The brain is an immune privileged organ so there is a restrictive influence of the immune response which makes it harder to treat. They have recently discovered some kind of fluid transfer system but it lacks the normal lymphoid structure so antigen presentation and T-Cell infiltration is less well understood. Melanoma has more CD3+ and CD8+ TIL Density in Melanoma BMs and more FOXP3 TIL. The role of Microglial Macrophages (these are the main macrophages in Brain tissue and are the main form of active immune defence in the brain and central nervous system) in BMs is complicated : they are both tumour-promoting and tumour-suppressing depending on where in the metastatic cascade they are - brain tumour cells seem to co-opt them in some way - does inhibiting microglia reduce BM cell invasion ?
The Biology of Brain Mets :
A couple of nice slides of the Venue of action of Checkpoint Inhibitors in BMs :
And a summary :
(http://meetinglibrary.asco.org/content/50918?media=vm)
One Melanoma Abstract -
Abstract 2071 - The retrospective analysis of Brain mets in Melanoma by the Boston team did show clinical activity on Brain Mets by Pembrolizumab - there is an ongoing study of patients with untreated BMs : NCT02085070
One Poster presentation :
Poster : Another retrospective study on the effect of Pembro using real world data from the french MELBASE registry - POSTER - the results were not that conclusive because results were complicated by radiotherapy treatment and pretreatment with Ipilimumab before Pembrolizumab - but overall they concluded that Pembrolizumab PROBABLY better than Ipilimumab in Melanoma Brain Mets - apart from testing how to use registry data - there is not much we can take from this.
Use of SRS in treating BMs - Is there a role for Whole Brain Radiation ?
The initial treatment of most patients with limited brain metastases is stereotactic radiosurgery (SRS). SRS is a type of radiotherapy that aims beams precisely at the area of the brain tumor. After SRS, some patients also receive adjuvant whole-brain radiation therapy (WBRT).
The use of WBRT in patients with limited brain metastases has been controversial. Although WBRT does control tumor growth, it can have detrimental effects on quality of life. Preliminary findings from a federally funded study (NIH) have provided new insights into the impact of adjuvant WBRT on cognition
Patients with one to three small brain metastases who received WBRT after SRS were more likely to experience cognitive decline within the first 3 months than those who received SRS alone. Specifically, those who received WBRT had a greater decline in memory and verbal communication. There was no significant survival benefit from WBRT, compared with SRS alone.
The results strongly suggest it may be preferable to forgo WBRT in favor of SRS, because SRS can preserve a patient’s cognitive function as long as possible. Longer-term follow-up to assess late neurocognitive effects of WBRT is pending.
Nonetheless, WBRT decreases recurrence of brain metastases, and it is possible that it may prolong survival in certain patients. A smaller Japanese study identified one such patient group. Patients with NSCLC who had one to four brain metastases and a favorable prognosis lived 6 months longer when treated with SRS and WBRT compared with SRS alone. No such survival advantage was observed among patients with a poor prognosis. Larger prospective studies are needed to confirm these findings.
A few slides on Adjuvant WBRT - basically dont do it ...
and is there ANY place for WBRT :
From Melanoma perspective : this is 2015 but a useful summary :
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