Treating IMNs?

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BraggPeak

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What are peoples thoughts on treating IMNs with the following EORTC study (much like MA.20)

Irradiation of the internal mammary and medial supraclavicular lymph nodes in stage I to III breast cancer: 10 years results of the EORTC Radiation Oncology and Breast Cancer Groups phase III trial 22922/10925

P. Poortmans(1), H. Struikmans(2), C. Kirkove(3), V. Budach(4), P. Maingon(5), M.C. Valli(6), S. Collette(7), A. Fourquet(8), H. Bartelink(9), W. Van den Bogaert(10)

(1)Institute Verbeeten, Radiation Oncology, Tilburg, Netherlands
(2)RCWEST, Radiation Oncology, Den Haag, Netherlands
(3)University Hospital St Luc, Radiation Oncology, Brussels, Belgium
(4)Charité Universitaetsmedizin, Radiation Oncology, Berlin, Germany
(5)Centre G.F.Leclerc, Radiation Oncology, Dijon, France
(6)Hospital Sant Anna, Radiation Oncology, Como, Italy
(7)EORTC, Headquarters, Brussels, Belgium
(8)Institute Curie, Radiation Oncology, Paris, France
(9)The Netherlands Cancer Institute, Radiation Oncology, Amsterdam, Netherlands
(10)University Hospitals Leuven, Radiation Oncology, Leuven, Belgium
Background:

Locoregional radiation therapy (RT) improves overall survival in patients with involved lymph nodes (LN). EORTC trial 22922-10925 investigates how much RT to the internal mammary and medial supraclavicular LN (IM-MS) contributes to this effect (Clinicaltrials.gov NCT00002851).

Material and methods:

Eligible patients had involved axillary LN and/or a medially located primary tumour. Randomisation was to yes or no IM-MS RT to 50 Gy in 25 fractions. The final trial design aimed at detecting a 4% increase in 10-year overall survival (OS) (from 75 to 79%, HR=0.82) with 2-sided unadjusted Logrank test at the 5% significance level. Secondary endpoints are disease-free survival (DFS), metastases-free survival (MFS) and cause of death.

Results:

Between 1996 and 2004, 4004 patients were randomized in 43 centres. Median age was 54 years; 59.0% were postmenopausal; 55.6% had involved axillary LN; 33.8%, 52.0% and 14.2% had stage I, II and III, respectively. The majority (76.1%) was treated with breast conserving therapy, in 85.1% with a boost to the primary tumour bed. After mastectomy, chest wall irradiation was applied to 73.2% of patients in both arms. Axillary RT was given in 6.8% patients of the no IM-MS group and in 7.8% patients of the IM-MS group. Nearly all LN-positive (99.0%) and 66.3% of LN-negative patients received adjuvant systemic treatment.

At a median follow-up of 10.9 years, 811 patients have died. IM-MS RT improved outcome at 10 years: 82.3 vs. 80.7% OS (HR=0.87 (95%CI: 0.76, 1.00), Logrank p=0.056); 72.1 vs. 69.1% DFS (HR=0.89 (95%CI: 0.80, 1.00), Logrank p=0.044); 78.0 vs. 75.0% MFS (HR=0.86 (95%CI: 0.76, 0.98), Logrank p=0.020). The treatment effect on OS was independent from the number of involved LN: HR = 0.79 (95%CI: 0.61, 1.02) for LN-negative; 0.89 (95%CI: 0.73, 1.09) for 1-3; 0.85 (95%CI: 0.61, 1.18) for 4-9 and 1.00 (95%CI: 0.59, 1.71) for 10+ involved axillary LN (p>0.1 for heterogeneity). In the IM-MS group 382 patients died vs. 429 patients in the no IM-MS group. The causes of death were similar except for breast cancer (259 vs. 310). No increase in lethal complications was observed so far.

Conclusions:

With a median follow-up of 10 years, postoperative RT to the IM-MS LN shows to improve overall, disease free and metastases free survival in patients with stage I-III breast cancer without an increase in non-breast cancer related mortality. Combined with the earlier report of good tolerance and limited toxicity up to 3 years, we advise radiation therapy to the internal mammary and medial supraclavicular lymph nodes for patients with involved axillary LN and/or a medially located primary tumour.
 

Gfunk6

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Nicely designed trial, I have to say.

Still would not treat IMNs however. The OS benefit is of marginal benefit statistically and the absolute value is tiny - also the study did not meet their initial hypothesis of 4% improvement in OS.

The latency for cardiac morbidity is long and most probably > 10 years so I am not yet satisfied that treating IMNs does not worsen cardiac mortality.
 

Brim

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It's an intriguing study just like MA.20, and it's exciting that they were able to complete this trial with such a large study population.

However, the results while interesting are underwhelming. The hazard ratios were not impressive, and the confidence intervals all include unity.

Not practice changing in my mind.
 

ramsesthenice

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We are a little more liberal and have been for a while. If we can we use part wide tangents to cover the top 3-4 interspaces of IMNs and use DIBH to get a good heart block on there if it's left sided. We do this for almost all node positive patients.

I'm not sure how I feel about it. Like Gfunk said its a fairly small benefit overall at a frankly unknown cost in terms of cardio toxicity. The other problem with this will be matching up fields in the future if they recurr contralaterally. These part wides reach well across midline to cover the IMMs. That could carry its own issues down the line.
 

ShirleyT

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Looks like more people are treating IMNs now with this paper and now MA-20. Now I see NCCN is saying to strongly consider treating IMN as category 2B when regional nodal RT is indicated, when before it was left up to the treating radiation oncologist. Personally I have found it very hard to treat the IM nodes in patients with an intact breast (unhappy with matching tangents with electron because of the junction is generally not ideal unless the breast is very small and flat) and I have been hesitant to use partially wide tangents because of the contralateral breast dose that ramsesthenice brought up.
 

ramsesthenice

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I have a loner lap top and no citations but the Red Journal recently had an RCT from a French group that randomized women to +/- IMN irradiation. Its 10 year follow up. There are a number of issues but one thing that was interesting, 25% of the patients were node negative. In the node negative groups there was a clear and consistant trend towards worse overall survival whereas in all of the node + groups there was a trend towards improved survival. Can't conclude anything specific from this paper except it further supports the idea that IMN irradiation is likely not free of toxicity even in the 3D planning era (unclear how many of those patients got 3D planning in that study) but it may have a role in appropriate patients. Who they are is the question that hasn't been answered well to date.
 

Palex80

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I think one important point, which should be stressed out, is which group actually profits from IMN-RT?

The low-risk node-negative patients probably don't, cause the risk of recurrence in all is small and node-negative patients tend to get lots of more chemo nowadays, than they did before.
The high-risk node-positive (pN2) patients probably don't profit as well, cause the risk of systemic relapse is high and preventing an IMN-recurrence won't change prognosis.

It's probably the intermediate-risk patients (only few nodes involved) which will profit the most from IMN-RT.

No study can be designed to actually address this issue with adequate numbers of patients.
 

Palex80

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Looks like more people are treating IMNs now with this paper and now MA-20. Now I see NCCN is saying to strongly consider treating IMN as category 2B when regional nodal RT is indicated, when before it was left up to the treating radiation oncologist. Personally I have found it very hard to treat the IM nodes in patients with an intact breast (unhappy with matching tangents with electron because of the junction is generally not ideal unless the breast is very small and flat) and I have been hesitant to use partially wide tangents because of the contralateral breast dose that ramsesthenice brought up.
Do IMRT! :)
 

Neuronix

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British Columbia post-mastectomy trial radiated regional nodal including IMNs with overall survival benefit
Danish post-mastectomy trial radiated regional nodal including IMNs with overall survival benefit

Note, no excess cardiac mortality in either of those trials for regional nodal irradiation.

MA-20 lumpectomy trial regional nodal arm including IMNs will very likely show survival benefit
Now EORTC trial specifically randomizing IMN irradiation shows a very strong trend towards survival benefit, will very likely become significant at some point in the near future


If all of that can't convince other rad oncs to irradiate the IMNs, we'll just have to agree to disagree.
 

Brim

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British Columbia post-mastectomy trial radiated regional nodal including IMNs with overall survival benefit
Danish post-mastectomy trial radiated regional nodal including IMNs with overall survival benefit

Note, no excess cardiac mortality in either of those trials for regional nodal irradiation.

MA-20 lumpectomy trial regional nodal arm including IMNs will very likely show survival benefit
Now EORTC trial specifically randomizing IMN irradiation shows a very strong trend towards survival benefit, will very likely become significant at some point in the near future


If all of that can't convince other rad oncs to irradiate the IMNs, we'll just have to agree to disagree.

Of course all of these positive trials were randomized to:
  • +/- (CW + SCLV + IMN)
And not:
  • +/- IMN

It can be said that these trials show a benefit for irradiating these patients. We know that it's useful to irradiate "something" but these trials don't identify the target. For example, it could be the chest wall or the supraclav that's important to irradiate.

These trials are not de facto evidence of benefit for treating the IMNs specifically. Treating the IMNs *may* not be important, but the trials aren't designed to tease that out. It would take a randomized trial specifically looking at +/- IMN radiation.

We do have some trials that have looked at randomizing solely to +/- IMN RT

(There may be some others I'm forgetting about)

Unfortunately these trials are small and old, may be underpowered to detect a small survival advantage.

An additional comment from the recent French trial:
"The stratification by tumor location inside the breast, histopathology nodal status and adjuvant chemotherapy defined 6 groups. In none of these subgroups did IMN-RT significantly improve overall survival (Fig. 2). However, in pN0 patients with internal/medial tumors, the patients in the IMN-RT− (i.e. negative) group, with or without adjuvant chemotherapy, showed a nonsignificant benefit in terms of 10-year overall survival. For pN+ patients and medial/central tumors or lateral tumors, the opposite was observed." (emphasis and italics mine)

So, in short, adding IMN RT may be harmful in node-negative pts and may be beneficial in node-positive patients, although these differences were non-significant. You can argue that the trial was underpowered to detect such small differences in survival.
 

Neuronix

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Of course all of these positive trials were randomized to:
  • +/- (CW + SCLV + IMN)
And not:
  • +/- IMN

In the EORTC trial posted by the op, the randomization actually is +/- matched en face electron/photon strip covering IMNs and medial SCV. You could be a naysayer and say the benefit is coming from the medial part of the SCV that is providing the benefit, but I find that implausible.

At the end of the day, my point was that there is a lot of evidence for IMN irradiation. It doesn't mean that there's no argument against it, but the EORTC actually directly asked the question, and provides even more evidence for IMN irradiation. When it is published, assuming a survival benefit for their trial, the EORTC trial would be considered NCCN Category 1 evidence for IMN irradiation in the studied group (central/medial breast cancer, any node positive, though may depend on the subgroup analysis of course).

I do agree that you probably needed 4000+ patients to be randomized to find such a small survival benefit. But it is there. Given all the many things that we radiate without a survival benefit, this seems like a slam dunk to me.
 
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BraggPeak

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OK on to a real patient:

68 year-old with a 2.0 cm RUQ lesion, invasive ductal carcinoma with extensive mucinous differentiation, nuclear grade 1, but triple negative. Patient had lumpectomy (negative margins), and SLN with 1 positive node with ECE and went on to have an additional 19 nodes dissected, and all negative (1/20 nodes).

What would you do following chemotherapy:

1. Whole breast
2. Whole breast + SCV
3. Whole breast + SCV + IMN
 
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Palex80

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Well, either 1 or 2 for me.

ECE is considered as a facultative indication for SCV in my institution. I don't see a clear point for IMN.
 

BraggPeak

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I choose #1 given that only 1/20 nodes were involved...but not sure what the best option is! It's an easy one to argue either way..
 

medgator

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Well, either 1 or 2 for me.

ECE is considered as a facultative indication for SCV in my institution. I don't see a clear point for IMN.

I'd do 1 or 2 as well. Never heard about ece as an indication for scv field before.

I agree with others regarding the hesitancy to do imns. I pretty much only treat them when they are involved
 

Neuronix

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68 year-old with a 2.0 cm RUQ lesion, invasive ductal carcinoma with extensive mucinous differentiation, nuclear grade 1, but triple negative. Patient had lumpectomy (negative margins), and SLN with 1 positive node with ECE and went on to have an additional 19 nodes dissected, and all negative (1/20 nodes).

That's a strange case. How extensive is the ECE? You could make an argument for axillary XRT if it's extensive. Mucinous grade 1 triple negative is an odd histology also. Mucinous is typically ER+ and often a less aggressive histology. Who did the pathology? Could it be reviewed?

Anyway, I'd be more hesitant to comment on that case. Also in a 68 year old my answer would depend in part on their performance status. To illustrate the point I'd rather pick something a bit more typical that will split opinions, like a 45 year old otherwise healthy woman s/p lumpectomy with a central T2 G3 triple negative and one positive lymph node. Or the other controversy, s/p mastectomy of a medially located T2 G3 triple negative with no positive axillary lymph nodes.
 

medgator

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1st case- Whole breast alone, no axilla/SCV/IM

2nd- 45 year old- Whole Breast + SCV, no IM

3rd- T2G3- Whole Breast, no axilla/SCV/IM

Mastectomy... You would radiate chest wall though?

I would. The more data I see coming out about triple negative recurrences in the setting of mastectomy (and seeing pts with those recurrences who got chemo after mastectomy) and the possible benefit of pmrt, I've started incorporating it into my decision making.
 

Palex80

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Never heard about ece as an indication for scv field before.

It's all retrospective...

http://www.ncbi.nlm.nih.gov/pubmed/16169678

"However, patients with > or = 4 involved axillary lymph nodes, >20% involved axillary nodes, or gross extranodal extension are at increased risk of failure in the supraclavicular fossa/axillary apex and should receive radiation to undissected regions in addition to the chest wall."

SCV is the area of regional lymphatics in breast cancer I am the MOST comfortable treating. SCV-RT causes considerably less lymphedema than axillary-RT and bears no risk to the heart compared to IMN-RT or axillary-RT with wider tangents.

However the MA20 data so far shows, that the major benefit of regional RT comes from preventing recurrences in the axilla, not in the IMN- or SCV-area. This has to be kept in mind.
 

seper

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Regarding EORTC IM study, don't kill the messenger.
I don't treat IM electively, but now as the data are accumulating, I'm thinking of changing my practice.
 

Neuronix

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I don't treat IM electively, but now as the data are accumulating, I'm thinking of changing my practice.

Interesting paper for everyone just published online from the EBCTCG in The Lancet:

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)60488-8/fulltext

Two interesting points:

1) Main point of the article: "After mastectomy and axillary dissection, radiotherapy reduced both recurrence and breast cancer mortality in the women with one to three positive lymph nodes in these trials even when systemic therapy was given." Hopefully this ends the debate about need for postmastectomy radiation in the N1 population.

2) "All were in trials in which radiotherapy included the chest wall, supraclavicular or axillary fossa (or both), and internal mammary chain." This survival benefit is based on a meta-analysis of 22 trials of post-mastectomy radiation. All of them radiate IMNs.
 
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seper

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Great study (as all EBCTCG's are), but to point out the obvious:
1. No relationship between irradiating IMN's and cancer outcomes could be established.
2. Comprehensive nodal XRT as done in these trials increases non-cancer death (example: Appendix page 54).
 

johnboy12

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I would. The more data I see coming out about triple negative recurrences in the setting of mastectomy (and seeing pts with those recurrences who got chemo after mastectomy) and the possible benefit of pmrt, I've started incorporating it into my decision making.


There's level 1 evidence for this. In this Chinese trial, PMRT for stage I/II TNBC led to improved overall survival.

http://www.ncbi.nlm.nih.gov/pubmed/21852010
 

Gfunk6

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There's level 1 evidence for this. In this Chinese trial, PMRT for stage I/II TNBC led to improved overall survival.

http://www.ncbi.nlm.nih.gov/pubmed/21852010

Based on consensus from breast cancer experts in North America this trial was poorly designed and the results can essentially be ignored.

That's not to say PMRT in these patients is unecessary, but rather this trial is not a good proof of concept.
 

medgator

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Based on consensus from breast cancer experts in North America this trial was poorly designed and the results can essentially be ignored.

That's not to say PMRT in these patients is unecessary, but rather this trial is not a good proof of concept.

It certainly isn't the only evidence on the subject, however, and along with another study:

http://jco.ascopubs.org/content/29/...318eaabfe95d0c3baca1581d&keytype2=tf_ipsecsha

It is definitely is thought provoking... no reason to think TNBC cant be a bad actor loco-regionally as much as it is distantly.
 

Palex80

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That's a surprise now, isn't it? It seems that the DFS-benefit reported in the abstract of the MA20 trial shrunk and the anticipated OS-difference vanished with time...

The key message here is probably that the number of nodes is not the main factor, one should keep in mind. It's the biology of the tumor as the sum of multiple factors, that counts the most.
That's why the NEJM-editorial is in my opinion flawed, when it states:
"There is no rationale for nodal irradiation in patients with negative axillary nodes because nodal recurrence rates after negative results on sentinel-node biopsy are less than 1%,9 and isolated internal mammary metastases are very uncommon, even in patients with medial tumors."
That's probably wrong... Look at the MA20-data: Although only few patients are in that subgroup, it seems that the "high-risk-node-negative" subgroup benefited the most from RNI.

My conclusion:
A 48year old patient with a pT2 pN0 cM0 G3 L1 ER10%/PR10% tumor is probably going to benefit more from RNI than a 65 year old patient with pT1 pN1 (1/12) cM0 G1 ER90%/PR90% tumor...

Keep the discussion going!
 

BobbyHeenan

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I'm not sure if it's the right thing to do or not, but often when I'm questioning IMN coverage (for example > 4 axillary nodes but a lateral tumor), I just sit down and see what kind of plan I can develop. Like a lot of what we do, it's risk/benefit.

If I'm having trouble covering IMN's without exceeding heart and lung constraints, then I will omit them. Usually with a combo of medial electrons and lateral photons I can get an OK plan, but sometimes it can be difficult.

Where I trained we had one attending that always covered them (rationale: they covered them in the randomized trials that showed benefit, so we need to cover them), then you have folks like Gary Freedman that say he pretty much never covers them unless clinically involved (source: ASTRO spring refresher 2015, rationale: modern series suggest low failure rates, we don't know how much the IMN-specific part of the comprehensive XRT helped, and the negative +/- IMN trials). So even the world's experts in breast cancer radiation can't agree with what is right here.
 
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seper

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I've been feeling pressure to start doing 4 field XRT for breast conservation patients with 1/15 positive axillary nodes. Thankfully, that idea is now out.
 
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Mandelin Rain

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Looking at the data....

0

There were 0 IMN failures in either group of MA.20. NNT to prevent 1 IMN failure = infinity.


0

There was 0.8 vs. 0.2% IMN failures inEORTC. NNT = 166.

So, you need to treat somewhere between 166 and infinity women with IMN irradiation, to prevent 1 IMN failure? (if you pool the patients, the NNT is 250)

Pass.
 
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radmonckey

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I think using the concept of IMN failure as your benchmark for the utility of IMN radiation is flawed. Older surgical data has demonstrated IMN involvement to be >10%, even in tumors less than 2cm (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1251002/pdf/annsurg00106-0044.pdf). These nodes may never become clinically evident, but may represent a "halfway house" for cancer cells before they become distant metastases. There may be something about the anatomy and/or cellular milieu of these nodes that makes them unlikely to manifest as clinically enlarged, despite having microscopic tumor deposits.

We all know in our hearts that there are some patients that will benefit from IMN radiation, outside of those with clinically enlarged nodes. Unfortunately we don't have great tools to figure out who they are yet. It makes decision making difficult, especially as heart dose has been stressed more and more in recent years.
 
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Mandelin Rain

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Sure hypothetically, that's possible. What you describe is the (somewhat ironically) Halsted theory on metastases, where systemic metastases run through an orderly progression via the nodes. I'm not sure how many people agree with this nowadays, but it's possible. Though if we use that pre-screening mammogram data AND we assume that regional irradiation works on microscopic disease, there would be no argument that every single patient diagnosed with an invasive breast cancer should undergo IMN irradiation.

Breast cancer outcomes certainly haven't worsened since we stopped doing Halsted mastectomies and removed IMNs surgically.
 
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radmonckey

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It's not hypothetical that if you leave gross disease behind, lymph nodes or primary, it may in fact eventually spread systemically. You can pretend like it's some fringe line of archaic thinking if you want, but it is directly corroborated by the MA.20 results themselves showing a distant DFS of 86.3 vs 82.4% (p=0.03).

Oh wait, that's a secondary endpoint in a massive phase 3 clinical trial executed by a well respected body published in a major journal, so it doesn't really count right????

We all know that each one of us routinely makes important treatments decisions on the firm foundations of secondary endpoints, secondary analyses, and retrospective investigations. Like it or not, they do influence our field.

I do not routinely treat IMNs as of this second. I am in the camp of "I don't know what the right answer is" not "Everyone else is a dunce, this is clearly the right answer". These trials absolutely influence my generally understanding of the topic and are landmark.
 

medgator

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I think using the concept of IMN failure as your benchmark for the utility of IMN radiation is flawed. Older surgical data has demonstrated IMN involvement to be >10%, even in tumors less than 2cm (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1251002/pdf/annsurg00106-0044.pdf). These nodes may never become clinically evident, but may represent a "halfway house" for cancer cells before they become distant metastases. There may be something about the anatomy and/or cellular milieu of these nodes that makes them unlikely to manifest as clinically enlarged, despite having microscopic tumor deposits.

We all know in our hearts that there are some patients that will benefit from IMN radiation, outside of those with clinically enlarged nodes. Unfortunately we don't have great tools to figure out who they are yet. It makes decision making difficult, especially as heart dose has been stressed more and more in recent years.

I'd trust the halfway house to chemo personally....
 

Mandelin Rain

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I don't think anyone knows what the right answer is. No one is advocating leaving gross disease untreated. In MA.20 even if you assume that every single metastatic recurrence as first event was caused by occult IMN involvement (in the absence of a single clinically or radiographically apparent IMN) rather than occult disease in commonly involved nodes or the skin/chest wall marginal to the typical tangent fields that would be better covered with regional nodal irradiation.... you'd still need to treat 50 womens' IMNs to prevent 1 metastatic recurrence. I probably won't toss IMN irradiation at everyone on the assumption that this is true, but others may. That's cool. I'm sure that there is a very refined subset of patients for whom this is the correct thing to do, but I'm not sure it's all comers with node positive or high risk node negative disease. As with many cancers, the more you treat, the less the recurrence and the greater the toxicity. Finding the balance is what is important.

I guess I'm more shocked that there wasn't more of a difference than there was.
 
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grayharbor

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These two trials have become a hotbed of discussion at our institution. As we try to make sense of all of it, I will say, its saddening that the official editorial/response was penned by a surgical and medical oncologist for a +/- RT trial. While I don't disagree with all of their assertions, its hard for me to read the opinion that "Our recommendations with respect to radiotherapy..."

I don't advocate dismissing their opinions, but one of the respected RadOncs at their institutions (or nationally) should have been included. Its just a part of mutual multidisciplinary respect that must exist in order for us to effectively team up in cancer care. Can you imagine an ACOSOG trial without a surgical opinion?
 
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CharlestonRadOnc

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Too exhausted from a busy clinic day to read this entire thread but no - I do not treat the IMNs unless they are clearly involved on CT or PET/CT imaging. (I never order PETs on breast cancer patients but often they come to me with a PET ordered by surgery or med/onc).

Not to be too dramatic - but as a field we really need to do a better job of limiting toxicity when we can .... and I really can't justify increasing the heart dose to try to eliminate potential microscopic disease that is likely not there (and if it is there - it is likely eradicated by neoadjuvant or adjuvant chemo).
 

medgator

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Too exhausted from a busy clinic day to read this entire thread but no - I do not treat the IMNs unless they are clearly involved on CT or PET/CT imaging. (I never order PETs on breast cancer patients but often they come to me with a PET ordered by surgery or med/onc).

Not to be too dramatic - but as a field we really need to do a better job of limiting toxicity when we can .... and I really can't justify increasing the heart dose to try to eliminate potential microscopic disease that is likely not there (and if it is there - it is likely eradicated by neoadjuvant or adjuvant chemo).
You don't order PET scans on your stage III pts? I'd at least get CT and bone scans at a minimum there.

Often I see them before med onc, straight from the surgeon so I will order a PET at least in those patients or if they present with symptoms. I can't argue with some who order it in node-positive triple negative pts also
 

CharlestonRadOnc

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Hey @medgator... I should clarify that patients typically come to me after being worked up by Med/Onc or surgery so the PET has already been ordered. My general point was that we have really good imaging that can tell us if there is macroscopic disease in the IMNs.... and if there's not... I do not treat them electively. Also - per NCCN PET scans are optional (category 2B) even for locally advanced disease... so it's really dealer's choice.
 

medgator

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Hey @medgator... I should clarify that patients typically come to me after being worked up by Med/Onc or surgery so the PET has already been ordered. My general point was that we have really good imaging that can tell us if there is macroscopic disease in the IMNs.... and if there's not... I do not treat them electively. Also - per NCCN PET scans are optional (category 2B) even for locally advanced disease... so it's really dealer's choice.
Yeah agree, hence why I offered the CT/WBBS as an alternative, but IMO, all stage IIIs should get something.
 

Palex80

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OMG!

It's all retrospective but unless someone can find a reason why left-sided breast cacner bears a more unfavorable prognosis than right-side cancer, the Danish data may change my practice.
This is a 3% survival benefit caused solely by IM-RT in node positive patients...
 

radmonckey

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Haha, OMG, my thoughts exactly. This looks pretty dang compelling to me. I would have thought this would generate fervent discussion, since others seemed so ready to explain their carefully constructed logical house of cards for or against treated IMNs earlier in this thread. Is everyone too busy picking their jaws up off the floor? Or is everyone so ingrained in their thought camps that even a fairly slam dunk positive result doesn't matter either way? Personally, I've been somewhere in the middle recently, and this will likely push me to treat more patients IM nodes.
 

medgator

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OMG!

It's all retrospective but unless someone can find a reason why left-sided breast cacner bears a more unfavorable prognosis than right-side cancer, the Danish data may change my practice.
This is a 3% survival benefit caused solely by IM-RT in node positive patients...
Have to echo that. I've been more cognizant to do it when I can (I.e. not blasting the heart, not getting V20s as bad/worse than my lung Ca pts etc)
 

Gfunk6

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Call me a true believer/stubborn/dogmatic or whatever, but this will not change my practice. The problem with population based studies of this is that you have so many patients that you can generate low magnitude but statistically significant endpoints. Maybe the increase in left-sided mortality was driven by coronary atherosclerosis s/p XRT? Why is there no benefit in terms of DM? I would expect this with occult LN mets.

I need a Phase III randomized trial.
 

medgator

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Call me a true believer/stubborn/dogmatic or whatever, but this will not change my practice. The problem with population based studies of this is that you have so many patients that you can generate low magnitude but statistically significant endpoints. Maybe the increase in left-sided mortality was driven by coronary atherosclerosis s/p XRT? Why is there no benefit in terms of DM? I would expect this with occult LN mets.

I need a Phase III randomized trial.
The L sided pts didn't get IMN treatment and if you are speaking in terms of general xrt, I would have expected the RCTs in pmrt to show a difference in terms of L vs. R sided treatment. Would hope they weren't hitting the heart with R sided comprehensive pmrt :arghh:

Not sure we'll see a prospective phase III study coming out anytime soon. Short of that, I try to do it where I can when the plan allows for it and there are multiple risk factors.
 

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I think risk stratification is key, medial breast cancers have a higher tendency to drain to the IMN because that is part of their natural drainage pattern, so IMN treatment in a medial node positive breast cancer is highly likely if not proven to improve OS. You may argue that its a small benefit, but you could say that for any small benefit.. it only takes 1 IMN nodal recurrence to realize that mistake because they are quite hard to salvage (I've seen those with many many years of breast cancer experience treating IMN because of this). Lateral breast cancers are less likely to drain to IMN, but nevertheless in unstratified studies IMN treatment still showed some benefit! I'm not really sure what the major controversy is now.. the cardiac toxicity is possible, but has it been proven to outweigh the benefit of IMN treatment? I don't think so.. plus you are also making an assumption for the patient that years 10-20 post treatment are more important than years 0-10 if you are trying to avoid 20 year cardiac toxicity by slight increasing the risk of 0-10 year mortality....
 

Palex80

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Call me a true believer/stubborn/dogmatic or whatever, but this will not change my practice. The problem with population based studies of this is that you have so many patients that you can generate low magnitude but statistically significant endpoints. Maybe the increase in left-sided mortality was driven by coronary atherosclerosis s/p XRT? Why is there no benefit in terms of DM? I would expect this with occult LN mets.

I need a Phase III randomized trial.


Death by ischemic heart disease was the same in left and right treated patients.
Distant metastasis was less common in patients treated with IMRT by 2.5% and showed a trend to significance (p=0.07)
 
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