Tuesday, 27 March 2018

Mobility Just Keeps Getting Worse

Hi everyone
I have raised my daughters mobility issues in a previous post, and as there was no real response at the time, i can only gather that this must be fairly uncommon.
Her left side is now likened to Hemiparesis which is more common in stroke victims.
She is still able to feel and move her limbs, but has absolutely no strength at all, cant balance or walk.
I think also that she has become severely depressed, which i have also read can often make it worse.
Her last 3 scans have remained stable without further progression, and yet mobility has deteriorated very rapidly.
Very confusing?
Has anybody else experienced anything similar?

Friday, 23 March 2018

Progress towards identifying immunotherapy targets for IDH1-mutant low grade glioma

Identification of CRKII, CFL1, CNTN1, NME2, and TKT as Novel and Frequent T-cell Targets in Human IDH-Mutant Glioma
click here for abstract.

"By analyzing the repertoire of T-cell target antigens in IDH mut glioma patients, we identified five novel immunogenic TAAs [tumor associated antigens] and confirmed their expression on IDH mut tumors and GSCs [glioma stem cells]."

Thoughts on ALA and Hydroxycitrate

Hi all,
I haven't posted before and am fairly new to the blog. I've been visiting it frequently over the past few weeks and I really appreciate all of the shared knowledge, opinions and helpful advice that I see here.

I am wondering if anyone has tried the alpha-lipoic acid/hydroxycitrate combination in addition to CCNU. My husband is 31 and is about to begin his second round of chemo, this time trying CCNU. He was diagnosed last April and went through the standard TMZ/radiation but had a recurrence in January. He had his second surgery in February and they were able to do a complete resection this time.

I've been reading a lot about alpha-lipoic acid and hydroxycitrate, also in combination with naltrexone, and I think it's something we want to try. I'm wondering if there are certain supplements or medications he shouldn't take at the same time... also curious what the recommended doses would be. Some of the studies I've read show that the ala was administered via IV which I don't think will be possible for us, especially because I expect his oncologist to be really hesitant about this treatment plan.

Also, is it possible to combine this type of treatment with CCNU and another drug like tamoxifen or Keytruda? So many options and I'm not sure which is the best to make a case for to his doctor.

He takes a number of supplements, including turmeric, garlic, goldenseal, resveratrol, boswellia, and vitamin D. He's also on metformin, a dose of 500mg twice a day. He's been on the ketogenic diet for almost a year.

I appreciate any insight.


*Edit: I should also mention that we are still waiting on the more extensive genetic testing results. His first pathology last year showed MGMT methylation-positive, IDH1 positive. ip19q negative.

Thursday, 22 March 2018

Here's the Problem with Today's Human Clinical Trials

Just published in Fortune magazine regarding  the 2018 Fortune Brainstorm Health conference.  http://fortune.com/2018/03/20/human-clinical-trials/

You may recall Matt da Silva from the Surviving Terminal Cancer movie.

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. 

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.

Tuesday, 20 March 2018

Targeted at treatment of newly-diagnosed GBM -- on the horizon

Stephen - thought you might appreciate this heads-up


Sunday, 18 March 2018

Cocktail mini breaks

Dear community, I'd like to ask a question on behalf of my husband. He has been on a quite extensive cocktail for about 9 months. The other day he brought up the topic of cocktail mini breaks because sometimes he feels overwhelmed with so many pills (at least 30 pills a day+ a liquid solution two times a day). Occasionally he has heavy heartburn (although he is on daily cimetidine, 800 mg + even 2x40 mg omeprazole on chemo days+the surrounding days), stomach issues and easily gets nauseated. Since the beginning of the year he even vomited 4 times. The root cause is generally some kind of a disgust from a taste or smell. Maybe it is the cumulative effect of chemo (he just passed his 9th cycle of TMZ) but we were wondering if a 1 day break once in a while (for example 1 day break after every chemo cycle) would decrease the effectiveness of the cocktail. Personally I don't think that this mini pause would make a difference (either in a good or bad way) but he feels that his body needs the occasional breaks to recover. His latest MRI (February 26) showed further shrinkage on both tumor sites and there's no considerable swelling. He also was weaned off of steroids gradually. Please share your experiences on this topic. Maybe this shouldn't be the biggest concern of a brain tumor patient but I if it meant an increase in his quality of life, then why not?

Need advice....IDH1+, (maybe) unmethylated GBM..MANY conflicting opinions

I have been reading this message board for years and been impressed with the knowledge of many of the participants.  I was hoping I would never need to post...

As posted by Stephen previously,  my now 25 y/o son was diagnosed in 2011 with OA Grade 2 (now felt to be AA3) and treated with surgery and then surgery to get "leftover" in 2012.  He was found to be IDH1+. Because of the infiltrative nature of tumor on path, he then entered into a clinical trial on the cognitive effects of proton therapy, which he completed 11/12.  No chemo was given.  (No apparent cognitive effects in his case either...did very well in college and is/was in med. school.)  On routine MRI 12/17, he was found to have a 6-7 mm area of enhancement in the middle of his resection cavity (tumor never enhanced before).  Advice was to watch for 2-3 months, but we moved up the surgery.  Note that his tumor grew about 1 mm in each dimension in 6 weeks.  He had a very generous GTR 2/15 and has had a pretty easy recovery--no apparent deficits.
Unfortunately, the path showed GBM IDH1+ unmethylated.  They also looked at his tumor from 2012 and it was also unmethylated.    Foundation One is not back yet.  We have been looking at different options and consulted physicians from several different areas.  Many have been very generous with their time and there is no consensus.  Opinions below...

(he didn't qualify for TOCA due to small tumor size and no prev. treatment)
--Local neuro-onc:  olaparib + Temodar + more proton.  Wasn't really certain of dosing.  (PARADIGM2 could provide that)
--Tumor board at Mass. General....some said NO treatment, some said Temodar.  Told to wait on radiation as scans might be too difficult to interpret
--Physician who is expert on IDH1....feels that IDH1+ GBM shouldn't be considered as really a GBM.  Rec. no radiation and PC(noV) since it has been shown to work.
--Physician at another institution who is involved with IDH1 studies...PCV.  He said to delay radiation because of  "better things coming" and it will probably take radiation + chemo to really eradicate tumor
--Second Opinion from well-regarded cancer institute....PCV has not been shown to work.  Use Temodar and radiation, though consider immunotherapy.
--UCLA...IDH1+ more indolent, possibly PARP + Temodar...perhaps immunotherapy depending on mutation burden.  Not good luck with olaparib, though don't know about mutant status of those patients. Told that IDH1+ SHOULD  be methylated and that test not very accurate.

So....he just missed a slot on the BGB-290(pamiparib) + Temodar (but without radiation) trial...expansion cohort likely opening in 4 weeks.   Evidently fairly well tolerated.  He strongly wants to return to school in August, which seems somewhat unrealistic, but not impossible.  Waiting 4 weeks for treatment doesn't seem like a great idea, unless one accepts the idea that this is a more indolent tumor.

Would really appreciate advice in this matter!  Thanks,   Marcia
(And thank you so much, Stephen!)

Methylation fingerprinting improves brain tumour diagnosis

It’s a little disconcerting that 12% of tumors are misdiagnosed. 

Methylation fingerprinting improves brain tumour diagnosis. ecancer - News


Can Celecoxib and Ibuprofen be used interchangeably?

Hi folks/Stephen,

My mother is a grade 4 brain cancer patient. We have been using Celebrex(Celecoxib) as a part of her drug cocktail.

However, in situations of heavy head/headaches and/or body aches, she often asks for Ibuprofen which we've observed helps relieve her pain.

Both being COX-2 inhibitors, I wanted to ask if both Ibuprofen and Celebrex can be used interchangeably, or is there some reaction that I should know of? If there is a reaction between the two, how much difference in time should I keep between the two medicines?

Would love to hear from you guys.

Friday, 16 March 2018

University of California Los Angeles Brain Tumor Conference May 18-19 2018

Hello everyone!

Is anyone (patient and/or caregiver/family member) going to the University of California Los Angeles Brain Tumor conference on May 18th and 19th, 2018?  My wife and I have just registered for the conference and we would love to meet up with anyone else that will be attending the conference.

Link to register and information on the sessions:

Best regards,
Mike B

Tuesday, 13 March 2018

COC Protocol and study

Hey Stephen,

This article came to my attention - http://dailym.ai/2tJq8aJ and I decided to investigate a little.

That article relates to this study/trial --
Study of the Safety, Tolerability and Efficacy of Metabolic Combination Treatments on Cancer (METRICS)   https://clinicaltrials.gov/ct2/show/NCT02201381

The protocol is all about repurposing 4 well know drugs. It originated in London - http://careoncologyclinic.com/ and is now in the US https://careoncology.com/  They mention some strong data related to GBM OS of 27.1 months.

Here's their paper on their Metabolic Combination Therapy http://bit.ly/2tOUKHU  

Here's their patent info https://patentimages.storage.googleapis.com/96/0b/f7/6cab0db42f7dab/US9622982.pdf

Are you at all familiar with this?  Thank you.

4 drug cocktail in DailyMail article

Interesting article Al Musella linked to today:  http://www.dailymail.co.uk/health/article-5492485/Could-400-year-drug-cocktail-beat-one-deadliest-cancers.html#ixzz59efGLD2c

Cocktail of just 4 meds (listed below).

1. Atorvastatin
2. Metformin
3. Doxycycline
4. Mebendazole

I'm curious how this works. Wouldn't you need an active agent too?

Monday, 12 March 2018

TOCA gets orphan status In Europe


Thursday, 8 March 2018

MDMX and PD-1 inhibitors

So the genetic testing came back on my partner’s tumor (GBM, first recurrence), and while researching the mutations, I found Stephen W’s account of the hyperprogression study linking use of checkpoint inhibitors with accelerated progression in people with certain mutations, including amplification in MDM2 or MDM4.  All 6 of the people in the cohort with MDM2/MDM4 amplifications experienced hyperprogression (across 5 different cancer types, none of which were primary CNS, although several had metastases in the brain; 5 were MDM2 amplified, 1 was MDM4).

My partner’s genetic report includes copy number gain in MDM4.  No indication of the size of the gain; I’ve asked the company if they can clarify.

As it happens, we started pembrolizumab 2 weeks ago.  I figured the worst that would happen was that it was ineffective; it never occurred to me that it might accelerate progression.

The study doesn’t prove that checkpoint inhibitors caused the hyperprogression.  It’s possible that MDM2/MDM4 amplification caused the hyperprogression on its own.   The possible mechanism seems understood: MDM2 suppresses p53, a major tumor suppressor (p53 is mutated in over 50% of all cancers).  I found one study that showed MDM2 amplification is prognostic for poor survival in breast cancer.  On other hand, the chart at the end of the hyperprogression study sure makes it look like acceleration began with the onset of checkpoint therapy.

My partner’s tumor showed high expression of PD-L1 (50%), and also has mutations in NF1 and TERT.  All three of those are correlated with better response to PD-1 inhibitors in other cancers.

The next pembro infusion is scheduled for March 19.  We have to decide by then whether to continue with it or not.  Thankfully we’ll have an MRI that morning.  The tough call will be if there’s no evidence of progression.  I know there’s no clearcut rationale for making a decision either way, but I’m curious if anyone here has any advice.

Other biologically relevant mutations found are TERT, PTPN11, NFE2L2, PTEN, and CDKN2A.  IDH1 is wildtype.  MGMT is reported as unmethylated by sequencing.  The tumor mutational burden increased from 2.05 to 5, and the MSI status is stable (i.e., no mismatch repair defect).  

Our current regimen: CCNU, pembrolizumab, Vitamin D, melatonin, PSK, curcumin (also levetiracetam, Vimpat, Xarelto)
Planned additions: boswellia
Actively considering: ECGC, THC/CBD, Hydro+ALA, celexocib, metformin, everolimus



Tuesday, 6 March 2018

What a crusher. It’s been almost 2 years to the day since this journey started and today we were told that this beast has returned. Waiting until Thursday for the tumor board to meet and provide their take. Meanwhile our NO threw out all the options...so we’ve got some though decisions to make. I hate this rolling the dice crap - at least that’s what if feels like.

Noteworthy regarding my wife's tumor testing -- was Methylated, IDH1 negative, there's EGFR amplification, positive for EGFRvIII, P53 positive, ATRX positive, and some PTEN imbalance. She's had a great 18 months since the end of SOC treatment -- as a matter of fact she's at the gym right now -- we've been lucky. 

My questions to the group are:

- do you have a success story since having a 2nd resection?
- who's having success in a trial and what is that trial?
- what's hot in world of trials?

FYI - we're located in Boston. Thank you all!

Friday, 2 March 2018

Keto recipes

Hi all,

A few months ago some questions were asked about sugar free and keto recipes. I thought I’d maybe share a few that I’m into right now.

(As a side note I’ve found out the hard way that it is very easy for me to go deep and quickly into ketosis. The doctor I’m working with warned that using stevia or anything sweet may throw you out of ketosis. I don’t have that problem but be careful to see if you do. Instead I must track everything’s my very carefully because I’m susceptible to ketoacidosis. Most of the literature brushed this off since I’m not diabetic. So I’d like to warn that it’s not impossible! I am nursing, and so that likely played a part.)

Tom Kha Soup - is a coconut milk based soup with lime and lemon grass. Here is a good recipe but you can experiment with it some. https://www.smallfootprintfamily.com/authentic-tom-kha-gai-recipe I used bamboo shoots which are low in carbs, chicken and mushrooms.

Milk chocolate - in a double burner (a bowl inside a pan of water) I warmed about 6 tbsp of heavy cream, a few drops of stevia and about a tbsp of erythritol (not sure how you spell it), and alcohol free vanilla extract 1 tsp. Then added in small batches about 28 grams of grated baking chocolate (non-sweetened) and melted it slowly. Do not let the water get into the chocolate mix. Poured it on wax paper and refrigerated it.

The heavy cream makes it a pretty fatty snack. But don’t over do it.

Gummy - I had raspberry zinger tea by celestial Seasonings (Tazo’s passion tea or orange tea would be good too. Celestial Seasonings has a lot of “zinger” flavors. Lemon is good.Just check to see if they contain anything that shouldn’t be in the diet). I brewed about 1-1.25 cups. Then added 2 tsp now of agar agar to the tea in a saucepan and simmered until the agar was dissolved. Then I poured it into a glass dish and refrigerated until it was set as a jelly. You could add a little stevia or erythritol if you’d like.

I think this made about 8 large sized pieces and I added it to a keto app that had them at less that 1 gram of carbs.

Next!! I sliced up the chocolate and gummy jellies and made little jelly chocolates sandwiches out of them! My kids tried to eat them all!

These things really helped me the other day when I was feeling really down about my very bland diet and a bit sick of avocados! Hope they are helpful to some of you. I’m happy to answer questions if I haven’t been clear.


Replication and Immunotherapeutic Effects of DNX-2401 in Recurrent Malignant Glioma

Some hopeful results.  http://bit.ly/2FMbuBT

Thursday, 1 March 2018

Salt Tablets

Hi Everyone
Given that my daughters normal blood pressure has always been on the lower end of the scale, i have been giving her some OTC salt tablets (600mg Sodium Chloride) 4-5 times a day to counteract the Trandolapril and the higher dose of Verapamil over the week surrounding chemo treatments.
In reading an article from the library (Thank you Stephen for giving me access to the library) titled;
Losartan versus Enalapril on celebral edema, it states that lab rats were given a high salt intake to accelerate the appearance of celebral edema.
It concludes that chronic treatment with the AT receptor blocker Losartan prevents the development of celebral edema, and causes manifest cerebral edema to disappear in salt loaded rats?
I am totally new to all of this, and i struggle to understand the medical and scientific interpretations, so i guess my question is;
By giving my daughter a salt supplement to counteract her angiotensin medications, could i in fact be escalating the risk of additional edema.
Any feedback greatly appreciated.

Conflicting advice from ND

Hi all,

My ND is suggesting the following things. I’ve read reports that state the opposite in these cases and wanted to get opinions. She is going to supply me with the studies she is basing her recommendations on as well.

During radiation and TMZ treatment:

No Boswellia - this is because of TMZ, not radiation. I was hoping to use Boswellia to avoid swelling and steroid use.
Fish Oil is okay during radiation. She says this can also counteract swelling.
Melatonin during radiation, she says it’s good to do.
Medical marijuana higher CBD than THC - I’ve seen advice that it should have higher THC than CBD

I have all of my files into Duke now and am hoping they’ll offer treatment alternatives. Mostly, I’m not sure I will be doing the TMZ, since the tumour is unmethylated. So some of these things may not be an issue.



Nativis Voyager clinical trial

Stephen, what are your thoughts about this trial:

Nativis Voyager® System in Patients With Recurrent Glioblastoma Multiforme (GBM)


Cocktail Interactions with Chemo and Radiation

Stephen, I can’t remember what RX/supplements to hold or continue during radiation and/or TMZ?
Can you help?

*Oct 2013 husband diagnosed GBM#4, left frontal lobe, total resection, no seizures. 
*Total 6 wks SOC, TMZ & Radiation. Drug cocktails below. 
*Dec 2013- Oct 2015 Optune Trial/TMZ. Stopped Optune due to skin issues.
*Jan 2015, NO thought recurrence so changed him to CCNU cuz TMZ “failed him”. The CCNU was brutal on him so he stopped it July 2015.
*I did not agree it was recurrence as looked like necrosis to me. I was upset off TMZ since Methylated. June 2015 took him to UCSF/Berger. He agreed didn’t think recurrence either so we decided to ”watch and wait". Since “supposed” recurrence never materialized, he stopped all treatments July 2015 except Drug Cocktails. 

*Jan 2018, GBM recurrence a little forward of original tumor (not area they watched b4). Full resection. Since still methylated and was treatment free since July 2015, decided to try TMZ for 12 mos and Cyberknife radiation for 5 days. 

Tumor is: IDH-1 R132H wildtype. ATRX retained, Mib 10%, MGMT Methylated 
Will have the gene testing results soon.

Hubby is 76.5 yrs old, has some cognitive/motivation issues from 2013 treatment but physically adept. 
Due to his age, I am light on the cocktails:
A) Chemo: TMZ, 300mg 5/23
1) Divalproex Sodium (Valproex Acid) 250 mg DR x 2 daily 
2) Sulfamethox-TMP DS 800 – 160 MG TAB 3 days a wk 
3) Celecoxib 200 mg x 2 
4) Cimetidine, 200 mg x 2 
5) Maitake D fraction Pro 4x, 100 mg x 6 
6) Coriolus – PSP, 400 mg x 6 
7) LEF European Milk Thistle: 240 Silymarin, 90mg Silybin, 24 mg Isosilybin A & B, phospholipids x 2 
8) D3-5,000 IU 1 pill x 1 
9) BroccoMax Broccoli seed extract (sulforaphane Glucosinolate), 30 mg x 1 
10) pTeroPure (Pterostilbene) 50 mg x 1 
11) Mega Lycopene, 15 mg x 1 
12) Melatonin, 20 mg x 1 
13) Longvida curcumin, 1000 mg x 1 
14) Multi-vitamin (not sure if I should give him??) 
15) Pro Omega, 1175 mg x 1 
16) Berberine, 500 mg x 1 
17) Probiotic x 1 
18) Decaf Mega Green Tea Extract, 725 mg x 2 
19) LEF Ultra Soy Extract, genistein not taking right now 
20) Boswellia, not taking currently

Thank you and Blessings to you all!