E3311 Results, TORS and reduced postoperative RT dose in Intermediate Risk HPV+ OPC

[fiji128]

In JCO this week.

https://ascopubs.org/doi/abs/10.1200/JCO.21.01752

Basically T1-2 HPV+ OPC SSC resected to negative or <3mm margins, N1-N2 with <1mm ENE or up to 4 positive nodes were randomized to 50 Gy (100 pts) vs 60 Gy (108 pts). 2 year PFS 94.9% with 50 Gy and 96.0% with 60 Gy.

So I guess 50 Gy would be new standard in these patients? Anyone already doing this off protocol?

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[evilbooyaa]

Was published online in October and the discussion already happened on the bird app. Unable to find the discussion now.

Seems like many a H&N Rad Oncs are willing to adopt with this current data for the Arm B and C randomized cohorts.

I think not unreasonable for someone who strictly meets inclusion criteria for the trial - 70% of all patients on trial had smoking history < 10 pack year, although I unable to quickly tease out that broken down by each Arm of the trial.

Therefore, I may be slightly cautious of using 50Gy in a heavy smoker who met Arm B/C criteria (because 30% of 100 is 30 patients per arm), because what they published in their analysis does not tell me what I need to know about whether smoking history is predictive of lower response rate to 50Gy (below is all they write about the role of smoking history):

Those with smoking history (> 10 v ≤ 10 pack-years) did not have a detectably worse 3-year PFS in arms B or C (97%; 90% CI, 92.2 to 100 v 93.9%; 90% CI, 89.1 to 98.9 in arm B; 95.2%; 90% CI, 87.9 to 100 v 92.8%; 90% CI, 87.8 to 98.1 in arm C; 93.1% 90% CI, 85.7 to 100% v 89.6%; 90% CI, 84.0 to 95.5% in arm D).

Given that I am OK treating as per Ph II randomized trials (such as SABR-COMET/Gomez trials), I would be OK recommending 50Gy off trial for someone who met the inclusion criteria AND had < 10 pack year smoking history. Might be more cautious for someone who met inclusion criteria w/ > 10 pack year history.

 

[RadOncMegatron]

In JCO this week.

https://ascopubs.org/doi/abs/10.1200/JCO.21.01752

Basically T1-2 HPV+ OPC SSC resected to negative or <3mm margins, N1-N2 with <1mm ENE or up to 4 positive nodes were randomized to 50 Gy (100 pts) vs 60 Gy (108 pts). 2 year PFS 94.9% with 50 Gy and 96.0% with 60 Gy.

So I guess 50 Gy would be new standard in these patients? Anyone already doing this off protocol?

Just phase II so wouldn't adopt, but I do let my plans be "less hot" without worrying too much, and take a little less coverage for OAR sparing.

 

[seper]

We need many more pts and events to prove non-inferiority, IMO
Post-TORS IMRT is messy. Sticking to 60 Gy for now

 

[temujim]

Was published online in October and the discussion already happened on the bird app. Unable to find the discussion now.

Seems like many a H&N Rad Oncs are willing to adopt with this current data for the Arm B and C randomized cohorts.

I think not unreasonable for someone who strictly meets inclusion criteria for the trial - 70% of all patients on trial had smoking history < 10 pack year, although I unable to quickly tease out that broken down by each Arm of the trial.

Therefore, I may be slightly cautious of using 50Gy in a heavy smoker who met Arm B/C criteria (because 30% of 100 is 30 patients per arm), because what they published in their analysis does not tell me what I need to know about whether smoking history is predictive of lower response rate to 50Gy (below is all they write about the role of smoking history):



Given that I am OK treating as per Ph II randomized trials (such as SABR-COMET/Gomez trials), I would be OK recommending 50Gy off trial for someone who met the inclusion criteria AND had < 10 pack year smoking history. Might be more cautious for someone who met inclusion criteria w/ > 10 pack year history.

Are you good with 60 Gy + cis for low risk definitive? Based on UNC/UF and NRG HN-002. Internal consistency check.

I'm going to wait for a phase III trial -- which honestly will likely never come. In the meantime have reamed out more than one surgeon for telling patients that TORS justifies de-escalation of RT.

 

[Newquagmire]

So I guess 50 Gy would be new standard in these patients?

Didn't the authors specifically state a statistical comparison was not intended?

 

[Radonc90]

For this intermediate group, many people already de-escalate the Tx down to 60Gy + chemo (no surgery) anyway.
The next question is: is 50 Gy + chemo (no surgery) good enough?

Maybe one of these days we settle down to 54 Gy a la anal canal (similar disease, biology)...

 

[Radonc90]

Somewhat related but ORATOR has low accrual, n =34/each arm.
Just reported now on JCO.

Randomized Trial of Radiotherapy Versus Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma:
Long-Term Results of the ORATOR Trial

 

[madchemist89]

I would not de-escalate without a phase iii trial. De-escalation of chemo resulted in decreased survival in multiple trials. De-escalation of rt may reduce survival in a disease with very good outcomes.

 

[medgator]

I would not de-escalate without a phase iii trial. De-escalation of chemo resulted in decreased survival in multiple trials. De-escalation of rt may reduce survival in a disease with very good outcomes.

itll hit the NCCN when it's ready for mainstream implementation.

 

[jondunn]

Yeah I don’t know anyone doing dose deesclalation off trial. I wouldn’t.

 

[fiji128]

I have never done it off trial. But this concept has been around for 15 years plus? Clearly there are patients that would benefit but it never seems to be ready to move from trial to guidelines/prime time.

 

[jondunn]

I have never done it off trial. But this concept has been around for 15 years plus? Clearly there are patients that would benefit but it never seems to be ready to move from trial to guidelines/prime time.

It will be SOC once the phase III of HN-005 reports out.

 

[evilbooyaa]

Are you good with 60 Gy + cis for low risk definitive? Based on UNC/UF and NRG HN-002. Internal consistency check.

I'm going to wait for a phase III trial -- which honestly will likely never come. In the meantime have reamed out more than one surgeon for telling patients that TORS justifies de-escalation of RT.

Fair point - I do mention 60Gy + Cis as an option for true low-risk definitive that would've been eligible for that trial with the lack of smoking history.
See a lot of HPV+ Tonsil, almost none that don't have an invalidating smoking history.
That being said, I don't recommend it because outcomes will be able to be de-escalated safely - 2yr PFS 90% in HN-002 looks similar to the 2-yr outcomes in RTOG 1016, and that's including patients with all risk categories disease. But, it is being evaluated in Ph III form so I generally advocate for the 'standard' arm of that phase III trial off protocol.

If someone sees a Ph III confirmation trial in this space, then OK. I suppose I'm OK with 50 in minimal smoking history patients because Mayo has suggested you can go even lower with their institutional stuff in post-op TORS. Maybe I'm a hypocrite though.

All this being said, I am happy that my frequency of seeing post-op TORS patients is extremely extremely low based on the very reasonable H&N surgery team I work with. Much more reasonable than I have seen at least 2-3 other institutions.

 

[Palex80]

We were discussing the topic of therapy deescalation with a colleague the other day and a very good argument was:
"Why not lower the elective dose first, before lowering the dose to GTV?"

Why not go for 40 Gy when giving Cisplatin in the cN0 parts of the neck?

 

[deleted1111261]

We were discussing the topic of therapy deescalation with a colleague the other day and a very good argument was:
"Why not lower the elective dose first, before lowering the dose to GTV?"

Why not go for 40 Gy when giving Cisplatin in the cN0 parts of the neck?

Sloan does! 30 Gy to elective neck.

 

[temujim]

Fair point - I do mention 60Gy + Cis as an option for true low-risk definitive that would've been eligible for that trial with the lack of smoking history.
See a lot of HPV+ Tonsil, almost none that don't have an invalidating smoking history.
That being said, I don't recommend it because outcomes will be able to be de-escalated safely - 2yr PFS 90% in HN-002 looks similar to the 2-yr outcomes in RTOG 1016, and that's including patients with all risk categories disease. But, it is being evaluated in Ph III form so I generally advocate for the 'standard' arm of that phase III trial off protocol.

If someone sees a Ph III confirmation trial in this space, then OK. I suppose I'm OK with 50 in minimal smoking history patients because Mayo has suggested you can go even lower with their institutional stuff in post-op TORS. Maybe I'm a hypocrite though.

All this being said, I am happy that my frequency of seeing post-op TORS patients is extremely extremely low based on the very reasonable H&N surgery team I work with. Much more reasonable than I have seen at least 2-3 other institutions.

Mayo data powered for toxicity superiority, not equivalence. The 2 year PFS in the lower dose arm was ~85% or so. And absolutely brutal for pN2 or ENE+. There was handwaving about lower risk subgroup, but the equivalency stats on that are even more underpowered.

And I put in fewer PEG tubes with definitive doses than Mayo TORS+60 Gy which is weird.

 

[RSAOaky]

We've been de-escalating to 50 Gy for about a year now in appropriate patients. I have a fairly aggressive ENT group at our academic center and my biggest issue with the approach is patient selection for TORS. I do feel that in poorly selected patients the swallowing/voice dysfunction from surgery is significantly worse than it would have been from definitive dose radiation and I still wind up giving patients a similar degree of long-term xerostomia and taste changes. If a patient has gone through surgery and still need RT I am happy that I can at least give a slightly lower dose (50 Gy vs. 60 Gy), but I think many of these cases would be better served with primary RT or CRT to begin with from a toxicity standpoint.

 

[metallica81788]

We've been de-escalating to 50 Gy for about a year now in appropriate patients. I have a fairly aggressive ENT group at our academic center and my biggest issue with the approach is patient selection for TORS. I do feel that in poorly selected patients the swallowing/voice dysfunction from surgery is significantly worse than it would have been from definitive dose radiation and I still wind up giving patients a similar degree of long-term xerostomia and taste changes. If a patient has gone through surgery and still need RT I am happy that I can at least give a slightly lower dose (50 Gy vs. 60 Gy), but I think many of these cases would be better served with primary RT or CRT to begin with from a toxicity standpoint.

Ding ding ding

The real question is who should be getting TORS - answer is not most people

 

[theradiator]

Ding ding ding

The real question is who should be getting TORS - answer is not most people

Also, why other related specialties seem impervious to randomized data - head and neck surgeons continue to offer TORS despite ORATOR, ProtecT not moving the needle in terms of radical prostatectomy market share, neurosurgeons continuing to treat AVM despite ARUBA just to name 3. Meanwhile, we continue to happily reduce our footprint based on non-inferiority trials. There has to be some sociological explanation of the markedly divergent responses to trial data.

 

[temujim]

Also, why other related specialties seem impervious to randomized data - head and neck surgeons continue to offer TORS despite ORATOR, ProtecT not moving the needle in terms of radical prostatectomy market share, neurosurgeons continuing to treat AVM despite ARUBA just to name 3. Meanwhile, we continue to happily reduce our footprint based on non-inferiority trials. There has to be some sociological explanation of the markedly divergent responses to trial data.

The response of prominent TORS surgeons to ORATOR 1 & 2 is... "don't go to Canada to get TORS". That's a verbatim quote by the way. And then they pivot to ECOG 3311 outcomes. What blows my mind are the rad oncs who back them up and agree with them.

 

[RSAOaky]

The response of prominent TORS surgeons to ORATOR 1 & 2 is... "don't go to Canada to get TORS". That's a verbatim quote by the way. And then they pivot to ECOG 3311 outcomes. What blows my mind are the rad oncs who back them up and agree with them.

Right, the typical response is that "the toxicity at high volume centers isn't nearly as bad as it is reported in this trial." I think my ENT surgeons are absolutely fantastic and I'd put their surgical skills up against anyone in the country, but I think the outcomes that I've seen are pretty on par with what's reported. The patients that do well do exceptionally well, but those that don't have to suffer the cumulative toxicities of bimodality if not trimodality therapy which is a shame.

 

[medgator]

Right, the typical response is that "the toxicity at high volume centers isn't nearly as bad as it is reported in this trial." I think my ENT surgeons are absolutely fantastic and I'd put their surgical skills up against anyone in the country, but I think the outcomes that I've seen are pretty on par with what's reported. The patients that do well do exceptionally well, but those that don't have to suffer the cumulative toxicities of bimodality if not trimodality therapy which is a shame.

Which we invariably get blamed for

 

[DoctwoB]

Also, why other related specialties seem impervious to randomized data - head and neck surgeons continue to offer TORS despite ORATOR, ProtecT not moving the needle in terms of radical prostatectomy market share, neurosurgeons continuing to treat AVM despite ARUBA just to name 3. Meanwhile, we continue to happily reduce our footprint based on non-inferiority trials. There has to be some sociological explanation of the markedly divergent responses to trial data.

Lot of reasons. Obviously for all of us in surgery or rad onc there is the bias of holding a hammer and looking at a nail, both for financial reasons as well as cognitive (we want to believe we are helping people). And I can't speak to the other fields, but there are also a ton of nuances that inform the topline data. In the PROTECT cohort, treatment reduced mets but not survival compared to AS, so survival difference is likely forthcoming. XRT looked better from a toxicity standpoint, but also had a lot higher rate of biochemical progression, to which radoncs will say that modern dosing would fix etc. etc.

It can also be because the toxicity data doesn't match what many of us are seeing with our eyes (I haven't had a RALP patient of mine need a pad or liner after 3 months) while I get consults every week for urologic complications of prostate xrt. So what should I tell patients? Historical prostate data? Big center robot data? My data? A big part of my outcomes is also clearly patient selection, in whom my own outcomes are most representative?

Most of us try to be honest with ourselves and our patients and do what we would recommend for our loved ones.

 

[evilbooyaa]

Lot of reasons. Obviously for all of us in surgery or rad onc there is the bias of holding a hammer and looking at a nail, both for financial reasons as well as cognitive (we want to believe we are helping people). And I can't speak to the other fields, but there are also a ton of nuances that inform the topline data. In the PROTECT cohort, treatment reduced mets but not survival compared to AS, so survival difference is likely forthcoming. XRT looked better from a toxicity standpoint, but also had a lot higher rate of biochemical progression, to which radoncs will say that modern dosing would fix etc. etc.

It can also be because the toxicity data doesn't match what many of us are seeing with our eyes (I haven't had a RALP patient of mine need a pad or liner after 3 months) while I get consults every week for urologic complications of prostate xrt. So what should I tell patients? Historical prostate data? Big center robot data? My data? A big part of my outcomes is also clearly patient selection, in whom my own outcomes are most representative?

Most of us try to be honest with ourselves and our patients and do what we would recommend for our loved ones.

In regards to your second paragraph - you don't know the denominator of folks who have gotten prostate XRT, you only know the numerator. We rely on evidence as oncologists, not anecdotes. You want to track your incontinence rate in your cases and report that to your patients, sure, go ahead. How do you measure their incontinence by the way in F/U? It's very interesting that the IPSS/AUA form, written by urologists, does not mention urinary incontinence.

You want to tell patients that you see consults every week for urologic complciations of prostate XRT, and thus the numbers from national trials are invalid, that's not cool.

I never fault a prostate cancer patient who chooses prostatectomy. They meet the urologist who does the biopsy that confirms the cancer. I fault the urologist who does not offer for the patient meet with a Radiation Oncologist first to discuss alternative options. (Not saying you do that, but clearly this is an issue at the national level). If we can advocate for every prostate cancer patient nationwide to meet both a Urologist and a Radiation Oncologist, patients will be better off.

Similarly, I never fault a P16+ SCC patient who chooses TORS. They meet the ENT who takes them for tonsil biopsy or scopes and finds the mass or whatever. I fault the ENT that does it without multidisciplinary input. Sure, some places probably discuss every single case in MDT, and I'm sure those patients do better (like Mayo's data), but I'm not sure that this is common practice. If we can advocate for every P16+ SCC patient nationwide to meet both an ENT and a Radiation Oncologist, patients will be better off.

In regards to TORS, what we need is a MSKCC style nomogram that predicts their likelihood of ending up as that magical 10% patient cohort from E3311 that didn't need adj. RT.

 

[temujim]

In regards to your second paragraph - you don't know the denominator of folks who have gotten prostate XRT, you only know the numerator. We rely on evidence as oncologists, not anecdotes. You want to track your incontinence rate in your cases and report that to your patients, sure, go ahead. How do you measure their incontinence by the way in F/U? It's very interesting that the IPSS/AUA form, written by urologists, does not mention urinary incontinence.

You want to tell patients that you see consults every week for urologic complciations of prostate XRT, and thus the numbers from national trials are invalid, that's not cool.

I never fault a prostate cancer patient who chooses prostatectomy. They meet the urologist who does the biopsy that confirms the cancer. I fault the urologist who does not offer for the patient meet with a Radiation Oncologist first to discuss alternative options. (Not saying you do that, but clearly this is an issue at the national level). If we can advocate for every prostate cancer patient nationwide to meet both a Urologist and a Radiation Oncologist, patients will be better off.

Similarly, I never fault a P16+ SCC patient who chooses TORS. They meet the ENT who takes them for tonsil biopsy or scopes and finds the mass or whatever. I fault the ENT that does it without multidisciplinary input. Sure, some places probably discuss every single case in MDT, and I'm sure those patients do better (like Mayo's data), but I'm not sure that this is common practice. If we can advocate for every P16+ SCC patient nationwide to meet both an ENT and a Radiation Oncologist, patients will be better off.

In regards to TORS, what we need is a MSKCC style nomogram that predicts their likelihood of ending up as that magical 10% patient cohort from E3311 that didn't need adj. RT.

Even that magical TORS cohort that didn't need RT had worse swallowing than definitive RT in the ORATOR data. Small numbers, but the onus is now on HN surgery to show any different. Using TORS to "de-escalate" toxicity doesn't look like it is panning out.

To your other point, have seen a lawsuit of a patient who underwent surgery and had a CN injury. The claim is they never would have undergone surgery if they had a prior consult with rad onc. Multidisciplinary clinics really are the way forward where possible.

 

[medgator]

Even that magical TORS cohort that didn't need RT had worse swallowing than definitive RT in the ORATOR data. Small numbers, but the onus is now on HN surgery to show any different. Using TORS to "de-escalate" toxicity doesn't look like it is panning out.

To your other point, have seen a lawsuit of a patient who underwent surgery and had a CN injury. The claim is they never would have undergone surgery if they had a prior consult with rad onc. Multidisciplinary clinics really are the way forward where possible.

Wonder if an ED lawsuit has ever happened after a pt got an RP or cryo and wasn't offered RT....