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Let's say the results are real and side effects are less. My issue is what it will do for the cost of healthcare and how are we supposed to give patients the "standard of care" if they can't afford it or can't travel to a proton facility or if insurance just flat out says no? They could just say it's a reasonable alternative for patients but as an option and should not be the preferred treatment.
 
Let's say the results are real and side effects are less. My issue is what it will do for the cost of healthcare and how are we supposed to give patients the "standard of care" if they can't afford it or can't travel to a proton facility or if insurance just flat out says no? They could just say it's a reasonable alternative for patients but as an option and should not be the preferred treatment.
What MDACC and their like will never say, but is undoubtedly true (take a look at the demographics that Palex posted), is that protons are for the rich elite. Either people who are comfortably wealthy with good insurance who can afford to spend a couple of months in Houston or the obscenely rich for whom money is never an object.
 
Let's say the results are real and side effects are less. My issue is what it will do for the cost of healthcare and how are we supposed to give patients the "standard of care" if they can't afford it or can't travel to a proton facility or if insurance just flat out says no? They could just say it's a reasonable alternative for patients but as an option and should not be the preferred treatment.
Just try and offer the protons. Really hype them. Put the patient on a guilt trip to make a proton trip. And then if all that fails, you did the right thing and the burden of feeling like you have mistreated the patient is removed. Let the insurance thing fall on the academic center. (If it’s Medicare, no problemo.) I’m sure if they can’t get protons approved they will send the patient back to you for IMRT.
 
Just try and offer the protons. Really hype them. Put the patient on a guilt trip to make a proton trip. And then if all that fails, you did the right thing and the burden of feeling like you have mistreated the patient is removed. Let the insurance thing fall on the academic center. (If it’s Medicare, no problemo.) I’m sure if they can’t get protons approved they will send the patient back to you for IMRT.
Actually seeing a patient who has a GBM demanding they receive protons. I'm sure we all have had these experiences because they all fed false hopes of a cure with protons and nothing else is acceptable.
 
Just try and offer the protons. Really hype them. Put the patient on a guilt trip to make a proton trip. And then if all that fails, you did the right thing and the burden of feeling like you have mistreated the patient is removed. Let the insurance thing fall on the academic center. (If it’s Medicare, no problemo.) I’m sure if they can’t get protons approved they will send the patient back to you for IMRT.
The centers around here will kidnap my patients even if they were to give IMRT. They use protons as a marketing tool to get them through the door. By the time I see them again, they were already told how much better their Trubeam is compared to mine.
 
A large cancer center just told a patient their right breast radiation was better than mine, so it definitely was worth leaving their hometown and getting a hotel for a few weeks to leave their family with young children. Not even the machine. Just the whole kit n' kaboodle. I would prefer to have been surprised by the news. I am not.
 
A large cancer center just told a patient their right breast radiation was better than mine, so it definitely was worth leaving their hometown and getting a hotel for a few weeks to leave their family with young children. Not even the machine. Just the whole kit n' kaboodle. I would prefer to have been surprised by the news. I am not.
Oh the centers here always get a new set of imaging studies and work up because their radiologists, pathologists, staff, labs and machines are the best!
 
Didnt you hear?? "Local doctors can't keep up"!

A large cancer center just told a patient their right breast radiation was better than mine, so it definitely was worth leaving their hometown and getting a hotel for a few weeks to leave their family with young children. Not even the machine. Just the whole kit n' kaboodle. I would prefer to have been surprised by the news. I am not.
 
I find the trial to be hard to believe too, but are some of you being intentionally obtuse?

The abstracts says "a new standard of care" treatment, not "the new standard of care" treatment. They're not overselling the results in the abstract.
 
Def a fair question to ask and want to avoid piling on. Personally, I would have preferred the below, but maybe we are splitting hairs:

Interpretation
IMPT showed non-inferiority to IMRT for progression-free survival and reduced high-grade toxicity relative to IMRT. Treatment-related and post-progression deaths occurred more frequently with IMRT. IMPT is a standard-of-care treatment option for patients with oropharyngeal cancer.


Theirs:
Interpretation
IMPT showed non-inferiority to IMRT for progression-free survival, improvement in overall survival, similar disease control, and reduced high-grade toxicity relative to IMRT. Treatment-related and post-progression deaths occurred more frequently with IMRT. IMPT is a new standard-of-care treatment option for patients with oropharyngeal cancer.



I find the trial to be hard to believe too, but are some of you being intentionally obtuse?

The abstracts says "a new standard of care" treatment, not "the new standard of care" treatment. They're not overselling the results in the abstract.
 
I find the trial to be hard to believe too, but are some of you being intentionally obtuse?

The abstracts says "a new standard of care" treatment, not "the new standard of care" treatment. They're not overselling the results in the abstract.
I mean we all know what happens next.
 
I mean we all know what happens next.

1765873323976.png


😛 😛 😛
 
Color me skeptical.

Any difference in PFS on that trial is seen after 4 years (curves literally superimposed until then). Yet, progression in OPX cancer occurs within 2 years in 90-95% of patients. OPX cancer almost "never" progresses after 4 years. Yet, there's a flurry of events between 4-5 years in the IMRT group (around the time an interval analysis may be taking place) and after that the groups track exactly together again, never widening over further follow up. Seems........odd.

As-Treated IMRT (171 patients):
raw progression: 14.6% (25/171)
death without progression: 8.1% (14/171)
lost to follow up: 7.0% (12/171)

As-treated IMPT (226 patients)
raw progression: 12.8% (29/226)
death without progression: 5.7% (13/226)
lost to follow up: 2.6% (6/226)

1.8% difference in actual, raw progression. Increased deaths without progression and greater lost to follow-up, points to a less-healthy, less socioeconomically advantaged as-treated IMRT vs IMPT group. Which we always knew.
 
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Color me skeptical.

Any difference in PFS on that trial is seen after 4 years (curves literally superimposed until then). Yet, progression in OPX cancer occurs within 2 years in 90-95% of patients. OPX cancer almost "never" progresses after 4 years. Yet, there's a flurry of events between 4-5 years in the IMRT group (around the time an interval analysis may be taking place) and after that the groups track exactly together again, never widening over further follow up. Seems........odd.
Well keep in mind there are two downward ticking events in PFS curves: progression or death. And protons tended to show survival advantage so PFS separation at longer interval could make sense if protons are less murdery than photons. That said divining much from the way the KM curves dance or don’t is bootless mostly.
 
Well keep in mind there are two downward ticking events in PFS curves: progression or death. And protons tended to show survival advantage so PFS separation at longer interval could make sense if protons are less murdery than photons. That said divining much from the way the KM curves dance or don’t is bootless mostly.
Perhaps the protons are indeed less murdery betwixt the 4 and 5-year mark and then similarly murdery once again. Seems unlikely, but possible.

I think non-inferior to IMRT and "a" standard of care is a very reasonable conclusion.
 
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My gestalt on all the data is that protons and well-planned IMRT are more or less equivalent. More ORN risk with protons, more lymphopenia and salivary changes with IMRT.

My main issue with the recently-published phase III trial is what I would describe as a dramatically unacceptably high rate of PEG use. I've never see close to those numbers in my practice with IMRT. It takes a lot of physician, nursing, and patient work to avoid a PEG, but the data's pretty clear there's a benefit to avoiding it.
 
My gestalt on all the data is that protons and well-planned IMRT are more or less equivalent. More ORN risk with protons, more lymphopenia and salivary changes with IMRT.

My main issue with the recently-published phase III trial is what I would describe as a dramatically unacceptably high rate of PEG use. I've never see close to those numbers in my practice with IMRT. It takes a lot of physician, nursing, and patient work to avoid a PEG, but the data's pretty clear there's a benefit to avoiding it.
100% agree. Working hard to avoid the PEG makes recovery so much better.
 
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Perhaps the protons are indeed less murdery betwixt the 4 and 5-year mark and then similarly murdery once again. Seems unlikely, but possible.

I think non-inferior to IMRT and "a" standard of care is a very reasonable conclusion.
This could happen if the proton patients receive adequate palliative (and sometimes even curative) treatment of the recurrence they experienced at 2 years out of primary treatment. Not necessarily because they had protons, but because perhaps as more wealthy patients had better follow-up, access to more salvage treatments and overall supportive services.

These things kept them alive for a few more years. This of course would mostly make sense in the per-protocol treated patients.
 
This could happen if the proton patients receive adequate palliative (and sometimes even curative) treatment of the recurrence they experienced at 2 years out of primary treatment. Not necessarily because they had protons, but because perhaps as more wealthy patients had better follow-up, access to more salvage treatments and overall supportive services.

These things kept them alive for a few more years. This of course would mostly make sense in the per-protocol treated patients.
The initial recurrence would/should have registered as an event at the time it occurred for PFS for those patients though. They'd have been censored as an event prior to death.

The IMRT patients had higher death without progression (murdery-ness of treatment vs. co-morbid health status), and higher censoring due to lost to follow up which accounts for most (almost all) of the difference seen in PFS. At least, looking at the raw stats.
 
The initial recurrence would/should have registered as an event at the time it occurred for PFS for those patients though. They'd have been censored as an event prior to death.

The IMRT patients had higher death without progression (murdery-ness of treatment vs. co-morbid health status), and higher censoring due to lost to follow up which accounts for most (almost all) of the difference seen in PFS. At least, looking at the raw stats.
Fully correct, I was adressing the dip of the OS, not the PFS curve. The PFS would not mirror that.

Perhaps it‘s also other things that temd to be picked up in more wealthy and better cared-for patients, besides recurrences. A second primary, cardiovascular disease, whatever.
 
As-Treated IMRT (171 patients):
raw progression: 14.6% (25/171)
death without progression: 8.1% (14/171)
lost to follow up: 7.0% (12/171)

As-treated IMPT (226 patients)
raw progression: 12.8% (29/226)
death without progression: 5.7% (13/226)
lost to follow up: 2.6% (6/226)
This is all missing the exceedingly important element of temporality. The raw can be very much different than the actuarial, and can even be flipped one versus the other. (And lost to follow up when? Day 0? Day 1000? Either way they’re censors; this is normal.)
They'd have been censored as an event prior to death.
??? That needs to be better explained


I don’t have access to the actual paper. Please don’t make me get it 🙂
 
Fully correct, I was adressing the dip of the OS, not the PFS curve. The PFS would not mirror that.

Perhaps it‘s also other things that temd to be picked up in more wealthy and better cared-for patients, besides recurrences. A second primary, cardiovascular disease, whatever.
Gotcha. Agree with you as well. We were talking about 2 different things, lol.
 
This is all missing the exceedingly important element of temporality. The raw can be very much different than the actuarial, and can even be flipped one versus the other. (And lost to follow up when? Day 0? Day 1000? Either way they’re censors; this is normal.)

??? That needs to be better explained


I don’t have access to the actual paper. Please don’t make me get it 🙂
I understand all of the above and agree. I don't have access to the temporal data. But we can "assume" some elements of temporality from historic observational trials that show 95% of oropharyngeal recurrences occur within 24 months, and almost 0% occur after 48 months.

Unless this cohort was (literally) historically unique, the events between 48-60 months that form the basis of the entire difference between the PFS curves were likely deaths without progression. Could be related to murdery-ness of treatments or patient specific issues. Given patients were essentially allowed to pick their treatment after randomization, my guess would be the latter.
 
what proportion of these patients had HPV mediated disease? The 5 yr OS would suggest essentially all right? (I can't access the full pub)
About 52% never smokers, 42% had quit smoking, 8% smokers. 95% HPV positive. 76% ECOG 0.

I wish those were my average oropharyngeal cancer patients, too...
 
About 52% never smokers, 42% had quit smoking, 8% smokers. 95% HPV positive. 76% ECOG 0.

I wish those were my average oropharyngeal cancer patients, too...
Could explain feeding tube rates. I'm cool with my grizzled old population. They tank far less frequently than the young healthy guys.
 
Another question popped up, maybe a silly one, I am not familiar with how this works out in the US.

From the manuscript
Radiation target volumes were delineated by the treating radiation oncologist before randomisation.
...
Patients were treated in their assigned group except in two scenarios: patients assigned to receive IMPT were denied insurance and therefore crossed over to the IMRT group; or patients assigned to receive IMRT were approved for IMPT insurance, refused randomisation to the IMRT group, and crossed over to the IMPT group. The treating physicians had no role in crossover consideration.


How does this work out?

a) Did they ask for insurance coverage BEFORE randomizing the patients?
If so, what's the point of randomizing a patient, if you know IMPT was denied (likely the result was there in some patients prior to planned randomization)?

b) Did they ask for insurance coverage AFTER randomizing the patients?
If so, how old were the contours when they started treatment?
 
Could explain feeding tube rates. I'm cool with my grizzled old population. They tank far less frequently than the young healthy guys.

I find the "guidelines" for feeding tube placement rather vague. Do they mean 5% weight loss from baseline?

Guidelines for feeding tube placement/removal: Consideration of feeding tube insertionsshould occur at 5% weight loss, with recommended tube insertions at 10% body weightloss. The removal of a feeding tube can occur when patient does not use the feeding tubefor 3 weeks.
 
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