Defining intermediate risk nodal volumes in HPV oropharynx

[dieABRdie]

This might be a stupid question but I had two attendings that did two different things so I've been confused and I'd like to see what others think. In particular since I have a patient to treat soon...

The general paradigm I initially learned in defining "intermediate" risk nodal levels would be any involved level as well as the next echelon of nodal drainage. Any levels after that could be considered "low" risk.

For example:
p16 positive, SCC of the right base of tongue which crosses the midline.
One single node in right level II measuring 5.5cm.
No other nodes. The left neck is node negative.

So obviously you would include the primary aspects of the oropharynx and right level II to intermediate doses as they are involved with tumor.
I would typically also consider right level III as intermediate risk because it is next echelon.
But the tumor crosses the midline, and base of tongue is considered a midline structure.... so shouldn't we also treat left level II as intermediate risk? I had one attending I trained with at first that would... but a second attending that would treat the node negative neck to low risk doses (if HPV+).

So how would you risk classify left level II in this case?

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[Bequerel]

Low risk

 

[Neuronix]

Where I trained with fairly prominent head and neck specialists, there was only two dose levels for the vast majority of cases.

1. High risk areas (typically 70 Gy / 35 fx) -- Gross disease and involved nodes with margin
2. Low risk areas (dose paint 56 Gy / 35 fx or 2 phase 46 Gy / 23 fx) -- uninvolved nodal regions or other "at risk" areas without gross disease

Another prominent head and neck doc from another institution once visited as guest lecturer and made fun of the idea of an intermediate dose region.

It's certainly simpler this way, and I post this to basically to tell you not to worry about the intermediate dose volume. Though I think this approach does depend on you trusting your PET/CTs, laryngoscopy, physical exam, etc.

 

[PhotonBomb]

I also would make fun of the idea of an intermediate dose region

It’s very easy. A 70 volume and a 56 volume.

 

[ramsesthenice]

I also would make fun of the idea of an intermediate dose region

It’s very easy. A 70 volume and a 56 volume.

That’s how I was trained as well.

 

[w00tz]

< Team three doses levels here.

To answer OP, I would consider left neck as low risk.

 

[OTN]

Whether or not to use an intermediate-risk dose level is institutionally-dependent, and neither answer appears to be wrong from what I can tell.

 

[Haybrant]

This might be a stupid question but I had two attendings that did two different things so I've been confused and I'd like to see what others think. In particular since I have a patient to treat soon...

The general paradigm I initially learned in defining "intermediate" risk nodal levels would be any involved level as well as the next echelon of nodal drainage. Any levels after that could be considered "low" risk.

For example:
p16 positive, SCC of the right base of tongue which crosses the midline.
One single node in right level II measuring 5.5cm.
No other nodes. The left neck is node negative.

So obviously you would include the primary aspects of the oropharynx and right level II to intermediate doses as they are involved with tumor.
I would typically also consider right level III as intermediate risk because it is next echelon.
But the tumor crosses the midline, and base of tongue is considered a midline structure.... so shouldn't we also treat left level II as intermediate risk? I had one attending I trained with at first that would... but a second attending that would treat the node negative neck to low risk doses (if HPV+).

So how would you risk classify left level II in this case?

There are no nodes in the left neck and you’re going to cover level II as if its involved? You’re kind of in the realm where oncology is magic, it’s not. Take a step back and think about it for a minute, but I hear you when attendings don’t have it clear in their mind it confuses the residents too

 

[radiation]

Good paper from David Palma showing the normal dose gradients you get from a 5 mm PTV actually gives you pretty similar dose levels comparable to intentionally created low risk volumes

Does 5 + 5 Equal Better Radiation Treatment Plans in Head and Neck Cancers? - PubMed

Adding a CTV-P2 structure using the 5 + 5 mm rule had no dosimetric impact, adds contouring time, adds treatment planning complexity, and could potentially introduce errors. The 5 + 5 mm rule may have value in other settings, such as when smaller PTV margins are used, and warrants further...

www.ncbi.nlm.nih.gov

 

[scarbrtj]

FWIW, here's what I do in general. I make an initial plan to ~50/25 to traditional ENI levels, whatever they may be per primary site, and the gross dz (the only hard parameter I have here is keep cord+margin max at ~35 Gy). And, gasp, I just contour what is visible/suspicious and put a 5mm margin around that. Then around ~40Gy I rescan and replan. I will then do either a 20/10 plan or a 21/14 bid plan to the gross disease (and the only hard parameter I have here is keep cord+margin max at ~10 Gy). Even if you have a TPS that doesn't easily sum doses from disparate CT sets, this works. Potential advantages: 1) keeps up with anatomic changes/weight loss/tumor shrinkage that may affect IMRT dose distribution, 2) allows for small volume tx toward end of tx that gives pharynx/throat a "break" that a full ~7 week/single plan/70/56 approach does not. YMMV.

As iffy as "intermediate risk" levels are, this concept has got to be super-iffy in p16+ cases. Unavoidable dose spillover is probably enough to sterilize microscopic p16+ disease. And hasn't someone somewhere even looked at just targeting gross disease only in H&N? I'm not doing that, ever, but I think in chemoIMRT for p16+ disease it is appealing.

 

[evilbooyaa]

For HPV+ I do two dose levels, 70 and 56. This is supported (in my head) by the fact that RTOG 1016 allowed use of 2 dose levels for HPV+ disease and had very good outcomes in the Cis arm.

In your scenario, I would do 70 and 56 given that it is HPV+ as others have said.

For HPV- getting definitive CRT I generally prefer 3 dose levels. I'm not aware of any rationale to suggest that cutting to two dose levels for HPV- OPHx.

However, on a related note, If it was HPV- I would do the following for your case:
70 to GTV + 5mm.
63 to the remainder of the nodal level (R Level II)
For say R level III you could consider 63 but I'd probably favor 56.
L level II definitely gets 56 from me. That's not to say that 63 is malpractice, but it would not be my practice.
Remainder gets 56.


With a 5.5cm node I would look at location within level II. I usually try to spare IB and V but would probably end up covering R IB and V to 56Gy for this patient. Left IB and V definitely gets no radiation dose.

This is all just for the nodal levels. I think use of an lower dose minimum CTV for the primary is important. Again, this would be 56Gy in HPV+ disease. Generally the gross tumor + 5mm (cropped as it's a CTV) + PTV margin (3-5mm) gets a prescription dose of 56Gy.

 

[thaddeus]

FWIW I've seen nodal failures in areas of an ipsi neck in levels adjacent to gross disease that were only taken to 56, even for HPV+. I tend to stick with traditional Nancy Lee-esque volumes and dosing. I personally think we are getting way too cute with how we treat HPV+ disease. Lower your toxicity with precise contours, small PTV expansions with CBCT, and aggressively pushing your dosimetrists to optimize normal structures with your plans, not by skimping on volumes or dose.

 

[medgator]

FWIW I've seen nodal failures in areas of an ipsi neck in levels adjacent to gross disease that were only taken to 56, even for HPV+. I tend to stick with traditional Nancy Lee-esque volumes and dosing. I personally think we are getting way too cute with how we treat HPV+ disease. Lower your toxicity with precise contours, small PTV expansions with CBCT, and aggressively pushing your dosimetrists to optimize normal structures with your plans, not by skimping on volumes or dose.

Well said.

 

[PhotonBomb]

FWIW I've seen nodal failures in areas of an ipsi neck in levels adjacent to gross disease that were only taken to 56, even for HPV+. I tend to stick with traditional Nancy Lee-esque volumes and dosing. I personally think we are getting way too cute with how we treat HPV+ disease. Lower your toxicity with precise contours, small PTV expansions with CBCT, and aggressively pushing your dosimetrists to optimize normal structures with your plans, not by skimping on volumes or dose.

Agree with pushing planners, daily CBCT, and drawing tight volumes. That should be a given.


However your example is silly. We have all had in field failures when stuff has gotten 70 also. biology exists. Your example doesn’t justify an intermediate dose. Microscopic disease is microscopic disease and gross disease is gross disease. Done.

 

[medgator]

.


However your example is silly. We have all had in field failures when stuff has gotten 70 also. biology exists. Your example doesn’t justify an intermediate dose. Microscopic disease is microscopic disease and gross disease is gross disease. Done.

Adjacent lymph nodes don't carry the same risk nodes a couple levels away. Disagree

 

[scarbrtj]

Agree with pushing planners, daily CBCT, and drawing tight volumes. That should be a given.


However your example is silly. We have all had in field failures when stuff has gotten 70 also. biology exists. Your example doesn’t justify an intermediate dose. Microscopic disease is microscopic disease and gross disease is gross disease. Done.

Like all stentorian statements, lacks nuance. One time one guy said "Hey, there may be an 'intermediate step' between microscopic and gross; let's call it 'subclinical.'" Not that I am a proponent of it in H&N, but there is some logic to it. You can find some reports from the 80's and 90's where people found ~60-63Gy doses had better outcomes than 50-54Gy in certain "subclinical" situations. Specifically and Fletcherianally, microscopic (maybe ≤10E6 cells) requiring ~50Gy, gross (≥10E8 cell)s requiring ≥70Gy, subclinical (~10E7 cells) requiring ~60Gy. A subclinical deposit might be a 1mm deposit, undetectable on clinical exam or scan but visible by the pathologist were there an excision; but, bigger than microscopic. There's a classic graphic of this somewhere that I can't put my finger on right now.

 

[PhotonBomb]

yeah there is old MDACC data showing that in the absence of chemo, resected oral cavity patients with positive margins needed a higher dose than 57.6. that's the closest corollary I can think of this is quite different, in the context of chemo as well as a different biology with pharyngeal squams.

regardless, people are free to draw an intermediate volume if they wish. doing it for HPV positive disease seems silly in the context of modern trial data, but whatever.

most important think is drawing tight, small PTV margins, and pushing your planners, I agree.

 

[thaddeus]

Agree with pushing planners, daily CBCT, and drawing tight volumes. That should be a given.


However your example is silly. We have all had in field failures when stuff has gotten 70 also. biology exists. Your example doesn’t justify an intermediate dose. Microscopic disease is microscopic disease and gross disease is gross disease. Done.

Yes of course one can find anecdotal evidence to justify anything, hence my "FWIW" qualification at the beginning. I don't think the example is silly though - there is a big difference biologically between gross disease not responding to the full 70 Gy (which we've all experienced) and a nodal recurrence in an area without initial gross disease that should have been sterilized with your elective dose (which should be rare if we are using correct dosing).

 

[PhotonBomb]

‘there is a big difference biologically between gross disease not responding to the full 70 Gy (which we've all experienced) and a nodal recurrence in an area without initial gross disease that should have been sterilized with your elective dose (which should be rare if we are using correct dosing).’

What? No, these are the same thing. Disease that ‘should’ have responded to the dose it was given for either macroscopic or microscopic dosing and did not respond.

 

[Palex80]

We give to everyone 50/2 for elective and 70/2 for gross disease.
With our without chemo. We don't do any SIBs, we sequentially treat the volumes.
Probably we are giving more than 50/2 to a sizable portion of the elective neck, because some of that 20/2 in the boost phase get's there too, I feel comfortable with that, knowing that it's landing in probably "high-risk" elective areas (areas in the vicinity of the primary or gross nodes).

I do believe that one can deescalate dose in elective volumes lower than 50/2, especially in HPV+ non-smokers and patients getting chemo, but there's not an awful lot of data to back it up.

The Dutch looked at 40/2 for elective nodes and their results were not bad, but the trial was certainly underpowered to prove it.

 

[radiation]

How low can you go? MSKCC went down to 30 gy in selected pts, will be interested to see how data matures

https://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.6076

 

[mavrik13]

Agree with two dose levels. Doesn't make sense to treat a subclinical volume to 63 IMO. However, on rare occasions where there is a visible node that doesn't quite meet size or morphology criteria, but is adjacent, I've done a 63 volume just to the note. Honestly we're probably all splitting hairs - the issue is that the incremental toxicity or disease control benefit is probably so small that you'd need 2000+ patients to see a difference, so until we get that desperate for clinical questions to answer, lets just agree to disagree.

 

[Palex80]

Agree with two dose levels. Doesn't make sense to treat a subclinical volume to 63 IMO. However, on rare occasions where there is a visible node that doesn't quite meet size or morphology criteria, but is adjacent, I've done a 63 volume just to the note. Honestly we're probably all splitting hairs - the issue is that the incremental toxicity or disease control benefit is probably so small that you'd need 2000+ patients to see a difference, so until we get that desperate for clinical questions to answer, lets just agree to disagree.

Absolutely. Patterns of recurrence studies clearly show that the highest risk for recurrence is in the area of the primary tumor and positive. Recurrences in elective levels are rather rare and when seen often in conjuction with a simultaneous recurrence in the primary.

 

[PhotonBomb]

whatever approach you take is fine as long as your feeding tube rate isn't too high (like above 20 percent)

 

[medgator]

whatever approach you take is fine as long as your feeding tube rate isn't too high (like above 20 percent)

Some believe in prophylactic tube placement prior to chemo rt

 

[PhotonBomb]

Some believe in prophylactic tube placement prior to chemo rt

I disagree with some.

 

[medgator]

I disagree with some.

So you'd let a p16- smoker with a large oropharynx tumor proceed on to tx, even if his BMI was 20 and he had underlying tumor dysphagia?

 

[PhotonBomb]

if someone had a feeding tube placed for nutritional support for tumor-related reasons, it would have been before they saw me, usually during diagnosis work-up. It would be a rare scenario that I would put a feeding tube in for someone before starting. In your example, the p16 negative, smoker, large oropharynx, BMI (normal btw) parts wouldn't matter at all. The underlying tumor dysphagia, sure, if they couldn't get food down at all, then yeah, but then that's not a prophylatic tube is it?

 

[medgator]

if someone had a feeding tube placed for nutritional support for tumor-related reasons, it would have been before they saw me, usually during diagnosis work-up. It would be a rare scenario that I would put a feeding tube in for someone before starting. In your example, the p16 negative, smoker, large oropharynx, BMI (normal btw) parts wouldn't matter at all. The underlying tumor dysphagia, sure, if they couldn't get food down at all, then yeah, but then that's not a prophylatic tube is it?

It is to a degree if they are swallowing mostly everything before they start and the BMI is 19.xx. There really isn't data to go one way or another, but I bet you'll see tube rates go up if practitioners get penalized for patients ending up in the hospital for malnutrition/dehydration etc with ocm in the future.

And remember resources can be a lot different out in the real world than an academic center (lack of a dietician/nutritionst etc).

It's interesting that your ENTs will order tubes during the diagnostic w/u, usually they leave that to me and/or med onc

 

[PhotonBomb]

It's interesting that your ENTs will order tubes during the diagnostic w/u, usually they leave that to me and/or med onc

well again this is a pretty rare occurrence, and it's not usually the ENTs. If this happens, it's because someone is hospitalized with dysphagia as their presenting symptom, and during the work-up while in house someone gets a tube in, because they need it for support. Should be rare, but def happens. It's the same with an esophageal patient, avoid it if possible, but some need it because they're totally obstructed.

I think most people these days try to avoid tubes if they can, because data shows worse long-term swallowing outcomes in patients who have a tube in for any significant amount of time.

 

[medgator]

well again this is a pretty rare occurrence, and it's not usually the ENTs. If this happens, it's because someone is hospitalized with dysphagia as their presenting symptom, and during the work-up while in house someone gets a tube in, because they need it for support. Should be rare, but def happens. It's the same with an esophageal patient, avoid it if possible, but some need it because they're totally obstructed.

I think most people these days try to avoid tubes if they can, because data shows worse long-term swallowing outcomes in patients who have a tube in for any significant amount of time.

I get a fair number of patients out in the community where they've already lost several lbs secondary to tumor and have just been getting outpt wu until they see me in the office.

I generally don't try to put tubes in patients that are asymptomatic, and will even defer them in mildly symptomatic ones if they have good social support at home

 

[Palex80]

whatever approach you take is fine as long as your feeding tube rate isn't too high (like above 20 percent)

It depends on:
a) primary's site
b) swallowing function prior to treatment
c) "aggressiveness" on controlling weight loss
d) BMI of patients prior to treatment
e) institutional policy on whether to enter tubes in "prophylactically" or wait until necessity arises

Thus I do not think that you can state what your overall feeding tube rate should be. Radiation therapy is just another factor on that list.

Perhaps the only hard endpoint is long-term feeding tube dependancy, although this too can be influenced by factor b.

 

[evilbooyaa]

FWIW I've seen nodal failures in areas of an ipsi neck in levels adjacent to gross disease that were only taken to 56, even for HPV+. I tend to stick with traditional Nancy Lee-esque volumes and dosing. I personally think we are getting way too cute with how we treat HPV+ disease. Lower your toxicity with precise contours, small PTV expansions with CBCT, and aggressively pushing your dosimetrists to optimize normal structures with your plans, not by skimping on volumes or dose.

Well the local recurrence numbers from 1016 in the Cis arm looked pretty good and they did 70/56.

I really hesitate to use one off examples as a reason to not do something. If 60 to gross disease with cisplatin is 'OK' you're going to be hard pressed to convince me that 56 + cisplatin to microscopic disease is not 'OK'.

Out of curiosity, how many of those patients had < 10 pack year smoking history? I could see an argument being made that those > 10 pack years maybe should get a higher dose of RT for microscopic disease.



In regards to discussion of feeding tubes, I do not routinely place prophylactic feeding tubes. I think part of running a successful patient centered H&N clinic is the capability to get feeding tubes placed within 3 business days, especially if you work near a location (like an academic facility) that offers these services.

I'm not saying that no community place should treat H&N, but if you don't have the institutional support to do this in an expedited manner, this is the first type of patient I would consider referring out to your local large center. Especially if the patient is at high risk of requiring it (separate risks for T1N1 well lateralized tonsil cancer vs a T3N2 HPV- Hypopharynx).