Two (tough IMHO but) interesting cases for discussion

[Palex80]

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1.

24 year old female with a Stage II DLBCL in the mediastinum. She received 6x R-CHOP + 2x R, the underwent mediastinal consolidation with 36 Gy. Two months after RT completion she had a seizure and was diagnosed with 2 cm mass in the frontal lobe in the MRI. Liquor exam was not made, stereotactic biopsy of the mass showed DLBCL, whole body PET-CT scan showed CR of the mediastinal mass.
She then underwent high dose Methotrexat treatment and then had high dose chemotherapy with carmustine, rituximab and thiotepa followed by autologous HSCT. MRI scans during the chemotherapies showed the mass decreasing, in the final MRI there was no more enhancement in the area (residual scar?)
No comorbidities.

The patient is now sent to us for evaluation of radiotherapy options.
The responsible medical oncologist had the idea of us performing a stereotactic treatment of the residual scar only. 😕

I am thinking of offering her WBRT and then a stereotactic boost.
I am kind of troubled concerning the dose, but I am leaning towards a hyperfractionation schedule like in RTOG 9310, perhaps a bit more deescalated.
Perhaps 36 Gy (1 Gy bid) and then a stereotactic boost with 3x3 Gy to the initial volume with a 5 mm margin?

Your thoughts?


2.

46 year old male with a pT1 (11mm) pN2a (1/24) (44mm, no extranodal extension) cM0 G3 R0 (at least 8 mm) tonsillar cancer right.
He got a primary tumor resection and a right side neck dissection. Additionally one enlarged node was dissected on the right neck side and it was negative.
No comorbidities.

The patient is now sent to us for evaluation of radiotherapy options.

It is clear to me that he needs radiation therapy.
The critical question is:
Unilateral neck irradiation or bilateral neck irradiation?
If it had been a pN1, I would have probably offered him unilateral irradiation and would have not recommended bilateral irradiation (with a bit of a strange feeling, since it was a G3-tumor and he's just 46 years old).
However with this big pN2a node I don't feel comfortable with unilateral irradiation. He has a risk of at least 10% IMO for micrometastatic disease in the left side of the neck, although most of the data we have come from pN1-patients and there were only few pN2a patients in the published patterns of recurrence studies.

Your thoughts?

 

[Brim]

Two months after RT completion she had a seizure and was diagnosed with 2 cm mass in the frontal lobe in the MRI. Liquor exam was not made, stereotactic biopsy of the mass showed DLBCL, whole body PET-CT scan showed CR of the mediastinal mass.

Liquor exam?
I should have done residency in Switzerland! 😍

 

[Palex80]

Liquor exam?
I should have done residency in Switzerland! 😍

Liquor cerebrospinalis = CerebroSpinal Fluid (CSF).

 

[Brim]

Liquor cerebrospinalis = CerebroSpinal Fluid (CSF).

Ohhh... that's not as much fun as I was thinking.

 

[Palex80]

No comments on the cases?
🙁🙁🙁

 

[deleted4401]

Case #1 - no comments. have no idea. would have to read a bunch

Case #2 - though the series had fewer N2a patients, the two largest series included >20% (from what I remember) that were N2, and still very low neck failures. In fact, in the PMH series, no T1s or N0s failed in the contra neck. If well lateralized lesions, even if N2a, you can probably safely not treat the other side of the neck, even though this is a post-op case, not an intact case like the series that define patients that you can only tx the ipsi neck. In reality, I'd probably treat it. Kind of scary not to.

I don't take grade into account for HNC. Does anybody else?
-S

 

[Brim]

Case 1:
As far as I know, there's not a whole lot of data to guide us on what dose of RT to use in this setting. The dose you suggested is extrapolated from primary CNS lymphoma. While it's a bit of a stretch to extrapolate PCNSL to metastatic secondary CNS involvement, it's not unreasonable to use that evidence to guide your dose.

Unfortunately, secondary CNS involvement from lymphoma is very, very bad. Here's a link from a series from MDACC. The median survival was only 88 days and the 1yr OS was 25%.

So, it should be recognized that the goal of therapy is for palliation only. In this case, any regimen that you typically use for palliation of CNS metastases ought to be used (30/10; 37.5/15; whatever).

However, with that being said, this patient is only 24 years old, so you might try to be more aggressive. I think your regimen is reasonable.

Case 2:
I'd just treat the unilateral neck, since I feel there's an acceptably low risk of contralateral nodal failure. But, there's nothing wrong with treating bilaterally.

 

[RadRadRad]

Case 1: ???

Case 2:
Reminds me somewhat of the post a few months ago for post-op oral cavity.

As in the majority of post-op H/N cases, bilateral neck RT is a reasonable option in my opinion, as this is what was done in RTOG and EORTC postop trials. I think ipsilateral is also reasonable, however In post-op patients there are several theoretical concerns at this point:

1. My recollection of the ipsilateral tonsil RT data from PMH is that none of the pts were postop and for Colorado (a small series of ~20 pts) the majority were postop. IT may be possible that recurrence patterns after neck dissection-->RT are different than those after definitive RT. It would be nice to have a larger series of post-op N2 patients, but I don't know of any.

2. How much do you trust your ENT's evaluation of the primary tumor extent. With a 11mm primary this is less concerning, but for a larger primary you might prefer to have seen the patient preop so you are sure there is no BOT or midline palate involement.

At my institution, with an ENT we know well, we would strongly consider ipsilateral RT.

 

[OTN]

Case 1: I would go with single-fraction radiosurgery, likely ~12 Gy x 1, depending on size of the original lesion, location to critical structures, etc. I would contour the original (pre-CTx) T1 enhancing mass without a GTV --> CTV margin and add a PTV margin depending on your particular setup. I would avoid whole brain in this case if possible- you can always add it later if necessary. I'd be wary of CNS toxicity in a patient who received both MTX and WBRT.

Case 2: As long as the primary tumor was well-lateralized you could treat the ipsilateral neck alone.

 

[Palex80]

Thanks for all the input. A couple of comments from my side.

Case 1:
I am not aware of any data on SRS or SFS. Therefore if I am going to treat, I have to treat the whole brain (+boost the original site).
Since this is a 24 year old patient and an "all or nothing" situation, we are gonna do the whole package with WBRT+Boost.

Case 2:
I trust the ENT's evaluation, the tumour is out and was well lateralized. What bother's me the most is the size of the affected lymph node. Had it been only 25mm, it would have been a whole different situation, but this one is 44mm!
I hope the pathologists have done their work right, since at this size there's seldom no extracapsular spread. Extracapsular spread would have meant chemo as well.

The data is there for T1 N0 and T1 N1, however there are only few patients mentioned in the literature with pN2 disease.
I don't think I can totally ommit contralateral irradiation and actually feel good about it. If this patient relapses, he probably has a very bad prognosis. He's also young and has no comorbidities, meaning that he needs a good treatment now. I don't think I can actually extrapolate the data from the primary RT-series, because there is one bias there:
There's a difference between treating a cT1 cN2a and a pT1 pN2a neck. The difference is local control.
Patients who failed locally in the publiched cT1 cN2a series were removed from the analysis of contralateral failure. In our patient the risk for local failure after RT is quite low in comparison to these series, since we are actually treating adjuvantly. Therefore the competing risk of local failure is lower, making a contralateral failure more probable.
I hope you understand what I mean.
I am gonna go with bilateral irradiation and treat the contralateral neck only down to the level of the larynx. I will do my best to limit the field cranially as well, in order to safeguard the parotid gland.

 

[temujim]

Case 2:

There is a paper in the Nov 1 issue of IJROBP regarding this issue. 5 yr contralateral neck failure was 12% for N1/2a patients (though only 15% of their sample were oropharyngeal primaries). Some would radiate CL neck for that risk, some would not.

Though I agree, with a 44 mm node, that if the pathologists looked hard enough, they would probably find ECE.

 

[deleted4401]

Nice pick up ... 12% is high enough for me, but with 71% salvage rate, that means total failure of 3.5%, can easily make the argument to not treat. In IMRT era, parotid sparing pretty easy and so I think it's gotta be physician and patient preference.

Case 2:

There is a paper in the Nov 1 issue of IJROBP regarding this issue. 5 yr contralateral neck failure was 12% for N1/2a patients (though only 15% of their sample were oropharyngeal primaries). Some would radiate CL neck for that risk, some would not.

Though I agree, with a 44 mm node, that if the pathologists looked hard enough, they would probably find ECE.

 

[medgator]

Some would radiate CL neck for that risk, some would not.

I would look at the morbidity of Tx vs. possible benefit. As simulD alluded to, in the era of IMRT, I think the morbidity of 50-55 Gy to the contralat neck is low so I would do it.

 

[SchwettieBalls]

Does anyone else have a problem with the way they describe this as "results of a prospective management approach?" They are implying that this was a prospective protocol with predefined patient eligibility criteria, RT parameters, and endpoints, etc, which it clearly wasn't if you read the methods. This basically is a retrospective series of their experience with unilateral neck RT for tonsil cancer. Seems like they should have called it as such.

 

[Palex80]

Does anyone else have a problem with the way they describe this as "results of a prospective management approach?" They are implying that this was a prospective protocol with predefined patient eligibility criteria, RT parameters, and endpoints, etc, which it clearly wasn't if you read the methods. This basically is a retrospective series of their experience with unilateral neck RT for tonsil cancer. Seems like they should have called it as such.

This sounds to me like an unfinished study protocol, that never made it to the ethics committee. Basically a group of physicians agreeing to treat all patients presenting at this stage with this kind of an approach, but never formulating this concept as a trial with strict criteria, methods, follow-up, etc.