Erin Gillespie, the mother of all gaslighters, being excited about any topic makes me want to completely ignore it.
I actually thought this was quite innovative and out of the box.
What did you feel was innovative about it
RadOnc is a fascinating anthropological study in this respect. We can't forget that a big draw for students applying into RadOnc is the alleged lifestyle benefits it offers. So for many years now we have attracted some of the best med students who, whether they want to openly admit it or not, don't want to work as hard as a surgeon.
@ramsesthenice stop being so likeable with your reasonable treatment of residents and expansion of RadOnc indications and efficacy
MISSILE was interesting but it had a fatal flaw. It was looking at (or looking for) cancer cells under a microscope 10 weeks after radiotherapy. Seeing a living cancer cell 10 weeks after radiotherapy gives unclear (and more onerously false) information about the ultimate LC probability. Seeing zero cancer cells would admittedly be informative, but the MISSILE saw ~40% patients having viable cancer cells after SBRT at that 10 week mark. A viable cancer cell can easily be non-clonogenic however and have mitotic catastrophe when it attempts cell division some far-flung time after irradiation. If I were designing a MISSLE like study, I would surgerize at 10 weeks, 30 weeks, and 60 weeks. (And I would of course not surgerize anyone obviously failing before the surgerization.) Now one obviously needs to get comfortable with the premise that light microscopy results after radiotherapy correlate 1:1 with clinical results after radiotherapy for this type of exploration to have clinical utility. On second thought, why don't I do something far simpler and just look at patient survival in a randomized trial of SBRT patients and surgerized patients 🙂
Bingo. The time scale of the surgery was so pitifully off the mark. Give the immune system time to remove the cancer cells instead of surgerizing too early and making everyone feel that the SBRT local control is actually 60% and everything else is a fluke. Pathetic.
To be fair to Palma, he said somewhere (probably Twitter IIRC) that he wanted a longer interval but this was the compromise he was able to get with the surgeons. They were pushing for shorter than he wanted.
Accurate Molecular signatures is a great way to get rid of much of radonc.
This is what you get when bargaining with surgeons. I'd rather not run the trial at all if I had to bargain with surgeons. Palma proceeded with running the trial and now everyone will associate him (not the surgeons) with that trial's horrendous design.
Early pathologic endpoints can be tricky. Look at rectal cancer. With TNT the pCR at 8 weeks is 25-30% but cCR approaches 50-60%. If all non pCRs are destined to fail you would expect local control with W/W to be around 50% but it is closer to 75-80%. Seems like those isolated cells may not be relevant...
Intolerable endocrine therapy is much more bothersome to pts, just seems to get swept under the rug though
Sure, but at the end of the day 70-80% of favorable pts don’t need either.
100% agree... This is exactly why we shouldn't have trials with endpoints like MISSILE did. As I mentioned in another post, Merck thought they were being smart doing just that with their golden child Keytruda for neoadjuvant therapy of TNBC. Their attempt for FDA approval in that setting has been stonewalled (for now, at least) because of the questionable value of that endpoint.
This was a phase 2 trial which generates further questions. I thought it did that. Local control was 100%. Pcr 60% is pretty good imo. Surgery alone path cr is 0%. Also a study looked at neoadjuvant chemo which showed a path cr of 8%. Path cr was predictive for survival.
There was a good editorial on the missile study and this was an important point that was brought up.
Yes it does generate further questions...like the surgeons questioning whether SBRT actually works, since their underdeveloped brains are trained like Pavlovian dogs to think that cutting is the only "true" way to kill cancer. Is this really a good look for radonc to other onc specialties? That trial did us a huge disservice to other specialties. We spend a lot of time on this forum talking about trials that "hurt" the use of RT for certain indications. SBRT for early-stage operable NSCLC is shining, and even many surgeons are scared to the point that they refuse to enroll on many of these trials. Then Palma's MISSILE comes out and that missile backfires onto our own specialty and gives the surgeons fodder to use against us. But I'm sure Palma can use it on his CV and for academic promotion at the expense of the perception of our field. Way to go.
Who the heck knows. Yet another reason why the trial was utterly poorly designed. The expected pCR was 90% because they thought that clinical LC = pCR rate. Whoops!
Totally agree, no beef with this statement. If "purism" is to be practiced that's fine. But in practicality and reality there are tons of trials all the time that are never published, especially single-arm nonrandomized studies like MISSILE. I don't think either "the purist" or "the pragmatic" approach is necessarily good or bad - I don't think cookie-cutter generalizations such as "all completed trials should be published" are necessarily true (like nearly all cookie-cutter generalizations), so if there is any trial that's not worth publishing, it's a trial like this, which is a remarkably poorly designed self-immolating dumpster fire.
In this case I think publication is helpful. There are plenty of prospective series showing excellent local control with SBRT alone. These results are helpful in that they inform how not to make pathologic assessments in early stage NSCLC. Educated readers will quickly assume these tumor cells are probably of limited significance. I realize that some surgeons will seize on it to suggest SBRT is an insufficient therapy but they would have to ignore so much data to get there, they almost certainly already felt that way before this publication.
I would not hesitate to say that surgeons would use anything and everything to belittle SBRT and aggrandize their own modality. Hell with logic, reasoning, prior data, etc. In other words ... I think you are giving surgeons too much credit 🤣
I don’t think you can just decide NOT to publish a study because the results were opposite of your hypothesis.
That's not what I am saying. If the results will actively hurt your field/disease site/indication and its perception especially with referring physicians, and it's a single-arm single-center investigator-initiated nonrandomized phase II study that was never designed properly in the first place, then maybe one should be a little more thoughtful about that whole process.
Im going to go out on a limb and say it is not because you asked Mrs. Cleo?There's cooperative group too, but that's got its own issues. At the end of that, they're still NCI funded and NCI still "disapproves" (rejects) plenty of those concepts. Ask me how I know
I'm having a grant reviewed in early March. If I get not discussed, I am coming after you!!!
Maybe Miss Cleo can revive my cooperative group protocol from the dead.
Damn buzz killer!
That trial should never have been approved by the IRB / the competent authorities.
No guarantee that they do that sort of thing well (or even close) 🤣
