I am not sure why there is an assumption that pazopanib crosses blood-brain barrier? Lynette - I just read your excellent answer to kajer where you point out that "we don't know if Sutent can go through her Blood Brain Barrier to work on the brain mets." The same applies to pazopanib (and cediranib or any TKI) - or did I miss any relevant publication? The absence of new brain mets in Brittany case being on cediranib could not be a proof because we know numerous cases when there were single digit brain ASPS mets - resected/gamma knifed - gone and no new brain mets without any systemic treatment. On the other hand since we know that there are the cases of the brain mets bleeding on the TKI - could that be considered a proof that their do cross blood-brain barrier to be able to damage the feeding blood vessels and to cause the bleeding?
There is a full free text review about TKI in RCC
http://www.ncbi.nlm.nih.gov/pubmed/22754592
Novel agents in renal carcinoma: a reality check.
and they conclude: "the role of these therapies in the treatment of brain metastases remains unclear"
It looks like TKI are able to reduce the
incidence of the new brain mets in RCC and even improve the OS in it (we always look for a reference to this disease as they have more cases/more testing done and its clinical character is somehow resembles ASPS)
http://www.ncbi.nlm.nih.gov/pubmed/21484781 but it is a more aggressive/fast growing disease so the influence on the overall survival might be difference from ASPS - i.e. if the disease can kill the patient in 6 months and the drug gives a stability for 9 months you gain 3 months in OS, but if the disease can kill the patient in 3 years and the drug gives a stability for 9 months and grows faster after that - there might be a loss in OS not gain.
There is a big problem with TKI acquired resistance - it is hard to say what the result will be with in ASPS for the OS, when to use them, how to discontinue them etc.
About role of Ki67 in ASPS - as I understand it is an indicator for the probability to develop distant mets but not it being more aggressive. There is an older article:
http://www.ncbi.nlm.nih.gov/pubmed/10919382
We still have to result from Ivan's brain MRI. It is getting done slow in Canada. His brain surgeon was going to run all the tests on his brain met tissue removed last time but we did not get to see the results.
Alveolar soft part sarcoma: the role of prognostic markers.
"There was no correlation of these markers with prognosis or clinicopathologic parameters...Our preliminary data suggest that Ki-67-positive immunostaining may be a prognostic indicator for the development of metastases in ASPS."
Let me know if you have seen other articles on the subject.
Also you have to take into consideration that there is a very frequent genetic heterogeneity between the primary tumor and distant metastases and that CNS metastases and other - lungs, soft tissue ets. - are going to differ a lot as well, so to plan for the brain mets to be treated you would need to have a brain mets tissue etc. Hard.
