PMRT in a patient previously irradited for NHL

[Kroll2013]

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Dear Colleagues, I need your expert opinion concerning this case:
41-year old lady with excellent performance status, treated since 2011 for a stage IB PMBCL s/p 6 R-CHOP followed by consolidation 3D Conformal IFRT 30.6Gy in 17 fractions, currently in remission, self-palpated a lump in the UIQ of the left breast.
o The left mammogram shows 2 spiculated lesions one of which in the UOQ harboring microcalcifications, the other located in the UIQ lacking microcalcifications BIRADS-5
- US-guided core biopsies of both left breast lesions came back positive for ILC, grade 2, ER/PR (+), Her2 (-), Ki-67=15%
- MRI breasts: 24x20x23mm centrally-located mass in the UOQ of the left breast at 2 o’clock 26mm away from the nipple, 9mm deep to the lateral skin, 19x15x19mm similar lesion noted in the UIQ at 11 o’clock, 43mm from the nipple, 10mm deep to the lateral skin, - 20x11x13mm similar 3rd lesion noted at the edge of the UIQ at 2 o’clock, superficial, few millimeters away from the nipple, contacting the subcutaneous fat. This lesion is associated with thickening and retraction of the overlying skin
- FDG Pet-CT staging
o 3 hypermetabolic sites within the left breast in the UIQ, retroareolar and UOQ
o No regional hypermetabolic nodes
o No distant disease
- Bilateral nipple-sparing mastectomies + left sLND + bilateral expander insertion: mpT2N1a
o ILC, grade 2, T=2.5+2.1+2+0.6+0.1, LVi (+)
o Closest margin on ILC 1mm from the anterior retroareolar margin
o LN 0/4, 5mm tumor deposit in one SN, ECE (-)
o ER/PR (+), Her2 (-), Ki-67=20%
Oncotype Dx low risk : she will not receive chemotherapy.

would you give adjuvant RT for this patient taking into consideration the highlighted RF?

 

[Palex80]

Tricky case,

Correction: technically, this is LN 1/4. A 5 mm tumor deposit in a LN is 1/4, this is not even a micrometastasis.

Lymphatics do not worry me that much, limited involvement there and giving axillary RT, will not interfere with her previous irradiation, since it was a PMBCL.
Combining young age, LVSI+ and pN1, you have some arguments for axillary RT. However, she may be postmenopausal after her PMBCL-chemo and this is luminal-A breast cancer. Personally, I would not treat lymphatics.

The chest wall is my main concern. Multiple tumors and at least one with a close margin. Expander placement may complicate issues with RT. Technically, the cancer s completely resected, but the risk of locoregional failure is IMHO > 10% (combining LVSI, multiple tumors, margin).
It‘s on the left side, her heart has seen alot of dose from the previous treatment and it is imagineable that you may not see good heart separation with DIBH due to scaring of the prior lymphoma site behind the chest wall. So you may end up with a lot of heart in your volumes. Perhaps she has had a CT in inspiration for response assessment of her lymphoma that you can have a look at, to estimate if DIBH would work?
Frankly, I think I would observe here too, given the favorite biology of the tumor. I would have treated, if it had been more aggressive (like TNBC).

 

[TheWallnerus]

On the routine, rad oncs don’t mention sidedness and the cardiovascular risks of PMRT/IMN RT enough… and couple that with patient age and prior RT (assuming thoracic?) in this case, it has to go into decision making matrix somehow. It certainly doesn’t not affect the risk benefit ratio.

Disease was multifocal. Would be interesting to know if that correlates with previous RT fields, or if case meets classic definition for radiation induced malignancy. The expanders in this case don’t not affect the risk/benefit ratio either.

The benefit of PMRT in this N1a case is already mild, the number needed to treat pretty high; if one deviates from “the classic” RT volumes here, I would argue the benefit becomes even more difficult to suss. The late toxicity risk is higher than average if prior RT overlap, and higher than in a non-expander case.

Guess what my answer is.

 

[fiji128]

Even with the above mentioned considerations, I probably favor RT so long as typical cardiac dosing can be maintained.

 

[Bequerel]

Weak indication to offer PMRT. I’d lean towards omitting.

 

[RickyScott]

Would omit

 

[Ray D. Ayshun]

Multifocal disease with significant inner quadrant burden plus N+, LVI+ in a young patient seems like a reasonable nodal RT candidate, prior RT notwithstanding.

 

[OTN]

I would treat the chest wall. Multifocal, close margin, and LVI in a premenopausal woman.

 

[communitydoc13]

Lymphatics do not worry me that much, limited involvement there and giving axillary RT, will not interfere with her previous irradiation, since it was a PMBCL.

Likelihood of subclinical involvement of IM nodes here? I'm guess 50% or more?

Time course and location make secondary malignancy likely IMO. Not that this changes management.

Patient has likely incurred sigificant cardiac risk already. Unclear what added risk would be with breast plan.

Is this the rare proton breast case? (RN + IM/chest wall).

 

[TheWallnerus]

Likelihood of subclinical involvement of IM nodes here? I'm guess 50% or more?

And yet less than 1 in 100 N1 women recurred in the IMNs in the pre PMRT for N1 era; and the “systemic treatment” is only even better since then even for this non chemo patient. My only point to that is subclinical involvements don’t correlate well with recurrence risks in breast cancer.

If treating, how will everyone fractionate it. If forced to treat I’d give 48.6Gy/27fx (or maybe 49.95 Gy) to the CW only (CW, expanders, overlying skin) without bolus and enforce extreme homogeneity with 2 field inversely optimized opposing skin flashing tangents. Although I still think 0 Gy even better.

 

[Palex80]

Likelihood of subclinical involvement of IM nodes here? I'm guess 50% or more?

Good point, but that area may have been involved by the PMBCL and likely preirradiated. Do 30 Gy to the IMN when treating PMBCL alter the lymphatic spread pattern of a breast cancer down the road?

Patient has likely incurred sigificant cardiac risk already. Unclear what added risk would be with breast plan.

She may have already seen a heart Dmean of 15 Gy, unclear what adding another 5 Gy to that may do. No good, likely.

 

[TheWallnerus]

Good point, but that area may have been involved by the PMBCL and likely preirradiated. Do 30 Gy to the IMN when treating PMBCL alter the lymphatic spread pattern of a breast cancer down the road?

She may have already seen a heart Dmean of 15 Gy, unclear what adding another 5 Gy to that may do. No good, likely.

Do you think PMRT without ENI will affect OS in this case.

 

[Palex80]

If treating, how will everyone fractionate it.

28 x 1.8 Gy to the chest wall, sequential boost to the close margin region.
Likely another 5 x 1,8 Gy

Do you think PMRT without ENI will affect OS in this case.

Little data to back it up, but likely yes. I think highest risk of recurrence is still in the CW.
The fact that she will get implants, may make early recurrence detection trickier.

I am assuming something like 10% CW-recurrence risk and 4% lymphatics-recurrence risk.
I just made those numbers up.

What do you think?

 

[TheWallnerus]

28 x 1.8 Gy to the chest wall, sequential boost to the close margin region.
Likely another 5 x 1,8 Gy



Little data to back it up, but likely yes. I think highest risk of recurrence is still in the CW.
The fact that she will get implants, may make early recurrence detection trickier.

I am assuming something like 10% CW-recurrence risk and 4% lymphatics-recurrence risk.
I just made those numbers up.

What do you think?

Why the boost? What will you boost??

Whatever percent LRR risks I guess we won’t be far off from one another because the absolute risks are so small

There’s “no way” CW only PMRT can improve survival here imho. That’s why I asked 😉 At least there is no cogent way to guess what the OS benefit would be.

I think a strict textualist reading of current guidelines (not saying a guideline is the Bible by any means) would lead me to say: do no RT here in this case, there is no evidence for a boost absent weird factors like positive margins, and there is no evidence to do CW only PMRT in N+ disease

https://ascopubs.org/doi/10.1200/JCO-25-01747

 

[communitydoc13]

And yet less than 1 in 100 N1 women recurred in the IMNs in the pre PMRT for N1 era; and the “systemic treatment” is only even better since then even for this non chemo patient. My only point to that is subclinical involvements don’t correlate well with recurrence risks in breast cancer.

If treating, how will everyone fractionate it. If forced to treat I’d give 48.6Gy/27fx (or maybe 49.95 Gy) to the CW only (CW, expanders, overlying skin) without bolus and enforce extreme homogeneity with 2 field inversely optimized opposing skin flashing tangents. Although I still think 0 Gy even better.

Can internal mammary lymph nodes irradiation bring survival benefits for breast cancer patients? A systematic review and meta-analysis of 12,705 patients in 12 studies - PMC

To evaluate the effect of prophylactic irradiation of internal mammary lymph nodes in breast cancer patients. The computer searched PubMed, EMBASE, Web of science, CNKI, Wanfang Medical Network, the Chinese Biomedical Literature Database to find ...

pmc.ncbi.nlm.nih.gov

No need for us to rehash all the trials.

What I wouldn't do is irradiate IMN to reduce nodal recurrence. I think there is likely more to this.

Mutltifocal, medial, LVSI with positive axilla, young and ER+? If I were to pick a patient that might derive breast cancer survival benefit from IMN radiation, it might be this one?

 

[TheWallnerus]

What I wouldn't do is irradiate IMN to reduce nodal recurrence. I think there is likely more to this.

Then why make the point that there’s a 1 in 2 chance they harbor cancer cells

I agree on the point that PMRT makes the most sense/is most evidence based when adding ENI of some sort

 

[communitydoc13]

Then why make the point that there’s a 1 in 2 chance they harbor cancer cells

Those cells may impact late distant recurrence risk. See Danish IMN trial for instance.

Of course benefit modest in that trial (3% distant recurrence benefit at 15 years). But young age, medial location and tumor size all indicative of potentially more benefit.

That trial was laterality based, so cardiac toxicity not addressed in any reasonable way.

What would be wrong with a proton consult for this one? (you all know my general stance on protons).

 

[TheWallnerus]

What would be wrong with a proton consult for this one?

Would be fine. Insurance would approve too, after initial denial and appeal.

 

[Palex80]

Why the boost? What will you boost??

The close margin, it seems identifiable?

Whatever percent LRR risks I guess we won’t be far off from one another because the absolute risks are so small

There’s “no way” CW only PMRT can improve survival here imho. That’s why I asked 😉 At least there is no cogent way to guess what the OS benefit would be.

Why do you think so? Local recurrences can end up being deadly, by setting out mets themselves. Depending on biology, 1:1 (seldom) to 1:4 (common).

Have a look at this small retrospective analysis from S. Korea.

https://www.researchgate.net/publication/258057042_Treatment_results_of_breast_cancer_patients_with_locoregional_recurrence_after_mastectomy/

More than half of them had a locoregional failure involving only the chest wall and subsequently half of them developed mets.

I think a strict textualist reading of current guidelines (not saying a guideline is the Bible by any means) would lead me to say: do no RT here in this case, there is no evidence for a boost absent weird factors like positive margins, and there is no evidence to do CW only PMRT in N+ disease

https://ascopubs.org/doi/10.1200/JCO-25-01747

The margin is close. We boost the breast if the margin is close, why shouldn’t we boost the CW here too?

 

[RickyScott]

The close margin, it seems identifiable?


Why do you think so? Local recurrences can end up being deadly, ba setting out mets. Depending on biology, 1:1 (seldom) to 1:4 (common).

Have a look at this small retrospective analysis from S. Korea.

https://www.researchgate.net/publication/258057042_Treatment_results_of_breast_cancer_patients_with_locoregional_recurrence_after_mastectomy/

More than half of them had a locoregional failure involving only the chest wall and subsequently half of them developed mets.


The margin is close. We boost the breast if the margin is close, why shouldn’t we boost the CW here too?

Not sure if close chest wall margin is predictor of local failure vs lateral margin as there is nothing left to take against the pec.

 

[Palex80]

Not sure if close chest wall margin is predictor of local failure vs lateral margin as there is nothing left to take against the pec.

True, but OP mentioned that the close margin was „anterior retroareolar“. Which to me sounds like a nipple sparing mastectomy, preserving the areolar region. That is a true margin to me and tissue where a recurrence may happen.

 

[RadOncDoc21]

Breast is the worst 2025 version

 

[SneakyBooger]

No RT.

 

[evilbooyaa]

RT - 45-50.4 at 1.8Gy/fx, ignore the previous dose, counsel on increased risk of cardiac toxicity, keep heart mean ALARA (ideally < 4)

Treat traditional CW/RNI fields. Recommend DIBH as feasible.

A 41yo w/ all these risk factors, I think recommending RT is pretty defensible. < 10 LNs removed, I'm doing RNI here.

I don't love boosting pts w/ expanders/implants but if the close margin is identifiable, go for it.