Prostate Hypofractionation Discussion

[Palex80]

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3) 26 vs 27 Gy seems insignificant, but there are threshold effects like this - there is a hypoFX prostate study showing 1 less fraction was either less effective or less toxic, I forget which. Shoulders, and what not.

CHHiP-trial

Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial - PubMed

Cancer Research UK, Department of Health, and the National Institute for Health Research Cancer Research Network.

pubmed.ncbi.nlm.nih.gov

 

[scarbrtj]

CHHiP-trial

Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial - PubMed

Cancer Research UK, Department of Health, and the National Institute for Health Research Cancer Research Network.

pubmed.ncbi.nlm.nih.gov

Since we are now talking about prostate in the breast thread 🙂


Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer (HYPO-RT-PC): patient-reported quality-of-life outcomes of a randomised, controlled, non-inferiority, phase 3 trial


I read this and before hitting conclusion section I thought "well I don't like this ultrahypofx very much." And then in the conclusions: "We are telling you to like this ultrahypofx very much."

 

[OTN]

Since we are now talking about prostate in the breast thread 🙂


Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer (HYPO-RT-PC): patient-reported quality-of-life outcomes of a randomised, controlled, non-inferiority, phase 3 trial


I read this and before hitting conclusion section I thought "well I don't like this ultrahypofx very much." And then in the conclusions: "We are telling you to like this ultrahypofx very much."

For health systems in which a central authority rations resources, they seem to be arguing that increased acute treatment toxicity for patients is an acceptable trade-off. Hard to tell from this data what the patients themselves would think of that conclusion.

 

[medgator]

For health systems in which a central authority rations resources, they seem to be arguing that increased acute treatment toxicity for patients is an acceptable trade-off. Hard to tell from this data what the patients themselves would think of that conclusion.

Yup

"Men should be counseled about the small increased risk of acute gastrointestinal (GI) toxicity with moderate hypofractionation. Moderately hypofractionated EBRT has a similar risk of acute and late genitourinary and late GI toxicity compared with conventionally fractionated EBRT. However, physicians should discuss the limited follow-up beyond 5 years for most existing RCTs evaluating moderate hypofractionation."

 

[evilbooyaa]

Since we are now talking about prostate in the breast thread 🙂


Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer (HYPO-RT-PC): patient-reported quality-of-life outcomes of a randomised, controlled, non-inferiority, phase 3 trial


I read this and before hitting conclusion section I thought "well I don't like this ultrahypofx very much." And then in the conclusions: "We are telling you to like this ultrahypofx very much."

Not anymore we're not (in regards to bolded). Moved a few posts to a new thread.

 

[evilbooyaa]

Yup

"Men should be counseled about the small increased risk of acute gastrointestinal (GI) toxicity with moderate hypofractionation. Moderately hypofractionated EBRT has a similar risk of acute and late genitourinary and late GI toxicity compared with conventionally fractionated EBRT. However, physicians should discuss the limited follow-up beyond 5 years for most existing RCTs evaluating moderate hypofractionation."

I quote this line from the Prostate hypofx guidelines to patients 100% of the time in a definitive case. Most pick hypofx, but I'd say 1 in 5 choose conventional.

 

[FrostyHammer]

For health systems in which a central authority rations resources, they seem to be arguing that increased acute treatment toxicity for patients is an acceptable trade-off. Hard to tell from this data what the patients themselves would think of that conclusion.

I use CHHIP and PROFIT fractionation almost exclusively (except patients that need nodes treated where I do 28 with an SIB) and love it. Patients love it too because they'll almost always accept a slightly higher risk of acute SEs if the late SEs are the same and they don't have to come for weeks longer. Most even tell me that they prefer 4 weeks to 5.5 weeks as well.

 

[GI_RadOnc]

I can't help but think this is the 'ceiling' of acute toxicity; and not the floor. I get it, these patients live way way longer than my GI patients; but this QOL study wouldn't defer most of our patients from considering this therapy.

80% of patients with 3DCRT, and aligned by implanted gold markers versus a urinary catheter.

 

[ramsesthenice]

I use CHHIP and PROFIT fractionation almost exclusively (except patients that need nodes treated where I do 28 with an SIB) and love it. Patients love it too because they'll almost always accept a slightly higher risk of acute SEs if the late SEs are the same and they don't have to come for weeks longer. Most even tell me that they prefer 4 weeks to 5.5 weeks as well.

Me too. If there are any differences in GI toxicity they are subtle at best. If anything, there have been a couple guys who had pretty noticeable urinary frequency right after finishing that hung around for 10-14 days before resolving. Nothing major but easy to see it getting overlooked if you don't see them for a couple months after finishing. How closely you follow your patients and when you see them can affect your perception of a given treatment. I probably follow patients closer than most and I just haven't come across anything worrisome yet. Been doing it for a couple years now.

 

[drewdog1973]

20fx for everyone who’s not getting nodes treated. 28fx if nodes are being treated... for now. Will eventually switch when more HF nodal accrues

 

[Palex80]

Yup

"Men should be counseled about the small increased risk of acute gastrointestinal (GI) toxicity with moderate hypofractionation. Moderately hypofractionated EBRT has a similar risk of acute and late genitourinary and late GI toxicity compared with conventionally fractionated EBRT. However, physicians should discuss the limited follow-up beyond 5 years for most existing RCTs evaluating moderate hypofractionation."

CHHiP now has 8 years of follow up reported. No increase in late toxicities with 20 x 3 Gy compared to 37 x 2 Gy.

https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.6_suppl.325

 

[madchemist89]

For those of you who use PROFIT regimen, do you have a copy of the protocol? I haven't been able to find it anywhere. If you use PROFIT, do you contour whole rectum or rectal wall?

 

[evilbooyaa]

For those of you who use PROFIT regimen, do you have a copy of the protocol? I haven't been able to find it anywhere. If you use PROFIT, do you contour whole rectum or rectal wall?

Second this - anyone have good dose constraints in this setting? Never saw good ones that make sense, make me anxious for the regimen myself.

 

[Chartreuse Wombat]

For those of you who use PROFIT regimen, do you have a copy of the protocol? I haven't been able to find it anywhere. If you use PROFIT, do you contour whole rectum or rectal wall?

Very straightforward

 

[Chartreuse Wombat]

For those of you who use PROFIT regimen, do you have a copy of the protocol? I haven't been able to find it anywhere. If you use PROFIT, do you contour whole rectum or rectal wall?

Complete protocol attached (from JCO website)

 

[madchemist89]

Thanks!

 

[evilbooyaa]

Very straightforward

Do you do the bladder and rectal wall (rather than the whole organ) as recommended?

 

[ramsesthenice]

Do you do the bladder and rectal wall (rather than the whole organ) as recommended?

I don’t. They are so mobile I’m not sure how meaningful they are.

 

[goodkerma]

Second this - anyone have good dose constraints in this setting? Never saw good ones that make sense, make me anxious for the regimen myself.

I've found this review helpful, Table 3 includes some realistic modified constraints to consider

Error - Cookies Turned Off

onlinelibrary.wiley.com

 

[evilbooyaa]

Thanks for the above paper

Anyone have any information that any of these constraints have been validated from a clinical toxicity standpoint? Would love to have some actual EBM constraints and not just extrapolations of already questionable standard fx constraints.

 

[RickyScott]

I don’t worry about “constraints”. (In eclipse) Just make sure your dose fall off 1 to 1.1 cm posterior to ptv is 50%. Can’t get a better plan than this without higher than 8-10% hot spots.
No 50% with 7% boost to left mid/base prostate 28 x 250

 

[scarbrtj]

I don’t worry about “constraints”. (In eclipse) Just make sure your dose fall off 1 to 1.1 cm posterior to ptv is 50%. Can’t get a better plan than this without higher than 8-10% hot spots.
No 50% with 7% boost to left mid/base prostate 28 x 250
View attachment 327499

You can even go tighter w/o "hot spots" (not hot spots). I like to call the upper left view the bobcat sign. When I see the bobcat, I know it's a good plan too. I dunno. Looks like a bobcat to me. Maybe a nittany lion?

 

[ramsesthenice]

I don’t worry about “constraints”. (In eclipse) Just make sure your dose fall off 1 to 1.1 cm posterior to ptv is 50%. Can’t get a better plan than this without higher than 8-10% hot spots.
No 50% with 7% boost to left mid/base prostate 28 x 250
View attachment 327499

In principle I love the approach. In tough cases we don't compromise tumor coverage because of normal tissue constraints. This is basically what I end up looking at also. I look at the overall dose shaping and then check hot spots. Constraints can be helpful as a starting point for inverse planning. More or less going to get the same place

You can even go tighter w/o "hot spots" (not hot spots). I like to call the upper left view the bobcat sign. When I see the bobcat, I know it's a good plan too. I dunno. Looks like a bobcat to me. Maybe a nittany lion?

It took me a minute to see it but I love it. Bobcat sign!!!

 

[FrostyHammer]

You can even go tighter w/o "hot spots" (not hot spots). I like to call the upper left view the bobcat sign. When I see the bobcat, I know it's a good plan too. I dunno. Looks like a bobcat to me. Maybe a nittany lion?

I think your patient forgot to fill his bladder...hope his bladder DVH looked OK

 

[RickyScott]

You can even go tighter w/o "hot spots" (not hot spots). I like to call the upper left view the bobcat sign. When I see the bobcat, I know it's a good plan too. I dunno. Looks like a bobcat to me. Maybe a nittany lion?

Love the plan. Is it vmat? I have planned hundreds of Prostates and always found falling off to 50% at 1 cm is achievable (including nodes)and this will far exceed any possible DVH constraints. Have not tried less than 1cm; .8 cm is impressive (6-7% per mm) but I would think that may be dependent on the overall size of the ptv.

 

[Chartreuse Wombat]

Thanks for the above paper

Anyone have any information that any of these constraints have been validated from a clinical toxicity standpoint? Would love to have some actual EBM constraints and not just extrapolations of already questionable standard fx constraints.

The paper at the link is the CHHiP analysis looking at rectal/anal constraints. To be honest it is incredibly complicated for me and I prefer the straightforward approach summarized on the PROFIT document. I have using this simple method for more than five years and the GU/GI toxicity is low.

Derivation of Dose/Volume Constraints for the Anorectum from Clinician- and Patient-Reported Outcomes in the CHHiP Trial of Radiation Therapy Fractionation - PubMed

Dose constraints differed among symptoms, indicating potentially different pathogenesis of radiation-induced side effects. Derived dose constraints were stricter than those used in CHHiP and may reduce bowel symptoms after radiation therapy.

pubmed.ncbi.nlm.nih.gov

 

[Gfunk6]

We do extreme hypofrac, all day every day.

Patient below was favorable intermediate risk prostate cancer. Prescribed 36.25 Gy in five fractions to 45.7% (yes you read that right) of maximum dose.

Isodose lines below are as follows: Orange (36.25), White (45.0), Green (64.0); Purple (27.0 Gy)

Mean dose to PTV = 46.66 Gy
Max dose to PTV = 79.32 Gy

Was able to create HDR like distribution per Fuller's protocol, note "hole" where the urethra was. SpaceOAR facilitated very low rectal dose. Patient had 3T multiparametric MRI which was fused to CT sim to intelligently dump dose into gross tumor which received 69.0 Gy (mean).

Accomplished on a CyberKnife M6 system using 58 non-coplanar beams with MLC collimation. Beam on time per each of five treatments was 27 minutes.

BED calcs
- Mean dose to entire PTV is equivalent to about 110 Gy with conventional fractionation
- Mean dose to gross tumor is equivalent to about 235 Gy with conventional fractionation

 

[MegaVoltagePhoton]

Would anyone ever hypofrac in the postop setting? I see these small studies in the red journal but am holding off for the NRG trial to report. I think there are even some SBRT studies.

 

[Gfunk6]

Would anyone ever hypofrac in the postop setting? I see these small studies in the red journal but am holding off for the NRG trial to report. I think there are even some SBRT studies.

I have done SBRT before if there is a biopsy proven recurrence in the bed as established by PSMA or Axumin PET.

 

[Chartreuse Wombat]

Would anyone ever hypofrac in the postop setting? I see these small studies in the red journal but am holding off for the NRG trial to report. I think there are even some SBRT studies.

The NRG trial should be reported this year. Probably too late for ASCO likely at ASTRO.

I don't use hypo in the postop setting but I use routinely in the intact setting

 

[Ray D. Ayshun]

I have done SBRT before if there is a biopsy proven recurrence in the bed as established by PSMA or Axumin PET.

And ignore the rest of the bed, or treat to a lower dose?

 

[Gfunk6]

And ignore the rest of the bed, or treat to a lower dose?

Ignore

 

[scarbrtj]

I would think that may be dependent on the overall size of the ptv.

Prob true.
1) Not VMAT; 9 field/40 degree spacing
2) I turn the fluence smoothing lower in the photon optimizer dose calculation model from the 40/30 default (as long as it doesn't bork the QA); will set to 0 in certain SRS cases. This is moot for VMAT.

3) VMAT can do even better. But at 1% improvement (most times) for up to 10 times as long to plan and calc, it ain't worth it (for me). Were I in a super crankin' clinic where patients need on/off table quickly, it would be.

BED calcs
- Mean dose to entire PTV is equivalent to about 110 Gy with conventional fractionation
- Mean dose to gross tumor is equivalent to about 235 Gy with conventional fractionation

I think you got it lol

 

[Burt Radnolds]

DEFINE_ME

In the recent NRG update to the pelvic prostate atlas they include some constraint tables in the end for doing SIB to prostate with nodal coverage for 28 and 20fx regimens.

 

[Palex80]

Was able to create HDR like distribution per Fuller's protocol, note "hole" where the urethra was. SpaceOAR facilitated very low rectal dose. Patient had 3T multiparametric MRI which was fused to CT sim to intelligently dump dose into gross tumor which received 69.0 Gy (mean).

This is an excellent plan. Very nice, it's clearly the way forward. One question, though:

Do you feel comfortable using the Cyberknife system in terms of where the urethra is during the whole treatment course?
27 minutes beam on time means more than 30 minutes of treatment. The prostate will change its shape and position during that time quite a bit and although I see fiducials (which will be tracked by the Cyberknife system), do you feel comfortable about the urethra's position during the whole treatment? I believe the only way to actually "track" the urethra (other than placing a Foley catheter) is an MR-Linac.
Now, if you just use "normal" doses of SBRT that shouldn't be an issue, but you have prescribed a very high dose only a few mms next to the urethra...

 

[Gfunk6]

This is an excellent plan. Very nice, it's clearly the way forward. One question, though:

Do you feel comfortable using the Cyberknife system in terms of where the urethra is during the whole treatment course?
27 minutes beam on time means more than 30 minutes of treatment. The prostate will change its shape and position during that time quite a bit and although I see fiducials (which will be tracked by the Cyberknife system), do you feel comfortable about the urethra's position during the whole treatment? I believe the only way to actually "track" the urethra (other than placing a Foley catheter) is an MR-Linac.
Now, if you just use "normal" doses of SBRT that shouldn't be an issue, but you have prescribed a very high dose only a few mms next to the urethra...

Palex, this is a fair question and often posed in other contexts where ablation is given near critical structures.

For CT sim and all treatments we have patients empty their bladder and use a fleet enema. For tracking we always do so with 3-4 fiducials thereby providing rotational (yaw, pitch, roll) correction in addition to usual translational shifts.

At times, we definitely see rectal gas that deforms the prostate - sometimes too much so to accurately deliver treatments. In those cases we beam off for a few minutes until it passes or less often have the patient get off and try to pass the gas before resuming.

There has to be a certain amount of trust in the CyberKnife AI - this accrued over a couple of years. We initially did homogenous SBRT to the prostate but started to SIB to high risk gross disease. Eventually we went full on “Fuller.”

The side effects acutely are similar to brachytherapy. I have never seen a urethral structure or necrosis yet.

We also routinely irradiate prostate cancers that have biochemically failed after IMRT/brachy albeit with tighter constrains and a slightly lower dose but still extremely hot. This is also per Fuller.

 

[Palex80]

At times, we definitely see rectal gas that deforms the prostate - sometimes too much so to accurately deliver treatments. In those cases we beam off for a few minutes until it passes or less often have the patient get off and try to pass the gas before resuming.

But actually you don't really "see" that during treatment, right? The Cyberknife system does not have a CBCT option yet. I read that they are preparing something like that, but so far all you can do is trust the AI is following the fiducials and the bony anatomy of the pelvis with the X-Ray system. You cannot really visualize rectal / bladder filling. Or do you do a CT every time before treatment?

 

[Gfunk6]

But actually you don't really "see" that during treatment, right? The Cyberknife system does not have a CBCT option yet. I read that they are preparing something like that, but so far all you can do is trust the AI is following the fiducials and the bony anatomy of the pelvis with the X-Ray system. You cannot really visualize rectal / bladder filling. Or do you do a CT every time before treatment?

We don't use CBCT, but the oblique imaging system of the CK does provide three-dimensional data. We can definitely see the rectal gas and we can definitely see it deforming the fiducials.

 

[evilbooyaa]

Would anyone ever hypofrac in the postop setting? I see these small studies in the red journal but am holding off for the NRG trial to report. I think there are even some SBRT studies.

No. There has been initial data that probably went too high on hypofx dosing that showed bad toxicities. Non-randomized evaluation of Radicals (which allowed 55/20, I believe?) are not sufficient for me to change practice.

@Gfunk6 I would definitely be clenching butt cheeks tightly going that high next to urethra - do you a urethral PRV? I guess I personally don't see the utility of extreme dose escalation given that 37.25 or 40/5 already has such good LC numbers (the new meta-analysis may suggest that 40/5 is maginally better than 37.5/5 whole gland). Like what's the point of EQD2 of 235 to gross tumor beyond just putting patient at higher risk of toxicity?

 

[Gfunk6]

No. There has been initial data that probably went too high on hypofx dosing that showed bad toxicities. Non-randomized evaluation of Radicals (which allowed 55/20, I believe?) are not sufficient for me to change practice.

@Gfunk6 I would definitely be clenching butt cheeks tightly going that high next to urethra - do you a urethral PRV? I guess I personally don't see the utility of extreme dose escalation given that 37.25 or 40/5 already has such good LC numbers (the new meta-analysis may suggest that 40/5 is maginally better than 37.5/5 whole gland). Like what's the point of EQD2 of 235 to gross tumor beyond just putting patient at higher risk of toxicity?

Well, one could make the same argument re HDR/LDR brachytherapy - why dose escalate so high? Surely similar levels of biochemical control can be secured with lower toxicity?

All I can say is that there is long-term (5 year data) to support this level of dose escalation with low toxicity as well as excellent biochemical control. Doses this high have never shown OS improvement but bPFS improvements have been validated. To a much lesser extent, it is a market differentiator for us compared to convetionally fractionated photons/protons.

 

[RadOncDoc777]

We do extreme hypofrac, all day every day.

Patient below was favorable intermediate risk prostate cancer. Prescribed 36.25 Gy in five fractions to 45.7% (yes you read that right) of maximum dose.

Isodose lines below are as follows: Orange (36.25), White (45.0), Green (64.0); Purple (27.0 Gy)

Mean dose to PTV = 46.66 Gy
Max dose to PTV = 79.32 Gy

Was able to create HDR like distribution per Fuller's protocol, note "hole" where the urethra was. SpaceOAR facilitated very low rectal dose. Patient had 3T multiparametric MRI which was fused to CT sim to intelligently dump dose into gross tumor which received 69.0 Gy (mean).

Accomplished on a CyberKnife M6 system using 58 non-coplanar beams with MLC collimation. Beam on time per each of five treatments was 27 minutes.

BED calcs
- Mean dose to entire PTV is equivalent to about 110 Gy with conventional fractionation
- Mean dose to gross tumor is equivalent to about 235 Gy with conventional fractionation

View attachment 327524

We use this approach as well

 

[evilbooyaa]

Well, one could make the same argument re HDR/LDR brachytherapy - why dose escalate so high? Surely similar levels of biochemical control can be secured with lower toxicity?

All I can say is that there is long-term (5 year data) to support this level of dose escalation with low toxicity as well as excellent biochemical control. Doses this high have never shown OS improvement but bPFS improvements have been validated. To a much lesser extent, it is a market differentiator for us compared to convetionally fractionated photons/protons.

Can you link the Fuller paper you use as a template for this technique? Would be interested in learning more.

 

[Gfunk6]

Can you link the Fuller paper you use as a template for this technique? Would be interested in learning more.

Here is the latest one.

Virtual HDR CyberKnife SBRT for Localized Prostatic Carcinoma: 5-Year Disease-Free Survival and Toxicity Observations - PubMed

Virtual HDR prostate SBRT creates a very low PSA nadir, a high rate of 5-year disease-free survival and an acceptable toxicity incidence, with results closely resembling those reported post-HDR brachytherapy.

pubmed.ncbi.nlm.nih.gov

It is available online for free.

 

[drewdog1973]

Are there a lot of capitated payment schemes in CA? I know that UCLA, Fuller/San Diego have been big proponents of 5 fx prostate for many (most?) of the patients they see. Was wondering if that had anything to do with it. Not saying it isn't a good treatment, but you certainly will increase uptake if it's capitated.

 

[Gfunk6]

Are there a lot of capitated payment schemes in CA? I know that UCLA, Fuller/San Diego have been big proponents of 5 fx prostate for many (most?) of the patients they see. Was wondering if that had anything to do with it. Not saying it isn't a good treatment, but you certainly will increase uptake if it's capitated.

No, it's all fee for service where we are. As far as I know, capitation is still fairly limited to select payors.

Here is some recently published data showing the bDFS of this approach: https://ascopubs.org/doi/abs/10.1200/JCO.20.02873