Recurrant anaplastic astrocytoma treatment options

Hey all,
Need suggestions for treatment options and supplementation for my brother
His clinical history is-

clinical history	date	remarks
diagnosed in	september 2009	assumed to be begnin tumour
		observation through mri
Tumour surgical resection	18th feb 2016	tumour started to enhance in size
		gross resection of more than 95%
		tumour size 7.2x5.5x5.1( anaplastic oligoastrocytoma)
RT PLUS  CONCURRENT TEMOZOLOMIDE	2ndAPRIL 2016 TO 17th MAY 2016	59.4 gy ,33 fractions plus 120 mg temozolomide
Temozolomide	june 2016 -december 2016	6 cycles
Recurrence                                                  may-18
reradiation +concurrant temozolomide	18th jul 18-16th aug 18	36gy, 20 fractions plus 120 mg temozolomide
temozolomide chemo	1st jan 19-5thjan 19	200mg per day for 5 days
HIS BIOMARKERS ARE- BIOMARKER AND GENOMIC FINDING STATUS MICROSATELLITE STATUS MS-STABLE TUMOUR MUTATIONAL BURDEN  TMB-LOW (4 MUTS/MB) ATRX  LOSS IDH1 R132H NOTCH1 A465T SUBCLONAL,E450K-SUBCLONAL,R353C-SUBCLONAL SMARCA4 T910M TP53 G245S,R273C MGMT UNMETHYLATED(METHYLATION SCORE-0.49) ANTIBODY TYPE RESULT GFAP POSITIVE IDH1 R132 POSITIVE KI-67 POSITIVE PROLIFERATIVE INDEX APPROX 10-15% FISH TEST 1P/19Q CO-DELETION NEGITIVE EGFR NEGITIVE FOR EGFR AMPLIFICATION PTEN LOSS POSITIVE (39.3% OF NUCLEI EXAMINED) His current medications are- Part of Day Medicine Name Medicine count Notes PRE MORNING BROMELAIN 500 MG NOW 3 EMPTY STOMACH TAB PAN 40 MG RT OD 1 STOP ON 30TH JAN 2019 MORNING BREAKFAST CURCUMIN TABLETS 3 NOT WITH AVASTIN OR TAGRISSO/TARCEVA GLYCEROL 30 ML 1 DIAMOX 250 MG 1 METAFORMIN 500MG 1 TWICE DAILY FROM 1ST FEB IBUPROFEN 200 MG 1 CBD OIL 2 FULL DROPPERS 1 LEVIPILL 750 MG RT 1 LASILACTONE 20/50 MG RT 1 TAB DEXA 4 MG RT 1 STOP AFTER 21ST JAN TAB BACLOFEN 5MG RT 1 REFRESH EYE DROP 2 BOTH EYES 2 DROPS LEVOLIN NEBULISATION .63MG 1 STOP ON 25TH JAN 2019 TAB GLYCOPYRROLATE 1 MG 1 STOP ON 20TH JAN TO BE ADDED VALGANCICLOVIR 450 MG 2 CHLOROQUINE 250 MG 1 CELEBRAX 200MG 1 WHEY PROTIEN 2 SCOOPS  WHEN RECD FROM USA GRAPESEED EXTRACT 250 MG 1 STRESS B COMPLEX 2 LUNCH CURCUMIN TABLETS 3 MEBENDAZOLE 100 MG 1 START DOXYCYCLINE ON 18 TH APRIL GLYCEROL 30 ML 1 IBUPROFEN 200 MG 1 LASIX 40 MG 1 REFRESH EYE DROP 2 DROPS STOP AFTER 21ST JAN LEVOLIN NEBULISATION .63MG 1 TIME STOP ON 25TH JAN 2019 TAB GLYCOPYRROLATE 1 MG 1 STOP ON 2O TH JAN TO BE ADDED CELEBRAX 200MG 1 NIGHT CURCUMIN TABLETS 3 ATORVASTATIN 40 MG 1 80 MG FROM 1ST FEB GLYCEROL 30 ML 1 DIAMOX 250 MG 1 IBUPROFEN 200 MG 1 CBD OIL 2 FULL DROPPERS 1 AFTER HALF HOUR GIVE THC 6 DROPS THC OIL 6 DROPS 1 LEVIPILL 750 MG 1 LASILACTONE 20/50 MG 1 TAB BACLOFEN 5MG RT 1 REFRESH EYE DROP 1 BOTH EYES LEVOLIN NEBULISATION .63MG 1 TIME STOP ON 25TH JAN 2019 TAB GLYCOPYRROLATE 1 MG 1 STOP ON 2O TH JAN TO BE ADDED VALGANCICLOVIR 450 MG 2 STOP ON 9TH FEB 2019 CELEBRAX 200 MG 1 BERBERINE 500 MG 1 BEDTIME ARTEMISIA 500 MG 2 WHEN RECD FROM PATRICE TAB FRISIUM 5MG RT 1 PLEASE SUGGEST 1.SUPPLEMENTS TO ADD OR TO BE DISCONTINUED 2.AVASTIN OR LOUMUSTINE OR ANY OTHER TRIAL DRUG BEST SUITED FOR HIM 3.ANY OTHER EFFECTIVE THERAPY TO HELP HIS QUALITY OF LIFE.

Long term analysis of NOA-04 for anaplastic (grade 3) gliomas published today

This was a randomized phase 3 trial testing radiation therapy (followed by chemotherapy with PCV or TMZ at recurrence) versus chemotherapy (followed by radiation therapy at recurrence). Half the chemotherapy patients were randomized to PCV and the other half to temozolomide.

In this new update, patients are divided into three molecular groups:  CIMP negative, CIMP positive 1p/19q codeleted, and CIMP positive 1p/19q non-codeleleted.  CIMP positivity in this study is essentially another way of saying "IDH-mutant" as IDH mutation virtually always leads to the CpG Island Methylator Phenotype (CIMP).   The latter two subgroups correspond to molecular oligodendroglioma and molecular astrocytoma, respectively.

One of the more important findings in this study is that PCV was superior to TMZ in the molecular oligodendroglioma subgroup.  (This image shows progression-free survival, but the same trend was evident in time-to-treatment failure analysis and overall survival).

On the other hand, PCV and TMZ were more or less equivalent in efficacy for the molecular astrocytoma group (CIMP+ non-codel).

These findings support the use of the PCV regimen for molecular oligodendrogliomas, however it's still an open question whether the addition of vincristine (V) to procarbazine (P) and CCNU (C) adds any benefit.  Some retrospective evidence suggests that PC chemotherapy (without vincristine) is comparable in efficacy to PCV.

This study was published in the November 2016 edition of Neuro-Oncology, and the figures above are taken from the Supplementary figures.

http://neuro-oncology.oxfordjournals.org/content/18/11/1529.abstract?etoc