Race to the bottom

[DoctwoB]

I actually love grade groups. It makes sense both conceptually, since 3+4 and 4+3 are such different beasts while 9vs 10 barely matters, and to explain to patients, since 1-5 with 2 and 3 and 4 being favorable, unfavorable, and high, is a lot easier then parsing Gleason 7 IMO.

Very reasonable to be a focal therapy skeptic and blast those doing it off trial. I am one myself. But if it plays a role in the future, I see it being in an optional adjunct to active surveillance, not a primary treatment in the *trigger warning* 😛 GG3-5 patients.

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[DireMoose]

I actually love grade groups. It makes sense both conceptually, since 3+4 and 4+3 are such different beasts while 9vs 10 barely matters, and to explain to patients, since 1-5 with 2 and 3 and 4 being favorable, unfavorable, and high, is a lot easier then parsing Gleason 7 IMO.

Very reasonable to be a focal therapy skeptic and blast those doing it off trial. I am one myself. But if it plays a role in the future, I see it being in an optional adjunct to active surveillance, not a primary treatment in the *trigger warning* 😛 GG3-5 patients.

Also a fan of grade groups. Although 5+3 being GG4 is ridiculous. A dominant 5 pattern should buy you highest grade group.

 

[evilbooyaa]

I actually love grade groups. It makes sense both conceptually, since 3+4 and 4+3 are such different beasts while 9vs 10 barely matters, and to explain to patients, since 1-5 with 2 and 3 and 4 being favorable, unfavorable, and high, is a lot easier then parsing Gleason 7 IMO.

Very reasonable to be a focal therapy skeptic and blast those doing it off trial. I am one myself. But if it plays a role in the future, I see it being in an optional adjunct to active surveillance, not a primary treatment in the *trigger warning* 😛 GG3-5 patients.

I get the love for GGs. It's just a weird part of my old crotchety man brain yelling at a cloud "all this change is too much!"

 

[elementaryschooleconomics]

I get the love for GGs. It's just a weird part of my old crotchety man brain yelling at a cloud "all this change is too much!"

"Sir this is a Wendy's drive through"

 

[DoctwoB]

Also a fan of grade groups. Although 5+3 being GG4 is ridiculous. A dominant 5 pattern should buy you highest grade group.

Fair. Likewise tertiary 5 should mean you can’t be GG2. Can’t remember the last time I saw that. Lot more 3+5 out there.

 

[medgator]

"Hydrogel Spacer Rectal Wall Infiltration Associated with Severe Rectal Injury and Related Complications following Dose Intensified Prostate Cancer Stereotactic Ablative Radiotherapy"

Hydrogel Spacer Rectal Wall Infiltration Associated With Severe Rectal Injury and Related Complications After Dose Intensified Prostate Cancer Stereotactic Ablative Radiation Therapy

Radiation therapy (RT) for prostate cancer remains associated with a dose-dependent and dose-limiting risk of rectal toxicity.1 Contemporary dose-escalated RT regimens,2-5 have improved biochemical control at the cost of higher rectal toxicity. Temporary hydrogel spacer placement between the...

www.advancesradonc.org

 

[SubserviantToABR]

"Hydrogel Spacer Rectal Wall Infiltration Associated with Severe Rectal Injury and Related Complications following Dose Intensified Prostate Cancer Stereotactic Ablative Radiotherapy"

Hydrogel Spacer Rectal Wall Infiltration Associated With Severe Rectal Injury and Related Complications After Dose Intensified Prostate Cancer Stereotactic Ablative Radiation Therapy

Radiation therapy (RT) for prostate cancer remains associated with a dose-dependent and dose-limiting risk of rectal toxicity.1 Contemporary dose-escalated RT regimens,2-5 have improved biochemical control at the cost of higher rectal toxicity. Temporary hydrogel spacer placement between the...

www.advancesradonc.org

Walk in with intermediate risk prostate cancer, walk out crapping and peeing in a bag.

 

[RadOncDoc21]

I wasn’t always a big fan of SpaceOar especially since the urologists have all started placing them in on everyone and the sales rep are super aggressive. I always felt that with VMAT planning, IGRT with fiducials and CBCT and limiting posterior margin, patients did pretty well IMO. I actually had more patients have complications related to the SpaceOar or procedure.

 

[Ray D. Ayshun]

"Hydrogel Spacer Rectal Wall Infiltration Associated with Severe Rectal Injury and Related Complications following Dose Intensified Prostate Cancer Stereotactic Ablative Radiotherapy"

Hydrogel Spacer Rectal Wall Infiltration Associated With Severe Rectal Injury and Related Complications After Dose Intensified Prostate Cancer Stereotactic Ablative Radiation Therapy

Radiation therapy (RT) for prostate cancer remains associated with a dose-dependent and dose-limiting risk of rectal toxicity.1 Contemporary dose-escalated RT regimens,2-5 have improved biochemical control at the cost of higher rectal toxicity. Temporary hydrogel spacer placement between the...

www.advancesradonc.org

Not much of a fan of prostate sbrt. If it ain't broke don't fix. But are people really doing 9gy x 5 on a regular basis? Geez. Not sure the authors are focused on what actually caused this problem.

 

[BobbyHeenan]

That case report is really scary.

I have patients that do get spaceOAR. I discuss it but don’t push it.

I mostly do 70/28 (no spaceOAR) VMAT but I do 36.25-40 Gy SBRT with spaceOAR in some patients.

 

[TheWallnerus]

SpaceOAR is a wonderful technology for those who don't use daily IGRT. Or even worse, they use daily IGRT yet still insist on expanding significant amounts of PTV into the rectum.

 

[Gfunk6]

As I've posted on another thread, we (the Radiation Oncologists) place SpaceOAR and fiducial markers in all intact prostate patients. We treat 7.25 Gy x 5 fractions but using Fuller's published "virtual HDR" approach with prescription isodose lines of 50% or less. We've had tremendous success both in terms of efficacy and acute rectal/urinary toxicity. We are a physician owned private practice.

I've been able to cannibalize patients from competing practice due to this approach. I only treat lymph nodes in high risk and the current evidence shows that ADT contributes nothing for intermediate risk with dose escalation.

We've all had "routine" cases which have had clinically disastrously outcomes - these are interesting to read and appreciate but should not be the basis of the way others practice medicine nationwide.

Extreme hypofractionation, love it or hate it, is the future of modern Radiation Oncology.

Recently had a patient who was considering prostate SBRT with us vs proton beam therapy elsewhere. The patient asked me which I would choose and why. I chose to employ the Socratic method:

Me: Did the proton Rad Onc tell you protons were more accurate, had less exit/entry dose and mention the "Bragg peak?"
Patient: Yes.
Me: I see. And using this wonderfully accurate technology which delivers radiation with such extreme precision with such minimal side effects, how long would it take?
Patient: 43 fractions over nine weeks.
Me: The difference is that I am willing to put my money where my mouth is - there is precisely zero reason to receive nine weeks of treatment if you claim extreme precision.

 

[thesauce]

 

[Linaculous]

... and the current evidence shows that ADT contributes nothing for intermediate risk with dose escalation.

Curious about this statement. I hear this from time to time but have never interpreted the data this way. With PCS 3, one could make the opposite argument (that dose escalation contributes nothing with ADT).
Talking about unfavorable int risk.

 

[Chartreuse Wombat]

"the current evidence shows that ADT contributes nothing for intermediate risk with dose escalation"

Change is gonna come...

 

[communitydoc13]

We've all had "routine" cases which have had clinically disastrously outcomes - these are interesting to read and appreciate but should not be the basis of the way others practice medicine nationwide.

Not sure about this. The flip side of efficacy is safety and avoiding disastrous outcomes is part of our mandate. We do IMRT QA prior to fraction 1 because of a well publicized disastrous outcome, and rare bad outcomes are hard to evaluate with the standard tools we use to study efficacy.

Lots of examples of rare disastrous outcomes driving approval, recommendations and practice patterns. (Morcellation and J&J Vaccine come to mind but there are innumerable examples.)

Fractionation is itself a safety measure.

 

[RickyScott]

"Hydrogel Spacer Rectal Wall Infiltration Associated with Severe Rectal Injury and Related Complications following Dose Intensified Prostate Cancer Stereotactic Ablative Radiotherapy"

Hydrogel Spacer Rectal Wall Infiltration Associated With Severe Rectal Injury and Related Complications After Dose Intensified Prostate Cancer Stereotactic Ablative Radiation Therapy

Radiation therapy (RT) for prostate cancer remains associated with a dose-dependent and dose-limiting risk of rectal toxicity.1 Contemporary dose-escalated RT regimens,2-5 have improved biochemical control at the cost of higher rectal toxicity. Temporary hydrogel spacer placement between the...

www.advancesradonc.org

Ever had a g3 rectal complication from standard xrt in 15 years

Not sure about this. The flip side of efficacy is safety and avoiding disastrous outcomes is part of our mandate. We do IMRT QA prior to fraction 1 because of a well publicized disastrous outcome, and rare bad outcomes are hard to evaluate with the standard tools we use to study efficacy.

Lots of examples of rare disastrous outcomes driving approval, recommendations and practice patterns. (Morcellation and J&J Vaccine come to mind but there are innumerable examples.)

Fractionation is itself a safety measure.

I have never had a conventionally fractionated or moderately hypofractionated prostate or breast cancer with a disasterous outcome, nor do I know of any in the several large academic departments where I trained and started out. (One of which had one of the largest databases) I do know of several cases where pts ended up on vent in the icu after biopsy or placement of calypso.

 

[medgator]

70/28+fiducials and chill. Can do 50.4/28 to nodes if needed

 

[RickyScott]

70/28+fiducials and chill. Can do 50.4/28 to nodes if needed

A better use of Space oar would be injecting it into the chest wall to prevent all the pneumonitis and rib fractures we see from xrt for dcis.

 

[FrostyHammer]

Not sure about this. The flip side of efficacy is safety and avoiding disastrous outcomes is part of our mandate. We do IMRT QA prior to fraction 1 because of a well publicized disastrous outcome, and rare bad outcomes are hard to evaluate with the standard tools we use to study efficacy.

Lots of examples of rare disastrous outcomes driving approval, recommendations and practice patterns. (Morcellation and J&J Vaccine come to mind but there are innumerable examples.)

Fractionation is itself a safety measure.

If one delivers RT to enough patients over a career, there's bound to be a few disastrous outcomes no matter how one tries to avoid them. These things happen, just the nature of the beast.

 

[seper]

does SpaceOAR placement have a favorable therapeutic ratio? That is the question

 

[OTN]

I do a decent amount of prostate SBRT. No high risk patients. 40 in 5. No SpaceOAR. They’ve all done just fine.

 

[TheWallnerus]

I do a decent amount of prostate SBRT. No high risk patients. 40 in 5. No SpaceOAR. They’ve all done just fine.

I feel like I would have to launch a 1000+ patient study to detect toxicity differences with *any* add-on versus my standard of care. I would certainly make my tests of statistical significance two-sided, too.

 

[RickyScott]

I do a decent amount of prostate SBRT. No high risk patients. 40 in 5. No SpaceOAR. They’ve all done just fine.

Is the 40 gy to the whole prostate, or just the mri defined lesion and lower dose to rest of prostate.

 

[deleted969641]

I do a decent amount of prostate SBRT. No high risk patients. 40 in 5. No SpaceOAR. They’ve all done just fine.

Bold. Do you use fiducial?

Anybody seen Rectafix? They have in Europe and would love to see that come to the US.

My regimen is 40 to prostate, 37 to PTV, 45 to nodule shaving to respect urethra and rectum. But I would not do without fiducial (with intrafraction tracking) and spacer.

 

[OTN]

Bold. Do you use fiducial?

Anybody seen Rectafix? They have in Europe and would love to see that come to the US.

My regimen is 40 to prostate, 37 to PTV, 45 to nodule shaving to respect urethra and rectum. But I would not do without fiducial (with intrafraction tracking) and spacer.

Is the 40 gy to the whole prostate, or just the mri defined lesion and lower dose to rest of prostate.

Whole prostate, no fiducials

 

[deleted969641]

Is the 40 gy to the whole prostate, or just the mri defined lesion and lower dose to rest of prostate.

Whole prostate, no fiducials

I contour the prostate on MRI and prescribe 40 Gy to the whole volume. Then give 3-5mm PTV margin and prescribe 37 to that volume. I limit urethra hotspot to 38. Any gross disease on MRI I try to boost up to 45. If I'm doing a SBRT Boost for SVI and need to cover SVs, I will try to keep the gross disease in SV > Rx boost dose (typically 20Gy in 2 fractions). The data from texas scares me beyond 45 Gy, but I don't it's unreasonable to go to 50 if you've got a small focus well away from the rectum and urethra. Although these tend to be in the PZ requiring me to dose paint to protect rectum and heat it up a bit.

I also like to moderately SIB nodules when doing 20 fraction or 28 fraction. Was pleased to see FLAME data come out although they dose escalated much further. I can see both sides. We know dose matters. But at the same time you don't want to ruin the quality of life for somebody with a 15+ year life expectancy even if the case of progression. It was a step from me to go to 3625 to 40. so that's why I still don't expand the 4000 volume. Definitely wouldn't take whole gland to 45. In general trying to moderately escalate dose whenever I can see something on MRI but not going balls to the wall.

 

[thesauce]

I do a decent amount of prostate SBRT. No high risk patients. 40 in 5. No SpaceOAR. They’ve all done just fine.

Honestly, I have had really bad luck with both prostate SBRT and hypofractionation in 28fx. Bad cystitis, urinary retention requiring an indwelling foley for a long period after treatment, etc. Patients ended up (understandably) very upset.

I truly thought it was going to be no big deal to hypofrac, but I’ve never had these issues with standard frac. I guess there’s something to basic radiobiological principles.

 

[Chartreuse Wombat]

Honestly, I have had really bad luck with both prostate SBRT and hypofractionation in 28fx. Bad cystitis, urinary retention requiring an indwelling foley for a long period after treatment, etc. Patients ended up (understandably) very upset.

I truly thought it was going to be no big deal to hypofrac, but I’ve never had these issues with standard frac. I guess there’s something to basic radiobiological principles.

1) Your experience is not evident in the RCTs
2) The basic radiobiologic principles argued that efficacy would be improved with similar toxicity. WHich principles are you referring to?

 

[TheWallnerus]

2) The basic radiobiologic principles argued that efficacy would be improved with similar toxicity. WHich principles are you referring to?

This is not untrue but misses some nuance. There was an estimation/hypothesis that the α/β of CaP was less than normal tissue (we are talking the 1990s when these first rumblings appeared). However, even then, the α/β estimate confidence interval upper limits were still greater than normal tissue (which would not have favored hypofractionation). Put another way, the clinical data antecedent to hypofractionation favored hypofractionation via linear quadratic modeling with a high probability that CaP control would be better (but those probabilities were not 100%) and that normal tissue toxicities could be the same... but the probability of keeping normal tissue toxicity isotoxic was not 100% either. The modeling was/is sound; but the α/β's chosen (for CaP and normal tissue) have big implications on the "efficacy would be improved" assumptions. We are bumping up against the limits of our guesswork there with single fraction EBRT and HDR. The ultimate implication of α/β CaP<α/β normal tissue is single fraction treatment: it will achieve the maximization of tumor control with the minimization of normal tissue toxicity. Anyone arguing for hypofractionation based on "radiobiologic principles" must, to remain logically consistent, argue for single fraction.

 

[BobbyHeenan]

Honestly, I have had really bad luck with both prostate SBRT and hypofractionation in 28fx. Bad cystitis, urinary retention requiring an indwelling foley for a long period after treatment, etc. Patients ended up (understandably) very upset.

I truly thought it was going to be no big deal to hypofrac, but I’ve never had these issues with standard frac. I guess there’s something to basic radiobiological principles.

My most common regimen is 70/28. I've done a fair amount of 36.25-40.0 in 5 and standard frac as well.

I haven't had these dramatic cystitis events, but I think acute and sub acute GU toxicity is worse with hypofrac and sbrt. At 3-4 months they're pretty similar, but at week 4-8 during/after treatment, I think the hypofrac patients are having worse toxicity. I have more men requiring flomax at 1-2 tabs with shorter courses than my longer course patients.

I *think* the convenience is worth is most of the time, but if the patient has a high AUA IPSS score and already on a bunch of bladder/prostate meds (and not a candidate for urolift or something) then I may do standard fractionation.

 

[Chartreuse Wombat]

This is not untrue but misses some nuance. There was an estimation/hypothesis that the α/β of CaP was less than normal tissue (we are talking the 1990s when these first rumblings appeared). However, even then, the α/β estimate confidence interval upper limits were still greater than normal tissue (which would not have favored hypofractionation). Put another way, the clinical data antecedent to hypofractionation favored hypofractionation via linear quadratic modeling with a high probability that CaP control would be better (but those probabilities were not 100%) and that normal tissue toxicities could be the same... but the probability of keeping normal tissue toxicity isotoxic was not 100% either. The modeling was/is sound; but the α/β's chosen (for CaP and normal tissue) have big implications on the "efficacy would be improved" assumptions. We are bumping up against the limits of our guesswork there with single fraction EBRT and HDR. The ultimate implication of α/β CaP<α/β normal tissue is single fraction treatment: it will achieve the maximization of tumor control with the minimization of normal tissue toxicity. Anyone arguing for hypofractionation based on "radiobiologic principles" must, to remain logically consistent, argue for single fraction.

Agree but too lazy to provide nuance. TLidn't write
The early evidence on single fraction is far from encouraging.

Single fraction high-dose-rate brachytherapy as monotherapy for low and intermediate risk prostate cancer: toxicities and early outcomes from a single institutional experience

High-dose-rate brachytherapy (HDR-BT) delivered in a single fraction as monotherapy is a potential treatment modality for low- and intermediate-risk prostate cancer (LIR-PC); however, outcome data with this technique remain limited. Here we describe our ...

www.ncbi.nlm.nih.gov

Five-Year Outcomes of a Single-Institution Prospective Trial of 19-Gy Single-Fraction High-Dose-Rate Brachytherapy for Low- and Intermediate-Risk Prostate Cancer - PubMed

With extended follow-up, toxicity rates after single-fraction 19-Gy HDR brachytherapy remain low. Higher-than-expected rates of biochemical and local failure, however, raise concerns regarding the adequacy of this dose. Additional investigation to define the optimal single-fraction HDR...

pubmed.ncbi.nlm.nih.gov

DEFINE_ME

 

[communitydoc13]

Honestly, I have had really bad luck with both prostate SBRT and hypofractionation in 28fx. Bad cystitis, urinary retention requiring an indwelling foley for a long period after treatment, etc. Patients ended up (understandably) very upset.

I truly thought it was going to be no big deal to hypofrac, but I’ve never had these issues with standard frac. I guess there’s something to basic radiobiological principles.

I have noticed some increase in acute GU toxicity with 28 fraction hypo. The constraints on RTOG 0415 are totally unreasonable and too liberal in my opinion and we use institutional standards from an academic place where one of us trained. Much more rigorous constraints on bladder.

 

[TheWallnerus]

Agree but too lazy to provide nuance. TLidn't write
The early evidence on single fraction is far from encouraging.

Single fraction high-dose-rate brachytherapy as monotherapy for low and intermediate risk prostate cancer: toxicities and early outcomes from a single institutional experience

High-dose-rate brachytherapy (HDR-BT) delivered in a single fraction as monotherapy is a potential treatment modality for low- and intermediate-risk prostate cancer (LIR-PC); however, outcome data with this technique remain limited. Here we describe our ...

www.ncbi.nlm.nih.gov

Five-Year Outcomes of a Single-Institution Prospective Trial of 19-Gy Single-Fraction High-Dose-Rate Brachytherapy for Low- and Intermediate-Risk Prostate Cancer - PubMed

With extended follow-up, toxicity rates after single-fraction 19-Gy HDR brachytherapy remain low. Higher-than-expected rates of biochemical and local failure, however, raise concerns regarding the adequacy of this dose. Additional investigation to define the optimal single-fraction HDR...

pubmed.ncbi.nlm.nih.gov

DEFINE_ME

They just chose the wrong dose (and it also means they "chickened out" on their α/β estimate). I guarantee a 30 Gy* single dose (~2.5x the normal toxicity risk of 70/28 but maybe ~3.5x the CaP control prob) e.g. would show great biochemical control if the patients and their rectums survive it.

A truism: the less fractions you use the more sensitive outcomes will be to α/β estimates. Single fraction leaves little room for (α/β choice) error, 5 fractions leaves a bit more, 28 even more, and you get the picture. Those who harp on radiobiologic principles and frown on >=40 fractions in prostate deny strict LQ adherence if they don't single-fractionate; and if they don't, they tacitly admit at least the theoretic potential for dose escalated multi-fraction utility. "The early evidence on single fraction is far from encouraging" also means CaP α/β estimates are not encouraging.

* "only" ~2.4x the CaP control and normal tissue toxicity probability of 19/1

 

[deleted969641]

My most common regimen is 70/28. I've done a fair amount of 36.25-40.0 in 5 and standard frac as well.

I haven't had these dramatic cystitis events, but I think acute and sub acute GU toxicity is worse with hypofrac and sbrt. At 3-4 months they're pretty similar, but at week 4-8 during/after treatment, I think the hypofrac patients are having worse toxicity. I have more men requiring flomax at 1-2 tabs with shorter courses than my longer course patients.

I *think* the convenience is worth is most of the time, but if the patient has a high AUA IPSS score and already on a bunch of bladder/prostate meds (and not a candidate for urolift or something) then I may do standard fractionation.

If you're doing moderate hypofrac I see no reason to do 28 over 20 unless you're doing nodes. I was hesitant at first to do 20 but patients have done great. And I've even done nodes in 20 before without a problem. 28 seems like dragging it out another two weeks for no good reason. If you're on the fence about 20 vs. 28 due to prostate size, urination, having to cover a lot of SVs or boost borderline nodes near bowel or something, then I'd say just forget it and go straight to 45.

Curious if there is any data comparing 28 vs. 20. Nothing randomized that I know of, but I know how much people like to compare across trials.

 

[BobbyHeenan]

If you're doing moderate hypofrac I see no reason to do 28 over 20 unless you're doing nodes. I was hesitant at first to do 20 but patients have done great. And I've even done nodes in 20 before without a problem. 28 seems like dragging it out another two weeks for no good reason. If you're on the fence about 20 vs. 28 due to prostate size, urination, having to cover a lot of SVs or boost borderline nodes near bowel or something, then I'd say just forget it and go straight to 45.

Curious if there is any data comparing 28 vs. 20. Nothing randomized that I know of, but I know how much people like to compare across trials.

I need to look at this in my practice.

I just trained doing a ton of 70.28, felt comfortable with it and it nicely integrates into dose panting for nodes and SV (50.4 and 56).

But yes, I don't have a strong(er) rationale for 20 vs 28.

 

[Chartreuse Wombat]

They just chose the wrong dose (and it also means they "chickened out" on their α/β estimate). I guarantee a 30 Gy* single dose (~2.5x the normal toxicity risk of 70/28 but maybe ~3.5x the CaP control prob) e.g. would show great biochemical control if the patients and their rectums survive it.

A truism: the less fractions you use the more sensitive outcomes will be to α/β estimates. Single fraction leaves little room for (α/β choice) error, 5 fractions leaves a bit more, 28 even more, and you get the picture. Those who harp on radiobiologic principles and frown on >=40 fractions in prostate deny strict LQ adherence if they don't single-fractionate; and if they don't, they tacitly admit at least the theoretic potential for dose escalated multi-fraction utility. "The early evidence on single fraction is far from encouraging" also means CaP α/β estimates are not encouraging.

* "only" ~2.4x the CaP control and normal tissue toxicity probability of 19/1

I should have been more clear. All radiobiological models are wrong in that they are only descriptive but some are helpful. I could care less what the models show-rigorous evidence on living patients trumps (sorry) all models. I doubt anyone will try 30Gy in single fraction because many of these men don't need treatment or the existing treatment works "well enough"

 

[TheWallnerus]

I should have been more clear. All radiobiological models are wrong in that they are only descriptive but some are helpful. I could care less what the models show-rigorous evidence on living patients trumps (sorry) all models. I doubt anyone will try 30Gy in single fraction because many of these men don't need treatment or the existing treatment works "well enough"

I could talk about this for days. I, personally, would love to have a redo on a lot of the radiobiology-in-rad-onc lingo, and first on the list for me would be calling linear quadratic a "model." We don't say the equation y=mx+b is a "model" for linear equations in algebra e.g. It is true that you can plate cells and study their death in vitro and that when you expose the cells to X-rays they die (fail to divide). The amount of death matches the equation y=e^(-ax-bxx) plotting surviving cells on the log-linear y-axis and dose on the x-axis. That's always going to be true so it's not a model per se. Where the "modeling" comes in is that when a patient walks in the clinic we don't know what THAT PATIENT'S TUMOR CELLS' a-constant and b-constant are for the equation y=e^(-ax-bxx).

So we guess.

 

[FrostyHammer]

If you're doing moderate hypofrac I see no reason to do 28 over 20 unless you're doing nodes. I was hesitant at first to do 20 but patients have done great. And I've even done nodes in 20 before without a problem. 28 seems like dragging it out another two weeks for no good reason. If you're on the fence about 20 vs. 28 due to prostate size, urination, having to cover a lot of SVs or boost borderline nodes near bowel or something, then I'd say just forget it and go straight to 45.

Curious if there is any data comparing 28 vs. 20. Nothing randomized that I know of, but I know how much people like to compare across trials.

100%. I don't think of ever using 28 fractions if nodes aren't being treated. What dose do you use to nodes for 20 fx?

 

[Ray D. Ayshun]

I need to look at this in my practice.

I just trained doing a ton of 70.28, felt comfortable with it and it nicely integrates into dose panting for nodes and SV (50.4 and 56).

But yes, I don't have a strong(er) rationale for 20 vs 28.

Have they done a study comparing 57/19 to 60/20 or a study comparing 67.5/27 vs 70/28? Yes to the former and not that I'm aware to the latter. In any case, 57/19 was not noninfereior, so a reason for not doing 20 is that it's awful close to 19.

 

[RSAOaky]

If you're doing moderate hypofrac I see no reason to do 28 over 20 unless you're doing nodes.

I may not be Urorads but I'm not Canada either, I got kids to feed!

 

[deleted969641]

Have they done a study comparing 57/19 to 60/20 or a study comparing 67.5/27 vs 70/28? Yes to the former and not that I'm aware to the latter. In any case, 57/19 was not noninfereior, so a reason for not doing 20 is that it's awful close to 19.

Did that study also include a 60/20 arm?

BED1.5 57/19 = 171 Gy
BED1.5 60/20 = 180 Gy
BED1.5 70/28 = 186.67 Gy
BED1.5 81/45 = 178.2 Gy

But I do agree that dose matters which is why I try to mildly heat up the nodule if I can identify and do it safely.

100%. I don't think of ever using 28 fractions if nodes aren't being treated. What dose do you use to nodes for 20 fx?

44/20 to nodes.

 

[Ray D. Ayshun]

Did that study also include a 60/20 arm?

BED1.5 57/19 = 171 Gy
BED1.5 60/20 = 180 Gy
BED1.5 70/28 = 186.67 Gy
BED1.5 81/45 = 178.2 Gy

But I do agree that dose matters which is why I try to mildly heat up the nodule if I can identify and do it safely.



44/20 to nodes.

ASCO GU 2020: Update from the CHHiP Trial: Eight-Year Outcomes of a Phase III Randomized Trial of Conventional Versus Hypofractionated High-Dose Intensity Modulated Radiotherapy For Prostate Cancer

ASCO GU 2020 The CHHiP trial is a phase III non-inferiority study

www.urotoday.com

 

[udrag14]

If you're doing moderate hypofrac I see no reason to do 28 over 20 unless you're doing nodes. I was hesitant at first to do 20 but patients have done great. And I've even done nodes in 20 before without a problem. 28 seems like dragging it out another two weeks for no good reason. If you're on the fence about 20 vs. 28 due to prostate size, urination, having to cover a lot of SVs or boost borderline nodes near bowel or something, then I'd say just forget it and go straight to 45.

Curious if there is any data comparing 28 vs. 20. Nothing randomized that I know of, but I know how much people like to compare across trials.

More RVUs with longer fractions. It hurts your bottom line before RO APM is implemented if you are RVU based

 

[RadOncDoc21]

Is prostate competing with breast as being the worst now? I’m sure 10 rad oncs will give their rationale for 10 different regimens and their anecdotal experience. At the end of the day, there are no jobs.

 

[medgator]

More RVUs with longer fractions. It hurts your bottom line before RO APM is implemented if you are RVU based

That's true if you're PP also

 

[deleted969641]

ASCO GU 2020: Update from the CHHiP Trial: Eight-Year Outcomes of a Phase III Randomized Trial of Conventional Versus Hypofractionated High-Dose Intensity Modulated Radiotherapy For Prostate Cancer

ASCO GU 2020 The CHHiP trial is a phase III non-inferiority study

www.urotoday.com

Sorry, yes we know that 57/19 has been compared to 60/20. The question I was asking is if could convince me that 70/28 is superior to 60/20. From a BED standpoint, yes 28 fraction is better, but both are better than conventional even if you escalate all the way to 45.

The do-it-for-the-RVUs edge to it doesn't make sense to me. If that's your goal, then we know 81 Gy works really well and is well tolerated (and it probably gives you more room to safely dose escalate with an SIB as below), so do that. Unless you are at a high volume urorads center or are the only game in town I don't see giving your moderate hypofrac candidates an extra 8 treatments making a dramatic impact on your practice's success or your own takehome, and could very well be a wash if you are losing patients to surgery because you are not offering 20 or 5 fraction treatments. Plus your patients and staff will appreciate you.

60/20 is great for low risk patients. Intermediate/high risk -- how does 35 sound? Good compromise between 45 and 28? Focal Boost to the Intraprostatic Tumor in External Beam Radiotherapy for Patients With Localized Prostate Cancer: Results From the FLAME Randomized Phase III Trial | Journal of Clinical Oncology (ascopubs.org)

BED1.5 77/35 = 189.9 Gy
BED1.5 up to 95/35 = 266.6 Gy (GTV had no margin and was trimmed as needed to meet normal dose contraints)

For reference, BED1.5 of 46/23 + 20/2 SBRT boost = 260 Gy. (common used on SBRT boost trial). There is a much more complicated equation to calculate EDD2 for an LDR implant (D (α/β + [2*{t–1+exp(- t)} / ( t)^2]*D*R) / (α/β + 2) and figure out what the BED of the combo is, but my Ti-89 is in storage somewhere, so I'll just assume this is about what you get with the ASCENDE-RT regimen.

It would be interesting to compare the focal boost method to SBRT boost to LDR boost in a 3 arm trial in terms of efficacy and toxicity given that evidence that escalating gross disease to a BED > 220 Gy provides better control. If that is really true, then 57/19, 60/20, 81/45 all fall well short of that and we are missing the forest for the trees in our bickering.

 

[Ray D. Ayshun]

Sorry, yes we know that 57/19 has been compared to 60/20. The question I was asking is if could convince me that 70/28 is superior to 60/20. From a BED standpoint, yes 28 fraction is better, but both are better than conventional even if you escalate all the way to 45.

The do-it-for-the-RVUs edge to it doesn't make sense to me. If that's your goal, then we know 81 Gy works really well and is well tolerated (and it probably gives you more room to safely dose escalate with an SIB as below), so do that. Unless you are at a high volume urorads center or are the only game in town I don't see giving your moderate hypofrac candidates an extra 8 treatments making a dramatic impact on your practice's success or your own takehome, and could very well be a wash if you are losing patients to surgery because you are not offering 20 or 5 fraction treatments. Plus your patients and staff will appreciate you.

60/20 is great for low risk patients. Intermediate/high risk -- how does 35 sound? Good compromise between 45 and 28? Focal Boost to the Intraprostatic Tumor in External Beam Radiotherapy for Patients With Localized Prostate Cancer: Results From the FLAME Randomized Phase III Trial | Journal of Clinical Oncology (ascopubs.org)

BED1.5 77/35 = 189.9 Gy
BED1.5 up to 95/35 = 266.6 Gy (GTV had no margin and was trimmed as needed to meet normal dose contraints)

For reference, BED1.5 of 46/23 + 20/2 SBRT boost = 260 Gy. (common used on SBRT boost trial). There is a much more complicated equation to calculate EDD2 for an LDR implant (D (α/β + [2*{t–1+exp(- t)} / ( t)^2]*D*R) / (α/β + 2) and figure out what the BED of the combo is, but my Ti-89 is in storage somewhere, so I'll just assume this is about what you get with the ASCENDE-RT regimen.

It would be interesting to compare the focal boost method to SBRT boost to LDR boost in a 3 arm trial in terms of efficacy and toxicity given that evidence that escalating gross disease to a BED > 220 Gy provides better control. If that is really true, then 57/19, 60/20, 81/45 all fall well short of that and we are missing the forest for the trees in our bickering.

No trials comparing 70/28 to 60/20. And if one gets done we truly will have arrived at the bottom. It boils down to having evidence that 60/20 and 70/28 are not statistically better or worse than conventional, but also having evidence that 60/20 appears to be right on the edge. My preference is to stay a couple steps away from it, toxicity being more or less equivalent, and recognizing I don't know if 67.5/27 is not noninfereior, though as you posted, there are radiobiological reasons to thinks 67.5/27 might be Noninfereior to 60/20.

 

[Mandelin Rain]

*Anecdote alert*

I've noticed too many of my 20 fx guys have had miserable urinary symptoms at the end of treatment and the month after. The few 28 fx patients I've done to treat nodes, have done well. Going to switch to that as my standard.

"Too close for missiles, I'm switching to guns."
- Lt. Pete Mitchell, 1986

 

[communitydoc13]

The ultimate implication of α/β CaP<α/β normal tissue is single fraction treatment: it will achieve the maximization of tumor control with the minimization of normal tissue toxicity. Anyone arguing for hypofractionation based on "radiobiologic principles" must, to remain logically consistent, argue for single fraction.

I disagree.

My understanding is that α/β is really only the ratio of the coefficients of a 2nd order polynomial used to "fit" outcomes (most classic example is fractional cell kill in vitro) relative to dose fractionation. In the clinical setting, you can take retrospective data and come up with outcomes vs dose fraction curves that are always going to be a little bit bendy, are almost always going to seem monotonic and the data is always going to be fuzzy. This means that fitting these outcomes with a 2nd order polynomial is fine and the added value of a 3rd order term is meaningless in the real world. So you can have an α/β for cell kill, or early clinical outcomes (diarrhea) or late clinical outcomes (bleeding, late cystitis). My confidence in the particulars of these clinical curves is very low.

This α/β is not a model (I guess I heard some handwaving regarding 1 vs 2 photon interactions back in the day) it's just a fit. And by definition it is a fit regarding a single outcome. Most of our clinical and pre-clinical data does not control very well for time course of treatment (not explicitly included in α/β calculations), and the various relative contributions of "the 4Rs" as you shrink treatment time or course from 20-10-5-3-1 treatments is not well defined to my understanding. So you can claim that "cell kill for prostate cancer" demonstrates an α/β less than any pertinent competing toxicity risk, but still believe that single fraction or 3 fraction treatment is not prudent and is not the sweet spot in terms of therapeutic ratio.

Heck, you can just take the well known inverse correlation between total time frame of 5 fraction prostate SBRT and acute toxicity, combine this with the known possibility of "consequential late toxicity" or acute toxicity that becomes late toxicity (This may be particularly pertinent in prostate cancer, where CPPS is a known entity and total pain in the ass to manage.) and make a good argument for not going below 5 fractions and not treating more than 2x a week.

Regarding moderate hypofractionation, the same arguments apply. (BTW, I am not aware of any mature 7920 or 7800 vs 7000 or 6000 hypo trials.)

I *think* the convenience is worth is most of the time, but if the patient has a high AUA IPSS score and already on a bunch of bladder/prostate meds (and not a candidate for urolift or something) then I may do standard fractionation.

I agree with this entirely. I have converted to 28 fxns from 44 fxns because of convenience, cost and developing community standard. In fact, under an APM, I would probably be less hesitant to recommend 44 fractions because I wouldn't feel like I was causing undo financial toxicity.

What is the terrible sin of 44 fractions (particularly if it is compensated as 28 fractions)? Out in my community (I'm guessing many places apply outside of really high powered metro areas, where your average patient is rich and 60 yo), 44 fractions meant groups of older, retired men bonding with other similar patients in the waiting room while falling in love with the therapists and nursing staff, having minimal toxicity and believing that their radiation experience was great. They developed close bonds with the treating or covering physician. If even 1% of these men were spared CPPS, 44 fractions might be the way to go.