Wednesday, 29 May 2019

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 3rd 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.


Monday, 27 May 2019

Anaplastic Astrocytoma Grade 3

Hi Everyone,

My husband is considering starting Radiation/Chemotherapy combination to treat the Anaplastic Astrocytoma Grade 3 (located in right hemisphere) and I would like some feedback on your experience and suggestions for additional cocktails.

Here is a timeline and the current diagnosis:

  • May 2001 - First craniotomy and at that time it was diagnosed as Astrocytoma Grade 2
  • September  2013 - Second craniotomy and diagnosis as Anaplastic Oligoastrocytoma Grade 3
  • August 2018 - Third craniotomy and diagnosis Anaplastic Astrocytoma Grade 3, IDH1 mutated, ATRX mutated, MGMT methylated, 1 P19Q no LOH detectable, proliferation index mib-1 to 10% 
He never wanted to do Radiation/Chemo due to concerns of long term effects, so after the second surgery, he had declined further treatment.  During this time he did not take any constant supplements but did do Ketogenic diet for about 2 years.  The concern was always not to have some side effects. 

He recently had another MRI check and it shows a further progression of the remaining tumor.  The biggest part of the tumor is located in an area where they cannot operate without causing handicap.  His left arm is already damaged and is showing signs of difficulty with walking (left leg) as the tumor is pressing on those fibers.

With all of your experience, I would like your feedback on where should we start.  I am reading other posts to come up with a list of possible supplements.

He is almost 40 and we live in Switzerland. 

Thank you for your feedback.

N

Sunday, 26 May 2019

Saturday, 25 May 2019

Meds during radiation + daily TMZ



In the library, the “A” list shows these meds may be beneficial during radiation:
Chloroquine,CBD/THC,Celebrex,Boswellia, DCA, Disulfiram, and Pterostilbene. Doer this mean that the other “A” list meds should be avoided during a combined treatment of radiation/TMZ?

Thanks,
Mike B


Friday, 24 May 2019


Vladimir’s healing cocktail



Hello to everyone!


I’ve just learnt about this great blog and would like to get some useful information and advice about my father-in-law’s treatment.

Vladimir M., 71 years.
He was diagnosed with glioblastoma (Grade IV), frontal area, size 52 mm*39 mm *23mm, operated on 21/05/19. After the resection, he was O’K. I mean he could speak, walk, he remembered everything. At the moment he is receiving dexamethasone injections (4 mg./3 times a day).  

Histology results: 
- glioblastoma;
- positive reaction to GFAP;
- Ki-67 index - 25%;
- negative to SYN, IDH, ki-67 10-12%

Now we are waiting for radiation and TMZ (probably started in 2 weeks).
I’m a little bit frustrated at the moment about what medicine to start with to make the treatment most effective. Stephen’s list contains such a lot of drugs that I cannot decide which of them should be included in our drug cocktail.
What do you think about this cocktail?

Drug
Dosage
For how long time should the patient take these drugs?
Keppra
1000 mg.
hydroxychloroquine
400mg daily
Metformin
500mg
Celebrex
200-400mg daily
Mebendezole 100 mg for 3 months + Doxycycline 100 mg for 1 month

Do we actually need it or it’s excessive?


Supplements
Dosage

Boswellia (Wokvel Brand)
500-1000mg

Green Tea or Extract
700 mg 40% EGCG

Molybdenum Glycenate
1g

Berberine
500-100mg daily (divided doses)

Melatonin
10-20 mg.

Omega 3 Fish Oil
tbd

Probiotic
tbd

Quercetin
865 mg

Bromelain
500 mg

Marrow Plus
tbd

Milk thistle
1000-2000mg


1)    Is there anything you would suggest I add or remove?
2)    When do we have to start taking these drugs? Right now or during radiation?
3)    Is it OK if we start taking supplements a week later after the drugs (I need some time to get them from USA to Russia)?
Thanks to everyone for your help

Sunday, 19 May 2019

Optune during radiation?


My tumor has returned and my NO has recommended more radiation and daily TMZ. Does anyone know if it is ok to wear the Optune during radiation treatment - obviously I won’t have it on during the 20 minutes of radiation, but how about the rest of the time?

I often get scalp sores from the Optune so I am concerned about infections, etc.

Thanks,
Mike

Saturday, 18 May 2019

Avastin injection into the spinal canal. PVSRIPO.

  • Dear Stephen! Dear all!

    Question # 1. Avastin

    One oncologist told me that there is a practice in Europe of Avastin injection not into the general bloodstream, but into the spinal canal. And that this technique has shown much better results.
    However, I cannot find any articles or clinical trials on this topic. Please help me, as our team of oncologists is ready to reproduce this.
    Unfortunately, absolutely not clear for me and our team:
    1) How many ml of Avastin should be injected into the spinal canal if we inject 600 ml into the general bloodstream (once every 2 weeks)? Our oncologist is talking about dose reduction, but it is only his assumption.
    2) Would it really be effective in the case of glioblastoma, given that it is located just next to the ventricles?
    3) Could we use standard Avastin or some other “special” Avastin, which is more purified?

    Please share any information, links to articles and researches on this issue!

    Question # 2. PVSRIPO

    Due to the fact that Duke will not take us to clinical trials of PVSRIPO (size of the tumor and absence of insurance), I chose Germany. However, I want to be sure that their methodology is the same as in Duke.
    4) How much virus is introduced in Duke? In the first phase of clinical trials (https://clinicaltrials.gov/ct2/show/NCT01491893?term=..)
    there were 5 dosages (maximum - 1.0 x 10 ^ 10), however, I do not understand what dosage they stopped in phase 2 clinical trials (https://clinicaltrials.gov/ct2/show/NCT02986178?term=.. 3)?
    5) Are there any specific tests (blood, tumor analysis) that will show the effectiveness of PVSRIPO in advance for a particular person?
    6) How dangerous is injection of this virus? Our oncologist says that the reaction from the injection is similar to acute encephalitis. Is it true?

    Thank you!

Monday, 13 May 2019

Update on my husband (25 months with GBM), second irradiation questions

Dear Stephen and blog visitors, 

I've posted multiple times about my husband's case but this is his disease history in a nutshell: 

He is IDH negative wild type, MGMT methylated. 

2017/03/27 Diagnosed with multifocal GBM IV (walnut sized thalamic tumor + possibly lower grade frontal lobe mass in an area measuring 51 mm x 38 mm x 11 mm)

2017/04/05 surgery only on the thalamic site where 80% of the tumor was removed. He had a diffuse early progression with edema 3 weeks after the surgery throughout the surgical cavity and beyond. He received the traditional chemoradiation protocol for 6 weeks only in the thalamic area. 3 months after that, the first MRI showed slight progression on both tumor sites (despite the fact that the other mass wasn't even radiated so I guess there's some signaling between the two area) 

After starting the maintenance Temodal courses, both tumor sites gradually reduced in size for almost a year. 

2018/June The frontal lobe area stopped shrinking.
2018/ October scan: Thalamic area also stopped shrinking. 
2019/ January scan: Both sites were stable.
2019/ April 30 Thalamic site is still stable, the oncologist is very satisfied with this area but the frontal lobe area started to invading towards the temple (temporal lobe?) so he decided to send him to radiation therapy. He said surgery is not an option at this stage because thanks to the chemo this is not a mass anymore. So not a solid tumor with clear margins, "just" infiltrating  signaling (the report said: we can't state for sure that it became malignant). Sorry, my vocabulary is not enough to define it correctly. I'm worried that this frontal lobe thing is currently going through some transition to be an actual GBM. In the past 1 week he also started having complex partial seizures. During the 2 years of journey his only seizure case was a long and scary grand mal a year after diagnosis while the scans were great. Nothing else prior or after that, up until now. Is it a bad sign, right? 

Stephen, do you think RT is the right path? Don't you think that treating the frontal area aggressively will make the thalamic tumor "irritated"? My husband just finished his 24th and last TMZ cycle last week and we'll have an appointment on Thrusday to schedule the date of the first treatment so we don't have much time to weigh our options and actually we don't have too many of them. 

Also, I asked the NO about lomustine but he said that this should be our 3rd "plan B". First thing we need to do is RT. Then Avastin if RT won't work and last chance is lomustine because it's very hard to obtain in our country. Last time it took him 3 months to get it for another patient. I said that I can put it on his desk within 2 weeks on my expense in its generic form but he said "We need to spare it for later."

My radiation cocktail plan is the following:
* ketogenic diet 
* Metformin (reducing the dose to 2x 500 mg because of the ketogenic diet)  
* Minocycline 200 mg
* Valproic Acid (25 mg/kg)
* chloroquine (250 mg)
* continuing with DCA (10-12 mg/kg x 2)
* Sulforaphane (Jarrow Formulas, 2 capsules)
* EGCG (600 mg)
* melatonin 20 mg 
* steroid-sparing plans to avoid swelling (Boswellia, 3 capsules of the Wokvel brand + Celebrex 400 mg - is it enough?)
* memantine 20 mg
* D,L methadone 1,75 ml x 2
* Perillyl Alcohol 

Would you change anything?

# I have a concern with Minocycline. Considering that they're in the same class of drugs, would this apply to Minocycline, too? The publication concludes that radiosensitization doesn't neccesarily enlengthens the life span and causes skin damage.

# IV C therapy. Maybe we could do this here in Hungary with a naturopathic doctor based on the protocol in the clinical trials. But the only thing that the NO was clearly advised against in the beginning was anything that involves his veins because as he said "we need to spare them for Avastin." Also, there's a line in the current IV C trial for GBM among the exclusions that: "Patients who are on the following drugs and cannot have a drug substitution: warfarin, flecainide, methadone..." And he is still taking D,L methadone, although that is low dose compared to what addicts take. 

Does IV C have an importance as a maintenance therapy, without chemo and radiation? Because that seems to me the most complicated option and I'd rather spare it for later if there's rationale behind using it in itself because I feel that with all this cocktail meds, the 3 infusions weekly and the POH inhalations every 6 hours we would overdo it a bit...

# Finally I found a source to get both Sativex and cannabis oil, although they're very expensive. Do you recommend to change methadon to cannabis? I know the evidence is quite anecdotal for both of them but considering that he progressed while taking it, I don't think that methadone is effective for him anymore. 

# My keto concerns: almost all of his meds contain artificial sweeteners, the low quality types like sorbit and sacharins. Is it likely that this will take him out of ketosis? 

Just for other patient's information, we also tried the CLOVA cocktail without olanzapine from this January until now but I don't think it worked for him. We increased the dose a little bit because we have different packaging here: lithium 500 mg, cimetidine 900 mg, Valproic acid 900 mg. 
We made some changes in the cocktail (dropped Celebrex because it increases lithium's concentration and also fluoxetine because we were afraid to use two antidepressants at the same time) but I don't think this is the reason behind the progression. 

I thought he could do some break with all the antidepressants during RT. Or do you know something that can be useful especially during this period? We talked to doctor Pilkington just before we got the bad news and we decided to start clomipramine. But now, with this new seizure activity I don't have the courage to give him clomipramine as it reduces the seizure threshold, just like chloroquine and memantin.

Sorry for my long text of wall.

Clemastine-treatment - Exploiting a Chink in the Armour of Glioblastoma Cells

https://www.technologynetworks.com/cancer-research/news/exploiting-a-chink-in-the-armor-of-brain-tumor-cells-319276

Saturday, 11 May 2019

Avastin, to do or not to do? ( I beg for an urgent help)

Dear all,
One month after finishing radio/ chemo of my father, we had done an MRI that shows both bigger tumor and lots of edema.( We increase dexa to 8 mg and I stop boswellia and curcomin because of " foci of hemorrhage", which I deeply  regret doing that. Then around 16 days ago he found a ptosis in his left eye and pupiledema in the other eye. We add dexa to 16 for 3 days and acetozolamid (2*250). Left eye still has lots of problem and my father is sleeping most of the time. I start the supplements again.

Now in our meeting with our NO he said that we should take avastin 10 mg/ kg and temodal (second cycle) still 150 mg/ kg.
I was very interested in avastin before I have a more serious look of previous discussions here.
1) I really need to know whether it is not too much avastin to take with temodal? 5mg or 2.5 would not be more wiser?

2) if it be a pseudo-progrresion should we stop right after control of edema? and if the egfr is amplified would it harm to take few dose even  fore controlling edema?

I have to decide in two days about dosage  and I really appreciate any suggestion. (P.s. today I painfully found that there are few labs doing mutation tests here and I wasnot aware! I will do the mgmt, egfr amp. and cmv tomorrow. Could not convince the NO to write more test!)
Thanks in advance

Friday, 10 May 2019

Young adult / Adolescent GBM: Seeking advice

Dear Stephen and all,
My 15 year old has been diagnosed with GBM in March 2019.  We live in Tokyo, Japan and she is being treated by the hospital famous for treating most of the GBM patients in Japan.  I would like to get some advice and insight regarding my daughter's GBM, treatment option, etc.  Here is some background information about my daughter:

Initial diagnosis: She was admitted to the hospital after having a facial seizure on the left-hand side.  She had a CT and MRI scan, which showed a brain tumor.
Location of the GBM: Right Frontal Lobe, near the Temporal Lobe (near the "surface" of the brain).  Size was 2cm.
Result of the Pathology Report (Only received information verbally.   Seems to be normal in Japan):
Primary GBM
Negative for IDH 1 / IDH 2
Negative for 1q / 19q deletion
MDMT Methylation: Unknown at this time (although the Neurosurgeon told us that we can get this tested if necessary)
Rx Drug: Keppra 500mg twice a day

My daughter had surgery in March, and she had complete resection.  Neurosurgeon told us that 95% or more was resected and everything seen by "eye" was taken out.  As of now, she has been recovering without any problems with paralysis or seizures.

Currently she is going to school everyday and getting the Radiation / Temodal (100mg) treatment on an outpatient basis.  Thereafter, we have been told that she will be on the 12 cycle Temodal treatment.  In addition to this, she is also getting the autologous formalin-fixed tumor vaccine (immunotherapy) for 6 weeks.  This is a personally made vaccine using my daughter's tumor that was resected from the surgery.  This is not a standard treatment in Japan and the neurosurgeon has told us that there is no guarantee that this will "cure" my daughter but there has been studies done where there has been a prolonged PFS time for some GBM patients who received this treatment.  Although this is an expensive treatment, we took a chance because we wanted to try everything we can for our daughter.

Having said that, I would like to get some advice regarding my daughter's GBM:
1) The neurosurgeon team at the current hospital and the former hospital where she was at both told us that my daughter had a lower grade brain tumor (most likely Grade 2, maybe 1 and very unlikely that it would be 3).  We were shocked that the actual pathology report came out as Grade 4 / GBM.  In addition, the tumor size did not change much from the time of the initial diagnosis in December and when she had surgery in March.  Has anyone had experience with this kind of a turnout? 
2) Having read many research or studies on GBM, I have been told that being young and being a female seems to have a better prognosis but are there any young adults or adolescents with GBM who can relate to this?  GBM seems to be rare in young people so I don't see a lot of researches or studies in this area. 
3) Has anyone heard or experienced the autologous formalin-fixed tumor vaccine?  I'm wondering if this is just available in Japan.  In addition to this, I am thinking of having my daughter participate in the Peptide vaccine clinical trial that is being done at a university hospital here.  This is if my daughter meets their criteria and the HLA status, but has anyone had the Peptide vaccine treatment?  If so, do you have any feedback?
4) I am thinking of putting her on the cocktail regimen but I haven't found any recipe for adolescents.  I'm also not sure if our neurosurgeon will be supportive in my daughter taking supplements.  Is there any advice on the supplements that she might be able take at her age?  If I want her to take a minimal amount, what supplements should we prioritize?
5) If there are any young adult / adolescent GBM survivors, have you had any difficulties from the side effects of radiation therapy?  Our radiation oncologist told us that she will most likely suffer from brain function deterioration and memory issues, which I have been freaked out about.  She is a HS student and she would like to go to college.  I would like to hear of any experiences from long-term survivors and any advices if possible.
6) After getting the surgery, my daughter seems to be more emotional and seems to get angry easily.  She has a hard time controlling her anger.    She is a teenager and an adolescent so that may add to this, but she is more short tempered than she was before the surgery.  Has anyone had any experience with this kind of issue?  If so, is this something that we need to live with, or does it get better?

I have accepted the reality and the GBM survival rate data, but I have lots of hope for my daughter.   I would like to do everything possible for her to live a happy life.  Any kind of help would be appreciated.

Thank you for your help.





Thursday, 9 May 2019

Reviewing my mom's cocktail after 18 months of progression free survival

Hi folks/Stephen,

We had my mom's MRI about a month back, and her last MRI showed no growth of the disease, had no choline elevation(in the spectroscopy report) and didn't show perfusion either. She had a gross total resection and was diagnosed in Sep 2017.

She has completed her radiotherapy, 3 cycles of temozolomide and 6 cycles of lomustine+temozolomide. We moved to the Lomustine + Temozolomide protocol because her disease was methylated.

I'd like to get my cocktail reviewed from all of you, and want to know what are the next things that I should consider adding/updating on my cocktail so that things stable. I'd like to be prepared on what I should do next, and be prepared for a recurrence:

Following is my mom's current cocktail:

Diet: Low Carb High Fat/Ketogenic Diet

Supplements:


SupplementCap count
Boswellia Serratta 500 mg8
Keppra 500 mg2
Curcumin + Piperine 1 g4
Longvida 400 mg2
Metformin 500 mg3
Quercetin 865 mg4
Resveratrol 200 mg2
Bromelain 500 mg6
TMG 1 g3
Reishi 1g2
Mebendezole 100 mg for 3 months + Doxycycline 100 mg for 1 month
(We have skipped the statins from the care oncology protocol fearing it might be too heavy on her liver)
1
Artimisia 1 g2
Chloroquine 250 mg1
Ashwagandha 500 mg1
Selinium 200 mcg1
Vitamin A + D + K2 - 5000 IU1
Molybdenum Glycenate 1g1
Celebrex 200 mg2
Green tea extract 500 mg 40% EGCG2
Marrow Plus6
Echinisea 500 mg3
Astragalus tea 3g1
Juice from 5g of Ginger1
Garlic 2 cloves3

Following are the details from her biopsy

IDH1 and IDH2: Not detected
CHR 1p and CHR 19q: Negative for CHR 1p and CHR 19q codeletion
Methylation: Detected
Ki67 labelling index is 15-20%

Following is her FoundationOne report:

Genomic Alterations Identified
EGFR A289V – subclonal, amplification, EGFRvIII
PTEN I67T
CDKN2A/B loss
TERT promoter -124C>T

Additional Findings
Microsatellite status MS-Stable
Tumor Mutational Burden TMB-Low; 3 Muts/Mb

Additional Disease-relevant Genes with No Reportable Alterations Identified†
IDH1
PDGFRA


MY QUESTIONS

1. Has any one of you gone beyond 6 cycles of lomustine+temozolomide? How was your experience like, if you did? Because my mom's scans have been stable - the chemotherapy along with the supplements have definitely been working.

But because my mom's WBC counts have constantly been low(between 2-3k), and she gets affected by even the slightest of the infections - I'm not sure if I should go beyond the 6 cycle mark.

2. Should I consider adding anything, or updating anything in the current cocktail?

I have the following supplements that I plan to add:

- Low dose Naltrexone
- Valcyte(She was positive was CMV in her blood a a year back)
- Ruta 6 and Calceria Phos

Any other supplements that you would consider adding, which you think are high priority ones and that I've missed out on?

3. Are there any clinical trials/additional treatments that you would suggest doing beyond the current line of treatment that we currently are on? 

4. The next important step that we want to consider is immunotherapy/dendritic cell therapy. Which places in your opinion are the best places that we should consider for immunotherapy? My mom's tumor is stored in formalin/paraffin, sadly.

5. Which are the doctors that we should consider speaking to next for an integrative approach to the disease? We are already in touch with Patrice Surley for naturopathic supplements. Would love to know about more doctors who you've had good experience speaking to, and how they can help.

I look forward to hear from you all!