Dose to eye choroidal melanoma.

[Kroll2013]

Dear colleagues,

I have a 50 yo patient, diagnosed of a choroidal melanoma 2 years ago, that he neglected.
he came back with a local tumor progression. Surgical enucleation is not possible.
Pet CT shows no secondary lesions-M0.
the optimal option for him would be radical EBRT.
there is no accessible proton facility.
What is the most efficient dose/fractionation protocol to optimize his local control chances?

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[Radonc90]

I use I-125 brachytherapy plaque.
Anywhere between 8500-9000 cGy prescribed at max depth of tumor (based on ultrasound measurements).
I'd not use photon EBRT, whose data is nowhere near brachy data.
Brachy is the way to go for ocular melanoma.

 

[seper]

I use I-125 brachytherapy plaque.
Anywhere between 8500-9000 cGy prescribed at max depth of tumor (based on ultrasound measurements).
I'd not use photon EBRT, whose data is nowhere near brachy data.
Brachy is the way to go for ocular melanoma.

BCT does not work well for thick lesions, which sounds like this is. If pt is blind to that eye, I’d try for 66.6 Gy.

 

[Radonc90]

Fair enough, simply bc no tumor detail provided by the original poster.

 

[ramsesthenice]

Dear colleagues,

I have a 50 yo patient, diagnosed of a choroidal melanoma 2 years ago, that he neglected.
he came back with a local tumor progression. Surgical enucleation is not possible.
Pet CT shows no secondary lesions-M0.
the optimal option for him would be radical EBRT.
there is no accessible proton facility.
What is the most efficient dose/fractionation protocol to optimize his local control chances?

Enucleation is not possible? That sounds bad. And impossible to plaque. Agree with mid-60s. Might be worth seeing if you could sprinkle some pembro in there with it?

 

[FrostyHammer]

Enucleation is not possible? That sounds bad. And impossible to plaque. Agree with mid-60s. Might be worth seeing if you could sprinkle some pembro in there with it?

Yes because off-label immunotherapy doesn't cost the government/patients/healthcare system a dime. And unlike med oncs expanding indications for RT, here we have rad oncs baselessly expanding indications for immunotherapy.

And FWIW, this is a patient I would SERIOUSLY consider sending for protons even if that means in another country (though not sure of the logistics of all that).

 

[ramsesthenice]

Yes because off-label immunotherapy doesn't cost the government/patients/healthcare system a dime. And unlike med oncs expanding indications for RT, here we have rad oncs baselessly expanding indications for immunotherapy.

And FWIW, this is a patient I would SERIOUSLY consider sending for protons even if that means in another country (though not sure of the logistics of all that).

You are right. Clearly I was telling them they should prescribe immune therapy themselves instead of talking to their colleagues in oncology about the possibility.

 

[thecarbonionangle]

Lots of regimens out there. Stereo technique, 60/10.

 

[ramsesthenice]

Yes because off-label immunotherapy doesn't cost the government/patients/healthcare system a dime. And unlike med oncs expanding indications for RT, here we have rad oncs baselessly expanding indications for immunotherapy.

And FWIW, this is a patient I would SERIOUSLY consider sending for protons even if that means in another country (though not sure of the logistics of all that).

I can admit when I am wrong. Ran the topic by our melanoma med oncs who throw CPIs at basically everything. They like the idea but agreed it would probably be hard to get a compassionate use for this indication. Also feel like the data for advanced choroidals really is pointing to dual checkpoint therapy more so than cutaneous melanomas and since the toxicity of dual therapy can be significant they wouldn't want to do it in this setting. Their preference would be to give radiation and use immune therapies down the line in the very likely even this person progresses.

I would argue though, that these conversations, if framed correctly, should be encouraged, not discouraged. If you tell a surgeon or med onc, "Hey look, this person has X condition that is different from our normal discussions because Y. Radiation is the usual treatment and I think we should do it but admittedly control for large tumors is not great. Should we consider also trying (blank) in this case?" they are far more likely to appreciate it and reciprocate with collaborative discussions regarding complex cases in the future. Patients with truly unresectable choroidal melanoma are pretty rare and not well-represented in any high level study. They never will be either because (fortunately) there are not enough of them. Their outcomes are poor.

 

[FrostyHammer]

I can admit when I am wrong. Ran the topic by our melanoma med oncs who throw CPIs at basically everything. They like the idea but agreed it would probably be hard to get a compassionate use for this indication. Also feel like the data for advanced choroidals really is pointing to dual checkpoint therapy more so than cutaneous melanomas and since the toxicity of dual therapy can be significant they wouldn't want to do it in this setting. Their preference would be to give radiation and use immune therapies down the line in the very likely even this person progresses.

I would argue though, that these conversations, if framed correctly, should be encouraged, not discouraged. If you tell a surgeon or med onc, "Hey look, this person has X condition that is different from our normal discussions because Y. Radiation is the usual treatment and I think we should do it but admittedly control for large tumors is not great. Should we consider also trying (blank) in this case?" they are far more likely to appreciate it and reciprocate with collaborative discussions regarding complex cases in the future. Patients with truly unresectable choroidal melanoma are pretty rare and not well-represented in any high level study. They never will be either because (fortunately) there are not enough of them. Their outcomes are poor.

Thanks for the nice anecdote, and what they said makes sense.

I will say though that reciprocity highly depends on the particular med onc/surgeon. Most don't give a crap about RT and will just take their opportunities to cut/throw CPIs without throwing RT a bone in return. Regardless of throwing bones to one another, though, the data should do the talking, especially for immensely expensive drugs. At least for metastatic uveal melanoma cases there are prospective (nonrandomized) studies, but for nonmet cases there's nothing. And FWIW the prospective trial data don't even look that great despite the rosy spin they all try to put on it.

 

[Lamount]

EBRT dose with Protons is 50-70Gy(RBE) in 5 fractions. I would anticipate that delivering this with photons would destroy their vision... raising the question of just doing enucleation if protons are not an option

Another important consideration is that the certain cytogenetic mutations (present about 50% of the time) portend a high risk of liver mets.. which could help inform the use of immunotherapy.
*apologies if this was discussed above

 

[ramsesthenice]

I would anticipate that delivering this with photons would destroy their vision... raising the question of just doing enucleation if protons are not an option

How hard one pushes for protons really depends on his current visual function and how much useful vision this person can expect even after proton therapy. Its been neglected for a couple years and is unresectable. It is entirely possible this person has useful vision in the affected eye and has an unusual degree of extraoccular extension that is rendering it unresectable in which case protons would clearly afford him a better chance of keeping useful vision. Its also possible it involves > 50% of the retina and we are kidding ourselves to think any form of EBRT will spare enough retinal tissue to matter. If they live close to a proton center that is one thing. If they don't, should probably make sure protons have a realistic chance of helping before telling him he needs to travel for treatment. Same for opthalmaplegia. The risk for post-treatment pain is going to be high no matter what. This is not the typical choroidal melanoma.

 

[Lamount]

How hard one pushes for protons really depends on his current visual function and how much useful vision this person can expect even after proton therapy. Its been neglected for a couple years and is unresectable. It is entirely possible this person has useful vision in the affected eye and has an unusual degree of extraoccular extension that is rendering it unresectable in which case protons would clearly afford him a better chance of keeping useful vision. Its also possible it involves > 50% of the retina and we are kidding ourselves to think any form of EBRT will spare enough retinal tissue to matter. If they live close to a proton center that is one thing. If they don't, should probably make sure protons have a realistic chance of helping before telling him he needs to travel for treatment. Same for opthalmaplegia. The risk for post-treatment pain is going to be high no matter what. This is not the typical choroidal melanoma.

Ugh. Sounds like a tricky situation.

 

[Kroll2013]

BCT does not work well for thick lesions, which sounds like this is. If pt is blind to that eye, I’d try for 66.6 Gy.

the target would be his whole ocular globe. would 60Gy/10 fr be safe?

 

[Kroll2013]

EBRT dose with Protons is 50-70Gy(RBE) in 5 fractions. I would anticipate that delivering this with photons would destroy their vision... raising the question of just doing enucleation if protons are not an option

Another important consideration is that the certain cytogenetic mutations (present about 50% of the time) portend a high risk of liver mets.. which could help inform the use of immunotherapy.
*apologies if this was discussed above

he already lost all vision in this eye. the target encompasses the whole ocular globe.
would a dose of 60Gy/10fr to the whole globe (eyelids and cornea included) safe? what the possible toxicities and side effects with such high doses?

 

[ramsesthenice]

he already lost all vision in this eye. the target encompasses the whole ocular globe.
would a dose of 60Gy/10fr to the whole globe (eyelids and cornea included) safe? what the possible toxicities and side effects with such high doses?

That sounds like a bad idea. Necrosis and painful opthalmaplegia would be possible. The reality is this is probably palliative. I would be inclined to treat it as such and not take chances treating it like a typical choroidal melanoma because it’s not. I get your thinking. He’s had this for a long time without progressing distantly. The biology of this thing is a little weird but a good long term outcome is still unlikely. Definitive doses are reasonable but I would be inclined to use more modest hypofractionation.

 

[Radonc90]

To me, this is a case of enucleation.
RT will cause a lot of issues (pain, etc.).

In the original post, you mentioned that "Surgical enucleation is not possible"...I am just wondering why?
Is it high risks of anesthesia or pt's refusal to undergo enucleation?

 

[deleted605854]

To me, this is a case of enucleation.
RT will cause a lot of issues (pain, etc.).

In the original post, you mentioned that "Surgical enucleation is not possible"...I am just wondering why?
Is it high risks of anesthesia or pt's refusal to undergo enucleation?

It sounds like this thing has invaded the orbital socket and would require not enucleation but rather an en bloc resection which would then need some type of recon

That's my understanding at least

 

[Kroll2013]

To me, this is a case of enucleation.
RT will cause a lot of issues (pain, etc.).

In the original post, you mentioned that "Surgical enucleation is not possible"...I am just wondering why?
Is it high risks of anesthesia or pt's refusal to undergo enucleation?

high risk of anesthesia secondary to patient's comorbidities.

 

[Neuronix]

he already lost all vision in this eye. the target encompasses the whole ocular globe.
would a dose of 60Gy/10fr to the whole globe (eyelids and cornea included) safe? what the possible toxicities and side effects with such high doses?

Absolutely not safe.

60 Gy in 10 fractions to the entire globe will result in severe conjunctivitis, radiation keratopathy, and severe xerophthalmia. Patient will have a painful, chronically irritated eye and will hate you for the rest of their life (or be enucleated palliatively).

You could give this kind of dose to a small area while being mindful to limits of anterior chamber, surface of the eye, and lacrimal gland. If you cause retinopathy or optic neuropathy in a blind eye, so what?

If you cannot give the radiation safely, have the eye taken out.

It sounds like this thing has invaded the orbital socket and would require not enucleation but rather an en bloc resection which would then need some type of recon

That's my understanding at least

That's even more difficult in a previously radiated field. At least with the eye out you can treat the soft tissue (tumor and normal structures) in the area without having to worry about the eye coming out later.

 

[gmsquid]

Absolutely not safe.

60 Gy in 10 fractions to the entire globe will result in severe conjunctivitis, radiation keratopathy, and severe xerophthalmia. Patient will have a painful, chronically irritated eye and will hate you for the rest of their life (or be enucleated palliatively).

if V1 wasn’t destroyed by the tumor

 

[Kroll2013]

Absolutely not safe.

60 Gy in 10 fractions to the entire globe will result in severe conjunctivitis, radiation keratopathy, and severe xerophthalmia. Patient will have a painful, chronically irritated eye and will hate you for the rest of their life (or be enucleated palliatively).

You could give this kind of dose to a small area while being mindful to limits of anterior chamber, surface of the eye, and lacrimal gland. If you cause retinopathy or optic neuropathy in a blind eye, so what?

If you cannot give the radiation safely, have the eye taken out.



That's even more difficult in a previously radiated field. At least with the eye out you can treat the soft tissue (tumor and normal structures) in the area without having to worry about the eye coming out later.

the man is oxygen dependent. any kind of surgery is not possible.

 

[medgator]

the man is oxygen dependent. any kind of surgery is not possible.

Palliate when he becomes symptomatic?