Motivation
Important topic as brain mets remain one of the biggest challenges in Melanoma.
Isolated progression in the brain while stable disease outside the brain.
Grant McArthur
Incidence and prognosis of Melanoma brain mets
- Melanoma is Number 3 reason for brain mets (after lung and breast cancers)
- Melanoma has the highest level of cerebral tropism (Wen 2012)- means it likes to metastasize to the brain
- 40-50% patients with metastatic Melanoma will develop brain mets
- brain metastasis huge impact on survival
Biology of brain mets
The brain is a special organ.
NOTE
Metastasis from metastasis occurs
Melanoma has the highest level of CD3, CD8 and PD1 positive T-cells in brain mets of all cancers = could explain why checkpoints also work in brain mets in Melanoma
Adler 2017- it seems that BRAFpos patients more likely to develop brain mets than BRAF Wt
https://www.ncbi.nlm.nih.gov/pubmed/28787433
Neo-angenesis (new blood vessels forming) promotes growth of brain mets- means blocking it could help controlling brain mets
Surveillance of brain mets in Melanoma
Lewin- 2018
5/ 43 patients with Stage 3C (with follow-up for 47 months) recurred with brain mets, 3 also had mets elsewhere but 2 were asymptomatic.
So challenge is to argue for tight MRIs as many will not progress but for those who progress in particular in the brain, this is dangerous.
Caroline Robert
Combinations of local and systemic treatments to treat brain mets
BRAFi works in the brain but less well than outside the brain
BRAFi plus MEKi- Davies 2017
Ipi- Margolin 2011- response in brain similar to outside the brain
Pembro- Goldberg 2017- also works in brain
Nivo plus Ipi- Tawbi ASCO2017- 55% response rate in brain
also Long 2018- Lancet
CR- what is missing are trials how to combine systemic and SRT- AGREE
Parallel systemic immuno therapy and radiotherapy did not seem to increase the risk of necrosis but timing essential as both radiotherapy and immune therapy can induce inflammation in the brain.
Bottom line is that the treatment of brain mets is evolving very fast, there is a lot that can be done, so it's not the time to just give up.
Hussein Tawbi, MD Andersson
First-line treatment of brain mets
Timing if IO and SRS critical
synergy only if both at same time or very close to each other.
NOTE
Metastasis from metastasis occurs
Melanoma has the highest level of CD3, CD8 and PD1 positive T-cells in brain mets of all cancers = could explain why checkpoints also work in brain mets in Melanoma
Adler 2017- it seems that BRAFpos patients more likely to develop brain mets than BRAF Wt
https://www.ncbi.nlm.nih.gov/pubmed/28787433
Neo-angenesis (new blood vessels forming) promotes growth of brain mets- means blocking it could help controlling brain mets
Surveillance of brain mets in Melanoma
Lewin- 2018
5/ 43 patients with Stage 3C (with follow-up for 47 months) recurred with brain mets, 3 also had mets elsewhere but 2 were asymptomatic.
So challenge is to argue for tight MRIs as many will not progress but for those who progress in particular in the brain, this is dangerous.
Caroline Robert
Combinations of local and systemic treatments to treat brain mets
BRAFi works in the brain but less well than outside the brain
BRAFi plus MEKi- Davies 2017
Ipi- Margolin 2011- response in brain similar to outside the brain
Pembro- Goldberg 2017- also works in brain
Nivo plus Ipi- Tawbi ASCO2017- 55% response rate in brain
also Long 2018- Lancet
CR- what is missing are trials how to combine systemic and SRT- AGREE
Parallel systemic immuno therapy and radiotherapy did not seem to increase the risk of necrosis but timing essential as both radiotherapy and immune therapy can induce inflammation in the brain.
Bottom line is that the treatment of brain mets is evolving very fast, there is a lot that can be done, so it's not the time to just give up.
Hussein Tawbi, MD Andersson
First-line treatment of brain mets
Timing if IO and SRS critical
synergy only if both at same time or very close to each other.
Also interesting was in the questions at the end : after SRS how do you avoid problems associated with radiation-induced necrosis while trying to avoid cortico-steroids because you are treating checkpoint immunotherapies : two suggestions 1 dose of Bevacizumab (Avastin) or putting the patient back on anti BRAF for a short time
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