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I do 46 because I care more then you do.I always do 45
MidwestRadOnc
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I also do, but some payors have a hard limit of 40 fractions even when treating nodes. Funny enough I've never seen them mandate 200 over 180/fraction in any other site, except prostate which has the lowest alpha/beta.I always do 45
Speaking of nodes, this trial treated nodes in 23 fractions. Not sure it will do much with Evicore as they only let you use conventional if you are treating nodes, and this is also a 40 fraction trial, not 45.
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Nice post but I would emphasize the best evidence for RT improving survival by overcoming resistance to androgen blockage alone in high risk non-metastatic prostate cancer is quite compelling indeed. Established conventionally fractionated radiation as the standard of care and great to see the new standard raised to 80 Gy. This is signal (helping patients) while endless non-inferiority trials = shiny objects/plenary presentation/career advancement etc.
Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial - PubMed
In patients with locally advanced or high-risk local prostate cancer, addition of local radiotherapy to endocrine treatment halved the 10-year prostate-cancer-specific mortality, and substantially decreased overall mortality with fully acceptable risk of side-effects compared with endocrine...
pubmed.ncbi.nlm.nih.gov
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Old school high risk patients. Wonder what their PSMA pet scans would look like.Nice post but I would emphasize the best evidence for RT improving survival by overcoming resistance to androgen blockage alone in high risk non-metastatic prostate cancer is quite compelling indeed. Established conventionally fractionated radiation as the standard of care and great to see the new standard raised to 80 Gy. This is signal (helping patients) while endless non-inferiority trials = shiny objects/plenary presentation/career advancement etc.
Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial - PubMed
In patients with locally advanced or high-risk local prostate cancer, addition of local radiotherapy to endocrine treatment halved the 10-year prostate-cancer-specific mortality, and substantially decreased overall mortality with fully acceptable risk of side-effects compared with endocrine...
But a trial I still think about regularly when counseling very locally advanced men to incorporate XRT into their treatment. Very important work.
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There is also the Canadian trial
Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial - PubMed
Canadian Cancer Society Research Institute, US National Cancer Institute, and UK Medical Research Council.
pubmed.ncbi.nlm.nih.gov
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Oh man do the PSMA on the biology guided RT machine and youre really cookin.
Or doing something. Yes, were doing things.
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Noninferiority trials show non inferiority 85% of the time - what kind of science is that?
PI's love noninf trials to pad their CV while also leading to biocreep.
Survival outcomes - the French have shown OS analysis can (and should) be done. IMO, surrogates also pad one's CV and lead to biopcreep. Surrogates are not needed in prostate ca trials.
This study had 550 pts with long term followup. Maybe STAMPEDE will be able to produce a similar trial with hypofrac - until then, I wait.
The standard for high risk prostate ca is conventional EBRT to 80 Gy with 3 yrs ADT.
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They "let you" treat with 45. You have to appeal.
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Didn't msk have a study going to 86.4/48 fx?
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Of course they did. Gets you another weekly charge
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Double digit OTVs per pt. Unheard of otherwise
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Anyone have the info?
This may (probably will) IMPROVE outcomes rather than just “proving” non-inferiority
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It’s interesting how we have just ignored the FLAME trial.
I know a lot of people dose escalating dominant nodule. Makes total sense to me.
New Study in Red Journal Reveals Growth in Use of Proton Therapy for Treating Wider Variety of Conditions
NAPT NEWSFor Immediate Release:January 23, 2024 – The National Association for Proton Therapy (NAPT), the nation’s leading organization dedicated to increasing patient access to on
proton-therapy.org
The NAPT creep is insidious
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Ultra-high dose (86.4 Gy) IMRT for localized prostate cancer: toxicity and biochemical outcomes - PubMed
This report represents the largest data set of patients treated to ultra-high radiation dose levels of 86.4 Gy using IMRT for localized prostate cancer. Our findings indicate that this treatment is well tolerated and the early excellent biochemical control rates are encouraging.
pubmed.ncbi.nlm.nih.gov
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But are they using conventional fractionation per the trial?
I see people doing hypofrac and boosting that area with SIB.
know people doing both.
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This is a great example of the disconnect between "the RadOnc conversation" and "the RadOnc reality".
I also know many people doing FLAME-style regimens as well.
But why would they talk about it, or worse: publish? For almost a decade the only real "safe" thing to openly discuss was hypofrac or omission.
It's why I'm so happy for these high risk results. It forces a topic change.
Idk I guess I may be missing your circles or social media view but I feel like lots of stuff gets talked about in prostate cancer other than hypofrac or omission. It’s changed quite a bit over the past few years. The sequencing and types of hormonal therapy, the impact of PSMA on staging, volume delineation, and prognosis in the high risk and salvage settings, the treatment of the primary or metastases in the metastatic setting, dominant nodule boosting, POP-ART - all of these to me are interesting and are discussed quite a bit I see in the literature and social media. Prostate RT has gotten a lot more interesting as of late IMO
MidwestRadOnc
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How do you convince them to “let you” do 81 in 45 instead of 80 in 40?
I prefer to do 1.8/fx so I can more gently do an integrated boost. I also prefer to treat nodes to 50.4
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I have never been affiliated with MSKCC. But the change in paradigm in the late 2000s/early 2010s was remarkable. A colleague (who had been affiliated with MSKCC) informed me in the early/mid 2010s that MSKCC was now SBRTing tons of people (I had previously thought of them as fractionation maximalists regarding prostate cancer). Zelefsky's own research output changed to emphasize ultra hypofractionation.Ultra-high dose (86.4 Gy) IMRT for localized prostate cancer: toxicity and biochemical outcomes - PubMed
This report represents the largest data set of patients treated to ultra-high radiation dose levels of 86.4 Gy using IMRT for localized prostate cancer. Our findings indicate that this treatment is well tolerated and the early excellent biochemical control rates are encouraging.
Dose-Escalated Intensity Modulated Radiation Therapy for Prostate Cancer: 15-Year Outcomes Data - PubMed
This report represents the longest follow-up data set to our knowledge of patients treated with high-dose IMRT for PC. Our findings indicate that it is well tolerated with 1.0% and 2.3% incidence of long-term grade 3+ GI and GU toxicity, respectively. The cohort had excellent PC-specific survival.
pubmed.ncbi.nlm.nih.gov
Above is 15 year f/u for high dose IMRT at MSKCC.
A couple things pop out to me. First, CSS is great, and cause specific mortality is only over 10% (and there just barely) in the high risk cohort. IMO, it gets very hard to improve on any CSS ~90% or better. My guess is judicious use of abiraterone or similar, combined with long course IMRT and ADT would have gotten their high risk cohort below 10%. There is very little room for academics to improve survival outcomes in this setting.
So what do academics do when they get CSS in a disease up around 90%? They start to de-escalate therapy and study impact through non-inferiority studies. This is not wrong.
However, it should also be noted that the reported toxicity in this series is unbelievably good. (This is not like trying to drop bleomycin from HL therapy). I must admit, MSKCC always seems to report close to zero toxicity long term for their patients (they do report significant acute toxicity in some of their SBRT work).
The main toxicities that academics address though hypofractionation studies in pCA are inconvenience and cost (perhaps not even germane to the MSKCCs of the world...hypofractionation begets larger market share). Often at the expense of some other toxicities (acute GU/GI).
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Right - those are all either 1) diagnostic/workup or 2) metastatic setting.
I don't disagree.
I'm talking specifically about definitive radiotherapy in the primary, non-salvage, non-metastatic setting.
Show me ANYTHING that isn't hypofrac, SBRT, or surveillance in that topic.
I mentioned them in my post, among others:
1) pop ART - elective nodal radiation.
2) trials and literature on PSMA on volume delineation in definitive setting
3) dominant nodule boost!
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Let's add to this intensified systemic therapy together with RT+ADT, e.g. STAMPEDE with abiraterone.
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Pop-ART:
"This phase III, single center, randomized controlled trial enrolled eligible patients undergoing radical radiotherapy for node-negative prostate adenocarcinoma, with estimated nodal risk ≥ 20%. Randomization was 1:1 to PORT (68 Gy/25# to prostate) or whole-pelvic radiotherapy (WPRT, 68 Gy/25# to prostate, 50 Gy/25# to pelvic nodes, including common iliac)..."
Hypofrac.
PSMA Volume Delineation:
The most cited papers don't really mention the radiation regimen, but if you have one using conventional, I'd love to see it.
Dominant nodule boost:
I'm assuming DELINEATE is what most people are referencing right now for this? While that trial did have a version of convention (37 fractions), here's the conclusion:
"The DELINEATE trial has shown safety, tolerability, and feasibility of focal boosting in 20 or 37 fractions. Efficacy results indicate a low chance of prostate cancer recurrence 5 years after radiation therapy. Evidence from ongoing phase 3 randomized trials is awaited."
They lead with hypofrac. Here's the review/editorial that has the most citations for a recent paper, with recognizable authors (Use of focal radiotherapy boost for prostate cancer: radiation oncologists’ perspectives and perceived barriers to implementation):
"Additionally, some participants had concerns about focal boost in the setting of larger doses per fraction than used in FLAME. Data on this topic are emerging [21]. Hypo-FLAME was a phase II, single-arm study of ultra-hypofractionation (5 weekly fractions) with a focal boost up to 50 Gy. This study incorporated a urethral dose constraint, as recommended by Groen et al., and found acceptable toxicity [22]. Phase III trial evidence is not available for focal boost with ultra-hypofractionated regimens. DELINEATE was a single-center phase II trial in the UK that recently demonstrated safety and feasibility of using a focal boost of 67 Gy in 20 fractions or 82 Gy in 37 fractions. The efficacy and toxicity rates at 5 years were comparable to those in published trials, including FLAME. PIVOTALboost is an ongoing phase III randomized trial in the UK evaluating a focal boost of 67 Gy in a 20-fraction hypofractionated regimen [23]. Ideal constraints are still under investigation, and some patients may not be good candidates for boosting [24]. On the other hand, if hypofractionation is considered a key barrier to boosting, the logistic advantages of hypofractionation must be weighed against the oncologic benefit of focal boost."
They conclude:
"In conclusion, in responses from over 250 international radiation oncologists, we found that almost half are routinely offering focal RT boost. Of note, there was overrepresentation in our study of subspecialists in genitourinary cancers, who might be earlier adopters. Based on commonly cited barriers, further adoption of focal RT boost might be aided by increased access to high-quality MRI, better registration algorithms of MRI to CT simulation images, more clinical data (especially for larger fraction sizes), physician education on benefit-to-harm ratio, and physician training on how to contour prostate lesions on MRI. Addressing these barriers would likely increase the adoption of focal RT boost and improve the efficacy of RT for more patients with prostate cancer."
The gist of the paper is CLEARLY towards hypofrac.
STAMPEDE is metastatic. What's your favorite intensified therapy paper?
Regardless, @drowsy12, you clearly agree with me. Zero examples thus far have a positive attitude towards conventional in the upfront, definitive setting.
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I should also clarify, because the height of the "great hypofrac wars" was now...ugh...6 years ago, in 2018, so an entire residency cycle has passed and younger lurkers/posters won't understand why some of us harp on this:
In 2018, ASTRO (and others) published white papers/guidelines pushing hypofrac for breast and prostate. And just to be clear, I don't dislike hypofrac as a concept - I personally exclusively use it for intact breast. I don't like how it has been approached in prostate, because I think non-inferiority trials are statistical voodoo and we shouldn't be basing guidelines on them. While I default to conventional for high risk prostate, I will almost always use hypofrac for intermediate risk, and I always ask patients how far away they live. If a high risk prostate is coming from a great distance, or has other schedule limitations, I will offer hypofrac. I also will do high risk hypofrac if a patient comes in insisting on it.
But the push for hypofrac in breast and prostate had two key consequences:
1) It gave eviCore and other insurance entities ammunition to draft guidelines to deny treatments based on fractions.
2) It created another clear division between academics and community.
Because the trial data is significantly better in breast, you don't hear about it as much - and as we're seeing now, even the Ivory Tower is fighting back against the omission narrative they themselves created.
Prostate is different. Those of us who have dabbled in every prostate regimen on planet Earth have our own opinions about preferred regimens. Personally, I like conventional because the urinary side effects show up later, and in my own biased opinion, I think they can be more mild. If/when I get prostate cancer myself, I would perform conventional...on myself.
Hypofrac is the ultimate "built in marketing" for expensive, large academic medical centers. It's very easy to convince patients to get treatment at Big Fancy Hospital by saying "oh man, it's so much quicker now", and simultaneously, you can imply - even unintentionally - that those silly community RadOncs are out-of-touch for even considering conventional.
To be super clear, I do think the Prostate Hypofrac Evangelical RadOncs™ have drastically reduced their preaching. It's somewhat more neutral now, so if you didn't live through the transition of 2018, I'm sure some of this seems like nonsense.
I mostly continue to beat this drum because I know how easily the narrative can be shifted if an idea is unopposed. Just look at the last 20 years in our specialty - we have one of the worst "pendulum of opinions" in medicine because of how small we are. There needs to be checks and balances, and the collective RadOnc memory seems to exist in 5-year cycles.
In 2018, ASTRO (and others) published white papers/guidelines pushing hypofrac for breast and prostate. And just to be clear, I don't dislike hypofrac as a concept - I personally exclusively use it for intact breast. I don't like how it has been approached in prostate, because I think non-inferiority trials are statistical voodoo and we shouldn't be basing guidelines on them. While I default to conventional for high risk prostate, I will almost always use hypofrac for intermediate risk, and I always ask patients how far away they live. If a high risk prostate is coming from a great distance, or has other schedule limitations, I will offer hypofrac. I also will do high risk hypofrac if a patient comes in insisting on it.
But the push for hypofrac in breast and prostate had two key consequences:
1) It gave eviCore and other insurance entities ammunition to draft guidelines to deny treatments based on fractions.
2) It created another clear division between academics and community.
Because the trial data is significantly better in breast, you don't hear about it as much - and as we're seeing now, even the Ivory Tower is fighting back against the omission narrative they themselves created.
Prostate is different. Those of us who have dabbled in every prostate regimen on planet Earth have our own opinions about preferred regimens. Personally, I like conventional because the urinary side effects show up later, and in my own biased opinion, I think they can be more mild. If/when I get prostate cancer myself, I would perform conventional...on myself.
Hypofrac is the ultimate "built in marketing" for expensive, large academic medical centers. It's very easy to convince patients to get treatment at Big Fancy Hospital by saying "oh man, it's so much quicker now", and simultaneously, you can imply - even unintentionally - that those silly community RadOncs are out-of-touch for even considering conventional.
To be super clear, I do think the Prostate Hypofrac Evangelical RadOncs™ have drastically reduced their preaching. It's somewhat more neutral now, so if you didn't live through the transition of 2018, I'm sure some of this seems like nonsense.
I mostly continue to beat this drum because I know how easily the narrative can be shifted if an idea is unopposed. Just look at the last 20 years in our specialty - we have one of the worst "pendulum of opinions" in medicine because of how small we are. There needs to be checks and balances, and the collective RadOnc memory seems to exist in 5-year cycles.
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If/when we get a bundled payment program, pay close attention to the opinions of people working in different systems. We will learn a lot about them in that time. In theory, bundled will remove the marketing advantage of hypofrac... Im worried large networks will instead start trying to differentiate by just saying they do a better job on the same treatment (without posting outcomes)
Maybe it is only obvious to me because I lived it in my first job as someone who treated rare cancers. If academic centers did not care about growth and consult conversion rate, there would be far less American writing about hypofractionation. I explored both moving my service to hypofractionation to better treat patients myself and better training my community colleagues to do standard fractionation close to home. You can guess which was better supported by my administration of the two strategies.
Mark Storey has a great article out this morning that I think really efficiently captures the true motivation for why places like MSKCC are so over the top with hypofractionation.
It really bothers me that these "health economics researchers" in our field have become comfortable with publishing propaganda.
protons101.substack.com
Maybe it is only obvious to me because I lived it in my first job as someone who treated rare cancers. If academic centers did not care about growth and consult conversion rate, there would be far less American writing about hypofractionation. I explored both moving my service to hypofractionation to better treat patients myself and better training my community colleagues to do standard fractionation close to home. You can guess which was better supported by my administration of the two strategies.
Mark Storey has a great article out this morning that I think really efficiently captures the true motivation for why places like MSKCC are so over the top with hypofractionation.
It really bothers me that these "health economics researchers" in our field have become comfortable with publishing propaganda.
Market trends: A Rebuttal
A recent article made my blood boil. We'll look deeper and see if my gut was right or wrong.
protons101.substack.com
MidwestRadOnc
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I have moved away from the hour long consults discussing every possible treatment permutation.
It’s simply “side effects may be worse if you want to get done quicker”
I just had one guy who would only do 5 fractions or nothing at all. He is getting 5 fractions. Without gel because I can’t do it and nobody else will either. I still prefer this to obs in intermediate risk.
For high and very high risk there is a discussion about how aggressive they want to be and pursue a brachy or SBRT boost although im starting to just prefer flame boosts now.
It’s simply “side effects may be worse if you want to get done quicker”
I just had one guy who would only do 5 fractions or nothing at all. He is getting 5 fractions. Without gel because I can’t do it and nobody else will either. I still prefer this to obs in intermediate risk.
For high and very high risk there is a discussion about how aggressive they want to be and pursue a brachy or SBRT boost although im starting to just prefer flame boosts now.
MidwestRadOnc
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Practicing in a non competitive rural environment is the ultimate rad onc life hack.If/when we get a bundled payment program, pay close attention to the opinions of people working in different systems. We will learn a lot about them in that time. In theory, bundled will remove the marketing advantage of hypofrac... Im worried large networks will instead start trying to differentiate by just saying they do a better job on the same treatment (without posting outcomes)
Maybe it is only obvious to me because I lived it in my first job as someone who treated rare cancers. If academic centers did not care about growth and consult conversion rate, there would be far less American writing about hypofractionation. I explored both moving my service to hypofractionation to better treat patients myself and better training my community colleagues to do standard fractionation close to home. You can guess which was better supported by my administration of the two strategies.
Mark Storey has a great article out this morning that I think really efficiently captures the true motivation for why places like MSKCC are so over the top with hypofractionation.
It really bothers me that these "health economics researchers" in our field have become comfortable with publishing propaganda.
Market trends: A Rebuttal
A recent article made my blood boil. We'll look deeper and see if my gut was right or wrong.
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I still do the hour long consult, but spend very little time on things like side effects.
The bulk of my time is now spent on coordination of care and basically...emotional comfort? I can probably find a better word/phrase at some point.
In my (rural) area, there's a significant lack of coordination, availability of various services, and many of my patients have had very little contact with the healthcare system.
Though I'm fortunate to not be in a location where I experience significant attempts at "poaching", there is one nearby place that does occasionally try to flex their reputation.
By the sadly simple fact that I treat patients as...people, and give them more time than any doctor they've ever seen, 100% of my consults who need radiation stick with me.
It's...really sad, actually.
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Ultra-high dose (86.4 Gy) IMRT for localized prostate cancer: toxicity and biochemical outcomes - PubMed
This report represents the largest data set of patients treated to ultra-high radiation dose levels of 86.4 Gy using IMRT for localized prostate cancer. Our findings indicate that this treatment is well tolerated and the early excellent biochemical control rates are encouraging.
No updates since 2008?
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Yet in that environment you have patients asking for prostate sbrt? Sounds odd
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Are you talking to the ROCR people? Please go talk to the ROCR people. I hope you're talking to the ROCR people.
MidwestRadOnc
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Definitely not common. Didn’t know what sbrt was. But didn’t want to come in for even 20 treatments. Was agreeable to 5. Not the first time that has happened. Have had people quit head and neck radiation halfway through because of seasonal farm duties.
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STAMPEDE also studied instensified therapy in non-metastastic tumors.
Abiraterone on top of ADT is considered s.o.c. by many for these (very) high risk non-metastastic tumors, when giving RT+ADT.
agreed, the Stampede trials show the best ever data for node positive prostate cancer and make the case that they should all be getting RT
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I mean, the seminal vesicles are very important organs
Impossible it was explained to me that there were never any complications ever no matter what misanthropes say
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I may have, but I really can't recall.
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Memantine past six months after WBRT I discuss with patient.
If they want to continue, I use indefinitely. I don't push.
I would say on the order of half of surviving patients don't take memantine the recommended six months for a variety of reasons.
Of the half who make it to six months, half extend it indefinitely while the other half don't.
If they want to continue, I use indefinitely. I don't push.
I would say on the order of half of surviving patients don't take memantine the recommended six months for a variety of reasons.
Of the half who make it to six months, half extend it indefinitely while the other half don't.
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I'm not sure I've ever had anyone tolerate the full dose of memantine. Feels like mid way through the ramp up, they start hallucinating or go into mania or something and we have to stop. Not a fan.
EDIT: I don't do much WBRT
EDIT: I don't do much WBRT
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my understanding is that in alzheimers momentine improves some symptoms. It does not help with progression of disease.
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77Gy in 35 fractions to the entire prostate is not conventional fractionation. It's an in-between between conventional and mod hypofx.
Memantine past 6 months is fine if they're alive
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This 100%
You don't even have to be an amazing doctor, but give patients the time and speak to them like people and you're good. Occasionally it takes some extra work but pays off.
I've been surprised by the questions some of my patients have for me re HIFU, cryo, etc, in my rural area without much competition.
I have been shocked how little time our med onc colleagues spend with patients.
they don't seem to give patients time to ask much if anything.
i don't always use the full hour for consults (SBRT to an oligomet to the lung is pretty short for me...), but always make sure to address all of their concerns at the initial visit.
