ESTRO 2024 abstract. First ORATOR trial also presented, with no sig difference in OS between RT (70 Gy) and TORS (if adj RT 60 Gy). But feel confident the friendly local HNS will ignore these results.
Based on a 61-patient trial? Unlikely.View attachment 385820
ESTRO 2024 abstract. First ORATOR trial also presented, with no sig difference in OS between RT (70 Gy) and TORS (if adj RT 60 Gy). But feel confident the friendly local HNS will ignore these results.
Exactly. it's like telling a uro not to do surgery on very high risk prostate cancer. We need to debulk!Gungho TORS zealots ignored ORATOR and ORATOR-2 so I have to imagine they'll continue to ignore whatever this is. But, agree w/ Neuronix, full link to abstract/presentation would be valuable.
Honestly with some of these honker triple digit cc glands, I think the GUs probably have a better leg to stand on than any of these tors fanaticsExactly. it's like telling a uro not to do surgery on very high risk prostate cancer. We need to debulk!
Based on a 61-patient trial? Unlikely.
This is axiomatic in that at lower sample sizes statistical significance REQUIRES larger effects.but statistical significance at lower sample size is likely MORE clinically significant than statistical significance at huge sample size
We do not know the specifics of the abstract, but I do not think people think there are big differences in OS between TORS and RT.
The "good" thing about TORS is the fact that some patients get away with TORS only (without adjuvant RT) and with a rather favorable functional outcome.
If I was diagnosed with a cT1 (hell, even a cT2!) cN0 SCC of the tonsil tomorrow, and my H&N-surgeon would say he can resect it without the need for a flab reconstruction, I would likely go for TORS.
Link to figure, please? I want to share this with others, but need more details.
This may not change a lot of care patterns in TORS zealots, but should at minimum start discussions at institutions about what % of your patients go on from TORS to have XRT. If that number is > (?30%?) then you've got some selection problems and need to do a better job figuring out which patients likely won't need XRT....because it's clear that if you're going to get XRT either way you have a great chance of local control, so maybe omit the surgery.
I don't practice in a TORS-heavy environment, but I've heard from colleagues in other parts of the country about this being a problem.
The real disaster is when these pt need trimodality because the ENT selected badly. Or they just tell you to skip the chemo for extensive ece because it's p16+ (data free zone afaik)This may not change a lot of care patterns in TORS zealots, but should at minimum start discussions at institutions about what % of your patients go on from TORS to have XRT. If that number is > (?30%?) then you've got some selection problems and need to do a better job figuring out which patients likely won't need XRT....because it's clear that if you're going to get XRT either way you have a great chance of local control, so maybe omit the surgery.
I don't practice in a TORS-heavy environment, but I've heard from colleagues in other parts of the country about this being a problem.
The real disaster is when these pt need trimodality because the ENT selected badly. Or they just tell you to skip the chemo for extensive ece because it's p16+ (data free zone afaik)
I think there's a bit of reality distortion going on. Sometimes they will say, you only need to radiate the neck, tors handled the primary site etcYeah that's what I'm getting at. I would hope the goal of up front TORS would be a chance (should be a realistic, good chance) you don't need adjuvant after that surgery. But if that is your goal, but your institutional rates of needing adjuvant are high, then you're not selecting well.
Going into the plan with plans for adjuvant xrt or chemo XRT is a bad idea. But I've heard from colleagues this is going on out there.
A study's power is determined relative to an anticipated difference in outcomes.A 61 patient trial (if that's what this is and not some retrospective analysis) that sees a statistically significant difference in outcome is appropriately powered to see the large effect present.
Excellent point and the real controversy regarding this trial (not author order). They managed to get ~5000 patients on trial to demonstrate a very small difference in outcomes with a 60% neutropenia rate...this should be discussed more. This may not have even been an ethical trial IMO (will have to think harder about it).(see Riboclib trial in NEJM - statistically signficant improvement, but absolute improvement of < 2%, buoyed by the huge sample size).
It's not just the 2 "on treatment" deaths. Looking at the OS curve there are a few more at later timepoints in the TORS arm, as well as additional PFS events. ORATOR2 had their pre-specified stopping rules, just like most phase II trials. With a highly curable cancer, cannot justify such a decrement in a trial scenario. No one accruing to a trial when you say 6.4% died on treatment. A pharma company would have killed any drug that gave these TORS results.So this is ORATOR-2. We knew ORATOR-2 closed early because TORS was having post-op deaths due to severe bleeding post TORS. This is where the OS difference comes from.
True, but pharma would never run a phase II trial with 60 patients for fear of committing a Type II error.It's not just the 2 "on treatment" deaths. Looking at the OS curve there are a few more at later timepoints in the TORS arm, as well as additional PFS events. ORATOR2 had their pre-specified stopping rules, just like most phase II trials. With a highly curable cancer, cannot justify such a decrement in a trial scenario. No one accruing to a trial when you say 6.4% died on treatment. A pharma company would have killed any drug that gave these TORS results.
Um what? I see a large number of these 30-75 patient phase II pharma trials. Pharma will seed a few varying designs or approaches in different regions/countries. The negative ones are never published or buried in some no name journal. The positive ones? Well they're in NEJM and Lancet these days.True, but pharma would never run a phase II trial with 60 patients for fear of committing a Type II error.
While not a fan of TORS…(and admittedly a fan of elective nodal irradiation in pCa) a small trial like this should be viewed with some skepticism. Do you really think there are 10% excess early deaths with TORS? Some **** luck going on here.
Do those pharma sponsored phase II trials have a comparison arm?Um what? I see a large number of these 30-75 patient phase II pharma trials. Pharma will seed a few varying designs or approaches in different regions/countries. The negative ones are never published or buried in some no name journal. The positive ones? Well they're in NEJM and Lancet these days.
ORATOR1 in same abstract booklet, 68 patients. TORS arm had same ~90% ish 2 year OS. Not great for such a low risk population. And these were relatively large HN centers. Who knows what is happening with TORS in unsupported inexperienced sites? One hospital I worked at, new HNS started a TORS program -- only found out about the trachs, bleeds, and/or deaths bc I wandered into their M&M for the free pizza.
Yeah. 5 sec on clinicaltrials.gov to find an example; here from BMS with a search for nivolumab. 4th trial on list of 52 phase II trials. Most will have early stopping rules just like ORATOR2, which was planned to go to 140 total patients.Do those pharma sponsored phase II trials have a comparison arm?
True, but pharma would never run a phase II trial with 60 patients for fear of committing a Type II error.
While not a fan of TORS…(and admittedly a fan of elective nodal irradiation in pCa) a small trial like this should be viewed with some skepticism. Do you really think there are 10% excess early deaths with TORS? Some **** luck going on here.
You are right, but there is a big difference.Yeah. 5 sec on clinicaltrials.gov to find an example; here from BMS with a search for nivolumab. 4th trial on list of 52 phase II trials. Most will have early stopping rules just like ORATOR2, which was planned to go to 140 total patients.
View attachment 385909
This could change everything. If we have a good reason to believe that surgeons are killing patients with TORs, the outcomes of ORATOR2 become much more believable IMO (you always have to consider all of the data).If vessel ligation isn’t mandatory in the protocol, you be stacking bodies in the morgue with TORS for sure
Institution dependent it sounds like. Curious to see if they were high volume places where those deaths occurred...What the surgeons argue is that the surgical mortality seen in a large multi institutional North American trial like 3311 differ greatly.
My personal belief is that I don’t think the mortality risk is that high. There are other reasons to avoid TORS, mainly the possibility of patients needing trimodality therapy or two local therapies when they don’t need it
It needs to be used in very well selected patients. I agree if I had no nodes and had a T1N0, don’t think TORS would be a bad choice. RT alone to unilateral side decent option too of course.
Pretty much. Title of this thread tongue in cheek. ORATOR2 will not convince any HN surgeon. The "my hands" argument is undefeated.A few years ago at ASTRO, when ORATOR was presented, there was a TORS study out of Mayo right after. They basically stated their outcomes show it is “safe” and a good approach. This sums up the TORS debate.
Used to think ENTs were better than GUs, but nope. You're absolutely right, at least in the large centers. Out in the community, where TORS isn't as prevalent, many of the community ENTs are skeptical too, esp. once they end up seeing the post TORS complications locally when the pts need adjuvant therapyPretty much. Title of this thread tongue in cheek. ORATOR2 will not convince any HN surgeon. The "my hands" argument is undefeated.
But can say one thing for sure... if the curves were reversed, and RT was inferior... this field would never see another definitive RT patient again (unless medically inoperable). There would be no mercy. All the arguments about small samples size, variability, chance alone would go nowhere. So I guess we can be the bigger field and explain away our own success?
I've never seen it done in the community honestly, only at big centers. Probably for good reason. Doesn't mean they select any better, patient wise.In my experience, the community ENTs are the worst on TORS. hack jobs I get sent. sometimes no imaging before TORS, etc.
Pretty much. Title of this thread tongue in cheek. ORATOR2 will not convince any HN surgeon. The "my hands" argument is undefeated.
But can say one thing for sure... if the curves were reversed, and RT was inferior... this field would never see another definitive RT patient again (unless medically inoperable). There would be no mercy. All the arguments about small samples size, variability, chance alone would go nowhere. So I guess we can be the bigger field and explain away our own success?
💯This. We really need to, as a field, develop a spine and start understanding that wringing of our hands when RT is better and trying to bend over backwards for other specialties just because we're at the end of a referral chain with them is a long-term losing play.
RT is the better option as per randomized data. Until there is a RANDOMIZED trial again of TORS vs RT (and I'm not saying I wouldn't enroll patients on it) I'm unclear as to when we should ever be offering TORS to p16+ OPhx patients. Single institution retrospective or single arm prospective ph II trials are useless to me in the face of a ph III trial (which was stopped early due to safety signals).
This. We really need to, as a field, develop a spine and start understanding that wringing of our hands when RT is better and trying to bend over backwards for other specialties just because we're at the end of a referral chain with them is a long-term losing play.
RT is the better option as per randomized data. Until there is a RANDOMIZED trial again of TORS vs RT (and I'm not saying I wouldn't enroll patients on it) I'm unclear as to when we should ever be offering TORS to p16+ OPhx patients. Single institution retrospective or single arm prospective ph II trials are useless to me in the face of a ph III trial (which was stopped early due to safety signals).