Monday, 28 August 2017

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

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)?


Sunday, 27 August 2017

First recurrence final decisions - KPS score improvement and DCVax trial?

Hi all,

My Dad completed his 6th round of TMZ (after completing the standard chemo-radiation) and unfortunately his most recent MRI (8/10/17) showed the first sign of recurrence. Substantial tumor growth for it only being two months from his last image. He is MGMT methylated but TMZ seems to no longer be effective.

We were not surprised to see tumor growth on his recent scan, as his condition had declined. This was in part due to us weaning off decadron. We got down to 2mg/day from 4mg/day.

At this point he is very weak, back to 6-8mg/day decadron and has a KPS score of 50 (due to the daily care necessary).

Our NO at UCSF, who we do trust, feels it is time to bump the decadron up and live out life with quality. He feels trying other chemos could be too toxic for his current condition and he wouldn't have a chance at getting into various clinical trials due to his decadron usage and KPS score. I understand this point of view.

One thought that our family is discussing is getting another Avastin Infusion. This would be his 3rd infusion, last one being in April. We know this is not a cure, but we think it may be able to lower his decadron use (to the <2mg/day as required by trials) and hopefully bump his KPS score back up to 70 (for trial entry). We had good results with his first two infusions.

Our NO understands this plan, but has stated that an Avastin infusion near the end of life may extend life a few weeks to months, but often times a very poor quality for the patient.

This is obviously a tough decision as we would only use the Avastin if we thought it could give us a chance to get into a worthy clinical trial. The DCVax trial at UCLA is our top pick currently. I meet with Dr. Timothy Cloughesy (UCLA NO director) tomorrow and will ask his opinion. We have also heard rumors that some trials will not allow you to take Avastin infusions right before treatments that involve resections, such as this one.

I know it's not an easy post to respond too. Any advice would be appreciated. I will update after my meeting with Dr. Cloughesy.



Duke trial below was our second favorite trial, but we would not be able to get my Dad to the East Coast -

Saturday, 26 August 2017

Information on DCA and methadone

Hello all,
I'm looking for information on DCA. My dad was diagnosed with an inoperable glioblastoma in December 2015. He's doing pretty well at the moment and we're happy with his treatment. But we want to be prepared for the worst case and that's why I'm interested in DCA.
We live in Germany and as many other cancer patients my dad is taking methadone as part of his cocktail. That's also my main concern because I couldn't find any information on whether methadone and DCA can be combined (I read that you need to be careful with cannabinoids which could be problematic as methadone uses the same receptors). My dad's tumor was stable for a year and then started shrinking in December 2016. As you can imagine we're extremely happy and don't want to omit any of the drugs he's taking at the moment:
- Temodar (still on 5/23)
- methadone
- Optune TTF
- dexamethasone  (tapering 0,5 mg)
- Omega 3
- Vitamin D
- Levetiracetam
- Coriolus versicolor (PSK)
- broccoli sprouts
- Eliqius (blood-thinner)
If you have any information on the combination of DCA with our cocktail, please let me know. I'd also like to know whether you really have to be careful with the dosage in brain tumor patients. I read some really scary stories online, they said that the combination of DCA and caffeine was dangerous.
Thanks a lot!!

Thursday, 24 August 2017

Boron-Neuron Capture Therapy (BNCT) to start in 2018

BNCT will be launched next year in Finland. They will start with head and neck cancers and include brain cancers in future.

Tuesday, 22 August 2017

FDA Accepts Investigational New Drug Application for VBI’s Therapy to Treat Brain Cancer

Car-T cells

Dear all,
Does anyone know any other center besides City of Hope is doing/planning on doing T-cells for GBM? Thanks!

PCV vs Temodar in IDH1 mutated unmethylated astrocytoma

There must be a lot of people who have already dealt with this issue but I didn't see any discussions on it.

I'm 47 years old with a recurrent grade 2 Astrocytoma previously treated with surgeries. Just over 12 years ago it was also treated with radiation, but not with chemotherapy. It's IDH1 mutated, unmethylated and 1p/19q are intact. I'm deciding between radiation followed by PCV or radiation with Temodar and adjuvant Temodar.

The results of RTOG 9802 make PCV appear to be a reasonable option, but RTOG 0424  Temodar results are just as good. My doctor's say Temodar will be as effective as PCV and more tolerable. The advantages of PCV are: the RTOG 9802 survival plot for IDH1 mutations looks good, it's a multi-agent treatment, the methylation status isn't a factor, and there seems to be less risk of hypermutation.

Has anyone with similar tumor characteristics chosen PCV over Temodar, if so what influenced your decision and how did it work out?


I'm updating this discussion for anyone in the future who might be interested.

I've had the 3 opinions below.

They didn't give me any new information about hypermutation. Results of trials will be released in 3 or 4 years.
They confirmed my diagnosis and recommended SOC with 6 cycles. They said there was no information more cycles or a different dose schedule provided any benefit. I wasn't eligible for the Everolimus or the other 2 trials for low-grade tumors.

This is where the recurrence was initially diagnosed.
They recommended SOC. With the following expected response rates for patients similar to me
50% without radiation.
75% response rate with radiation.
I didn't get a definition of response, but I think it means either shrinkage or cessation of growth.
Said there's no data to indicate the ketogenic diet helps, but it won't hurt

Confirmed diagnosis.
Said preliminary study results indicate Temodar works about as well as PCV.
10 or 15 % experience hypermutation.
12 cycles recommended.
Most tumors cease growing and about 15% of patients see a reduction in tumor size.
MGMT is less important in low-grade tumors than high-grade tumors.
IDH1 mutated tumors are more chemosensitive.

Treatment: I decided to go with proton radiation + Temodar. I can always change my mind after radiation if new information indicates switching chemo is best. I'm also taking various supplements and started the ketogenic diet.

I had my first proton and Temodar yesterday and woke up surprised by how much it affected me. Symptoms included: fatigue, headache, and I threw up after only 3 sips of coffee. An extra Ondanestron cleared up the nausea after about 1/2 hour.

Wednesday, 16 August 2017

Progress update

Hi Everyone,
Just wanted to post an update from my Dad and I since a fair bit has happened the past couple of months since he finished the 6 rounds of TMZ (in Jan this year). So in June (14 months post diagnosis) Dad’s MRI showed regrowth approx 40mm wide in a region deeper and close to the original GBM site. He had a 2nd resection at the end of July using 5-ALA and the surgeons have told us they managed to get 95% out, the last bit was attached to a blood supply so they didn't want to risk removing it. He is doing well and thankfully hasn't had any effects from the surgery other than being a bit tired. The team looking after him have recommended him going back on the TMZ as he seemed to do well while he was on it, which they will start at the end of this month providing his scar has healed well.
Since my last post we added Cimetidine and I have recently managed to get Dad to up the Chloroquine to half a table per day (but he is still worried about the potential seizure risk). I am working on him to take the full 250mg per dayI am concerned that since we have had regrowth the tumour that is still there is becoming resistant to our efforts both in terms of the TMZ and all the additional prescription/supplements we have been taking and wondering if we should be increasing/changing the cocktail. We welcome any thoughts on going back to TMZ and what more we can do. 


(Link to our previous posts)

Updated list of what Dad is taking (TMZ etc will be added from end of Aug):

Prescription by special request:
Celebrex (Pfizer 100mg capsule)    1x morning 
Chloroquine (Avloclor - Alliance Pharma 250mg tablet) 1/2 tablet every day in morning (available off prescription), GP recommended dosage as higher could cause fitting.Cholecalciferol 800IU (Fultium D3 - MA Hodder Internis, equiv. to 20 micrograms Vitamin D),  1x capsule in morning (available off prescription under other brands)Levetiracetam (Keppra 500mg tablet) 1x morning and 1x evening.

Additional Supplements:
Cannabinoids (CBD Brothers CBD Oil Blue Edition) 4x drops under tongue morning and evening
Mycelium Extract psp50 (ORIVeDA 350mg capsule) 3x morning and 3x evening
Fish Oil (Omega 3 - Solgar 950mg capsule) 1x morning and 1x evening
Berberine (Swanson 400mg capsule)     1x morning and 1x evening
Boswellia (Solgar 420mg capsule) 1x morning and 1x evening
Ashwagandha (Solgar 400mg capsule)   1x morning and 1x evening
Milk Thistle Fruits (Silamarie - Bio-Health 450mg capsule) 1x morning and 1x evening
Cruciferous Vegetable Extract (LifeExtension 400mg capsule )1x morning and 1x evening
Optimised Curcumin Extract (LONGVIDA RD 500mg capsule) 1x morning
Mega Green Tea Extract  (LifeExtension 725mg capsule)1x morning
Optimized Resveratrol (LifeExtension 250mg capsule) 1x morning
Zinc (Solgar 50mg tablet) 1x morning
Selenium (Solgar 200mcg tablet) 1x morning
Cimetidine 200mg tablet from Jan 2017 1x morning and 1x evening
Melotonin (Eurovital 10mg tablet) 2x evening

Tuesday, 15 August 2017

Cocktail for 11 year old child

Greeting All,

I am hoping someone here can give me some advice. My 11 year old son has recently been diagnosed with Glioblastoma. In 2013 he was diagnosed with a Medulloblastoma and just when we thought we were out of the woods this new tumour has popped up. His Oncologist believes it is caused by the previous radiotherapy he had for the original tumour.

He recently under went surgery, but unfortunately not all of the tumour was able to be removed. He is currently on oral chemo Temozolomide. This is all they have available for Gliomas from a chemo perspective here in New Zealand. After much research I have composed the following cocktail for him based on what I can access here.

What I really need to know is what daily dosages I should be giving him, given his age. I have found adult dosages for all on my list, but no luck for children. I would also appreciate any feedback on the list itself. The list is as follows:

Cannabis oil, high THC & CBD
Rhodia Rosea
Tumeric / Cucumin
Omega 3 - Fish Oil
D3 drops
Gamma linolenic acid (GLA)
Green tea extract (standardised to 50 %EGCG)
Bowellic acid
Coriolus versicolor (Mushroom) - PSK
Coriolus versicolor (Mushroom) - PSP
Metaformin – diabetic medication

Atorvastin – cholesterol medication

Thanking you for your time.


Monday, 14 August 2017

Astrocytoma Options technical difficulties

My other website, Astrocytoma Options, will be down for... several days? due to a viral infection.

Sunday, 13 August 2017

DCVax-L presentation at ASCO 2017, June 5

The most recent public information on the phase 3 DCVax-L trial was given in the form of a presentation with slides by Dr. Marnix Bosch, chief technical officer of Northwest Biotherapeutics, during the recent ASCO conference in June. The presentation covers both DCVax-L and DCVax-Direct.

The DCVax-L (phase 3 trial) part of the talk is from approximately minute 6 to minute 25.  The most interesting part where new information is presented is from approximately minute 17 to 25.  The remainder of the presentation is devoted to DCVax-Direct.

Watch the video here:

Here are some slides from the talk:

We can assume based on this presentation that the threshold for the overall survival analysis to begin has now been reached and is likely underway.  He mentioned that a publication of the preliminary data is in preparation.

The only survival data publicized so far is for the patients who were excluded from the trial due to early progression and were given DCVax on a Compassionate Use protocol, aka the "informational arm".  In the "indeterminate" subgroup of 25 patients within this informational arm who had early evidence of progression followed by a period of stability, 40% have made it to nearly 3 years or more, and 24% have made it to 4 years.

24% surviving at 4 years compares very favorably with the control arm (receiving standard of care) of the recent phase 3 Optune trial, which had 10% surviving at 4 years, and the study arm (standard of care + Optune) of that trial had 4 year survival rate of 17%

It would be reasonable to expect survival outcomes in the phase 3 trial to be better than those from the indeterminate group of the "informational arm" given that the latter group was excluded from the trial for at least some form of evidence of early progression, while patients included in the trial had no evidence of progression.

The next step to improve outcomes further is now being taken by UCLA, where a phase 2 trial is slated to open soon combining DCVax-L with nivolumab (anti PD-1), although this trial is for recurrent, rather than newly diagnosed GBM.

Primer on CAR T-cell therapy for GBM

This is a useful overview of CAR (chimeric antigen receptor) T-cell therapy and its application to GBM published a few days ago at CancerCommons, written by their chief scientist.

Reengineering Immune System Cells to Fight Glioblastoma (click on link)

Friday, 11 August 2017

BGB-290 (brain penentrant PARP inhibitor) trial now open in USA

Formerly this drug was only available in 2 Australian clinical trials.  A trial has now opened in the USA (Arizona, Colorado, Tennessee, not yet open in Oklahoma) for newly diagnosed GBM with unmethylated MGMT, or for recurrent GBM (methylated/unmethylated MGMT), combined with standard treatments (temozolomide + BGB-290 in the recurrent group).

Past post that mentioned BGB-290 and PARP inhibitors.

Thursday, 10 August 2017

Oligo 2 plan for surgery

Hi all,

I met with Ennio Chiocca at Brigham and Women's/Dana Farber earlier this week. He will do my surgery to remove the presumed Oligo 2 from my left frontal lobe. It will be awake surgery. Currently we are planning to do the surgery around mid-November to allow me to nurse our newborn until he is at least 6 months (I'll try to continue after the surgery but this way he'll at least get a solid 6 months of nursing for sure).

I like Dr. Chiocca's nature and the positive things he had to say about my prognosis. Has anyone worked with him? What he said that stood out is that there is a good chance this tumor won't come back. I questioned him in that, since no one else has said such a thing. He said technically this tumor was only discovered in 2008 (IDH and co-deleted), and so we can't say for sure how they function and it could be that they don't always come back. He said there's an 80%  chance it will not be back in 10 years. Thoughts on that?

Like others, though, he was not able to address the other symptoms I'm experiencing (sense that my left eye is bulging slightly, blurry spot in my left vision, drop in BP since the seizure, etc.)

Can someone talk about how they measure these things? UVM measures it as 2.9APx31.5transverse x 1.7 craniocaudal. BW has it at 3.3AP, I'm told that's a trivial difference. It didn't grow during pregnancy (at least not after it was discovered), so that seems positive.

Additionally, at my last check up with my local NO he mentioned a second spot. It is a white matter lesion 3mm, nonspecific. Everyone has told me not to worry about this but it seems worrisome to me!

Thanks for any input.


Saturday, 5 August 2017

Angiotensin system inhibitors + low dose Avastin

This June a study was published by Victor Levin et al. of Kaiser Permanente Hospital, Redwood City, which follows up on a previous study on the use of Avastin doses lower than the standard dose.  (I've uploaded the full study to the Brain Tumor Library -> Folder 1. Therapies - Human Studies -> Angiotensin System Inhibitors)

The current study looked at the use of angiotensin system inhibitors, including both ACE inhibitors (benzapril, captopril, etc.) and angiotensin II receptor blockers (losartan, telmisartan, etc.) used for hypertension simultaneously with chemotherapy and/or Avastin in newly diagnosed and recurrent glioma patients.

In a very large cohort of 1186 infiltrative glioma cases (grades 2-4), use of an angiotensin system inhibitor (ASI) was significantly associated with better survival (hazard ratio 0.82), in a multivariate analysis adjusted for other variables such as age, extent of resection, GBM versus other grade, use of Avastin, etc.  This advantage of ASI treatment was even more significant in patients who were also treated with Avastin (HR 0.75).

A previously published cohort of 181 recurrent GBM patients treated with various doses of Avastin was examined with regard to their use of ASI drugs (for hypertension).  The previous study had shown trend toward longer survival in the group treated with lower-dose Avastin, and this study has been summarized elsewhere.   (Page 90)

Remarkably, of the 89 patients treated with doses of Avastin lower than 3.6 mg/kg/week (the standard dose amounts to 5 mg/kg/week),  the 47 patients also using an ASI drug had a very impressive median survival of 99 weeks (22.8 months) versus 55.6 months (12.8 months) for the 42 patients receiving low dose Avastin without ASI drugs.

99 week (nearly 23 month) median survival (from treatment for recurrence) for a sizeable (n=47) group of recurrent glioblastoma patients in virtually unheard of.  Although all the usual caveats apply because of the retrospective, non-randomized nature of this study,  the outcomes are too impressive to ignore.

As Levin et al. conclude "Prospective clinical trials combining ASIs with low-dose BEV in GBM patients are now needed to confirm whether ASIs can enhance the efficacy of VEGF-targeted therapies and thereby improve clinical outcome."

As a side note, Victor Levin is the founder of the Society for Neuro-Oncology (SNO) and often described as the "father of neuro-oncology", at least in America.

Friday, 4 August 2017