Adjuvant Reirradiation in H&N cancer

[Palex80]

What is your general approach on H&N adjuvant reirradiation?

There are a lot of retrospective series out there covering the field of reirradiation in H&N cancer, but I feel most publications / guidelines throw everything in a single bucket.

- From true reirradiation (recurrent tumor completely in the CTV of the first treatment), to marginal misses, to recurrences outside the initial CTV (e.g. contralateral neck recurrences).
- From retreatment with the goal of durable control, to palliation.
- From retreatment as definitive treatment, to discussing the value of adjuvant treatment after resection of a recurrence.

I am mostly interested in the last topic, based on a current case.
Elderly patient with an oral cavity cancer, treated with resection and adjuvant RT to 60 Gy about 3 years ago.
Initially it was a pT3 pN0 primary.

She now presented, 2 years following treatment of the initial tumor, with a large tumor of the hard palate, with involvement of the maxilla. It's difficult to tell, if it's a second primary or a recurrence (perhaps through perineural involvement?). No nodes. Most of the recurrent tumor was within the inital CTV, some parts of it (esp. in the maxillary sinus) grew outside the initially treated volumes.

An extensive resection with reconstruction was carried out. The margins came out clear >5mm, there was no perineural involvement, it was pT4 due to bone/muscle involvement.

The question popped up now, if one should retreat with RT in an adjuvant fashion.
On paper, there are enough risk factors present (i..e. pT4) and a local re-recurence will not be salvageable. On the other hand, it would be a retreatment with >120 Gy at parts of the upper jaw and non resected maxilla, after a rather short time interval and potentially jeopardizing the reconstruction / functional outcome (which isn't great right now, anyhow).

I am reluctant to retreat.

Thoughts?

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[TheWallnerus]

What is your general approach on H&N adjuvant reirradiation?

There are a lot of retrospective series out there covering the field of reirradiation in H&N cancer, but I feel most publications / guidelines throw everything in a single bucket.

- From true reirradiation (recurrent tumor completely in the CTV of the first treatment), to marginal misses, to recurrences outside the initial CTV (e.g. contralateral neck recurrences).
- From retreatment with the goal of durable control, to palliation.
- From retreatment as definitive treatment, to discussing the value of adjuvant treatment after resection of a recurrence.

I am mostly interested in the last topic, based on a current case.
Elderly patient with an oral cavity cancer, treated with resection and adjuvant RT to 60 Gy about 3 years ago.
Initially it was a pT3 pN0 primary.

She now presented, 2 years following treatment of the initial tumor, with a large tumor of the hard palate, with involvement of the maxilla. It's difficult to tell, if it's a second primary or a recurrence (perhaps through perineural involvement?). No nodes. Most of the recurrent tumor was within the inital CTV, some parts of it (esp. in the maxillary sinus) grew outside the initially treated volumes.

An extensive resection with reconstruction was carried out. The margins came out clear >5mm, there was no perineural involvement, it was pT4 due to bone/muscle involvement.

The question popped up now, if one should retreat with RT in an adjuvant fashion.
On paper, there are enough risk factors present (i..e. pT4) and a local re-recurence will not be salvageable. On the other hand, it would be a retreatment with >120 Gy at parts of the upper jaw and non resected maxilla, after a rather short time interval and potentially jeopardizing the reconstruction / functional outcome (which isn't great right now, anyhow).

I am reluctant to retreat.

Thoughts?

Whatever reirradiation dose is given, the potential for late effects increases by a factor of that dose times (3+x)/3, where x is the fractional dose, so I will til the day I die think keeping ‘x’ small is smart.

I would consider 21 days of 1.2 twice a day with weekly low dose cis, treating the local recurrence site. That will be complex contouring.

 

[thecarbonionangle]

these situations can have morbidity so I always discuss it with patient and get a sense of their values. if im going to retreat try to keep carotid below 120-125Gy, follow Neider/monkey data for the cord.

Yeah I would likely treat. I would even ask med onc what they think about chemo.

 

[drowsy12]

for me - if I understand correctly it’s T4N0, no PNI, LVI, clear margins.

If it’s T4 because of bone invasion and the bone that was involved is cleanly resected, I would not treat. There’s not a lot of compelling reason to treat as I understand the case, other than T4, and it sounds like it was a big resection. My view may differ if there was soft tissue extension of disease into fat planes that were not resected, but I would keep volume as confined to where you have reason to believe there is microscopic disease if I was going to treat in a re-RT setting

 

[Palex80]

for me - if I understand correctly it’s T4N0, no PNI, LVI, clear margins.

If it’s T4 because of bone invasion and the bone that was involved is cleanly resected, I would not treat. There’s not a lot of compelling reason to treat as I understand the case, other than T4, and it sounds like it was a big resection. My view may differ if there was soft tissue extension of disease into fat planes that were not resected, but I would keep volume as confined to where you have reason to believe there is microscopic disease if I was going to treat in a re-RT setting

pT4 because of bone & muscle (pterygoid) invasion. All of the disease has been resected, clear margins.

 

[drowsy12]

pT4 because of bone & muscle (pterygoid) invasion. All of the disease has been resected, clear margins.

so maybe only the pteryoid space that is still present, unless all the muscle is gone? but I wouldn't treat with that as only factor.

 

[Pointless]

I had something similar a year or so back only it was laryngeal cancer... resected at a big academic center, referred back to me for adjuvant radiation, we talked it out and elected to forego radiation. He recurred within months, unfortunately, and I ended up re-irradiating after a second resection. Went fine.

What do you think about treating just the high risk areas for recurrence (e.g. no elective nodal coverage)? You're right that it is high risk for complications but, if you know already that further recurrence would not be surgically salvageable, that really would push me toward treatment.

 

[thecarbonionangle]

I had something similar a year or so back only it was laryngeal cancer... resected at a big academic center, referred back to me for adjuvant radiation, we talked it out and elected to forego radiation. He recurred within months, unfortunately, and I ended up re-irradiating after a second resection. Went fine.

What do you think about treating just the high risk areas for recurrence (e.g. no elective nodal coverage)? You're right that it is high risk for complications but, if you know already that further recurrence would not be surgically salvageable, that really would push me toward treatment.

Yup exactly my thoughts

 

[Palex80]

so maybe only the pteryoid space that is still present, unless all the muscle is gone? but I wouldn't treat with that as only factor.

All gone. This was a radical resection.

 

[drowsy12]

All gone. This was a radical resection.

Without seeing the imaging, I’m not sure what you would be treating then, don’t see a strong rationale for RT now. This sounds like a massive resection.

 

[communitydoc13]

I wouldn’t treat. It’s a weird recurrence. Short interval and if from PNI there is a competing risk of failure to other places that you likely won’t treat prophylactically in the setting of re-irradiation.

I’d opt for close surveillance.

Agree with above that if you are compelled to treat and patient fit…consider concurrent chemo.

 

[Radiator20]

Practice is all over the place on this topic but I would treat. 2 years is a decent interval. Within the region of prior treatment, target vol would be tumor bed + adjacent postop changes only. If there is area of non-overlap, can cover elective volumes there (e.g., if there's PNI, would chase at least to skull base if outside prior field - possibly cav sinus if you really felt this was a perineural recurrence of the original tumor. And if PNI is a factor, would get postop MRI before treating if one not obtained preop). I would do 60/30. Agree with consideration of concurrent chemo based on GORETEC data, though it is not definitive. Many reasonable answers, but as you note a recurrence will be unsalvageable and that would weigh heavily on me.

 

[medgator]

Practice is all over the place on this topic but I would treat. 2 years is a decent interval. Within the region of prior treatment, target vol would be tumor bed + operative bed only. If there is area of non-overlap, can cover elective volumes there (e.g., if there's PNI, would chase at least to skull base if outside prior field - possibly cav sinus if you really felt this was a perineural recurrence of the original tumor). I would do 60/30. Agree with consideration of concurrent chemo based on GORETEC data, though it is not definitive. Many reasonable answers, but as you note a recurrence will be unsalvageable and that would weigh heavily on me.

What's your thoughts on a 15-20 year interval? Ignore any previous dose?

 

[udrag14]

What is your general approach on H&N adjuvant reirradiation?

There are a lot of retrospective series out there covering the field of reirradiation in H&N cancer, but I feel most publications / guidelines throw everything in a single bucket.

- From true reirradiation (recurrent tumor completely in the CTV of the first treatment), to marginal misses, to recurrences outside the initial CTV (e.g. contralateral neck recurrences).
- From retreatment with the goal of durable control, to palliation.
- From retreatment as definitive treatment, to discussing the value of adjuvant treatment after resection of a recurrence.

I am mostly interested in the last topic, based on a current case.
Elderly patient with an oral cavity cancer, treated with resection and adjuvant RT to 60 Gy about 3 years ago.
Initially it was a pT3 pN0 primary.

She now presented, 2 years following treatment of the initial tumor, with a large tumor of the hard palate, with involvement of the maxilla. It's difficult to tell, if it's a second primary or a recurrence (perhaps through perineural involvement?). No nodes. Most of the recurrent tumor was within the inital CTV, some parts of it (esp. in the maxillary sinus) grew outside the initially treated volumes.

An extensive resection with reconstruction was carried out. The margins came out clear >5mm, there was no perineural involvement, it was pT4 due to bone/muscle involvement.

The question popped up now, if one should retreat with RT in an adjuvant fashion.
On paper, there are enough risk factors present (i..e. pT4) and a local re-recurence will not be salvageable. On the other hand, it would be a retreatment with >120 Gy at parts of the upper jaw and non resected maxilla, after a rather short time interval and potentially jeopardizing the reconstruction / functional outcome (which isn't great right now, anyhow).

I am reluctant to retreat.

Thoughts?

Yea I would consider close observation here after discussing with surgeon. If they feel like they got it all out, I'm not keen on re treatment without other high risk features.

For re radiation for HN, I like this paper. I preferred BID given decreased risk of long term toxicity

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00269-6/abstract

 

[TheWallnerus]

so maybe only the pteryoid space that is still present, unless all the muscle is gone? but I wouldn't treat with that as only factor.

Well that’s not the ONLY factor. It’s a local in-field recurrence.

 

[Palex80]

It is staggering, how little evidence we have in a scenario which is not such uncommon. I appreciate all the input!

 

[TheWallnerus]

It is staggering, how little evidence we have in a scenario which is not such uncommon. I appreciate all the input!

Would really love to see your volumes and DVH if you decide to treat.

 

[evilbooyaa]

I would treat primary site alone. 60Gy in 30fx, or consider BID if patient is agreeable. Counsel on toxicity risks. Limit carotid to < point dose as feasible. Cord should be fine based on location.

This pt is overwhelmingly likely to recur locally despite the large resection. If surgeon is leaning towards re-RT, do it.

No nodes. I think adding chemo not at all unreasonable but no obvious indication for it I can see.

 

[drowsy12]

‘This pt is overwhelmingly likely to recur locally despite the large resection’

Not sure how you arrive at that based on what we know about the case and what has been described? Where is the microscopic disease you are wanting to chase?

Neither one of us have seen the imaging but I’m trying to figure how you get to overwhelmingly likely.

If that was my estimation then I would for sure radiate.

Are you radiating all salvage post op?

 

[TheWallnerus]

‘This pt is overwhelmingly likely to recur locally despite the large resection’

Not sure how you arrive at that based on what we know about the case and what has been described? Where is the microscopic disease you are wanting to chase?

Neither one of us have seen the imaging but I’m trying to figure how you get to overwhelmingly likely.

If that was my estimation then I would for sure radiate.

Are you radiating all salvage post op?

For an oral cavity/hard palate/maxillary sinus s/p surgery and adjuvant RT, that recurs in 2y, and is s/p surgery again, what do you think the recurrence risk is? I think it’s gotta be… 67.382%.

 

[communitydoc13]

For an oral cavity/hard palate/maxillary sinus s/p surgery and adjuvant RT, that recurs in 2y, and is s/p surgery again, what do you think the recurrence risk is? I think it’s gotta be… 67.382%.

And with adjuvant XRT a second time?

Might not be that much better. The adjuvant XRT either didn’t work the first time; this is another primary in the setting of field cancerization (more will emerge) or this is from PNI (you aren’t going to prophylactically tx to Meckel’s cave in the reirradiation setting are you)?

Series on de-novo T4 OC with bone invasion s/p surgery and adjuvant tx don’t have the best LC…never mind competing risks.

Still, tx is OK IMO…I just wouldn’t do it based on what little I know. I wouldn’t give my partners grief if they did tx.

MRI and exam q3 mos. Tx definitively with chemorads at recurrence would be my plan.

 

[TheWallnerus]

Tx definitively with chemorads at recurrence would be my plan.

At re-recurrence

 

[evilbooyaa]

‘This pt is overwhelmingly likely to recur locally despite the large resection’

Not sure how you arrive at that based on what we know about the case and what has been described? Where is the microscopic disease you are wanting to chase?

Neither one of us have seen the imaging but I’m trying to figure how you get to overwhelmingly likely.

If that was my estimation then I would for sure radiate.

Are you radiating all salvage post op?

Because a big ugly recurrence at 2 years is unlikely to have maximum rates of salvage with surgery alone. I don't have an obvious number.

Most primary tumor recurrences that get salvage surgery I would recommend post-op re-RT to the primary, doubly so if the surgeon was concerned.

Nodal recurrences are a bit more plus/minus in my head and would be worth shared decision making.

I don't think it's unreasonable to just observe, but as someone else noted above, they had a similar case int he larynx that they observed instead of delivering re-RT and the patient then developed a third recurrence requiring another (presumably large) surgery. I would just like to minimize that risk, especially in someone who is unlikely to be able to go another surgery and thus oncologic outcomes for an oral cavity tumor would not be expected to be equal with definitive chemoRT vs post-op RT (kinda like how we think about oral cavity in general).

And with adjuvant XRT a second time?

Might not be that much better. The adjuvant XRT either didn’t work the first time; this is another primary in the setting of field cancerization (more will emerge) or this is from PNI (you aren’t going to prophylactically tx to Meckel’s cave in the reirradiation setting are you)?

Series on de-novo T4 OC with bone invasion s/p surgery and adjuvant tx don’t have the best LC…never mind competing risks.

Still, tx is OK IMO…I just wouldn’t do it based on what little I know. I wouldn’t give my partners grief if they did tx.

MRI and exam q3 mos. Tx definitively with chemorads at recurrence would be my plan.

If part of the new tumor is squarely in the previous high-dose post-op CTV, i'm not sure how one calls this a new primary at 2 years down the line. I don't know that we have evidence of field cancerization. Sounds like most of the PNI volumes were not covered initially.

de-Novo T4 OC s/ps urgery is getting RT nearly 100% of the time. If the risk of recurrence is even higher in the recurrent T4 setting, shouldn't we be considering re-RT?

Yes, patient is at risk for toxicity. But, carotids are hopefully far and hopefully can be limited on dose. Spinal cord likely not an issue or something that can be maintained safely if both treatments planned with contemporary IMRT techniques. I think putting the patient at risk for maxillary ORN (hypothetically less of a concern than say mandibular ORN) in hopes of trying to reduce her LC risk (which will likely be lethal) is worth it. However, if patient didn't want to do it, that would be reasonable too.

To think that a local recurrence would be equally salvageable with definitive chemoRT to post-op RT goes against everything we know about oral cavity SCC, which is controlling microscopic disease is generally a better oncologic option than treating gross disease.

 

[communitydoc13]

If part of the new tumor is squarely in the previous high-dose post-op CTV, i'm not sure how one calls this a new primary at 2 years down the line. I don't know that we have evidence of field cancerization. Sounds like most of the PNI volumes were not covered initially.

@Palex80 where was the initial tumor? Also, rough age of patient might be helpful.

If it was oral tongue, buccal mucosa, FOM or alveloar ridge, I'm calling a hard palate tumor something other than a typical local recurrence/marginal miss. Field cancerization concept is often applied in the OC. I have seen this clinical course before. Adjuvant OC fields should be fairly comprehensive IMO for this (and other) reasons.

https://onlinelibrary.wiley.com/doi/full/10.1002/hed.10042

Also, just ensuring that this is a squamous cell carcinoma? Even if squamous cell, it is possible that this is a salivary gland phenomenon in the hard palate.

carotids are hopefully far

Much more concerned with functional outcomes in this patient. I'm assuming obturator in place already? A second course of full dose XRT to resected and previously treated palate/alveolar bone can easily result in bone necrosis/chronic wounds. It happens without a second course of XRT.

Also, this was clearly a large recurrence, level of surveillance and suspicion of recurrence will be higher going forward, hopefully facilitating treatment of re-recurrence while incipient (and perhaps surgically).

 

[drowsy12]

For me when I am considering re-RT after a salvage surgery, I think about the therapeutic ratio. Where can RT actually help? To me that means a confined area where you are actually worried about there being residual microscopic disease.

In the upfront setting, for a T4 tumor, a big part of why you are treating is for nodes too. In this patient, there were no nodes the first time, no nodes the second time, we all agree we are not treating the neck.

So the next question becomes, okay, what is left behind that we are worried about?

Specifically with oral cavity, patients can be called T4 for say an alveolar ridge tumor that went into mandible, even if small, and then the mandible is gone. We radiate them, but there are some T4 with no PNI, no LVI, no other bad factors, that we radiate (presumably for the nodal concern risk) that I wonder why we are treating the primary site on. So that is what is drawing my attention in this case, was T4 by extension into bone, the bone is all gone (Palex says ALL the muscle is gone too, which I have not heard of before, but if all the pterygoids are truly gone, I am not sure where the microscopic disease concern is).

In my experience in these cases, my guess is the entire hard palate is gone, there is an obturator in place, it sounds like there was an infrastructure matxillectomy at least (maybe total?). Hence the question I asked about soft tissue extent of tumor into pterygoid muscles upfront. IF there is no muscle left behind, then I can't figure out where to treat that isnt just hardware that is otherwise resting in air, that is where the microscopic disease is that im supposed to be radiating.


A lot of ifs and buts here when we don't know about the case (other than Palex) but this is where I am coming from. I don't think patients need RT just because something is called T4, in the re-RT setting (questionable for some in the upfront setting, but that is a different story), without there being a specific concern from the surgeon or imaging. Positive margins or ECE - absolutely. I know where I'm chasing and where RT has the most chance to help. This one doesn't even have PNI.

The most common scenario that is seen for most of us is salvage laryngectomies. The data published is fairly clear that a lot of these patients are salvaged with a proper TL and don't need more treatment.

*MAJOR caveats here that we are speculating about something we know on paper, which one should never do with head and neck cancer. I just wanted to express where I was coming from.

 

[evilbooyaa]

I think both of the above posters present very reasonable thoughts and opinions. \
Given a relative data-free zone, I could certainly understand reticence to do so and varying aggressiveness in management.

I cannot think of a time that I would not recommend post-op RT (for primary, mainly, although probably for nodes as well) for a pT4N0 in the upfront setting. I understand there is a question, but until we can confirm it's safe to actually spare these patients from post-op RT, I can't imagine that I would.

 

[TheWallnerus]

For an oral cavity/hard palate/maxillary sinus s/p surgery and adjuvant RT, that recurs in 2y, and is s/p surgery again, what do you think the recurrence risk is? I think it’s gotta be… 67.382%.

And with adjuvant XRT a second time?

Might not be that much better.

It would easily be in the 57.382% range or better with the adjuvant RT imho. Possibly 52.382% with chemoRT.

 

[Palex80]

The initial tumor was in the mucosa of the cheek. The recurrent tumor grew in the hard palate.
The initial tumor did not show perineural invasion, neither did the recurrent one.

There is overlap in parts of the CTV of the initial plan to parts of the new tumor between hard palate and the cheek.

It‘s only a wild guess of mine, that the recurrence may have occured due to undetected perineural invasion.

The patient is in her early 80s. I wouldn‘t say overly fit, but also not really frail.

 

[drowsy12]

so a buccal tumor and now a hard palate one. may be some field canceriztion going on. Not sure I buy undetected PNI for a recurrence elsewhere in mucosa.

 

[Palex80]

After discussing extensively with the patient, she opted for follow-up. Thank you to everyone here!