Familiar theme?

This forum made possible through the generous support of SDN members, donors, and sponsors. Thank you.
The trial that showed a 14% path cr rate with cross regimen which is less than half the expected path cr rate based on almost every modern neoadj crt regimen

Original cross trial showed 28% path cr rate and rates with 50.4 gy probably closer to 35%

Major red flag to this trial
 
RickyScott said:
Click to expand...
Curious to know how this has impacted people’s practice. I have been surprised how thoughtful many academic med oncs and surgeons have been with this study. The notion that toxicity is comparable between FLOT and CROSS is definitely not widely accepted. The FLOT group fell very short of the projected outcomes, compliances with carbo/tax was bad, and pathologic responses to CRT were inexplicably low. The general interpretation for many has been that FLOT could be a little better but it’s toxic and they are still being selective who they think can really tolerate it. My esophageal volume has definitely not decreased yet.

Don’t get me wrong. I know there are chemo zealots out there and I feel for the people who have to deal with concrete thinking. But this trial has issues that affect its interpretation.
 
RadRadRad said:
The trial that showed a 14% path cr rate with cross regimen which is less than half the expected path cr rate based on almost every modern neoadj crt regimen

Original cross trial showed 28% path cr rate and rates with 50.4 gy probably closer to 35%

Major red flag to this trial
Click to expand...

I disagree. the results are the results. I don't think this matters at all (the pCR rate).

If it was me I would want FLOT. esophageal cancer is systemic. need something way stronger than weekly carbo/taxol.

If I was older and frail, then no, I would take CROSS.

more interested in future of FLOT --> chemoRT as an option for organ preservation.
 
Now all I get are palliative cases.
Another year another loss esp in GI
Do GI radoncs even exist at this point? have they all given up and essentially agree the modality has no role in this space?

Nonoperative? Maybe if there are even still RT centers around to do it at that time
 
Last edited:
drowsy12 said:
I disagree. the results are the results. I don't think this matters at all (the pCR rate).

If it was me I would want FLOT. esophageal cancer is systemic. need something way stronger than weekly carbo/taxol.

If I was older and frail, then no, I would take CROSS.

more interested in future of FLOT --> chemoRT as an option for organ preservation.
Click to expand...

When a trial is done that has results that don’t align with any other major trial you are not concerned? We know path cr corresponds to improved outcomes. If the path cr is inexplicably low one could reasonably conclude the pfs and os are lower than they should be too. This trial is huge outlier from path cr standpoint

I agree with you that the concept of more chemo makes sense for this disease. Just suspect there is something flawed in methodology or quality control of radiation in this trial
 
I think FLOT is best for adenoca of the esophagus, but it is toxic. I've treated a few patients since the trial came out who the medoncs appropriately were concerned couldn't make it through FLOT or might not make it through surgery, so we've done CROSS. I did have a patient who I thought was appropriate for FLOT rather than CROSS, so I sent back to the medonc and they agreed. For squamous cell we continue to do CROSS.

As far as the rest of GI, I haven't seen any ground lost in rectal whatsoever and continue to treat plenty of anal cancer. Neither of those are going away soon. If I were a GI radonc I would be pushing VERY aggressively into liver. Our data there is better than IR's data, but we need strong radonc voices to move the needle.
 
RickyScott said:
Click to expand...

Once actual physician gestalts and behaviors (of rad oncs and med oncs and surgeons) begin to more closely correlate with ever-releasing, ever-growing data—and not just for esophageal but in some other disease sites too—the incidence of radiotherapy will decrease in oncology. Or maybe to paraphrase/mangle Max Planck, the incidence of radiotherapy in oncology will decrease as med oncs and rad oncs who were practicing in the 2000s and 2010s die.

1737646414213.jpeg
 
RadRadRad said:
The trial that showed a 14% path cr rate with cross regimen which is less than half the expected path cr rate based on almost every modern neoadj crt regimen

Original cross trial showed 28% path cr rate and rates with 50.4 gy probably closer to 35%

Major red flag to this trial
Click to expand...
This may have several underlying factors. First, the data:

ESOPEC, all adenocarcinoma
>75% cT3, 6% T4
>75% cN+
pCR-RCT: 10.1%, pCR-CT: 16.7%

CROSS, 75% adenocarcinoma, 23% SCC
80% cT3, 0% T4
65% cN+
pCR adenocarcinoma: 23%, pCR SCC: 49%

Possible issues:
1. Patient selection. Perhaps more advanced disease in ESOPEC.
2. Different pathologists. ESOPEC featured a central pathology review, although this is surprisingly not noted in the manuscript. CROSS did not.
3. Treatment adherence. Around 10% in ESOPEC skipped neoadjuvant treatment, but they are included in the analysis. Patients who withdrew consent in CROSS were excluded from the analysis.
 
drowsy12 said:
I disagree. the results are the results. I don't think this matters at all (the pCR rate).

If it was me I would want FLOT. esophageal cancer is systemic. need something way stronger than weekly carbo/taxol.

If I was older and frail, then no, I would take CROSS.

more interested in future of FLOT --> chemoRT as an option for organ preservation.
Click to expand...

Local recurrence is a major issue
 
lilshopta said:
We need a trial looking at FLOT --> +/- RT Alone (ie. 40/15 fx) --> Surgery. This seems like the best way to maximize distant and locoregional control.
Click to expand...
Conceptually I agree but I wouldn't hold my breath. In gastroesophageal, we already have negative trials in TOPGEAR and CRITICS. Granted, these used chemo which was probably not as good as FLOT. But this contrasts greatly with say, rectal cancer. In every rectal TNT trial completed, there was nothing ambiguous about the results. Complete response rates are roughtly doubled with TNT compared to either modality alone. That does not appear to be the case in gastroesophageal tumors for unclear reasons.
 
Palex80 said:
Local recurrences: 17/221 (FLOT) vs. 9/217 (CROSS)

That's a 3% absolute benefit in terms of less local recurrences with CROSS.
Is it worth it? Likely not.
Click to expand...
A few major trials, including this one and RAPIDO, have made me think that when we try to get into the detail of local vs regional vs distant failure, we end up making too much of random chance. In both cases, the arm with substantially better local and survival outcomes had inferior local control. How do you explain that? Its not impossible, but it requires a lot of handwaving.

Even if you are a hardcore chemo zealot, this trial is a disappointment. Take the concerns out and grant that it offers a relatively small survival advantage over CROSS. It was supposed to be unequivocally better and not only change which treatment patients got, but realistically change their survival expectations. Recall, the projected 3 year OS was 72% with FLOT. Based on PRODIGE with pancreas, it sure seemed possible going from doublet to triplet could do it. Instead, we got a treatment that is pretty hard to get through with survival outcomes that are indistinguishable from those achieved in prior studies. Patients can still expect about a 50/50 chance of living more than 3-5 years. That's a set back for all of us.
 
Based on PRODIGE with pancreas, it sure seemed possible going from doublet to triplet could do it. Instead, we got a treatment that is pretty hard to get through with survival outcomes that are indistinguishable from those achieved in prior studies. Patients can still expect about a 50/50 chance of living more than 3-5 years. That's a set back for all of us.
Click to expand...
IO on top of chemo may enhance results, but so far it doesn't look like it's gonna add a lot
 
lack of adjuvant immunotherapy for the 85% of patients with residual disease in cross arm also makes this trial hard to interpret. Lack of immuno in either arm may be an issue
Immuno benefit in checkmate 577 > immuno benefit in keynote 585 (flot subset)???
Maybe bc some squam in checkmate ?
Or maybe immuno has more benefit in weaker chemo regimen
 
ramsesthenice said:
A few major trials, including this one and RAPIDO, have made me think that when we try to get into the detail of local vs regional vs distant failure, we end up making too much of random chance. In both cases, the arm with substantially better local and survival outcomes had inferior local control. How do you explain that? Its not impossible, but it requires a lot of handwaving.

Even if you are a hardcore chemo zealot, this trial is a disappointment. Take the concerns out and grant that it offers a relatively small survival advantage over CROSS. It was supposed to be unequivocally better and not only change which treatment patients got, but realistically change their survival expectations. Recall, the projected 3 year OS was 72% with FLOT. Based on PRODIGE with pancreas, it sure seemed possible going from doublet to triplet could do it. Instead, we got a treatment that is pretty hard to get through with survival outcomes that are indistinguishable from those achieved in prior studies. Patients can still expect about a 50/50 chance of living more than 3-5 years. That's a set back for all of us.
Click to expand...

A 7 percent OS difference is a big deal, all things considered. We give chemo in head and neck cancer for 5 percent Os benefit
 
1737673471523.png


Lets take this back to Fisher - "Variations in local-regional therapy are unlikely to substantially affect survival". Why do all this radical surgery if systemic disease is the main driver of mortality and locoregional failure rates still quite high with preop chemo/surgery. If it were me I would get FLOT then some pseudo-palliative RT for QOL and keep my esophagus.
 
Honestly happy to get rid of eso. Saw a fair amount of "regional" nodal recurrences over the years especially things like distal eso recurring in SCLAV, cervical recurring in gastrohepatic, etc. I'm not sure there was ever a consensus on appropriate fields. Always felt like a systemic-ish disease to me.
 
You must log in or register to reply here.
Top