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DoctwoB

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use of composite endpoints to increase power are well-accepted in RCTs. I see TTB as a composite endpoint to capture all the toxicities a patient experiences, but weighted by their burden on the patient. With conventional toxicity outcomes, we usually ignore anything less than grade 3, and make it binary such that a patient who has three grade 3 GI toxicities is counted the same as someone who has one grade 3 GI toxicity. I think the conventional outcomes as described have a high risk of measurement bias. TTB could as well, but I think it’s probably better at measuring what we are interested in.

To be honest as a non-radonc this is one of my biggest gripes against the field and interpretation of studies. Your grade 2 toxicity that is poo-pood or seen as irrelevant is my patient that I'm seeing q6m for the rest of their lives, putting them on anticholinergics (which likely exacerbate their cognitive decline) or having them pay $$$ for B-3 agonists, or catheterizing them and dealing with their recurrent UTIs (which significantly effects QOL) etc.

Likewise when I listened to a lecture where prostate hypofx was discussed, while the overall thesis was "its so much faster with similar toxicity" I came out from looking at the data thinking that If I got xrt I'd take conventional fractionation 10/10 times. I'd much rather get an extra 20 treatments then take the additional risk of dealing with symptoms lifelong.
 
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Tigerstang

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Word has it that a proton center in eastern Tennessee is on the ropes. Countdown to closure. The headwinds have been strong. Evicore deciding to cap all prostates at 28 fractions may be playing a role too who knows.

closure or restructuring of debt and sale? My suspicion is the latter, much like Oklahoma.
 
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scarbrtj

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To be honest as a non-radonc this is one of my biggest gripes against the field and interpretation of studies. Your grade 2 toxicity that is poo-pood or seen as irrelevant is my patient that I'm seeing q6m for the rest of their lives, putting them on anticholinergics (which likely exacerbate their cognitive decline) or having them pay $$$ for B-3 agonists, or catheterizing them and dealing with their recurrent UTIs (which significantly effects QOL) etc.

Likewise when I listened to a lecture where prostate hypofx was discussed, while the overall thesis was "its so much faster with similar toxicity" I came out from looking at the data thinking that If I got xrt I'd take conventional fractionation 10/10 times. I'd much rather get an extra 20 treatments then take the additional risk of dealing with symptoms lifelong.
You know that scene in Beverly Hills Cop where Billy decides to take Axel Foley to the warehouse so they can bust Victor Maitland and Eddie Murphy looks over at Judge Reinhold and says "I just fell in love with you a little, Billy..."

closure or restructuring of debt and sale? My suspicion is the latter, much like Oklahoma.
words were "rats leaving a sinking ship" ... fwiw
 
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SneakyBooger

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I have a little proton-ish experience. Surprisingly, I have had several prostate ca patients over the past many years call my office and explain they were treated at an out of town proton facility, usually by one of my friends. Despite those unbelievably beautiful isodoses they somehow developed severe proctitis. The triage nurse at the proton facility must not have discussed the case with the pt's Rad Onc because she routinely instructed them to not come to their facility. Instead, she instructed them to see me due to convenience. I have always politely declined and instructed those patients to return to the facility at which they were treated as I am certain my good friend would wish to continue to provide exceptional care for them. And to be sure to add it to their toxicity database so that they can get a more accurate measurement. I haven't had any of those calls in a couple of years though so it appears their nursing has changed to a different routine. Or perhaps my nurse handles those calls now without needing my input. Maybe they are sending those patients to one of my other good friends across town. I will inquire as I am sure you and my other friends want to know.

I think someone posted a promotion with isodoses earlier and asked which would I want to be treated with. I wouldn't be treated with either of those unless I had metastases to my LN(s). When the time comes I will not have my own prostate treated with protons. Nor will I choose hydrogel spacer given the very low rates of rectal toxicity that I see in my IMRT patients and the recent concerns regarding previously unreported toxicities of hydrogel spacer. IMO, if the mostly gray haired (at least 50%) Rad Onc that I choose to treat me needs spacer then something seems amiss, both figuratively and literally. I suppose there may be some inauspicious techniques that have such a high rate of rectal toxicity that it is perhaps compulsory. :thinking:

Fire away. :corny:
 
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Neuronix

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Buddy of mine tells me a story about how they rejected a paper with outstanding results for protons for prostate in the red journal because the data was unbelievably good. They basically told me they had seen several rectal bleeds requiring intervention from the proton center that had written the paper, yet they were not in the paper.

Paper was published anyway.

Reminds me of a patient of mine who ran off to a proton center for treatment. Protons were no better than what I planned with VMAT. A dosimetrist who left that center later told me they were frantically trying for some way to make the IMPT plan better to justify it for insurance. Patient demanded protons and so it ended up being delivered in the end.
 
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RickyScott

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Florida? Penn? Other? in line with reports of institutions not reporting unflattering proton data. Over the next decade we'll be able to extend the same critiques to FLASH once proton centers start transitioning to FLASH treatments.
Probably uf -have published bs on prostate in past. (Love the department overall but recall sketchy prostate paper.) Anecdotally, it seems protons give more rectal toxicity than re irradiation of prostate!
 
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BobbyHeenan

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Buddy of mine tells me a story about how they rejected a paper with outstanding results for protons for prostate in the red journal because the data was unbelievably good. They basically told me they had seen several rectal bleeds requiring intervention from the proton center that had written the paper, yet they were not in the paper.

Paper was published anyway.

Reminds me of a patient of mine who ran off to a proton center for treatment. Protons were no better than what I planned with VMAT. A dosimetrist who left that center later told me they were frantically trying for some way to make the IMPT plan better to justify it for insurance. Patient demanded protons and so it ended up being delivered in the end.

You mean we maybe can't trust the data that shows a survival difference for protons vs. photons in prostate?

While we can't show survival differences when we actually randomized hundreds of men to AS versus treatment, yet somehow modality of radiation is impacting survival? No selection bias at all as I"m sure it was all accounted for in the careful MVA.

/sarcasm.
 

Mandelin Rain

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Nor will I choose hydrogel spacer given the very low rates of rectal toxicity that I see in my IMRT patients and the recent concerns regarding previously unreported toxicities of hydrogel spacer.

What did I miss?
 
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BobbyHeenan

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What did I miss?

I do the procedure, but I get nervous about stuff like this....


Aminsharifi A, Kotamarti S, Silver D, Schulman A
Major Complications and Adverse Events Related to the Injection of the SpaceOAR Hydrogel System Before Radiotherapy for Prostate Cancer: Review of the Manufacturer and User Facility Device Experience Database.
J Endourol 2019 Oct ;33(10) 868-871 PMID:31452385 PubMed - in process
Hide Abstract
Purpose: SpaceOAR® is a Food and Drug Administration-approved hydrogel injection used to create space between the prostate and rectum during prostate radiotherapy. It has shown to significantly reduce the rectal radiation dose with lower rates of rectal toxicity. Despite a high safety performance in initial trials, SpaceOAR remains in early clinical use. Thus, we examined emerging safety reports as the system becomes more widely utilized. Methods: We reviewed the SpaceOAR manufacturer website for the safety profile and complications associated with the SpaceOAR hydrogel. We then compared this with reports submitted to the Manufacturer and User Facility Device Experience (MAUDE) database. Results: The manufacturer website reported risks including pain, needle penetration, and/or gel injection into a nearby organ or blood vessel, local inflammation, infection, urinary retention, and local rectal injury or symptoms. There were 22 unique reports discussing 25 patient cases in the MAUDE database from January 2015 to March 2019, with an increasing number of reports each year up through 2018. Unique major complications including acute pulmonary embolism, severe anaphylaxis, prostatic abscess and sepsis, purulent perineal drainage, rectal wall erosion, and rectourethral fistula were reported. Conclusion: Despite well-documented clinical benefits of the SpaceOAR System, there are a number of severe and debilitating complications recently reported in proximity to gel injection. This highlights the need for further study of device complications in light of its increasing clinical use.
This citation was also selected in the following Editor's Choice Editions: Radiation Oncology May 2020


Here is Lawton's commentary on it:


Toxicities related to radiation therapy for prostate cancer should be mitigated as much as possible, as they should be for all cancers that are treated with radiation therapy. The most common toxicities associated with radiation therapy and the treatment of prostate cancer are bowel and bladder related. Although uncommon, some of the toxicities can be severe. Thus, the development of the system described in this article to increase the distance between the prostate and the rectum seems very reasonable.

The spacer system developed here was tested in a randomized trial which showed a 25% relative reduction in rectal radiation dose and an associated decrease in Grades I-III clinical rectal toxicity and improved bowel quality of life at 15 months and three years. Yet even though there was an invasive procedure done to place the spacer, and a foreign body (the spacer system) was placed, no device related toxicities were reported, except local fullness/tenderness at the injection site.

The data presented here is a report from an FDA-maintained archive for anonymous reporting of device-related adverse events during procedures. This report shows 25 patients (2015-2019) who had adverse events ranging from venous injection with no sequelae (2 patients) to severe complications of rectal ulcers, perirectal fistulas, prostatic abscess, urosepsis and even death. This information is critical for the patient considering this procedure and the medical personnel placing the spacer. The risk of significant rectal toxicity in the era of image guided radiation therapy and intensity modulated radiation therapy is low with less than 1% Grade 4 toxicity and less than 5% Grade 3 toxicity. The risk of a severe injury with this spacer is also low, but not zero and must be discussed. To the credit of the manufacturer, their website reports possible adverse events ranging from pain to local rectal injury and fistula formation. It is imperative that we as radiation oncologists discuss these possible toxicities if we choose to recommend the spacer system.
 
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RickyScott

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The MAUDE link above. Anecdotally did have one pt who developed a rectal abscess towards the end of tx, ended up needing a temporary diverting colostomy. Have never seen that in years of practice pre S-OAR
Very act of placing space oar needs to be defined as grade 2 toxicity
 
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Mandelin Rain

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Mild pruritic erythema = Grade 2 toxicity
Thoracotomy scar = Grade 0 toxicity

Radiation is indeed VERY toxic.
 
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Mandelin Rain

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Very act of placing space oar needs to be defined as grade 2 toxicity
I wish I could like this post a million times.

EDIT: Really, it's more of a Grade 3 toxicity as it's an invasive procedure. But instead of doing an invasive procedure on a small subset of the population who do experience toxicity, you just do the invasive procedure on everyone.
 
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BobbyHeenan

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I have a lot of mixed feelings on spaceOAR. Glad to see some takes out there that don't uniformly just put it in everyone because there are some zealots out there that made me worry I was doing harm by not putting it in everyone.

I've only been doing it for SBRT right now and/or if patient is incredibly interested in it. I feel like I'm just playing with fire at times for bad infection or rectal wall issue though.
 
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Tigerstang

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Anyone have an update on what's going on in Knoxville?
 
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seper

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I don't recommend it and reports of side effects are real.

I have a lot of mixed feelings on spaceOAR. Glad to see some takes out there that don't uniformly just put it in everyone because there are some zealots out there that made me worry I was doing harm by not putting it in everyone.

I've only been doing it for SBRT right now and/or if patient is incredibly interested in it. I feel like I'm just playing with fire at times for bad infection or rectal wall issue though.
 

ramsesthenice

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I have a lot of mixed feelings on spaceOAR. Glad to see some takes out there that don't uniformly just put it in everyone because there are some zealots out there that made me worry I was doing harm by not putting it in everyone.

I've only been doing it for SBRT right now and/or if patient is incredibly interested in it. I feel like I'm just playing with fire at times for bad infection or rectal wall issue though.

Im like you. Some patients come asking for it and even if you show them their MRI with decent spacing between rectum and prostate they still insist. I also use it for most SBRT patients. That’s about it. I’ve probably used it 20 times or so over the last couple years and only seen one person who had anything other than minimal post procedural pain. I bet some of it is operator dependent but there is no reason to doubt the complications discussed are real and almost certainly outweigh the possible benefits of just blindly putting these in every patient. Spacers will only help with late GI toxicity which Really just isn’t an issue that often.

I even saw where people have tried using these with HDR (single fraction PRADA study). Again, the main issue with single fraction Brachy is GI tox and there is no logical reason Spacer will help this. Might even make it worse. Doubt it does anything good for TRUS imaging either.
 
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OTN

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Im like you. Some patients come asking for it and even if you show them their MRI with decent spacing between rectum and prostate they still insist. I also use it for most SBRT patients. That’s about it. I’ve probably used it 20 times or so over the last couple years and only seen one person who had anything other than minimal post procedural pain. I bet some of it is operator dependent but there is no reason to doubt the complications discussed are real and almost certainly outweigh the possible benefits of just blindly putting these in every patient. Spacers will only help with late GI toxicity which Really just isn’t an issue that often.

I even saw where people have tried using these with HDR (single fraction PRADA study). Again, the main issue with single fraction Brachy is GI tox and there is no logical reason Spacer will help this. Might even make it worse. Doubt it does anything good for TRUS imaging either.

I would want to see long-term data of 50 Gy in 5 fx for high-risk disease with SBRT with spacer placed. GI toxicity was too high without it.
 
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ramsesthenice

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I would want to see long-term data of 50 Gy in 5 fx for high-risk disease with SBRT with spacer placed. GI toxicity was too high without it.

Anecdotally I agree with you. We did a fair bit of 4 fraction SBRT where I trained and long term proctitis and Tenesmus were noticeably higher than what I see reported in the literature. that’s why I use a spacer for SBRT cases.
 
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RickyScott

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Convenience wise, sbrt marginally more conevenient than 20 x 3 gy, but often requires invasive procedures and may carry additional risks. Psychologically, I think a lot of this boils down to the name “sbrt”sounding cool and high tech.
 
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Mandelin Rain

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The thing I don’t get is if you have the patient in a procedure room, numbed, sedated, with a TRUS in his butt and a needle in his perineum, why not just drop some seeds and be done with it?
 
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BobbyHeenan

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Convenience wise, sbrt marginally more conevenient than 20 x 3 gy, but often requires invasive procedures and may carry additional risks. Psychologically, I think a lot of this boils down to the name “sbrt”sounding cool and high tech.

PACE and NRG trials should help answer some of this...though I'm starting to think that the SBRT dose on those trials may be a tad low. I have enrolled one patient on the NRG trial.

50 Gy in 5 prob too high though (see UTSW experience). I *think* the sweet spot may be 40/5. Dose painting 40+/5 MRI suspicious areas (especially if path concordant) seems reasonable to me.
 
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RickyScott

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PACE and NRG trials should help answer some of this...though I'm starting to think that the SBRT dose on those trials may be a tad low. I have enrolled one patient on the NRG trial.

50 Gy in 5 prob too high though (see UTSW experience). I *think* the sweet spot may be 40/5. Dose painting 40+/5 MRI suspicious areas (especially if path concordant) seems reasonable to me.
I dose paint presently in about non stereo 30% cases - if cores or lesion lateralized or anterior, will ask for that half of prostate to be 4-5% hot. As a pt, personally wouldn’t enter trial as sbrt will not be better for os, but may have worse se. I think intensification should focus on systemic agents with xrt ie 6 months of zytega.
 
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OTN

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Convenience wise, sbrt marginally more conevenient than 20 x 3 gy, but often requires invasive procedures and may carry additional risks. Psychologically, I think a lot of this boils down to the name “sbrt”sounding cool and high tech.

Disagree. 40 in 5 has been very well-tolerated in my practice in the short- and near-short term (I've been doing it for three years). I don't place fiducials and don't use a spacer. Going weekly instead of 2-3x/week has helped with acute toxicity.
 
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DebtRising

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You give 40/5 weekly for prostate? That’s pretty cool, never heard of that.

SpaceOAR’s flaw is the human body. There is an incredible amount of diversity in the prostate rectal Interface when you start going in there and injecting things. Pretty neat for what was supposed to be just a line of connective tissue
 
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Chartreuse Wombat

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Disagree. 40 in 5 has been very well-tolerated in my practice in the short- and near-short term (I've been doing it for three years). I don't place fiducials and don't use a spacer. Going weekly instead of 2-3x/week has helped with acute toxicity.
 

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evilbooyaa

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the future in H&N XRT?

I've anecdotally heard from proton folks that H&N IMPT is 'sooooooooo amazing! Like ZERO oral mucositis in a OPhx patient! We see how beautifully the dose just STOPS at the medial surface of the mandible, NO low-dose bath through the oral cavity!'

I continue to encourage them to publish their results compared to contemporary IMRT plans showing decrease in clinical toxicity, Or do a randomized clinical trial. I'd even take retrospective data as some signal of it, compared to contemporary IMRT patients.
 
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Gfunk6

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I've anecdotally heard from proton folks that H&N IMPT is 'sooooooooo amazing! Like ZERO oral mucositis in a OPhx patient! We see how beautifully the dose just STOPS at the medial surface of the mandible, NO low-dose bath through the oral cavity!'

I continue to encourage them to publish their results compared to contemporary IMRT plans showing decrease in clinical toxicity, Or do a randomized clinical trial. I'd even take retrospective data as some signal of it, compared to contemporary IMRT patients.

I understand that protons can be quite helpful if you are treating H&N unilaterally. However, I also understand that bilateral treatment is equally toxic as photons.
 

RickyScott

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Unilateral treatment with IMRT and conservative fields/dose levels (hpv+) is also not very toxic.
 
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scarbrtj

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Unilateral treatment with IMRT and conservative fields/dose levels (hpv+) is also not very toxic.
Amen to this. O'Sullivan was first real populizer of the unilateral approach which was a bit anathema for certain sites at the time. Unilateral, pre-IMRT, usually meant a wedged pair and you'd have ~50% of dose flying out somewhat contralaterally/orally even then. With IMRT ~10-20% (ie 7-14 Gy in ~35fx) of dose flies out where it shouldn't, and these doses don't produce mucositis. It was revelatory and exciting and heartening to see these kinds of outcomes in clinic (as compared to old techniques) for the first time. Protons may be good in H&N, but unlikely it can be substantially better in terms of clinically significant toxicities when in the unilateral setting. That trial would fail. The proton people tell me side effects are just better overall, as if there's something radiobiologically sparing in the protons themselves. Now that we need trials for.
 

RickyScott

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Amen to this. O'Sullivan was first real populizer of the unilateral approach which was a bit anathema for certain sites at the time. Unilateral, pre-IMRT, usually meant a wedged pair and you'd have ~50% of dose flying out somewhat contralaterally/orally even then. With IMRT ~10-20% (ie 7-14 Gy in ~35fx) of dose flies out where it shouldn't, and these doses don't produce mucositis. It was revelatory and exciting and heartening to see these kinds of outcomes in clinic (as compared to old techniques) for the first time. Protons may be good in H&N, but unlikely it can be substantially better in terms of clinically significant toxicities when in the unilateral setting. That trial would fail. The proton people tell me side effects are just better overall, as if there's something radiobiologically sparing in the protons themselves. Now that we need trials for.
Treated several pts 220 x 30 (no chemo) unilateral tonsil with very low toxicity/pt decline pain meds. H/N toxicity declining as we decrease margins. Thought I saw Nancy lee mention on twitter that she adds 3-5 mm to GTV for ptv and has very low elective nodal levels.
 
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