Whatever happened to the MSK prostate dose escalation studies?

[thesauce]

I feel like MSK was driving prostate doses up higher and higher a few years ago (90+ Gy) and seeing better bPFS and excellent tolerability. I went to a couple ASTRO sessions on this and figured it would be the future.

All of a sudden, I didn't hear anything else about it and the focus has been on hypofrac. Did the powers-that-be decide they just wanted to change the direction of the field or were there adverse outcomes? Anyone know?

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[RickyScott]

I feel like MSK was driving prostate doses up higher and higher a few years ago (90+ Gy) and seeing better bPFS and excellent tolerability. I went to a couple ASTRO sessions on this and figured it would be the future.

All of a sudden, I didn't hear anything else about it and the focus has been on hypofrac. Did the powers-that-be decide they just wanted to change the direction of the field or were there adverse outcomes? Anyone know?

Sbrt is much better for their business model. 40 Gy/5

 

[Chartreuse Wombat]

Sbrt is much better for their business model. 40 Gy/5

Hard to get executives to commit 10 weeks to treatment

 

[jondunn]

Sbrt is much better for their business model. 40 Gy/5

If you don’t offer a great treatment to your patients, they will go elsewhere. Welcome to America baby.


I wouldn’t survive in my market if I didn’t do a ton of prostate SBRT. Bonus is it’s a slam dunk treatment that I would want for myself.

 

[RickyScott]

If you don’t offer a great treatment to your patients, they will go elsewhere. Welcome to America baby.


I wouldn’t survive in my market if I didn’t do a ton of prostate SBRT. Bonus is it’s a slam dunk treatment that I would want for myself.

Why would you want it for yourself? You presumably work in a radonc center so the treatment is not incovenient and you wouldn’t news space oar or a market with conventional xrt.

 

[OTN]

Why would you want it for yourself? You presumably work in a radonc center so the treatment is not incovenient and you wouldn’t news space oar or a market with conventional xrt.

You don’t need SpaceOAR with 40 in 5 SBRT, either

 

[TheWallnerus]

I feel like MSK was driving prostate doses up higher and higher a few years ago (90+ Gy) and seeing better bPFS and excellent tolerability. I went to a couple ASTRO sessions on this and figured it would be the future.

All of a sudden, I didn't hear anything else about it and the focus has been on hypofrac. Did the powers-that-be decide they just wanted to change the direction of the field or were there adverse outcomes? Anyone know?

Still an NCCN accepted standard treatment. (Well 81/45.)

And maybe the reports of high dose escalation’s death are still premature

https://ascopubs.org/doi/abs/10.1200/JCO.20.02873

 

[RickyScott]

Still an NCCN accepted standard treatment. (Well 81/45.)

And maybe the reports of high dose escalation’s death are still premature

https://ascopubs.org/doi/abs/10.1200/JCO.20.02873

As someone who trained using the 81/45, and then few years later worked at institution where 80/4O was standard, definitely had to use more flomax and naproxen with change in fractionation.

 

[xyz01]

FLAME came out this year. Focal boost to BIRADS leason up to 95gy.

https://ascopubs.org/doi/10.1200/JCO.20.02873?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

 

[Radonc90]

Usually, when things go south (such as high complications rates from escalation), the institution quietly switches gear...

Remember the old HN textbook by Million showing rigid radium needles for tongue cancer?
When asked, he said, well we don't use Radium needles any longer...
Lol...

 

[medgator]

Usually, when things go south (such as high complications rates from escalation), the institution quietly switches gear...

Remember the old HN textbook by Million showing rigid radium needles for tongue cancer?
When asked, he said, well we don't use Radium needles any longer...
Lol...

Did a few ir-192 tongue implants for unresectable recurrences

 

[CptCrunch]

As others have stated, they've switched to pushing SBRT. In the New York market Winthrop had been advertising their Cyberknife everywhere for quite a while (Cancer Center Spending on Advertising) and opened up a center in Manhattan. I figure everyone else including MSK had to follow suit which led to marketing SHARP (stereotactic blah blah radiation to the prostate) and now MSK Precise.

 

[CptCrunch]

You don’t need SpaceOAR with 40 in 5 SBRT, either

Maybe not, but that doesn't stop them from using it for everyone anyway Open Payments Data - CMS

 

[Ray D. Ayshun]

Is anyone here who hypofracs generally using standard frac in certain cases?

 

[jondunn]

Is anyone here who hypofracs generally using standard frac in certain cases?

This is probably most people I gather. Standard 20-28 fx. Most of my friends do this

 

[Ray D. Ayshun]

This is probably most people I gather. Standard 20-28 fx. Most of my friends do this

Fair enough. Wondering if there are patient factors that would be make someone do 44 instead. One of the recent Astro refreshers a doc from UPenn I think said he still does 44 in high risk.

 

[theradiator]

As others have stated, they've switched to pushing SBRT. In the New York market Winthrop had been advertising their Cyberknife everywhere for quite a while (Cancer Center Spending on Advertising) and opened up a center in Manhattan. I figure everyone else including MSK had to follow suit which led to marketing SHARP (stereotactic blah blah radiation to the prostate) and now MSK Precise.

When Memorial Sloan Kettering needs to have an emergency meeting to change course to address their declining prostate volumes, we are definitely living in a dystopia.

In a bizarre twist of irony, here Memorial Sloan Kettering is bitterly complaining about Cancer Treatment Centers of America spending too much on cancer marketing.

Cancer Hospital Advertising and Outcomes: Trust the Messenger?

www.ncbi.nlm.nih.gov

 

[jondunn]

In my market CTCA is terrible. I’m sure there are good branches, but I haven’t seen it yet. Just terrible, sad stuff. Med onc more so.

 

[Palex80]

Is anyone here who hypofracs generally using standard frac in certain cases?

We treat all (without nodes) with 20 x 3 Gy.
We only advise for standard fractionation if:
- bowel disease
- recently conducted extensive TUR-P

Do you feel comfortable offering hypofractionation after extensive TUR-P. My boss is worried about risks of late urinary toxicity (mainly urethral stenosis).

Fair enough. Wondering if there are patient factors that would be make someone do 44 instead. One of the recent Astro refreshers a doc from UPenn I think said he still does 44 in high risk.

Perhaps he is treating elective lymphatics in high-risk disease?

 

[jondunn]

Same reason Med onc/rad onc practices have in house pharmacy!

 

[Ray D. Ayshun]

We treat all (without nodes) with 20 x 3 Gy.
We only advise for standard fractionation if:
- bowel disease
- recently conducted extensive TUR-P

Do you feel comfortable offering hypofractionation after extensive TUR-P. My boss is worried about risks of late urinary toxicity (mainly urethral stenosis).


Perhaps he is treating elective lymphatics in high-risk disease?

I think his reasoning for standard frac was that only a limited number of patients in the best done hypofrac trials were high risk.

 

[Ray D. Ayshun]

We treat all (without nodes) with 20 x 3 Gy.
We only advise for standard fractionation if:
- bowel disease
- recently conducted extensive TUR-P

Do you feel comfortable offering hypofractionation after extensive TUR-P. My boss is worried about risks of late urinary toxicity (mainly urethral stenosis).


Perhaps he is treating elective lymphatics in high-risk disease?

What's the definition of recently conducted TURP? So far, have been able to wait several months for anyone to recover from TURP.

 

[BobbyHeenan]

Is anyone here who hypofracs generally using standard frac in certain cases?

I do mostly 20 or 28 fractions. I do some SBRT 36.25 to 40 Gy.

But I will once in a while do 78 Gy in 2 Gy/fraction. Just had a guy that failed Cryo and did standard frac on him. Had another guy with a large prostate with AUA IPPS score in the 20's.

Anecdotally I see more acute GU symptoms with hypofrac. Long term I haven't seen much difference at 6-12 months, but I use more flomax, quicker, on hypofrac than standard frac. I trained at a place that was 20-28 and was dabbling in SBRT a decade ago. Some of my partners still do standard frac so I did some earlier on in my practice and I think it is "gentler" anecdotally. I have zero issues with anyone that prefers standard frac, I don't bat an eye at chart review for 40 fraction prostate cases.

 

[Ray D. Ayshun]

I do mostly 20 or 28 fractions. I do some SBRT 36.25 to 40 Gy.

But I will once in a while do 78 Gy in 2 Gy/fraction. Just had a guy that failed Cryo and did standard frac on him. Had another guy with a large prostate with AUA IPPS score in the 20's.

Anecdotally I see more acute GU symptoms with hypofrac. Long term I haven't seen much difference at 6-12 months, but I use more flomax, quicker, on hypofrac than standard frac. I trained at a place that was 20-28 and was dabbling in SBRT a decade ago. Some of my partners still do standard frac so I did some earlier on in my practice and I think it is "gentler" anecdotally. I have zero issues with anyone that prefers standard frac, I don't bat an eye at chart review for 40 fraction prostate cases.

I have no real experience doing std frac in intact prostate, but I use it for salvage, and do see less urinary and bowel tox in salvage. Obv, there's no prostate there to swell up and cause problems.

 

[Palex80]

What's the definition of recently conducted TURP? So far, have been able to wait several months for anyone to recover from TURP.

Exactly, that's the point. If I can wait for several months, I am comfortable with offering hypofractionation. But sometimes, I have this "borderline" favorable intermediate risk cases, when I am concerned that if I wait 6 months after TUR-P, I may end up "having" to give ADT then.
Or sometimes I have patients who simply don't want to wait after TUR-P for 6 months.
In those cases, I may have to treat within 2 months after TUR-P and then I normofractionate (out of concern).
With RTOG0815 results out now, this may however be less of an issue?

 

[elementaryschooleconomics]

I do mostly 20 or 28 fractions. I do some SBRT 36.25 to 40 Gy.

But I will once in a while do 78 Gy in 2 Gy/fraction. Just had a guy that failed Cryo and did standard frac on him. Had another guy with a large prostate with AUA IPPS score in the 20's.

Anecdotally I see more acute GU symptoms with hypofrac. Long term I haven't seen much difference at 6-12 months, but I use more flomax, quicker, on hypofrac than standard frac. I trained at a place that was 20-28 and was dabbling in SBRT a decade ago. Some of my partners still do standard frac so I did some earlier on in my practice and I think it is "gentler" anecdotally. I have zero issues with anyone that prefers standard frac, I don't bat an eye at chart review for 40 fraction prostate cases.

These are my observations as well. All anecdote for me too, of course.

The older docs I work with still prefer standard frac, and I'll cover OTVs for them if they're at a different site. It's probably recall bias on my part but those patients seem to sail through, and seeing this phenomenon week in and week out compared to my hypofrac patients really has me questioning some things.

Now, it should go without saying - 9 weeks is a LONG TIME to be working with someone with an...interesting personality. They should do a study on doctor quality of life for hypofrac vs conventional. Enrollment criteria: only the guys who are prone to making their own spreadsheets of all of their PSA values, ever, and don't completely understand the concept of standard deviation.

 

[Lamount]

These are my observations as well. All anecdote for me too, of course.

The older docs I work with still prefer standard frac, and I'll cover OTVs for them if they're at a different site. It's probably recall bias on my part but those patients seem to sail through, and seeing this phenomenon week in and week out compared to my hypofrac patients really has me questioning some things.

Now, it should go without saying - 9 weeks is a LONG TIME to be working with someone with an...interesting personality. They should do a study on doctor quality of life for hypofrac vs conventional. Enrollment criteria: only the guys who are prone to making their own spreadsheets of all of their PSA values, ever, and don't completely understand the concept of standard deviation.

I can't quote data on the topic, but it is very logical that hypofrac would have worse acute toxicity, as it is accelerated

 

[MegaVoltagePhoton]

In residency I did very little SBRT. When I started as an attending I did more gyn but due to some people leaving I am now doing a fair share of prostate and it is mainly SBRT. I honestly think there might be a little more acute urinary issues and bowel issues after the radiation is done with SBRT, but it goes away pretty quickly. In the location I practice in, it would be a no-brainer to do SBRT and I cant blame the patients at all. Sure an old retired guy could PROBABLY come to the doctors office daily for radiation but nearly everyone would be willing to cut that down to five treatments even if the side effects were a little worse and I don't think I can blame them.

The side benefit for me with SBRT is being hit on way less by the patients. #womenwhocurie

 

[Krukenberg]

I can't quote data on the topic, but it is very logical that hypofrac would have worse acute toxicity, as it is accelerated

I don’t believe the prostate hypofrac regimens are accelerated, because the total dose is lower? My understanding is that accelerated would be completing the same total conventional dose but in a shorter total treatment time. I think of the DAHANCA 6 fax/week regimen as a prototypical example.

 

[TheWallnerus]

I don’t believe the prostate hypofrac regimens are accelerated, because the total dose is lower? My understanding is that accelerated would be completing the same total conventional dose but in a shorter total treatment time. I think of the DAHANCA 6 fax/week regimen as a prototypical example.

The semantics are tricky. The total dose is lower numerically. However the total radiobiologically effective dose is usually built to be the same. Thus from a radiobiology and “4 Rs” perspective hypofractionation regimens designed to give equal LC are accelerated. But strictly speaking it is not accelerated based on old school rad onc jargon. However I too like to say that hypofractionation is accelerated. A fraction takes time; less fractions, less time.

 

[Lamount]

I don’t believe the prostate hypofrac regimens are accelerated, because the total dose is lower? My understanding is that accelerated would be completing the same total conventional dose but in a shorter total treatment time. I think of the DAHANCA 6 fax/week regimen as a prototypical example.

I think it is technically accelerated. Here is a classic (and horrible) 'acceleration" trial whereby 54 Gy was delivered with 1.5 Gy TID in 12 days for NSCLC. Anectdotally, pts seem to get more acute esophagitis when getting SCLC 1.5 Gy BID than 60 Gy conventionally fractionated... but the SCLC pts also seem to recover quicker

 

[TheWallnerus]

I think it is technically accelerated. Here is a classic (and horrible) 'acceleration" trial whereby 54 Gy was delivered with 1.5 Gy TID in 12 days for NSCLC. Anectdotally, pts seem to get more acute esophagitis when getting SCLC 1.5 Gy BID than 60 Gy conventionally fractionated... but the SCLC pts also seem to recover quicker

Why was CHART horrible. We tested it once and then dropped it like it was not hot. It showed a big survival advantage. I’ve always thought it should have gotten more love. However it would mean keeping an RT center open all day and on the weekends too. It did cause a few minor therapist labor strikes in the UK I think?!

 

[SneakyBooger]

Maybe not, but that doesn't stop them from using it for everyone anyway Open Payments Data - CMS

I don't recall seeing that in any COI declarations. Hmmmmm...

 

[DoctwoB]

Same reason Med onc/rad onc practices have in house pharmacy!

interesting. I wonder if it’s really a money maker or just helps keep patients in the practice rather then going to Med Onc. At my shop we do Lupron but send to med onc for abi/enza, mostly so they can deal with the insurance headache. Doubt we make much money on the lupron though, I started practice to late.

 

[elementaryschooleconomics]

I don't recall seeing that in any COI declarations. Hmmmmm...

Never forget: Rad Onc Twitter

At least $830,000 paid to virtually all the authors on the study which won SpaceOAR FDA approval.

interesting. I wonder if it’s really a money maker or just helps keep patients in the practice rather then going to Med Onc. At my shop we do Lupron but send to med onc for abi/enza, mostly so they can deal with the insurance headache. Doubt we make much money on the lupron though, I started practice to late.

I do all my own Lupron/Eligard. My department and I generate almost zero reimbursement from it (the way I structure it, I imagine there's a small nursing E&M charge +/- some kind of nursing administration charge, because I prescribe it at consult and am not officially involved when they come back for the injection, therefore, no MD pro fees specifically for ADT). I'm told, however, that each injection costs approximately $7,000. I'm not sure who is getting that money, I think it's the drug company that makes it (because it's sure as heck not me or the hospital).

 

[medgator]

interesting. I wonder if it’s really a money maker or just helps keep patients in the practice rather then going to Med Onc. At my shop we do Lupron but send to med onc for abi/enza, mostly so they can deal with the insurance headache. Doubt we make much money on the lupron though, I started practice to late.

I usually will hand it over to med onc once those drugs need to be used, easier for the pt

 

[Palex80]

I was having this funny thought the other day:
The MSKCC dose escalation trials went quite high with the dose, beyond 80 Gy. At the same time they featured rectal wall constraints which were considerably lower in terms of max dose and dose to small volumes than the prescribed dose to the prostate. This means that the posterior parts (part of the peripheral zone) of the prostate did not receive the full dose, while other parts did.
Were the MSKCC dose escalation in essence more or less a "blind" version of the FLAME trial?
You recall, in the FLAME trial isototic dose escalation was attempted in a randomized manner with the same constraints for OAR in both arms, delivering quite high doses to MRI-contoured GTVs in the prostate in the focal boost arms. However, tumors in posterior parts of the prostate did not receive higher doses in the focal boost arm, because of the isototix design of the trial (--> respecting OAR constraints). Does this mean that irradiating part of the tumor in the prostate with a higher dose, even one delivers standard dose to the rest of the GTV, will yield better results? This is in principle the argument for HDR-brachytherapy, actually.

 

[SneakyBooger]

Never forget: Rad Onc Twitter

At least $830,000 paid to virtually all the authors on the study which won SpaceOAR FDA approval.

WHAT THE HADES...

Something smells rotten in the House of Medicine

 

[DoctwoB]

Never forget: Rad Onc Twitter

At least $830,000 paid to virtually all the authors on the study which won SpaceOAR FDA approval.


I do all my own Lupron/Eligard. My department and I generate almost zero reimbursement from it (the way I structure it, I imagine there's a small nursing E&M charge +/- some kind of nursing administration charge, because I prescribe it at consult and am not officially involved when they come back for the injection, therefore, no MD pro fees specifically for ADT). I'm told, however, that each injection costs approximately $7,000. I'm not sure who is getting that money, I think it's the drug company that makes it (because it's sure as heck not me or the hospital).

As a Urologist we hear tales of the "old days" in which one could buy/bill for ADT and make $$$$ without getting up from one's chair. Probably for the best that it changed, as undoubtedly led to bad behavior in terms of folks getting ADT instead of definitive therapy, but Oh to have started practice 15 years earlier.

 

[TheWallnerus]

interesting. I wonder if it’s really a money maker or just helps keep patients in the practice rather then going to Med Onc. At my shop we do Lupron but send to med onc for abi/enza, mostly so they can deal with the insurance headache. Doubt we make much money on the lupron though, I started practice to late.

I'm not sure who is getting that money, I think it's the drug company that makes it (because it's sure as heck not me or the hospital).

When you run your own in house pharmacy it reminded me of day trading. You were constantly looking for the "hot stock" or in this instance the top few drugs that had the highest profit margins. There was never much rhyme or reason to it. But I remember for topical androgel e.g. we would pay like $300 for a bottle and the insurance companies would reimburse us like $700. But for something like phenergan? We would pay $10 and get reimbursed something like $11. I think memantine had a great profit margin. Pharmacy is a miasma but on the whole this is true: if you do a lot of prescribing, and there are ~5 or more docs in the practice, you should have your own in house pharmacy. An in house pharmacy will NEVER make sense for a pure rad onc group (almost no matter how big they are).

Were the MSKCC dose escalation in essence more or less a "blind" version of the FLAME trial?

I was thinking this even 20y ago, although of course FLAME was to be a thing far in the future.

 

[elementaryschooleconomics]

When you run your own in house pharmacy it reminded me of day trading. You were constantly looking for the "hot stock" or in this instance the top few drugs that had the highest profit margins. There was never much rhyme or reason to it. But I remember for topical androgel e.g. we would pay like $300 for a bottle and the insurance companies would reimburse us like $700. But for something like phenergan? We would pay $10 and get reimbursed something like $11. I think memantine had a great profit margin. Pharmacy is a miasma but on the whole this is true: if you do a lot of prescribing, and there are ~5 or more docs in the practice, you should have your own in house pharmacy.


I was thinking this even 20y ago, although of course FLAME was to be a thing far in the future.

Based on a few conversations I've had this week, I'm gonna open my own pharmacy and stock only pentosan and Analpram-HC

 

[dieABRdie]

FLAME came out this year. Focal boost to BIRADS leason up to 95gy.

https://ascopubs.org/doi/10.1200/JCO.20.02873?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

My approach is this:
1) Can this person get SBRT? Then SBRT it is.... I would offer it pretty much to any low risk or favorable intermediate risk.

2) If not SBRT... I do FLAME regimen with integrated boost.... assuming they have an MRI defined lesion.

3) if no MRI defined lesion and no SBRT... then 70Gy/28 fractions. Unless, they have horrible IPSS or prior TURBT etc. then I would do standard old conventional fractionation.

It has been very interesting seeing my partners absolute refusal to use FLAME simply because of the longer fractionation scheme. Clearly the "fraction shaming" has scarred them deep to their psyche.

Better bPFS without increased toxicity? Yes.... you do have to come in an extra 10 treatments. I do explain that to the patients and they rarely have a problem with it.

I really don't want them to start... then I can't brag about offering the most aggressive treatment in the region anymore.

 

[Palex80]

2) If not SBRT... I do FLAME regimen with integrated boost.... assuming they have an MRI defined lesion.

I was thinking: FLAME was isotoxic, same constraints for both arms. bPFS superior when using focal boost. So why not simply do CHHiPish-60/3 and add a SIB up to 70/3.5 for GTV, still using all the same constraints. Yes, it hasn't been proven that focal boost can be done outside of standard fractionation, but if you are meeting all constraints, why not?

 

[dieABRdie]

I was thinking: FLAME was isotoxic, same constraints for both arms. bPFS superior when using focal boost. So why not simply do CHHiPish-60/3 and add a SIB up to 70/3.5 for GTV, still using all the same constraints. Yes, it hasn't been proven that focal boost can be done outside of standard fractionation, but if you are meeting all constraints, why not?

That is the beauty of radiation oncology. No matter how we do it.... it just works.

I have no doubt it would be as effective. Only reason I haven't is because if someone has a major complication I'd like to be able to point to a randomized trial. Some of the older docs give me a "deer in the headlights" look when I tell them I'm treating a prostate to 95Gy, lol.

 

[jondunn]

I was thinking: FLAME was isotoxic, same constraints for both arms. bPFS superior when using focal boost. So why not simply do CHHiPish-60/3 and add a SIB up to 70/3.5 for GTV, still using all the same constraints. Yes, it hasn't been proven that focal boost can be done outside of standard fractionation, but if you are meeting all constraints, why not?

I know people doing this in practice. it of course makes sense.

 

[elementaryschooleconomics]

but if you are meeting all constraints, why not?

I find myself often arriving at this answer!

 

[jondunn]

It’s one of the few places where dose escalation wasn’t a massive failure! See lung, esophagus, etc etc etc

 

[evilbooyaa]

I was thinking: FLAME was isotoxic, same constraints for both arms. bPFS superior when using focal boost. So why not simply do CHHiPish-60/3 and add a SIB up to 70/3.5 for GTV, still using all the same constraints. Yes, it hasn't been proven that focal boost can be done outside of standard fractionation, but if you are meeting all constraints, why not?

Because people who miss the good old days of conventional Fx can get back to it with justification of doing it "the same way the trial did".

I'm sure people are doing mod Hypofx FLAME

People are also doing SBRT-FLAME off trial

 

[xyz01]

My approach is this:
1) Can this person get SBRT? Then SBRT it is.... I would offer it pretty much to any low risk or favorable intermediate risk.

2) If not SBRT... I do FLAME regimen with integrated boost.... assuming they have an MRI defined lesion.

3) if no MRI defined lesion and no SBRT... then 70Gy/28 fractions. Unless, they have horrible IPSS or prior TURBT etc. then I would do standard old conventional fractionation.

It has been very interesting seeing my partners absolute refusal to use FLAME simply because of the longer fractionation scheme. Clearly the "fraction shaming" has scarred them deep to their psyche.

Better bPFS without increased toxicity? Yes.... you do have to come in an extra 10 treatments. I do explain that to the patients and they rarely have a problem with it.

I really don't want them to start... then I can't brag about offering the most aggressive treatment in the region anymore.

Do you restrict dose to the urethra while doing the FLAME regimen? To my knowledge there are no urethra dose constraints in the study protocol used?

 

[tomhobbes]

NRG GU 010 adds a 2 mm urethra PRV.
Conventionally and moderately hypofractionated prescription constraint D0.035cc to 110% per protocol, or 120% variation acceptable, of the prescription.
Ultrahypofractionated SBRT prescription constraint D0.03cc <= 43.5 Gy per protocol. There isn't an additional "variation acceptable" constraint for SBRT.