Triple Neg with residual post neoadjuvant....

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Mandelin Rain

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.... med onc wants to give Xeloda during radiation. Are you hypofractionating or standard fractionation?

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Are you doing breast / chest wall only or RNI too?
 
I have done standard fractionation for this scenario. Anecdotally I have not seen any worse acute toxicity.
 
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I have had zero issues in this circumstance doing concurrent xeloda and hypofractionation. Haven't done it with RNI but I would definitely offer hypofractionation without hesitation.
 
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Damn, I need to read more!
 
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Sequential per study. Standard fractionation. Why the need to do concurrent?
 
Actually "back in the good old days", s/p CMF, during RT phase, M was dropped bc of skin toxicity
(see Barbara Fowble's articles).
Concurrent "CF" was fine with standard fractionation.
If "F" is OK, then my guess is that Xeloda is OK too, but I am guessing.
Probably no harm, but probably no significant gain from concurrent Xeloda bc you are not treating gross disease, you are treating microscopic disease (assuming the pt already had lumpectomy and SLN sampling.
 
Actually "back in the good old days", s/p CMF, during RT phase, M was dropped bc of skin toxicity
(see Barbara Fowble's articles).
Concurrent "CF" was fine with standard fractionation.
If "F" is OK, then my guess is that Xeloda is OK too, but I am guessing.
Probably no harm, but probably no significant gain from concurrent Xeloda bc you are not treating gross disease, you are treating microscopic disease (assuming the pt already had lumpectomy and SLN sampling.

Had a patient receiving chest wall xrt last year who med onc decided to give Xeloda to without informing me...pretty darn gnarly skin reaction.
 
I’ll say it again... breast is the worst!
 
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I'd want to know why concurrent? Agree that concurrent toxicity probably OK in terms of skin but Xeloda not really benign and if patient has significant GI or other toxicity then XRT may get interrupted.

Hard to imagine circumstance where medonc so worried that they want concurrent Xeloda and regional nodal wouldn't be recommended. (Subset data from NEJM trial showed strong correlation of benefit with residual nodal disease). These were also fit, young women on average. I'd guess there is no way your medonc is giving that dosing of Xeloda to an American woman?

In the NEJM trial, I think they enrolled women who got XRT after surgery once radiation was complete. This makes for some confounding as the time point for enrollment (the starting point used for their survival analysis) is really later relative to surgical assessment of response for those patients who received XRT relative to those who don't. They don't analyze any interactions between XRT administration and outcomes but this does worry me a little bit. It also makes those super early deviations in disease free survival in this trial not a great argument for starting Xeloda pronto.

A Phase II Study of Preoperative Capecitabine and Concomitant Radiation in Women with Advanced Breast Cancer This is also interesting to me. Futility was the rule in terms of systemic progression for really bad players who responded locally to concurrent therapy to the breast.

You can always give XRT after Xeloda. (This was allowed on the NEJM trial and again makes for some confounding in my opinion.)
 
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Nejm study was sequential. Not sure what's going on here
Agreed that it was sequential... But some hemeoncs want to give concurrent because they are ingrained to think concurrent is better than sequential for everything. Can't argue with many of them, you just deal with it...
 
Agreed that it was sequential... But some hemeoncs want to give concurrent because they are ingrained to think concurrent is better than sequential for everything. Can't argue with many of them, you just deal with it...
This is true, I’m sure if you told the med onc no, the very next rad onc would be happy to do it. That’s just how we rad oncs roll.

Better yet, that rad onc would recommend the opposite fractionation or fields just to emphasize they know more about breast cancer then you do especially since breast ca is the Wild West for radiation oncology (tangents only, high tangents, RNI +\- IM, standard fx, hypofx, +\- boost). Now concurrent vs sequential, nothing matters!
 
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Are you doing breast / chest wall only or RNI too?
Breast only

But also have a chestwall and nodes that is definitely getting standard.

Apparently, a run of residual disease triple negatives in my clinic.
 
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I wou
Breast only

But also have a chestwall and nodes that is definitely getting standard.

Apparently, a run of residual disease triple negatives in my clinic.
I would use hypofractionation for breast / chest-wall. I would not use a flap if chest-wall, unless I had to (inflammatory or whatever).
If RNI, I would still do hypofractionated if it's only axilla, but if I had to do comprehensive RNI (especially left-sided) I would rather normofractionate.
 
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First off, CREATE-X allowed user discretion on whether to give Xeloda sequentially or concurrently, so it was not built into the protocol or NEJM paper. However, Dr. Mutter personally communicated with the senior author and learned that it was given sequentially (Xeloda after RT) in the vast majority of patients: theMednet - Login

Therefore, 'per-protocol' either sequential or concurrent Xeloda is fine (in response to those who said sequential is 'per study').

Xeloda is used as a radiation sensitizer, and I have no reason to expect it would not act as a radiosensitizer in breast cancer, thus putting patient at higher risk for skin reaction if treated concurrently.

For a patient with residual node positive disease, especially ypN2 or ypN3 disease, I would actually favor given it concurrently, as I would feel the risk of metastatic disease in this patient subgroup would be high enough that a 6 week delay might be significant. A patient with ypN1 disease would be more of a grey zone for me - if they had some initially gnarly nodal disease or had pN1 and showed no response in both primary and LNs, then would consider concurrent.

For a patient that I was going to treat whole breast alone (meaning cN0 at initial diagnosis) I would NOT be a fan of concurrent Xeloda, regardless of fractionation. I would favor sequential with a hypofx regimen. This would be my first attempt - to discuss with med onc that her risk of metastatic disease is quite low and most patients on trial were treated with sequential Xeloda.

However, in the setting of a patient that is already committed to concurrent Xeloda, I would still offer breast hypofx. I would understand if somebody wanted to do conventional to 50/25, but given that the skin toxicities appear to be similar or even BETTER with 'standard' hypofx than conventional, I would personally favor use of hypofx.

Side note: This is discordant with how TDM-1 is given in Her2+ patients with residual disease (as per KATHERINE) trial, which mandated that TDM-1 be given concurrently with radiation (the way maintenance Herceptin is currently). I have seen worse toxicities with TDM-1 + RT in breast patients, but if anyone has a good series defining this in comparison to Herceptin + RT, that'd be greatly appreciated!

@Mandelin Rain can you provide more of a clinical history to the situation? I'm assuming cN0 patient (say T2 or T3N0) that got a lumpectomy?
 
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First off, CREATE-X allowed user discretion on whether to give Xeloda sequentially or concurrently, so it was not built into the protocol or NEJM paper. However, Dr. Mutter personally communicated with the senior author and learned that it was given sequentially (Xeloda after RT) in the vast majority of patients: theMednet - Login

Therefore, 'per-protocol' either sequential or concurrent Xeloda is fine (in response to those who said sequential is 'per study').

Xeloda is used as a radiation sensitizer, and I have no reason to expect it would not act as a radiosensitizer in breast cancer, thus putting patient at higher risk for skin reaction if treated concurrently.

For a patient with residual node positive disease, especially ypN2 or ypN3 disease, I would actually favor given it concurrently, as I would feel the risk of metastatic disease in this patient subgroup would be high enough that a 6 week delay might be significant. A patient with ypN1 disease would be more of a grey zone for me - if they had some initially gnarly nodal disease or had pN1 and showed no response in both primary and LNs, then would consider concurrent.

For a patient that I was going to treat whole breast alone (meaning cN0 at initial diagnosis) I would NOT be a fan of concurrent Xeloda, regardless of fractionation. I would favor sequential with a hypofx regimen. This would be my first attempt - to discuss with med onc that her risk of metastatic disease is quite low and most patients on trial were treated with sequential Xeloda.

However, in the setting of a patient that is already committed to concurrent Xeloda, I would still offer breast hypofx. I would understand if somebody wanted to do conventional to 50/25, but given that the skin toxicities appear to be similar or even BETTER with 'standard' hypofx than conventional, I would personally favor use of hypofx.

Side note: This is discordant with how TDM-1 is given in Her2+ patients with residual disease (as per KATHERINE) trial, which mandated that TDM-1 be given concurrently with radiation (the way maintenance Herceptin is currently). I have seen worse toxicities with TDM-1 + RT in breast patients, but if anyone has a good series defining this in comparison to Herceptin + RT, that'd be greatly appreciated!

@Mandelin Rain can you provide more of a clinical history to the situation? I'm assuming cN0 patient (say T2 or T3N0) that got a lumpectomy?

I'm pretty sure in CREATE-X the "choice" was related to sequencing (RT first or xeloda first), not to concurrent vs. sequential. At least that's my interpretation of the protocol (which is available as an appendix to the NEJM paper):

1611861318989.png


Likewise, my interpretation of the mednet discussion you linked is that they were clarifying that most patients were treated w/ RT first (not xeloda first), not clarifying that most were treated sequentially in general.

Another point brought up in that mednet discussion is that the xeloda dose is not your mother's chemosensitization dose (it's higher), and can be tough to tolerate even without concurrent RT.

We've adapted the create paradigm in our practice and never give concurrently for these reasons.
 
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I'm pretty sure in CREATE-X the "choice" was related to sequencing (RT first or xeloda first), not to concurrent vs. sequential. At least that's my interpretation of the protocol (which is available as an appendix to the NEJM paper):

View attachment 328502

Likewise, my interpretation of the mednet discussion you linked is that they were clarifying that most patients were treated w/ RT first (not xeloda first), not clarifying that most were treated sequentially in general.

Another point brought up in that mednet discussion is that the xeloda dose is not your mother's chemosensitization dose (it's higher), and can be tough to tolerate even without concurrent RT.

We've adapted the create paradigm in our practice and never give concurrently for these reasons.
This was my understanding as well. We're good at muddying the waters, but allowing concurrent or sequential seems a bridge too far.
 
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This was my understanding as well. We're good at muddying the waters, but allowing concurrent or sequential seems a bridge too far.
It’s breast, so muddying up the waters is expected. I’m sorry but it’s true!
 
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I'm pretty sure in CREATE-X the "choice" was related to sequencing (RT first or xeloda first), not to concurrent vs. sequential. At least that's my interpretation of the protocol (which is available as an appendix to the NEJM paper):

View attachment 328502

Likewise, my interpretation of the mednet discussion you linked is that they were clarifying that most patients were treated w/ RT first (not xeloda first), not clarifying that most were treated sequentially in general.

Another point brought up in that mednet discussion is that the xeloda dose is not your mother's chemosensitization dose (it's higher), and can be tough to tolerate even without concurrent RT.

We've adapted the create paradigm in our practice and never give concurrently for these reasons.

This was my understanding as well. We're good at muddying the waters, but allowing concurrent or sequential seems a bridge too far.
While these posts may be one way to look at it, per the MedNet poll, 22% of people are already giving it concurrently.... and I don't think see any suggestion that concurrent is 'wrong' per se.
 
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Re: regional nodes and HF.

The studies we base our treatment on (British Columbia, The Danes) utilized HF (one for all patients, one for some)

If anything is outside of the box, it's 50.4/28fx, not 37.5/15 ... I'm doing all hypo, now. Won't go back.

"Flap" = 100x better than bolus. Please use that terminology! Speaking of, I don't like using it for PMRT.

Have never used Kad, would have used concurrently as per Katie, but after reading MedNet / SDN, changed my mind. Sequential. Why chance it without knowing?

Concurrent Xeloda + RT = quite common in community practice (without evidence) but certainly seems logical for high risk disease.
 
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Re: regional nodes and HF.

The studies we base our treatment on (British Columbia, The Danes) utilized HF (one for all patients, one for some)

If anything is outside of the box, it's 50.4/28fx, not 37.5/15 ... I'm doing all hypo, now. Won't go back.

"Flap" = 100x better than bolus. Please use that terminology! Speaking of, I don't like using it for PMRT.

Have never used Kad, would have used concurrently as per Katie, but after reading MedNet / SDN, changed my mind. Sequential. Why chance it without knowing?

Concurrent Xeloda + RT = quite common in community practice (without evidence) but certainly seems logical for high risk disease.
I wish I could like your comment on dose/fractionation a million times. ALL rad oncs should know this because 90% still balk at the idea of hypofractionating RNI.
 
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Saw another today. Three in a week :(

They run the gambit of cT3N2 ypT1N1, cT2N1 ypT1bN0, and cT2N0 ypT1bN0
 
Re bolus in PMRT

British Columbia had a paper in red journal this month addressing that topic

tldr no difference for ‘usual’ cases
 
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Re bolus in PMRT

British Columbia had a paper in red journal this month addressing that topic

tldr no difference for ‘usual’ cases
If you look, when it's been studied, bolus use much more common in North America than rest of world (especially Europe). And yet PMRT XRT control rates seem to be the same regardless the geography. I can recall other studies too where erythema was correlated with better local control (but they were small and specious). There are SO MANY myths and dogmas that need to die in rad onc and needing to use bolus on everyone is one of 'em. Bolus Believers will still attend Bolus Church every Sunday tho.
 
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If you look, when it's been studied, bolus use much more common in North America than rest of world (especially Europe). And yet PMRT XRT control rates seem to be the same regardless the geography. I can recall other studies too where erythema was correlated with better local control (but they were small and specious). There are SO MANY myths and dogmas that need to die in rad onc and needing to use bolus on everyone is one of 'em. Bolus Believers will still attend Bolus Church every Sunday tho.
I almost never use bolus unless there's skin involvement. Easier for the therapists and patients don't hate you. I also am not a big fan of boosting the scar. Unlike a lumpectomy, the mastectomy scar is the same place regardless of tumor location, so it doesn't really portend the highest risk area for failure.
 
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I almost never use bolus unless there's skin involvement. Easier for the therapists and patients don't hate you. I also am not a big fan of boosting the scar. Unlike a lumpectomy, the mastectomy scar is the same place regardless of tumor location, so it doesn't really portend the highest risk area for failure.
I agree with the 1st part regarding bolus and the 2nd portion regarding scar boost should be intuitively true, but I'd say 85% of local mastectomy recurrences I've seen have been on the scar (at least at first).
 
I almost never use bolus unless there's skin involvement. Easier for the therapists and patients don't hate you. I also am not a big fan of boosting the scar. Unlike a lumpectomy, the mastectomy scar is the same place regardless of tumor location, so it doesn't really portend the highest risk area for failure.
The old school radbio rationale i learned was that the scar was the site of more hypoxia, hence the need for a boost
 
I hear you guys on the boost portion, but I definitely haven't seen the same thing. They nearly all fail regionally and/or distantly - which make sense because nearly all patients that I see who get a mastectomy in the first place have advanced regional disease to begin with.
 
I hear you guys on the boost portion, but I definitely haven't seen the same thing. They nearly all fail regionally and/or distantly - which make sense because nearly all patients that I see who get a mastectomy in the first place have advanced regional disease to begin with.
Not all, got a general surgeon who is a chop shop for all stages... it’s sad.
 
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The old school radbio rationale i learned was that the scar was the site of more hypoxia, hence the need for a boost


The radiobiologists would like to add something...

1612510538530.png
 
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There's one or two of those in town... Can't do a SLN either so everyone gets a full axillary dissection. He doesn't get a lot of referrals as a result...
You ever see those “mastectomies” that look like they just sewed two pieces of fat together? I was fooled once thinking it was just a terrible lumpectomy. Since he does such a horrible job with breast conservation, he usually ends up doing bilateral mastectomies and then just ask plastics to fix his mess.
 
I agree with the 1st part regarding bolus and the 2nd portion regarding scar boost should be intuitively true, but I'd say 85% of local mastectomy recurrences I've seen have been on the scar (at least at first).
That number is representing just pattern of failure, not that it needs additional dose, as far as I can see with the data. Danish study didn’t have a bolus or boost and had substantial portion of recurrences in the quadrant where the scar is. American data with bolus shows the same proportion of recurrences..

Modern data doesn’t seem to show a role for increasing the skin dose, but it’s certainly not “wrong” to bolus or boost.
 
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I agree with the 1st part regarding bolus and the 2nd portion regarding scar boost should be intuitively true, but I'd say 85% of local mastectomy recurrences I've seen have been on the scar (at least at first).

That number is representing just pattern of failure, not that it needs additional dose, as far as I can see with the data.
*DING* Drewdog but I didn't wanna say it. But the pattern of failure does show what a hard climb IMN XRT has, e.g., in affecting outcomes (*GROAN*).
 
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