.

[anonymuncule]

.

---

Members don't see this ad.

 

[Palex80]

I can think of very few scenarios where I'd have to radically treat breast cancer.

I've come across a few patients in their late 80s and 90s which rejected or were too ill to undergo surgery. I treated those with moderate doses of hypofractionated RT, usually in the range of 45-51 / 3. I've also had a lady who got 7 sessions of 5 Gy every other day. It's palliative treatment and I confined the volume to the tumor site (none of them had nodal disease) and did not treat the entire breast. It worked fine.
But that's palliative treatment, not radical treatment. It will suffice to control the tumor together with hormonal treatment for a few years, which is what the goal is, since all of these patients would die after a few years anyway.

I once came across a patient with a huge inflammatory-like tumor that extended bilaterally, but she already had metastatic disease. It was clearly inoperable. I treated her with 45 / 1.5 b.i.d. to all disease extension and controlled the disease quite well locally until she died from metastatic disease. The entire breast on the one side was involved and when the tumor shrank it looked like she had undergone a skin sparing mastectomy. I've never seen something like that before.

In some other cancer you are "forced" to perform radiation therapy rather than surgery, if the patient has a major contraindication for surgery. What I am confronted with once per year is a patient with an thromboembolic event (hear or brain) with maximum anticlot-drug therapy, which cannot be paused. These patients are very hard to operate on, because of the grave risk of bleeding and cannot go into the OR for 6 months or so. In breast cancer you can treat them with hormonal treatment or even chemo as "neoadjuvant" treatment and go for surgery later.

 

[OTN]

I've done this once. The patient had metastatic breast ca for several years and refused to have a mastectomy once her primary started growing through the skin. No other sites of progression. I tried very, very hard to talk her into mastectomy, but she refused. I treated to 70.2 Gy in 1.8 Gy daily fractions to the GTV + margin, 50.4 Gy to the entire breast. It responded very, very well and has not recurred in 2.5 years.

 

[Radiator20]

It would help to know what the patient's goal is here.

Curing her cancer? (implied by your asking about "radical" RT) I'm not sure whether there's data to speak to whether that’s possible. From a purely theoretical perspective, something like what OTN proposed seems reasonable, but I’m having trouble imagining a scenario in which she’s too unhealthy to undergo surgery, yet has low enough competing risks that she might benefit from such dose escalation.

Decreasing the chance that her cancer causes her problems over the remainder of her life (Ie, prophylactic palliative)? If she's medically inoperable (usually also means high competing risks / fairly short life expectancy), doesn't have local symptoms that need palliation now, and ER+, one option would be HT alone. I’d probably favor that over RT. If ER-... I don’t know, maybe a “high dose palliative” regimen like 45/3 to GTV plus a margin, like Palex mentioned?

 

[Burt Radnolds]

There is a more robust experience than one might expect. Refer to the attached tables for experiences with both radiation and chemoradiation.

 

[radtothebone]

SBRT might also be a reasonable approach....https://www.practicalradonc.org/article/S1879-8500(18)30081-X/abstract

 

[medgator]

I always wondered about chemoradiation if confronted with this scenario.

As radiator said, if I saw a patient who needed some local control at dx without surgery, I'd see what kind of mileage I got with hormonal therapy first if the tumor was ER+

 

[2014XRT]

SBRT might also be a reasonable approach....https://www.practicalradonc.org/article/S1879-8500(18)30081-X/abstract

yeah for a select patient with a small tumor, this is the way I would think about going. if the patient is limited by comorbidities, 5 fx is a nice easy way to go.

 

[OTN]

My situation was pretty unique, to be honest. Patient was perfectly healthy to undergo surgery and had been on HT for some time when her primary progressed. She had already had metastatic disease for several years and had no evidence of progression other than in the breast. As a result, I thought her expected survival was to be measured in years rather than months. She adamantly refused to have a mastectomy, despite my really trying to convince her.

Most of the data we do have as shown above in Table 8 with RT alone (she refused any chemo at that time as well) has used traditional fractionation to ~70 Gy, and I was happy with both the short- and long-term outcomes of her case.

 

[Radiator20]

There is a more robust experience than one might expect. Refer to the attached tables for experiences with both radiation and chemoradiation.

View attachment 234431

View attachment 234432

Radmonckey, those are great tables. Thank you. Where do they come from?

My situation was pretty unique, to be honest. Patient was perfectly healthy to undergo surgery and had been on HT for some time when her primary progressed. She had already had metastatic disease for several years and had no evidence of progression other than in the breast. As a result, I thought her expected survival was to be measured in years rather than months. She adamantly refused to have a mastectomy, despite my really trying to convince her.

Most of the data we do have as shown above in Table 8 with RT alone (she refused any chemo at that time as well) has used traditional fractionation to ~70 Gy, and I was happy with both the short- and long-term outcomes of her case.

OTN, it's interesting to hear more of the background of the case. Hats off to you for doing that--I would have felt some trepidation but apparently it was the right call! Thanks for sharing.

 

[seper]

Did not read that PRO paper, but I'd worry about lack of reproducibility for supine breast SBRT

 

[emt409]

yeah for a select patient with a small tumor, this is the way I would think about going. if the patient is limited by comorbidities, 5 fx is a nice easy way to go.

I just got a pilot trial funded at my institution to do 30Gy/5fx adjuvant SBRT for APBI candidates, long term, we would like to do a pre-op SBRT trial, which of course would give us pCR rates.

 

[seper]

I would imagine one would need to push higher that 30Gy/5 to get response rate > 10%.

I just got a pilot trial funded at my institution to do 30Gy/5fx adjuvant SBRT for APBI candidates, long term, we would like to do a pre-op SBRT trial, which of course would give us pCR rates.

 

[Palex80]

I just got a pilot trial funded at my institution to do 30Gy/5fx adjuvant SBRT for APBI candidates, long term, we would like to do a pre-op SBRT trial, which of course would give us pCR rates.

Are you planning to give that dose in one week? Daily fractions?

 

[2014XRT]

I just got a pilot trial funded at my institution to do 30Gy/5fx adjuvant SBRT for APBI candidates, long term, we would like to do a pre-op SBRT trial, which of course would give us pCR rates.

I think Janet Horton from Duke has been doing this, pre-op, single fraction actually. I think she has more recent data since this time but here is her paper

Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers. - PubMed - NCBI

 

[emt409]

Are you planning to give that dose in one week? Daily fractions?

Daily fractions. We want to let women be done in a week. Treated prone, with biozorb fiducials.

I think Janet Horton from Duke has been doing this, pre-op, single fraction actually. I think she has more recent data since this time but here is her paper

Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers. - PubMed - NCBI

Yea, our group is a bit more conservative, and will probably still want to do 5fx, I'd love to do single fraction like Horton though.

I would imagine one would need to push higher that 30Gy/5 to get response rate > 10%.

For neoadjuvant, agreed; for adjuvant 30Gy/5fx is basically same BED as Canadian without boost for alpha/beta of ~6. We will dose escalate after pilot.

 

[napoleondynamite]

I'll rain on the parade here a little. I had a patient once in her 80's with locally advanced disease, excellent performance status. She came to me with gross residual disease after mastectomy at the chest wall. R0 would have required radical mastectomy, which she refused. Refused any chemo. I treated to 70Gy. The tumor grew. She died a horrible death from local progression.

Sent from my Pixel 2 XL using SDN mobile

 

[Palex80]

Daily fractions. We want to let women be done in a week. Treated prone, with biozorb fiducials.

Just some thoughts:
You may be overtreating them with this dose & fractionation.
39.9/2.66 in 3 weeks has been proven as adequate PBI in IMPORT low with almost no recurrent disease.
30 / 6 is more than 39.9 / 2.66 in terms of BED for healthy tissue, I'd be cautious. The British have published preliminary data on WBRT with 30 / 6 but with 1x/week fractions.

I'd be concerned about toxicity with 30 /6 in 1 week, remember the RTOG trial tried also to put all the dose in in one week and had not so good cosmetic results.

My guess: 25 /5 should be enough and better tolerated.

For neoadjuvant, agreed; for adjuvant 30Gy/5fx is basically same BED as Canadian without boost for alpha/beta of ~6Gy

Perhaps, but not for healthy tissue.
START-B used a lower BED when they tried figuring out what dose to give instead of 50/2 and they were proven right with 39.9/2.66.
Plus, if you are giving all the dose in 1 week the linear-quadratic model is probably not the best to use with single doses of 6 Gy. The acceleration of treatmemt time is not been taken enough into account.

 

[emt409]

Just some thoughts:
You may be overtreating them with this dose & fractionation.
39.9/2.66 in 3 weeks has been proven as adequate PBI in IMPORT low with almost no recurrent disease.
30 / 6 is more than 39.9 / 2.66 in terms of BED for healthy tissue, I'd be cautious. The British have published preliminary data on WBRT with 30 / 6 but with 1x/week fractions.

I'd be concerned about toxicity with 30 /6 in 1 week, remember the RTOG trial tried also to put all the dose in in one week and had not so good cosmetic results.

My guess: 25 /5 should be enough and better tolerated.



Perhaps, but not for healthy tissue.
START-B used a lower BED when they tried figuring out what dose to give instead of 50/2 and they were proven right with 39.9/2.66.
Plus, if you are giving all the dose in 1 week the linear-quadratic model is probably not the best to use with single doses of 6 Gy. The acceleration of treatmemt time is not been taken enough into account.

All good points, BED for normal breast is roughly 20% higher for this fraction, however, it must be considered that we are only treating the cavity (and a very precisely defined cavity by fiducials at the boundary) plus 1.5CM expansion (CTV and PTV) to that dose, the fall-off is very rapid because of a non-coplanar IMRT beam distribution. The amount of normal breast tissue receiving this dose is far lower than the amount of breast tissue getting between 100 and 107% in even a very well planned set of tangents.

Cosmesis results for the Timmerman phase II trial with this fractionation have been excellent, and our plans (hopefully) will be superior to his because his trial required greater expansions and had more cavity uncertainty. Additionally, our fiducials allow amplitude-based triggered imaging/treatment.

If I get a chance today, I'll post the results from my pre-clinical dosimetry.

 

[BobbyHeenan]

I occasionally use the 30 Gy in 5 fraction APBI regimen as outlined in this Italian Randomized Trial. That's at least a robust clinical experience suggesting they have good cosmesis with this. When I have a small cavity and clips or biosorb I have used it and had good success. I do treat every other day though. Cleveland Clinic does this as well - at least according to one of their breast attendings on themednet.

For larger cavities not amenable to HDR APBI or 30 Gy in 5 (or I'm having trouble delineating a clear seroma) I then sometimes use 40/15 a la UK IMPORT LOW with a generous "partial breast" volume with aggressive heart/lung blocking.

 

[MDACCRules]

Horton is preop to the identified tumor. This 5 fraction / 30 Gy is adjuvant. I'd presume that you do different doses for preop/intact vs adjuvant? What's the rationale for preop by the way?

 

[emt409]

Horton is preop to the identified tumor. This 5 fraction / 30 Gy is adjuvant. I'd presume that you do different doses for preop/intact vs adjuvant? What's the rationale for preop by the way?

We would indeed. Rationale for pre-op is better control for high-risk cancers. There's a JCO paper showing that women with triple negative, luminal B/HER2–negative–like tumors, and HER2 positive nonluminals do much better with pCR to neoadj chemo. Hypothesis would be that addition of preop SRS to NA chemo would increase pCR rate. Women with high risk tumors could get MRI before and after chemo to assess for residual disease, if residual disease, then SRS before surgery.

What do you guys think?

 

[evilbooyaa]

Women with triple negative cancer met out more right? Which is why showing that they have a response to chemo (AKA pCR) is useful to their survival. I don't really think doing pre-op RT adds to that paradigm. I don't think it's forcing a patient to pCR above all else that is going to improve outcomes.

 

[MDACCRules]

Yeah.. it's not necessarily true that NAC is better than adjuvant, but it does give you something you can actually assess pathologically - great for drug companies to get things out to market faster. Anyway ... I don't think it's a bad idea. I just don't know if it changes anything as far as outcome. Maybe get everything done a little faster?

 

[Radiator20]

I'm with evilbooyaa on this. I have always understood the fact that pts with a pCR do better to be a reflection of (even a test of) underlying biology - the women who have a pCR also likely would have done better than other women had everybody gotten adjuvant chemo intead, b/c they have more treatment-responsive disease. At least with neoadjuvant chemo, you're (theoretically) also addressing micrometastatic disease earlier. While neoadjuvant RT might increase pCR rates, not sure that means those women are going to do any better than if they'd gotten adjuvant RT. That, of course, is a testable question (akin to the upfront/outback chemo trial)...

 

[Palex80]

All good points, BED for normal breast is roughly 20% higher for this fraction, however, it must be considered that we are only treating the cavity (and a very precisely defined cavity by fiducials at the boundary) plus 1.5CM expansion (CTV and PTV) to that dose, the fall-off is very rapid because of a non-coplanar IMRT beam distribution. The amount of normal breast tissue receiving this dose is far lower than the amount of breast tissue getting between 100 and 107% in even a very well planned set of tangents.

Cosmesis results for the Timmerman phase II trial with this fractionation have been excellent, and our plans (hopefully) will be superior to his because his trial required greater expansions and had more cavity uncertainty. Additionally, our fiducials allow amplitude-based triggered imaging/treatment.

If I get a chance today, I'll post the results from my pre-clinical dosimetry.

Thank you for clarifying this. It's just that we have the negative experience with the RTOG0413-trial (which used an even higher dose that you are planning to within 1 week). Noone is using the RTOG-schedule anymore.

 

[medgator]

86 y/o smoker with a 3 cm ER+/H2N- breast CA with bx-proven LNs that have grown since bx after 2 months of AI therapy. Surgeon says she will "die" if she gets surgery and she smells like an ashtray. Lymph nodes are literally the size of oranges now, med onc has no interest in giving her neoadjuvant IV chemo.

Thinking of getting a PET/CT to confirm no distant mets and 63-66 Gy with Xeloda? Thoughts?

 

[evilbooyaa]

Not ideal, but if surgery and med-onc are completely abandoning her, then so be it. Multiple other co-morbidities to really justify complete lack of surgical intervention outside of just age and smoking?? If you disagree with surgeon assessment, can't hurt to send referral to local tertiary center for evaluation by (likely) more aggressive surgeons, after discussion with local surgeon of course given private practice environment.

 

[medgator]

Not ideal, but if surgery and med-onc are completely abandoning her, then so be it. Multiple other co-morbidities to really justify complete lack of surgical intervention outside of just age and smoking?? If you disagree with surgeon assessment, can't hurt to send referral to local tertiary center for evaluation by (likely) more aggressive surgeons, after discussion with local surgeon of course given private practice environment.

Thought about it but clearly it will need conventional chemo before aggressive surgery and that chemo would likely need to be done locally....

 

[DebtRising]

Thank you for clarifying this. It's just that we have the negative experience with the RTOG0413-trial (which used an even higher dose that you are planning to within 1 week). Noone is using the RTOG-schedule anymore.

RTOG 0413 posted good cosmetic results at interim. It was the RAPID trial that posted poor cosmesis with a 3DCRT approach. A number of single institution prospective trials also refuted RAPID using IMRT.

The RTOG 0413 APBI schema is very much alive, and deserves to be. 0413 also has a cohort above 'low risk' - import low and the IORT trials had populations of ultra low risk only.

As for doing a pre-op trial - it's a great idea. The data for pCR rates is needed to inform trials for non-surgical management of breast cancer. Single fraction or SBRT is probably not the way to go for that question due to the need for greater total dose for gross disease and ultimate lack of scarring, but what do I know

 

[Reaganite]

86 y/o smoker with a 3 cm ER+/H2N- breast CA with bx-proven LNs that have grown since bx after 2 months of AI therapy. Surgeon says she will "die" if she gets surgery and she smells like an ashtray. Lymph nodes are literally the size of oranges now, med onc has no interest in giving her neoadjuvant IV chemo.

Thinking of getting a PET/CT to confirm no distant mets and 63-66 Gy with Xeloda? Thoughts?

I've seen more "patient will die with surgery" breast cases than I ever expected and have been pleasantly surprised with the durable control I've seen with XRT alone. I've typically gone to 60-66 Gy targeting GTV only (especially if using concurrent xeloda since you can get pretty dramatic skin reaction if you treat whole breast).

 

[Radiator20]

86 y/o smoker with a 3 cm ER+/H2N- breast CA with bx-proven LNs that have grown since bx after 2 months of AI therapy. Surgeon says she will "die" if she gets surgery and she smells like an ashtray. Lymph nodes are literally the size of oranges now, med onc has no interest in giving her neoadjuvant IV chemo.

Thinking of getting a PET/CT to confirm no distant mets and 63-66 Gy with Xeloda? Thoughts?

1) Might still be worth referral to academic center for both med onc and surg onc. Could be that med onc there would have more enthusiasm for neoadjuvant chemo f/b surgery there. Even if she is unable to get chemo there, that second opinion might sway local med onc into reconsidering chemo locally.

2) If we’re really off the path of standard curative-intent tx, wonder if med onc would consider adding palbo or another CKDi, prior to RT? With short interval f/u, see if you get any downstaging? (Might even allow you to delay/defer RT) Would not do palbo concurrent with RT, of course.