Ultra Hypofrac - Data from ESTRO

[Gfunk6]

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https://www.estro.org/binaries/cont...ro37-media/widmark-uhf-final_estrp37-logo.pdf

Phase III HYPORT-PC trial, five year follow-up
Arm 1 - 78 Gy in 39 fractions to prostate
Arm 2 - 42.7 Gy in 7 fractions to prostate (delivered over 2.5 weeks)

No difference in 5 year bPFS, no difference in late toxicity; slightly worse acute toxicity in Arm 2

https://www.estro.org/binaries/cont...media/schafer_estro-37-press-release-logo.pdf

Phase III GEC ESTRO trial, five year follow-up
Arm 1 - Conventionally fractionated whole breast RT
Arm 2 - Multi-catheter based APBI

No difference in QoL in 5 years, acute/subacute toxicity worse in Arm 1

-----------------------------------------------------------------------------------------------------------------------

This is your future, embrace it.

 

[MDACCRules]

https://www.estro.org/binaries/cont...ro37-media/widmark-uhf-final_estrp37-logo.pdf

Phase III HYPORT-PC trial, five year follow-up
Arm 1 - 78 Gy in 39 fractions to prostate
Arm 2 - 42.7 Gy in 7 fractions to prostate (delivered over 2.5 weeks)

No difference in 5 year bPFS, no difference in late toxicity; slightly worse acute toxicity in Arm 2

https://www.estro.org/binaries/cont...media/schafer_estro-37-press-release-logo.pdf

Phase III GEC ESTRO trial, five year follow-up
Arm 1 - Conventionally fractionated whole breast RT
Arm 2 - Multi-catheter based APBI

No difference in QoL in 5 years, acute/subacute toxicity worse in Arm 1

-----------------------------------------------------------------------------------------------------------------------

This is your future, embrace it.

Interesting that it was "medium and high risk" patients, but no ADT allowed

 

[Chartreuse Wombat]

Interesting that it was "medium and high risk" patients, but no ADT allowed

Eligibility from previous abstract below; looks like mostly intermediate

It is probably a better test of BED if ADT is not included. Wait for the paper but in capitated environments this is potentially a game changer.

 

[DebtRising]

Something here isn’t right - this may be a better BED comparison but it seems unethical to not include ADT - either this patient population warranted that or that country accepts inferior outcomes without ADT (the absolute control rates here are absolutely inferior to chhip, noting differences in study pop).The second is that other single institution series of 40gy plus sbrt have generally had higher toxicity.

There is already an rtog study with much lower doses due to toxicity concerns, and I doubt the every other day schedule made a huge difference, but maybe.

Trials to cut our role back will continue, but skepticism about trials without a standard of care control arm is warranted.

And no erectile dysfunction rates. Because who cares about that, right? Only patients.

 

[Chartreuse Wombat]

Something here isn’t right - this may be a better BED comparison but it seems unethical to not include ADT - either this patient population warranted that or that country accepts inferior outcomes without ADT (the absolute control rates here are absolutely inferior to chhip, noting differences in study pop).The second is that other single institution series of 40gy plus sbrt have generally had higher toxicity.

There is already an rtog study with much lower doses due to toxicity concerns, and I doubt the every other day schedule made a huge difference, but maybe.

Trials to cut our role back will continue, but skepticism about trials without a standard of care control arm is warranted.

And no erectile dysfunction rates. Because who cares about that, right? Only patients.

No need to get defensive. The trial began in 2005 before the trials demonstrating that ADT was helpful in XRT patients (at low doses remember 66-70 Gy and maybe not in all intermediate risk patients). The value of ADT in intermediate risk disease remains an open question that hopefully will be answered by RTOG 0815; a study opened in the US and Canada in 2008 with a no ADT arm.

If ADT is not on board then the trial is cleaner experiment testing the BED of two different regimens. The results suggest that the efficacy and late toxicity is similar.

Of course wait for the publication before changing practice but a no ADT study in intermediate risk patients was entirely ethical (as was a no ADT arm for RTOG 0815). As GFunk said...this is your future, embrace it.

 

[DebtRising]

I am sorry for being defensive. But I stand by the comment regarding adt use. In my defense(pun not intended) the TROG study was published in 2005 - that start of this trial enrollment, and while I was not in practice then, from my mentors palable disease was commonly receiving adt. T3a or even T2b disease not receiving adt with RT was not standard of care for almost the entire accrual of this trial. Chhip is also a good reference of contemporary standard of care practices in another European country. RTOG 0815 was not a question of adt effectiveness - it was a question of wether increased RAd dose could provide the same benefit.

I promise to continue to be crotchety about the lack of erectile dysfunction rates in any prostate dose change trials, because that is wrong and a different standard of care than the cosmetic outcome focus included broadly in breast dose change trials.

Grade 3 GU toxicity tells us nothing about absolute ED change rates, which I spoke about all morning.

 

[Chartreuse Wombat]

I am sorry for being defensive. But I stand by the comment regarding adt use. In my defense(pun not intended) the TROG study was published in 2005 - that start of this trial enrollment, and while I was not in practice then, from my mentors palable disease was commonly receiving adt. T3a or even T2b disease not receiving adt with RT was not standard of care for almost the entire accrual of this trial. Chhip is also a good reference of contemporary standard of care practices in another European country. RTOG 0815 was not a question of adt effectiveness - it was a question of wether increased RAd dose could provide the same benefit.

I promise to continue to be crotchety about the lack of erectile dysfunction rates in any prostate dose change trials, because that is wrong and a different standard of care than the cosmetic outcome focus included broadly in breast dose change trials.

Grade 3 GU toxicity tells us nothing about absolute ED change rates, which I spoke about all morning.

You are wrong about 0815. Look it up here. Radiation Therapy With or Without Androgen-Deprivation Therapy in Treating Patients With Prostate Cancer - Full Text View - ClinicalTrials.gov

RTOG 0815 is in fact an ADT question. What is the value of ADT in the setting of contemporary high dose irradiation (79.2 Gy, brachy boost, etc). TROG used 66 Gy, RTOG 9408 used 66.6 Gy, D'Amico used 70 Gy. many argue that these trials are not germane to contemporary methods

I expect Widmark will report ED outcomes eventually.

 

[evilbooyaa]

From the first-link:
"Although patients who had the ultrahypofractionated treatment suffered slightly worse side-effects
at the end of treatment, long-term side-effects were the same as those experienced by patients who
had the standard treatment"

Here we go again. Ignore worse acute toxicity to push people through treatment faster. Great for doctors who get paid more for treating the patient LESS.
No signs of cancer returning? Is that the same bPFS? Look forward to the paper.

Seems like the prostate study enrolled a mix of favorable and unfavorable intermediate risk, depending on which of the risk factors were the ones that enrolled them on the trial. I don't think ADT is mandatory in that group. Not sure where the press release got 'high-risk' patients from.

For the second link: "Ma'am, would you rather have 10-20 spears pierced through your breast hanging around for a week, where you have to come in to treatment twice every day at least 6 hours apart, before they have to be removed as well as the additional healing time of having those removed, all while keeping it clean and infection free, or would you rather come for daily treatment without any spears or anything that touches your skin, where you get an x-ray and don't feel anything, for a total of 15-20 sessions? A study showed that a full 6 week regimen (which I wouldn't recommend for you) had slightly worse arm swelling and breast swelling compared to the regimen with the spears."

 

[MDACCRules]

Ha. Spears.

CW - would you not give hormones to someone with T3a disease? That's been standard of care since people here were little boys and girls (RTOG8531, RTOG8610, EORTC22863). How about GS 8 or higher? I'd even give it for certain 7s (particularly if 4+3 or >50% cores).

That's like saying compare 60 Gy to 70 Gy in stage III NSCLC without chemotherapy, just to do a true BED comparison. The control arm should get standard of care. That's just my opinion, though.

 

[medgator]

Unlike the breast data which is a clear slam dunk towards hypo-fractionation, the prostate data feels like it being fit into a conclusion for insurers and managed care systems to run with

 

[evilbooyaa]

Ha. Spears.

CW - would you not give hormones to someone with T3a disease? That's been standard of care since people here were little boys and girls (RTOG8531, RTOG8610, EORTC22863). How about GS 8 or higher? I'd even give it for certain 7s (particularly if 4+3 or >50% cores).

That's like saying compare 60 Gy to 70 Gy in stage III NSCLC without chemotherapy, just to do a true BED comparison. The control arm should get standard of care. That's just my opinion, though.

That's the issue, it's a heterogeneous group of patients. Forgot about the T3a component. The issue is not all of them were T3a, which would be the only component that makes you 'high risk' per NCCN. But yes, I agree that specifically for the subset that are T3a but otherwise intermediate risk, I'd probably lean towards ADT, especially if the Zumsteg delineation of unfavorable intermediate risk (4+3, >50% cores, etc.) would push people towards ADT then as well.

 

[MDACCRules]

That's the issue, it's a heterogeneous group of patients. Forgot about the T3a component. The issue is not all of them were T3a, which would be the only component that makes you 'high risk' per NCCN. But yes, I agree that specifically for the subset that are T3a but otherwise intermediate risk, I'd probably lean towards ADT, especially if the Zumsteg delineation of unfavorable intermediate risk (4+3, >50% cores, etc.) would push people towards ADT then as well.

>7 makes you high risk.

 

[Chartreuse Wombat]

Ha. Spears.

CW - would you not give hormones to someone with T3a disease? That's been standard of care since people here were little boys and girls (RTOG8531, RTOG8610, EORTC22863). How about GS 8 or higher? I'd even give it for certain 7s (particularly if 4+3 or >50% cores).

That's like saying compare 60 Gy to 70 Gy in stage III NSCLC without chemotherapy, just to do a true BED comparison. The control arm should get standard of care. That's just my opinion, though.

Today yes I would recommend ADT in that patient a patient with T3a, Gleason 8 but I think you are overestimating the risks of patient included in this study. As the abstract above says these are INTERMEDIATE risk patients. To be dispositive we must wait for the paper or more specifics of the population. My recollection from 2 years ago when the early toxicity was reported as a late breaker at ASTRO is that the Widmark study is MOSTLY intermediate risk disease; e.g. T1c Gleason 7 PSA 8 and NOT high risk. One can argue that ADT is SOC in intermediate risk disease but there are plenty of people that feel otherwise. Several trials open during the last decade in intermediate risk disease have included a no ADT arm (RTOC 0815, RTOG 0232, PROFIT). I think you are biased against the result and want to ignore it by arguing that the standard arm was not SOC. What if 80% of the patients have intermediate risk disease? Sweden has ethics protections and if there was a consensus that the standard arm was not SOC then presumably the study would not have taken place.

 

[kristofer]

For the second link: "Ma'am, would you rather have 10-20 spears pierced through your breast hanging around for a week, where you have to come in to treatment twice every day at least 6 hours apart, before they have to be removed as well as the additional healing time of having those removed, all while keeping it clean and infection free, or would you rather come for daily treatment without any spears or anything that touches your skin, where you get an x-ray and don't feel anything, for a total of 15-20 sessions? A study showed that a full 6 week regimen (which I wouldn't recommend for you) had slightly worse arm swelling and breast swelling compared to the regimen with the spears."

Eh, you'd be surprised. What's really interesting to me is the (seemingly surgeon-driven) explosion of Xoft in the community recently. Want to talk about an easy sell to patients.

 

[evilbooyaa]

Are they really taking G8-10 in this trial as well and not doing ADT? I certainly agree that would not be SOC either. We'll have to see what their baseline characteristics are in terms of enrollment. I think I'd question rad oncs who enrolled G8-10 patients on this trial.

I imagine this will end up being a mostly intermediate-risk paper (hopefully). I do agree with CW's point above, that this will likely end up being mostly intermediate-risk. Agree that we should wait for the paper before utilizing our jump to conclusions mat.

 

[Chartreuse Wombat]

>7 makes you high risk.

Eligibility say > or = to 7. Wait for the details.

 

[evilbooyaa]

Eh, you'd be surprised. What's really interesting to me is the (seemingly surgeon-driven) explosion of Xoft in the community recently. Want to talk about an easy sell to patients.

Every non rad-onc (and some rad-oncs) wants to say that Xoft IORT is the same as all other APBI (Interstitial, mammosite, SAVI, whatever), when we have zero data to suggest that, and guidelines which explicitly state that the are NOT the same.

 

[kristofer]

Every non rad-onc (and some rad-oncs) wants to say that Xoft IORT is the same as all other APBI (Interstitial, mammosite, SAVI, whatever), when we have zero data to suggest that, and guidelines which explicitly state that the are NOT the same.

Oh I agree, but my point is that it is happening a lot now, both on and off trial. Imagine the scenario where good data comes out.

 

[MDACCRules]

Today yes I would recommend ADT in that patient a patient with T3a, Gleason 8 but I think you are overestimating the risks of patient included in this study. As the abstract above says these are INTERMEDIATE risk patients. To be dispositive we must wait for the paper or more specifics of the population. My recollection from 2 years ago when the early toxicity was reported as a late breaker at ASTRO is that the Widmark study is MOSTLY intermediate risk disease; e.g. T1c Gleason 7 PSA 8 and NOT high risk. One can argue that ADT is SOC in intermediate risk disease but there are plenty of people that feel otherwise. Several trials open during the last decade in intermediate risk disease have included a no ADT arm (RTOC 0815, RTOG 0232, PROFIT). I think you are biased against the result and want to ignore it by arguing that the standard arm was not SOC. What if 80% of the patients have intermediate risk disease? Sweden has ethics protections and if there was a consensus that the standard arm was not SOC then presumably the study would not have taken place.

There's enough data out there to support treatment with hypofx and even 5-7 fx. I'm just saying that was a quirk. I don't think it would make a difference. I'm not biased. I just said it was interesting that it said intermediate and high risk but ADT wasn't allowed. I'm pro-HF.

 

[ramsesthenice]

Eligibility from previous abstract below; looks like mostly intermediate
View attachment 232819
It is probably a better test of BED if ADT is not included. Wait for the paper but in capitated environments this is potentially a game changer.

I have done a fair bit of prostate SBRT for low and LIR patients on trial and if there was increased toxicity it was subtle though admittedly its easy to miss acute toxicity when the patient is done with treatment before they really have time to experience it.

The thing that will keep me from doing more SBRT is that I think brachy is probably better for a lot of patients. Most of the data we have for SBRT in low and LIR patients suggests its no better in terms of bPFS. If I am going to accept a little more GU toxicity in the name of convenience, I would rather do it with a technique which has less erectile dysfunction and maybe better bPFS. I also think the post-EBRT brachy boost data for unfavorable IR and HR patients is looking pretty good to be better than conventional too. Obviously, my opinion is largely speculative until all of the data has more time to mature.

 

[Chartreuse Wombat]

According to Dr Widmark, the PI of the prostate study: 89% intermediate, 11% high risk

 

[MegaVoltagePhoton]

From the first-link:
"Although patients who had the ultrahypofractionated treatment suffered slightly worse side-effects
at the end of treatment, long-term side-effects were the same as those experienced by patients who
had the standard treatment"

Here we go again. Ignore worse acute toxicity to push people through treatment faster. Great for doctors who get paid more for treating the patient LESS.
No signs of cancer returning? Is that the same bPFS? Look forward to the paper.

Seems like the prostate study enrolled a mix of favorable and unfavorable intermediate risk, depending on which of the risk factors were the ones that enrolled them on the trial. I don't think ADT is mandatory in that group. Not sure where the press release got 'high-risk' patients from.

For the second link: "Ma'am, would you rather have 10-20 spears pierced through your breast hanging around for a week, where you have to come in to treatment twice every day at least 6 hours apart, before they have to be removed as well as the additional healing time of having those removed, all while keeping it clean and infection free, or would you rather come for daily treatment without any spears or anything that touches your skin, where you get an x-ray and don't feel anything, for a total of 15-20 sessions? A study showed that a full 6 week regimen (which I wouldn't recommend for you) had slightly worse arm swelling and breast swelling compared to the regimen with the spears."

Meh...yes, but I find lots of people conveniently ignore that the two hypo trials showing more acute toxicities showed either equal late toxicity or better late toxicity. The only hypofrac trial showing worse late toxicity (in all comers) was the RTOG 0415 where the comparator arm was only 73.8 Gy. We know from multiple studies including 0126 that late toxicity is worse with higher doses. So, are you going to treat anyone with 73.8 Gy?

So a more fair comment is, are you willing to endure slightly more tenesmus/diarrhea acutely to (a) finish treatment much faster and (b) potentially have less chronic diarrhea/tenesmus?

 

[evilbooyaa]

Couple things about the planning requirements for PROFIT (http://ascopubs.org/doi/suppl/10.1200/JCO.2016.71.7397), the only trial to show a 'benefit' of late toxicity.

Rectal diameter > 2cm forced a re-sim.

The planning constraints from that protocol (in the supplement) make no sense to me. They're below if somebody wants to help me figure out how the bolded constraints.

They also use 1cm CTV-PTV and 7mm posteriorly, which are gigantic margins for definitive prostate cancer. I find it truly unlikely that late toxicity is better with hypofractionation. At best I'd say it's a wash in appropriately selected doses, given that 3 trials have shown each of the 3 possible options for late GI toxicity. And then we have essentially consensus that acute toxicity is worse with hypofrac.

"Hypofractionated Treatment arm:
CTV D99 ≥ 60Gy
PTV D99 ≥ 57Gy (-5%)
The volume of PTV exceeding 63Gy should not exceed 1 cubic centimetre (+5%)
Contoured rectal wall: 50% to receive less than 37Gy
70% to receive less than 46Gy
Contoured bladder wall: 50% to receive less than 37Gy
70% to receive less than 46Gy
Femoral head and neck: 5% to receive less than 43Gy
Dose prescription: 60Gy in 20 (3Gy) fractions over 4 weeks prescribed to CTV
minimum

Conventional Treatment arm:
CTV D99 ≥ 78Gy
PTV D99 ≥ 74.1Gy (-5%),
The volume of PTV exceeding 81.9 Gy should not exceed 1 cubic centimetre (+5%)
Contoured rectal wall: 50% to receive less than 53Gy
70% to receive less than 71Gy
Contoured bladder wall: 50% to receive less than 53Gy
70% to receive less than 71Gy
Femoral head and neck: 5% to receive less than 53Gy
PROFIT Protocol, V3 Revised: January 31, 2011 Page 49 of 53
Dose prescription: 78Gy in 39 (2Gy) fractions over 7.8 weeks prescribed to CTV
minimum"

 

[MegaVoltagePhoton]

Respectfully disagree, strongly.

How can it be a wash? The one trial that showed worse late toxicity had a LOW DOSE CONTROL ARM. Even the authors of that trial suggest that a higher (i.e., standard) dose conventional fractionation arm would have had more late toxicity. Regardless, CHHiP was nearly 3 times the size and found absolutely no difference in late toxicity. And PROFIT was similarly sized and found BETTER late toxicity. There is simply no way to honestly look at those data and call it a wash. 2/3 trials (accounting for close to 60/70% of patients on any hypofrac trial) showed no worse toxicity (at minimum), and the one trial that showed worse toxicity had a low dose control.

Further, that's only those trials. There's also the Fox Chase trial which showed no worse toxicity overall (worse urinary toxicity for patients with bad urinary function, granted), and the MDACC trial which also showed no worse late toxicity. And Arcangeli with 10 years following showing no worse late toxicity overall either (minor grade 1 hematuria specifically was worse).

So, ask your patients --> would you risk more acute diarrhea/tenesmus (keep in mind these are generally grade 1 and 2 toxicity), to be done with treatment in 1/2 the time? That would be an honest presentation of the data.

 

[evilbooyaa]

So, ask your patients --> would you risk more acute diarrhea/tenesmus (keep in mind these are generally grade 1 and 2 toxicity), to be done with treatment in 1/2 the time? That would be an honest presentation of the data.

Completely agree with this statement. I was simply arguing against your second point of "lower toxicity with hypofrac". I think prostate hypofrac is an option to be presented with patients with a frank discussion regarding the increased risk of acute side effects, exactly as you've stated.

 

[MegaVoltagePhoton]

Completely agree with this statement. I was simply arguing against your second point of "lower toxicity with hypofrac". I think prostate hypofrac is an option to be presented with patients with a frank discussion regarding the increased risk of acute side effects, exactly as you've stated.

To be clear, I stated that the people who cite increased acute toxicity often ignore that one of the trial showed better late toxicity, and the other showed no increase in late toxicity. The lack of increase in late toxicity needs to be emphasized if we are going to stress an increase in short term toxicity.

 

[medgator]

ASTRO/ASCO/AUA guidelines in JCO this month

http://ascopubs.org/doi/full/10.1200/JCO.18.01097

 

[Palex80]

Data on the value of ADT in the setting of dose escalation from preliminary analysis of the latest Bolla trial...

Short Androgen Suppression and Radiation Dose Escalation for Intermediate- and High-Risk Localized Prostate Cancer: Results of EORTC Trial 22991. - PubMed - NCBI

ADT still valuable even if giving 80 Gy for intermediate risk disease.

 

[medgator]

https://www.redjournal.org/article/S0360-3016(18)34006-9/pdf

At 3-year follow-up, the incidence of clinically relevant deterioration of urinary symptoms was 33% for both treatments (difference 0.49% in favor of conventional fractionation, 90% CI: -7.20%- 8.18%), whereas such deterioration of gastrointestinal symptoms was reported in 38% for hypofractionation versus 36% for conventional fractionation (2.03% in favor of conventional fractionation, 90% CI: -6.18%- 10.23%). Therefore, we could not demonstrate non-inferiority of hypofractionation for genitourinary and gastrointestinal quality-of-life.

 

[scarbrtj]

https://www.redjournal.org/article/S0360-3016(18)34006-9/pdf

Add to this another very recent paper looking at SBRT vs IMRT vs protons for prostate. My read of this data is IMRT is better than SBRT ("extreme" hypofract) is better than protons.

Adding this data to *all* the hypofract data, the data support that standard fx IMRT has the best overall outcomes profile for prostate cancer.

 

[OTN]

The rush/push/shame on the rest of us to embrace hypofractionation for prostate ca by academica is a prime example of virtue-signaling in our field. I agree with scarbrtj- if I were diagnosed with high-risk prostate cancer, for example, I would go with standard-fractionation IMRT with HT and would refuse hypofractionation.

 

[Chartreuse Wombat]

https://www.redjournal.org/article/S0360-3016(18)34006-9/pdf

No one is advocating the regimen used in HYPRO (19 fractions of 3.4 Gy three times per week). The comparison is not germane to the accepted moderate hypo regimens like that used in CHHiP, PROFIT (60 Gy/20 fractions) or 0415 (70 Gy/28).

 

[medgator]

The rush/push/shame on the rest of us to embrace hypofractionation for prostate ca by academica is a prime example of virtue-signaling in our field. I agree with scarbrtj- if I were diagnosed with high-risk prostate cancer, for example, I would go with standard-fractionation IMRT with HT and would refuse hypofractionation.

Glad I waded into the prostate hypofx pond slowly... started 70/28 in a few ideal patients.... Will make me think twice about going above 2.5/day.

There really has been a rush into all of this, without the slam dunk data like in breast to back it up

 

[medgator]

No one is advocating the regimen used in HYPRO (19 fractions of 3.4 Gy three times per week). The comparison is not germane to the accepted moderate hypo regimens like that used in CHHiP, PROFIT (60 Gy/20 fractions) or 0415 (70 Gy/28).

Yet nccn blesses everything from 1.8 to 7.25

 

[scarbrtj]

The rush/push/shame on the rest of us to embrace hypofractionation for prostate ca by academica is a prime example of virtue-signaling in our field. I agree with scarbrtj- if I were diagnosed with high-risk prostate cancer, for example, I would go with standard-fractionation IMRT with HT and would refuse hypofractionation.

What with all the stuff happening in France (it's kind of inspiring!), resisting against the "virtue signalling" there... maybe we just need a good 'ol fashioned protest.

 

[Chartreuse Wombat]

Yet nccn blesses everything from 1.8 to 7.25

Again, not germane. They don't advocate for 19 fractions of 3.4Gy which is the issue at hand.

 

[scarbrtj]

No one is advocating the regimen used in HYPRO (19 fractions of 3.4 Gy three times per week). The comparison is not germane to the accepted moderate hypo regimens like that used in CHHiP, PROFIT (60 Gy/20 fractions) or 0415 (70 Gy/28).

We are approaching the point where the word "hypofractionation" doesn't mean anything anymore. (We've got standard hypofractionation. Ultra-hypofractionation. Moderate hypofractionation. Perhaps minty-fresh or hardcore hypofractionation is next.) There is a vast range of doses available to the modern rad onc and "hypofractionation" is too subjective, too obtuse a term to be anything but a "Are you a hypofractionator or not... confess!" thing to show you aren't an intellectual Luddite. And a 19-fraction regimen to ~64Gy is germane IMHO to 60 Gy/20 fractions, especially given that the 19-fraction regimen is giving 10.2 Gy per week and the 60/20 gives 15 Gy/week. One regimen is not, on paper, more moderate than the other. One can easily predict (sans calcs) acute effects equivalence e.g. with 64.9/19 (~6 weeks) and 60/20 (4 weeks). San calcs, san time correction, I get 66 Gy-10 for 64.9/19 and 64 Gy-10 for 60/20 (and 67 Gy-10 for 78/39)... all essentially equivalent. 70/28 has a Gy-10 of ~69 Gy-10... it would technically be the "least moderate" regimen. For acute effects.

 

[Chartreuse Wombat]

We are approaching the point where the word "hypofractionation" doesn't mean anything anymore. (We've got standard hypofractionation. Ultra-hypofractionation. Moderate hypofractionation. Perhaps minty-fresh or hardcore hypofractionation is next.) There is a vast range of doses available to the modern rad onc and "hypofractionation" is too subjective, too obtuse a term to be anything but a "Are you a hypofractionator or not... confess!" thing to show you aren't an intellectual Luddite. And a 19-fraction regimen to ~64Gy is germane IMHO to 60 Gy/20 fractions, especially given that the 19-fraction regimen is giving 10.2 Gy per week and the 60/20 gives 15 Gy/week. One regimen is not, on paper, more moderate than the other. One can easily predict (sans calcs) acute effects equivalence e.g. with 64.9/19 (~6 weeks) and 60/20 (4 weeks). San calcs, san time correction, I get 66 Gy-10 for 64.9/19 and 64 Gy-10 for 60/20 (and 67 Gy-10 for 78/39)... all essentially equivalent. 70/28 has a Gy-10 of ~69 Gy-10... it would technically be the "least moderate" regimen. For acute effects.

Lots of words without rebutting the claim that no one is advocating 19 fractions of 3.4 Gray.

 

[scarbrtj]

Lots of words without rebutting the claim that no one is advocating 19 fractions of 3.4 Gray.

Words, yes. You advocate 19*3.4 when you advocate 20*3, 'tis truly 6 of one and half-dozen of the other. That "no one is advocating 19 fractions of 3.4 [G]ray" (S.I. units never capitalized!) is not intellectually honest as clearly the launching of a trial required some advocacy, somewhere.

 

[evilbooyaa]

https://www.redjournal.org/article/S0360-3016(18)34006-9/pdf

I mean, in all honesty, they're saying it's not non-inferior. At a cut-off of 8%, GU toxicity 95% CI went to 8.18, while GI went to 13%. I agree with most that the prostate hypofrac data is not nearly as slam dunk as breast hypofrac. I don't think there's a significant difference in GU toxicity, my main concern would be GI toxicity (both acute and late). However, I don't foresee it necessarily being like breast (at least not right now) where hypofrac is the only recommended option. Even the recently published hypofrac guidelines say, "it can be offered" not "it should be offered" (as it says for the most recent breast hypofrac data).

All that being said, 19 x 3.4 at 3x/week is different from 70/28, which is probably the most common hypofrac regimen in the US.

I think if you have data saying 19 x 3.4 may be worse but 60 in 20 is OK, you can't just dismiss that and say it's all the same because outdated radiation biology BED calcs tells you it should be.

 

[ramsesthenice]

However, I don't foresee it necessarily being like breast (at least not right now) where hypofrac is the only recommended option.

It won't and that was always an unrealistically high bar. The potential for increased toxicity with prostate is much higher than breast. Patients with recurrent breast cancer die of cancer. Most patients with recurrent prostate cancer are none the wiser without someone telling them their PSA is high. The bar to accept a potentially more toxic treatment was always much higher for prostate than breast or most other disease sites.

FWIW, I mostly do modest hypofractionation now (70/30 or there about). Haven't seen any differences in toxicity and it gets them done a couple weeks faster. I don't care about BED, I think it is very unlikely to be demonstrably better. I do it to be convenient for the patient. But I make it very clear that there is the possibility it might be a little more toxic and give them the option of conventional. Almost no one opts for 42 treatments which frankly surprises me.

 

[Chartreuse Wombat]

Words, yes. You advocate 19*3.4 when you advocate 20*3, 'tis truly 6 of one and half-dozen of the other. That "no one is advocating 19 fractions of 3.4 [G]ray" (S.I. units never capitalized!) is not intellectually honest as clearly the launching of a trial required some advocacy, somewhere.

is=present tense, required=past tense; nice try though

 

[scarbrtj]

outdated radiation biology BED calcs tells you it should be.

Without any hint of irony we call the BED calcs "outdated," yet they are the entire raison d'être of prostate CA hypofractionation itself. BTW... why are BED calcs outdated? AFAIK, cellular response to radiation, and math, haven't changed since alpha/beta, BEDs, and so forth, were originally conceived, validated in vivo/vitro, etc.

is=present tense, required=past tense; nice try though

I'm not trying anything (certainly not arguing what "is" is). Only saying that in a world where five-fraction prostate SBRT is advocated at daily doses of 7-8 Gy, and 70/28 is advocated, and 60/20 is advocated, and smart people launch trials looking at ~64/19, and smart people publish trials re: ~64/19 showing ~64/19 is not non-inferior... ~64/19 is ipso facto advocated. 60/20/4 weeks vs ~64/19/6 weeks is a distinction without a difference.

 

[scarbrtj]

I don't care about BED, I think it is very unlikely to be demonstrably better.

Just to be clear:
1) All prostate hypofractionation schemes which varied from the de rigueur 1.8-2Gy/day were designed around BED; if no one had cared about BED, we wouldn't have prostate hypofractionation.
2) AFAIK, all the prostate hypofractionation schemes were never designed to be oncologically better... only oncologically equivalent. Any assumption of "betterness" was in the side-effect arena where any hope of "betterness" hinged on prostate alpha/beta being less than late tissue alpha/beta and the BED calcs showing lower late tissue BEDs with prostate hypofractionation (because hypofractionation, per tradition but not necessarily by definition, always results in a lower total Rx dose... and it is total dose vs fraction size which MOST governs late effect outcomes within the range of feasible human XRT dose schemes). The chase for hypofractionation in our field has almost never been a chase for the clinically better—only for the financially cheaper, the temporally quicker.

 

[evilbooyaa]

Scarbrtj, I agree with you on principle, that there is concern for toxicity (mainly acute GI) with hypofractionated regimens. This is reflected in the recent consensus statement as well. I also have concerns about late GI from a couple of the reported trial (understanding that not all hypofrac trials showed this).

Did anybody think 57/19 was going to be inferior to 60/20 using BED calcs? We do the calcs for hypothesis generation (as was done in prostate hypofrac) and then we confirm the calcs in trials. Our understanding of all this is not as good as radiation biologists would have you believe. Does the higher than 3Gy fraction size of the HYPRO regimen (even with 3x a week treatment) lead to higher toxicity than 3Gy per Fx daily from CHHiP or PROFIT? That's the most likely explanation, right?

 

[RollTideRadOnc]

It amazes me to no end how some people (ahem... mostly in private practice) will engage in all sorts of solipsism to obscure the fact that hypofractionation is equivalent to longer protracted courses of treatment across all disease and toxicity endpoints. Frankly, it strikes me as very selfish indeed to subject patients to 9 weeks of treatment when 4 weeks or fewer will do.

Of course, I'm sure these same folks will claim that in "their hands" 9 weeks of IMRT has simply the most amazing outcomes.

Go ahead... tie yourself in intellectual knots to justify outdated techniques that reimburse better. I'm sure there are no conflicted motives here whatsoever...

 

[evilbooyaa]

It amazes me to no end how some people (ahem... mostly in private practice) will engage in all sorts of solipsism to obscure the fact that hypofractionation is equivalent to longer protracted courses of treatment across all disease and toxicity endpoints. Frankly, it strikes me as very selfish indeed to subject patients to 9 weeks of treatment when 4 weeks or fewer will do.

Of course, I'm sure these same folks will claim that in "their hands" 9 weeks of IMRT has simply the most amazing outcomes.

Go ahead... tie yourself in intellectual knots to justify outdated techniques that reimburse better. I'm sure there are no conflicted motives here whatsoever...

Here we go, another holier-than-thou resident to tell the attendings on this forum how they're all dirty money-grubbers.

Most of the attendings at multiple academic institituions (outside of those that pioneered hypofrac) don't do hypofractionation for prostate. A number of them don't do it routinely in breast. Bashing private practice primarily for this phenomenom is outrageous, especially when academic centers are still doing protons for breast or prostate.

Your second bolded statement is frankly incorrect. There is higher acute GI toxicity across nearly every hypofrac trial with prostate hypofrac. Just like the consensus guidelines on prostate hypofrac state. Fraction shaming when doctors want to give their patient a treatment that MINIMIZES toxicity and is the standard is NOT unreasonable. Once again, the data for prostate hypofrac is NOWHERE near as good as the data for breast hypofrac, and academicians push to equate the two and demonize those who don't fall in line continues to be outrageous. None of this means that prostate hypofrac is an incorrect treatment - if the patient understands the risk of more acute GI toxicity and is OK with that, then great. But if they would prefer NOT to have more acute GI toxicity and are OK with 9 weeks of treatment, that's OK too.

 

[Gfunk6]

It amazes me to no end how some people (ahem... mostly in private practice) will engage in all sorts of solipsism to obscure the fact that hypofractionation is equivalent to longer protracted courses of treatment across all disease and toxicity endpoints. Frankly, it strikes me as very selfish indeed to subject patients to 9 weeks of treatment when 4 weeks or fewer will do.

Of course, I'm sure these same folks will claim that in "their hands" 9 weeks of IMRT has simply the most amazing outcomes.

Go ahead... tie yourself in intellectual knots to justify outdated techniques that reimburse better. I'm sure there are no conflicted motives here whatsoever...

Well, I'm in private practice. I advocate extreme hypofractionation in all my low and favorable-intermediate risk prostate cancer patients. We use a robotic platform with four fiducials, spaceOAR and real-time tracking. Five consecutive days, no breaks. 3 mm PTV expansion.

Since the proton guys are so fond of using dosimetry to justify clinical superiority, I can tell you that I am easily able to meet all rectal constraints all the time thanks to spaceOAR.

Patients have zero acute side effects; many men have asked me jokingly if the "beam was on."

NCCN allows for SBRT as an option in the clinical category of patients that I am discussing. We have the technology and we use it - it is good for patients, good for society, and good for me. I don't need a Phase III randomized trial with 1,500 patients and 20 years of long-term follow-up to make clinical decisions on 0.1% increase in late GI toxicity.

 

[RollTideRadOnc]

Your second bolded statement is frankly incorrect. There is higher acute GI toxicity across nearly every hypofrac trial with prostate hypofrac. Just like the consensus guidelines on prostate hypofrac state.

Ha! Love it. Let me correct my prior statement by adding the word *meanignful*. There are no meaningful differences. And thanks for pointing out that I forgot to update my status to attending. That can be confusing... especially since it's so relevant to the discussion at hand.

 

[RickyScott]

It amazes me to no end how some people (ahem... mostly in private practice) will engage in all sorts of solipsism to obscure the fact that hypofractionation is equivalent to longer protracted courses of treatment across all disease and toxicity endpoints. Frankly, it strikes me as very selfish indeed to subject patients to 9 weeks of treatment when 4 weeks or fewer will do.

Of course, I'm sure these same folks will claim that in "their hands" 9 weeks of IMRT has simply the most amazing outcomes.

Go ahead... tie yourself in intellectual knots to justify outdated techniques that reimburse better. I'm sure there are no conflicted motives here whatsoever...

I assume you are academic based on name. If that is the case, "In your hands," radiation for prostate cancer- even hypofractionated- is almost certainly much more costly than the outpatient center down the street. Differences in my market can be easily 3 x price. Why dont you choose wisely, help out society and send your patients there? Tell them you are sick of the out of control prices at your facility that are ruining health care. (I am sure what your center charges insurances is protected by an NDA, and they will never tell you, but if you can, please, disclose the rates that were negotiated leveraging monopolistic pricing power.)

The bottom line is that hypofractionation falsely allows you to feel good that you are doing the "right thing," when ironically you are the real problem.

edit: i use hypofractionation in about half prostate cancers in a community hospital where I am emplyed with almost no incentive, but most importantly, the prices at our hospital are at least 50% less than a nearby academic center.