

[Palex80]

Interesting observation.

Some time ago, our gynecologists decided to start staging all N+ breast cancer patients with FDG-PET-CT.

What we are seeing seeing now are quite a few patients with suspicious findings in the internal mammary lymph node chain.
Morphological not enlarged nodes, but suspicious FDG-uptakes in the region. This generally happens in patients with large primary tumors or extensive axillary N+.

How you approach these cases? We generally treat IM-nodes (in many of those patients we would have done that anyhow), but should we boost those nodes?
And to what dose?

Breast is the worst!

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[drowsy12]

Interesting indeed. Have you biopsied any of them? If you feel they are real tbis would be a good use of a boost if they’re not coming out!

 

[Palex80]

Interesting indeed. Have you biopsied any of them? If you feel they are real tbis would be a good use of a boost if they’re not coming out!

Unfortunately not. But they are not really "enlarged", it's just small (subcentrimetric) nodes with FDG-uptake.
And they are certainly not coming out.

When I was in training, these patients received only a bone scan, an ultrasound of the liver and a chest x-ray.
Now, we do FDG-PET-CT and have little data on what to do with these findings.

 

[TheWallnerus]

Interesting observation.

Some time ago, our gynecologists decided to start staging all N+ breast cancer patients with FDG-PET-CT.

What we are seeing seeing now are quite a few patients with suspicious findings in the internal mammary lymph node chain.
Morphological not enlarged nodes, but suspicious FDG-uptakes in the region. This generally happens in patients with large primary tumors or extensive axillary N+.

How you approach these cases? We generally treat IM-nodes (in many of those patients we would have done that anyhow), but should we boost those nodes?
And to what dose?

Breast is the worst!

“How do you approach these cases”

You do absolutely nothing with these cases that’s what. They are not interesting at all.

Boosting IMNs here would be like having your bitcoin double in value and immediately selling, or something.

About 30% of all breast cancer patients have positive IMNs... and positive bone marrows... at diagnosis.

So if you boost the IMNs (PETs are fraught with false positives in breast cancer... that's a fun rabbit hole) you need to irradiate the bone marrow too.

ADDENDUM: About 1 in 3 breast ca pts will have breast cancer cells in the IMNs. But less than 1 in 500 will have isolated IMN relapse, regardless of IMN local therapy (dissection or irradiation).

 

[drowsy12]

I think there’s certainly good points you make - what would you say about the role of taking axillary nodes out.

 

[TheWallnerus]

I think there’s certainly good points you make - what would you say about the role of taking axillary nodes out.

I say we proved we don't have to, most of the time.

ADDENDUM #2: I really hope that for a woman with a T1 ER+ breast cancer an cN0 at presentation that if she's SLN+ and somehow PET+ in the axilla (especially if "Morphological not enlarged nodes, but suspicious FDG-uptakes in the region"), we neither irradiate or surgerize that axilla. The PET+ finding here is not a marker for anything except a dumb ordering doctor.

 

[deleted1180461]

I’ve noticed med oncs ordering pets on early stage breast. I’m not sure how they’re getting paid for.

I boost enlarged IMNs to 66 and was taught that not doing so was a failable offense on boards. If you believe that disease is there but intentionally not treating it then why are you treating the breast at all?

 

[TheWallnerus]

D

I’ve noticed med oncs ordering pets on early stage breast. I’m not sure how they’re getting paid for.

I boost enlarged IMNs to 66 and was taught that not doing so was a failable offense on boards. If you believe that disease is there but intentionally not treating it then why are you treating the breast at all?

Define enlarged, state how often you see this and how often you boost IMNs to 66, and why do we need PETs to identify enlarged nodes. Why does God need a starship?

 

[Palex80]

ADDENDUM #2: I really hope that for a woman with a T1 ER+ breast cancer an cN0 at presentation that if she's SLN+ and somehow PET+ in the axilla (especially if "Morphological not enlarged nodes, but suspicious FDG-uptakes in the region"), we neither irradiate or surgerize that axilla. The PET+ finding here is not a marker for anything except a dumb ordering doctor.

 

[deleted1180461]

D

Define enlarged, state how often you see this and how often you boost IMNs to 66, and why do we need PETs to identify enlarged nodes. Why does God need a starship?

I never said I agreed with ordering pets to evaluate IMN status. Radiographically enlarged nodes on CT are treated as involved and boosted. With VMAT it is easy to push a small boost volume there while keeping heart and lung where they need to be.

If you’re not giving comprehensive RNI for patients with involved axillary AND IM nodes I assume you never give it and just treat for a LC benefit in the breast. Would you even do it in TNBC?

 

[TheWallnerus]

Radiographically enlarged nodes on CT are treated as involved and boosted. With VMAT it is easy to push a small boost volume there while keeping heart and lung where they need to be.

There's many thoughts that go through my mind reading this. First... I can't remember the last time I ever saw an enlarged IMN on CT (>1.5cm). I think prob pre-Obama era last time I saw one (thanks Obama). Second, "because we can" is maybe not the greatest rationale for applying >60 Gy of radiation to a site where the data is equivocal (or, really, negative) that treating said site does anything. Third, it must logically follow that since VMAT is more facile, safer, conformal, etc., than the older methods that VMAT has improved survival in breast cancer 😉

I guess it's hopefully improved cosmesis/late tissue effects.

 

[TheWallnerus]

View attachment 387518

I am tongue in cheek on my angry reaction. But really why. Such wonderful data that we don't have to treat them.

 

[deleted1180461]

There's many thoughts that go through my mind reading this. First... I can't remember the last time I ever saw an enlarged IMN on CT (>1.5cm). I think prob pre-Obama era last time I saw one (thanks Obama). Second, "because we can" is maybe not the greatest rationale for applying >60 Gy of radiation to a site where the data is equivocal (or, really, negative) that treating said site does anything. Third, it must logically follow that since VMAT is more facile, safer, conformal, etc., than the older methods that VMAT has improved survival in breast cancer 😉

I guess it's hopefully improved cosmesis/late tissue effects.

View attachment 387519

1. 5mm is the conventional limit for radiographic suspicion for IMNs, not 15 mm (27 times smaller volume).

2. It is disingenuous to suggest that is a typical late skin toxicity for delivering 50 Gy in 25 fractions to the IMNs with a small area taken to 66/33, especially with VMAT. I have never seen anything like that. Looks like where the 120% "hot spot" of an electron patch would be (medially on the photon tangent border). I no longer use electron patches in favor of VMAT, but even when I did, again I saw nothing like that.

3. I may or may not have had this kind of question on boards. The node on the image I may or may not have been shown was nowhere near 1.5 cm (if in fact I was shown it, which of course I cannot confirm or deny).

 

[TheWallnerus]

1. 5mm is the conventional limit for radiographic suspicion for IMNs, not 15 mm (27 times smaller volume).

2. It is disingenuous to suggest that is a typical late skin toxicity for delivering 50 Gy in 25 fractions to the IMNs with a small area taken to 66/33, especially with VMAT. I have never seen anything like that. Looks like where the 120% "hot spot" of an electron patch would be (medially on the photon tangent border). I no longer use electron patches in favor of VMAT, but even when I did, again I saw nothing like that.

3. I may or may not have had this kind of question on boards. The node on the image I may or may not have been shown was nowhere near 1.5 cm (if in fact I was shown it, which of course I cannot confirm or deny).

Only people who had already likely passed breast got the IMN-to-66 Gy question 😉

But we are moving into a different area vs the original question imho, which was PET+ or PET-suspicious nodes, not enlarged (a 5mm cutoff seems not right?). You didn't get that question on the boards.

 

[Palex80]

I am tongue in cheek on my angry reaction. But really why. Such wonderful data that we don't have to treat them.

I am simple guy

But we are moving into a different area vs the original question imho, which was PET+ or PET-suspicious nodes, not enlarged (a 5mm cutoff seems not right?). You didn't get that question on the boards.

 

[TheWallnerus]

3. I may or may not have had this kind of question on boards. The node on the image I may or may not have been shown was nowhere near 1.5 cm (if in fact I was shown it, which of course I cannot confirm or deny).

Haha, CYA. I like it.

 

[TheWallnerus]

I am simple guy

View attachment 387528

Is a PET-suspicious IMN node harboring microscopic or macroscopic disease? I can't change your mind until I know what's lurking inside it!

* Maybe the SUV determines the dose. The more the SUV, the more the dose. It's like no breast IM node is ever fully positive or fully negative. The cancer cell burden exists on a continuum. These are like Wernicke-Korsakoff (no one is ever fully Wernicke, or fully Korsakoff) nodes.

 

[Palex80]

Is a PET-suspicious IMN node harboring microscopic or macroscopic disease? I can't change your mind until I know what's lurking inside it!

Just boost it.
The solution is the answer to the question.

 

[TheWallnerus]

Just boost it.
The solution is the answer to the question.

It will be hard/impossible to change a mind here, admittedly, if the mind has decided that boosting PET suspicious IMNs is needed. My mind says there's gotta be a risk from this (although it's "easy" to boost them), and there is very uncertain benefit. What is the hypothesized benefit? Prevent IMN recurrence? Improve survival? Stop the IMNs from "seeding"? While I think it's fair (but a little muddled vis-a-vis IMNs) to bring EBCTCG 2023 into this, I would love pondering the benefit outside that.

 

[deleted1180461]

Is a PET-suspicious IMN node harboring microscopic or macroscopic disease? I can't change your mind until I know what's lurking inside it!

* Maybe the SUV determines the dose. The more the SUV, the more the dose. It's like no breast IM node is ever fully positive or fully negative. The cancer cell burden exists on a continuum. These are like Wernicke-Korsakoff (no one is ever fully Wernicke, or fully Korsakoff) nodes.

Schrödinger’s IMN?

 

[Palex80]

It will be hard/impossible to change a mind here, admittedly, if the mind has decided that boosting PET suspicious IMNs is needed. My mind says there's gotta be a risk from this (although it's "easy" to boost them), and there is very uncertain benefit. What is the hypothesized benefit? Prevent IMN recurrence? Improve survival? Stop the IMNs from "seeding"? While I think it's fair (but a little muddled vis-a-vis IMNs) to bring EBCTCG 2023 into this, I would love pondering the benefit outside that.

Well, some data do point in the direction that irradiating IMNs, can lead to a more favorable metastasis free survival.
Since all those patients in the IMN trials did not have PET, it´s hard to tell who benefits the most.

 

[TheWallnerus]

Well, some data do point in the direction that irradiating IMNs, can lead to a more favorable metastasis free survival.
Since all those patients in the IMN trials did not have PET, it´s hard to tell who benefits the most.

And this is the rub. Because now we're getting into the "philosophy of science" type stuff.

I think, and correct me if I'm wrong, that on the whole, studies where IMN RT have been specifically addressed have shown no benefit to IMN RT. Lack of PETs in those studies is certainly not helpful, either, to make good arguments that PET-suspicious IMNs should/shouldn't be treated.

On one hand, there's the Fisherian alternative hypothesis. It made predictions, like good hypotheses/theories do. One prediction was that elective nodal RT wouldn't improve survival (at the single-trial level, that prediction held true, EBCTCG notwithstanding). On the other hand, there is another hypothesis that has to do with seed/soil, etc, and that irradiating nodes, or minor variations in locoregional treatments, will improve breast cancer survival. If it takes just one negating piece of info to invalidate an entire hypothesis, we have negating pieces cutting each theory both ways.

(I won't even mention if we should look at PET-suspicious IMNs in HER2+ different than non-HER2 positive. Woops. Just did.)

If we assume a 50% sensitivity and 90% specificity for PET for IMNs, and the disease is cT1-2N0 early stage, the pretest IMN+ likelihood is in the ~10% range (historical data). So PET-positive IMNs would have a ~36% probability of being bx+, and PET-suspicious even lower than that. I leave it to others if they decide to use doses >50 Gy to these areas on the basis of PET-positive-predictive odds worse than a coin flip. If the patient is pN+, the pretest likelihood goes up, and PET has better IMN PPV than a coin flip then...

... but you are irradiating the IMNs anyways in that situation.

 

[Palex80]

Wait, I am not irradiating nodes in T1 N0 anyhow and these patients do not get a PET.

I mostly irradiate IMN/nodes in pN+ patients, and those are the ones that get the PET-staging. Some of them come back with positive findings on FDG PET.

 

[Gfunk6]

Does the patient have ER positive breast cancer? If so, 18F-FES PET is superior to tradiaitonal FDG-PET.

NCCN Guidelines Recommend Use of FES PET Imaging in ER+ Breast Cancer

18F-Fluorestradiol is currently the only imaging agent approved by the FDA for assessing estrogen receptor–positive lesion status to better guide treatment decision-making.

www.cancernetwork.com

 

[TheWallnerus]

Wait, I am not irradiating nodes in T1 N0 anyhow and these patients do not get a PET.

I mostly irradiate IMN/nodes in pN+ patients, and those are the ones that get the PET-staging. Some of them come back with positive findings on FDG PET.

How about T1 ER positive in a 60yo lady with positive sentinel node. I am going to assume/hope she doesn’t get ax dissection. Does she get a PET ordered by the other docs? (I got hasty with mentioning T1N0.)

 

[Palex80]

How about T1 ER positive in a 60yo lady with positive sentinel node. I am going to assume/hope she doesn’t get ax dissection. Does she get a PET ordered by the other docs? (I got hasty with mentioning T1N0.)

Unlikely. But even if she did, the chance of a positive residual node on PET is low. I mostly see those positive nodes in more advanced and/or biologically aggressive disease.

 

[gvsudew]

I say we proved we don't have to, most of the time.

ADDENDUM #2: I really hope that for a woman with a T1 ER+ breast cancer an cN0 at presentation that if she's SLN+ and somehow PET+ in the axilla (especially if "Morphological not enlarged nodes, but suspicious FDG-uptakes in the region"), we neither irradiate or surgerize that axilla. The PET+ finding here is not a marker for anything except a dumb ordering doctor.

Breast cancer decades ago was on average more advanced and likely to be node positive. Pet/ct is a better staging tool than bone scan and CT. False positives can occur. Point was a little dramatic.

 

[TheWallnerus]

Breast cancer decades ago was on average more advanced and likely to be node positive. Pet/ct is a better staging tool than bone scan and CT. False positives can occur. Point was a little dramatic.

I hadn't eaten my Snickers yet.

But yes breast cancer decades ago was on average more advanced. There's a little irony though isn't there that breast cancer used to be higher stage when patients weren't staged with the "better staging tool" versus now, when they are less advanced... and getting staged with the better staging tool. (I think this is ironic; I'm never really sure about irony.)

What if I were to say breast cancer PETs have lower sensitivities than bone scans for bone mets. If true, why is PET clearly "better"? Better is a tough word to pin down.

ADDENDUM #3: Palex originally said the med oncs are now staging all N+ patients with PETs. So in my mind I immediately leapt to T1N1 patients getting PETs. And I think all the PET does in those instances is increase the likelihood of making a therapeutic mistake, needlessly stressing out patients, wasting healthcare dollars, or all three. Dramatic!

 

[Palex80]

ADDENDUM #3: Palex originally said the med oncs are now staging all N+ patients with PETs. So in my mind I immediately leapt to T1N1 patients getting PETs. And I think all the PET does in those instances is increase the likelihood of making a therapeutic mistake, needlessly stressing out patients, wasting healthcare dollars, or all three. Dramatic!

You are correct, I did say that. But they don't really do it for T1 pN1 (sn) luminal A.
Patients need to have some risk factors, next to having a positive node, for instance luminal B or LVSI or a larger pT2 or more extensive nodal involvement.

 

[evilbooyaa]

I find myself in the middle of Palex and Wallnerus on this.
On one hand, how many patients with non-enlarged IMNs would have had FDG avidity in them if they had had a PET/CT. And despite that, isolated IMN failure is essentially unheard of. So maybe 50Gy for a non-enlarged, FDG avid node is fine.

That being said, with contemporary techniques (Wallnerus boomer RO toxicity picture aside) sequentially boosting a node to 60Gy assuming receipt of chemotherapy and the node no longer being visible, vs 60-66Gy if still visible, is probably relatively limited, especially for most IMN nodes (above the level of the heart generally).

I have not been in OP's situation. That being said, I probably would boost them. How much? Who knows. Maybe 60Gy 'middle ground' if non-enlarged but FDG avid (assuming pre-chemo) and still visible at end of chemo. But maybe just stick with 66Gy.

Maybe 56Gy if non-enlarged but FDG avid and no longer visible at end of chemo. But maybe just stick with 60Gy.

Is there a statistic on what percentage of nodes that show FDG uptake in breast cancer are pathologically negative? Even say in the Axilla?

 

[TheWallnerus]

You are correct, I did say that. But they don't really do it for T1 pN1 (sn) luminal A.
Patients need to have some risk factors, next to having a positive node, for instance luminal B or LVSI or a larger pT2 or more extensive nodal involvement.

So many varied presentations one could concoct from the above

Eg could be a 4cm primary with 2 LNs positive and HER2+ and ER- PR+ Grade 2. Would be stage clinical IIA. ACR says PET not rec here. They are more sanguine about PET with higher stage but in general the position is that PET has no great role in locoregional staging

 

[TheWallnerus]

I find myself in the middle of Palex and Wallnerus on this.
On one hand, how many patients with non-enlarged IMNs would have had FDG avidity in them if they had had a PET/CT. And despite that, isolated IMN failure is essentially unheard of. So maybe 50Gy for a non-enlarged, FDG avid node is fine.

That being said, with contemporary techniques (Wallnerus boomer RO toxicity picture aside) sequentially boosting a node to 60Gy assuming receipt of chemotherapy and the node no longer being visible, vs 60-66Gy if still visible, is probably relatively limited, especially for most IMN nodes (above the level of the heart generally).

I have not been in OP's situation. That being said, I probably would boost them. How much? Who knows. Maybe 60Gy 'middle ground' if non-enlarged but FDG avid (assuming pre-chemo) and still visible at end of chemo. But maybe just stick with 66Gy.

Maybe 56Gy if non-enlarged but FDG avid and no longer visible at end of chemo. But maybe just stick with 60Gy.

Is there a statistic on what percentage of nodes that show FDG uptake in breast cancer are pathologically negative? Even say in the Axilla?

Great opinion 😉

 

[TheWallnerus]

Is there a statistic on what percentage of nodes that show FDG uptake in breast cancer are pathologically negative? Even say in the Axilla?

This is what I would have guessed

It will be higher obv if the pre test likelihood is lower

Try and imagine the percentage of false negative PETs for women entered into Z0011

 

[Palex80]

Eg could be a 4cm primary with 2 LNs positive and HER2+ and ER- PR+ Grade 2. Would be stage clinical IIA. ACR says PET not rec here. They are more sanguine about PET with higher stage but in general the position is that PET has no great role in locoregional staging

 

[TheWallnerus]

View attachment 387599

Ok

Above case

The surgeon is not going back for axillary dissection

There is a 0.8cm axillary node with SUV 4.

There is ipsi IMN node 0.7cm SUV 4.1.

I’m going to assume you are treating axilla and IMN already

How much extra do the PET positive sites get

I would think the ONLY logic for a boost here would be to prevent axillary or IMN recurrence

But … with or without the boost … isn’t the in breast recurrence risk a lot higher than either axillary or IMN recurrence risk?

Are you using hypofx for ENI? What is boost node dose with hypofx?

What if we move to 5 fraction ENI? What will our boost doses be then?

 

[Palex80]

The surgeon is not going back for axillary dissection

I am buying her lunch, and trying tio talk her into it.

How much extra do the PET positive sites get

Wonderful, we are back to the original thread question.
Likely 25 x 2 Gy for everything, then 5 x 2 Gy for the rest (IMN node, axillary node, boost primary tumor site)?
But since we hypofractionate everyone nowadays... 40 Gy over 3 weeks for everything, then another 10 Gy for the boosts?

But … with or without the boost … isn’t the in breast recurrence risk a lot higher than either axillary or IMN recurrence risk?

Well, if that's macroscopic tumor in the IMN or axilla, I'd say risk of not controlling that is higher than not controlling any microscopic disease in the breast.

What if we move to 5 fraction ENI? What will our boost doses be then?

I haven't done ENI in 5 fractions yet and I have no idea what to do in that case.


BREAST IS THE WORST

 

[taserlaser]

Re indication for PET - this came out last year, and it lead to our group discussing potentially introducing it as standard for our more high risk patients. "Impact of 18F-Labeled Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography Versus Conventional Staging in Patients With Locally Advanced Breast Cancer" - Impact of 18F-Labeled Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography Versus Conventional Staging in Patients With Locally Advanced Breast Cancer - PubMed
Caveat of course being while it affected treatment, we do not have data on final outcomes

Re boosting IMN - I would also be inclined to boost a PET positive IMN however almost data free zone to say whether that is 'helpful' or not. Historically we would have just covered with our usual 4-field dose and leave it at that. Now is that underrating some - maybe. But probably was sufficient for a good portion, as it tends to be with low volume axilla disease.

Re hypofrac boost dose - locally we would just tend to sequential 10 Gy / 4-5 fr or 12.5 Gy / 5 for margin positive say, 15 Gy / 6 for gross disease if we are using moderate hypofrac, though most patients with gross disease probably get taken to 60-66 Gy with conventional fractionation

re 5 fr ENI - our current Canadian trial protocol for breast boost at least is 10 Gy / 5 fr on top of the 26 Gy / 5. Is that enough for gross disease? I would hazard against that probably. Even 66 Gy in some high grade/larger unresectable tumors isn't sufficient in my experience. Not sure if we have a good answer otherwise. We're starting at least to get some SBRT/high dose palliation results for unresectable/metastatic breast cancer but that is a totally different population

Breast & over investigation is the worst...

 

[TheWallnerus]

The surgeon is not going back for axillary dissection
I am buying her lunch, and trying tio talk her into it.

Isn't that paying for someone's food so that they'll deliver bad care

if that's macroscopic tumor in the IMN or axilla, I'd say risk of not controlling that is higher than not controlling any microscopic disease in the breast.

In Z0011, for SLN+ women who got ALND, about 3 in 10 had another positive node or more. So we can assume that the about 3 in 10 women in the other 450-patient arm had undissected, left-behind, cancerous nodes. Only about 2 of these 450 women had axillary recurrences... and many of these 450 women had no axillary RT, or "accidental" axillary RT, or who-knows-what-RT, or even no RT at all (in violation of protocol).

Veronesi randomized ~700 T1-3N0-1 women to IMN dissection or not. About 2 in 10 women in the IMN dissection group had "occult" IMN metastases, but only about 4 in 100 women in the non-IMN dissection group had IMN recurrence. One in 100 women in the IMN dissection group had an IMN recurrence, but (shocker) this translated to no difference in any other outcome (like OS or DFS).

These facts and math (and biology), if then taken into account with the false negative and positive rates of PET (in T2N1 disease, just for example), mean you might have to treat... two hundred or more?... PET+ IMNs to "help" (whatever that means) one lady. (There will definitely be times PET+ disease will be needless boosted.) If you can boost 200 IMN cases without adding any additional toxicity in 199 cases, the math might be in favor of IMN RT dose escalation on the basis of PET scans.

 

[deleted1180461]

Isn't that paying for someone's food so that they'll deliver bad care

View attachment 387620


In Z0011, for SLN+ women who got ALND, about 3 in 10 had another positive node or more. So we can assume that the about 3 in 10 women in the other 450-patient arm had undissected, left-behind nodes. Only about 2 of these 450 women had axillary recurrences... and many of these 450 women had no axillary RT, or "accidental" axillary RT, or who-knows-what-RT, or even no RT at all (in violation of protocol).

Veronesi randomized ~700 T1-3N0-1 women to IMN dissection or not. About 2 in 10 women in the IMN dissection group had "occult" IMN metastases, but only about 4 in 100 women in the non-IMN dissection group had IMN recurrence. One in 100 women in the IMN dissection group had a recurrence, but (shocker) this translated to no difference in any other outcome (like OS or DFS).

These facts and math (and biology), if then taken into account with the false negative and positive rates of PET (in T2N1 disease, just for example), mean you might have to treat... two hundred or more?... PET+ IMNs to "help" (whatever that means) one lady. (There will definitely be times PET+ disease will be needless boosted.) If you can boost 200 IMN cases without adding any additional toxicity in 199 cases, the math might be in favor of IMN RT dose escalation on the basis of PET scans.

You lost me at “In Z0011.” I’m sorry, I can’t take anything after those words seriously.

 

[TheWallnerus]

You lost me at “In Z0011.” I’m sorry, I can’t take anything after those words seriously.

Why? It completely changed the standard of axillary care worldwide. (Not to mention the NCCN guideline I copy/pasted above.)

True fact: the uptake of Z0011's findings into practice is correlated with a significant increase in breast cancer survival 🙂

 

[deleted1180461]

Why? It completely changed the standard of axillary care worldwide.

My bad for the fake news. I forgot that it was a perfect trial.

 

[TheWallnerus]

My bad for the fake news. I forgot that it was a perfect trial.

Well I'm trying to take you seriously! What is a "perfect trial"? Should Z0011 be retracted? It is cited pretty extensively in every modern breast cancer guideline/consensus. Do you try and get your surgeons to do completion axillary dissections for T1-2 SLN+ disease?

 

[deleted1180461]

Well I'm trying to take you seriously! What is a "perfect trial"? Should Z0011 be retracted? It is cited pretty extensively in every modern breast cancer guideline/consensus. Do you try and get your surgeons to do completion axillary dissections for T1-2 SLN+ disease?

Do you offer 26/5 APBI for sn+ patients who met criteria for z0011?

 

[TheWallnerus]

re 5 fr ENI - our current Canadian trial protocol for breast boost at least is 10 Gy / 5 fr on top of the 26 Gy / 5. Is that enough for gross disease? I would hazard against that probably.

I think it would be pretty wild to give a woman three times as long (or more) RT regimen in order to treat a PET+ IMN finding. I.e., you can't "safely chase" the "gross" node in 5 fractions, so you feel compelled to do 3 weeks (or 6.5 weeks!). That is kind of a possible logical offshoot of some of the logic here. Seems like a reductio ad absurdum.

 

[TheWallnerus]

Do you offer 26/5 APBI for sn+ patients who met criteria for z0011?

Before I directly answer your question, I'll tell you what I wouldn't offer to a 65 yo lady wtih T1 ER+ disease and 1 of 3 SLN positive: axillary RT.

Now I will answer directly: I would not do partial breast. I would really want to a la IMPORT-LOW, but it would be too cutting edge. But I would only irradiate the breast. I would not intentionally put one picogray in the axilla. Z0011 gives us a lot of comfort there. I would likewise not let a PET finding, with normal conventional imaging, cause a devation. (Of course, since I am not the PET-orderer, that may be out of my hands, or Palex's hands.)

"The role of nodal irradiation, specifically in ACOSOG Z0011 and in the management of patients with node-positive breast cancer, is controversial. Although 19% of patients received prohibited third-field irradiation, nodal irradiation was distributed similarly by treatment group, as was omission of irradiation and the use of high–tangent-field irradiation, indicating that choice of radiotherapy fields was unlikely to have affected the study outcome. In addition, the unplanned analysis showed that no survival differences were observed among patients treated with conventional tangent-field irradiation or nodal-field irradiation."

I am interested why (many) rad oncs gainsay Z0011 and the rest of oncology seems to have moved on.

 

[deleted1180461]

Before I directly answer your question, I'll tell you what I wouldn't offer to a 65 yo lady wtih T1 ER+ disease and 1 of 3 SLN positive: axillary RT.

Now I will answer directly: I would not do partial breast. I would really want to a la IMPORT-LOW, but it would be too cutting edge. But I would only irradiate the breast. I would not intentionally put one picogray in the axilla. Z0011 gives us a lot of comfort there. I would likewise not let a PET finding, with normal conventional imaging, cause a devation. (Of course, since I am not the PET-orderer, that may be out of my hands, or Palex's hands.)

"The role of nodal irradiation, specifically in ACOSOG Z0011 and in the management of patients with node-positive breast cancer, is controversial. Although 19% of patients received prohibited third-field irradiation, nodal irradiation was distributed similarly by treatment group, as was omission of irradiation and the use of high–tangent-field irradiation, indicating that choice of radiotherapy fields was unlikely to have affected the study outcome. In addition, the unplanned analysis showed that no survival differences were observed among patients treated with conventional tangent-field irradiation or nodal-field irradiation."

I am interested why (many) rad oncs gainsay Z0011 and the rest of oncology seems to have moved on.

What percentage of practicing rad oncs in the U.S. do you think would treat this hypothetical patient with “high tangents” instead of regular whole breast? Why do you think that is? And why are you not comfortable radiating anything other than the full breast in this situation?

 

[deleted1180461]

Let me ask you a more direct question.

Statements are either objectively judgements or facts.

Z0011 was a good trial.

This obviously cannot be a fact. It’s a judgement. So, can you tell me whether you agree with this judgement or not? Or do you reject that and want to call that a fact? Because the ability to honestly discern between facts and judgements are important. And as demonstrated in my post above, something that’s been lost, quite shamefully, in the medical profession recently.

 

[Palex80]

Isn't that paying for someone's food so that they'll deliver bad care

View attachment 387620

There is no PET-CT in this scenario showing residual macroscopic disease left behind. This is no longer cN0, as far as I am concerned, I have a finding from an exam now which says it‘s cN3b.

In Z0011, for SLN+ women who got ALND, about 3 in 10 had another positive node or more. So we can assume that the about 3 in 10 women in the other 450-patient arm had undissected, left-behind, cancerous nodes. Only about 2 of these 450 women had axillary recurrences... and many of these 450 women had no axillary RT, or "accidental" axillary RT, or who-knows-what-RT, or even no RT at all (in violation of protocol).

Veronesi randomized ~700 T1-3N0-1 women to IMN dissection or not. About 2 in 10 women in the IMN dissection group had "occult" IMN metastases, but only about 4 in 100 women in the non-IMN dissection group had IMN recurrence. One in 100 women in the IMN dissection group had an IMN recurrence, but (shocker) this translated to no difference in any other outcome (like OS or DFS).

Isolated axillary or IMN recurrences are not well studied in both trials.
And both trials did not have macroscopic disease left behind.
The whole philosophy is that by avoiding leaving disease behind, one influences MFS.

 

[TheWallnerus]

And both trials did not have macroscopic disease left behind

Isn’t nodal microscopic disease N1mic? Every single one of the ~150 women in Z0011 who had positive nodes with their ALND was N1mic from the ALND? If not, then *many* women in Z0011 in the SLN only arm had macroscopic nodal disease left behind… if that arm was well balanced versus the ALND arm. We don’t get to call it microscopic just because our scans or fingertips didn’t detect it.

What percentage of practicing rad oncs in the U.S. do you think would treat this hypothetical patient with “high tangents” instead of regular whole breast? Why do you think that is?

Statements are either objectively judgements or facts.

Z0011 was a good trial.

This obviously cannot be a fact. It’s a judgement

Treating a patient a certain way just because a certain percentage of doctors do it that way is totally a… judgement call. I remember a provocative paper from 10 or 15y ago that something like 30% of European rad oncs used bolus routinely for PMRT while 90% of US rad oncs did. Right now 90% of all breast cancer patients in the UK get a 5 fraction regimen; this rate is 1% or less in the US. Even single fraction bone met palliation is used on something like 1-10% of Medicare patients eligible for it. Rad oncs are way more prone to keep up with the Radiotherapy Joneses than the radiotherapy evidence.

Z0011 was a practice changing trial. That’s a fact (citations available on req). Applying “high tangents” in Z0011-type patients where the axillary failure rates are ~1% regardless the surgery or the radiotherapy is judgment (as is how high you set the tangent).

 

[Palex80]

If not, then *many* women in Z0011 in the SLN only arm had macroscopic nodal disease left behind

Probably yes, but not detectable with the methods/tools used in the trial.

We don’t get to call it microscopic just because our scans or fingertips didn’t detect it.

I thought that's the distinction. Otherwise, everything is macroscopic?