Zietman Editorial

[Damn_Daniel]

In JCO and worth a read. He's a very good writer. Irony is they are pumping out residents by the dozens at Harvard, and he's also advocating less fractions. Real push - pull there.

Choice lines:

"If treatment is unnecessary in the first place, better treatment does not represent an advance."

"These schedules should now be discussed as options with patients, who must be also be made aware of a small, perhaps trivial, increase in the risk of toxicity. It is probable that these short courses will appeal strongly to many elderly patients and to those who travel a great distance to undergo treatment."

"A different explanation may be inferred from the fact that, in our fee-for-service payment system, radiation oncologists are paid by the fraction, and hypofractionation thus threatens income. This is not the case in either the United Kingdom or Canada, and, with bundled payments in the future, may cease to be an issue in the United States."

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[Gfunk6]

Thanks for posting this, it was a good read. I agree with what you wrote in the first paragraph.


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[BobbyHeenan]

I thought it was a good read.

I've been using hypofractionation for patients with low AUA symptoms scores (the previous Pollack/Fox Chase trial suggested scores >12 did worse with GU toxicity). Not sure if that played out in 0415.

I hate to continue the ASTRO/Ivory tower academics bashing that goes on...but an article about "societal benefits" and "cost" for prostate radiation that does not address proton therapy is incomplete in my opinion. To Zeitman's credit he wrote a good opinion piece earlier on proton for prostate (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863190/), but to discuss cost for prostate XRT in the JCO and fail to mention protons is an oversight in my estimation.

 

[Mandelin Rain]

Couple problems here.

1. Radiation biology is largely hocus pocus based on sketchy modeling. The a/B is based on a calculation rather than any physical or biologic property, and this calculation is to be applied broadly across a disease which is assumed to be homogenous (as if all prostate cancers are the same biologically). The calculated a/B for prostate has varied wildly from less than normal tissue to twice that of normal tissue. There seems to be a consensus that there exists a "hypothesis" that prostate cancer a/B "may be" low, but definitive proof is lacking. From the article, "Depending on the hypothetical α/β variables put into the linear-quadratic model, the hypofractionated courses may have been too much, not enough, or ideal in terms both of cancer control and normal tissue tolerance." Sure... let's put faith in that model.

2. The studies cited suck. Who is treating prostate cancer to 74 Gy or less? We know dose escalation works in prostate cancer. Comparing hypofractionation to sub-standard doses of radiation and coming out with more toxicity regardless of how trivial it is, sucks.

3. How do you rectify that the standard arms of our cooperative group trials are 44 fractions and then freely offer treatment in 20 fractions based on sketchy data. Good luck ever putting anyone on a trial that may say something meaningful.

4. "A different explanation may be inferred from the fact that, in our fee-for-service payment system, radiation oncologists are paid by the fraction, and hypofractionation thus threatens income. " Please shut down the cyclotron at your institution and then get after this point.

 

[BobbyHeenan]

Couple problems here.

1. Radiation biology is largely hocus pocus based on sketchy modeling. The a/B is based on a calculation rather than any physical or biologic property, and this calculation is to be applied broadly across a disease which is assumed to be homogenous (as if all prostate cancers are the same biologically). The calculated a/B for prostate has varied wildly from less than normal tissue to twice that of normal tissue. There seems to be a consensus that there exists a "hypothesis" that prostate cancer a/B "may be" low, but definitive proof is lacking. From the article, "Depending on the hypothetical α/β variables put into the linear-quadratic model, the hypofractionated courses may have been too much, not enough, or ideal in terms both of cancer control and normal tissue tolerance." Sure... let's put faith in that model.

2. The studies cited suck. Who is treating prostate cancer to 74 Gy or less? We know dose escalation works in prostate cancer. Comparing hypofractionation to sub-standard doses of radiation and coming out with more toxicity regardless of how trivial it is, sucks.

3. How do you rectify that the standard arms of our cooperative group trials are 44 fractions and then freely offer treatment in 20 fractions based on sketchy data. Good luck ever putting anyone on a trial that may say something meaningful.

4. "A different explanation may be inferred from the fact that, in our fee-for-service payment system, radiation oncologists are paid by the fraction, and hypofractionation thus threatens income. " Please shut down the cyclotron at your institution and then get after this point.

Amen on number 4. If you start preaching from the pulpit about cost for prostate radiation yet have had a cyclotron for what, ?20 years now?, are just now running phase III prostate trials (IMRT vs. proton) on it, yet have treated (and continue to do so) patients on it with little to no data saying it's better than IMRT (and even some poor quality data saying it may be worse)....then it's hard to swallow the preaching about fee-for-service from the plebeians out here in practice having to explain (sometimes unsuccessfully) to patients why they shouldn't empty their 401K to get protons for their low risk prostate cancer.

 

[Damn_Daniel]

1. Sure. But, there is evidence building that it's the case, and it's worthwhile to build the hypothesis. It's just as hocus pocus to say a/b is 2 as it is to say it's 10. My money is on lower, rather than higher.

2. That's true we don't treat to 74 Gy, but what were the doses in the dose escalation trial? 78 Gy (MDACC)? 79.2 Gy (PROG)? 78 (Dutch)? These were all to isocenter. My plans are about 105-7% hot, typically. So, 73.8 presribed to 98% of PTV (This trial) = 77-79 Gy. People always forget that all of those trials are prescribed to isocenter. It's not substandard doses of RT, it's actually equivalent to what the trials used. What were they supposed to do? Just make up a new high dose? That's not very scientific.

3. ???

4. Total hypocrisy ... But, the Anthonies probably make less than most private practice docs, and work much harder, so maybe Harvard as the institution is the hypocrite.

 

[Mandelin Rain]

So you prescribe 74 Gy to 98% of PTV (which is what the question was), or no?

 

[BobbyHeenan]

1. Sure. But, there is evidence building that it's the case, and it's worthwhile to build the hypothesis. It's just as hocus pocus to say a/b is 2 as it is to say it's 10. My money is on lower, rather than higher.

2. That's true we don't treat to 74 Gy, but what were the doses in the dose escalation trial? 78 Gy (MDACC)? 79.2 Gy (PROG)? 78 (Dutch)? These were all to isocenter. My plans are about 105-7% hot, typically. So, 73.8 presribed to 98% of PTV (This trial) = 77-79 Gy. People always forget that all of those trials are prescribed to isocenter. It's not substandard doses of RT, it's actually equivalent to what the trials used. What were they supposed to do? Just make up a new high dose? That's not very scientific.

3. ???

4. Total hypocrisy ... But, the Anthonies probably make less than most private practice docs, and work much harder, so maybe Harvard as the institution is the hypocrite.

I don't care how much Zeitman makes. I don't care that these academic docs are making bank. He and many others have done tremendous things for the field, present residency/proton issue notwithstanding.

What I do care about is how ASTRO is basically silent on protons for prostate and he has a HUGE platform in the JCO to discuss cost, fails to address protons. He's not hypocritical because he is or isn't making bank, he's hypocritical because he's suggesting "other" doctors will use standard fractionation for monetary incentives and addressed cost in the component of prostate radiation....yet treats patients (and now many many other physicians do as well) with a technique that is of questionable benefit but is way more costly than IMRT.

 

[Damn_Daniel]

Unless something has changed, I don't think they routinely treat prostates with protons in Boston, when not on study (he said that at a talk). Maybe he was being cheeky? Maybe he gave a big wink before he said that? Maybe I was ****-faced at the lecture and mis-remember? I don't know. I was under the impression that they didn't feel it was cost effective and don't use it off study.

 

[BobbyHeenan]

Unless something has changed, I don't think they routinely treat prostates with protons in Boston, when not on study (he said that at a talk). Maybe he was being cheeky? Maybe he gave a big wink before he said that? Maybe I was ****-faced at the lecture and mis-remember? I don't know. I was under the impression that they didn't feel it was cost effective and don't use it off study.

If that is the case then I commend him. I would like to see him preaching this in the JCO, but so be it. Like I posted earlier, his previously published commentary (in a far far lesser journal) was very well done.

 

[Damn_Daniel]

So you prescribe 74 Gy to 98% of PTV (which is what the question was), or no?

No, I do 77.4 Gy covering 95% of the volume. I'm not saying I follow the old study. As I've said a million times, I just follow the NCCN for everything, as I'm just a simpleton.

I'm just saying, if you are writing a dose escalation trial in 2005, and your basis for the high dose is 3 published RCTs using 76-79 Gy to isocenter, and now you live in an ICRU/volume based world, and you can't go back to a non-ICRU/volume-based world because that's not how IMRT works, than you're sort of stuck. Say they prescribed 79.2 Gy to PTV. Then, that harm showed more toxicity. The editorial would say, "Dude, why did you pick a dose way higher than what was used be 3 published randomized trials."

How would you have justified 77.4-79.2 to PTV as the control arm at that time? Would have became a phase II trial, because both doses were non-standard.

 

[radiaterMike]

Zietman has been an advocate of treating with proton therapy for prostate cancer only on trial.

Also not fair to say that ASTRO has been silent on proton therapy for prostate cancer. The Choosing Wisely campaign stated:

"Don’t routinely recommend proton beam therapy for prostate cancer outside of a prospective clinical trial or registry... There is no clear evidence that proton beam therapy for prostate cancer offers any clinical advantage over other forms of definitive radiation therapy. Clinical trials are necessary to establish a possible advantage of this expensive therapy."

Also, the ASTRO model policy and the ASTRO 2013 position statement states the same:
https://www.astro.org/uploadedFiles/Main_Site/Practice_Management/Reimbursement/ProtonProstateStatement.pdf

 

[BobbyHeenan]

Zietman has been an advocate of treating with proton therapy for prostate cancer only on trial.

Also not fair to say that ASTRO has been silent on proton therapy for prostate cancer. The Choosing Wisely campaign stated:

"Don’t routinely recommend proton beam therapy for prostate cancer outside of a prospective clinical trial or registry... There is no clear evidence that proton beam therapy for prostate cancer offers any clinical advantage over other forms of definitive radiation therapy. Clinical trials are necessary to establish a possible advantage of this expensive therapy."

Also, the ASTRO model policy and the ASTRO 2013 position statement states the same:
https://www.astro.org/uploadedFiles/Main_Site/Practice_Management/Reimbursement/ProtonProstateStatement.pdf

Yeah - "quiet" was hyperbole for me. You're right, those are fair statements from ASTRO that I support, though I think "registry" trials can be junk though in the proton/prostate setting - it's basically just a way to get the patient on a "study" to get insurance to pay for it.

I guess I should have clarified that I have perceived ASTRO to have been underwhelming in not addressing rapid proton expansion, the bulk of which relies on treatment of prostate to keep it profitable.

And I agree with Zietman on the trial thing. I am fully supportive of the phase III trial. The problem is in my market (and some colleagues) across the country a TON of their prostates are being treated on "registry trials" at the newer proton centers (some of them private centers) where marketing trumps all.

 

[Damn_Daniel]

You're right. Registry trials are rubbish.

There is another model for proton centers that a very smart health system is doing. Essentially, they are opening a full on proton center (not single gantry nonsense), but running it like a state utility - as it is a state supported system. They are offering partnerships with the private practices in the community to send patients for treatment. If you send patients, and send a doctor to the center every so often, you collect the entire professional fee for the patients you send. They aren't treating any site off protocol. The expectation is that prostates will not need to be the majority of patients, if there is support from the community.

 

[Mandelin Rain]

Are people really that attached to their professional fees, that they either won't refer people who could genuinely benefit from protons or want to drive to some foreign facility with foreign technology to play proton doctor?

I see maybe 1 patient every year that I think would legitimately benefit from protons. I happily send them and charge it to the game.

 

[Damn_Daniel]

Sigh....

People complain when these centers come up, and here is a facility saying "hey, we know this is threatening to you, but let's play nice". They could overwhelmingly flood the market with ads to take away patients from the community with no opportunity to partner. Or, they can do it in a way that is much more cooperative.

If it weren't for cost .. If it wasn't a financial toxicity issue.. If you could buy protons for the cost of a linac, and it didn't cost more to treat, wouldn't you want it? I would. I'd treat everyone with protons. But, it's costly. So, we have this problem.

 

[medgator]

Sigh....

People complain when these centers come up, and here is a facility saying "hey, we know this is threatening to you, but let's play nice". They could overwhelmingly flood the market with ads to take away patients from the community with no opportunity to partner. Or, they can do it in a way that is much more cooperative.

If it weren't for cost .. If it wasn't a financial toxicity issue.. If you could buy protons for the cost of a linac, and it didn't cost more to treat, wouldn't you want it? I would. I'd treat everyone with protons. But, it's costly. So, we have this problem.

Why would you treat everyone with protons? Where's the data? Lung CA? Bronchial stenosis?

 

[Mandelin Rain]

Cough....

My point is that I wouldn't change my referral patterns to proton centers in any material way based on whether or not I received a professional charge. I doubt many would, unless you're treating an inordinate number of pediatric craniospinals or retinal melanomas. But that's in this world.

In your hypothetical world, where everyone carries lightsabers and cyclotrons grow on trees; carbon ion facilities would pop up and we'd still have this problem. Alas, we live in a non-lightsaber world, where treating most every cancer with conformal photons is just as good as treating with protons. If not better.

 

[thecarbonionangle]

I know of multiple people who have done a fellowship and gotten an academic job at that institution, coming from another program. To consider doing a fellowship, a "bad thing" seems pretty unfair. Everything has risks but you may have a shot at staying in some places. With the way the job market is looking, I hope this "bad" perception changes. I can see the appeal of fellowships for some people, especially if you went to a very solid but clinical program and would like to be in a research environment to give yourself a better shot at an academic career or you want to study for boards while solidifying what you know, if you fancy that.

 

[Damn_Daniel]

I had no idea that people sincerely felt photons are better. I never thought of it that way. People use IMRT without data all the time because of better DVH. They were using it for HNC way before there was RCT data. And that was a good thing! Same with laparoscopic surgery. Thank god people didn't keep doing open choles until there was a study.

My presumption is that if you had comparative DVHs for a proton plan vs photon plan, based on the lower integral dose, and lower dose to critical structures, most people would choose the proton plan, if money wasn't an issue. But, I guess everyone wouldn't.

That study is garbage, btw. It went to 74 Gy and one person died from bronchial stenosis. Do you really think that was because of the particle? People died on the Timmerman study. Does not diminish photons or SBRT, in anyway.

 

[radiaterMike]

There are dosimetric uncertainties with proton planning so what you see might not be what you get. Because of range uncertainties you are limited in what beam orientations you can use. Spot scanning may have less dosimetric uncertainty.


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[seper]

I would not treat lung Ca with protons even if they were cheaper than photons.

 

[Phantom1]

Last time I spoke with Zietman he told me this:

"I don't always recommend radiation... but when I do, I prefer protons."

 

[medgator]

I've spoken with a high-volume urologist before who gets referrals for robotic salvage RP. He says the worst salvage cases in terms of dealing with scar tissue etc are after protons. Worse than with imrt, cryo, hifu etc, fwiw

 

[Damn_Daniel]

Okay, so....

When people are applying to residency, they are excited about protons. When people are in residency, they are excited about protons. When they leave, suddenly, they are not. A database study with limited info says there is more toxicity. A terrible lung study mentions a grade 5 toxicity. An anecdote about salvaging prostates treated with it. The people excited about it are people that have them. The people not excited about it are people that don't have them. Hmm....

This reminds me of the old Eli Glatstein article denigrating IMRT. Old coot couldn't get comfortable with the newfangled technology.

Like it or not, it's happening. It's expensive. When it's not, it will be commonplace. We should be open to learning more about it. Anecdotes and bad database data can't be enough. If I had a kid who needed RT, you'd better believe that bastard child (I'd never marry) would get protons.

 

[medgator]

It's clear we need a proton center in every city (maybe 2 even) to treat Gleason 6, t1c prostate ca, you know, since there is clearly proven superiority of protons over photons in prostate ca, esp low risk

It's less clear that we need that many centers to treat peds, chordomas and ocular melanomas, right DD?

The cheaper single gantry units are still several fold more expensive than a well equipped linac currently, much worse than the differential between imrt vs 3D

 

[xrthopeful]

I would not treat lung Ca with protons even if they were cheaper than photons.

If anything there is much more of a dosimetric theoretical benefit for using protons in something like lung cancer rather than prostate cancer. The Bragg Peak doesn't save you much rectal dose, but it can actually improve integral lung dose etc in lung cancer.


I don't use protons at all, but seems silly to single out lung cancer as the place where you would never use it.

 

[Linaculous]

If anything there is much more of a dosimetric theoretical benefit for using protons in something like lung cancer rather than prostate cancer. The Bragg Peak doesn't save you much rectal dose, but it can actually improve integral lung dose etc in lung cancer.


I don't use protons at all, but seems silly to single out lung cancer as the place where you would never use it.

I believe the point is that some of the dosimetric uncertainties inherent to protons are particularly evident when treating lung.

 

[Damn_Daniel]

I never said we need more or less centers. Not my argument. I'm saying they exist. I'd love to know the technology works or not. I believe it does. I believe it's not cost effective. I wouldn't recommend it, based on that. I believe in cost effective medicine. That's why I don't give 61 Gy in 33 fx for DCIS. The cost for that over omission of RT and hypofractionation is higher than utilizing protons where they are needed.

My thought is that it's probably better. If it was cheaper, everyone would use it. They'd look at the DVH and it wouldn't be a question. Just like it was with imrt before data was out there. The problem is most of us can't start a proton center, but most of us could update our linacs to utilize imrt,, without data. So we did. The hypocrisy that exists in our field continues. We used a DVH to justify imrt. We will ignore it to bat off proton centers. Unless it's a kid. Because of course it works better on kids. WTF

It's clear we need a proton center in every city (maybe 2 even) to treat Gleason 6, t1c prostate ca, you know, since there is clearly proven superiority of protons over photons in prostate ca, esp low risk

It's less clear that we need that many centers to treat peds, chordomas and ocular melanomas, right DD?

The cheaper single gantry units are still several fold more expensive than a well equipped linac currently, much worse than the differential between imrt vs 3D

 

[Mandelin Rain]

So you value cost effectiveness over medical effectiveness when determining how to treat a patient? You should move to England and get a good tail policy.

If I honestly believe a treatment is better for my patient (as you do with protons in, apparently, every case) and I can't provide it, I refer them for that treatment. Let them decide if the cost to themselves or society is worth it. It's their health.

Paternalism is not in my nature, though.

 

[Damn_Daniel]

No, it's just that the logic being used above is bad. People automatically refer for kids, without randomized trials, because the DVH is better. Why? Is it dangerous to use that technology without trials? No, b/c like Cox's editorial a long time ago, sometimes you don't need an RCT to show that parachutes are helpful when jumping out a plane. But, DVH are better for other types of cancers, and its all like "PROTONS ARE TURRIBLE, UR STUPID DANIAL GO BACK TO THE COUNTRY U COM FRUM!!" That's so xenophobic, Bro Montana.

This is the decision tree that everyone should be using -

1. Cost effective and medically effective > 2. Medically effective but expensive > 3. medical benefit unclear but cost effective > 4. medical benefit unclear but expensive > 5. The Gator's treatment (I'm just keeeeeeeding)

But somewhere ranked above 2 or below 3, depending on the situation is this nether region of "medically probably better, but we aren't 100% positive, but it's expensive". Like IMRT in 1995. Like laparascopic surgery in the mid 80s. Like CT scans in the early 70s. Or any other new medical technology. Can just say "no, it's too expensive let's not use it", or we let the science play out. What freaks everyone out is the magnitude of the cost. If it was just like $1mil more, no one would be freaking out. It's just so much more, and people are crapping their pants when they think about it at night. Or, if you're like me and don't wear pants at night, you think about it, put on pants, and then crap in them.

 

[medgator]

Proton center at UF 10 years ago - $100-150 million+?
Single-gantry Mevion units popping up now after years of talk, $20-25 million minimum?
Trubeam Linac, very capable - $2-4 million.

Come back to present-day reality, and do the math, DD. I don't see the cost curve for protons getting even close to the 3D/IMRT argument anytime soon. IMRT was much easier to adopt at its cost peak than protons are, even now with single-gantry units.

 

[Mandelin Rain]

As long as you inform all your consultative patients that there exists a treatment that is "medically probably better, but we aren't 100% positive, but it's expensive", you should be able to sleep at night. If not, you suck.

I for one, don't believe as you do. So my sleep is easier to come by.

 

[Damn_Daniel]

Fair points, by both. Appreesh. I do suck! And I don't live in reality!

But why do you think we send kids for treatment and also for base of skull/chordomas without randomized trials? I guess those clinicians are willing to risk kids lives on untested, unreliable, costly technology that hasn't been proven to be better. And also using it for tumors near very sensitive areas without RCTs. Crazy!

 

[RadOncDoc21]

I hope you guys are not crapping in your pants at night... If that's the case, worrying about the cost of proton therapy should be least of your problems!

 

[RadOncDoc21]

For those of you with ongoing nocturnal fecal incontinence, this article may help:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711681/

 

[Damn_Daniel]

Hilarious fun fact:

Proton center in Flint, MI put up by this Russian company that went out of business, and doesn't really provide tech support any more. So, they found that the isocenter moves when the gantry moves and they can't fix the problem. They haven't treated a patient yet. They are thinking of fixing the gantry in one position in each room, and having the patient go into each room to get each field. So, for a prostate with laterals, they'd get the right lateral, then hop on over to the room next door and get the left lateral. Flint is so awesome! A model of good governance, and a model of good planning by the hospital admin!

 

[mpdoc2]

Hilarious fun fact:

Proton center in Flint, MI put up by this Russian company that went out of business, and doesn't really provide tech support any more. So, they found that the isocenter moves when the gantry moves and they can't fix the problem. They haven't treated a patient yet. They are thinking of fixing the gantry in one position in each room, and having the patient go into each room to get each field. So, for a prostate with laterals, they'd get the right lateral, then hop on over to the room next door and get the left lateral. Flint is so awesome! A model of good governance, and a model of good planning by the hospital admin!

LOL

 

[Gfunk6]

Hilarious fun fact:

Proton center in Flint, MI put up by this Russian company that went out of business, and doesn't really provide tech support any more. So, they found that the isocenter moves when the gantry moves and they can't fix the problem. They haven't treated a patient yet. They are thinking of fixing the gantry in one position in each room, and having the patient go into each room to get each field. So, for a prostate with laterals, they'd get the right lateral, then hop on over to the room next door and get the left lateral. Flint is so awesome! A model of good governance, and a model of good planning by the hospital admin!

Sounds solid. Just don't drink the water in the waiting room.


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[BobbyHeenan]

I never said we need more or less centers. Not my argument. I'm saying they exist. I'd love to know the technology works or not. I believe it does. I believe it's not cost effective. I wouldn't recommend it, based on that. I believe in cost effective medicine. That's why I don't give 61 Gy in 33 fx for DCIS. The cost for that over omission of RT and hypofractionation is higher than utilizing protons where they are needed.

My thought is that it's probably better. If it was cheaper, everyone would use it. They'd look at the DVH and it wouldn't be a question. Just like it was with imrt before data was out there. The problem is most of us can't start a proton center, but most of us could update our linacs to utilize imrt,, without data. So we did. The hypocrisy that exists in our field continues. We used a DVH to justify imrt. We will ignore it to bat off proton centers. Unless it's a kid. Because of course it works better on kids. WTF

There are DVH improvements that matter (ie reducing lung V20, reducing V70 rectum in prostate, reducing parotid mean dose) that have clinical correlates with outcomes...then there's just making the DVH look better and making you "feel better" without clinical benefit. I think the distinction needs to be made. I personally know of proton centers treating off protocol unresectable GBM's, anal cancer, right sided breast amongst others. I bet those DVH's look better than IMRT, but does that matter?

I'll send patients not infrequently for some things, but just blanket use of it at this time is hurting more than it's helping in my mind.

Hilarious fun fact:

Proton center in Flint, MI put up by this Russian company that went out of business, and doesn't really provide tech support any more. So, they found that the isocenter moves when the gantry moves and they can't fix the problem. They haven't treated a patient yet. They are thinking of fixing the gantry in one position in each room, and having the patient go into each room to get each field. So, for a prostate with laterals, they'd get the right lateral, then hop on over to the room next door and get the left lateral. Flint is so awesome! A model of good governance, and a model of good planning by the hospital admin!

Did they try restarting it in safe mode? How about just pouring some vodka rather than water in the cooling mechanism? Maybe the Johnson rod is out. Lots of things here that could be fixed I bet.

 

[RadOncDoc21]

Man, Flint can't win this year.

 

[Damn_Daniel]

How did they come up with that number for prostate/rectum constraint? People treated a bunch of people with prostate cancer with imrt and then analyzed it. Didn't come out of a clinical trial. Same with parotids by Avi Eisbruch. Same with pharyngeals. Someone's gotta treat the patients to come up with this stuff...

And IMRT blew the budget for radiation oncology... This field was not a big part of the Medicare pie, until IMRT ballooned spending. It's not as different as you think, other than the capital cost. The magnitude of the change in spending is probably less.

The Johnson rod is out! I don't know what that means but I like it.

 

[Chartreuse Wombat]

Couple problems here.

1. Radiation biology is largely hocus pocus based on sketchy modeling. The a/B is based on a calculation rather than any physical or biologic property, and this calculation is to be applied broadly across a disease which is assumed to be homogenous (as if all prostate cancers are the same biologically). The calculated a/B for prostate has varied wildly from less than normal tissue to twice that of normal tissue. There seems to be a consensus that there exists a "hypothesis" that prostate cancer a/B "may be" low, but definitive proof is lacking. From the article, "Depending on the hypothetical α/β variables put into the linear-quadratic model, the hypofractionated courses may have been too much, not enough, or ideal in terms both of cancer control and normal tissue tolerance." Sure... let's put faith in that model.

2. The studies cited suck. Who is treating prostate cancer to 74 Gy or less? We know dose escalation works in prostate cancer. Comparing hypofractionation to sub-standard doses of radiation and coming out with more toxicity regardless of how trivial it is, sucks.

3. How do you rectify that the standard arms of our cooperative group trials are 44 fractions and then freely offer treatment in 20 fractions based on sketchy data. Good luck ever putting anyone on a trial that may say something meaningful.

4. "A different explanation may be inferred from the fact that, in our fee-for-service payment system, radiation oncologists are paid by the fraction, and hypofractionation thus threatens income. " Please shut down the cyclotron at your institution and then get after this point.

Question-

Assume a large, randomized study compares 1200 prostate cancer patients; 600 treated to 78 Gy/39 fractions and 600 treated to 60 Gy/20 fractions. Non-inferiority endpoint and no difference in efficacy with slightly less toxicity in the 60 Gy arm.

Does this study suck as well?

 

[napoleondynamite]

Does this study suck as well?

yes, probably.

in low risk prostate cancer the number of events is so small that you would probably need many more patients than 1200 and probably much more follow-up than just 6-8 years to truly demonstrate non-inferiority

 

[BobbyHeenan]

How did they come up with that number for prostate/rectum constraint? People treated a bunch of people with prostate cancer with imrt and then analyzed it. Didn't come out of a clinical trial. Same with parotids by Avi Eisbruch. Same with pharyngeals. Someone's gotta treat the patients to come up with this stuff...

And IMRT blew the budget for radiation oncology... This field was not a big part of the Medicare pie, until IMRT ballooned spending. It's not as different as you think, other than the capital cost. The magnitude of the change in spending is probably less.

The Johnson rod is out! I don't know what that means but I like it.

Off the top of my head, regarding the rectal constraints, in the earlier moderate hypofractionated prostate trials (see Kupelian IJROBP 2005), the volume of rectum getting > 70 Gy showed significant correlation to rectal events. So you've got some DVH correlate with clinical toxicity there to guide you. Then all the Quantec stuff....what we don't have DVH/clinical correlate data on (at least not that I'm aware of), is the lower dose proton dose dose on the DVH having any clinical impact - NCCN guidelines discuss this more eloquently than I can in the narrative section on protons for prostate.

Regarding the Johnson Rod - see here (surprisingly safe for work clip)

 

[Chartreuse Wombat]

yes, probably.

in low risk prostate cancer the number of events is so small that you would probably need many more patients than 1200 and probably much more follow-up than just 6-8 years to truly demonstrate non-inferiority

Intermediate risk...No hormones...

yes, probably.

in low risk prostate cancer the number of events is so small that you would probably need many more patients than 1200 and probably much more follow-up than just 6-8 years to truly demonstrate non-inferiority

My apologies for not being more precise. Intermediate risk disease; no hormones. Predefined non-inferiority HR <1.32. Expect about 300 events within five years. If this "hypothetical" study demonstrates non-inferiority does it still suck?

Specifically trying to determine if suckness is related to 1) Non-inferiority design 2) Low dose in comparator arm 3) General antipathy towards randomized trials.
Cheers

 

[OTN]

Intermediate risk...No hormones...

My apologies for not being more precise. Intermediate risk disease; no hormones. Predefined non-inferiority HR <1.32. Expect about 300 events within five years. If this "hypothetical" study demonstrates non-inferiority does it still suck?

Specifically trying to determine if suckness is related to 1) Non-inferiority design 2) Low dose in comparator arm 3) General antipathy towards randomized trials.
Cheers

Well first off, they're not exactly shooting for the moon with an HR of <1.32. If the HR for recurrence in the 60 Gy in 20 fx arm is 1.25 they consider that to be "non-inferior"? How?

 

[Mandelin Rain]

Has PROFIT resulted? Or are we just talking hypotheticals?

 

[napoleondynamite]

Well first off, they're not exactly shooting for the moon with an HR of <1.32. If the HR for recurrence in the 60 Gy in 20 fx arm is 1.25 they consider that to be "non-inferior"? How?

Did you know that Lebron is no better at basketball than I am? This one time I challenged him to a free throw contest. He only sunk 9/10 and I sunk 8/10. The HR is 1.2, so there you have it, I'm not inferior.

 

[Chartreuse Wombat]

Did you know that Lebron is no better at basketball than I am? This one time I challenged him to a free throw contest. He only sunk 9/10 and I sunk 8/10. The HR is 1.2, so there you have it, I'm not inferior.

Touche. The possibility of Type II error exists for any comparison. In your example glancing at the CI for the HR would make it clear that your inference is weak. Let's hypothesize that the HR in the hypothetical trial is 0.91. Confidence interval is 0.75-1.08. Is this sufficient to accept non-inferiority?