The end of TORS?
Started by temujim
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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.
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Based on a 61-patient trial? Unlikely.
Exactly. it's like telling a uro not to do surgery on very high risk prostate cancer. We need to debulk!
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 fanatics
A 61 patient trial that does not see statistically significant differences in outcome - underpowered.
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. One can talk about fragility of this low of sample size, but statistical significance at lower sample size is likely MORE clinically significant than statistical significance at huge sample size (see Riboclib trial in NEJM - statistically signficant improvement, but absolute improvement of < 2%, buoyed by the huge sample size).
I wonder if it was TORS alone without ability to receive adjuvant RT. We all know TORS alone is insufficient therapy for 90%+ of HPV+ OPhx candidates (based on E3311).
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.
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.
This is axiomatic in that at lower sample sizes statistical significance REQUIRES larger effects.
A TORS arm that perhaps was inappropriately felt to 'not need RT' could have worse PFS and certainly have a difference in salvage capability leading to worse oncologic outcomes.
How many TORS Zealots have said no RT necessary for < 2mm margin, or no chemo necessary for positive margin, in absence of prospective data? Maybe they were prospectively evaluating it now.
But a link with the actual abstract would be of value.
Thanks. This could be a really big deal for some programs, especially if they do not have an oncology trained ENT and/or TORS immediately available.
Ive already shared this around my group.
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.
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.
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I’ve heard horror stories of certain ENTs threatening to stop referring patients if they don’t go along with upfront tors.
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)
Yeah 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.
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 etc
The whole thing is just absurd
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.
ORATOR 2 initial results were published a couple years ago in JAMA onc. The abstract is now with mature FU with enough time to give p values. Its clear it really hasnt changed much as many ENTs have downplayed the excess mortalities on the TORS arm.
jamanetwork.com
Treatment Deescalation With Radiotherapy vs Transoral Surgery for HPV-Associated Oropharyngeal Squamous Cell Carcinoma
This randomized clinical trial examines a primary radiotherapy approach vs a primary transoral surgical approach in treatment deescalation for HPV-related oropharyngeal squamous cell carcinoma.
jamanetwork.com
A study's power is determined relative to an anticipated difference in outcomes.
But even positive small studies are always dubious (Patchell anyone?). I think this is true even though the p-value...or alpha...or likelihood of committing at Type-1 error isn't supposed to scale with sample size. This is a big part of the failure to replicate phenomenon IMO.
The reason is that random stuff impacts small trials more. When we say that our likelihood of rejecting a true null hypothesis is 0.05, what we are really saying is: Assuming that these study populations are truly equivalent, the chance that an observed difference based on intervention is due to random variance of outcomes is only 5%.
But even random populations are more and more variant (in a relative sense) the smaller they are! Randomized, small samples are much more likely to not be truly equivalent from a statistical point of view.
ORATOR 2 is a perfect example (I am not pro TORs BTW).
They literally had to close a trial due to an aggregate number of events (whether post-op death or recurrence) on the order of 3-5 total events. Could easily be rando (or real and representative of an infinite number of TORs cases).
Don't do small trials.
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).
Pharma can game the system this way by having trials that are too big. It's totally the opposite world of radiation oncology.
"The reason is that random stuff impacts small trials more." Amen
Not exactly the same idea but a nice post from Andrew Gelman below
Not exactly the same idea but a nice post from Andrew Gelman below
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.
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.
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.
Do those pharma sponsored phase II trials have a comparison arm?
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.
If vessel ligation isn’t mandatory in the protocol, you be stacking bodies in the morgue with TORS for sure
You are right, but there is a big difference.
The endpoint here (pCr) has much less variance than OS or even PFS over time.
As we know, the correlation between these end points is not always great.
Even radoncs have had success with this sort of endpoint.
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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).
I could be convinced. There has to be some other data on this? Anyone?
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.
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.
Institution dependent it sounds like. Curious to see if they were high volume places where those deaths occurred...
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.
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?
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 therapy
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.
Invariably these patients end up needing post op treatment and the resultant morbidity gets blamed on us for being the last to hold the "hot potato"
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).
💯
I see the issue as being easier if you are outside of a TORS-heavy institution. Referral chain in my practice is ENT ---> ME ---> PET/CT and imaging ---> med onc (for CRT) and gen surg (PEG/port if needed)/dentist/OMFS OR tertiary center (big surgery/whack) followed by f/u with me to determine post-op therapy. I have shared this data with all of my local ENTs, can't remember the last time I saw a post-op TORS case in my neck of the woods.
T1N0 patients are a specific subset. single modality treatment should be the goal.
The horror stories I see are not those patients though. Total hack job surgeries in node positive patients, no imaging before hand, etc.
I think tumor board discussion is super important for HN patients, and that’s more likely to happen in academics than in the community. At least my local ENTs don’t present their cases.
My local academic shop doesn’t do much TORS but they send me patients sometimes and at least the decision making is usually more defensible
This sounds very location dependent
The horror stories I see are not those patients though. Total hack job surgeries in node positive patients, no imaging before hand, etc.
I think tumor board discussion is super important for HN patients, and that’s more likely to happen in academics than in the community. At least my local ENTs don’t present their cases.
My local academic shop doesn’t do much TORS but they send me patients sometimes and at least the decision making is usually more defensible
This sounds very location dependent
It's not all ENTs that are TORS zealots. There are some at major academic institutions that are, however. And that needs to be called out in TB locally or written in the Rad Onc note if at an outside institution (patient underwent TORS by Dr. ENT So-and-so for unclear reasons despite radiographic evidence of ENE in the node that underwent neck dissection, essentially guaranteeing that the patient would need tri-modality treatment as opposed to just chemo + RT which would've had an equivalent chance of oncologic control, and thus the patient is now at increased risk of toxicity due to TORS).
testified in one malpractice case in my entire life. Tors surgeon at major institution removed an oropharyngeal lymphoma without path and patient almost bled out and died and was left with major swallowing issues.
Nobody here needs to be carrying any water for an inferior and more morbid treatment. Take the win.
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