H & N Question

[yeasterbunny]

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A case:
73 y.o. M with SCC of the floor of mouth s/p resection. Path shows 3.0 cm tumor invading the mandible, (+) perineural invasion, (-) lymphovascular invasion, closest surgical margin < 0.1 cm.
Bilateral neck dissections negative (0/45).
pT4aN0

I think it's pretty clear post-op RT is indicated based on close margin, T4, with PNI, but what would y'all say about treating just the tumor bed and not the necks? He had a pretty thorough bilateral neck dissection and we could really spare him a lot of toxicity.

 

[Gfunk6]

I think RT to the tumor bed only would be appropriate given the negative (I assume) modified radical neck dissections.

 

[deleted4401]

I'd think so too, but the way I've been taught is that if it's been dissected, then it's a target b/c of theoretical chance of seeding and the altered lymphatic flow/contralateral re-direction. I.e. - all the post-op trials in the past included both necks and tumor bed, but they didn't have the option of targeting selectively b/c they were practicing in pre-historic times. The bulk of what I've seen post-op recently tends to include the dissected neck.

The experts really never discuss this during the case discussions at the 'Stro.

Hanson/Roach - says you tx the "post-operative bed" which to me sounds like it includes the neck.

Anyone else want to chime in?
-S

 

[RadRadRad]

Probably ok to avoid neck (we frequently do this at my institution in similar situations), however standard of care is probably bilateral neck RT (ala EORTC, RTOG post-op studies).

Given the primary tumor location, bone invasion, and PNI, I would consider tracking the path of inferior alveolar nerve/cranial nerve V3 towards base of skull to avoid infratemporal fossa failures, etc. (Reference: University of Iowa paper, Yao et al; PMID: 17276613)

 

[yeasterbunny]

Hanson/Roach - says you tx the "post-operative bed" which to me sounds like it includes the neck.

Yeah, the Ang book and the old Million book say to treat the dissected necks too, but that's why I ask, it seems to me like with adequate (yes, modified radical) neck dissections with 0/45 nodes, the necks have been pretty well addressed.

 

[deleted4401]

Trust me, I totally agree - if 0/45 LNs dissected isn't enough, what is? And in theory, I wouldn't mind skipping the neck and just treating the tumor bed with a margin.

But, I don't believe there is even one good single-institution dataset. Florida, MDACC have the most outcomes data, and they treat the dissected neck. I think other places are starting to be a bit more selective with treatment, but no one has a very good dataset of outcomes based on tx volumes in the post-op setting.

Fletcher says, paraphrasing, that comprehensive treatment of bilateral necks and the primary site are required in the adjuvant setting because there is much higher rate of failure when the necks are not included (failure rate of 58% vs 73%). It's a reference from 1970, and it's unclear whether or not that holds true today.

My thought in private practice is if I go against the teachings of Fletcher and Million and Ang and my handy UCSF book and a patient fails in the neck, I'd better have a nice suit for my "vacation" in front of the jury. If they get a dry mouth because I treated both sides, well, that is a standard complication of RT. Kind of wimpy, but until there is some outcomes data, kind of nerve-wracking to do non-standard things.

-S

 

[Gfunk6]

My thought in private practice is if I go against the teachings of Fletcher and Million and Ang and my handy UCSF book and a patient fails in the neck, I'd better have a nice suit for my "vacation" in front of the jury.

Well put. It's easy to follow the "logical" path and forgo standard of care . . . until it's your ass on the line. I'd wager this kind of thing is easier to pull off in an academic instiution where you can bounce your ideas of senior H&N attendings.

 

[temujim]

Both the Gunderson and Chao IMRT textbook indicate it's ok (actually preferred) to forgo RT to the pN0 neck. Chao references an old Emami textbook that I haven't read, so can't help with source data.

It seems logical; the neck has been appropriately addressed and found to be free of disease. What is the risk of an isolated neck failure? Maybe 10%? I'd be surprised if it's that high. So in practice I'm just treating the primary tumor bed for this situation - maybe I'll have a solid dataset for everyone in a couple of years.

 

[Palex80]

I wouldn't treat the neck either. 45 dissected lymph nodes are enough.

One possible compromise would be to limit the target volume of the neck to only the immediate lymphatic regions (level I+II) and leave out all the other levels.
"Flour of mouth" is quite a big region, so whether or not you need both a/b "sublevels" of Level I+II on both sides depends on the exact location of the tumor, its lateralization etc. I would do this kind of treatment with IMRT, respecting the parotids.
I presume that the submandibular glands were removed during the neck dissection, right? So, there shouldn't be much toxicity coming from irradiating those areas.

My thought in private practice is if I go against the teachings of Fletcher and Million and Ang and my handy UCSF book and a patient fails in the neck, I'd better have a nice suit for my "vacation" in front of the jury. If they get a dry mouth because I treated both sides, well, that is a standard complication of RT. Kind of wimpy, but until there is some outcomes data, kind of nerve-wracking to do non-standard things.

Discussing the whole problem with the patient is the other alternative to "bypass" this situation.
Just hit him with the facts, tell him your opinion (that you want to treat only the primary tumor site), address the issue of about 10% recurrence rate in the neck, if you don't electively treat it, inform him of the increased risk of xerostomia coming from irradiating the neck and let him decide what he wants to have.
We practice this kind of "informed consent" and "treatment based on patients's preference" as a standard in my institution in another group of patients, where there's no clear data on what the target volume has to be: Carcinoma of unknown primary with only one neck side involved after unilateral neck dissection.
We let the patients choose if they want bilateral neck irradiation, including pharynx irradiation or if they want unilateral neck irradiation of the involved side.
We generally see 30% of the patients opting for bilateral and 70% for unilateral irradiation.

 

[deleted4401]

I don't know where this 10% number is coming from. Come on, if it's 10%, I'm not sure if the dogma for the last 40 years would be to treat such a large volume. The fact that the question arises is because nobody has a true modern number. Since Fletcher's days, a surgically disturbed neck bought itself 60 Gy b/c of altered lymphatics/hypoxia, and few brave souls have tried to do anything other than that.

From the old Anderson papers that tried to group risk factors for post-operative patients, the risk of recurrence after radiating the neck even in the low-risk patients remained ~10%. In the post-op group with no risk factors, the failure rate without RT was 10%. In none of these do they give a good breakdown whether its local or regional recurrence.

I'm not saying there is or isn't a high risk of recurrence. I'm saying in the past, the risk was thought of as high and we don't know if they were wrong or right.

I guess, it may be just mental 'sturbing at this point, but it may be the only action I get:

1) How many nodes dissected makes you feel that it is adequate? This isn't as cleanly defined as it is for colorectal or breast ca. I don't know. I don't really look at the number, unless very minimal. But, in those cases where it's just a few nodes dissected, I only see them if they have another indication for RT. Otherwise, they wouldn't have even have sent them to me, so I can't say I'd know what I would do.

2) How many nodes positive or how many nodes percentage positive make you feel there is still disease left, and why? B/c, in breast ca, even if 3 nodes positive, if 25 were negative, you'd leave the axilla alone. Yet, in general, N2b disease is enough to radiate the neck, regardless of how many nodes were dissected. But if the argument is that a "full dissection" has sterilized the neck than perhaps N2b isn't as clear as an indication, if many nodes were dissected? Is there any case anyone would avoid radiating neck for N2b disease?


3) A close margin buys you RT and a positive margin buys you ChemoRT. If this was the only risk factor, would anyone skip treating the neck? I.e. T1N0 FOM tumor, no LVSI, no PNI, zillion nodes dissected on each side, but a close margin, would you tx neck? If + margin, would you tx neck?

-S

 

[Palex80]

How many nodes positive or how many nodes percentage positive make you feel there is still disease left, and why? B/c, in breast ca, even if 3 nodes positive, if 25 were negative, you'd leave the axilla alone. Yet, in general, N2b disease is enough to radiate the neck, regardless of how many nodes were dissected. But if the argument is that a "full dissection" has sterilized the neck than perhaps N2b isn't as clear as an indication, if many nodes were dissected? Is there any case anyone would avoid radiating neck for N2b disease?

Just some thoughts...
1. The lymphatics of the neck are far more complicated than the lymphatics of the axilla. You have a lot more parallel paths of tumor cells moving in the neck than in the axilla.
2. Some node levels in the neck cannot be reached surgically, retropharyngeal nodes for example. Therefore treating the neck also means treating those hard-to-reach levels.
3. A cN2b neck means (according to tumor localization and T-stage) a > 30% chance of microscopic contralateral lymph node involvement in many cases. A cN2 axilla does not mean a 30% chance of microscopic contralateral axilla involvement.
4. Systemic therapy is far more effective in breast cancer than it is in head&neck cancer and can thus eliminate micrometastatic disease in lymph nodes.
5. We are treating the axilla on a daily basis in breast cancer, even if we do not specifically encompass the axilla in our PTVs. Have a look at your dose distributions. If you don't use IMRT for breast/chest wall irradiation, you are giving the full dose to about half of the axillary levels I+II with normal tangents.
One group actually estimated the mean dose in the axilla in only breast RT and found it be over 30 Gy.

 

[qwert]

In my institution, this pt would receive B/L neck RT. Negative surgically disturbed neck requires 54-55, not 60 Gy. Any comparison to breast adenoCa is irrelevant.

 

[Palex80]

A close margin buys you RT and a positive margin buys you ChemoRT. If this was the only risk factor, would anyone skip treating the neck? I.e. T1N0 FOM tumor, no LVSI, no PNI, zillion nodes dissected on each side, but a close margin, would you tx neck? If + margin, would you tx neck?

Depends partially on the site.
I would probably treat the neck in the case of a hypopharynx tumor (although I would limit fields and omit high level II and supraclavicular fossae).
I would not treat the neck in the case of a small lateralized floor of the mouth tumor, which was resected with a positive/close margin but was pN0 after adequate neck dissection.
I would give 66 Gy only to the primary tumor bed.

 

[deleted4401]

I'm not saying we should treat head and neck cancer with Herceptin/Taxol. The relevance has to do with the fact that people (including myself) say that 45 lymph nodes dissected is "a lot". Why, other than the fact that it is a big number? Is 35 a "lot"? How about 25? 15? If we are basing our decisions on a number, than the number matters. Breast cancer and colorectal cancer surgeons have been able to tell us what number of nodes are a "lot" or adequate, and decisions can actually made with some sort of confidence rather than conjecture. That isn't the case, at this point with HNC.

I'm not sure that one can say that breast cancer as a whole is more sensitive to chemotherapy. There are groups in France with published data (JCO sometime 2009ish) treating larynx cancer with chemotherapy alone with very good results, and in general head and neck cancers are exquisitely sensitive to both radiation and chemotherapy. There is documented survival benefits with the addition of chemotherapy to NPC that are substantially higher than with breast cancer. The meta-analysis of the addition of cisplatin to HNC shows a survival benefit equal to that of the addition of chemotherapy to breast cancer (~6%), and that is without surgery as a component of treatment.

The minimum dose to the dissected areas was 60 Gy in the RTOG 9501 trial, and 54 Gy in the EORTC trial (with 90% of the patients getting a total dose of 66 Gy, they don't clarify what the undissected necks got). I'd say the accepted standard would be 54 to 60 Gy, with a boost to 66 Gy for + margin/ECE, if those studies are the modern benchmarks for adjuvant therapy, while Fletcher historically says 60 Gy. I think that MDACC used 57.6 Gy in their studies. I don't any answer between that range is "wrong".

1. The lymphatics of the neck are far more complicated than the lymphatics of the axilla. You have a lot more parallel paths of tumor cells moving in the neck than in the axilla.

2. Some node levels in the neck cannot be reached surgically, retropharyngeal nodes for example. Therefore treating the neck also means treating those hard-to-reach levels.

Two great reasons to treat the undissected neck!

-S

 

[Palex80]

I'm not saying we should treat head and neck cancer with Herceptin/Taxol. The relevance has to do with the fact that people (including myself) say that 45 lymph nodes dissected is "a lot". Why, other than the fact that it is a big number? Is 35 a "lot"? How about 25? 15? If we are basing our decisions on a number, than the number matters. Breast cancer and colorectal cancer surgeons have been able to tell us what number of nodes are a "lot" or adequate, and decisions can actually made with some sort of confidence rather than conjecture. That isn't the case, at this point with HNC.

It depends on which levels you dissect and if you perform a bilateral or unilateral neck dissection.
15 nodes dissected from one side are ok, 15 nodes dissected from both sides mean a suboptimal neck.
The risk for lymp node metastasis in pT2 hypopharynx tumor is larger than in a pT2 tongue cancer and the lymph node levels at risk are different as well.
This is a major flaw that disturbs any effort to bring a systematic approach in the matter of neck management. Different primary tumor localizations, different stages and some authors keep throwing all the tumors together in a pot, trying to draw conclusions.

I'm not sure that one can say that breast cancer as a whole is more sensitive to chemotherapy. There are groups in France with published data (JCO sometime 2009ish) treating larynx cancer with chemotherapy alone with very good results, and in general head and neck cancers are exquisitely sensitive to both radiation and chemotherapy. There is documented survival benefits with the addition of chemotherapy to NPC that are substantially higher than with breast cancer. The meta-analysis of the addition of cisplatin to HNC shows a survival benefit equal to that of the addition of chemotherapy to breast cancer (~6%), and that is without surgery as a component of treatment.

I was not talking only about chemotherapy. I said "systemic treatment". The overall benefit of chemotherapy, hormonal therapy and antibody therapy in breast cancer is clearly higher than in head&neck cancer.
Although there are some h&n tumors that respond very well to chemotherapy, neoadjuvant treatment is not common practice (other than for advanced larynx cancer in some cases). In the mean time neoadjuvant chemotherapy has become standard for locally advanced breast cancer.
While h&n patients generally gain very little from adjuvant chemotherapy (without RT), adjuvant treatment in breast cancer is current standard of care and given in to patients in all stages. Hell, even DCIS patients get adjuvant systemic treatment!
In the metastatic setting you have a huge battery of different substances to try out, better response rates to expect and longer overall survival with systemic therapy for breast cancer, than with chemotherapy for h&n cancer. We have all seen breast cancer patients surviving 5+ years after development of metastatic disease. Have you ever seen a hypopharynx patient surviving longer than 5 years after being diagnosed with lung metastasis?
I don't think so.

The minimum dose to the dissected areas was 60 Gy in the RTOG 9501 trial, and 54 Gy in the EORTC trial (with 90% of the patients getting a total dose of 66 Gy, they don't clarify what the undissected necks got). I'd say the accepted standard would be 54 to 60 Gy, with a boost to 66 Gy for + margin/ECE, if those studies are the modern benchmarks for adjuvant therapy, while Fletcher historically says 60 Gy. I think that MDACC used 57.6 Gy in their studies. I don't any answer between that range is "wrong".

We generally give 50-54 Gy in uninvolved node areas without any signs of disease. Lymph node areas with dissected involved lymph nodes generally get 60-64 Gy.

1. The lymphatics of the neck are far more complicated than the lymphatics of the axilla. You have a lot more parallel paths of tumor cells moving in the neck than in the axilla.
2. Some node levels in the neck cannot be reached surgically, retropharyngeal nodes for example. Therefore treating the neck also means treating those hard-to-reach levels.
Two great reasons to treat the undissected neck!

The point is:
You have to figure out, when treating the neck will have a significant contribution in reducing the patients recurrence risk and if this reduction is worth the additional toxicity.
If the neck recurrence risk is too low, then it's not worth it.