Respectfully, it was the MD regardless. I have worked with some nightmare medoncs.
No. Repeat offender. Couldn’t figure out what to do recently with an MSI high LARC that was totally resectable and didn’t respond to neoadjuvant IO. If only there were 30 years of data on how to manage LARC to fall back on …
First of all, a disclaimer: I do not believe in elective nodal irradiation for pancreatic cancer. I think it adds very little, apart from additional toxicity. I have rarely seen isolated nodal recurrences in pancreatic cancer in patients who have had preoperative treatment. Most recurrences are either distant or at the primary tumor area.
You are correct that the surgeons are the gate keepers on this one. Ours believe, so we do it. Another thing to consider is pointing out to them just how different of a beast preop and post op are because depending on their age and where they trained, they may be most familiar with postop.
Unfortunate. For some people the kool-aid blinds them to what's actually happening to the patient in front of them. If somebody got prostate SBRT and then recurred 6 months later, I wouldn't be recommending additional radiation to them.
Don't forget reducing risk of pancreatic leak/fistula with pre-op RT: https://www.surgjournal.com/article/S0039-6060(24)00055-2/fulltext
No, I meant the way I said. Mid 30s (what they did) is low for SBRT. Combine it with tight margins, and it doesn’t seem to be particularly effective in the preop setting. Dose escalated might be better, but I’m not holding my breath. I’m liking CrT in the preop setting. My point was, non rad oncs don’t care about everything I just said. To many, radiation is radiation. Even if you can point to specific flaws with one particular approach, they don’t care. A negative radiation trial means radiation don’t work. Which is crazy. We don’t point to negative single agent gem trials and say, “well, we tried chemo and it doesn’t work.”
The problem with PREOPANC-2 are the inclusion criteria. They threw everything in one basket. Resectable and borderline resectable.
Im somewhere in between you and Evil on this one. I am with you on the fact that I don't think ENI per say does much if anything in PDAC. Isolated nodal failures after surgery are rare, and the vast majority of failures in non-operative folks are in the primary, the liver, or peritoneum. That said, I think that there is value in treating more than just the GTV with a small margin to try to address perineural tracking towards the vasculature. That is a problem and likely where any benefit from preop radiation is going to come from. I don't personally follow the old nodal atlas guidelines, but I am pretty generous around the primary vasculature (which is easy since it is posterior and midline).
Quite interesting that pCR is also substantially higher with FLOT.
What would you want for yourself or a family member based on this? Survival doubled. That’s insane in oncology.
Median OS doubling exceeds even my expectations. Modest benefit to no diff.
Didn't look at treated population but didn't look like neo-Aegis allowed t1s.
Gastric vs GE-J. I agree XRT is already pretty much dead in gastric CA
The problem is however that we don't have the data to assume this.
Wish I had many of the neurons I sacrificed to learning all this stuff back. Not joking really.
I would want FLOT and this is a game changer but look at the curves and data. Survival is not doubled (regardless of what the median says). Reporting the mOS in this way is classic oversell. What you see overtime is essentially a 7% absolute improvement in survival at most time points. If you look at their assumptions, FLOT actually underperformed…by a lot. They conservatively estimated 3 year survival well into the sixties (and if you read the text closely they site a previous value of 72%). Both arms actually underperformed a decent bit from what was expected. But as they say in the sports world, a win is a win. Doesn’t have to be pretty.
Yep. Pretty much the only ones I treat are the non operative who do well with chemo or the operative patients with poor pathologic responses to FLOT.
Good luck. I commented on this above. Esophagus is pervasively viewed as a surgical disease. It will take extremely impressive results in non operative patients with something to get enough high volume surgeons to participate in OP for EAC. Then there are the CRITICS results suggesting CRT doesn’t add the periop chemo for GEJ or true gastric. I am afraid we got left behind on this one. We will still probably consolidate after chemo for non operative folks at many centers, but we are out of the curative game. The best our “thought leaders” had to offer was photon vs proton. Unless the proton arm magically wallops the FLOT data here (hint, it won’t) that will add nothing of significance.
Well, this sucks, but let’s not over react. This was bungled a long time ago. We ended up in a place of chemo vs RT which was never going to be a fair fight in the long run. Systemic therapy can always be intensified but there is really only so much you can do to intensify radiation, especially in a liminal organ. That’s the lesson here.
For those of us > 60 miles from an esophagectomy center of excellence, maybe it'll change the game for some but not all patients. Moreover, this data is all from a pre IO era.
Indeed, from the prior publication of the trial protocol
You and I are on the same page but a couple points. First, this trial will have the biggest impact on preoperative patients at high volume centers. I agree with palex 100%. These patients will now get shifted to periop FLOT and adjuvant IO just like primary gastric cancers. My center is very reasonable but even there, I am probably only going to see the ones who can’t tolerate FLOT or can’t/wont have surgery. Which, is not a trivial subset of our EAC volume.
We will continue to be marginalized over time. As long as we are purveyors of a single drug, this is as clearly inevitable as almost anything in medicine. Protons are of course not a different drug (despite being marketed as such).
One thing that I think will buy us time is your last point. These are not new drugs. What changed is we have ways of counteracting cytopenias and better antiemetic/diarrheal and other supportive therapies. That is why we are where we are with triplet chemo regimens. However, big pharma has largely abandoned chemo in favor of IO and biologics and personally, I think that’s a missed opportunity. Collectively, improvements with these have largely been incremental for most solid tumors (save for those with specific mutations). There are classes of “dirty” chemotherapeutics that got left behind because of toxicity that could be resurrected and incorporated into chemo backbones. Especially with better systemic delivery options (like ADCs). Fortunately for us (maybe not patients), many were previously patented on discovery and not financially appealing. That was a long winded way of saying I think we could have been left behind faster than we will. Plenty of potent drugs that already exist are not getting attention.
The trial is exceptionally well written, including rationale and surveillance details. My only complaint is the peculiar criteria regarding "proximal extent" of tumor. IMO, if the tumor is involving the anal canal, even a tumor extending more than 15 cm from the verge should be considered. Language here is difficult to interpret.
Ah yes. This is what it is. It stems from disagreements among surgeons about whether w/w is appropriate for patients with extension above the anterior peritoneal reflection (ie, into the "true" colon) with the idea being, early failures may not be anatomically confined and at higher risk of abdominal spread. I have a couple issues with this line of thinking. First, we get the same argument with esophageal and those of us who treat a decent number of unresectable candidates know first hand that local failures which don't immediately blossom into metastatic disease are fairly common. That's my nice way of saying I think its bu****** oncolore. Second, since that is the concern, why use 15 cm? we know endoscopic measurements are not particularly reliable or replicable and that distance from the verge is not a good estimate of the location of the peritoneal reflection. Since basically everyone is getting an MRI for staging, if we need to include this, it should have been anatomically defined IMO. But this is reality. I also had to exclude these patients from my ongoing TNT trials to get surgical buy in...though mine is based on MRI and not endoscopy.
It's impressive how the CROSS group here did so much worse than the actual CROSS study, which was published in 2012 and enrolled patients in the mid 2000s. Worse survival, worse treatment completion rates, in a study that's run 10 years later?
anyone thoughts about that?
Only 67% in the CROSS group seemed to complete neoadjuvant treatment. Way too low for my experience as even very frail patients seem to tolerate 50,4Gy + carbo/tax quite fine....
Also >50% recieved adjuvant treatment in the FLOT group...
CROSS population in the original study were quite fit patients, if you have a look at the demogaphics.
Ideally 100% of the FLOT group would get adjuvant chemo. It was a perioperative approach like in Magic. There is nothing funny going on here. If anything, I am a little surprised that half of the group "finished" post-op chemo. I assume this includes people with significant dose modifications who finished the total number of intended cycles.
anyone thoughts about that?
Only 67% in the CROSS group seemed to complete neoadjuvant treatment. Way too low for my experience as even very frail patients seem to tolerate 50,4Gy + carbo/tax quite fine....
Also >50% recieved adjuvant treatment in the FLOT group...
