- Joined
- Oct 4, 2017
- Messages
- 5,368
- Reaction score
- 10,504
This is sketchy. Not sure why GU effects would be different. Viewray plans generally are worse from what I heard, but let neuronix speak to that.
This is sketchy. Not sure why GU effects would be different. Viewray plans generally are worse from what I heard, but let neuronix speak to that.
- Joined
- Dec 17, 2007
- Messages
- 3,717
- Reaction score
- 5,238
4 mm or 2 mm into bladder neck could make a difference perhaps (cranial margin)?
- Joined
- Apr 3, 2019
- Messages
- 4,806
- Reaction score
- 11,079
Maybe.
If these guys ran the trial with differing PTVs in the two groups, either they are not so smart or they think the readers are not so smart.
- Joined
- May 7, 2014
- Messages
- 1,770
- Reaction score
- 3,803
Purchase a fancy machine because physician-reported (read unblinded) acute GU toxicity is improved at 1 month (but the difference dissipates by 3 months). Seems like Flomax early on is cheaper than an MR-Linac. Another example of gizmo idolatry and technology advocacy dressed up as science. What a waste of time
- Joined
- Dec 17, 2007
- Messages
- 3,717
- Reaction score
- 5,238
- Joined
- Mar 14, 2002
- Messages
- 15,121
- Reaction score
- 9,508
The old Co-60 plans were not very good. We didn't treat certain disease sites on Cobalt-60 for that reason. It wasn't just Co-60 penumbra--the MLC width was 1 cm.
The linac plans are decent. Like anything else it's in the hands of the planner and the planning system is goofy. It's still step-and-shoot IMRT so it's slower and it can be hotter and a little less conformal than VMAT plans. MLC width is now 4 mm I believe
- Joined
- Apr 3, 2019
- Messages
- 4,806
- Reaction score
- 11,079
Very nice. There’s not too shabby data that you can “leverage the power” of implanted fiducials to achieve 2mm PTVs (with plain X-rays) also!
- Joined
- Apr 3, 2019
- Messages
- 4,806
- Reaction score
- 11,079
I recently had a resident say “step and shoot” to me and what he really meant was static beam IMRT. Step and shoot means the leaves are not moving during beam on. Almost no (early adopter) linac IMRT users used step and shoot in the long run; it was dynamic MLCs aka dMLC aka sliding window. Does Viewray do static beam dMLC or step and shoot? (And VMAT is different than both of these; would be a form of dMLC though.)
Why would an MRI linac allow for decreased margins? My therapists can find the prostate and rectum just fine with CBCT, as I can tell when I approve the SBRT images.
Additionally, my understanding is that there are certain issues with MRI which bring their own problems. The MRI linac crew seems to just ignore those.
Additionally, my understanding is that there are certain issues with MRI which bring their own problems. The MRI linac crew seems to just ignore those.
D
deleted1111261
Only one person asked about that (My Friend From Georgetown, Sean Collins) and it was described as “a feature not a bug”. I pushed back, as well. Let’s see if people want to discuss that further.
- Joined
- Apr 3, 2019
- Messages
- 4,806
- Reaction score
- 11,079
- Joined
- Mar 14, 2002
- Messages
- 15,121
- Reaction score
- 9,508
I've got a lot of stuff cooking so I can't spend much time posting on SDN these days. I'll have to make it short and say that I like the VR for the power to give highly accurate SBRT plans without any implanted fiducials or spacers. Cost effectiveness analyses have shown that the extra cost of fiducials vs. MRI-guidance are roughly equivalent.
We used step and shoot all the time in the early days of VMAT or before VMAT. I've never used sliding window. The transition from static gantry to arc therapy regarding step and shoot or sliding window was vendor/machine dependent. Viewray is step and shoot.
Pulling out papers from 2005 on MRI distortions?
This reminds me of when I applied to residency all those years ago with the specific goal to do MRI-guided RT, told the faculty that was my plan, and in almost every interview got told that it would never work.At least give me a real issue like pacemakers and claustrophobia...
This trial will eventually be a DVH trial, which is still useful because it will apply outside of the MRI linac world. OAR dose from reduced PTV and intrafraction motion management will matter more, so people who don't have MR linac will use exactrac, triggered gating, Cyberknife tracking to achieve the lowered doses
- Joined
- Dec 17, 2007
- Messages
- 3,717
- Reaction score
- 5,238
I have doubts about this.
It costs the equivalent of less than 1000 dollars to get 3 fiducials into the prostate, in our setting.
Is MRI-guided prostate RT less than 1000 dollars pricier than CBCT-guided prostate RT?
Don't get me wrong: MRI-guided treatments are great for several indications. But primary prostate RT? I do not think so.
- Joined
- Apr 3, 2019
- Messages
- 4,806
- Reaction score
- 11,079
There really shouldn’t be confusion on this. Are you sure the leaves didn’t move during beam on? Your physicists commissioned all these linacs to do step and shoot when dMLC was 1) available 2) much quicker than step and shoot 3) able to give much better plans than step and shoot (because it uses more segments)? Having the leaves move during beam on was a significant engineering challenge for Varian and became a selling point for them.
- Joined
- Apr 3, 2019
- Messages
- 4,806
- Reaction score
- 11,079
Any cost effectiveness comparison will also require pricing the MRgRT technology itself against a plain X-ray option (such as Exactrac eg, or even an OBI). And then MRgRT can in NO WAY be as cost effective.
D
deleted1111261
I know as an employed person (as opposed to me!) you have far less time on your hands, but how is installing an MRI cheaper than fiducials, @Neuronix ??!!
- Joined
- Mar 14, 2002
- Messages
- 15,121
- Reaction score
- 9,508
Ugh... I have papers on both of these topics and don't want to out myself.
I'm sorry to have misrepresented even my own data. Somehow I got in my head that it is cost neutral, but it isn't. The MRI is a bit more expensive, though not by much. It depends on a lot of assumptions.
Here's WashU's analysis for liver
"much quicker than step and shoot" .. A few minutes at best for a prostate? "Much better plans" .. Slightly more conformal and homogenous?
The difference was not that much. So yes, we did step and shoot.
For MRI-linacs they don't want metal moving all the time during the imaging. Linac on with nothing moving around gives the steadiest imaging without magnetic field changes for position verification.
It's not really the employment part. It's the physician-scientist part. Seven consults this week, a lot of follow-ups, a bunch of OTVs, and keeping the funding and lab going. It's too much.
I do need to sign off for today. Will come back when I can. You know I can't stay away for long.
I'm sorry to have misrepresented even my own data. Somehow I got in my head that it is cost neutral, but it isn't. The MRI is a bit more expensive, though not by much. It depends on a lot of assumptions.
Here's WashU's analysis for liver
"much quicker than step and shoot" .. A few minutes at best for a prostate? "Much better plans" .. Slightly more conformal and homogenous?
The difference was not that much. So yes, we did step and shoot.
For MRI-linacs they don't want metal moving all the time during the imaging. Linac on with nothing moving around gives the steadiest imaging without magnetic field changes for position verification.
It's not really the employment part. It's the physician-scientist part. Seven consults this week, a lot of follow-ups, a bunch of OTVs, and keeping the funding and lab going. It's too much.
I do need to sign off for today. Will come back when I can. You know I can't stay away for long.
- Joined
- May 7, 2014
- Messages
- 1,770
- Reaction score
- 3,803
One could hypothesize that the smaller margin decreases efficacy....
- Joined
- Apr 3, 2019
- Messages
- 4,806
- Reaction score
- 11,079
- Joined
- Oct 4, 2017
- Messages
- 5,368
- Reaction score
- 10,504
I would think fiducials would be placed at the same time as space-oar, so cost should be around 300$. Was space oar used in this trial?
D
deleted1111261
If the mri linac makes it that much easier to be comfortable with smaller margins, I guess that’s something. The toxicity numbers are kind of incredible, though.
I wonder if you did 2mm with CT, would the recurrence rate be higher ? I bet not
I wonder if you did 2mm with CT, would the recurrence rate be higher ? I bet not
- Joined
- Oct 4, 2017
- Messages
- 5,368
- Reaction score
- 10,504
why can you reduce to 2mm with MRI, but not cyberknife, exactract, calypso, all of which allow imaging when the beam is on and have shorter treatment times (in case of varian machine). I do believe true beam has capability for real time imaging of fiducials?
i think the the smaller margins will actually be the take home of the trial and useful information once they get the OAR data analyzed and should be agnostic to machine/technique
- Joined
- Apr 3, 2019
- Messages
- 4,806
- Reaction score
- 11,079
Within the last two years there was an opinion piece entitled something like "PTV Margin Reduction is the True Future of Radiation Oncology." I can't find it. It was a good paper! I know 4mm vs 2mm circumferential margin doesn't sound like much but it can be a ~25% volume reduction in a normal sized (eg radius 1.7cm) prostate. (EDIT: I think I have it now. I'm on a fast.)
Last edited:
- Joined
- Apr 3, 2019
- Messages
- 4,806
- Reaction score
- 11,079
Would be, IDK, 100x easier to show an increase in Gr0 rectal toxicity w/ margin reduction than an increase in BCR.
- Joined
- Sep 13, 2021
- Messages
- 2,023
- Reaction score
- 2,263
I mean it IS a feature - the whole rationale is that mri Linac allows you to use smaller margin
The question I have is - for those of you that do a lot of CT based prostate SBRT - is 4 mm too big? Or is that what you use
Second question - it seems like transient grade 2 GU tox that is treated with flomax isn’t that big of a deal. Certainly not something warranting Spratt going full Spratt
The question I have is - for those of you that do a lot of CT based prostate SBRT - is 4 mm too big? Or is that what you use
Second question - it seems like transient grade 2 GU tox that is treated with flomax isn’t that big of a deal. Certainly not something warranting Spratt going full Spratt
- Joined
- Sep 13, 2021
- Messages
- 2,023
- Reaction score
- 2,263
Yeah no way would it be higher, I agree
agree whole heartedly. One thing I hope the mr linac folks will be able to do is to model CTV/ITV motion with OAR/PRV motion so that we can finally model what is happening with motion interaction between targets and OARs. Once that happens we can move away from the symmetric PTV and do something similar with proton robustness, further shrinking ptvs asymmetricallyWithin the last two years there was an opinion piece entitled something like "PTV Margin Reduction is the True Future of Radiation Oncology." I can't find it. It was a good paper! I know 4mm vs 2mm circumferential margin doesn't sound like much but it can be a ~25% volume reduction in a normal sized (eg radius 1.7cm) prostate. (EDIT: I think I have it now. I'm on a fast.)
- Joined
- Jul 14, 2020
- Messages
- 1,588
- Reaction score
- 4,670
Yeah, we're down in the weeds here. Possible very marginal improvements in short term, low grade toxicity in an indolent disease. Not exciting and also probably not true.
MRI-guided radiotherapy appears to lead to fewer side effects from treatment for prostate cancer | Newswise
An interim analysis of an ongoing Phase III study from UCLA Jonsson Comprehensive Cancer Center indicates that using magnetic resonance imaging (MRI) to guide precisely-focused high-dose radiation treatment for prostate cancer reduced side effects associated with the treatment. The findings are...
www.newswise.com
Borderline totally irresponsible to promote results of 100 patients with an early look and grade 2 toxicity endpoint in a non-blinded setting. What they're really talking about is urinary frequency, cause I'm guessing hematuria and incontinence are vanishingly rare. I don't have a good mechanism because urethral dose is probably the biggest culprit, and they are literally talking about tens of total toxicity endpoints. Bad data all around and should not be taken seriously.
My guess is if we were to do a sham experiment on 100 men in our clinics and look at toxicity differences in 2 random cohorts over a one month period, we would find differences quite a few times, because the natural variance of these outcomes is high, we may find a 30% variance month to month and I'm guessing experienced clinicians have a gut feeling that this happens in their clinic. If there is a real difference, the non-blinding alone is the likely culprit.
- Joined
- Oct 4, 2017
- Messages
- 5,368
- Reaction score
- 10,504
in total agreementYeah, we're down in the weeds here. Possible very marginal improvements in short term, low grade toxicity in an indolent disease. Not exciting and also probably not true.
MRI-guided radiotherapy appears to lead to fewer side effects from treatment for prostate cancer | Newswise
An interim analysis of an ongoing Phase III study from UCLA Jonsson Comprehensive Cancer Center indicates that using magnetic resonance imaging (MRI) to guide precisely-focused high-dose radiation treatment for prostate cancer reduced side effects associated with the treatment. The findings are...
Borderline totally irresponsible to promote results of 100 patients with an early look and grade 2 toxicity endpoint in a non-blinded setting. What they're really talking about is urinary frequency, cause I'm guessing hematuria and incontinence are vanishingly rare. I don't have a good mechanism because urethral dose is probably the biggest culprit, and they are literally talking about tens of total toxicity endpoints. Bad data all around and should not be taken seriously.
My guess is if we were to do a sham experiment on 100 men in our clinics and look at toxicity differences in 2 random cohorts over a one month period, we would find differences quite a few times, because the natural variance of these outcomes is high, we may find a 30% variance month to month and I'm guessing experienced clinicians have a gut feeling that this happens in their clinic. If there is a real difference, the non-blinding alone is the likely culprit.
I've got a lot of stuff cooking so I can't spend much time posting on SDN these days. I'll have to make it short and say that I like the VR for the power to give highly accurate SBRT plans without any implanted fiducials or spacers. Cost effectiveness analyses have shown that the extra cost of fiducials vs. MRI-guidance are roughly equivalent.
We used step and shoot all the time in the early days of VMAT or before VMAT. I've never used sliding window. The transition from static gantry to arc therapy regarding step and shoot or sliding window was vendor/machine dependent. Viewray is step and shoot.
Pulling out papers from 2005 on MRI distortions?
At least give me a real issue like pacemakers and claustrophobia...
Has the issue been settled since 2005? I don't know too much about it, but my understanding that geometric distortion is fundamental to MR imaging.
- Joined
- Apr 16, 2004
- Messages
- 4,916
- Reaction score
- 6,098
We've already scraping the bottom of the barrel in terms of improving prostate XRT acute and late toxicity. Whether you are talking about protons, MR-linacs, 1.8 Gy per fraction or brachytherapy - things are as good as they are going to get. To dissect out further differences you would need randomized trials of 10,000 patients to detect the minute differences in the arms.
The name of the game now is extreme hypofractionation and dose escalation. If you won't do it voluntarily, RO-APM will eventually drag everyone kicking and screaming.
The name of the game now is extreme hypofractionation and dose escalation. If you won't do it voluntarily, RO-APM will eventually drag everyone kicking and screaming.
Yup. And I have spoken with physicists who are comfortable with 1 mm margins on MRLinac. But ask them to go 0 PTV margin is a hard no.Within the last two years there was an opinion piece entitled something like "PTV Margin Reduction is the True Future of Radiation Oncology." I can't find it. It was a good paper! I know 4mm vs 2mm circumferential margin doesn't sound like much but it can be a ~25% volume reduction in a normal sized (eg radius 1.7cm) prostate. (EDIT: I think I have it now. I'm on a fast.)
- Joined
- Apr 3, 2019
- Messages
- 4,806
- Reaction score
- 11,079
True
It's wild some of the fears people have; many are irrational. It's not like with a 0mm PTV that the RT dose will be 0 Gy 1mm outside that PTV.
I believe the voxel size on one of the more common MR Linacs is about 3mm.
- Joined
- Oct 4, 2017
- Messages
- 5,368
- Reaction score
- 10,504
Why not blind or just have pts fill out score/survey.Yeah, we're down in the weeds here. Possible very marginal improvements in short term, low grade toxicity in an indolent disease. Not exciting and also probably not true.
MRI-guided radiotherapy appears to lead to fewer side effects from treatment for prostate cancer | Newswise
An interim analysis of an ongoing Phase III study from UCLA Jonsson Comprehensive Cancer Center indicates that using magnetic resonance imaging (MRI) to guide precisely-focused high-dose radiation treatment for prostate cancer reduced side effects associated with the treatment. The findings are...
Borderline totally irresponsible to promote results of 100 patients with an early look and grade 2 toxicity endpoint in a non-blinded setting. What they're really talking about is urinary frequency, cause I'm guessing hematuria and incontinence are vanishingly rare. I don't have a good mechanism because urethral dose is probably the biggest culprit, and they are literally talking about tens of total toxicity endpoints. Bad data all around and should not be taken seriously.
My guess is if we were to do a sham experiment on 100 men in our clinics and look at toxicity differences in 2 random cohorts over a one month period, we would find differences quite a few times, because the natural variance of these outcomes is high, we may find a 30% variance month to month and I'm guessing experienced clinicians have a gut feeling that this happens in their clinic. If there is a real difference, the non-blinding alone is the likely culprit.
- Joined
- Jul 14, 2020
- Messages
- 1,588
- Reaction score
- 4,670
I don't know enough about MRLinac to comment about that format, but I think physicists in general think of PTV as being dictated by uncertainties in target localization and even uncertainties in XRT delivery. These uncertainties will never be zero (even your Winston-Lutz doesn't show zero) so I get why physicists won't go there.
I think we (the docs) are more and more thinking of PTVs as being a measure of how important Dmin is, and in truth, this may not be that important. There is minimal literature on impact of Dmin on tumor control and some modalities (brachy) may have pretty damn small Dmin with good outcomes.
Below is study on impact of Dmin on GTV in NP carcinoma. They saw a correlation when Dmin dropped below 77% of prescribed dose. Depending on your planning, 77% of your peripheral planned dose may be ~3mm away.
Impact of minimum point dose on local control and toxicity in T3–4 nasopharyngeal carcinoma treated with intensity-modulated radiation therapy plus chemotherapy
Treatment for T3–4 NPC was trapped in a dilemma for increasing local control and protecting abutting neurologic structures. Dmin ≥ 54 Gy was found to confe
academic.oup.com
- Joined
- Jul 14, 2020
- Messages
- 1,588
- Reaction score
- 4,670
You'd have to blind the patients as well. Impact of knowing you're getting a particular intervention can be huge on self reported symptoms.
I was looking up data for efficacy of SSRIs in depression. One key paper used to justify their use was a blinded, randomized trial. Symptoms improved in 69% of drug recipients and 59% of placebo patients!
- Joined
- May 7, 2014
- Messages
- 1,770
- Reaction score
- 3,803
In the original Viagra trials 40% reported improvement in the placebo arm
- Joined
- Oct 4, 2017
- Messages
- 5,368
- Reaction score
- 10,504
You are on a role. Another excellent pointI don't know enough about MRLinac to comment about that format, but I think physicists in general think of PTV as being dictated by uncertainties in target localization and even uncertainties in XRT delivery. These uncertainties will never be zero (even your Winston-Lutz doesn't show zero) so I get why physicists won't go there.
I think we (the docs) are more and more thinking of PTVs as being a measure of how important Dmin is, and in truth, this may not be that important. There is minimal literature on impact of Dmin on tumor control and some modalities (brachy) may have pretty damn small Dmin with good outcomes.
Below is study on impact of Dmin on GTV in NP carcinoma. They saw a correlation when Dmin dropped below 77% of prescribed dose. Depending on your planning, 77% of your peripheral planned dose may be ~3mm away.
Impact of minimum point dose on local control and toxicity in T3–4 nasopharyngeal carcinoma treated with intensity-modulated radiation therapy plus chemotherapy
Treatment for T3–4 NPC was trapped in a dilemma for increasing local control and protecting abutting neurologic structures. Dmin ≥ 54 Gy was found to confe
Geometric error and dose deposition uncertainty is the explanation, which I buy to some extent.
- Joined
- Mar 20, 2013
- Messages
- 2,232
- Reaction score
- 4,158
I appreciate the team at least running the trial.
In retrospect, for a TON of the new radiation tech, CMS would be best off funding a massive, well done study and run it blinded (?at the NCI? or a few centers) and run some really good trials with proton, MRI linac, etc. The money spent up front on huge, well done trials could save them literally billions.
I understand this isn't a novel thought, but why hasn't this happened? Instead, we get an arms race and explosion of tech before we're really sure if it's definitely better...then by the time the most powerful cancer centers have invested millions it's too late to even think about designing or running a trial that could put your machine out of business.
This would probably slow innovation, but it's not like these tech's are going to move the overall survival needle - so it's not like with holding immunotherapy from a melanoma patient or something.
In retrospect, for a TON of the new radiation tech, CMS would be best off funding a massive, well done study and run it blinded (?at the NCI? or a few centers) and run some really good trials with proton, MRI linac, etc. The money spent up front on huge, well done trials could save them literally billions.
I understand this isn't a novel thought, but why hasn't this happened? Instead, we get an arms race and explosion of tech before we're really sure if it's definitely better...then by the time the most powerful cancer centers have invested millions it's too late to even think about designing or running a trial that could put your machine out of business.
This would probably slow innovation, but it's not like these tech's are going to move the overall survival needle - so it's not like with holding immunotherapy from a melanoma patient or something.
D
deleted941485
We got to attract dollars and expand even if it’s senseless and stupid. There’s no other way to survive. If you aren’t making noise then nobody cares about you.
- Joined
- Jan 10, 2010
- Messages
- 2,745
- Reaction score
- 3,847
Not just tech, but even more so for drugs.
Pharma pays for a trial so new drug X becomes standard of care in Y disease. But drug Z is like X but cheaper/generic, hence why pharma didn't include it in the trial. CMS could pay for the trial for the generic drug and save a bundle.
For example: Pembro + Axitinib is one of the SOC options for metastatic RCC, beating out Sunitinib in the RCT. But Sunitinib goes generic many years before Axitinib. Would Pembro + Sunitinib = Pembro + axitinib? Probably, but no one is funding that trial. Ditto for Abiraterone and nmCRPC (where enza, daro, and api have an indication), and Im sure a million other examples.
- Joined
- Oct 10, 2011
- Messages
- 8,935
- Reaction score
- 11,410
Again.. MRI-Linac shows an improvement in acute toxicity.
I thought all the prostate mod hypofx folks say to ignore acute toxicity (well, GI at least) in this setting. So acute GI toxicity doesn't matter when considering going from 28 to 39/44 fx, but does matter when we're going from CT-based SBRT to MRI-guided SBRT?
I thought all the prostate mod hypofx folks say to ignore acute toxicity (well, GI at least) in this setting. So acute GI toxicity doesn't matter when considering going from 28 to 39/44 fx, but does matter when we're going from CT-based SBRT to MRI-guided SBRT?
D
deleted1111261
Th
That’s a really good point !
- Joined
- Dec 17, 2007
- Messages
- 3,717
- Reaction score
- 5,238
This is a complicated issue. Bear with me, this is going to be a long post.
For starters, the trial specifics have been published before (Free access):
www.ncbi.nlm.nih.gov
1. CTV-contouring.
CTV-Contouring was not the same in both arms. Yes, CTV-contouring, it's unbelievable, but sadly true!
From the manuscript:
"A pelvic CT without contrast will be performed for radiotherapy simulation (i.e., treatment planning CT) with a slice thickness of 1.5 mm. For patients enrolled on the MRI-guided SBRT arm, an additional MRI will be obtained in the treatment position on the MRI-guided LINAC."
I have no idea why they did that in the trial. I thought acquiring a planning MRI for prostate RT is standard of care. We do it for 20 x 3 Gy in all patients, I would certainly do it for CBCT-based SBRT, and I have no idea whey they decided not to do it in the CBCT-arm of this trial.
Can anyone think of any reason?
2. Margins.
2mm for MRI-arm, 4mm for CBCT-arm.
From the manuscript:
"We adopted a smaller margin of 2 mm for the MRI-guided arm given its ability for real-time tracking and superior prostatic anatomy visualization (i.e., greater contour certainty), with little concerns of marginal misses related to excess motion or undercontouring."
...
"Implanted fiducial markers are routinely used to assist with motion management when treating prostate cancer patients with any form of external radiotherapy, including SBRT. These will be considered required for patients treated with CT-guided SBRT except in cases where a medical contraindication is present, as is consistent with our internal SBRT protocol."
...
"Gating-based treatment, with gating based on the imaged location of the prostate organ or on rectal distention, can be employed at the discretion of the treating physician."
They state two reasons for the reduced margins:
a) Excess motion.
Like many of you noted, excess motion in the CBCT-arm could have been negated by using non-MRI based tools, such as Calypso, Cyberknife, Novalis (or even perhaps the "poor (wo)man's" mid treatment CBCT/kV-image between arcs). Calypso offers real time motion management, Cyberknife and Novalis offer frequent management, the mid-treatment CBCT/kV-image offers the least possibilities. There is no mention in the paper if motion management was allowed in the CBCT-arm, although even the most basic motion management would have been possible with the implanted fiducials. There is also no mention of recommendations on when treatment was stopped in the MRI-arm, in case motion was detected. In theory, one would have to interrupt treatment, once the prostate moved 3mm, since parts of the CTV would then be underdosed. Did they do that? Noone knows.
b) Undercontouring.
I am not sure if they mean by that the CTV-contouring, since the MRI-guided arm only had initial MRI-assisted CTV-contouring or they mean identifying the prostate contour on the treatment-MRI more precisely than the prostate contour on the CBCT. I do not feel that this is a valid argument in the later case, since with fiducials implanted in the CBCT-arm patients, you do not really need to visualize the prostate, you can simply match to the implanted fiducials. Or am I missing something else?
3. Adaptive planning.
From the manuscript:
"If deemed necessary, online adaptive planning will be performed, wherein the planning GTVs, CTVs, and OARs are deformably transferred to the online MR images via registration, and the treatment plan is reoptimized to meet or exceed the original planning goals."
So, the MRI-guided treatment may lead to better organ sparing and target converage through adaptive planning. This is excellent and one of the main specialties of MRI-treatment, but is also available now on Varian's Ethos, CBCT-based. I am not aware of any comparative studies.
4. Physician and patient biases
The primary endpoint was "acute grade ≥ 2 GU physician-reported toxicity,, as assessed by the CTCAE version 4.03 scale".
Neither physicians, nor patients were blinded. It's impossible to blind the patients. However, one could indeed have blinded the ones that scored toxicity. One could have utilized blinded study nurses, for instance, that would have scored for acute toxicity.
There is no item such as "acute grade ≥ 2 GU toxicity" in CTCAE 4.03, so I presume they mean a combined endpoint of several CTCAE 4.03 endpoints, including urinary urgency, urinary tract obstruction, urinary frequency. The problem is that many of those automatically are grade 2 as soon as medication is prescribed. And who is prescribing medication (for instance Flomax)? The unblinded physician...
Thus there are 6 potential points that may have impacted the primary endpoint of the trial:
1. CTV-contouring
2. Margins
3. Adaptive planning
4. Motion management
5. Patient bias
6. Physician bias
Saying that treating on the MRI-Linac was the crucial factor, appears to me quite the stretch.
For starters, the trial specifics have been published before (Free access):
Magnetic resonance imaging-guided stereotactic body radiotherapy for prostate cancer (mirage): a phase iii randomized trial - PMC
Stereotactic body radiotherapy (SBRT) is becoming increasingly used in treating localized prostate cancer (PCa), with evidence showing similar toxicity and efficacy profiles when compared with longer courses of definitive radiation. Magnetic ...
www.ncbi.nlm.nih.gov
1. CTV-contouring.
CTV-Contouring was not the same in both arms. Yes, CTV-contouring, it's unbelievable, but sadly true!
From the manuscript:
"A pelvic CT without contrast will be performed for radiotherapy simulation (i.e., treatment planning CT) with a slice thickness of 1.5 mm. For patients enrolled on the MRI-guided SBRT arm, an additional MRI will be obtained in the treatment position on the MRI-guided LINAC."
I have no idea why they did that in the trial. I thought acquiring a planning MRI for prostate RT is standard of care. We do it for 20 x 3 Gy in all patients, I would certainly do it for CBCT-based SBRT, and I have no idea whey they decided not to do it in the CBCT-arm of this trial.
Can anyone think of any reason?
2. Margins.
2mm for MRI-arm, 4mm for CBCT-arm.
From the manuscript:
"We adopted a smaller margin of 2 mm for the MRI-guided arm given its ability for real-time tracking and superior prostatic anatomy visualization (i.e., greater contour certainty), with little concerns of marginal misses related to excess motion or undercontouring."
...
"Implanted fiducial markers are routinely used to assist with motion management when treating prostate cancer patients with any form of external radiotherapy, including SBRT. These will be considered required for patients treated with CT-guided SBRT except in cases where a medical contraindication is present, as is consistent with our internal SBRT protocol."
...
"Gating-based treatment, with gating based on the imaged location of the prostate organ or on rectal distention, can be employed at the discretion of the treating physician."
They state two reasons for the reduced margins:
a) Excess motion.
Like many of you noted, excess motion in the CBCT-arm could have been negated by using non-MRI based tools, such as Calypso, Cyberknife, Novalis (or even perhaps the "poor (wo)man's" mid treatment CBCT/kV-image between arcs). Calypso offers real time motion management, Cyberknife and Novalis offer frequent management, the mid-treatment CBCT/kV-image offers the least possibilities. There is no mention in the paper if motion management was allowed in the CBCT-arm, although even the most basic motion management would have been possible with the implanted fiducials. There is also no mention of recommendations on when treatment was stopped in the MRI-arm, in case motion was detected. In theory, one would have to interrupt treatment, once the prostate moved 3mm, since parts of the CTV would then be underdosed. Did they do that? Noone knows.
b) Undercontouring.
I am not sure if they mean by that the CTV-contouring, since the MRI-guided arm only had initial MRI-assisted CTV-contouring or they mean identifying the prostate contour on the treatment-MRI more precisely than the prostate contour on the CBCT. I do not feel that this is a valid argument in the later case, since with fiducials implanted in the CBCT-arm patients, you do not really need to visualize the prostate, you can simply match to the implanted fiducials. Or am I missing something else?
3. Adaptive planning.
From the manuscript:
"If deemed necessary, online adaptive planning will be performed, wherein the planning GTVs, CTVs, and OARs are deformably transferred to the online MR images via registration, and the treatment plan is reoptimized to meet or exceed the original planning goals."
So, the MRI-guided treatment may lead to better organ sparing and target converage through adaptive planning. This is excellent and one of the main specialties of MRI-treatment, but is also available now on Varian's Ethos, CBCT-based. I am not aware of any comparative studies.
4. Physician and patient biases
The primary endpoint was "acute grade ≥ 2 GU physician-reported toxicity,, as assessed by the CTCAE version 4.03 scale".
Neither physicians, nor patients were blinded. It's impossible to blind the patients. However, one could indeed have blinded the ones that scored toxicity. One could have utilized blinded study nurses, for instance, that would have scored for acute toxicity.
There is no item such as "acute grade ≥ 2 GU toxicity" in CTCAE 4.03, so I presume they mean a combined endpoint of several CTCAE 4.03 endpoints, including urinary urgency, urinary tract obstruction, urinary frequency. The problem is that many of those automatically are grade 2 as soon as medication is prescribed. And who is prescribing medication (for instance Flomax)? The unblinded physician...
Thus there are 6 potential points that may have impacted the primary endpoint of the trial:
1. CTV-contouring
2. Margins
3. Adaptive planning
4. Motion management
5. Patient bias
6. Physician bias
Saying that treating on the MRI-Linac was the crucial factor, appears to me quite the stretch.
Last edited:
- Joined
- Apr 3, 2019
- Messages
- 4,806
- Reaction score
- 11,079
This is a complicated issue. Bear with me, this is going to be a long post.
For starters, the trial specifics have been published before (Free access):
Magnetic resonance imaging-guided stereotactic body radiotherapy for prostate cancer (mirage): a phase iii randomized trial - PMC
Stereotactic body radiotherapy (SBRT) is becoming increasingly used in treating localized prostate cancer (PCa), with evidence showing similar toxicity and efficacy profiles when compared with longer courses of definitive radiation. Magnetic ...
1. CTV-contouring.
CTV-Contouring was not the same in both arms. Yes, CTV-contouring, it's unbelievable, but sadly true!
From the manuscript:
"A pelvic CT without contrast will be performed for radiotherapy simulation (i.e., treatment planning CT) with a slice thickness of 1.5 mm. For patients enrolled on the MRI-guided SBRT arm, an additional MRI will be obtained in the treatment position on the MRI-guided LINAC."
I have no idea why they did that in the trial. I thought acquiring a planning MRI for prostate RT is standard of care. We do it for 20 x 3 Gy in all patients, I would certainly do it for CBCT-based SBRT, and I have no idea whey they decided not to do it in the CBCT-arm of this trial.
Can anyone think of any reason?
2. Margins.
2mm for MRI-arm, 4mm for CBCT-arm.
From the manuscript:
"We adopted a smaller margin of 2 mm for the MRI-guided arm given its ability for real-time tracking and superior prostatic anatomy visualization (i.e., greater contour certainty), with little concerns of marginal misses related to excess motion or undercontouring."
...
"Implanted fiducial markers are routinely used to assist with motion management when treating prostate cancer patients with any form of external radiotherapy, including SBRT. These will be considered required for patients treated with CT-guided SBRT except in cases where a medical contraindication is present, as is consistent with our internal SBRT protocol."
...
"Gating-based treatment, with gating based on the imaged location of the prostate organ or on rectal distention, can be employed at the discretion of the treating physician."
They state two reasons for the reduced margins:
a) Excess motion.
Like many of you noted, excess motion in the CBCT-arm could have been negated by using non-MRI based tools, such as Calypso, Cyberknife, Novalis (or even perhaps the "poor (wo)man's" mid treatment CBCT/kV-image between arcs). Calypso offers real time motion management, Cyberknife and Novalis offer frequent management, the mid-treatment CBCT/kV-image offers the least possibilities. There is no mention in the paper if motion management was allowed in the CBCT-arm, although even the most basic motion management would have been possible with the implanted fiducials. There is also no mention of recommendations on when treatment was stopped in the MRI-arm, in case motion was detected. In theory, one would have to interrupt treatment, once the prostate moved 3mm, since parts of the CTV would then be underdosed. Did they do that? Noone knows.
b) Undercontouring.
I am not sure if they mean by that the CTV-contouring, since the MRI-guided arm only had initial MRI-assisted CTV-contouring or they mean identifying the prostate contour on the treatment-MRI more precisely than the prostate contour on the CBCT. I do not feel that this is a valid argument in the later case, since with fiducials implanted in the CBCT-arm patients, you do not really need to visualize the prostate, you can simply match to the implanted fiducials. Or am I missing something else?
3. Adaptive planning.
From the manuscript:
"If deemed necessary, online adaptive planning will be performed, wherein the planning GTVs, CTVs, and OARs are deformably transferred to the online MR images via registration, and the treatment plan is reoptimized to meet or exceed the original planning goals."
So, the MRI-guided treatment may lead to better organ sparing and target converage through adaptive planning. This is excellent and one of the main specialties of MRI-treatment, but is also available now on Varian's Ethos, CBCT-based. I am not aware of any comparative studies.
4. Physician and patient biases
The primary endpoint was "acute grade ≥ 2 GU physician-reported toxicity,, as assessed by the CTCAE version 4.03 scale".
Neither physicians, nor patients were blinded. It's impossible to blind the patients. However, one could indeed have blinded the ones that scored toxicity. One could have utilized blinded study nurses, for instance, that would have scored for acute toxicity.
There is no item such as "acute grade ≥ 2 GU toxicity" in CTCAE 4.03, so I presume they mean a combined endpoint of several CTCAE 4.03 endpoints, including urinary urgency, urinary tract obstruction, urinary frequency. The problem is that many of those automatically are grade 2 as soon as medication is prescribed. And who is prescribing medication (for instance Flomax)? The unblinded physician...
Thus there are 6 potential points that may have impacted the primary endpoint of the trial:
1. CTV-contouring
2. Margins
3. Adaptive planning
4. Motion management
5. Patient bias
6. Physician bias
Saying that treating on the MRI-Linac was the crucial factor, appears to me quite the stretch.
