ASCO 2023

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It’s better than the German arm

Is anyone using that any more?

TNT or surgery first with lower risk patients.

With TNT you get option of watchful waiting
 
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The way I see it, this trial may indeed have an impact.

It proves that in
a) well selected patients with not advanced tumors (not T4, not N2) and
b) those responding to neoadjuvant chemotherapy

RT can deferred.


What may happen now, is that medoncs will "forget" about a) and say...

We are going to do chemo-first, then "perhaps" RCT, depending on restaging.

This is not the most favorable sequence, as practiced in OPRA, but OPRA was merely a Phase-II.
 
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Members don't see this ad :)
Palex80 said:
The way I see it, this trial may indeed have an impact.

It proves that in
a) well selected patients with not advanced tumors (not T4, not N2) and
b) those responding to neoadjuvant chemotherapy

RT can deferred.


What may happen now, is that medoncs will "forget" about a) and say...

We are going to do chemo-first, then "perhaps" RCT, depending on restaging.

This is not the most favorable sequence, as practiced in OPRA, but OPRA was merely a Phase-II.
Click to expand...
There are very few T4 or N2 rectal cancers.
 
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RickyScott said:
There are very few T4 or N2 rectal cancers.
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Maybe in your neck of the woods, but not ours. N2 is very common.

RealSimulD said:
It’s better than the German arm

Is anyone using this anymore?
Click to expand...

Not really. The 2023 update of NCCN made TNT the preferred approach based on better tolerability and possibly improved survival. The old paradigm is dying out on the US.
RickyScott said:
Folfirinox is even more active than folfox. Even less of a need for xrt.


Click to expand...

Why do you see this as less need for CRT? It was not optional in the trial. Everyone who got FOLFIRINOX also got CRT. In my mind, this is where TNT will be going for high risk patients. We do a fair bit of this and the cCR is not off the charts. Meaning, it doesn’t melt tumors so dramatically we will suddenly treat with chemo only. Still have to do surgery and/or XRT and as we have all seen, in the US, the trend is to cut surgery. I personally don’t see this as a bad thing for us at all. Had the field been moving towards PROSPECT, we would be screwed. Fortunately, that is not how things are moving by and large.

Let’s say the quiet part out loud: watch and wait is a winner for more than just patients. Patients love the idea of not having surgery. Admins love the revenue stream of q4 month endoscopies and pelvic MRIs just as much. The net revenue of regularly scheduled outpatient procedures and imaging totally smokes a single surgery with admission. Do you think AS for prostate cancer would have been pushed and celebrated the way it was if patients just disappeared without a commitment for regular, billable procedures? I don’t.
 
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ramsesthenice said:
Maybe in your neck of the woods, but not ours. N2 is very common.



Not really. The 2023 update of NCCN made TNT the preferred approach based on better tolerability and possibly improved survival. The old paradigm is dying out on the US.

Why do you see this as less need for CRT? It was not optional in the trial. Everyone who got FOLFIRINOX also got CRT. In my mind, this is where TNT will be going for high risk patients. We do a fair bit of this and the cCR is not off the charts. Meaning, it doesn’t melt tumors so dramatically we will suddenly treat with chemo only. Still have to do surgery and/or XRT and as we have all seen, in the US, the trend is to cut surgery. I personally don’t see this as a bad thing for us at all. Had the field been moving towards PROSPECT, we would be screwed. Fortunately, that is not how things are moving by and large.

Let’s say the quiet part out loud: watch and wait is a winner for more than just patients. Patients love the idea of not having surgery. Admins love the revenue stream of q4 month endoscopies and pelvic MRIs just as much. The net revenue of regularly scheduled outpatient procedures and imaging totally smokes a single surgery with admission. Do you think AS for prostate cancer would have been pushed and celebrated the way it was if patients just disappeared without a commitment for regular, billable procedures? I don’t.
Click to expand...
Nailed it. All of it
 
Palex80 said:
The way I see it, this trial may indeed have an impact.

It proves that in
a) well selected patients with not advanced tumors (not T4, not N2) and
b) those responding to neoadjuvant chemotherapy

RT can deferred.


What may happen now, is that medoncs will "forget" about a) and say...

We are going to do chemo-first, then "perhaps" RCT, depending on restaging.

This is not the most favorable sequence, as practiced in OPRA, but OPRA was merely a Phase-II.
Click to expand...

All our colorectal patients are presented at a multi-D tumor board our group runs. It will be very easy to say "neoadjuvant CRT remains the standard of care after PROSPECT due to a doubling of Grade 3 toxicity with the chemotherapy alone arm", as that is the truth. Pushing for an equivalent treatment which is twice as toxic doesn't make sense. I was not expecting this trial to be a win for radiation, but it most certainly is.
 
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OTN said:
All our colorectal patients are presented at a multi-D tumor board our group runs. It will be very easy to say "neoadjuvant CRT remains the standard of care after PROSPECT due to a doubling of Grade 3 toxicity with the chemotherapy alone arm", as that is the truth. Pushing for an equivalent treatment which is twice as toxic doesn't make sense. I was not expecting this trial to be a win for radiation, but it most certainly is.
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But that’s because you’re a thinking person :)

Did you see the Times headline about brutal radiation ?

Folks like me that are not at an institution with a culture of multi D evaluation will see less rectal cancer since our referrals come from Med onc
 
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RealSimulD said:
Folks like me that are not at an institution with a culture of multi D evaluation will see less rectal cancer since our referrals come from Med onc
Click to expand...
This unfortunately is truth. Everything I said about TNT assumes multiD or care driven by surgeons who believe in it.

Even before this was presented I was seeing it first hand. My wife’s uncle had a T4N2 rectal cancer which was “emergently” resected by a general surgeon at a community hospital in central Florida. He’s only seen a med Onc who is giving chemo. Since his CEA responded so well (down to 5.3), he told him he doesn’t need radiation. I talked to they guy. His logic was that RT doesn’t improve survival. I pointed out that the only non TME trial (which is how he was managed) incidentally was the one that did. Jackass then brought up PROSPECT and refused to set up a consultation with a local rad onc. Let’s review: non-oncologic resection, T4N2b tumor. This is malpractice. Unfortunately, my wife’s uncle is going along with it because he’s fixated on getting back to working full time ASAP. For the first time in my life, I told someone (his wife) if she opts to bring forward a malpractice suit when it hits the fan, they can count me in as an expert witness.
 
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ramsesthenice said:
This unfortunately is truth. Everything I said about TNT assumes multiD or care driven by surgeons who believe in it.

Even before this was presented I was seeing it first hand. My wife’s uncle had a T4N2 rectal cancer which was “emergently” resected by a general surgeon at a community hospital in central Florida. He’s only seen a med Onc who is giving chemo. Since his CEA responded so well (down to 5.3), he told him he doesn’t need radiation. I talked to they guy. His logic was that RT doesn’t improve survival. I pointed out that the only non TME trial (which is how he was managed) incidentally was the one that did. Jackass then brought up PROSPECT and refused to set up a consultation with a local rad onc. Let’s review: non-oncologic resection, T4N2b tumor. This is malpractice. Unfortunately, my wife’s uncle is going along with it because he’s fixated on getting back to working full time ASAP. For the first time in my life, I told someone (his wife) if she opts to bring forward a malpractice suit when it hits the fan, they can count me in as an expert witness.
Click to expand...

Oh, I agree that's unfortunately how it's going to go down in lots of places.

The NYT "brutal radiation" quote just adds yet another data point which shows how our academic leaders have completely failed in one of their most important tasks: Convincing the public that we have improved over the decades and can deliver effective cancer treatment without the side effects of days gone by. It's as if nothing has changed, because none of our leaders have been telling anyone that it has.
 
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RealSimulD said:
Did you see the Times headline about brutal radiation ?
Click to expand...
It is a narrative we aren't going to be able to get rid of.

The elimination of XRT in any site is going to be perceived as a win societally. It's actually pretty sad....and not just lay people. Most docs will feel this way. The lymphoma story is our paradigmatic case. ISRT to 20-30Gy has almost no toxicity.

In my fantasies of the end of radonc, there is a big banquet where radonc "leading lights" are lauded by the larger oncology and medical community for their "bravery in the pursuit of the elimination of therapeutic radiation". All of these docs will have secure positions in academia through the remainder of their lifetime. The unwashed masses of recent trainees be damned.

ramsesthenice said:
Since his CEA responded so well (down to 5.3)
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Not the lowest CEA. Is this after surgery? If so, agree this is a recurrence waiting to happen.

MDC very important in this setting. Docs need to understand the limits of our evidence. Emergently resected T4N2 rectal cancers have never been studied in isolation and would not be representative in any trial that we have.
 
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OTN said:
Oh, I agree that's unfortunately how it's going to go down in lots of places.

The NYT "brutal radiation" quote just adds yet another data point which shows how our academic leaders have completely failed in one of their most important tasks: Convincing the public that we have improved over the decades and can deliver effective cancer treatment without the side effects of days gone by. It's as if nothing has changed, because none of our leaders have been telling anyone that it has.
Click to expand...
While NYT has been chasing down those brutal radiation effects, ASTRO was brutally attacking other rad oncs in private practice (Urorads), brutal in preventing rural or solo rad oncs the legal ability to take an hour or a day off work (supervision), brutal in attacking the workforce (hiding behind antitrust and doing fake workforce analyses and membership leaders glutting the market with too many trainees), and brutal in shamelessly supporting protons. Et tu, Brute?
 
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Members don't see this ad :)
Fwiw, I, and presumably others, sent an email in. They at least removed "brutal."
www.nytimes.com

Rectal Cancer Patients Could Be Spared the Effects of Radiation

A large “de-escalation” trial suggests that tens of thousands of people annually may be able to rely on only chemotherapy and surgery to treat their illness.
www.nytimes.com www.nytimes.com
It remains a fraught topic even in onc circles and MDTBs, and truthfully, there's no reason fo the times to even mention it, unless they'd like to title it, "cT2/3 N0/+ rectal cancer patients who are candidates for sphincter-sparing surgery may be eligible for more cycles of chemotherapy in lieu of chemoradiation."
 
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If a one is a scientist interest in the truth and a 'brutal' modality is being eliminated based on a dreaded non-inferiority trial, wouldn't it be nice for all other variables to be identical?

Could we imagine an alternate universe where this trial is framed as 50.4 Gy + Xeloda achieving non-inferior results FOLFOX even though only 63% of patients received Oxaliplatin? Also the duration of Oxaliplatin was shorter. But the medical oncologists and their media promoters sure love their Oxaliplatin.

1685981853173.png


1685981945470.png
 
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Let's call a spade a spade. Europeans for decades have rightfully resisted toxic chemotherapy for T3-4N0 rectal cancer - see Swedish and Dutch trials of RT alone. American medical oncologists (and their academic GI radiation oncology lackeys?) have promoted adjuvant FOLFOX for these patients when the same stage colon cancers largely do not benefit. Glad to see some European skepticism of possible medical oncology overreach.
 
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In other news… Novocure stock (TTF) crashing hard today.

BF02B46F-9B55-49D6-A563-4FC497309A09.jpeg
 
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ramsesthenice said:
This unfortunately is truth. Everything I said about TNT assumes multiD or care driven by surgeons who believe in it.

Even before this was presented I was seeing it first hand. My wife’s uncle had a T4N2 rectal cancer which was “emergently” resected by a general surgeon at a community hospital in central Florida. He’s only seen a med Onc who is giving chemo. Since his CEA responded so well (down to 5.3), he told him he doesn’t need radiation. I talked to they guy. His logic was that RT doesn’t improve survival. I pointed out that the only non TME trial (which is how he was managed) incidentally was the one that did. Jackass then brought up PROSPECT and refused to set up a consultation with a local rad onc. Let’s review: non-oncologic resection, T4N2b tumor. This is malpractice. Unfortunately, my wife’s uncle is going along with it because he’s fixated on getting back to working full time ASAP. For the first time in my life, I told someone (his wife) if she opts to bring forward a malpractice suit when it hits the fan, they can count me in as an expert witness.
Click to expand...

Surgeons are a nightmare to deal with. Just weird personalities.
Palex80 said:
In other news… Novocure stock (TTF) crashing hard today.

View attachment 372683
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wonder why
 
Instant Death Cross in one day. Horrendous negative cash flow. I'm amazed it was going for 80$. Book value is 4 dolla.

GLTA but this seems like a massive short opportunity that keeps on giving.
 
Damn, I took the wrong play on this one. A few months ago, the stock bounced on pending results then tapered down some. I went in and bought up a decent amount of shares hoping it would bounce again but alas here I am. I guess I still won’t be retiring anytime soon.
 
RadOncDoc21 said:
Damn, I took the wrong play on this one. A few months ago, the stock bounced on pending results then tapered down some. I went in and bought up a decent amount of shares hoping it would bounce again but alas here I am. I guess I still won’t be retiring anytime soon.
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And here’s how much my NVIDIA is up since 7/10/17

IMG_2601.jpeg
 
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I really do not understand NOVOCURE. They have a positive Phase III GBM trial. Why couldn't they publish Phase III results on more stuff by now?
They did a single arm Phase II trial for TTF in mesothelioma, that was published in Lancet Oncology back in 2020.
Why couldn't they pull off a phase III trial in mesothelioma by now?
Apparently, they have a big Phase III trial on ovarian cancer, that may report soon. Actually, targetting ovarian cancer (like mesothelioma) makes more sense than NSCLC. Go for a disease that stays local/regional for a long time and will kill the patient due to that progression. Do not go for a metastatic disease, where control of the primary may not be the issue (like NSCLC).
 
Palex80 said:
I really do not understand NOVOCURE. They have a positive Phase III GBM trial. Why couldn't they publish Phase III results on more stuff by now?
They did a single arm Phase II trial for TTF in mesothelioma, that was published in Lancet Oncology back in 2020.
Why couldn't they pull off a phase III trial in mesothelioma by now?
Click to expand...
Why not ph3 in mesothelioma? They’re probably trying asbestos they can
 
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Palex80 said:
I really do not understand NOVOCURE. They have a positive Phase III GBM trial. Why couldn't they publish Phase III results on more stuff by now?
They did a single arm Phase II trial for TTF in mesothelioma, that was published in Lancet Oncology back in 2020.
Why couldn't they pull off a phase III trial in mesothelioma by now?
Apparently, they have a big Phase III trial on ovarian cancer, that may report soon. Actually, targetting ovarian cancer (like mesothelioma) makes more sense than NSCLC. Go for a disease that stays local/regional for a long time and will kill the patient due to that progression. Do not go for a metastatic disease, where control of the primary may not be the issue (like NSCLC).
Click to expand...

You know. Perhaps there's some underlying fraud in the research.
 
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Palex80 said:
I really do not understand NOVOCURE. They have a positive Phase III GBM trial. Why couldn't they publish Phase III results on more stuff by now?
They did a single arm Phase II trial for TTF in mesothelioma, that was published in Lancet Oncology back in 2020.
Why couldn't they pull off a phase III trial in mesothelioma by now?
Apparently, they have a big Phase III trial on ovarian cancer, that may report soon. Actually, targetting ovarian cancer (like mesothelioma) makes more sense than NSCLC. Go for a disease that stays local/regional for a long time and will kill the patient due to that progression. Do not go for a metastatic disease, where control of the primary may not be the issue (like NSCLC).
Click to expand...
Don't you typically start these novel treatments in metastatic patients then work your way up to more localized disease? That's a a pretty common phenomena in chemo/immuno too.
 
salubalu said:
Don't you typically start these novel treatments in metastatic patients then work your way up to more localized disease? That's a a pretty common phenomena in chemo/immuno too.
Click to expand...
Of course you do. But the point is that TTF are a local/regional therapy.
This is not a systemic agent.

Which is why it may work in mesothelioma. Mesothelioma often kills the patients due to local/regional progression, so enhancing control in the thorax may increase survival. The same with ovarian cancer. It generally spreads in the peritoneum, so increasing control there and perhaps avoiding complications like intestinal obstruction may work.
But NSCLC? It spreads to multiple organs. TTFs on your thorax for the NSCLC that has already spread to the liver, bones, brain, will probably not work.
 
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Palex80 said:
Of course you do. But the point is that TTF are a local/regional therapy.
This is not a systemic agent.

Which is why it may work in mesothelioma. Mesothelioma often kills the patients due to local/regional progression, so enhancing control in the thorax may increase survival. The same with ovarian cancer. It generally spreads in the peritoneum, so increasing control there and perhaps avoiding complications like intestinal obstruction may work.
But NSCLC? It spreads to multiple organs. TTFs on your thorax for the NSCLC that has already spread to the liver, bones, brain, will probably not work.
Click to expand...
but it did work...we treat the prostate in low volume metastatic disease with some good data
 
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I just feel like if it was a drug it would have got standing ovations...ie kisqali improves outcomes by 3% and its the rave in the media
 
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sirspamalot said:
TTF: Tumor Treatment Fraud

Stop Motion Smile GIF by LAIKA Studios
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You don't believe the data? Have several multi year survivors on it now who swear by it. I think the problem was that the trial for NSCLC was an old design, mostly compared to people who failed chemo, not io, which is pretty much the standard now
 
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medgator said:
You don't believe the data? Have several multi year survivors on it now who swear by it. I think the problem was that the trial for NSCLC was an old design, mostly compared to people who failed chemo, not io, which is pretty much the standard now
Click to expand...
Yeah, I'm pretty skeptical..
 
Lots of academic radoncs weighing in on PROSPECT on The Bird now. Can someone please explain to me why no one- not a single academic GI radonc - is arguing that this trial supports the use of chemoRT rather than chemo alone? Outcomes were equivalent and the non-RT arm was more toxic: 2x grade 3 and 4x grade 4 toxicity. How is the conclusion "oh, we can now drop that terrible radiation, thank goodness"? How could anyone argue against the chemoRT arm with the data which was presented?

Someone please make it make sense.
 
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OTN said:
Lots of academic radoncs weighing in on PROSPECT on The Bird now. Can someone please explain to me why no one- not a single academic GI radonc - is arguing that this trial supports the use of chemoRT rather than chemo alone? Outcomes were equivalent and the non-RT arm was more toxic: 2x grade 3 and 4x grade 4 toxicity. How is the conclusion "oh, we can now drop that terrible radiation, thank goodness"? How could anyone argue against the chemoRT arm with the data which was presented?

Someone please make it make sense.
Click to expand...
The answer is obvious rt is brutal.
 
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OTN said:
Lots of academic radoncs weighing in on PROSPECT on The Bird now. Can someone please explain to me why no one- not a single academic GI radonc - is arguing that this trial supports the use of chemoRT rather than chemo alone? Outcomes were equivalent and the non-RT arm was more toxic: 2x grade 3 and 4x grade 4 toxicity. How is the conclusion "oh, we can now drop that terrible radiation, thank goodness"? How could anyone argue against the chemoRT arm with the data which was presented?

Someone please make it make sense.
Click to expand...
Do you have the link where they discuss the toxicity differences, already hearing about this from some med oncs.

Nothing listed here

 
OTN said:
Lots of academic radoncs weighing in on PROSPECT on The Bird now. Can someone please explain to me why no one- not a single academic GI radonc - is arguing that this trial supports the use of chemoRT rather than chemo alone? Outcomes were equivalent and the non-RT arm was more toxic: 2x grade 3 and 4x grade 4 toxicity. How is the conclusion "oh, we can now drop that terrible radiation, thank goodness"? How could anyone argue against the chemoRT arm with the data which was presented?

Someone please make it make sense.
Click to expand...
The discussant, a radiation oncologist, actually had a very balanced discussion about the tradeoffs of increased acute toxicity with upfront FOLFOX vs. late toxicity with RT (and outback chemo)
1686095177674.png

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