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I’m expecting the fact that it’s a plenary that there will be a OS benefit to FLOT.
Nbc Brooklyn 99 GIF by Brooklyn Nine-Nine
 
Noticed this when trying to figure out who that was tweeting.


In any case, most of my patients have been interested in trying to keep their esophagus.

Seems the only way to get ahead in that town is to be a criminal

He seems to have a way of getting inside information though
 
And even if FLOT does not overperform CROSS, the problem is just around the corner... FLOT+IO has already demonstrated better results (so far only in terms of pCR in the Matterhorn and Keynote585 trials).

So, if:

FLOT = CROSS
&
FLOT + IO > FLOT

Then the medoncs will safely assume that

FLOT+IO > CROSS

Cross used 4140. I know of no one that uses that dose. Maybe it’s more popular overseas?

Doubt this will change much - the same medoncs that hate RT will continue to hate RT.
 
Cross used 4140. I know of no one that uses that dose. Maybe it’s more popular overseas?

Doubt this will change much - the same medoncs that hate RT will continue to hate RT.
Tbh, if we really wanted to go nonoperative we'd combine flot and cross + 9 gy, which I thought was happening somewhere.
 
Ok guys take a seat. We are here to remember our great esteemed friend, the field of GI rad onc. These are our mates, the pancreas, the stomach, the rectum, the esophagus. RIP. AAAAAAAAAMEEEEEEEEN.
 
Ok guys take a seat. We are here to remember our great esteemed friend, the field of GI rad onc. These are our mates, the pancreas, the stomach, the rectum, the esophagus. RIP. AAAAAAAAAMEEEEEEEEN.
Don’t forget Liver where we were never invited to the party and have to crash in from time to time!
 
Cross used 4140. I know of no one that uses that dose. Maybe it’s more popular overseas?

Doubt this will change much - the same medoncs that hate RT will continue to hate RT.
I use it. If anything some papers showed a trend to better outcomes with lower doses. Not sure how boosting tissue that ends up in pathology helps. Almost never see positive margin in ge junction. Plus a pCR denies pt opdivo. My preference is larger fields and lower doses here
 
I use it. If anything some papers showed a trend to better outcomes with lower doses. Not sure how boosting tissue that ends up in pathology helps. Almost never see positive margin in ge junction. Plus a pCR denies pt opdivo. My preference is larger fields and lower doses here
Interesting logic. Try not to get the pCR so they can get immunotherapy?

My hopes are with organ preservation a la SANO. If we can skip the esophagectomy, that's a huge win win win
 
That statement is not one I agree with but it’s also true that the difference between 41.4 and 50.4 has no real bearing in this setting
 
I use it. If anything some papers showed a trend to better outcomes with lower doses. Not sure how boosting tissue that ends up in pathology helps. Almost never see positive margin in ge junction. Plus a pCR denies pt opdivo. My preference is larger fields and lower doses here
I think this is a situation where package time matters like in head and neck.... Just dosepaint 2 a day to involved gtv and get it done in 6 weeks or less. Not sure I buy that 41.4 is enough here, esp where surgery might not happen
 
That statement is not one I agree with but it’s also true that the difference between 41.4 and 50.4 has no real bearing in this setting
I've seen a few centers dose paint the gtvs to 56... That might help. Not sure I buy that 41.4 is worth anything. In the case maybe just do the Walsh 40/15 regimen and get 'er done in 3 weeks.

I'll do 41.4 when I'm forced into by dose constraints on a ridic tumor
 
We are talking about resectable esoohagus cancer here in the context of the forthcoming CROSS vs FLOT data
 
Resectable changes, esp based on how far away you are from a center you trust to do an esophagectomy/LAD and if the pt is marginal

I do 50.4 in practice too, in case they don't go to surgery.

I am speaking more on the interpretation of the trial. If there is a big OS benefit, I don't think there's much of a case to be made that the outcomes would have been different if the dose was 50.4 and not 41.4.

at any rate, we will see the data soon enough.
 
Agree. Kind of unbelievable and there are people supporting the comment!
I actually love Ricky's logic. In my mind, goal of XRT in the context of planned resection is sterilization of microscopic disease with as minimal morbidity as possible. Why do you need a pCR if you're gonna take it out anyway? pCR to chemo is a different story. I'll take that all day, every day.
 
Resectable changes, esp based on how far away you are from a center you trust to do an esophagectomy/LAD and if the pt is marginal
In the rural community you have no idea if the patient is going to get surgery or not. But anybody who thinks 50 gy is a curative dose for GI adenocarcinoma is delusional.
 
I actually love Ricky's logic. In my mind, goal of XRT in the context of planned resection is sterilization of microscopic disease with as minimal morbidity as possible. Why do you need a pCR if you're gonna take it out anyway? pCR to chemo is a different story. I'll take that all day, every day.
It’s been a while since i looked at the study, but i was under the impression that failure to receive opdivo is worse than not achieving a pCR. At my hospital pts always go to surgry
 
41.4 Gy is hard to salvage and palliate… at the time of relapse people would ask at tumor board if you’ve done the right thing.. at least after I’ve given 50.4 Gy I can say yes
 
I actually love Ricky's logic. In my mind, goal of XRT in the context of planned resection is sterilization of microscopic disease with as minimal morbidity as possible. Why do you need a pCR if you're gonna take it out anyway? pCR to chemo is a different story. I'll take that all day, every day.

Because you can’t guarantee they’re going to get it resected. Maybe that’ll happen but often they are not deemed fit by the time it comes to it or they just flat out refuse it.
 
Because you can’t guarantee they’re going to get it resected. Maybe that’ll happen but often they are not deemed fit by the time it comes to it or they just flat out refuse it.
Yeah but this goes back to the point of what’s the benefit over 28 vs 23 fx in the non operative setting? What do those extra 5 fx buy you (besides the obvious extra otv and igrt codes)?
 
Are we fraction shaming esophageal ca now?
Duh, that's what we're best at.

That's why I tell pretentious referrings or patients who spend too much time reading advertisements from MD Anderson that I will try to use the single-fraction regimen from the KAMEHAMEHA trial.

1714389048100.png


If I can't meet constraints, I'll be forced to use 28 fractions.
 
Yeah but this goes back to the point of what’s the benefit over 28 vs 23 fx in the non operative setting? What do those extra 5 fx buy you (besides the obvious extra otv and igrt codes)?
Is there new data suggesting that chemorads is unable to cure esophageal adeno?
 
Is there new data suggesting that chemorads is unable to cure esophageal adeno?
One hint came from the ARTDECO trial (although only 1/3 had an ACC and 2/3 had a SCC)

Dose intesification did not produce more cure in these patients and patients with ACC seemed to perform poorer than those with SCC.



1714391220309.png

This is not "proof" that RT cannot cure ACC.
But the best thing we can do (increase dose in the definitive setting) was unable to enhance results in this trial.

At the end of the day, we may have been doing the wrong trials.
Systemic failure is a main driver of death in ACC, and RT trials should have addressed that. We have not designed a novel package of full dose chemo + RT with the aim of organ preservation (as it was done in rectal cancer, for instance in the OPRA trial).

1.5 months of carboplatin/paclitaxel is simply not enough systemic treatment for a locally advanced ACC of the esophagus.
 
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One hint came from the ARTDECO trial (although only 1/3 had an ACC and 2/3 had a SCC)

Dose intesification did not produce more cure in these patients and patients with ACC seemed to perform poorer than those with SCC.



View attachment 386052
This is not "proof" that RT cannot cure ACC.
But the best thing we can do (increase dose in the definitive setting) was unable to enhance results in this trial.

At the end of the day, we may have been doing the wrong trials.
Systemic failure is a main driver of death in ACC, and RT trials should have addressed that. We have not designed a novel package of full dose chemo + RT with the aim of organ preservation (as it was done in rectal cancer, for instance in the OPRA trial).

1 months of carboplatin/paclitaxel is simply not enough systemic treatment for a locally advanced ACC of the esophagus.
I see 5 yr survivors there. I know some personally. Dose escalation doesn't seem to be effective and maybe that's midwest's point, but there are no data comparing 41.4 to 50.4 in the definitive setting as far as I know. Cross vs the CALGB trial does note a higher path CR rate with 50.4.
 
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I see 5 yr survivors there. I know some personally.
This is unfortunately a bias. I can name you all my GBM 5y-survivors too. I keep forgetting the names of all the ones that are dead.

Dose escalation doesn't seem to be effective and maybe that's midwest's point, but there are no data comparing 41.4 to 50.4 in the definitive setting as far as I know.
Well yes. It would be unethical to treat lower than 50.4 Gy, wouldn't you agree?

Cross vs the CALGB trial does note a higher path CR rate with 50.4.
I am certain that dose has an impact on pCR. But this may not influence PFS/OS in the definitive setting.
It's just not enough systemic chemo. We took CROSS for granted and have been using this for over a decade now in the neoadjuvant setting. What we should have been doing all that time, was to design something more potent. Something to counter FLOT.
Perhaps FOLFOX with RT would have worked nicely.
 
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This is unfortunately a bias. I can name you all my GBM 5y-survivors too. I keep forgetting the names of all the ones that are dead.


Well yes. It would be unethical to treat lower than 50.4 Gy, wouldn't you agree?


I am certain that dose has an impact on pCR. But this may not influence PFS/OS in the definitive setting.
It's just not enough systemic chemo. We took CROSS for granted and have been using this for over a decade now in the neoadjuvant setting. What we should have been doing all that time, was to design something more potent. Something to counter FLOT.
Perhaps FOLFOX with RT would have worked nicely.
Bias? the 5 yr PFS in GBM is 0%. The ARTDECO curve is essentially 50%. And I agree, 41.4 would be unethical, but there's an earlier remark that I'm doing 28 for an extra OTV. I mean CRT isn't great, but 50.4 Gy plus chemo can eradicate it without divine intervention.
 
Bias? the 5 yr PFS in GBM is 0%.
FAKE NEWS! I have a few alive. I suspect our pathologist has deceived us.



Median Follow Up on ARTDECO is 50 months and I should have posted the entire graph. Sorry about that.

1714397863005.png

"At risk" at 5 years are merely 8% of all patients (21/260) with the rest either dead or censored.

I would be cautious to state 5y-survival based on that data.
 
outcomes for esophagus adenoCA definitive chemoRT arent amazing but I would say that offer a chance at definitive cure the same we do in stage III lung. It's not HN, GYN, or anal, but it's not GBM either.

however I totally agree that we will need to rethink strategies from an RT perspective in esophageal cancer. Organ preservation a la rectal with systemic therapy intensification is worth exploring.

CROSS is an old treatment at this point, it should not be that surprising that better chemo is better.

I have more long term stage III lung survivors though to be clear. Esophagus treatment is very humbling.
 
Today I learned that 50 gy of radiation and xeloda can eradicate every cell of adenocarcinoma from your body.
 
Today I learned that 50 gy of radiation and xeloda can eradicate every cell of adenocarcinoma from your body.

im actually on your side mostly but im not sure where youre getting that 0 patients are cured? looking at PFS curves in ARTDECO, it's about 60% free of disease at 3 years for the AdenoCA. even if the 5 year numbers are 25% (stage III lung in PACIFIC is 33% at 5 years PFS for example) that's not zero.
 
im actually on your side mostly but im not sure where youre getting that 0 patients are cured? looking at PFS curves in ARTDECO, it's about 60% free of disease at 3 years for the AdenoCA. even if the 5 year numbers are 25% (stage III lung in PACIFIC is 33% at 5 years PFS for example) that's not zero.
Where is the data comparing 41,4 vs 50,4?

If you don’t have evidence of disease at 3 years but die of metastasic adeno at 5 years are you “cured”?
 
I use it. If anything some papers showed a trend to better outcomes with lower doses. Not sure how boosting tissue that ends up in pathology helps. Almost never see positive margin in ge junction. Plus a pCR denies pt opdivo. My preference is larger fields and lower doses here
Bruh, what??
 
That statement is not one I agree with but it’s also true that the difference between 41.4 and 50.4 has no real bearing in this setting
Data on lack of dose response to pCR?

Today I learned that 50 gy of radiation and xeloda can eradicate every cell of adenocarcinoma from your body.

This is one of the weirdest hills to die on I've seen in recent history.
You don't think 50Gy + Xeloda cures SOME fraction of esophageal adenoCA patients?

We can discuss pros cons of whether surgery is 'mandatory' for esophageal adenoCA (I still recommend it if they are a candidate), but are you calling 50Gy + Xeloda a palliative treatment?

Can't imagine what you would call 60/30 w/ Temodar for GBM then....
 
Data on lack of dose response to pCR?



This is one of the weirdest hills to die on I've seen in recent history.
You don't think 50Gy + Xeloda cures SOME fraction of esophageal adenoCA patients?

We can discuss pros cons of whether surgery is 'mandatory' for esophageal adenoCA (I still recommend it if they are a candidate), but are you calling 50Gy + Xeloda a palliative treatment?

Can't imagine what you would call 60/30 w/ Temodar for GBM then....
I would not ever use the word “cure” in GBM.

I still do 50 Gy for esophageal adeno. But I’m not sure what the benefit is over 41.4. It doesn’t make any sense why there is not a dose response in this disease and everyone knows it.

Chris Crane has basically made his entire career about screaming about what is and is not a definitive BED in GI adeno.
 
Data on lack of dose response to pCR?


@Reaganite nailed it on the last page. I am sure that 50.4 may increase pcR (how much it actually does, not sure. pCR is 50% in CROSS for squams) but regardless, like Reaganite said, pCR means diddly squat when talking about pre-op RT. What really matters is systemic effect. also agree with him that pcr between chemo regimens IS relevant (as it reflects what is happening elsewhere) but ultimately all that matters is PFS and OS.

We will see how big the OS difference is between FLOT and CROSS, but expecting a real difference.
 
You don't think 50Gy + Xeloda cures SOME fraction of esophageal adenoCA patients?
Sure, in cT1 cN0 maybe?

We can discuss pros cons of whether surgery is 'mandatory' for esophageal adenoCA (I still recommend it if they are a candidate), but are you calling 50Gy + Xeloda a palliative treatment?
I call it "pseudo-curative".
Can't imagine what you would call 60/30 w/ Temodar for GBM then....
I call that "definito-palliative".
 
@Reaganite nailed it on the last page. I am sure that 50.4 may increase pcR (how much it actually does, not sure. pCR is 50% in CROSS for squams) but regardless, like Reaganite said, pCR means diddly squat when talking about pre-op RT. What really matters is systemic effect. also agree with him that pcr between chemo regimens IS relevant (as it reflects what is happening elsewhere) but ultimately all that matters is PFS and OS.

We will see how big the OS difference is between FLOT and CROSS, but expecting a real difference.

I wish I could change my screenname lol, but the other question I'd ask is didn't some of the discussion regarding CROSS finally showing a benefit to preop chemo-XRT center around the potential value of dose REDUCTION? Could one ague that going above 41.4 is actually unethical if patient then proceeds on to surgery? (Semi-joking here 🙂 ).I'm mentioning this in reference to the usual argument that patient may not go on to get surgery so you need to go to 50.4.
 
I think the majority of pts with a path cr still fail distantly. Therefore assuming surgery is going to take place, optimal systemic therapy (opdivo) is key here. We have very aggressive surgeons and pts almost always go to surgery. local failure for typical t3n1 pt in the surgerized area is rare imo. Local failures tend to be lymph node stations near the margins of the field and would not be addressed by additional dose to the primary.
 
Another question is at what point is nodal disease “incurable”

I recently was lead into chasing nodes down near into the pelvis.
Do I treat them to 50.4 or 60+? They aren’t coming out at surgery. So any other adeno we are going to boost these nodes as high as bowel tolerance will allow. That’s what I did. But we stop the primary at 50.4? Cause esophageal is special. Ok. Makes zero sense.
 
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