Medical management of non-functioning pituitary adenomas

[Gfunk6]

I'm seeing a patient in her early 50s who presented with severe migraine HAs and did not respond to conservative medical management. Her PCP eventually ordered an MRI Brain which revealed a pituitary macroadenoma which extended into the R cavernous sinus.

She underwent visual and endocrinology testing, both were negative. She underwent a trans-sphenoidal resection and the sellar and suprasellar components were removed. Headaches resolved post-operatively.

We are now wondering what to do with the ~ 2 cm remnant in the R cavernous sinus. It has remained unchanged 8 months post-op. I was going to offer her adjuvant XRT, but one of my colleagues suggested bromocriptine, despite this adenoma being non-functioning.

Have you every heard of this?

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[Palex80]

I'm seeing a patient in her early 50s who presented with severe migraine HAs and did not respond to conservative medical management. Her PCP eventually ordered an MRI Brain which revealed a pituitary macroadenoma which extended into the R cavernous sinus.

She underwent visual and endocrinology testing, both were negative. She underwent a trans-sphenoidal resection and the sellar and suprasellar components were removed. Headaches resolved post-operatively.

We are now wondering what to do with the ~ 2 cm remnant in the R cavernous sinus. It has remained unchanged 8 months post-op. I was going to offer her adjuvant XRT, but one of my colleagues suggested bromocriptine, despite this adenoma being non-functioning.

Have you every heard of this?

Observation would be an option as well?
As long as the symptoms have disappeared and the patient doesn't seem to have any other problems, for example with visus.

UpTodate states: "Bromocriptine therapy for nonfunctioning adenomas has been disappointing [3]"
and points to this article:
http://www.ncbi.nlm.nih.gov/pubmed?term=18682516

 

[medgator]

Observation would be an option as well?

I would think so as well. Periodic MRI surveillance. Tx if enlarges or becomes symptomatic.

 

[Palex80]

I found an interesting article on bromocriptine:

http://www.ncbi.nlm.nih.gov/pubmed/3621623

 

[Gfunk6]

In this patient population, observation is always a reasonable choice that should be considered. However, in her case (young, long life expectancy, healthy) there is data to treat with adjuvant XRT. 10 yr local control of 95% with XRT compared to 22% with observation alone.

Also, no clear increased risk of strokes or panhypopit vs surgery alone per other data.

 

[Palex80]

Although certainly PFS may be better with adjuvant treatment, the same could be said for quite some "bening" tumors in the CNS like vestibular schwannoma, Grade I meningeoma, etc...
In my opinion PFS is not a valid endpoint to advocate for treatment in this case. You need to either show that early "adjuvant" treatment improves survival (which is basically impossible in benign tumors) or reduces the incidence of irreversible damage to healthy tissue or preserves quality of life.
If you could for example show that early "adjuvant" treatment for pituitary adenomas reduces the risk of permanent visual impairment or other neurological conditions, then you have a valid endpoint. If you can't, then sorry but in my opinion observation remains a valid option.

Your quoted article does demonstrate increased PFS but no difference in any other clinically meaningful endpoints.

 

[Gfunk6]

Although certainly PFS may be better with adjuvant treatment, the same could be said for quite some "bening" tumors in the CNS like vestibular schwannoma, Grade I meningeoma, etc...
In my opinion PFS is not a valid endpoint to advocate for treatment in this case. You need to either show that early "adjuvant" treatment improves survival (which is basically impossible in benign tumors) or reduces the incidence of irreversible damage to healthy tissue or preserves quality of life.
If you could for example show that early "adjuvant" treatment for pituitary adenomas reduces the risk of permanent visual impairment or other neurological conditions, then you have a valid endpoint. If you can't, then sorry but in my opinion observation remains a valid option.

Your quoted article does demonstrate increased PFS but no difference in any other clinically meaningful endpoints.

I agree with bolded statement. I also agree with the crux of your post that there is lack of meaningful data. However, 'meaningful endpoints' would require us perform detailed visual field/endocrine/neurologic testing on a periodic basis. Not clear if this data will ever be forthcoming. PFS is the best surrogate we have, albeit one with flaws as you note.

 

[Haybrant]

resurrecting super old thread. Got a nonfunctioning pituitary that is large and invading bilat cav sinus; it comes just up to and touches the chiasm, pt does not have visual deficit. Its a case im covering for so I don't know all the discussion, but decision was made for fractionated RT - no surgery. How do you plan these cases - fuse MRI draw the GTV and expand straight to a PTV while keeping the margin into chiasm to a minimum? Do you have a 5040 chiasm constraint you try to keep to (certain % < 5040?) Thanks

*apologies for rotated image cant seem to fix it

 

[Neuronix]

resurrecting super old thread. Got a nonfunctioning pituitary that is large and invading bilat cav sinus; it comes just up to and touches the chiasm, pt does not have visual deficit. Its a case im covering for so I don't know all the discussion, but decision was made for fractionated RT - no surgery. How do you plan these cases - fuse MRI draw the GTV and expand straight to a PTV while keeping the margin into chiasm to a minimum? Do you have a 5040 chiasm constraint you try to keep to (certain % < 5040?) Thanks

*apologies for rotated image cant seem to fix it

Yes fuse MRI to CT. A thin cut MRI helps. I put a 5 mm CTV on these and edit out of areas where the tumor clearly would not be, but that may be overkill. I then add a 3 mm PTV (thermoplast mask, daily CBCT).

5040 cGy is safe to chiasm. The QUANTEC constraint is 5500 cGy. Many people still use 5400 cGy. Keep hot spot 54 Gy out of optic apparatus and you're clean. For extra paranoia, just don't allow any hot spots greater than 7% (almost 5400 cGy) and you won't hurt chiasm or optic nerves.

 

[medgator]

Yes fuse MRI to CT. A thin cut MRI helps. I put a 5 mm CTV on these and edit out of areas where the tumor clearly would not be, but that may be overkill. I then add a 3 mm PTV (thermoplast mask, daily CBCT).

5040 cGy is safe to chiasm. The QUANTEC constraint is 5500 cGy. Many people still use 5400 cGy. Keep hot spot 54 Gy out of optic apparatus and you're clean. For extra paranoia, just don't allow any hot spots greater than 7% (almost 5400 cGy) and you won't hurt chiasm or optic nerves.

My gut reaction is that the optic constraints differ on the disease and life expectancy. The recent rtog GBM protocols allow 55-56 Gy iirc

 

[Neuronix]

I'd also suggest observation, to delay RT and to delay its late side effects for this young patient.

This is a good suggestion assuming that it's not growing. If it is growing and now touching chiasm, odds are high this tumor will affect his vision while odds are low that RT will.

 

[evilbooyaa]

I think seper's answer was to Gfunk's OP, while Haybrant has presented a new case. I agree with Neuronix on Haybrant's case. Point dose of 54 to the chiasm (not PRV) is what I would accept. No point of severely underdosing the one part that (if it grows) will cause the patient to lose their vision

Given GFunk's case was 5 years ago, I imagine our advice is not relevant at this point.

 

[Haybrant]

thanks guys, helpful info. Just curious are there any pituitary guidelines. Like I cant find anything. So this guy has normal hormone levels with elevated ACTH but only in the 70's - I think that is just stalk syndrome right. i was taught non-functioning pituitaries can be controlled at lower dose so i feel good w 5040

 

[Palex80]

t. i was taught non-functioning pituitaries can be controlled at lower dose so i feel good w 5040

Indeed local control seems to be good with that dose
Radiotherapy for pituitary adenomas: long-term efficacy and toxicity. - PubMed - NCBI
Long-term outcomes of radiotherapy for pituitary adenomas. - PubMed - NCBI
Non-functioning adenomas have a better PFS with SFRT than functioning ones.

 

[evilbooyaa]

thanks guys, helpful info. Just curious are there any pituitary guidelines. Like I cant find anything. So this guy has normal hormone levels with elevated ACTH but only in the 70's - I think that is just stalk syndrome right. i was taught non-functioning pituitaries can be controlled at lower dose so i feel good w 5040

I agree that 50.4 seems reasonable. Would have to review the literature though. However, that means you can give full dose to the PTV without having to underdose due to a conservative chiasm constraint (just keep it homogenous with < 107% hotspot to the chiasm)

 

[emt409]

Does your center not do SRS or hfSRT?

 

[Neuronix]

Does your center not do SRS or hfSRT?

What dose would you propose for this tumor in 1-5 fractions?

 

[emt409]

What dose would you propose for this tumor in 1-5 fractions?

There are lots of GK series on pituitary adenomas, and several CK & linac series as well. Doses are 12 - 20Gy for non-functioning, and 20-25Gy for functioning.

I would try and give this tumor 14 or 15Gy, and constrain to the chiasm to 8Gy. I would not constrain the hotspot, and I would expect a conformity in the vicinity of 1.05 - 1.1 for a 2cm tumor. I would also not isotropically enforce gradient, rather use tuning structures or high-penalty avoidance to push falloff out of chiasm.

If you're using a linac, use a couple non-coplanar arcs. I recently wrote a chapter on linac SRS and I put this table together for pituitary adenomas. Hope it's helpful.

If you're fractionating, you could do 24Gy/3fx or even 25-30Gy/5fx.

 

[evilbooyaa]

Haybrant's case has the tumor touching the chiasm per report. How do you propose to give the tumor even 14Gy while making 0 to 1mm away (my definition of 'touching') reach 8Gy without underdosing the tumor? Why underdose the one part that (if it grows) will cause blindness? Why not just do standard fractionation which has excellent outcomes, and as we've discussed here, requires zero underdosing of tumor?

Also, 20-25Gy single fraction for functioning adenomas? That seems excessively high. A secreting pituitary adenoma requires the same single fraction dose as a brain metastasis from an actual malignant cancer?

The series you posted in that table have a median GTV cc that is much lower than what this tumor would be (~2 x 2cm in just a 2D view)

I agree that it's a fine option for most non-surgical adenomas, but idk about one like this

 

[Neuronix]

Haybrant's case has the tumor touching the chiasm per report. How do you propose to give the tumor even 14Gy while making 0 to 1mm away (my definition of 'touching') reach 8Gy without underdosing the tumor? Why underdose the one part that (if it grows) will cause blindness? Why not just do standard fractionation which has excellent outcomes, and as we've discussed here, requires zero underdosing of tumor?

Bingo.

 

[Radiator20]

Although this case is being treated in a fractionated fashion, I would still sim in a stereotactic setup if you think the patient will be able to tolerate it every day. Certainly seems worthwhile to minimize PTV.

 

[emt409]

Haybrant's case has the tumor touching the chiasm per report. How do you propose to give the tumor even 14Gy while making 0 to 1mm away (my definition of 'touching') reach 8Gy without underdosing the tumor? Why underdose the one part that (if it grows) will cause blindness? Why not just do standard fractionation which has excellent outcomes, and as we've discussed here, requires zero underdosing of tumor?

Also, 20-25Gy single fraction for functioning adenomas? That seems excessively high. A secreting pituitary adenoma requires the same single fraction dose as a brain metastasis from an actual malignant cancer?

The series you posted in that table have a median GTV cc that is much lower than what this tumor would be (~2 x 2cm in just a 2D view)

I agree that it's a fine option for most non-surgical adenomas, but idk about one like this

I thought the thread was about gfunk's case, of which the sellar components have been resected. Consensus dose is that high for functioning adenomas. And yes, non-malignant adenoma requires a higher dose than malignant tissue. If you don't believe me, pull out the Regine or Roach books.

 

[Neuronix]

I thought the thread was about gfunk's case, of which the sellar components have been resected. Consensus dose is that high for functioning adenomas. And yes, non-malignant adenoma requires a higher dose than malignant tissue. If you don't believe me, pull out the Regine or Roach books.

I'm on board with you here. To get them to stop growing, 12 Gy is probably sufficient. To get them to stop functioning you have to slam them with on the order of 25 Gy.

This is a patient selection thing too. Microadenomas are usually functioning and they're usually far from the optic apparatus. Macroadenomas tend to be non-functioning, and they tend to present close to or abutting the optic apparatus. You give as much dose as you can sometimes.

 

[evilbooyaa]

I thought the thread was about gfunk's case, of which the sellar components have been resected. Consensus dose is that high for functioning adenomas. And yes, non-malignant adenoma requires a higher dose than malignant tissue. If you don't believe me, pull out the Regine or Roach books.

Fair enough. That's my own lack of education on the topic. Thanks for the info.

 

[emt409]

Fair enough. That's my own lack of education on the topic. Thanks for the info.

Sometimes there's just too much data...