Hypofractionated RT to regional nodes in breast cancer

[Mandelin Rain]

Anyone do it? 14% of CHART patients, but I can't find a great description of what they did.

Same dose? 4005 cGy in 15 fx or 4256 cGy in 16 fx? Same blocks/field design?

EQD2 = 4675 cGy assuming a/B of 2 Gy. Is plexus a worry?

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[medgator]

Nope. I guess maybe in Europe I would but not in the U.S. until astro/acr endorses it

 

[user_name]

Copy/paste of radiation methods from British Columbia (Ragaz) trial in NEJM:
Radiation
The radiation therapy was administered between the fourth and fifth cycles of chemotherapy. Sixteen daily treatments were delivered over a period of three to four weeks. The postmastectomy chest wall received a dose of 37.5 Gy through two tangential fields. The mid-axilla received a dose of 35 Gy through an anterior supraclavicular–axillary field with a posterior axillary boost. A direct internal mammary field delivered a dose of 35 Gy at a depth of 3 cm. All the fields were treated with cobalt-60. The interval between the fourth and fifth cycles of chemotherapy was five to six weeks. Also, as part of a second randomization, 68 patients with estrogen-positive tumors were treated with radiation-induced ovarian ablation that included 20 Gy over a period of five days plus prednisone (7.5 mg per day) for two years, as described by Meakin et al.16 Among these 68 patients, 33 were assigned to chemotherapy and 35 were assigned to chemotherapy and radiotherapy.
Full article link: http://www.nejm.org/doi/full/10.1056/NEJM199710023371402#t=articleMethods

I have never done it, btw. I presented a case in peer review once for a patient with significant travel difficulties and got shot down by my partners.

 

[Damn_Daniel]

Both Danes and BC did hypofractionation, and we completely ignored what the positive trials showed. CHART did it, as well. At my former institution it was done on a semi routine basis. As a believer, in "extreme hypofractionation" it seems rational. Oh wait, the rest of the world does it, so maybe we are doing "extreme hyperfractionation". Whatever the f that means.

(One of the First Rate Docs on themednet.org said that in the community if a DCIS patient delayed her diagnosis and waited til she had invasive cancer, she would get HF, but if she gets diagnosed with DCIS, it earns her CF. FTW!)

I'd say the worry would be about the heart, it's really hard to get a good plan when the anatomy isn't favorable. Keeping MHD under 5 is challenging, and nearly impossible with IMN treatment. The last two cases even on the left side, I couldn't get the lung dose to be reasonable, and skipped it. Tried everything, PWT, shallow tangents with electron match, true IMRT plan. The ipsilateral lung dosi metric parameters aren't well defined. I have a feeling that we are being a bit conservative with V20<30, because when compared to lung data, these patients typically have healthy lungs, it's only one lung, it's a very discrete area rather than diffuse areas of the lung. Hopefully the secondary analyses of the regional node trials look at this

As someone said, once we get paid case rates (as Kaiser is already doing to private docs in areas that don't have Kaiser radiation departments), people will suddenly see the light.

 

[seper]

I don't think 42.6 Gy will cause any brachial plexopathies, but Gary Freedman warned against hypofractionating nodal treatments at last ASTRO due to that fear. I thought it was weird.

 

[Burt Radnolds]

I've done it, and it doesn't really scare me, except in relatively young patients (although this fear may be irrational, not sure...). I know some academic physicians who use it liberally. 50/25 is my standard for regional nodal RT, but I'm willing to revisit that and its an evolving thought process for me. Especially for people with barriers to care, 40/15 is better than no radiation at all! I do always opt for 40/15 (UK START style) and not 42.56/16, just to make me feel a little better.

Think about it theoretically from a BED standpoint. Lets assume an ultra-conservative a/b of 1 for the brachial plexus. The BED for 40/15 would be 146.8 and the BED for 50/2 would be 150. Even assuming a worst case scenario, its still less dose!

I contour the plexus in these cases, but have never had a problem or even required an adjustment due to plexus alone. I use identical fields to what I would use for conventional fractionation. I do not require the blessing of the ACR or ASTRO to use my brain and apply sound logic to patient care.

 

[Damn_Daniel]

Well, it's 3 weeks instead of 5, but yeah we don't really hear too much about brachial plexopathy, so I don't think it's a yooge issue. And absolutely don't need ASTRO's blessing for anything. Their consensus guidelines for PBI were hooey. They just made stuff up. Places like Beaumont that were treating everyone and their mother with it, and were showing great local control despite being deemed "cautionary" or whatever. Just because a bunch of people get together in a room to make some guidelines doesn't mean they know what they are doing, plus they may be hungry for lunch. Just because people are considered experts, doesn't mean they are infallible. I like the point about using brains and logic to make patient care decisions. It's very easy to justify more or more expensive treatment without strong data (boost for DCIS, dose escalation for lung cancer/esophageal cancer, chemo AND Erbitux with RT for HNC (we were seeing that a lot before), IMRT for everything, look at abstract 104 , but the moment we start justifying less treatment WITH data, people get very defensive about it. It's 2nd nature to protect one's income. There is data that hypofractionation for breast and prostate is hurting the bottom line for many centers and there are discussions about long term consequences. We are seeing more consults than ever before, and revenues are down, as are incomes. But, for patients, it's a good thing. People with breast cancer finish faster and return to their lives quicker. Same with men with prostate cancer. People were screaming bloody murder about Cyber for prostate. I don't do it because I don't have it, but I get why it would be attractive to patients. And, it's now mentioned as a possible treatment by the NCCN. We should be excited about a 5-10 treatment regimen vs 9.5 weeks. How cool is that?? People that are dying are going back to enjoying the things they want to do in their last days (with single fx bone treatment, with SRS only for brain mets). It's really great when we de-escalate. We are doing less axillary dissections and that's a great thing. We are doing more active surveillance for prostate cancer and that's great, too. Less chemotherapy with OncoType testing. Less WBRT. Less pelvic RT for endometrial cancer, and much more vaginal cuff BT. This is GOOD for patient care. Yes, we will take a hit financially. Yes, I feel sorry for those graduating now - there just isn't going to be enough jobs. There are community centers that are going to close down and good doctors being forced to move or staff places they didn't plan on. Yet, we are blessed with the opportunity to save lives, improve quality of life, and make people feel better. Belushi always said that we should use our enormous opportunity to do things right.

Vote Trump. He has the biggest caucus.

 

[Burt Radnolds]

3 weeks instead of 5? Lol. You sound like the people you are railing against. Quit giving them more excuses.

 

[Damn_Daniel]

I appreciate the thought. I'm just saying the calculation you did doesn't account for the treatment time difference and that's why i think your argument with the BED won't sway some people. Unfortunately we have to be cognizant that 150 BED in 3 weeks is not the same as 5 weeks. They are dumb, but we still have to account for those idiots.

The problem is we don't know what the difference is with the heart and lung doses. The BP is safe, as is the cord, and I think we are in agreement with that. I think a lot of people are just acting ridiculous with the other organs and we have to be more scientific about it. We will have data soon. But it's interesting that in America we took money into account, while in Denmark and Canada we took time into account. Yet, in America we have people waiting for an organization to say something is okay, while in other countries we look at data to say it's okay. Seems backwards as we seem to be less centrally organized, but when it comes to protecting income we view things in an opposite way.

 

[Burt Radnolds]

In my opinion, calling upon the dying cluster of rad bio neurons remaining, 3 vs 5 weeks should theoretically have minimal difference as far as normal tissue toxicity as calculated by BED. 24 hours between fractions should allow for maximal repair. People use the simple BED formula all the time to compare treatment schedules of varying length, although it's admittedly imperfect. I really only start to wonder about treatment length when thinking about accelerated repopulation, extreme hypofractionation/SBRT, or the effects of BID fractionation, which don't apply in this situation.

You are totally right though, people will believe what they want to believe. We all participate in various forms of data cherry picking. Unfortunately some of this is reimbursement centric and not patient centric.

 

[Damn_Daniel]

There have been people calling this "extreme hypofractionation". Hahahaahaha

 

[Palex80]

Coming soon... Results from this trial:

http://www.ncbi.nlm.nih.gov/pubmed/21752481

You thought 15-16 fractions were bad for incone? Try 5 fractions...

 

[Damn_Daniel]

Let me guess typical American responses:

1) we need longer follow up

Answer: almost never changes the answer

2) there weren't DCIS patients

Answer: it's a less deadly disease, let's extrapolate

3) we are going to go broke

Answer: sorry, bro

 

[Brim]

Let me guess typical American responses:

1) we need longer follow up

Answer: almost never changes the answer

2) there weren't DCIS patients

Answer: it's a less deadly disease, let's extrapolate

3) we are going to go broke

Answer: sorry, bro

I would want longer follow-up for any hypofractionated treatment in which late toxicity / cosmesis is the biggest concern.

If you'd like to know why, here's my rationale...

 

[thesauce]

The ipsilateral lung dosi metric parameters aren't well defined. I have a feeling that we are being a bit conservative with V20<30, because when compared to lung data, these patients typically have healthy lungs, it's only one lung, it's a very discrete area rather than diffuse areas of the lung.

It's a good thought but the healthy lung argument may not hold up. The V20 constraint is based on the incidence of radiation pneumonitis and that risk is actually lower in smokers. Healthy lungs may be more sensitive to radiation.

 

[thesauce]

Let me guess typical American responses:

2) there weren't DCIS patients

Answer: it's a less deadly disease, let's extrapolate

???

The fact that it's a less deadly disease is exactly the point. Hypofrac carries a higher risk of delayed effects. Obviously more of a concern with a less deadly disease.

 

[Damn_Daniel]

What risk of higher long term effects? I've never seen that in any study of hypofractionation for breast cancer. The BED for treatment were calculated in a way to mitigate that and the protocols for those studies explain that well. So, it's not surprising that there never has been a study for breast cancer showing that. We do have data showing worse QOL and worse late skin/cosmesis effects with conventional fractionation. Shouldnt the question be: "Why would we subject someone with lower disease to that risk?"

 

[thesauce]

What risk of higher long term effects? I've never seen that in any study of hypofractionation for breast cancer. The BED for treatment were calculated in a way to mitigate that and the protocols for those studies explain that well. So, it's not surprising that there never has been a study for breast cancer showing that. We do have data showing worse QOL and worse late skin/cosmesis effects with conventional fractionation. Shouldnt the question be: "Why would we subject someone with lower disease to that risk?"

Why do you fractionate at all? Why not just calculate the BED and give it in a single fraction of whole breast EBRT? I mean, so long as you adjust the BED and explain it, you should be good right?

Now let's be serious: we need to be cautious about adopting new regimens when the standard already works quite well. Cardiac is the biggest concern in my mind. Adding an extra week or two of treatment is not the end of the world for anyone - and if it is, we need to be thinking about goals of care.

Ironically, the place that I worked before had zero financial incentive to treat more (no bonuses or RVU requirements AT ALL) and no one did hypofrac there. It was actually annoying to read the press reports where people go back and forth about how it was all money-driven when I could see for a fact that it wasn't.

 

[Burt Radnolds]

Why do you fractionate at all? Why not just calculate the BED and give it in a single fraction of whole breast EBRT? I mean, so long as you adjust the BED and explain it, you should be good right?

Well, if I had 10 year results from multiple very large phase 3 trials showing same or better outcomes with same or better toxicity, I would highly consider it. You are acting like this has been plucked out of thin air with some fuzzy math drawn up on a scratch pad to back it.

In regards to cardiac toxicity, whats the difference? On nearly all of my left breast patients that I hypofractionate, I can achieve a complete heart block with scatter dose only. Mean doses are ~1Gy, which is ~6 cGy per fraction. I should probably put them through 2 extra weeks of treatment though so I can get that down to 4 cGy per fraction.

Just because you can give some anecdotal story about working at some place where all the doctors used more resources, patient time, and money with no financial incentive doesn't justify anything. Many reasons can be behind the decision making at play outside of money, but that doesn't make it more or less correct.

 

[thesauce]

Well, if I had 10 year results from multiple very large phase 3 trials showing same or better outcomes with same or better toxicity, I would highly consider it. You are acting like this has been plucked out of thin air with some fuzzy math drawn up on a scratch pad to back it.

I do "highly consider it." In fact, I do it most of the time. But I don't fault those that want to be more cautious in adoption of it. There are many, many more important clinic questions and I think it's ridiculous how much time and effort is spent on this one nuance. People are trying to build an academic career out of this and that's aggravating to me.

No one is acting like these regimens were "plucked out of thin air." A question was asked ("what risk of higher long term effects?") and it was pointedly answered from the standpoint of a radiobiological principle. Again, I do it much of the time. I think it works and is a great option for most patients. But I won't demonize my colleagues for feeling differently about certain cases WHEN BOTH OPTIONS SHOW GREAT RESULTS.

In regards to cardiac toxicity, whats the difference? On nearly all of my left breast patients that I hypofractionate, I can achieve a complete heart block with scatter dose only. Mean doses are ~1Gy, which is ~6 cGy per fraction. I should probably put them through 2 extra weeks of treatment though so I can get that down to 4 cGy per fraction.

I'm glad you're so diligent in sparing the heart, but I can assure you that not all radoncs out there are. And if we push the hypofrac agenda to all the old timers (many of whom have fallen completely into breast treatment since it's not terribly difficult) who aren't being so diligent with heart blocking, maybe we WILL see more late effects. Given the ALARA principle, I think if you asked the patients if they would be willing to come another week or two for a slightly lower heart dose, you WOULD get a lot of takers.

Just because you can give some anecdotal story about working at some place where all the doctors used more resources, patient time, and money with no financial incentive doesn't justify anything. Many reasons can be behind the decision making at play outside of money, but that doesn't make it more or less correct.

Out of curiousity, what other criticisms are made by the "eager adopters of hypofrac" versus the "non-adopters" as to why they don't do it? The only argument that I have ever heard is that they're greedy, but it sounds like you're heard "many reasons outside of money," so I'd like to hear them. Either way, it is by far the most common argument made, so I think it's worth addressing it. And yes, we are a small enough field that a large department with a couple dozen academic attendings all working harder to do what they feel is right is pretty convincing to me.

 

[Burt Radnolds]

I do "highly consider it." In fact, I do it most of the time. But I don't fault those that want to be more cautious in adoption of it. There are many, many more important clinic questions and I think it's ridiculous how much time and effort is spent on this one nuance. People are trying to build an academic career out of this and that's aggravating to me.

No one is acting like these regimens were "plucked out of thin air." A question was asked ("what risk of higher long term effects?") and it was pointedly answered from the standpoint of a radiobiological principle. Again, I do it much of the time. I think it works and is a great option for most patients. But I won't demonize my colleagues for feeling differently about certain cases WHEN BOTH OPTIONS SHOW GREAT RESULTS.

You are the one that was being condescending, making an example out of an extreme situation saying "why even fractionate at all" blah blah blah. This is you backpedaling.

I'm glad you're so diligent in sparing the heart, but I can assure you that not all radoncs out there are. And if we push the hypofrac agenda to all the old timers (many of whom have fallen completely into breast treatment since it's not terribly difficult) who aren't being so diligent with heart blocking, maybe we WILL see more late effects. Given the ALARA principle, I think if you asked the patients if they would be willing to come another week or two for a slightly lower heart dose, you WOULD get a lot of takers.

Heart dose has been stressed significantly recently in our literature, to the point where any self respecting rad onc knows it should be ALARA. You said you were worried about cardiac toxicity, I told you why I wasn't (heart block, low dose per fraction). Saying "well the old timers can't handle it so we should be careful" falls a bit flat to me. However, you may have a bit of a point there. Eventually though, they will retire and only practitioners well versed in proper CT based planning will remain, who can all block the heart.

Out of curiousity, what other criticisms are made by the "eager adopters of hypofrac" versus the "non-adopters" as to why they don't do it? The only argument that I have ever heard is that they're greedy, but it sounds like you're heard "many reasons outside of money," so I'd like to hear them. Either way, it is by far the most common argument made, so I think it's worth addressing it. And yes, we are a small enough field that a large department with a couple dozen academic attendings all working harder to do what they feel is right is pretty convincing to me.

I just stated that the fact a group of people does something does not in itself validate it, which I stand by. You have already touched on some reasons why people don't do it. Patient not a candidate in one's opinion, lack of awareness of data, innate lack of comfort changing after practicing a certain way for awhile, need for long term data to allay fear of toxicity outside of 10 years, money. You are right, conventional fractionation represents an appropriate version of standard of care. Hypofractionation is also an excellent option that I choose to practice in a large group of patients, which I do without any fear of increasing their toxicity. I am just trying to spread the good word, because I think it works as good or better, with the same or less side effects, with more convenience to the patient, while costing less money.

 

[thesauce]

You are the one that was being condescending, making an example out of an extreme situation saying "why even fractionate at all" blah blah blah. This is you backpedaling.

I'm sorry you took it that way as it was not the way it was intended. I am often interested to hear where people draw the line. There are theoretical concerns with hypofractionation and different physicians will have different theories, which is why we run these trials. Also various comfort levels in terms of followup, etc. I would love to know your definition of backpedaling because I used hypofrac before that post and use it just as much after. So not really sure where you're coming from with that comment.

Heart dose has been stressed significantly recently in our literature, to the point where any self respecting rad onc knows it should be ALARA. You said you were worried about cardiac toxicity, I told you why I wasn't (heart block, low dose per fraction). Saying "well the old timers can't handle it so we should be careful" falls a bit flat to me. However, you may have a bit of a point there. Eventually though, they will retire and only practitioners well versed in proper CT based planning will remain, who can all block the heart.

Even so, you recognize an opportunity to spare at least some heart dose with one accepted regimen and you use the other one. What difference in heart dose would you need to see in order to change your dose and fractionation? And in case you're wondering, I'm not being condescending.

I just stated that the fact a group of people does something does not in itself validate it, which I stand by. You have already touched on some reasons why people don't do it. Patient not a candidate in one's opinion, lack of awareness of data, innate lack of comfort changing after practicing a certain way for awhile, need for long term data to allay fear of toxicity outside of 10 years, money. You are right, conventional fractionation represents an appropriate version of standard of care. Hypofractionation is also an excellent option that I choose to practice in a large group of patients, which I do without any fear of increasing their toxicity. I am just trying to spread the good word, because I think it works as good or better, with the same or less side effects, with more convenience to the patient, while costing less money.

And that's great. And we can do that without making it seem like our colleagues are money grubbers looking out for only personal gain. I have somewhat different criteria for offering hypofrac that my colleagues do and I see no problem with that. Reasonable people can disagree.

The reasons that you've stated are the reasons why people don't do it and they should all be respected, aside from the financial concerns. My actual question was what other criticisms are made by the "eager adopters of hypofrac" versus the "non-adopters" as to why they don't do it (aside from being greedy)? The lay press has the public believing that it's completely money-driven and this is partially driven by quotes from oncology experts.

 

[Burt Radnolds]

Sorry for any misconceptions on your intents, lets keep it collegial. This conversation has had multiple people chipping in their 2 cents and was kind of taking on a life of its own. I didn't even know what aspect of hypofractionation was being debated towards the end.

I do believe that subconsciously a lot of people are holding on to conventional fractionation because it makes their bottom line look better. It may not be their sole reason, but it is part of it. Don't worry, I'm not going to go say that to any national outlet (no one wants my opinion anyway!). It's also fine if you disagree.

Regarding heart dose, I believe I disagree with how you are framing it. Please clarify, but you seem to be suggesting that I am using data that used 2Gy a fraction and am extrapolating it to 2.67 Gy a fraction? The infamous Darby et al. paper actually allowed a variety of fractionations and compared them using EQD2 with an a/b of 2. This is based off the same old BED equation I have been maligned for using by more than 1 person! Using this formula 40/15 directly to the heart with an a/b of 2 is actually less than 50/25. Furthermore we are only talking about scatter. So in truth, it's everyone else that is limited in their scope while I am analyzing dose in the same way our supposed best data on heart dose did. Using their same analytical methods, hypofractionation is gentler on the heart and all things equal will lead to less late cardiac toxicity.

I think I have already detailed out numerous times potentially criticisms users of hypofractionation have towards non-adopters, but I'll list them again.

It's easier on patients, local control is just as good, long term toxicity is better.

 

[Damn_Daniel]

... And short term toxicity is better, and QOL is better, and survival is better (one trial; no trials show conventional has better survival).

People continually justify conventional because of: 1) DCIS (non invasive disease, discredited) 2) high grade (discredited) 3) chemotherapy being used (discredited) 4) age (discredited) 5) long term toxicity (less in START trial) 6) acute toxicity (less in MDACC trial) 7) OAR doses (described well above).

Another thing I have to teach my very dumb residents about the Whelan paper is that the dose they refer to is central axis dose, not maximum dose. I have to go back to simple physics and explain that the central axis dose in a tangential plan is lower than the max dose in a plan, so unless you do 2D plans, don't use the number they give you in that trial. It differs substantially, sometimes. I have to tell these incompetent (until they graduate) dirtbags of human beings that if they bill for 3D sim, they should treatment plan with 3D parameters, and than they should look for volumes of ttheir PTV getting 105% (try to keep under 10%, but 15% is not unreasonable). The problem is people who don't know better say "max dose of 107%" because they only read press releases and abstracts, like these f-nuts I have to teach on a daily basis because I can't get a real job in a real city and make real money. Please tell me you all know this or I will have to go back to cutting to ease the pain.

It's not building a career off of it. It is doing the right thing.

Faster. Cheaper. Less side effects. More efficacy. Better QOL. Kanye could make a song about it.

If any other specialty had an intervention that did this, and 80% of that specialty did not adopt it, we would question them. The JAMA study shows that our field not adopting. I'm ashamed. Why aren't you?

The question shouldn't be: "Why are you hypofractionating this breast case?" It should be, "Why aren't you?"

Don't defend your outdated and suboptimal practice. No one thinks you're dumb. You're just uninformed. Be happy you took the time to learn and read and change it. That's what Belushi would have done. Watch Animal House. You'll understand.

Mike dropped