Adderall for focus/energy

The great puzzle of dosage and meds. My husband has been on Provigil for about a year. He took 100mg morning, 100mg at lunch time but with little effect. I have asked Greg's neuro-onc to switch to Adderall, and she has. As of Sunday, Greg is now taking 10mg of Adderall XR. Some people in various blogs talk about a light switching on, increased energy and focus, I have yet to see much change. As background, Greg is 62 yr-old, with GBM, right frontal lobe, diagnosed May 1, 2015.  No resection possible. He has been taking the Stephen Western/Ben Williams cocktail since about October. Greg is now about to begin Avastin this Wednesday with the hope of reducing edema since nothing else seems to work and that includes cannabis oil, curcumin, etc. Sorry, two different subjects but possibly related?

Cusp9?

Anyone know when CUSP9 is going to start?

Optimising cancer immunotherapy

Interesting information on immunotherapy

http://emjreviews.com/wp-content/uploads/Optimising-Cancer-Immunotherapy-Challenges-and-Opportunities.pdf

Towards precision medicine-based therapies for glioblastoma

Interesting article.  Thoughts?

https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-016-2908-7

Coley's Toxins and CHIPSA

I had heard about Coley's Toxins through this NPR article:

http://www.npr.org/sections/health-shots/2015/12/28/459218765/cutting-edge-cancer-treatment-has-its-roots-in-19th-century-medicine

and had forgotten all about it until someone mentioned it in a group that I'm a part of, specifically, the version being offered by CHIPSA in Mexico:

http://chipsahospital.org/coleys-dendritic-therapy/

The video is actually factually correct up until the service-selling portion. I was wondering if anyone had any experience with it and how they felt it rated against Dr. Raymond Chang's offerings here in my hometown of NYC?

Anyone have any experiences to share?

Intranasal delivery

This post is a response to Joanne's post about the cerebellum, as I wanted to include a visual.  For tumors in the cerebellum, the method of delivery might be the most important factor.  According to one study,

"The cerebellar uptake of IN delivered neurotherapeutics is found to peak at 12h rapidly declining by 24h. IP delivery does not exhibit peak cerebellar uptake at any particular time point, rather it is observed to be at the same level at all time-points. Cerebellar uptake of neurotherapeutics after IN delivery is ~5 ± 2 times greater than that after IP delivery"

In other words intranasal delivery results in far higher drug levels in the cerebellum compared to intraperitoneal injection, which is the usual method for delivering drugs to lab animals.

Click on image above to enlarge.  The 4 lines at the top represent levels of therapuetics (including curcumin) in the cerebellum after intranasal delivery.  The 4 flat lines on the bottom are the same therapies after intraperitoneal injection to mice.  Quite an impressive difference.

From the study: Brain Uptake of Neurotherapeutics after Intranasal versus Intraperitoneal Delivery in Mice

The question from here is which therapies are formulated for intranasal delivery.  Perillyl alcohol and chlorotoxin (scorpion venom) are taken this way, though neither of them are easy to access.  As we've discussed recently there are curcumin nasal sprays on the market, though I haven't seen any clinical research published with them.

http://store.bioponic.com/curecumin2.html

Let's make this the "intranasal therapy" thread.

Cerebellum

Trying to work out if there are any cocktail drugs that may help if recurrence is diffuse and has occurred in the Cerebellum,(original site was left temporal lobe.)

Any thought greatly appreciated.

Coffee intake and glioma risk

Interesting new study that found:

"a significant inverse association between coffee consumption and brain tumor risk in both total subjects (≥3 cups/day; HR=0.47, 95%CI=0.22-0.98) and in women (≥3 cups/day; HR=0.24, 95%CI=0.06-0.99), although the number of cases in the highest category was small. Furthermore, glioma risk tended to decrease with higher coffee consumption (≥3 cups/day; HR=0.54, 95%CI=0.16-1.80). No association was seen between green tea and brain tumor risk."

3-bromopyruvate questions

I was recently asked what I know about 3-bromopyruvate.

It certainly has all the preclinical rationale and demonstration of efficacy needed for clinical trials. My two main questions about it would be:

1) where a person would get it in a formula safe for human use.

"Hence, it is suggested that PET scan positive cancer types may be benefited after treatment with a patented and proprietary formulation of 3BP. It is worth noting that unformulated 3BP may be harmful in some cases."

"The patient was treated immediately via TACE with specially formulated 3BP (patented and proprietary)..."

http://www.ncbi.nlm.nih.gov/pubmed/22328020
The first author of this study quoted above is the person responsible for developing 3BP as a cancer treatment.  I'd recommend the book "Tripping over the Truth" for the highly interesting inside story on that.
http://beyondfunctional.com/review-tripping-truth-metabolic-theory-cancer/

2) who would administer it and how?

I've not heard of oral administration of 3-BP, it is given intravenously or directly injected into tumors. In the only in vivo glioma study I'm aware of, the 3-BP was inserted into the brain in the form of a biodegradable wafer (not unlike Gliadel).
http://www.ncbi.nlm.nih.gov/pubmed/25053853

In the most famous in vivo study of 3-BP, the 3-BP was also applied intratumorally to hepatocellular tumors.  http://www.ncbi.nlm.nih.gov/pubmed/15465013

For brain tumors, it's not even clear if intravenous administration would be sufficient.  There must have been a reason these animal studies applied the 3-BP intratumorally rather than the more common systemic method of intraperitoneal or intravenous injection.

Finally, since no phase 1 trial has been conducted, we have no knowledge of what the proper dose and safety profile would be for intravenous or direct application into the brain.  These are all significant problems that need to be overcome before 3-BP can become more commonly used for brain tumors.

Metrononmic TMZ for newly diag with amplified EGFR

My wife's 2nd 5/23 dose (which was doubled) has hit her hard.  I started looking into the metronomic TMZ option and found this very interesting clinical result for strong PFS and OS if you are EGFR amplified and on the metro dosage.

http://www.ascopost.com/issues/may-25-2015/egfr-amplificationoverexpression-associated-with-improved-response-of-glioblastoma-to-metronomic-temozolomide/

I'm curious:
1. what's your metro dosage been?
2. how have the side effects been?
3. is there anyone out there that has changed mid-stream from 5/23 to metro and if so, was it a significant help with daily QoL?

Thank you!

CO Consultants

We are getting ready for a visit to Husband's NO on Aug. 31st, gathering as much information as we can to take with us.  If his scan shows any GBM growth, we are going to ask about adding a couple more "bombs" in his carpet-bombing arsenal.  (The information we get here is so very, very valuable.  Many thanks to Stephen for starting this blog.  You are a missionary from God!)

My question concerns CO Consultants...can anyone recommend one that has helped them personally?  I see Aunt Zelda's, Miriam's Hope, and Green Health Consultants and know there are others out there.  Since Texas is a compassionate use state for epilepsy only, I guess we will have to fly to another state to get our card, but even then, I have no idea how we'll get the CO regularly.  We need to talk to someone who knows about this better than we do.  Help?

zinc + temozolomide regresses U87 GBM in mice

From a new study in Oncotarget.

The green line in the top graph shows tumor regression in mice treated with zinc + temozolomide, but not with temozolomide alone.  The bottom graph shows tumor volume at 7 time points in each of the groups (no tumor at the final two time points in the TMZ + zinc group).  

This was an orthotopic (intracranial) tumor implant model, with U87 (p53 wild-type) GBM cells, and TMZ and zinc were administered orally. The study does not say the dose of zinc used, and does not address whether zinc is normalizing the protein conformation of p53 in the U87 cells.  A prior publication showed that U87 cells had mostly mutant-type dysfunctional conformation of the p53 protein, even though there was no p53 gene mutation, due to high expression of metallothionein which steals zinc from the p53 protein.

Glutamate?

Hello,

there hasn't been much written about the role of glutamate in gliomas, so I was wondering if anyone had looked into it before? It caught my attention some time ago when someone posted a link to "medical food" Cronaxal, which "is a combination of oxaloacetate and ascorbic acid (vitamin C). Oxaloacetate reduces Glutamate levels in the brain in multiple laboratory animal tests.  Glutamate overproduction is directly tied to the growth of malignant gliomas, their invasiveness, and their ability to destroy neighboring brain tissue.  Patients with Glial Tumors have an impaired capacity to metabolize glutamate due to the high amount of glutamate produced by the tumor itself.  Oxaloacetate helps to metabolize glutamate to alpha-ketoglutarate."

Anyway, search on pubmed does return some hits on glutamate and glioma, for example Glutamate and the biology of gliomas (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107875/) where it states: "Glioblastoma tumors release Glu to enhance their highly malignant behavior, and that Glu release via system x_c^- and the excess extracellular Glu this system imparts a survival advantage by promoting resistance to apoptosis and by promoting glioma proliferation and invasion. In fact, the invasive nature of gliomas enhanced by Glu release is one of the most important limitations to effective disease control; experience demonstrates that more than 80% of glioblastoma recurrences occur within 2-3 cm of the original resection cavity. Successful treatment of malignant gliomas requires recognition of Glu and its receptors as potential targets and novel approaches modulating their influence are needed to improve upon existing ineffective therapies."

At the end of the article there are some suggestions for targeting glutamate with repurposed drugs, but I also found some supplements that could do that in some degree (like theanine, N-acetylcysteine and glycine). Anyone tried this approach to complement the cocktail?

 

Treatment Options for Glioblastoma and Other Glioma - 2016

I'm pleased to announce that the annual Ben Williams Treatment Options update was published today on the Virtual Trials website.  I've inherited the annual updates from Ben, and had been working on this for the past few weeks.

  https://virtualtrials.com/newsarticle.cfm?item=6140  (for Al's commentary and link to the PDF)

Direct link to the PDF here

My brother has been doing TMZ 5/23 for over 18mths. We are wondering about changing the dose to daily low dose to try and avoid the fatigue etc that he has for that week. Would low dose be as effective? He is MGMT methylated.
Thanks, Lisa

First MRI and follow-up

Hi,
My father is due on Tuesday for the first follow-up after radiation and two rounds of monthly 5/23 high dose TMZ.

No MRI was taken after radiation but prior to monthly TMZ. I asked the NO if it wouldn't be a good idea to have an MRI taken one month after the RT, but she said it was too early to see the effects of the radiation, and besides it simply wasn't their way of doing things.

So this will be the first MRI to compare to the post-op scan taken the day after surgical resection of the tumors.
Since he's MGMT unmethylated I suspect the TMZ will not have had that much of an effect, and thus the question: What to do if the scan shows progression or recurrence?

Continue the monthly TMZ or suggest something else - carboplatin, irinotecan, re-operation if possible, try the german clinics, something else?
I guess CCNU wouldn't really be any better, since it works the same way as TMZ?
What would be the least bad/unpromising "salvage therapy" - Stephen?

I had a quick check on clinical trials in Sweden but nothing targeting recurrent tumors.

Father's profile:
* EGFR positive/staining (but unknown if EGFRvIII mutated or not)
* IDH1 R132 negative/unmutated.
* Weak p53 staining (likely unmutated p53)
* No loss of 1p or 19q.
* MGMT unmethylated (9% methylation)

Thanks,
Peter

Hepatitis C

I would love some feedback about whether we should try and tackle my husband's Hepatitis C. He is not eligible for almost all clinical trials because of Hep C. My concern is using drugs like Epclusa or Harvoni could make things worse for him. Trying to get a liver specialist & his neuro-onc on the same page is difficult. Any feedback or experience would be most welcome. 

More progressive NO in Los Angeles

All -

I was just cleaning out my pile of notes from the UCLA Brain Tumor Conference last March.  I spoke with Dr. Albert Lai albertlai@mednet.ucla.edu;  310-825-5321 after his lecture and he said that he generally will prescribe something for GBM if the patient asks about it.  I know some of you ran into hurdles getting a NO who would give you some of the cocktail meds.  I believe Dr. Lai is open minded.  Also I had asked about seeing my Dad via Skype as we are in Seattle.  He said that he had never done that before but it may be an option.

Just wanted to share that with you as I know some folks have had trouble with their Oncologists.

Best.
Annie

SMPF Therapy V Novocure.

Any thoughts on which may be more effective?
I know Novocure has had more trials and data but as it needs to be used for
such a large part of the day on a shaved scalp my daughter isn't keen.
The small amount of information I have on SMPF, which is carried out in Bangalore seems quite promising.

Niclosamide

I was discussing options with Dr. Hercbergs (T4 suppression treatment) and he brought up Niclosamide.  A quick internet search brings up some interesting information.  Anyone familiar with this?

mTOR inhibitors

Does anyone have any knowledge of mTOR inhibitors and availability?

I am looking into them as a target for MYCN amplification due to the
 H3F3A G34r mutation that my daughter has.

We have today had recurrence confirmed in inoperable areas and are trying to decide what may be the best way forward.
There don't seem to be a lot of options with this mutation.

Curcumin rescues mice with GL261 mouse glioma syngrafts

The blue line represents survival of mice treated intranasally with an experimental curcumin-antibody conjugate.  The red line represents mice injected intraperitoneally with 100 mg/kg curcumin in the form of Meriva Curcumin phytosomes.  These treatments dramatically shifted the phenotype of microglia from a tumor-promoting M2 type to an anti-tumor M1 type.

from the study:

Curcumin Changes the Polarity of Tumor-Associated Microglia and Eliminates Glioblastoma

online August 20, 2016 in the International Journal of Cancer  

to be uploaded in the Brain Tumor Library, folder 2, Curcumin subfolder

When do you take your Temodar?

My wife is about to start the 2nd round of the 5/23 6-month regimen and as you know the dosage is doubled so the potential increased side effects concern me. I'm curious as to at what time of the day you are choosing to take the pill and if you make a point to eat prior or after etc. Have you switched it up and found another time works better? Thanks!

Comments

I am about to disable anonymous comments, as anonymous comments for some reason cause recent comments to disappear from the sidebar.

The options allowed by blogger are these:

I'm going to try the Registered User option, which allows commentators to use one of the following user ID options: Google account, Livejournal, WordPress, TypePad, AIM, OpenID.  This appears to allow the greatest flexibility while disallowing anonymous comments. Feedback welcome.

Article about hypoxia: How tumors adapt to become more aggressive

From an article at Sciencedaily.com, see link below.

"One of the many reasons tumors are so difficult to treat is that they are able to adapt whenever they are exposed to unfavorable conditions. Hypoxia, or a lack of oxygen, is one example of a phenomenon that should weaken the tumor, but instead, the malignant cells are able to compensate and drive more aggressive disease behavior.

Now, scientists at The Wistar Institute have identified a novel mechanism that selectively operates in hypoxic tumors to enable tumor cells to thrive and continue to proliferate despite a low oxygen environment. Dario C. Altieri, M.D., Wistar's President and CEO and lead author of the study, and colleagues showed how the activation of this pathway leads to an unfavorable prognosis for patients with gliomas -- a type of brain tumor -- and how the pathway could be a valuable therapeutic target in cancer. The findings were published in the journal Cancer Cell.

"Hypoxia is a nearly universal hallmark of aggressive tumor growth, and up until now, we really haven't been able to home in on a pathway responsible for this behavior," said Altieri, who is also director of The Wistar Institute Cancer Center and the Robert & Penny Fox Distinguished Professor. "Our study pinpoints a novel way in which tumor cells not only survive but actually continue to divide in spite of a low oxygen environment. In essence, this provides a much-needed answer for exactly how tumor cells are able to get the energy they need to persist when faced with unfavorable conditions."

Mitochondria, known as the "powerhouse" of cells because of their role in energy production, are the main source of hypoxia-induced reprogramming in tumors. The Altieri lab showed that the protein Akt, which plays a key role in cell signaling and metabolism, accumulates in mitochondria during hypoxia. When this happens, the protein PDK1 is phosphorylated at a unique site, and a complex responsible for cellular respiration is shut down. The pathway then uses the tumor's metabolism to break down glucose and use its energy to reduce cell death and maintain proliferation.
The mitochondrial signaling between Akt and PDK1 was analyzed in a cohort of 116 patients with gliomas. The activation of this signaling pathway progressively increased in different types of gliomas, with the highest activity seen in patients with glioblastoma, a particularly difficult-to-treat form of brain cancer that represents approximately 15 percent of all brain tumors.
"We are excited about our results because there are drugs that exist that specifically target Akt in cancer. These drugs have produced limited clinical responses to date, but we believe with further investigation that we may be able to repurpose these drugs as a viable approach to impair a tumor's ability to adapt to hypoxia," said Young Chan Chae, Ph.D., an associate staff scientist in the Altieri lab and first author of the study."

Link to the "news article":
https://www.sciencedaily.com/releases/2016/08/160808124042.htm?utm_source=feedburner&utm_medium=email&utm_campaign=Feed%3A+sciencedaily%2Fhealth_medicine%2Fbrain_tumor+%28Brain+Tumor+News+--+ScienceDaily%29

And the scientific journal (unfortunately no access to it):
Young Chan Chae, Valentina Vaira, M. Cecilia Caino, Hsin-Yao Tang, Jae Ho Seo, Andrew V. Kossenkov, Luisa Ottobrini, Cristina Martelli, Giovanni Lucignani, Irene Bertolini, Marco Locatelli, Kelly G. Bryant, Jagadish C. Ghosh, Sofia Lisanti, Bonsu Ku, Silvano Bosari, Lucia R. Languino, David W. Speicher, Dario C. Altieri. Mitochondrial Akt Regulation of Hypoxic Tumor Reprogramming. Cancer Cell, 2016; 30 (2): 257 DOI: 10.1016/j.ccell.2016.07.004

Pharma and non-pharma list

For those of you with access to the Brain Tumor Library on my Google Drive account (contact me for access), I've replaced the pharma and non-pharma top 10 lists with a new spreadsheet called "Pharma and non-pharma list, info and ranking".  This is a more complete listing, and is very much a work still in progress.  This is found in folder 0 of the library (Reference folder).

RSO and Turkey Tail

Has anyone tried RSO or Turkey Tail?

Is EBC 46 available anywhere

So there is this exprimental drug EBC 46 . Is it available from Sigma Aldrich or any other company?

Further Decline

Hello,

Since being hospitalized for pneumonia, my dad has declined even more. His TMZ and radiation are done for now and he is on IV medication for the pneumonia. He is not taking anything other than his necessary medications as he is refusing to swallow much else right now.

His processing has slowed considerably and it is as if he is on another planet. In other words, he is not with it and present. He will respond when we speak to him but then sort of checks out again. Sorry for the lack of medical terminology, but I am struggling to describe his state. When reaching for something it is slow and sometimes difficult. Sometimes he looks around for something and then he gives up or forgets. Everything has slowed considerably. Occasionally, he will say something that I don't expect him to know or remember and then he returns to the slower functioning soon after.

This seems like more than the aftermath of chemo and radiation that many of you have described. I feel as if something else is going on. His ct-scan does not suggest progression, and his doctors are still waiting to do an MRI.

Insurance and the doctors are telling us that he needs to be discharged soon and moved back to a rehab facility.

I am wondering if there is something else we should be trying/doing or if it truly is a wait and see.

Additionally, he is on Metformin; should I discontinue until he starts the TMZ again? His blood sugar was low recently. I am wondering if he could and should get a break from it.

Thanks again.

Chance Gilford's BT Cocktail Items Available

Hi Friends,

We have some items, mostly unopened, in case you can use them:

Unopened

2 EA DCA 60 Capsules 330 mg from Pharma DCA
2 EA Vitamin B1 500 mg from Pharma DCA
1 EA Life Extension Mega Green Tea Extract 100 Vegetarian Capsules 725 mg
1 EA Nutrivene Curcumin Longvida 60 Capsules 500 mg
1 EA Source Naturals Boswellia Extract 100 Tablets 243 mg
1 EA Natrol Melatonin 60 Tablets 3mg

Opened

1 EA Superior Labs Boswellia Extract 120 Vegetable Capsules 600 mg (about 100 remain)
1 EA JHS Natural Products Coriolus Super Strength 150 Vegetarian Capsules 600 mg (about 135 remain)
1 EA Liftmode Magnolia Bark Extract 50 grams (about 25 grams remain)

Let me know which you can use and your mailing address. No need to reimburse me but I would appreciate a donation to http://astrocytomaoptions.com/thank-you/. It does not need to be an equivalent amount; we just want Stephen to know how much we appreciate him!

T4 Suppression

Because T4 suppression therapy looks promising for GBM’s and other cancers based on a small observational study, I thought I would post my sons response to this treatment over time.  The study can be found in Stevens Brain Tumor Library, Therapies - human Studies. 

For those not familiar with my sons story, here it is.  Originally diagnosed with a large Oligo 2 in 2007.  It was located in the left parietal region.  Received radiation and TMZ.  There was no evidence of tumor until October 2014 when a GBM was diagnosed after personality changes.  This was treated with TMZ, radiation and Optune.  In Feb 2016 he experienced his first recurrence, three areas in the occipital lobe.  Treated with SRS and TMZ and was started on Nivo.  All 3 areas resolved within two months.  Then in June an area of enhancement showed up in the pons and one month later a recurrence in the occipital lobe and in the area of the 2007 resection cavity.  TMZ and Optune were discontinued.  The small enhancing area in the resection cavity was treated with SRS in an attempt to enhance the possibility of an immune response in conjunction with Nivo.  CCNU and Avastin were recommended.  Concerns over Avastin are the increased migration and invasive nature of GBM’s once exposed to it.  CCNU is myelosuppressive and we are trying to obtain an immune response from Nivo so we are not too excited about that. 

Which brings us to the T4 suppression therapy.  This was started yesterday.  We will see if a response occurs and if not, or if neurologic symptoms become worse, we will continue T4 suppression and add CCNU and Avastin.  The BELOB trial showed a relatively small benefit with CCNU and Avastin, with the exception of IDH-1 mutated tumors where the response was significant.  My son’s tumor is IDH-1 mutated.  At least the original GBM was, and I am told recurrent tumors maintain that mutation.  So maybe CCNU and Avastin will prove significantly beneficial.  For now, we are holding on the CCNU and Avastin.  That could change quickly.

Jeremy has been on a repurposed drug and supplement cocktail throughout his GBM treatment.  Both NO’s he sees have been supportive of the cocktail approach because they believe he is responding better than the typical IDH-1 mutated GBM patient.

I will keep you up to date.  If the T4 suppression approach is effective, it might be worth looking into as an additional treatment for those in our group.  I have contacted Dr. Hercbergs, the primary investigator in the Observational study on T4 suppression.  He provided me with additional information and target FT4 levels if anyone needs this information.

Anti seizure medications

Hi all,

Thanks to everyone for contributing to this amazing blog as always. Sorry I have been quiet for a while.

A quick update on Mum. She has been doing a cocktail with mainly natural supplements, Cbd oil and some repurposed drugs including Celebrex, Metformin and Mebendazole (Cimetadine on hold whilst she comes off Phenytoin). She has also been having treatment at the IOZK in Cologne. She completed 4 cycles of Temodar out of the standard regime in the UK of 6. She could not get onto her 5th round as her neutrophils have remained too low. She had her first Dendritic cell vaccine a few weeks ago after completing 6 cycles of Newcastle Disease virus and localised hyperthermia (which are given once a month and are planned out to time with the patients chemo rounds). They were not concerned that she was unable to complete chemo -it did not affect their treatment. The dendritic cell vaccine used Mums tumour tissue from her last operation in December and was cultured over 7 days immediately prior to the vaccine. They were able to produce 3.5million dendritic cells which they were happy with as a good vaccine contains 1 million apparently (not sure who counted them! :) .. )

Her scans have shown a tiny 6mm fleck that appeared in April but has remained unchanged since.

Her speech, reading and writing has been affected and her vision/balance slightly but she is doing really well right now in general.

Last week she had a series of partial seizures. Most of them occurred during the night and they did not last for too long but Dad took her to A & E for the first 3 of them. They got milder during the week and her last one was a week ago on Friday morning. Mum has been coming off Phenytoin which she was put on about 3 months ago when she had her last seizure. Not sure why they gave her that as it interacts with Cimetadine and has much worse side effects but for some reason it takes ages to come off safely. She is nearly completely off it and they have increased her Keppra to 1250mg twice a day. This seems a lot to me especially as her seizures have been fairly mild.

My question to the group is which anti seizure medication are you or your loved ones taking and what dosage?

I believe Keppra is the best in terms of less side effects but at that high a dosage perhaps it will cause some problems for Mum. I would like her to increase the dosage of Cbd oil too as this has anti seizure properties and she has been on a fairly consistent average dose for a while now.

Are there any other anti seizure medications that people are taking other than Keppra and has anyone been on a high dosage of this for a long period of time? If so, how have you/they found it?

Thanks all and warm wishes to everyone.

Alison

Some Changes

Hello,

My dad is weaker today than he has been. The staff at the rehab facility put him in bed because he kept slumping forward in his chair and they were afraid he would fall out. He is also very tired.

We are working hard to get him CBD/THC in the hopes of boosting his appetite. I am also considering the Remeron that people suggested the other day. He eats very little, so I know that is a problem. The doctors are talking about increasing the steroid (he is at 2 mg. now). I really want him to be done with it because it is a double-edged sword, but is increasing it the best option right now? He has very little edema at this point. They are also talking about doing an MRI sooner rather than later. He has two sessions of radiation left.

Is the extreme weakness all part of the treatment? Is the tumor causing this? I am guessing it is a combination of things, and I want to help him. Meanwhile the doctors are making their suggestions and I am trying to figure out what is best.

I appreciate your thoughts.

Best,
Stephanie

Solumedrol for brain edema.

We are having problem with edema that is difficult to control. I am posting this for information for anybody else. Prof Pierre Yvess Dietrich just suggested to us solumedrol 250mg/day as iv for brain edema. He stated that it is more potent than dex for brain edema.

Mark Murray - GBM Vaccine recipient

Has anyone heard whatever happened to Mark Murray, who received a "vaccine" made from his own tumor by Dr. Richard Komotar in South Florida?

Here is the video of that:  https://www.youtube.com/watch?v=bymg_2GQQb0

Suggestions?

Hi,

My dad is due to finish up his first round of TMZ and radiation on Wednesday. Over the last few weeks he has declined considerably. The nausea and vomiting kicked in and he is very weak. His balance and mobility are limited at best. He has been in a rehab facility for a few weeks because he fell at home and ended up there. We tried to get him back home last week, but he is unable to perform basic functions on his own and/or with help from my mom. There will be people (including the rest of us) stopping in to help him once he gets home, but it will not be consistent, so the two of them need to be able to manage.

At this point he is not taking much in terms of supplements because the nausea and lack of appetite prevent him from putting much in his mouth. He is also eating very little and nothing healthy.

Once the chemo and radiation end and the steroid stops (he is at 2mg as of tomorrow), I want to give him whatever I can to build up his strength and breathe some life into him. Any suggestions?

I know it will not happen over night and that there is no magic pill, but I want him to come home. He desperately needs to be at home, and he needs to build up his strength for that.

Thanks,
Stephanie

CUSP-ND and Prozac

Stephen, I recently re-read the paper on CUSP-ND at:

http://www.anticanceralliance.com/cusp-nd/

and am a bit concerned at all of the "severe" interactions between Prozac and all of the other drugs in the cocktail (starting on page 104). Particularly it's interaction with celebrex and chloroquine.

My questions are:

1. If you had to choose between prozac and chloroquine, which would you choose? 
2. Moreover, I note that in Kast's CUSP9, he utilizes Zoloft (Sertraline) instead. Was there a reason that the CUSP-ND swapped out zoloft for prozac?
3. Would one be more beneficial than the other if Optune is also utilized along with the protocols?

Where to get intravenous Diflunisal in Europe?

Diflunisal worked very well for my brother. He was fed via feeding tube 3 months ago then he improved very much on it but now today he is on the feeding tube again. We run out of Diflunisal bags few weeks ago. Tumor is small but edema is a problem. I don't want to buy the whole Diflunisal therapy at unifontis. Anybody knows where can I buy just the Diflunisal bags? Which pharmacy in Europe would sell it on doctors prescription? I was able to get intravenous aspirin but how to get the intravenous Diflunisal bags?

Atypical AA3 in a 20 YO

Hello everyone:

I am grateful to have this group. My sister, 20, has been recently diagnosed with an anaplastic astrocytoma, IDH wildtype. Her ATRX and p53 proteins are intact, and she has the TERT promoter (pTERT) mutation.

Her tumor is quite unique, in the sense that it is not exactly an adult glioma nor a pediatric one. It has a mutation in the ARID2 gene, which is commonly found in liver cancer and is associated with tumor recurrence.

She has had subtotal resection of her large left insular tumor, and her medical team are now “wrestling” to find an appropriate treatment for her. I have a few questions, and I appreciate your input on them:

1.   Notable labs: has anyone tried this start up? Its initial mission was to help brain cancer patients find FDA approved drugs that can control their disease but it seems to have changed its direction. It is running a clinical trial for leukemia patients.
2. Survivorship: is anyone aware of a long-term survivor of anaplastic astrocytoma, IDH wild type? Some papers on Pubmed indicate that very few make it past two years following treatment.
3. Depression: my sister is, quite understandably, depressed and resents the idea of having to undergo radiation and chemotherapy. I want to convince her of the benefits of the cocktail approach, but I have no idea how to open the subject to her. Is any of the caregivers here experienced in this matter?

Thank you all.

Meer

Hello everyone,

I have a question that I hope the community might be able to help me with.
I have a friend with GBM, and he is not doing well. His neuro-oncologist is at a loss as to what to try next to help him.
My friend recently had a conversation with his mother-in-law, and she told him about another patient she knows of who has GBM, also not doing well. The husband of this patient told my friend's mother-in-law about an alternative treatment, which he (the patient's husband) felt saved his wife's life. My friend's mother-in-law said it was called "blue water." Has anyone heard about this type of therapy? Or tried it? I'm trying to find out more information on it for my friend.
I thank you for any information or advice you can provide.
Blessings to you all.

Tina

Where to get intravenous aspirin in Europe

We need aspirin for IV. Is it possible to get it in Germany? Do you need a prescription? Maybe Czech Republic would be cheaper or Slovakia or any surrounding countries?

Melatonin for cerebral edema? Opinions?

My brother has a cerebral edema that is difficult to control. I'm trying to find some herbs supplements. What is your opinion on this?
http://www.ncbi.nlm.nih.gov/pubmed/24876075

Autophagy

Suppression of autophagy impedes glioblastoma development and induces senescence.

http://www.ncbi.nlm.nih.gov/pubmed/27304681

revisiting quercetin

Found this on another site.  In light of earlier observations about quercetin, maybe some reevaluation is warranted.   Thoughts Stephen


Here is what I have found out about the Temodar resistance of MGMT unmethylated:
"Our results demonstrated that U87/TR was MGMT negative, which indicated that MGMT made no contribution for TMZ-resistance of U87/TR.
It indicated that activation of Akt and Wnt/β-catenin pathways may be response for the chemo-resistance and increased invasion of U87/TR cells, and the phosphorylation of PRAS40 and inactivated mTOR may be related to cell cycle arrest in U87/TR cells."
http://www.ncbi.nlm.nih.gov/pubmed/27423571

And here they see that Quercetin could reverse that:

The cell survival rate was less than 50% in U87/TMZ group that was pretreated by quercetin combined with TMZ at the concentration of 50 μmol·L-1.Conclusion The drug-resistant U87/TR cell line was established. Combination of quercetin with TMZ could reverse drug resistance of U87/TR cells.  It suggests that quercetin combined with TMZ maybe enhances chemotherapeutic effect on glioma.

Artemisinin Revisited

Overview
I'd like to revisit the use of artemisinin and other natural compounds to add to the standard-of-care medicines and radiotherapy currently used in the fight against brain tumors.  So far, we've had limited but hopeful results.  Has anyone else had success with artemisinin or its derivatives? 

Our story
My husband, aged 61, was diagnosed with a glioblastoma-grade IV in April 2016.  The discovery of a mass in his left parietal lobe, accompanied by so much swelling was quite a shock, since he was such a productive person up to that point.  He rode his bike to work daily, went on lecture tours (he's a medical researcher, ironically), wrote endless grant proposals, played classical guitar, etc.  The only thing we could point to as being an issue was mild aphasia for about two years, which we had blamed on stress and insomnia.

He had 92% of the tumor removed at the end of April.  Three weeks later, the tumor had started to regrow to the point where they wanted to begin Temozolomide + radiation immediately.  He completed a 6-week regimen of both, taken concurrently, and with Chinese herbals (artemisinin, curcumin, and leukozepin) added during the last week.  Three weeks later, his scan showed a beaten-up, "leaky" tumor, that was about 50% larger - a combination of true tumor growth and inflammation.  Also noted on his path report:  "Exophytic growth towards splenium of corpus callosum and occipital lobe has progressed."

For those of you who are knowledgeable about genetic markers, he has the MDM4, PTEN, and TP53 mutations.  His IDH1 and IDH2 are wild type.  His MGMT promoter gene is 97% unmethylated, unfortunately.

I brought this abstract (link attached) to the last consult and gave it to his oncologist:  Artesunate enhances the antiproliferative effect of temozolomide on U87MG and A172 glioblastoma cell lines.  His oncologist was happy enough with this scan result that he let Husband continue on the artemisinin and temozolomide for Round 2, which will be higher doses of both but for only 5 days.  After that, another scan will be taken after letting the inflammation clear out, on August 29th.  We'll get the results on August 31st.

If you have any experience/information that you could share on combining artemisinin, artesunate, etc with traditional GBM meds, including immunotherapy, I would be so grateful to hear from you! - ABM

Blood baseline neutrophil count predicts bevacizumab efficacy in glioblastoma

Patients with higher baseline neutrophil counts or high tumor expression of CSF3 (G-CSF), the growth factor for neutrophils, especially benefit from Avastin in a large exploratory cohort and two clinical trial cohorts.

Click here for abstract and full text links.

Questions on Biopsy Results

My sister just got her results back from a recent biopsy. I wanted to get your guys input on it as it looks different from the original results we got from her resection and her genetic testing (which I knew would not b as in depth). I m wondering if this is sufficient to confirm its low grade glio cells? As doesn't have methylation or all the other stuff To determine grade (ki) auto correct sorry! Do u guys think I should aske her to ask for the biopsy report or this is sufficient? I would want as much info as possible but need others input before I mention to her as this may b enuf and I m missing it? Those results were from diff brain tumor centers then this one. Quick background: she's 34, dx Dec 14, secondary GBM, IDH1, partially methylated, P53, she had a Cple others that came up but I have to get her report from 14' and dble check. We were told they were ones nothing was being done w though and these were the major ones.  After rad/chemo an area of enhancement showed on MRI. She chose to stick w tmz. She's stayed on the 5/23 for over 16 months and the area has stayed stable. They did 2 PETs that showed no active cancer cells but we're still concerned so last month did biopsy to b sure. At first told her no more chemo as preliminary testing said it was necrosis. Well, then got call saying it had some low grade cancer glio cancer cells. At first dr Friedman recommended 6 more mths of 5/23 but cause my sis really does not want to do it they talked and he agreed to the metronomic sched. (80 mg tmz daily) but w my reading and the IDH1 I wanted your opinion on it or if something should b added? Read study from Perry. If I can upload her genetic testing what am I looking for, w regards to the idh1 that u were talking about earlier w Logan? She handled tmz 5/23 really fine (mostly gi issues, lost some weight, her absolute lymphocytes cont to drop but everything else ok and not low enuf to have to wait or anything for a cycle). She's only doing THC/CBD as Duke was against all supplements, other meds she was on. And they go by what they r mostly told, to a point. I still research, get info, trials ready (in case none at Duke work out and they don't go for avastin, if that's recommended). It's left parietal lobe.

Thanks u so much for any help w this and as always u guys and your luved ones r all in my thoughts daily.

Kylie

Unstained slides, SP16-22791 A1 (IDH1 Targeted Mutation Analysis with Reflex to IDH2 Mutation Analysis):

Positive.

IDH1 mutation detected. p.Arg132His (c.395G>A).
See comment and objective findings.

Comment: A single mutation was detected. The p.Arg132His IDH1 alteration is a previously cited mutation seen in CNS neoplasms (see references).

Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are NADP+ dependent enzymes that catalyze the conversion of isocitrate to alpha-ketoglutarate and are key components in the mitochondrial citric acid cycle. Acquired point mutations in primary CNS neoplasms have been described in codon 132 of IDH1 (predominantly Arg132His, but also Arg132Cys, Arg132Ser, Arg132Leu and Arg132Gly) and the analogous amino acid in IDH2 (Arg172Gly, Arg172Lys and Arg172Met). A high percentage of WHO grade II and grade III astrocytic and oligodendroglial neoplasms contain IDH1 or IDH2 mutations, including diffuse astrocytomas (II), oligodendrogliomas (II), anaplastic astrocytomas and oligodendrogliomas (III) and anaplastic oligoastrocytomas (III). IDH1 and IDH2 mutations are also common in secondary glioblastomas (IV) but are rarely found in primary adult or pediatric glioblastomas (IV). In patients with glioblastomas or anaplastic astrocytomas, the presence of an acquired IDH1 or IDH2 mutation is associated with longer overall survival. Multiple factors contribute to prognosis in patients with primary CNS neoplasms. Thus, this assay is intended for use as an aid in developing patient-specific prognostic predictions but is not a substitute for a complete pathologic and clinical evaluation, or physician's judgment and clinical experience.

The sensitivity and specificity of DNA sequencing is high for the detection of nucleotide base changes, small deletions, and insertions in the regions analyzed. This assay may not detect an acquired mutation that is present below the 15% detection limit (i.e., mutant cell population of <30%). Only amino acids 69-138 of the IDH1 gene and amino acids 126-178 of the IDH2 gene were examined. Changes outside of this region will not be detected. The presence of a mutant population containing a large deletion, duplication, insertion, aberrant splicing, or sequence alteration adversely affecting primer binding may not be identified using these methods. Mutations or polymorphisms in the DNA oligonucleotide primer binding regions, poor DNA quality, insufficient DNA quantity or the presence of PCR inhibitors can result in uninterpretable or (rarely) inaccurate results. For additional information or for help interpreting the results of this test, clinicians should contact the DUHS Clinical Molecular Diagnostics Laboratory. Patients should contact their healthcare provider with any questions related to this report.

References:

Balss J, et al. Analysis of the IDH1 codon 132 mutation in brain tumors. Acta Neuropathol. 2008;116:597-602.

Yan H, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009;360(8):765-73.

Laboratory Director:
                   Siby Sebastian, Ph.D., ABMG; DABCC
                   Associate Director, Molecular Diagnostics
   Clinical History
   
Persistent glioma, low grade
   Sample Type
   
Unstained slides, SP16-22791 A1
   Test Performed
   
IDH1 Targeted Mutation Analysis with Reflex to IDH2 Mutation Analysis
   Objective Findings
   
Complete coverage of IDH1 exon 4 (amino acids 69-138) was obtained using forward and reverse sequencing primers. These sequences were compared to the reference DNA sequence (GenBank Accession: NM_005896.2).

The following sequence change was detected: 
Gene
Location
Type
c.
p.
Normal sequence
IDH1
exon 4
missense
c.395G>A
p.Arg132His
Detected


   Methodology
   
This assay uses PCR amplification followed by Sanger DNA sequencing to detect point mutations in exon 4 of the IDH1 gene, with reflex testing to detect point mutations in exon 4 of the IDH2 gene for all IDH1 negative cases. An H&E stained slide for each case is first evaluated to identify the regions of greatest tumor content. These regions are then macro-dissected from adjacent unstained formalin-fixed paraffin-embedded sections and used to prepare genomic DNA. The protein coding and flanking intronic sequences of IDH1 exon 4 (containing codon 132), and, if reflex testing is performed, IDH2 exon 4 (containing codon 172) are amplified from this purified genomic DNA by PCR. The primers used in these PCR reactions contain M13 universal primer "tails" at their 5' ends, and have 3' ends that are complementary to their genomic target sequence. The resulting PCR products are treated with an exonuclease/phosphatase mixture (ExoSAP-IT) to remove excess PCR primers and nucleotides. These purified DNA amplicons are then sequenced using universal M13 forward and reverse sequencing primers (M13 Forward/-20 and M13 Reverse/-27) and the Big Dye Terminator v3.1 Cycle Sequencing Kit (Applied Biosystems). The products of the completed sequencing reactions are purified with the Big Dye XTerminator Purification Kit and resolved using the ABI Genetic Analyzer. Data is analyzed using the ABI Data Collection software, Sequencing Analysis software, and SeqScape software. Sequences are compared to the reference DNA sequence for the IDH1 and IDH2 genes (GenBank Accession IDH1: NM_005896.2; IDH2: NM_002168.2).
   Disclaimer
   
This test was developed and its performance characteristics determined by the DUHS Clinical Molecular Diagnostics Laboratory. It has not been cleared or approved by the U.S. Food and Drug Administration. This test is used for clinical purposes. It should not be regarded as investigational or for research. This laboratory is certified under the Clinical Laboratory Improvement Amendments of 1988 ("CLIA") as qualified to perform high complexity clinical testing.

Results
   Document on 7/31/2016  9:09 PM by Castellar Edgar R

Lab and Collection
   IDH1 Targeted Mutation Analysis with Reflex to IDH2 Mutation Analysis on 7/21/2016