Brain mets….treatments?

[Angela21]

My husband Tim finished his 4 Yervoy treatments with little side effects. Four weeks after completion, he had a CT scan and MRI. 12 brain mets were found. He began whole brain radiation on Thursday 5/9. He will have 10 radiation treatments. We are now considering what comes next. Does anyone know any anti-pd1 trials that allow brain mets? We are also considering TIL. Anyone do TIL with brain mets?

AngelaAngela21

Posts: 13

Joined: 05 Jan 2012 20:40

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[Catherine Poole]

Angela,

I can certainly understand how stressful this must be for both of you. Unfortunately, few treatments are effective for brain mets but radiation. The blood/brain barrier keeps systemic agents out for the most part. Is he BRAF positive? The new Braf/Mek combo by GSK should be approved shortly and did show some efficacy for brain mets. He could start Yervoy, also approved, to see if it might produce a good immune reaction in the body. Otherwise, most trials require he be finished with radiation treatment. He will need to recuperate from the whole brain radiation too. Where are you going for treatment? TIl therapy requires you be in very excellent health to endure it. I don’t think he would be able to do that. Tell us a little more..

[benp]

Hi Angela,

I have done TIL with brain mets that were treated with SRS just prior to the therapy. Most disappeared, except 1 that required excision. It has been shown that most current immunotherapies (TIL, Ipilimumab) are just as active in the brain as elsewhere. Braf inhibitors are also effective, if he is positive for the gene. May I ask why targeted radiation was not considered? Twelve is certainly not too many to treat, assuming they are all small.

Good luck,

Ben.

[Catherine Poole]

Ben,

Please let me know the studies that show these immunotherapies are effective for brain mets. I haven’t seen that research. I did see a small study of 15 patients that showed some response in the brain with the BRAF/Mek. As for TIL, I have not seen that evidence either. For TIL at NCI you can’t have more than 3 brain mets. In this situation, SRS or gamma knife couldn’t be used, there were multiple brain mets and whole brain radiation was used. After that therapy, I imagine TIL may be difficult to tolerate and he wouldn’t be accepted into a TIL program.

[benp]

Hi Catherine,

Unfortunately I spend a lot of my time reading research papers so I can best plan my treatment, so here are some references on immunotherapy activity in the brain.

Ipilimumab;

http://meeting.ascopubs.org/cgi/content/abstract/28/15_suppl/8523 (particularly see conclusion)

http://www.ncbi.nlm.nih.gov/pubmed/22456429

TIL;

http://clincancerres.aacrjournals.org/content/16/19/4892.short

BRAF;

I was actually part of the trial for the stage 2 trial . Happily had a response.

http://www.sciencedirect.com/science/article/pii/S0140673612603985

http://www.sciencedirect.com/science/article/pii/S147020451270431X

I have been told directly that up to 30 lesions have been treated at once with Gamma Knife (I had 10), but there does seem to be a limit on the cumulative volume of brain disease, which is probably common to all of the above. (Keeping in mind one 2cm diameter tumor has the same volume as ten 0.9cm tumors (assuming spheres).)

Hope this helps.

Ben.

[Angela21]

Thank you Catherine and Ben for your information. Tim is Braf negative. Two of his tumors are over 2cm, so the doctors went with WBR. We are at the James Center at Ohio State University. His doctor seems to feel the Yervoy could still do some work even though he finished it 5 weeks ago. He has finished 7 of 10 radiation treatments. Another MRI will be done in about 4 weeks. He is only experiencing some fatigue and is living quite normally otherwise.

[Catherine Poole]

There is a small study that shows that combining radiation with Yervoy can increase the response Angela. But PD1 has a higher response rate overall.

Thanks for posting the studies Ben, but the conclusion to the first one says: The analyses are ongoing and final data will be presented. I truly wish we had some conclusive evidence of these therapies working for brain mets, but don’t want to get hopes up without strong evidence of many people having a response.

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