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.

Our cocktail and report "OncoDeep". What do you recommend to pay attention to?

Since the tumor after surgery (removed 99%) increased again in the same size (3.5 x 5 x 5 cm) in 3 weeks and the tumor did not decrease after radiotherapy + TMZ, we probably have a very unusual cocktail for the first line:
- cycle 42 days: Avastin (3mg/kg/week) + CCNU (1 day 75mg/m2) + TMZ (5 days 90mg/m2),
- disulfiram 500mg (+Copper 5mg + DHA) and verapamil 200mg only on the days of TMZ + CCNU administration, and 2 days before and after.  I'm not sure, maybe it's advisable to take Disulfiram every day? Otherwise, disulfiram may not start to influence so quickly?
- every day: cloroquine phosphate 250mg, telmisartan 80mg, alfacalcidol 2mcg, oxaloacetate 100mg,  melatonin 20mg, curcumin longvida 2000mg,  Berberine 1000mg, DHA/EPA 1000mg, PSK / PSP 1800mg, Methimazole + T3, R-lipoic acid + hydroxycitrate + ketogenic diet, omeprazole 20mg + DCA 20mg/kg (10mg/kg/BID) + caffeine (2 cups of coffee and 5 cups of black tea) + vitamin B1 200mg

My mother has been responding well to taking DCA + caffeine for a week in the form of black tea and coffee. However, my mom's pulse increased to 90-95 after sleep or rest. To reduce it, we now take 10 mg of propranolol per day. An increase in the pulse may also be caused by the intake of the hormone T3.

Also I consider the addition of a low dose of naltrexone before bed.
We also ordered perillyl alcohol at www.sigmaaldrich.com and expect it soon.

Today we received a report from OncoDNA. The last 3 months I read and search for any information about glioblastoma, but unfortunately I find it difficult to understand this report. Doctors in Russia do not order such reports at all! Our doctor in Germany said that unfortunately, such reports will not help us in any way.

Maybe you can tell me what to look for in this report? Any comments?

For example, I can not understand, is there overexpression (amplification) of EGFR?
"Damaging TP53" = mutation of TP53? Not understanding this, I can not draw conclusions from this review (http://astrocytomaoptions.com/exploring-strategies-for-tp53-mutated-gliomas/) and other studies.
"Damaging PTEN" = loss or mutation PTEN? An interesting article in this case: http://btcocktails.blogspot.ru/2018/01/parp-inhibitors-for-pten-mutant-cancer.html
Which of the drugs on the list of potential clinical benefits to pay attention to ?

Here is a link to the report itself and some pictures of him:
https://drive.google.com/open?id=1A3dophOME6gY1GNdOHWE48wVYJUu_nHc

 

 

Predicting immunotherapy response

1. The company OncoDNA provides test OncoDeep: 70 genes + predicting immunotherapy response.
https://www.oncodna.com/en/immunotherapy/
Price: 2990Eur.
Are there any studies predict immune therapy in other laboratories? Is this study useful?

2. By the way, in Moscow (Russia) a study of 50 genes costs $480. Can this research give some useful information? Or these 50 genes is very limited and such information is not sufficient?

http://www.genomed.ru/onkokarta/

3. Here (https://www.cegat.de/en/diagnostics/tumor-diagnostics/ovarian-cancer/) it is reported that "The detection of a somatic or germline mutation in the BRCA1 or BRCA2 genes is a requirement for treatment with Olaparib (LynparzaTM)"

There are also 4 testing options.
"Option 1: BRCA1 and BRCA2 analysis in tumor tissue only
In option 1, only mutations in the tumor are analyzed, no differentiation between germline and somatic mutations can be made. We do not recommend this option, but will perform it when it is explicitly requested by a patient."

Is it necessary to do such a study to determine the possibility of treatment with Olaparib or is it enough to study Oncodeep (by OncoDNA)? But in Oncodeep only mutations in the tumor are analyzed.

Option 1: BRCA1 and BRCA2 analysis in tumor tissue only

Option 4: Somatic Tumor Panel

Preparing for surgery - tumor analysis & storing

Hello all,

My sister's tumor (AA3) has progressed and a surgery is scheduled.
Would you do tumor analysis and if so, which one:
-Caris Molecular Intelligence
-Foundation One
-OncoDna?

We already know her tumor is IDH1 and TP53 mutated and MGMT methylated. No other mutations we're found last time. Also CD8+, PD1 and PD-L1 were negative. I don't know if there's much to gain this time, because it seems that the number of suitable chemos is anyway quite limited and PD1-inhibitors have shown low efficacy on IDH1mutated tumors?

And do you see benefit to store tumor sample for later use (e.g. Vaccine)?

Br,
Juha