Another Unknown Primary Head and Neck Case

[communitydoc13]

71 year old with smoking hx, TxpN2b with 2 level II nodes without ECE (largest node 3.5 cm). s/p ipsilateral neck dissection to negative margins. p16/.HPV/ EBV all negative. Good performance status.

Recs are all over the place. Ipsilateral IB-V is a given for me.

Any thoughts on contralateral neck (would be II--IV)?, probably minimal toxicity and will likely do

Any thoughts on treating mucosa? This is the big question for me. oropharynx usual culprit but with true HPV/p16 negativity, I'm thinking combined risk to larynx/hypopharynx probably equivalent. On fence about treating ispilateral tonsil plus b/l BOT and larynx/hypophaynx to 50 Gy or not treating mucosa at all.

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[thecarbonionangle]

you could treat ipsi neck and observe assuming pan endoscopies and bx and pet are negative.

alternatively you could treat bilateral neck, nasopharynx, oropharynx and omit oral cavity and larynx/hypopharynx with close surveillance/scopes

 

[FrostyHammer]

71 year old with smoking hx, TxpN2b with 2 level II nodes without ECE (largest node 3.5 cm). s/p ipsilateral neck dissection to negative margins. p16/.HPV/ EBV all negative. Good performance status.

Recs are all over the place. Ipsilateral IB-V is a given for me.

Any thoughts on contralateral neck (would be II--IV)?, probably minimal toxicity and will likely do

Any thoughts on treating mucosa? This is the big question for me. oropharynx usual culprit but with true HPV/p16 negativity, I'm thinking combined risk to larynx/hypopharynx probably equivalent. On fence about treating ispilateral tonsil plus b/l BOT and larynx/hypophaynx to 50 Gy or not treating mucosa at all.

- If it's HPV, p16, and EBV negative then I'd guess OC or larynx are statistically the most likely, more than OPX, but I've seen a decent number of hypopharynx cases exactly like this, those suckers tend to hide nicely in the primary area and spread a lot to nodes. Usually skin is less likely in these smokers.

- I'd say that if you have a very good quality ENT to scope out the hypopharynx specifically and get blind biopsies, that's great, if not it might be worth sending him to a large volume center for this purpose.

- I would either treat bilateral neck only or bilateral neck plus larynx and hypopharynx. One can make arguments either way, and my 2 cents won't change anything. NPX and OPX are overkill IMHO because of the HPV/p16/EBV results. But you might want to be very careful about not aggressively covering high level II and high RPs in case this turns out to be OC or OPX and you need to re-treat the abutting area which is right there. In other words, assume you'll need to re-treat either the OC or OPX alone or the HPX/larynx if you're not covering them now and design the plan accordingly.

- The toughest part is to cover contra IB or not. If it's OC you'd definitely do it, but covering it would burn bridges if the primary reveals itself to be in the OC in the future and you're re-treating. I don't have a good answer for the contra IB issue provided that OC won't be covered.

- Overall I'd say treat the mucosa areas the inverse of how comfortable you are with re-treating.

- I'd do 35 fraction SIB with 70 to gross disease, 63 to involved ipsi levels, and 50-56 to contra neck, higher for level II and maybe III, lower to the remainder. Mucosal sites if being treated...tough one. 54 at minimum, 60-63 at maximum. Dose to each subsite should depend on your and ENT's clinical suspicion of how likely the primary is which sub site.

 

[evilbooyaa]

For HPV- would not treat Oropharynx alone. Would probably skip Nasophx in setting of EBV-. Would not treat OC electively. I think ~60Gy to larynx/hypopharynx/ipsi tonsil + BoT is probably sufficient.

I think need for contralateral neck RT is probably controversial, as would be whether one still needs to cover mucosal sites. However, nCCN still recommends it, so would keep it simple. Could be a case where discussion with patient is warranted, ranging from observation to the full gamut

 

[evilbooyaa]

- If it's HPV, p16, and EBV negative then I'd guess OC or larynx are statistically the most likely, but I've seen a decent number of hypopharynx cases exactly like this, those suckers tend to hide nicely in the primary area and spread a lot to nodes. Usually skin is less likely in these smokers.

- I'd say that if you have a very good quality ENT to scope out the hypopharynx specifically and get blind biopsies, that's great, if not it might be worth sending him to a large volume center for this purpose.

- I would either treat bilateral neck only or bilateral neck plus larynx and hypopharynx. One can make arguments either way, and my 2 cents won't change anything. NPX and OPX are overkill IMHO because of the HPV/p16/EBV results. But you might want to be very careful about not aggressively covering high level II and high RPs in case this turns out to be OC and you need to re-treat the abutting area which is right there. In other words, assume you'll need to re-treat either the OC alone or the HPX/larynx if you're not covering them now and design the plan accordingly.

- The toughest part is to cover contra IB or not. If it's OC you'd definitely do it, but covering it would burn bridges if the primary reveals itself to be in the OC in the future and you're re-treating. I don't have a good answer for the contra IB issue provided that OC won't be covered.

- I'd do 35 fraction SIB with 70 to gross disease, 63 to involved ipsi levels, and 50-56 to contra neck, higher for level II and maybe III, lower to the remainder. Mucosal sites if being treated...tough one. 54 at minimum, 60-63 at maximum. Dose to each subsite should depend on your and ENT's clinical suspicion of how likely the primary is which sub site.

A few points for educational purposes:

1) Can still get a HPV- Ophx cancer in a person with smoking history. HPV- doesn't allow you to spare the Ophx in CUP. It's that if it is HPV+ (especially with minimal smoking history) you can focus on just the OPhx.

2) Electively treating OC to 60 or even 50Gy is much more toxic than treating hypophx/larynx to same doses. If this was a level IB LN I may agree with you.

3) Would not be a fan of contra IB in this clinical scenario.

 

[FrostyHammer]

A few points for educational purposes:

1) Can still get a HPV- Ophx cancer in a person with smoking history. HPV- doesn't allow you to spare the Ophx in CUP. It's that if it is HPV+ (especially with minimal smoking history) you can focus on just the OPhx.

2) Electively treating OC to 60 or even 50Gy is much more toxic than treating hypophx/larynx to same doses. If this was a level IB LN I may agree with you.

3) Would not be a fan of contra IB in this clinical scenario.

Yes, I was just editing my statement to address OPX just now. It's still probably statistically less likely than OC, larynx. Agree with elective OC, it all depends how comfortable one is with re-treating. It all comes at a price. I'm not sold on either option.
#3 - want to share why you feel so strongly? Arguments either way.

 

[communitydoc13]

Great answers. I was going to skip Nasopharynx anyway as EBV negative and demography just makes not very likely and not treating OC electively under any circumstances.

 

[Ray D. Ayshun]

Any thoughts on the biology of HPV- CUP? I can come up with a basis, to some degree, for a CUP with a viral etiology, I have more trouble coming up with an explanation for an HPV-, smoking related upper aerodigestive tract cancer that has a big node and no primary. Cutaneous SCC is different.

 

[Palex80]

When are we ever going to carry out a randomized trial on H&N CUP randomizing patients to something like:
- observation vs. RT of affected areas in low risk patients
- RT of ipsilateral neck vs. RT of bilateral neck + mucosa in high risk patients

"Risk" defined by number, size of nodes and ECE.

 

[Palex80]

Any thoughts on the biology of HPV- CUP? I can come up with a basis, to some degree, for a CUP with a viral etiology, I have more trouble coming up with an explanation for an HPV-, smoking related upper aerodigestive tract cancer that has a big node and no primary. Cutaneous SCC is different.

I am not sure what you mean by that. I have seen a few HPV- SCC CUPs in smokers. Yes, they do tend to behave more aggressively.

 

[Ray D. Ayshun]

I am not sure what you mean by that. I have seen a few HPV- SCC CUPs in smokers. Yes, they do tend to behave more aggressively.

What I'm wondering is are HPV- CUPs in smokers cutaneous SCCs?

 

[evilbooyaa]

Yes, I was just editing my statement to address OPX just now. It's still probably statistically less likely than OC, larynx. Agree with elective OC, it all depends how comfortable one is with re-treating. It all comes at a price. I'm not sold on either option.
#3 - want to share why you feel so strongly? Arguments either way.

I think CUP from OC going directly to a level II LN is probably a rarer occurence than a CUP from HPV- OPhx goign to a level II LN.

Because, if I'm not treating OC electively (which I would personally never routinely do in this situation), then why would I treat the LN that OC would have drained to on the opposite side (but is not first echelon drainage for any of the other potential primary sites like OPhx/Larynx/Hypophx)?

Any thoughts on the biology of HPV- CUP? I can come up with a basis, to some degree, for a CUP with a viral etiology, I have more trouble coming up with an explanation for an HPV-, smoking related upper aerodigestive tract cancer that has a big node and no primary. Cutaneous SCC is different.

CUP was well defined as a thing before we knew about HPV when most H&N cancers were due to smoking. Yes, skin cancer should be on the differential here, but a isolated level II LNs in the setting of no cutaneous SCC history would be quite unlikely. Most of the nodal cSCC's I've seen have at least a history of having some scalp SCC treated. Are you suggesting you've seen CUP from a cSCC with 0 previous skin cancer history, like no basals, no squams, nothing, just bam out of no where gets a level II LN that is somehow identified as a cutaneous primary? I suppose I'm responding more to the recent post rather than maybe the OP.

When are we ever going to carry out a randomized trial on H&N CUP randomizing patients to something like:
- observation vs. RT of affected areas in low risk patients
- RT of ipsilateral neck vs. RT of bilateral neck + mucosa in high risk patients

"Risk" defined by number, size of nodes and ECE.

Everyone says there is not enough patients in the current era with advent of PET/CT to help find the primary. And lots of H&N folks think their way is best and wouldn't feel equipoise between the two arms of say the first proposed trial.
But I wouldn't be against observation with up to N2b disease on a protocol.... off protocol I'm probably treating at least ipsi neck on that if not more.

 

[Ray D. Ayshun]

CUP was well defined as a thing before we knew about HPV when most H&N cancers were due to smoking. Yes, skin cancer should be on the differential here, but a isolated level II LNs in the setting of no cutaneous SCC history would be quite unlikely. Most of the nodal cSCC's I've seen have at least a history of having some scalp SCC treated. Are you suggesting you've seen CUP from a cSCC with 0 previous skin cancer history, like no basals, no squams, nothing, just bam out of no where gets a level II LN that is somehow identified as a cutaneous primary? I suppose I'm responding more to the recent post rather than maybe the OP.

I'm wondering about the paradigm of CUP, and questioning it in smoking related disease as it's something to do while contouring. Here's a quick abstract from a surgical series.

Purpose: To evaluate the impact of tonsillectomy on the detection of the primary tumor, based on p16 immunohistochemistry analysis, in patients with cervical unknown primary of squamous cell carcinoma (SCC-CUP).

Methods: This was a retrospective study of 63 patients, included from January 2008 to December 2017 in a single institution. All patients had an initial assessment with physical examination, CT scan of the neck and chest, whole body FDG-PET CT, and endoscopy under general anesthesia, which failed to determine the primary tumor.

Results: Forty-seven out of the 63 patients had an ipsi- or bilateral tonsillectomy which revealed 12 tonsil cancers (26%). The tonsil primary was ipsilateral to positive nodes in 10 cases, contralateral in 1 case and, in 1 case, the patient had bilateral neck involvement. The analysis of the p16 status was carried out in 41/63 patients (65%). Among the 32 patients who had a p16 analysis and tonsillectomy, the rate of primary detection was 59% (10/17) for p16-postives and 0% (0/15) for p16-negatives (p < 0.001).

Conclusion: These results suggest that an extended work-up should be systematically proposed including bilateral tonsillectomy (+/- mucosectomy of the base of tongue) in SCC-CUP p16-positive patients but not in p16-negatives.

Sure, you can say that HPV- CUP isn't in the tonsil. Then where is it? It's a pretty common occurrence in HPV+ CUP to find the primary. As in, the concept of a very small, possibly regressing primary with adenopathy is a documented thing in HPV+ head and neck cancer. Is much known about finding occult primaries in HPV- cancers?

 

[FrostyHammer]

I think CUP from OC going directly to a level II LN is probably a rarer occurence than a CUP from HPV- OPhx goign to a level II LN.

Because, if I'm not treating OC electively (which I would personally never routinely do in this situation), then why would I treat the LN that OC would have drained to on the opposite side (but is not first echelon drainage for any of the other potential primary sites like OPhx/Larynx/Hypophx)?

I'm wondering if you have any data on the first statement. I don't know of any but am happy to change my viewpoint based on any data.

RE: the second point- I get your logic. But then why treat ipsi IB then like communitydoc said? I get the logic to do either way. I wrote in my original post that "I don't have a good answer for the contra IB issue provided that OC won't be covered." So I am assuming that OC won't be covered, which seems to be taken well, but it doesn't make sense to treat ipsi IB but not contra. I'd do both or none.

 

[gmsquid]

Ipsi 1B is a common drainage site for skin cancers

 

[Phantom1]

71 year old with smoking hx, TxpN2b with 2 level II nodes without ECE (largest node 3.5 cm). s/p ipsilateral neck dissection to negative margins. p16/.HPV/ EBV all negative. Good performance status.

Recs are all over the place. Ipsilateral IB-V is a given for me.

Any thoughts on contralateral neck (would be II--IV)?, probably minimal toxicity and will likely do

Any thoughts on treating mucosa? This is the big question for me. oropharynx usual culprit but with true HPV/p16 negativity, I'm thinking combined risk to larynx/hypopharynx probably equivalent. On fence about treating ispilateral tonsil plus b/l BOT and larynx/hypophaynx to 50 Gy or not treating mucosa at all.

Just checking you got PET scan which was negative without even a hint of asymmetric uptake anywhere? If workup including any directed biopsies is negative then I would treat Ipsilateral neck IB-V, Ipsilateral tonsil & BOT, larynx, and hypopharynx to 60Gy, and contralateral neck level II-III to 54Gy.

 

[Palex80]

What I'm wondering is are HPV- CUPs in smokers cutaneous SCCs?

Oh, I see! Well, some yes.
The most common appearance, in my opinion, are (intra)parotideal nodes with SCC without any primary. Usually the primary is/was a SCC of the scalp.

But there certainly are H&N SCC which are P16- and can appear as CUPs.

 

[communitydoc13]

All replies very helpful.

Just checking you got PET scan which was negative without even a hint of asymmetric uptake anywhere? If workup including any directed biopsies is negative then I would treat Ipsilateral neck IB-V, Ipsilateral tonsil & BOT, larynx, and hypopharynx to 60Gy, and contralateral neck level II-III to 54Gy.

PET was negative. I'm pretty much going to go with what you suggest above but will include b/l bot (not much sparing as whole supraglottic larynx is going to be treated and nodal cross over pretty common) and mucosal sites will only get 54 Gy as opposed to 60 Gy. Dose painting 54/60 plan with dissected positive neck getting 60.

Agree with all above regarding squamous of skin. Here, radiology will often call a level II node when on close inspection it's at inferior pole of parotid. In this case, these are true level IIA and IIB nodes so I think I have to hedge and cover high risk mucosa.

Maybe the occult OPX almost never the case here (P16 negative, smoker)? But my added toxicity not much and OPX tonsil gets significant spillover from nodal tx anyway.

 

[gmsquid]

I do not treat larynx but do treat hypopharynx for unknown primary. You can spare the infrahyoid larynx. I also do not treat oral cavity for unknown primary. Was hpv dna specifically done or was it just p16?

 

[communitydoc13]

I do not treat larynx but do treat hypopharynx for unknown primary. You can spare the infrahyoid larynx. I also do not treat oral cavity for unknown primary. Was hpv dna specifically done or was it just p16?

HPV DNA performed and negative. I also will not treat OC for unknown primary (morbidity of treatment high and early stage OC cancer is surgical only disease if occult primary emerges down the road).

 

[thecarbonionangle]

recs are all over the place. Very interesting

 

[evilbooyaa]

I'm wondering if you have any data on the first statement. I don't know of any but am happy to change my viewpoint based on any data.

RE: the second point- I get your logic. But then why treat ipsi IB then like communitydoc said? I get the logic to do either way. I wrote in my original post that "I don't have a good answer for the contra IB issue provided that OC won't be covered." So I am assuming that OC won't be covered, which seems to be taken well, but it doesn't make sense to treat ipsi IB but not contra. I'd do both or none.

Will try to take a look at stuff and get you a link when I get a chance on the first statement. I want to say some old surgical data about propensity of LN development from OC tumor vs Ophx tumors. Sanguinetti as an author if I remember correctly? I may be mistaken as well and this may be more of a dogmatic approach than an evidence based one.

Because of the size of the node is why I'm pushing for IB coverage, especially in the setting of a potential skin primary for ipsi IB. But If someobdy didn't want to cover ipsi IB that would be not completely unreasonable. Truly is the wild west when it comes to management.

 

[metview]

Very good learning case. I agree with ipsilateral Ib-V, contralateral II-IV, mucosal sites of ipsilateral tonsil, BL BOT, larynx, hypopharynx. Don't forget about soft palate as well. Would not include OC or NPX.

HPV/p16/EBV negative with smoking history makes me think larynx or HPV- OPX cancer. If it was p16+/HPV-, it would likely be a cSCC. I think oral cavity is a possibility but a good exam of the OC should identify a possible lesion. I would also do random biopsies of ipsilateral tonsil, BOT, hypopharynx.

The reason not to treat contralateral Ib is because you aren't treating OC or contralateral tonsil. Reason to treat ispi level Ib is the primary could be an ipsilateral tonsil SCC and level II node.

54 Gy to mucosal sites
63 Gy to intermediate risk node sites
70 Gy to gross node

 

[TheWallnerus]

Very good learning case. I agree with ipsilateral Ib-V, contralateral II-IV, mucosal sites of ipsilateral tonsil, BL BOT, larynx, hypopharynx. Don't forget about soft palate as well. Would not include OC or NPX.

HPV/p16/EBV negative with smoking history makes me think larynx or HPV- OPX cancer. If it was p16+/HPV-, it would likely be a cSCC. I think oral cavity is a possibility but a good exam of the OC should identify a possible lesion. I would also do random biopsies of ipsilateral tonsil, BOT, hypopharynx.

The reason not to treat contralateral Ib is because you aren't treating OC or contralateral tonsil. Reason to treat ispi level Ib is the primary could be an ipsilateral tonsil SCC and level II node.

54 Gy to mucosal sites
63 Gy to intermediate risk node sites
70 Gy to gross node

54/35 = 1.54

Does anyone else ever question why locally advanced head and neck cancer is the only carcinoma in the world that we treat definitively with ~1.5 Gy daily fractions? DEEP THOUGHTS.

 

[Ray D. Ayshun]

54/35 = 1.54

Does anyone else ever question why locally advanced head and neck cancer is the only carcinoma in the world that we treat definitively with ~1.5 Gy daily fractions? DEEP THOUGHTS.

I don't do it, but anal also has that fraction size in certain instances

 

[TheWallnerus]

I don't do it, but anal also has that fraction size in certain instances

Which instances? No one was using 1.5-1.6 Gy fraction sizes for carcinomas >20 years ago. There must have been a randomized trial which brought on the change in prescriptions *wink emoji*

 

[Phantom1]

54/35 = 1.54

Does anyone else ever question why locally advanced head and neck cancer is the only carcinoma in the world that we treat definitively with ~1.5 Gy daily fractions? DEEP THOUGHTS.

I only use 54Gy as elective low dose when treating in 33 fractions (1.64Gy/Fx). This equates to an EQD2 of 52Gy which is probably a little more than what is needed for microscopic disease. In 35 fractions my low dose is 56 (1.6Gy/fx) which is EQD2 of 54Gy...

 

[gmsquid]

Actually there is some randomized data Randomized clinical trial on reduction of radiotherapy dose to the elective neck in head and neck squamous cell carcinoma; update of the long-term tumor outcome - PubMed

 

[communitydoc13]

Which instances? No one was using 1.5-1.6 Gy fraction sizes for carcinomas >20 years ago. There must have been a randomized trial which brought on the change in prescriptions *wink emoji*

Yeah, even in the above citation, its chemorads. I think there is good data that chemotherapy mediates some of the time of treatment impact and likely even dose size impact in H&N cancer (and others). I don't typically treat post-op neck less than ~1.7 and usually 1.8. I try to keep fraction size at 1.8 or more without chemo.

Probably just a dinosaur, but I only use the lower dose per fraction dose painting levels with concurrent chemo.

 

[Ray D. Ayshun]

Which instances? No one was using 1.5-1.6 Gy fraction sizes for carcinomas >20 years ago. There must have been a randomized trial which brought on the change in prescriptions *wink emoji*

Wan not randomized, Was random, though.

 

[FrostyHammer]

Reason to treat ispi level Ib is the primary could be an ipsilateral tonsil SCC and level II node.

You routinely treat ipsi IB for a tonsil cancer and level II nodes?

 

[evilbooyaa]

54/35 = 1.54

Does anyone else ever question why locally advanced head and neck cancer is the only carcinoma in the world that we treat definitively with ~1.5 Gy daily fractions? DEEP THOUGHTS.

I generally do 70-63-56 in 35 fractions which are 1.6, 1.8, 2.0 Gy fx. Imagine the 54Gy folks are doing it in 30 or 33fx.

These are my dose levels with chemotherapy only. I do not routinely do 1.6Gy without chemotherapy. Post-op RT alone is 1.8/2.0 only. Definitive RT is 1.8Gy+/day.

You routinely treat ipsi IB for a tonsil cancer and level II nodes?

Not all, but a 3.5cm node in level II would make me consider. @communitydoc13 did not specify whether the 3.5cm node was in level IIA (closer to SMG, anterior to internal jugular) or level IIB (closer to posterior edge of SCM, posterior to internal jugular), but my personal practice is I don't routinely cover IB or V in a tonsil cancer. But, if it's > 3cm node in IIA, I cover IB, if it's > 3cm node in IIB I see how posterior it is and consider covering IB and/or V.

 

[evilbooyaa]

Lots of people saying this isn't a skin primary because it's P16-/HPV-. I know P16+/HPV- is a predictor for skin, but if it's negative on both does that give anyone confidence to call it NOT a skin cancer? I agree that level II LN from a cutaneous is rare given propensity more for intraparotid or IB, but suppose I'm asking on that last part.

As an aside - I have moved this case discussion into its own thread as it clearly has sparked more discussion than the initial case from that OP.

 

[evilbooyaa]

I think CUP from OC going directly to a level II LN is probably a rarer occurence than a CUP from HPV- OPhx goign to a level II LN.

Because, if I'm not treating OC electively (which I would personally never routinely do in this situation), then why would I treat the LN that OC would have drained to on the opposite side (but is not first echelon drainage for any of the other potential primary sites like OPhx/Larynx/Hypophx)?

@FrostyHammer

Looping back around to this:

Nodal yield and topography of nodal metastases from oral cavity squamous cell carcinoma - An audit of 1004 cases undergoing primary surgical resection - PubMed

This large series with high nodal yield, shows low level of metastasis to level IIb, IV and V, which can help modify future guidelines for extent of surgery and avoid targeted adjuvant radiation to specific levels.

pubmed.ncbi.nlm.nih.gov

This is a series of 1000 patients (from India, first series I could find on Pubmed that had a good N) with OC cancer. 43% had LN mets. They all had IB-III dissected, with nodal involvement rates of 25.3% for IB and 23.1% (IIA) + 3.9% (IIB) = 27% for II (Table 3).

Now, this did seem to be driven more by a gingivobuccal primary (buccal mucosa primary more common in Indian population due to Betel Nut chewing), where rates were 35% vs ~21%, while oral tongue primary itself was 16% for IB vs 33% for II (A+B).

Thus I think OC CUP going directly to level II is less likely than CUP from HPV- Ophx going to level II, because HPV- Ophx going directly to IB is much much lower than even the 16% seen in oral tongue.

 

[RickyScott]

I don’t treat mucosal sites when p16 negative although they still are going to get dose. GEORCC recommendations on target volumes in radiotherapy for Head Neck Cancer of Unkown Primary - PubMed

 

[FrostyHammer]

@FrostyHammer

Looping back around to this:

Nodal yield and topography of nodal metastases from oral cavity squamous cell carcinoma - An audit of 1004 cases undergoing primary surgical resection - PubMed

This large series with high nodal yield, shows low level of metastasis to level IIb, IV and V, which can help modify future guidelines for extent of surgery and avoid targeted adjuvant radiation to specific levels.

pubmed.ncbi.nlm.nih.gov

This is a series of 1000 patients (from India, first series I could find on Pubmed that had a good N) with OC cancer. 43% had LN mets. They all had IB-III dissected, with nodal involvement rates of 25.3% for IB and 23.1% (IIA) + 3.9% (IIB) = 27% for II (Table 3).

Now, this did seem to be driven more by a gingivobuccal primary (buccal mucosa primary more common in Indian population due to Betel Nut chewing), where rates were 35% vs ~21%, while oral tongue primary itself was 16% for IB vs 33% for II (A+B).

Thus I think OC CUP going directly to level II is less likely than CUP from HPV- Ophx going to level II, because HPV- Ophx going directly to IB is much much lower than even the 16% seen in oral tongue.

Well this isn't a comparative study between OC and OPX. Hard to conclude that last sentence without comparative data, which I've been trying to look for too but haven't found yet.

 

[FrostyHammer]

Not all, but a 3.5cm node in level II would make me consider.

That scenario isn't all that uncommon for p16 OPX cancer. Happens probably 1/3 of the time at least in my estimation. I wouldn't routinely cover IB for all those 1/3 of cases.

 

[evilbooyaa]

Well this isn't a comparative study between OC and OPX. Hard to conclude that last sentence without comparative data, which I've been trying to look for too but haven't found yet.

That scenario isn't all that uncommon for p16 OPX cancer. Happens probably 1/3 of the time at least in my estimation. I wouldn't routinely cover IB for all those 1/3 of cases.

Are you suggesting that the chances of OPhx cancer spreading to IB are potentially higher than the 16% seen in the tongue primaries seen in the paper I linked and simultaneously advocating for omission of IB when treating a OPhx primary?

Anyways,

Prevalence and distribution of cervical lymph node metastases in HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma

HPV-related squamous cell carcinomas of the oropharynx (HPV+ OP SCC) are known to have a better prognosis than HPV-negative (HPV−) OP-SCC in terms of loco-regional control, recurrence-free survival, overall survival after surgery, radiotherapy or concomitant chemo-radiotherapy [1–4]. This...

www.thegreenjournal.com

Table 2:
In HPV- cN0 OPhx patients, ipsi IB was dissected 41 out of 58 times, and identified 1/41 pathologically (2.4%) of the time, where as level II had nodes 13/57 or 22% of the time.
In HPV- cN+ OPhx patients, ipsi IB had LNs involved ~10%, while level II was involved 91.2% of the time. I'm actually surprised at the 10% involvement being as high as it is, but may be in part driven by the burden of disease of patients in that paper, but that's just speculation.
That is actually higher than it is for HPV positive (present within the same paper) and higher than what Sanguineti found in the JHU data: HPV-related oropharyngeal carcinoma with Overt Level II and/or III metastases at presentation: The risk of subclinical disease in ipsilateral levels IB, IV and V - PubMed

There may not be one exact comparative series looking at your specific question, so we kinda have to pull numbers from various series that did the same comparison and compare equally.

Hope that helps.

 

[Ray D. Ayshun]

Does anyone know of a paper, series, etc where a primary was located in the setting of an hpv- cup by tonsillectomy? This isnt rhetorical.

 

[FrostyHammer]

Are you suggesting that the chances of OPhx cancer spreading to IB are potentially higher than the 16% seen in the tongue primaries seen in the paper I linked and simultaneously advocating for omission of IB when treating a OPhx primary?

Anyways,

Prevalence and distribution of cervical lymph node metastases in HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma

HPV-related squamous cell carcinomas of the oropharynx (HPV+ OP SCC) are known to have a better prognosis than HPV-negative (HPV−) OP-SCC in terms of loco-regional control, recurrence-free survival, overall survival after surgery, radiotherapy or concomitant chemo-radiotherapy [1–4]. This...

www.thegreenjournal.com

Table 2:
In HPV- cN0 OPhx patients, ipsi IB was dissected 41 out of 58 times, and identified 1/41 pathologically (2.4%) of the time, where as level II had nodes 13/57 or 22% of the time.
In HPV- cN+ OPhx patients, ipsi IB had LNs involved ~10%, while level II was involved 91.2% of the time. I'm actually surprised at the 10% involvement being as high as it is, but may be in part driven by the burden of disease of patients in that paper, but that's just speculation.
That is actually higher than it is for HPV positive (present within the same paper) and higher than what Sanguineti found in the JHU data: HPV-related oropharyngeal carcinoma with Overt Level II and/or III metastases at presentation: The risk of subclinical disease in ipsilateral levels IB, IV and V - PubMed

There may not be one exact comparative series looking at your specific question, so we kinda have to pull numbers from various series that did the same comparison and compare equally.

Hope that helps.

Nah what I was saying was that 3+ cm nodes in p16 OPX occurs about 1/3 in my very rough estimation. If all pts with 3+ cm nodes in level 2 get elective IB coverage, that's a lot of patients. Way too many to routinely go after IB.

However I did like that data on IB risk of 10% in cN+ p16- OPX...I agree it's higher than I'd think, but it wouldn't be high enough for me to consider covering electively.

 

[evilbooyaa]

Nah what I was saying was that 3+ cm nodes in p16 OPX occurs about 1/3 in my very rough estimation. If all pts with 3+ cm nodes in level 2 get elective IB coverage, that's a lot of patients. Way too many to routinely go after IB.

Fair enough. I suppose these are variations in practice, although I'm not sure how common one approach is over another. Maybe time for an interested resident to do a survey.