Avastin + (Temodal or CCNU)?

Dear all

I’ve finally receive the test report for my father, however I am not sure to what extent are these results reliable, and what is the best way to go from now on based on this report. I highly appreciate your advice. We just started the Avestin (10 mg/kg) while being in our second cycle of Temodal due to hug oedema (left temporal, biopsy-only, facing left eye ptosis few days after the first cycle of Temodal)

Reports in the nutshell: MGMT methylated (36%), EGFR amplified, IDH wildtype, Tert (Mutant for C250T, wildtype for C228T), 1P/19q (does not carry deletion of the genetic region 1p/19q), CMV negative (FFTP tissue block)

1) How to decide when to stop Avastin, if ever?

2) Shall we reduce the Avastin dosage if we are going to stop it after a short period?

3) Whether after stopping it, the temodal+ccnu can be still a good option for us?

4) Shall we change temodal to CCNU now that we are facing decline in his situation? Or is it better to wait until the end of 3^rd cycle, do the MRS and then decide?

5) Any cocktail advice while we are starting Avestin? Maybe captopril and chloroquine (sadly, I just know about EGFR and not the EGFRviii)

 (his current Neutrophil is 6600 and Platelets 89000, sleeping most of the time in the last 12 days, 20 minutes’ walk everyday)

Semi-Cocktail: metformin 500 (just to hopefully prevent diabetes on dexa), CurcuMIND 2, Boswellia wokvel 3, acetazolamide 500, Keppra 750, valproate 500, Ranitidin 3, sulforaphane 1, Marrow plus (soon would be added 3), folic acid 1.

Report (the reason for quoting these in length is mostly because I feel it could be helpful for other ppl in my situation to know to what extant these tests are similar to what is done in other countries and maybe it can help them saving more time and money. Sorry for the length, we can delete it if it is inappropriate)

FFPT tissue block:

Positive for MGMT methylation (36.25% of methylation for all 4 CpG sites):

Genomic DNA was obtained from tissue using the Qiagen kit. The quality/quantity of the DNA was estimated in a Nanodrop spectrophotometer.

The MGMT methylation status was measured by Pyrosequencing technology for 4 CpG islands within the methylated promoter region of the MGMT encoding sequence.

Positive for EGFR amplification (approximately 11-fold larger)

DNA was extracted using the QIAamp FFPE DNA kit. EGFR gene amplification was analyzed by real-time PCR standard primers and probe using Lightcycler 480 II instrument.

Comparing to the normal copy number of control gene, EGFR gene was amplified in this sample.

Tert (Mutant for C250T, wildtype for C228T)

(QIAamp® DNA FFPE DNA Kit) Allele Specific PCR was performed for amplification of TERT promoter mutations (C228T, C250 T) by ABI Veriti instrument. Sequencing of PCR product were performed via Pyromark Q96 instrument and analyzed to detect Polymorphism.

 Wildtype for IDH1 (c.394-396 [R132H and variants])/ Wildtype for IDH2 (c.514-516 [R172K and R140Q and variants])

DNA extracted by FFPE QIAGEN kit and a segment of DNA containing IDH1 exon 2 and IDH2 exon 4 is amplified using ellele specific PCR primers and Pyrosequencing data at codons 132, 140 and 172 respectively, is interpreted by a pathologist.  

CMV negative (FFTP tissue block)

DNA was extracted using the Qiagen DNA micro kit and qualitative Real time PCR has been done using Taq-Man Probe assay to detect of viral nucleic acid.

1P/19q (the assayed sample does not carry deletion of the genetic region 1p/19q)

FISH analysis was performed on a section from a paraffin embedded tissue block using differentially labeled fluorescent probes targeting 1p36/1q25 and 19p13/19q13.

The fluorescence in situ hybridization on the paraffin tissue was positive for a co-deletion of 1p/19q. (???)FISh was performed using probes for the target at 1p36 and 19q13 and control probes at 1q25 and 19p13.