High risk prostate fractionation

[thesauce]

Saying that there is a controversy regarding fractionation or dose is not saying that hypofrac is wrong. It’s a different philosophy and interpretation of data. Get off your high horse and consider that maybe there are GU experts at notable academic institutions that still do conventional frac for high risk prostate cancer. Be open minded and don’t call people silly because you simply don’t agree with them.

Agreed. I wish the fraction-shaming would stop.

Before hypofrac, my prostate patients that went to the local academic centers would come back saying surgery was recommended - even for high risk disease. It was the recommendation EVERY SINGLE TIME. I spoke to one of the faculty that I knew well and he told me point blank that the radoncs would recommend surgery for those coming from out of town far more often than the local patients that came to see them because they knew it was going to be almost impossible to get someone to leave their home and family for 2 months to go there and be treated by them. The push for hypofrac was to get more patients treated at academic centers that they otherwise would have “lost” to the community.

In the community, many radoncs offer hypofrac (or omit RT) not because they truly believe it is better but to out-compete each other and to kiss the a$$ of the referrings who seem to want to dictate our role.

What I can genuinely say is that if my loved-one gets prostate cancer, I would want them to have standard frac.

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[elementaryschooleconomics]

What I can genuinely say is that if my loved-one gets prostate cancer, I would want them to have standard frac.

If (when?) I get diagnosed with prostate cancer, I would also want standard frac, and I want my Radiation Oncologist to have graduated residency after 2016.

 

[medgator]

If (when?) I get diagnosed with prostate cancer, I would also want standard frac, and I want my Radiation Oncologist to have graduated residency after 2016.

But before 2026.

Otherwise fine with anyone that graduated after 2003

 

[SneakyBooger]

I want a med student to treat my prostate cancer.

I am half serious -

 

[deleted1111261]

It’s not silly.

To me, it’s the idea that a truly balanced discussion is happening.

If we are both board certified, and 1/2 of my patients choose HF and 95% of @elementaryschooleconomics and @medgator choose CF, then I don’t think that we are presenting it the same way. Just like above example of all patients getting surgery at academic center. If you present “facts”, we can all present in a way that leads to outcome we want. I think rather than saying “my patients choose CF”, it’s more reasonable to say, “bc I prefer CF, my patients tend to choose CF”.

And yeah, I’d say I have “evolved” on this. The payment system incentivizing more treatments is the problem- not the doctor or the patient or the institution. CF works well. Use it. HF is very effective and depending on your interpretation- isotoxic or slightly more toxic, with several weeks shorter tx. Both are excellent options.

 

[deleted1111261]

And if you ever hear a patient is going to an academic center for “alternate opinion”, give your recs with your cell phone number on a post it and have the patient give it to big shot academic guy with CALL ME. If you don’t hear day of, call the next day. This poaching is war and we can’t be on the defensive.

 

[RadRadRad]

And if you ever hear a patient is going to an academic center for “alternate opinion”, give your recs with your cell phone number on a post it and have the patient give it to big shot academic guy with CALL ME. If you don’t hear day of, call the next day. This poaching is war and we can’t be on the defensive.

Done this several times and get a call from academic center about 5% of time

 

[deleted1111261]

Done this several times and get a call from academic center about 5% of time

Yah, I will hammer them w calls and e-mails. This is my patients’ time and money. Have respect for it.

One place told patient that I may not have prone breast. MFer, I have done prone longer than your institution has.

 

[elementaryschooleconomics]

It’s not silly.

To me, it’s the idea that a truly balanced discussion is happening.

If we are both board certified, and 1/2 of my patients choose HF and 95% of @elementaryschooleconomics and @medgator choose CF, then I don’t think that we are presenting it the same way. Just like above example of all patients getting surgery at academic center. If you present “facts”, we can all present in a way that leads to outcome we want. I think rather than saying “my patients choose CF”, it’s more reasonable to say, “bc I prefer CF, my patients tend to choose CF”.

And yeah, I’d say I have “evolved” on this. The payment system incentivizing more treatments is the problem- not the doctor or the patient or the institution. CF works well. Use it. HF is very effective and depending on your interpretation- isotoxic or slightly more toxic, with several weeks shorter tx. Both are excellent options.

I think it's pretty easy to have a "balanced" conversation end with the outcome you want (if you have a modicum of social skills, of course).

Honestly though, having now worked/trained in several institutions in very different settings, I actually think geography is playing a MUCH bigger role than we know.

My current department is in a small town, and most of our referrals are from the local catchment area. The nearest competitor is 20-30 minutes away. We have our entrance literally next to a parking lot which is designated for radiation patients. Many of my patients live within 10 minutes of the hospital. I usually have 1-2 patients on beam who walk to treatment because they live so close.

When presented with 44 or 28, I basically tell them that the outcomes appear equivalent, but the tradeoff is a slightly higher chance that some side effects show up earlier and they might be slightly worse. If a patient is truly ambivalent (meaning they walked through the door knowing nothing and stayed off Google), I will often get a shrug and hear something like "eh I live around the corner, I'll just come for the longer one".

At my residency institution, which is your standard downtown metro affair with a byzantine parking lot and significant traffic, people talked to me VERY different. I lost track with how many appointments opened with patients complaining about our parking situation, or apologizing they were late because they were stuck on the interstate, etc. This was before we got anywhere near the topic of treatment course, sometimes I didn't even get a chance to introduce myself.

All common talking points aside: there is a HUGE difference between how people perceive coming to get radiation when "treatment round trip" (home --> treatment--> home) is <30-45 minutes compared to a "round trip" of 1-2+ hours that involves downtown metro traffic (which elderly folks from the suburbs especially despise).

We have papers on treatment toxicity, on financial toxicity...I would like to see (and will probably work on myself) studies on "time and travel toxicity".

To be clear, this is a general phenomenon I have observed, not specific to prostate patients. This is just the main way I experience the difference.

I guess, as I write this, the other way is that almost all of my small cell patients agree to BID treatment, and almost none of my small cell patients in residency agreed to it (for the same reasons).

 

[medgator]

I think it's pretty easy to have a "balanced" conversation end with the outcome you want (if you have a modicum of social skills, of course).

Honestly though, having now worked/trained in several institutions in very different settings, I actually think geography is playing a MUCH bigger role than we know.

My current department is in a small town, and most of our referrals are from the local catchment area. The nearest competitor is 20-30 minutes away. We have our entrance literally next to a parking lot which is designated for radiation patients. Many of my patients live within 10 minutes of the hospital. I usually have 1-2 patients on beam who walk to treatment because they live so close.

When presented with 44 or 28, I basically tell them that the outcomes appear equivalent, but the tradeoff is a slightly higher chance that some side effects show up earlier and they might be slightly worse. If a patient is truly ambivalent (meaning they walked through the door knowing nothing and stayed off Google), I will often get a shrug and hear something like "eh I live around the corner, I'll just come for the longer one".

At my residency institution, which is your standard downtown metro affair with a byzantine parking lot and significant traffic, people talked to me VERY different. I lost track with how many appointments opened with patients complaining about our parking situation, or apologizing they were late because they were stuck on the interstate, etc. This was before we got anywhere near the topic of treatment course, sometimes I didn't even get a chance to introduce myself.

All common talking points aside: there is a HUGE difference between how people perceive coming to get radiation when "treatment round trip" (home --> treatment--> home) is <30-45 minutes compared to a "round trip" of 1-2+ hours that involves downtown metro traffic (which elderly folks from the suburbs especially despise).

We have papers on treatment toxicity, on financial toxicity...I would like to see (and will probably work on myself) studies on "time and travel toxicity".

To be clear, this is a general phenomenon I have observed, not specific to prostate patients. This is just the main way I experience the difference.

I guess, as I write this, the other way is that almost all of my small cell patients agree to BID treatment, and almost none of my small cell patients in residency agreed to it (for the same reasons).

Well articulated. The time issue never gets much airtime but so important

 

[deleted1111261]

Well articulated. The time issue never gets much airtime but so important

What is the quantitative difference in acute toxicity that you counsel your patients with regard to CF vs HF? Do you use numbers? Maybe if I say what you do, I’ll get a different outcome.

 

[RickyScott]

What is the quantitative difference in acute toxicity that you counsel your patients with regard to CF vs HF? Do you use numbers? Maybe if I say what you do, I’ll get a different outcome.

Went from 1.8 in training to 2 Gy per fraction at my first job. Flomax scripts increased from 25% to 50%+. Almost everyone with hypofrac needs flomax. Sure, it’s not a big deal, but increased acute toxicity is there. When I treat hospital employees (treatment is free and ultra convenient, no one wants hypofract.

 

[jondunn]

Imagine going from training to being an attending and seeing your low grade acute toxicity rates double and think it’s has to do with 2 gy/fx vs 1.8 and not plan quality, setup quality, or any other number of things that are probably more relevant.

 

[RickyScott]

Imagine going from training to being an attending and seeing your low grade acute toxicity rates double and think it’s has to do with 2 gy/fx vs 1.8 and not plan quality, setup quality, or any other number of things that are probably more relevant.

Took a (low paying) job with a leading academic center. Plans setup etc were excellent (and well published). others noticed this as well as 1.8 was more widespread.

 

[deleted1111261]

Went from 1.8 in training to 2 Gy per fraction at my first job. Flomax scripts increased from 25% to 50%+. Almost everyone with hypofrac needs flomax. Sure, it’s not a big deal, but increased acute toxicity is there. When I treat hospital employees (treatment is free and ultra convenient, no one wants hypofract.

Doubling of flomax scripts is a big deal.
I had not seen this in literature.

 

[RickyScott]

Doubling of flomax scripts is a big deal.
I had not seen this in literature.

Will let others weigh in, but in the days of 1.8 not uncommon for guys to complete treatment without flomax. Almost all my pts today are prescribed flomax or cialis. I only use 1.8 for the rare case where someone is maxed out on flomax and still having notcuria x4 (needs a turp but is refusing).

 

[Palex80]

Will let others weigh in, but in the days of 1.8 not uncommon at all for guys to complete treatment without flomax. Almost all my pts today are prescribed flomax or cialis. I only use 1.8 for the rare case where someone is maxed out on flomax and still having notcuria x4 (needs a turp but is refusing).

Dose escalation?

 

[RickyScott]

Dose escalation?

Sure, but this was happening during the first half of treatment. It could also be that we got a lot more comfortable with flomax and started using it more when it became generic (Used to give more Motrin and cardura). Nevertheless, today vast majority of my pts are prescribed flomax. Would love to hear from others who were in training/practiced in the early 2000s

 

[Palex80]

Sure, but this was happening during the first half of treatment.

I‘ve never seen localized prostate cancer getting treated with 1.8 Gy in my career, sorry.
It appears to me unlikely that 1.8 Gy vs. 2.0 Gy make such a difference.

 

[RickyScott]

I‘ve never seen localized prostate cancer getting treated with 1.8 Gy in my career, sorry.
It appears to me unlikely that 1.8 Gy vs. 2.0 Gy make such a difference.

Ok, but the larger point is that anecdotally it is easy to recognize increased use of flomax with fraction size. How many pts go through hypofrac without any flomax. (Put aside those who refuse to take meds but still needed it)

 

[thesauce]

I‘ve never seen localized prostate cancer getting treated with 1.8 Gy in my career, sorry.
It appears to me unlikely that 1.8 Gy vs. 2.0 Gy make such a difference.

Ironically, it’s been standard at every clinic where I trained as well as every community center where I’ve worked

 

[deleted1111261]

I cannot fathom a difference between 1.8 and 2.0. For real??

 

[Ray D. Ayshun]

I cannot fathom a difference between 1.8 and 2.0. For real??

Going from 5.2 to 5.4 daily in whole breast is significantly more toxic. The relative increase in daily dose there is less than half of that when going from 1.8 to 2.0...

 

[deleted1111261]

Going from 5.2 to 5.4 daily in whole breast is significantly more toxic. The relative increase in daily dose there is less than half of that when going from 1.8 to 2.0...

Yeah, I will choose to believe that though p-value was met, this still falls into “chance” !!

 

[Ray D. Ayshun]

Yeah, I will choose to believe that though p-value was met, this still falls into “chance” !!

6 Gy/week also significantly more toxic than 5.7 Gy/week.

 

[elementaryschooleconomics]

What is the quantitative difference in acute toxicity that you counsel your patients with regard to CF vs HF? Do you use numbers? Maybe if I say what you do, I’ll get a different outcome.

*sigh*

*puts on linen shirt, grabs crystal necklace, lights incense*

Counter to what feels like, well, everyone else in RadOnc does (especially oral boards), I try to never discuss actual trial numbers with patients.

Obviously, if really pressed and the person seems like they have the "health literacy" to understand what the numbers mean, I'll do it.

But the human brain does not natively understand the abstract concept of a population-level statistics. If that were true, no one would ever play Powerball. Additionally, people will absolutely latch onto a number if a doctor says it. A couple of weeks ago, I had a consult where a guy told me he only had 7 months left to live, and asked why he should get radiation if he was going to die so soon. On trying to figure out how he arrived at that belief, it sounds like someone in MedOnc gave him an estimate on what would happen if he elected to not receive any treatment, and by the time he got to me, he figured he should be ordering a casket.

I phrase things in various ways:

"How long do I have left to live" is discussed with the "hours to days, days to weeks, weeks to months, months to years" timeline.

"Are you going to cure my cancer" is discussed more organically, but I often say things such as "very good chance, good chance, 50/50, maybe 50/50 but it's worth a shot", etc (I modify this based on the literacy of the person I'm talking to).

For side effects, I go with "best case scenario, worst case scenario, and most likely scenario".

So, with that hippie context, when I get to the side effects portion of the consult, after discussing the more common side effects, I truthfully tell them that the most likely scenario is that guys tell me they feel a little tired, and that they have some more urinary urgency/frequency and/or difficulty starting to urinate, but get through from start to finish without severe issues (I don't know about y'all, but that's how my prostate courses usually go...even though I refuse to use the beloved SpaceOAR, I don't see much in the way of GI toxicity - sorry Boston Scientific).

After telling them the "most likely" scenario, I then tell them (again, truthfully) that the guys who do the shorter course regimen generally experience slightly more urgency/frequency earlier than the longer course patients, but they also have no trouble getting through. I then reiterate/summarize with something like "that's the choice, both options should have an equally excellent chance at controlling the cancer, and the tradeoff for being done faster is a slightly increased chance of some urinary side effects showing up earlier and maybe being a little more bothersome". I often make a stupid joke like "can't get anything for free in this world, right?" and then the three of us laugh (because there's usually a wife in the room).

That's all I say. No numbers, no doom and gloom. I'm absolutely CERTAIN that if I tried this in a department in a downtown metro area with someone driving in from the suburbs, I would have almost no one picking conventional, haha.

On my end, as I've said on SDN before: I vastly prefer conventional fractionation for psych/mental health reasons. Prostate patients are a nervous bunch. You get these older men who grew up in an era when men weren't supposed to show emotion, so they don't have great coping mechanisms. They're often generally healthy, so this is their first "real" big health issue. You can see the terror in their eyes, but they're trying to hold it in.

So you take someone like that, and you start them on a treatment they don't understand. Eventually, the treatment becomes "routine" for them, and the anxiety lessens.

EXCEPT if urinary side effects show up in Week 2, which is not uncommon in my experience (and consistent with the literature). Then it's just week after week of trying to dial in Flomax or whatever, and the anxiety is always lurking.

With conventional, if urinary side effects show up, it's usually in the final 10-14 days. By that point, guys have already "settled in" and it's MUCH easier to manage.

So...yeah. I'm a secret super hippie and like to use phrases such as "most likely" a lot. But I've had this conversation, and offered this choice, to a couple hundred prostate patients. None of these things I've observed are easily quantifiable, of course. But I hope the eviCores and AIMs of the world don't completely take away my ability to conventionally fractionate before I publish this in The Journal of New Age Chakra Radiation Doctors n' Stuff.

 

[Reaganite]

Yah, I will hammer them w calls and e-mails. This is my patients’ time and money. Have respect for it.

One place told patient that I may not have prone breast. MFer, I have done prone longer than your institution has.

Nothing infuriates me more than this. While it happens with basically every patient of mine who is seen at an academic place, I also used to see it a lot with pp guys invested in other private centers. I blow those mfers up like you and if I dont get an answer I go straight to their office and confront them. Luckily its never an orthopod I have to deal with 😁

 

[Palex80]

Ok, but the larger point is that anecdotally it is easy to recognize increased use of flomax with fraction size. How many pts go through hypofrac without any flomax. (Put aside those who refuse to take meds but still needed it)

I am sorry, but no. You said that your Flomax use increased by 100% when you switched from 1.8 Gy to 2.0 Gy. This is the point you made, anecdotally or not. And I am not aware of any data showing such a dramatic increase with fraction sizes. You even mentioned Cialis, I do not see why Cialis used would be increased with hypofractionation, you are frying the neurovascular bundle the same with hypo- or normofractionation down the road.

Do I think that I prescribe more Flomax with 20 x 3.0 Gy than with 39 x 2.0 Gy? Perhaps, but I cannot estimate how much more often. And I think my perception may be biased, since I only get to see my hypofractionated patients 4 times for OTVs, while I see the normofractionated ones 7-8 times for OTVs. Perhaps I may be thinking that I prescribed more Flomax per parient, but in reality I only prescribed more Flomax per OTV with hypofractionation?

 

[Palex80]

I phrase things in various ways:

"How long do I have left to live" is discussed with the "hours to days, days to weeks, weeks to months, months to years" timeline.

Never, never look at you armwatch when the patient asks that!

 

[SneakyBooger]

All my prostates get 180.

One of my friends across town treats with everything that they can, including spacer and SBRT.

Yet I continue to see more prostates than any other rad onc in the region. Maybe it is just that I have been here a long time and built up a lot of trust.

The urologists have many times commented that they see more toxicity when their patients are treated elsewhere.

It would be imprudent to change that.

Buy who knows, maybe things will change - every dog has their day.

@RickyScott, I do believe you when you say you see more toxicity with 200.

I am pretty sure I have a paper looking at 180 vs 200 - let me see if I can find it.

 

[Palex80]

I am pretty sure I have a paper looking at 180 vs 200 - let me see if I can find it.

Perhaps you mean this one?

Long-term toxicity following 3D conformal radiation therapy for prostate cancer from the RTOG 9406 phase I/II dose escalation study - PubMed

Tolerance to high-dose 3DCRT remains excellent. There is significantly more grade 2 or greater toxicity with a dose of 78 Gy at 2 Gy/fraction than with 68.4 Gy to 79.2 Gy at 1.8 Gy/fraction and with 74 Gy at 2 Gy/fraction.

pubmed.ncbi.nlm.nih.gov

It was for late toxicity though.

 

[communitydoc13]

Perhaps you mean this one?

Long-term toxicity following 3D conformal radiation therapy for prostate cancer from the RTOG 9406 phase I/II dose escalation study - PubMed

Tolerance to high-dose 3DCRT remains excellent. There is significantly more grade 2 or greater toxicity with a dose of 78 Gy at 2 Gy/fraction than with 68.4 Gy to 79.2 Gy at 1.8 Gy/fraction and with 74 Gy at 2 Gy/fraction.

pubmed.ncbi.nlm.nih.gov

It was for late toxicity though.

It's a pretty good paper IMO. I can see people dismissing because 3D (although impact on urinary bother not clear to me here) and the non-intuitive variability in toxicity (which is admittedly very hard to determine accurately).

The fact that lower dose/fraction preferentially spares late effects with low a/b ratio is never going to go away. Like everyone else, I've felt pressure to move to 28 fractions, but I'm confident it is somewhat worse than 44. Three weeks off of treatment is worth something to the patient, but mostly worth something to the payor.

 

[elementaryschooleconomics]

All my prostates get 180.

One of my friends across town treats with everything that they can, including spacer and SBRT.

Yet I continue to see more prostates than any other rad onc in the region. Maybe it is just that I have been here a long time and built up a lot of trust.

The urologists have many times commented that they see more toxicity when their patients are treated elsewhere.

It would be imprudent to change that.

Buy who knows, maybe things will change - every dog has their day.

@RickyScott, I do believe you when you say you see more toxicity with 200.

I am pretty sure I have a paper looking at 180 vs 200 - let me see if I can find it.

All my conventional prostates get 180cGy as well.

I desperately try to avoid getting into the whole 180 vs 200 debate.

I'll just say that, to me, 180cGy is the definition of "conventional". In training or in practice, I only have experience with folks doing 81Gy in 45fx, 79.2Gy in 44fx, 70Gy in 28fx, or 60Gy in 20fx (for non-SBRT, non-STAMPEDE cases).

79.2 in 44 is one of the "easiest" things for patients to get through.

I usually do 70/28 for mod hypo, but I also do 60/20 for the patients who come in with strong opinions (as appropriate). I don't really see a difference in side effects between the two.

I don't use SpaceOAR or fiducials, I do daily CBCT and have bladder/rectum instructions. Nothing crazy, but I give my patients a little piece of paper basically asking them to have a bowel movement if possible, and what to do in terms of fluid/urination an hour before treatment.

Doing this, it's very uncommon for guys to have GI issues (I will do a differential PTV expansion of 6-7mm in all directions except 5mm posteriorly and ask my therapists to match to prostate and pay attention to what the SVs are doing). The mod hypo guys will experience more urgency/frequency at the second OTV than the conventional.

The other thing I see more commonly from the mod hypo guys is the "burning with urination". AS PER USUAL, this specific symptom can be defined differently depending on which physician/institution/manuscript/system you're looking at. I'll use phenazopyridine with varying success. I actually like diclofenac but that's hard to use in our patient population (everyone is already on blood thinners or drugs to whack their kidneys etc).

Alright I'm going to stop my tangent before I start talking about referred pain from the pudendal nerve. I'll just reiterate my favorite talking point: we can't paint "hypofrac" with a broad brush. Breast hypofrac data, to me, is unimpeachable. I have never offered conventional frac to my routine early stage breast patients, and unless something changes in the literature, I plan to never offer it to them. Breast hypofrac is amazing.

Prostate is different. The GU side effects show up earlier, more often, and perhaps a little more severe. Most of the data is "non-inferiority" data. That makes me uncomfortable, objectively. "Hey we have this great treatment we know works, but then we have this other treatment that seems to be, you know, statistically, probably the same! Sign here."

 

[OTN]

Low-risk or intermediate-risk: 5-fx SBRT. High-risk: 44 fractions with nodal coverage. No SpaceOAR.

Breast hypofractionation is better in terms of side effects, in the short- and long-term. Prostate hypofx is worse. The data really are pretty clear on this.

 

[theradiator]

Low-risk or intermediate-risk: 5-fx SBRT. High-risk: 44 fractions with nodal coverage. No SpaceOAR.

Breast hypofractionation is better in terms of side effects, in the short- and long-term. Prostate hypofx is worse. The data really are pretty clear on this.

Aha, but there are fairly robust data suggesting SBRT is worse too



confirming the well known non-randomized studies

https://ascopubs.org/doi/full/10.1200/JCO.2013.53.8652

https://ascopubs.org/doi/full/10.1200/JCO.2017.75.5371

So the whole point of 5 fraction SBRT is that it is 'good enough' and offers enough in terms of convenience and competitive advantage (whether geographic or competing against urology owned practices) as opposed to a more lofty goal of actually improving public health.

 

[medgator]

So the whole point of 5 fraction SBRT is that it is 'good enough' and offers enough in terms of convenience and competitive advantage (whether geographic or competing against urology owned practices) as opposed to a more lofty goal of actually improving public health.

For some pts who understand the tradeoffs, they are going to take that option

 

[OTN]

For some pts who understand the tradeoffs, they are going to take that option

I offer both 44 fraction IMRT and 5 fraction SBRT for all low- and intermediate-risk patients (observation discussed with all those patients as well of course etc, hormone discussion pt dependent etc), and I do counsel about a chance of increased urinary irritation, grade 2, in the first 6-8 weeks after COT with SBRT compared with standard-fx IMRT. No one has taken me up on the 44 fx offer. Going to 1 fx/week has improved acute toxicity, which I did after a RCT showed no difference in control rates. (All other body site SBRTs: no more than 2 in a row, no more than 3 per week).

I did have one urologist specifically request standardized fractionation for his patient, as he was concerned hypofx or SBRT would be too toxic for him to tolerate in the short-term, and the risk of obstruction was higher. Seemed reasonable to me. In clinical practice everyone knows hypofx or SBRT are more acutely toxic, but IMO the late-term toxicity of SBRT with good image guidance and careful planning is very low.

 

[TheWallnerus]

For some pts who understand the tradeoffs, they are going to take that option

As a regimen is progressively hypofractionated, the tighter the therapeutic window; often times the control rate not changing is the primary driver for this, but sometimes (virtual prostatectomy eg) even that gets slightly worse. It’s a pure mathematics game. The alpha/beta choice is the sole constraint. The more one hypofractionates, the closer to reality the alpha/beta guess must be to stay in the “therapeutic window power band.” Part of me strongly thinks that since deciding what the alpha/beta is for an individual is such inaccurate guesswork, we should put limits on how far we push hypofractionation. Right now that limit seems to be 5 fractions, but there’s no reason single fraction prostate (or breast) won’t work. We probably would have seen more 6, 7, or 8 fraction regimens (there’s a “fractionation desert” between 5 and 15 or 20), but the alpha/beta guesses by the literati were strongly dictated by billing imho.

 

[A_DeMichele]

Aha, but there are fairly robust data suggesting SBRT is worse too



confirming the well known non-randomized studies

https://ascopubs.org/doi/full/10.1200/JCO.2013.53.8652

https://ascopubs.org/doi/full/10.1200/JCO.2017.75.5371

So the whole point of 5 fraction SBRT is that it is 'good enough' and offers enough in terms of convenience and competitive advantage (whether geographic or competing against urology owned practices) as opposed to a more lofty goal of actually improving public health.

Increasing XRT throughput and taking pts away from prostatectomy are reasonable public health goals.

 

[TheWallnerus]

Increasing XRT throughput and taking pts away from prostatectomy are reasonable public health goals.

Certainly lowers poverty rate and increases public health of children of economically disadvantaged rad oncs

 

[communitydoc13]

The more one hypofractionates, the closer to reality the alpha/beta guess must be to stay in the “therapeutic window power band.”

Agree. If one considers safety to be " the avoidance of rare but catastrophic side effects", the more hypofractionated we treat, the less safe we become. The catastrophic side effects (less some consequential late side effects) are late occurring things, presumably driven by low a/b phenomena. They are also impossible to study with our usual statistical tools.

Clear as mud to me. Single fraction spine and brain less safe than 3-5 fractions.

Regarding breast? This is an interesting site. I believe that 5 fractions whole breast somewhat less "safe" than 15 fraction, but here safety is determined by rare terrible cosmesis and hard/fibrotic or edematous breasts, not by myelopathy or CNS necrosis or fistula.

Why is ~15 fxns better than ~30 fxns for breast? For acute toxicity it's obvious. But for late toxicity, it may be that there is significant late breast toxicity that is consequential (i.e. driven by acute toxicity)?

 

[TheWallnerus]

Regarding breast? This is an interesting site. I believe that 5 fractions whole breast somewhat less "safe" than 15 fraction, but here safety is determined by rare terrible cosmesis and hard/fibrotic or edematous breasts, not by myelopathy or CNS necrosis or fistula.

The cadence of our march over the Hypofractionation Bridge in breast as you know has been completely linked (in every paper!) to alpha/beta guessing

And I am not throwing out the word “safe” per se, just therapeutic window (narrowing)… of which the 27 (more toxicity) vs 26 (less toxicity) Gy thing in breast is prototypical; this wasn’t just an infaust dose selection, it was an infaust alpha/beta guess (and no one talks about this this way)

 

[communitydoc13]

The cadence of our march over the Hypofractionation Bridge in breast as you know has been completely linked (in every paper!) to alpha/beta guessing

And I am not throwing out the word “safe” per se, just therapeutic window (narrowing)… of which the 27 (more toxicity) vs 26 (less toxicity) Gy thing in breast is prototypical; this wasn’t just an infaust dose selection, it was an infaust alpha/beta guess (and no one talks about this this way)

I would say it was faust, very faust. If you take the toxicity data seriously (not sure about this as they couldn't replicate their own toxicity data), you could not come up with two better data points to refine your toxicity a/b.

 

[communitydoc13]

As an aside, a/b is a lie. A construct from ensemble data that is not really true at the individual patient level. A given person may have a somewhat different a/b for a given toxicity than another person. (If you were to determine a/b's strictly from data on Li-Fraumeni patients, numbers would be wack.

So....even if you've gotten really cute with your hypofractionated schedule and gamed it so that things appear isotoxic by our usual statistical measures on a clinical trial, I'm still going to go with the hypofractionated schedule being somewhat "less safe".

 

[Lamount]

And if you ever hear a patient is going to an academic center for “alternate opinion”, give your recs with your cell phone number on a post it and have the patient give it to big shot academic guy with CALL ME. If you don’t hear day of, call the next day. This poaching is war and we can’t be on the defensive.

As an academic doc, I love this. More than happy to keep patients with their local rad oncs so long as they are a known quantity. I try to reach out when the patient knows their name… but don’t always get a call back. It’s hard to send a patient (back) to a question mark.

 

[SneakyBooger]

Aha, but there are fairly robust data suggesting SBRT is worse too



confirming the well known non-randomized studies

https://ascopubs.org/doi/full/10.1200/JCO.2013.53.8652

https://ascopubs.org/doi/full/10.1200/JCO.2017.75.5371

So the whole point of 5 fraction SBRT is that it is 'good enough' and offers enough in terms of convenience and competitive advantage (whether geographic or competing against urology owned practices) as opposed to a more lofty goal of actually improving public health.

American Urological Association

MP35-11
METABOLIC BIOMARKERS ARE PREDICTIVE OF RESPONSE TO RADIATION THERAPY IN PROSTATE CANCER PATIENTS

Amrita Cheema*, Washington, DC; Scott Grindrod, Rockville, MD; Simeng Suy, Xiaogang Zhong, Shreyans Jain, Khyati Mehta, Gaurav Bandi, Keith Kowalczyk, John Lynch, Sean Collins, Anatoly Dritschilo, Washington, DC

"METHODS: We performed multiple reaction monitoring based targeted metabolomic/lipidomic analyses using baseline (samples obtained before radiation therapy) from the plasma of a cohort of 100 prostate cancer patients."

"Metabolite signatures predictive of adverse responses to radiation therapy were developed in the patient cohort treated with stereotactic body radiation therapy (SBRT) for prostate cancer. Twenty nine patients developed transient, symptomatic urinary flare (USF) or obstructed voiding symptoms (UR) and twenty two patients experienced radiation proctitis (RP) or vascular changes on proctoscopy."

 

[OTN]

Asymptomatic vascular changes on proctoscopy means nothing

 

[ramsesthenice]

As an academic doc, I love this. More than happy to keep patients with their local rad oncs so long as they are a known quantity. I try to reach out when the patient knows their name… but don’t always get a call back. It’s hard to send a patient (back) to a question mark.

I have the good ones (which fortunately is most of the ones in the state) phone numbers programmed in my phone. We communicate very well. I know how they practice and, just as importantly, they know how I practice. Second opinions are usually not about fractionation. None of our community people in my state do SBRT or brachy for prostate. They refer the people who are interested in those to me for a discussion about options and I have spent a long time talking with our community partners about my patient selection preferences for these modalities. That way they are not wasting peoples time for pointless second opinions.

As for fractionation, it sometimes comes up. I do hypofrac (even 60/20) for prostate only. I think I frame it well. Its not better, just faster. So you need to decide, would you rather stay here for a month or drive an hour each way for a month vs driving 20 min each way for 2 months? I would say 80% of the time people (appropriately) opt to go local. I know I would. My favorite things to do day to day are walk my dogs and tend to my gardens. I wouldn't want to give that up for 2 months if I didn't have to, even if I was given free housing. Many of the people in our state are in agriculture. Stepping away during the late summer and fall is a really big deal for them. I don't take that lightly.

I also don't buy the "we can treat complex cases better than community centers" crap. For things like ugly cholangios or pancreatic tumors where we are getting outside the box with dose and MR guidance sure (or really bad GYN tumors where I am going to do a mix of EBRT and brachy boosts). But for most everything else if I am really honest, the new varian they installed at one of the near by centers will give better cone beams for most things than my Versa.

There is only one thing I will criticize some of of our community folks for and that is being overly conservative to the patient detriment. I recently had a case where a guy had a presacral recurrence of a rectal cancer 4 years after undergoing neoadjuvant chemoRT and LAR. They went to the biggest player in our region (ie, not mine) who recommended re-irradiation with 30/15 followed by immediate exenteration with IORT. There is a lot of data supporting palliative or preop RT in the range of 30 Gy after neoadjuvant RT for pelvic recurrences. The local person refused and sent them to me. I called and tried to convince them it was ok to do and even forwarded some papers but they still declined. So the patient had to drive an hour and a half each way for a simple conformal plan

Again, its all about communication. Far and away the biggest advantage at being at the mothership is not the equipment or the user experience. Its having the multidisciplinary care in the same place and being able to come up with and execute a comprehensive plan. I am more than happy to act as a go between with our surgeons and community rad oncs to make sure that everything gets coordinated smoothly.

 

[deleted1111261]

I have the good ones (which fortunately is most of the ones in the state) phone numbers programmed in my phone. We communicate very well. I know how they practice and, just as importantly, they know how I practice. Second opinions are usually not about fractionation. None of our community people in my state do SBRT or brachy for prostate. They refer the people who are interested in those to me for a discussion about options and I have spent a long time talking with our community partners about my patient selection preferences for these modalities. That way they are not wasting peoples time for pointless second opinions.

As for fractionation, it sometimes comes up. I do hypofrac (even 60/20) for prostate only. I think I frame it well. Its not better, just faster. So you need to decide, would you rather stay here for a month or drive an hour each way for a month vs driving 20 min each way for 2 months? I would say 80% of the time people (appropriately) opt to go local. I know I would. My favorite things to do day to day are walk my dogs and tend to my gardens. I wouldn't want to give that up for 2 months if I didn't have to, even if I was given free housing. Many of the people in our state are in agriculture. Stepping away during the late summer and fall is a really big deal for them. I don't take that lightly.

I also don't buy the "we can treat complex cases better than community centers" crap. For things like ugly cholangios or pancreatic tumors where we are getting outside the box with dose and MR guidance sure (or really bad GYN tumors where I am going to do a mix of EBRT and brachy boosts). But for most everything else if I am really honest, the new varian they installed at one of the near by centers will give better cone beams for most things than my Versa.

There is only one thing I will criticize some of of our community folks for and that is being overly conservative to the patient detriment. I recently had a case where a guy had a presacral recurrence of a rectal cancer 4 years after undergoing neoadjuvant chemoRT and LAR. They went to the biggest player in our region (ie, not mine) who recommended re-irradiation with 30/15 followed by immediate exenteration with IORT. There is a lot of data supporting palliative or preop RT in the range of 30 Gy after neoadjuvant RT for pelvic recurrences. The local person refused and sent them to me. I called and tried to convince them it was ok to do and even forwarded some papers but they still declined. So the patient had to drive an hour and a half each way for a simple conformal plan

Again, its all about communication. Far and away the biggest advantage at being at the mothership is not the equipment or the user experience. Its having the multidisciplinary care in the same place and being able to come up with and execute a comprehensive plan. I am more than happy to act as a go between with our surgeons and community rad oncs to make sure that everything gets coordinated smoothly.

This is great to read. Thanks for posting.

There is conservative nature to community practice. I think with the communication as you suggested - you can figure out who can be a good partner for your patients that are far away vs those that may not be as good partners. The equivalent is finding your academic colleagues that will send back routine cases. It is tricky when everyone is on production.

 

[TheWallnerus]

This is great to read. Thanks for posting.

There is conservative nature to community practice. I think with the communication as you suggested - you can figure out who can be a good partner for your patients that are far away vs those that may not be as good partners. The equivalent is finding your academic colleagues that will send back routine cases. It is tricky when everyone is on production.

Yes. The most amazing part of this post is the communicating aspect!