FLAME TRIAL

[BobbyHeenan]

Mods - please move this post if most appropriate.

I do some of this type of prostate paradigm in some SBRT cases (36.25 to PTV, 40 to prostate or dominant MRI nodule).

I'm looking to integrate the FLAME regimen (77 @ 2.2 to prostate, boost MRI nodule to up to 95 Gy) and maybe I'm missing it, but I've looked at the protocol and supplements and I don't see a lot of details on margins.


This pic below is in the supplement, and the original paper has this paragraph:

"A mean dose of 77 Gy in 35 fraction of 2.2 Gy is prescribed to the entire prostate gland [33,34]. The dose in the part of the PTV overlapping the rectum and bladder is limited to keep the risk of severe gastrointestinal and genitourinary toxicity acceptable....

The precise execution of the radiotherapy treatment can differ in each participation center, but the treatment will always meet the above mentioned criteria."

Maybe the european trials are more pragmatic, because I'm just so used to the NRG trials literally saying X mm to this margin, X mm to that margin, etc. Looks like a more classic "PTV" ?maybe prostate plus 4 mm posterior, 6-7 mm circumferential ? would get 70 Gy, the prostate should get 77 Gy, then boost the nodule to 95 Gy.

This pic is helpful, but was hoping for any tips you all have if you've been integrating this treatment into some options.

For me personally, if I have a younger patient with a clear MRI dominant area with biopsy mapping congruent (ie the high grade disease is on biopsy congruent with MRI location) I'm ready to start offering this.

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[brushbeamscanning]

I looked into this for some dosimetric studies, there are details about the margins used in their companion papers.

So they do not use a margin for the 95 Gy volume. In their safety paper (Standard whole prostate gland radiotherapy with and without lesion boost in prostate cancer: Toxicity in the FLAME randomized controlled trial - PubMed) they use a margin of 5-8 mm with specifics per institution in their supplementary section:

"The CTV was defined as the corpus of the prostate. In both UMCU and Leuven, seminal vesicles were always included in the CTV. At NKI and RadboudUMC, inclusion of seminal vesicles in the CTV was based on risk stratification as applied in the HYPRO trial (2).

At UMCU and Leuven, a PTV margin of 8 mm was applied around the CTV, but a reduction of PTV dose was accepted tot 66.5 Gy for the dorsal part of the PTV overlapping the rectum. At the Netherlands Cancer Institute, a margin of 7 mm was applied, with a reduction to 5 mm dorsally. In Radboudumc, a margin of 5 mm was applied."

So 7 mm radially with 5 mm posteriorly seems fine.

For their related hypo-FLAME study they use a 4-5 mm expansion for SBRT, 4 mm for MR-linac treatments (https://www.scienceopen.com/documen...tral/0f7c1ac7-5187-4bd7-a609-acef7d7e21af.pdf).

 

[BobbyHeenan]

I looked into this for some dosimetric studies, there details about the margins used in their companion papers.

So they do not use a margin for the 95 Gy volume. In their safety paper (Standard whole prostate gland radiotherapy with and without lesion boost in prostate cancer: Toxicity in the FLAME randomized controlled trial - PubMed) they use a margin of 5-8 mm with specifics per institution in their supplementary section:

"The CTV was defined as the corpus of the prostate. In both UMCU and Leuven, seminal vesicles were always included in the CTV. At NKI and RadboudUMC, inclusion of seminal vesicles in the CTV was based on risk stratification as applied in the HYPRO trial (2).

At UMCU and Leuven, a PTV margin of 8 mm was applied around the CTV, but a reduction of PTV dose was accepted tot 66.5 Gy for the dorsal part of the PTV overlapping the rectum. At the Netherlands Cancer Institute, a margin of 7 mm was applied, with a reduction to 5 mm dorsally. In Radboudumc, a margin of 5 mm was applied."

So 7 mm radially with 5 mm seems fine.

For their related hypo-FLAME study they use a 4-5 mm expansion for SBRT, 4 mm for MR-linac treatments (https://www.scienceopen.com/documen...tral/0f7c1ac7-5187-4bd7-a609-acef7d7e21af.pdf).

Thank you! Very helpful.

 

[Chartreuse Wombat]

Mods - please move this post if most appropriate.

I do some of this type of prostate paradigm in some SBRT cases (36.25 to PTV, 40 to prostate or dominant MRI nodule).

I'm looking to integrate the FLAME regimen (77 @ 2.2 to prostate, boost MRI nodule to up to 95 Gy) and maybe I'm missing it, but I've looked at the protocol and supplements and I don't see a lot of details on margins.


This pic below is in the supplement, and the original paper has this paragraph:

"A mean dose of 77 Gy in 35 fraction of 2.2 Gy is prescribed to the entire prostate gland [33,34]. The dose in the part of the PTV overlapping the rectum and bladder is limited to keep the risk of severe gastrointestinal and genitourinary toxicity acceptable....

The precise execution of the radiotherapy treatment can differ in each participation center, but the treatment will always meet the above mentioned criteria."



View attachment 349944

Maybe the european trials are more pragmatic, because I'm just so used to the NRG trials literally saying X mm to this margin, X mm to that margin, etc. Looks like a more classic "PTV" ?maybe prostate plus 4 mm posterior, 6-7 mm circumferential ? would get 70 Gy, the prostate should get 77 Gy, then boost the nodule to 95 Gy.

This pic is helpful, but was hoping for any tips you all have if you've been integrating this treatment into some options.

For me personally, if I have a younger patient with a clear MRI dominant area with biopsy mapping congruent (ie the high grade disease is on biopsy congruent with MRI location) I'm ready to start offering this.

Similar to what MSKCC did with the 86 Gy cohort. 86 Gy to the front part of the prostate but the posterior PZ (where most cancer is) received well under 86 Gy and some portions <81 Gy. NRG is trying to "operationalize" this approach but is finding it very difficult to extrapolate to the way they do things.

 

[Chartreuse Wombat]

 

[Burt Radnolds]

 

[deleted1111261]

View attachment 349947

Fascinating that they were going to 48 fx at the time, but now wondering why everyone doesn’t do 5 for everyone …

 

[Chartreuse Wombat]

Fascinating that they were going to 48 fx at the time, but now wondering why everyone doesn’t do 5 for everyone …

They are now.

 

[deleted1111261]

They are now.

That’s what I mean - they are doing it now and wondering why everyone else hasn’t switched. My wording was unclear!

 

[RickyScott]

That’s what I mean - they are doing it now and wondering why everyone else hasn’t switched. My wording was unclear!

Notice how they went to 48 not 47 (must have to do with billing)

 

[ramsesthenice]

View attachment 349946

This is key and what I teach all of my residents. FLAME worked, but I think the why is a little less clear. DIL on imaging does not come close to covering the extent of the tumor. It’s also technically challenging to do a focal DIL boost without using very generous margins (even with an MR linac). The intent was to do a DIL boost, but in reality it was closer to good ole fashion dose escalation and making sure the DIL was included in the high dose region.

 

[RickyScott]

This is key and what I teach all of my residents. FLAME worked, but I think the why is a little less clear. DIL on imaging does not come close to covering the extent of the tumor. It’s also technically challenging to do a focal DIL boost without using very generous margins (even with an MR linac). The intent was to do a DIL boost, but in reality it was closer to good ole fashion dose escalation and making sure the DIL was included in the high dose region.

good point. although the focal DIL boost may not totally cover the true pathological lesion, with setup uncertainties it will give a higher dose and margin to the true lesion over 30+ fractions . If only one side of prostate is involved on biopsy, i typically ask for 5% hot to that side.

 

[ramsesthenice]

good point. although the focal DIL may not cover the true pathological lesion, with setup uncertainties it will give a higher dose and margin to the true lesion over 30+ fractions . If only one side of prostate is involved on biopsy, i typically ask for 5% hot to that side.

Like G-funk, I have been in the habit of letting my prostate plans get hot for a long time.

when it comes to brachy, I have also been doing pseudoDIL boosts since the beginning of time and I assume most people do as well. When prescribing to D90, its absolutely key to make sure that the target lesion is not part of the under dosed area. I am always cognizant of where the lesion is and make sure to get a needle or 2 in there. I don't take the time to contour out the DIL with MR fusion like some centers, but I guarantee you they probably ride close to 150% of rx dose in most cases.

In general, the brachytherapist in me is really loving the broader "Make heterogeneity great again" movement. One of my biggest pet peeves with a lot of ongoing trials is still the relatively modest max point dose limitations in the PTV. Even in otherwise good SBRT trials.

 

[RickyScott]

Like G-funk, I have been in the habit of letting my prostate plans get hot for a long time.

when it comes to brachy, I have also been doing pseudoDIL boosts since the beginning of time and I assume most people do as well. When prescribing to D90, its absolutely key to make sure that the target lesion is not part of the under dosed area. I am always cognizant of where the lesion is and make sure to get a needle or 2 in there. I don't take the time to contour out the DIL with MR fusion like some centers, but I guarantee you they probably ride close to 150% of rx dose in most cases.

In general, the brachytherapist in me is really loving the broader "Make heterogeneity great again" movement. One of my biggest pet peeves with a lot of ongoing trials is still the relatively modest max point dose limitations in the PTV. Even in otherwise good SBRT trials.

In lung, stressing homegeneity in ptv increases dose to normal lung

 

[evilbooyaa]

In lung, stressing homegeneity in ptv increases dose to normal lung

This is true in all disease sites. Peak vs Plateau planning.

There is a concept of defining an area that, even with breathing, represents gross tumor in all aspects of the 4DCT (meaning it's never normal surrounding OAR) and depositing all hotspots there. I have not been routinely doing but is a way of "free" dose escalation not dissimilar to the idea behind the FLAME trial.

 

[RickyScott]

This is true in all disease sites. Peak vs Plateau planning.

There is a concept of defining an area that, even with breathing, represents gross tumor in all aspects of the 4DCT (meaning it's never normal surrounding OAR) and depositing all hotspots there. I have not been routinely doing but is a way of "free" dose escalation not dissimilar to the idea behind the FLAME trial.

Agreed. In lung, it is satisfying to watch the tumor regress entirely into a hot area on cone beam over the course of treatment.

 

[RadRadRad]

In lung, stressing homegeneity in ptv increases dose to normal lung

In all disease sites stressing homogeneity increases dose to normal tissue. This is physics of radiation

 

[RickyScott]

In all disease sites stressing homogeneity increases dose to normal tissue. This is physics of radiation

definitely. Conformality/fall off is a function of spreading out the dose and heterogeneity. Have had issues dealing with dosimetrists who previously worked in factory like settings of large institutions where a huge emphasis is placed on homogeneity. For most sites, I put in my own avoidance structures to force desired fall off, but limit hot spots to around 10%. Can quasi automate planning in pelvis and neck head and neck

 

[Lamount]

In lung, stressing homegeneity in ptv increases dose to normal lung

Agree. As a resident, I never got why we try to prevent hot spots in the tumor.

As an attending, I manufacture hotspots with sub-volumes with internal margins (in the ablative setting)

 

[Krukenberg]

definitely. Conformality/fall off is a function of spreading out the dose and heterogeneity. Have had issues dealing with dosimetrists who previously worked in factory like settings of large institutions where a huge emphasis is placed on homogeneity. For most sites, I put in my own avoidance structures to force desired fall off, but limit hot spots to around 10%. Can quasi automate planning in pelvis and neck head and neck

What are some avoidance structures you add for planning?

 

[RickyScott]

What are some avoidance structures you add for planning?

Imrt can fall off 4-5% per mm without hot spots increasing above 10% (depends on volume size and geometry)

In prostate, you can place a structure 1cm posterior to ptv and ask for fall off to half the dose. If treating nodes, ask for fall off to approximately 60% 2cm into pelvis away from nodal ptv.

For head and neck, add 2cm to ptv 70 and 1.5 cm to lower dose ptv. Ask for dose fall off to 20-25 gy over any mucosa that is excluded from this expansion.

 

[madchemist89]

Is anyone doing the flame regimen? What constraints do you use for bladder, rectum, urethra? I looked through the protocol, but it is unfortunately sparse.

 

[BobbyHeenan]

Is anyone doing the flame regimen? What constraints do you use for bladder, rectum, urethra? I looked through the protocol, but it is unfortunately sparse.

There’s a table in one of the publications (?maybe a supplement?) that had their constraints across three centers that enrolled.

I use it.

I’ve been offering this for patients with a dominant mri lesion with congruent biopsy in same area.

 

[TheWallnerus]

View attachment 349947

Sailed over everyone’s head

 

[madchemist89]

There’s a table in one of the publications (?maybe a supplement?) that had their constraints across three centers that enrolled.

I use it.

I’ve been offering this for patients with a dominant mri lesion with congruent biopsy in same area.

Thanks, I found it in the data supplement.