Cocktail for Yara’s father / help with drug side effects / 30% PD-l1 expression

Hello my dear friends and partners!

I had many doubts and I still have them despite of reading much.
And I decided to ask for your help at least.

My father had surgery 4 month ago. Chemoradiation finished 1 month ago. Left side of brain was damaged. He has Glioblastoma.

He has problems with speech and memory now.
That is why it is too hard to establish the cause of some uncomfortable and bad feelings after taking medicines and CAMs… He can not describe it correctly and can not remember when it was started for example…

---------He has no mgmt/idh1/braf/msi
---------He has 30% PD-l1 expression.
---------MRI shows continued growth (mono TMZ was not effective).

This month we started:
avastin+TMZ (5+23, 400 mg)

It is risky because TMZ did not worked well before. But I found it can do other work: reduce PD-l1 expression. And decided to use PSP(PSK) Oriveda together (6 pills =5 days with TMZ, 2 pills other days).

!) MAIN QUESTION: is this mechanism can work or not?
https://www.ncbi.nlm.nih.gov/pubmed/30709339

!) SECOND QUESTION IS: he is getting shakes. What can it be?  (inside based like fever). But temperature is ok. Blood pressure is pretty normal. Pulse is ok.
Problem is – he can not remember when it was started (may be after avastin). It was more than 1 time. He is hiding his condition may be…
And he sleeps much.

These supplements was added (after radiation/before or together with new chemo):
avastin (1 in 2 weeks) +TMZ (5/23)
++++++ melatonin 20mg only 5 days (or need to use all time?)

---------1) alpha lipoic acid (2x300=600)
---------2) curcubrain (1x400=400)
---------3) PSP(PSK) Oriveda (2x350 = 700  or 6 at TMZ days)
---------4) Carvedilol for pulse (1/2)
---------5) started to change carbamazepine (200mg) to keppra (250mg) – TOGETHER 1 week. Then more keppra less carb.

PS – keppra for unmethylated MGMT (still risk if TMZ not working)

Help me to connect his fever/shake with suppliments.
I can guess 1) it is avastin 2) keppra together carbamazepine 3) may be PSK/PSP… But may be you know bwtter?

Also he is taking (from the beginning)

---------metformin (1500)
---------Boswellia (2000)
---------D3 (4000)
---------Omega3 (1500)
---------allopurinol
---------Losartan
---------Nifedipine
---------Aspirine low dose

He has diabetes 2 type/hypertonia/


-----------What can I add or remove? (may be malatonin all days not only 5)? may be lower dose TMZ/ methronomic or replace TMZ with Irinotecan? (to not risk with combinations).
------------Is my combinations effective (TMZ+melatonin+PSP+keppra) with our mutations? (add/remove?)
------------What can be the reason of weakness and shake/fever?
------------Do you have link for Japan protocols (psk/psp)?
Thank you!

Clinical trial: IDH1 R132H peptide vaccine + avelumab (Germany)

A prior trial tested this vaccine (IDH1 R132H peptide vaccine) for gliomas with this IDH1 mutation.  The current trial is testing vaccine alone versus avelumab (PD-L1 inhibitor) alone versus combined vaccine + avelumab.

It is recruiting first recurrent gliomas of grade 2-4 with the IDH1 R132H mutation.

Open in Heidelberg and Mannheim Germany, and will also be open at several other centres in Germany.

https://clinicaltrials.gov/ct2/show/NCT03893903

Baseline corticosteroids reduce activity of PD-L1 blockade

https://www.ncbi.nlm.nih.gov/pubmed/30125216 
Impact of Baseline Steroids on Efficacy of Programmed Cell Death-1 and Programmed Death-Ligand 1 Blockade in Patients With Non-Small-Cell Lung Cancer

http://sci-hub.tw/https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30666-1/fulltext  (summary of study published in the Lancet)

"Baseline corticosteroid use was associated with decreased overall response, and shorter median progression-free survival and overall survival in patients who received the equivalent to 10 mg prednisone or more per day at the start of the PD-L1 blockade."

10 mg of prednisone is equivalent to only 1.6 mg of dexamethasone.

http://clincalc.com/corticosteroids/

Should we get the NGS done? If yes, from where?

Hi folks/Stephen,

Needed a bit of help from you all. My mom is a GBM patient who was diagnosed in Sep 2017. Her cancer is IDH1/2 -ve, methylated and 1p/19q codeletion negative, this is the information that we gauged from the initial gene testing that was done by our hospital post surgery. We are now considering a next generation gene sequencing test done, and I had the following questions on the same:

1. How helpful has the gene sequencing report been for you so far, if you have got one done? What questions should I look at getting answered from this test?

2. Since there is very little tumor tissue that we all have, which is the best place to get the gene sequencing done from? I currently have read and spoken to OncoDNA, StrandAdvantage, RGCC Greece and FoundationOne so far. Which one would you recommend, and why? The recommendation could be different from the mentioned five too.

I read the following doc shared by Stephen in the Brain Tumor library too, but I'm not quite able to figure out on which test is a more appropriate one for what kind of patient. 

https://docs.google.com/spreadsheets/d/1653spmu9DkVCKX16G0_ZUlsTuJOx_Ln2qVysJJI-uoU/edit#gid=0

There are so many genes written in all of them, that it's hard for me to be able to compare and make an informed call :/

Want to know if the gene testing will be of help in further treatment, and the drugs/supplements that we should use for her in the near future.

Her current status

1. Her MRI three months back showed no growth, but had choline elevation at two parts where there was tumor resection. We have her next MRI in about a week from now.

2. She will do her remaining chemotherapy cycles with Temozolomide+Lomustine, her cancer being methylated.

She currently is on ketogenic diet and lot of naturopathic supplements suggested by Nutrition Solutions. 

My plan going forward

After my mom is done with the chemotherapy, I plan to get her immunotherapy (Dendritic cell therapy) done.  Want to know if the gene sequencing will be an add on in this plan.

Blood-brain barrier and immune checkpoint inhibitors

Blood-brain barrier and immune checkpoint inhibitors

My partner has a recurrent and unoperable glioblastoma.
He is considering a therapy with immune checkpoint inhibitors (e.g. pembrolizumab or atezolizumab) as his tumor has extremely high mutation burden. Some doctors are in favour but some are not convinced and say that it won't work because of blood brain barrier (BBB).
Is there any research showing immune checkpoint inhibitors don't cross BBB?