Newly diagnosed family member hoping for some clarifications

Hi,
My name is Ashley. My mom was diagnosed with GBM unmethylated December 2017. She is 54 and healthy with a huge loving family that wants her around longer. She went in for emergent surgery due to headaches/pressure and this is how the tumor was found. They have removed the majority of the tumor. She is half way through radiation/chemo right now. She is essentially doing great as she has only hair loss and fatigue at the moment with some cognitive delays at time. I have researched extensively Ben Williams info, the Musella foundation, articles, journals etc. to help find the best treatments. Right now she is on these supplements:
fish oil 3g
melatonin 20mg
PSK trying for 3g
Genistein 125mg
Curcumin 4g
green tea (one-two cups a day)
Boswellia 1000mg but will be going up to 4200mg
Resveratrol 100mg/kg roughly 6000mg
Silibinin 420mg

Medications:
celebrex 200mg  BID (recently just started)
Metformin 2000mg (will start soon-introducing drugs one at a time)
Disulfiram (500mg on chemo days with 250 on non chemo days-4mg copper also with this)-starting soon
Aralen (chloroquinine) 150mg BID --starting soon
Doxycycline 100mg BID-unsure about starting this? (this was recommended by Ben but I just haven't seen many recent trials using this)

My biggest question is how long do we have our family members take this? Is it every day or on just chemo days? There isn't great detail on how long people should be taking these.

Thanks,
Ashley

2016 Classification of Diffuse Gliomas

This is a handy diagram showing the current (2016) classification of diffuse gliomas. I snipped it from Chapter 6. Molecular Classification of Gliomas (Kenta Masui et al) from the Handbook of Clinical Neurology, volume 134 (2016) edited by Mitchel Berger and Michael Weller.

leucine restriction for IDH1mut?

Hi all,

This article here says that leucine is an activator of GLUD2.

http://www.pnas.org/content/111/39/14217

This is the article they sited:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944346/

Leucine is an essential amino acid, which means we must eat it in order to get it. The first article seems to say that leucine is stored in IDH1 mutant gliomas…but I read another article that this depends on the concentrations of ADP and L-Leucine — which implies they can be diluted. Is there an ADP inhibitor? (An initial google search seems to say there is but I'm not sure how they will impact the brain or health in general. I'm going to search that when I have more time.)


Thanks.
Maria

Do statins, ACE inhibitors or sartans improve outcome in primary glioblastoma?

This is a new paper (click here for abstract) brought to us by some of the same authors who earlier produced:

Does Valproic Acid or Levetiracetam Improve Survival in Glioblastoma? A Pooled Analysis of Prospective Clinical Trials in Newly Diagnosed Glioblastoma

The group concluded:

"This secondary analysis of two large glioblastoma trials thus was unable to detect evidence for an association of the use of statins, ACEI or sartans with outcome in patients with newly diagnosed glioblastoma."

As with the previous study, there are some important caveats.  Some of the most intriguing data supporting the potential for angiotensin system blockers was in combination with bevacizumab:

Effect of angiotensin system inhibitors on survival in newly diagnosed glioma patients and recurrent glioblastoma patients receiving chemotherapy and/or bevacizumab

It would have been interesting to look at outcomes in those using/not using ACE inhibitors or sartans in combination with bevacizumab, for example in the Avaglio and RTOG-0825 trials.

Angiotensin-II has been shown to increase tumor-promoting macrophages in preclinical models:

https://www.ncbi.nlm.nih.gov/pubmed/23333075

and these tumor-infiltrating myeloid cells may play a significant role in resistance to anti-VEGF therapies such as bevacizumab.

https://www.ncbi.nlm.nih.gov/pubmed/26404753

Our cocktail and report "OncoDeep". What do you recommend to pay attention to?

Since the tumor after surgery (removed 99%) increased again in the same size (3.5 x 5 x 5 cm) in 3 weeks and the tumor did not decrease after radiotherapy + TMZ, we probably have a very unusual cocktail for the first line:
- cycle 42 days: Avastin (3mg/kg/week) + CCNU (1 day 75mg/m2) + TMZ (5 days 90mg/m2),
- disulfiram 500mg (+Copper 5mg + DHA) and verapamil 200mg only on the days of TMZ + CCNU administration, and 2 days before and after.  I'm not sure, maybe it's advisable to take Disulfiram every day? Otherwise, disulfiram may not start to influence so quickly?
- every day: cloroquine phosphate 250mg, telmisartan 80mg, alfacalcidol 2mcg, oxaloacetate 100mg,  melatonin 20mg, curcumin longvida 2000mg,  Berberine 1000mg, DHA/EPA 1000mg, PSK / PSP 1800mg, Methimazole + T3, R-lipoic acid + hydroxycitrate + ketogenic diet, omeprazole 20mg + DCA 20mg/kg (10mg/kg/BID) + caffeine (2 cups of coffee and 5 cups of black tea) + vitamin B1 200mg

My mother has been responding well to taking DCA + caffeine for a week in the form of black tea and coffee. However, my mom's pulse increased to 90-95 after sleep or rest. To reduce it, we now take 10 mg of propranolol per day. An increase in the pulse may also be caused by the intake of the hormone T3.

Also I consider the addition of a low dose of naltrexone before bed.
We also ordered perillyl alcohol at www.sigmaaldrich.com and expect it soon.

Today we received a report from OncoDNA. The last 3 months I read and search for any information about glioblastoma, but unfortunately I find it difficult to understand this report. Doctors in Russia do not order such reports at all! Our doctor in Germany said that unfortunately, such reports will not help us in any way.

Maybe you can tell me what to look for in this report? Any comments?

For example, I can not understand, is there overexpression (amplification) of EGFR?
"Damaging TP53" = mutation of TP53? Not understanding this, I can not draw conclusions from this review (http://astrocytomaoptions.com/exploring-strategies-for-tp53-mutated-gliomas/) and other studies.
"Damaging PTEN" = loss or mutation PTEN? An interesting article in this case: http://btcocktails.blogspot.ru/2018/01/parp-inhibitors-for-pten-mutant-cancer.html
Which of the drugs on the list of potential clinical benefits to pay attention to ?

Here is a link to the report itself and some pictures of him:
https://drive.google.com/open?id=1A3dophOME6gY1GNdOHWE48wVYJUu_nHc

 

 

Inhibitors of autophagy

Given the increasing role of inhibitors of autophagy, I would like to discuss the choice of an inhibitor of autophagy, as well as the possibility of enhancing their effect.
___________________________________

This study focuses on the comparison of some of these inhibitors:
2015 http://thejns.org/doi/10.3171/2014.12.FOCUS14748
"...the authors of this study set out to investigate whether chloroquine (CQ) analogs, in particular clinically established antimalaria drugs, would also be able to exert antitumor properties, with a specific focus on glioma cells.
...the authors treated different glioma cell lines with quinine (QN), quinacrine (QNX), mefloquine (MFQ), and hydroxychloroquine (HCQ) and investigated endoplasmic reticulum (ER) stress–induced cell death, autophagy, and cell death.
All agents blocked cellular autophagy and exerted cytotoxic effects on drug-sensitive and drug-resistant glioma cells with varying degrees of potency (QNX > MFQ > HCQ > CQ > QN)."

Thus, it follows from the study that cloroquine (CQ) shows a weak effect, even lower, that hydroxychloroquine (HCQ) (?!) Maybe this explains the choice of hydroxychloroquine instead of chloroquine in some tests?

And another quotes from the study:

"Cytotoxicity of QBAs for Glioma Cells:
To determine whether other quinoline-based antimalarial (QBA) compounds could mimic the cytotoxic effects of CQ in glioma cells, we used MFQ and QNX. Results showed that these drugs effectively killed U251 cells at much lower concentrations than CQ."

Blocking Autophagy and Inducing Apoptosis in Glioma Cells:
Based on information that CQ induces apoptosis by blocking autophagy, we analyzed whether the other QBA compounds can function in a similar manner.
Quinacrine, the most potent QBA, not only blocked autophagy, but at 20 μM it completely disrupted U251 cellular functioning, which was evidenced by a high level of PARP cleavage, as well as the absence of CHOP/GADD-153 and LC3B expression.

In Vivo Antitumor Activity:
The TUNEL assay for apoptosis demonstrated a significant increase in the number of TUNEL-positive cells in QNX- and QN-> MFQ-> CQ-treated tumors, as compared with untreated controls."

There are also many reports of another inhibitor of autophagy - 3-methyladenine (3-MA).

___________________________________

Since many people here take chloroquine, I would like to discuss the possibility of enhancing its effect. While I see there are the following options:

chloroquine + cimetidine
"Cimetidine pre-treatment caused a 53% decrease in the clearance rate of chloroquine, and a 49% increase in the elimination half-life. Cimetidine inhibited the conversion of chloroquine to monodesethylchloroquine in terms of reductions in the AUC, Cmax, and urinary excretion of monodesethylchloroquine. The serum Cmax of chloroquine was increased by approximately 30% in the cimetidine pre-treated group."
The downside is that since there are many medicines in the cocktail, numerous unpredictable interactions with cimetidine are possible.

increase in the dose of Chloroquine
Instead of using cimetidine, can it be easier to increase the dose of Chloroquine? The standard is 250 mg / day.

chloroquine + hypoxia-inducing agents
2017 https://www.ncbi.nlm.nih.gov/pubmed/28797031
"This work shows that inhibition of autophagy is a promising strategy against GBM and identifies ATG9 as a novel target in hypoxia-induced autophagy. Combination with hypoxia-inducing agents may provide benefit by allowing to decrease the effective dose of autophagy inhibitors."
What hypoxia-inducing agents are they talking about?
___________________________________

I also found several preliminary studies on the synergy of chloroquine and other drugs. It is interesting to study more ..

Dihydroartemisinin + Сhloroquine
2017 https://www.ncbi.nlm.nih.gov/pubmed/29033794
Dihydroartemisinin Exerts Anti-Tumor Activity by Inducing Mitochondrion and Endoplasmic Reticulum Apoptosis and Autophagic Cell Death in Human Glioblastoma Cells.
"Co-treatment with chloroquine (CQ) significantly induced the above effects. Furthermore, ER stress and mitochondrial dysfunction were involved in the dihydroartemisinin-induced autophagy."

Asparaginase + Сhloroquine
2017 https://www.ncbi.nlm.nih.gov/pubmed/29207624
"combination treatment with autophagy inhibitor CQ significantly enhanced anti-glioblastoma efficacy of asparaginase in U87MG cell xenograft model."

Sorafenib + Сhloroquine 
2016 https://www.ncbi.nlm.nih.gov/pubmed/26971793
"we combined sorafenib treatment in GBM cells (U373 and LN229) and tumors with the autophagy inhibitor chloroquine. We found that blockage of autophagy further inhibited cell proliferation and migration and induced cell apoptosis in vitro and in vivo. These findings suggest the possibility of combination treatment with sorafenib and autophagy inhibitors for GBM."

Blood-brain barrier and immune checkpoint inhibitors

Blood-brain barrier and immune checkpoint inhibitors

My partner has a recurrent and unoperable glioblastoma.
He is considering a therapy with immune checkpoint inhibitors (e.g. pembrolizumab or atezolizumab) as his tumor has extremely high mutation burden. Some doctors are in favour but some are not convinced and say that it won't work because of blood brain barrier (BBB).
Is there any research showing immune checkpoint inhibitors don't cross BBB?

Chloroquine for GBM with EGFRvIII mutation

EGFRvIII expression triggers a metabolic dependency and therapeutic vulnerability sensitive to autophagy inhibition
http://www.tandfonline.com/doi/pdf/10.1080/15548627.2017.1409926?needAccess=true

Some of the data contained in this study was used as justification for the CHLOROBRAIN trial
https://clinicaltrials.gov/ct2/show/NCT02378532

Final results of disulfiram pilot trial for newly diagnosed GBM

Final results of a phase I dose-escalation, dose-expansion study of adding disulfiram with or without copper to adjuvant temozolomide for newly diagnosed glioblastoma
http://sci-hub.la/https://link.springer.com/article/10.1007/s11060-018-2775-y

Sadly, median PFS and OS were not improved above historical controls receiving standard treatments alone.

However, only 6 of 18 patients also took copper supplements in this trial in addition to disulfiram, leading to another phase 1/2 trial of disulfiram + copper for newly diagnosed GBM which is still recruiting.
https://clinicaltrials.gov/ct2/show/NCT02715609

Intravenous zoledronic acid for cocktail?

There are many articles on the possible benefits zoledronic acid in the treatment of glioblastoma.
https://www.ncbi.nlm.nih.gov/pubmed/?term=Zoledronic+glioblastoma

For example, MTZ Regimen (2016) suggests using:
oral minocycline 100 mg three times daily, oral telmisartan 80 mg twice daily, and intravenous zoledronic acid 4 mg once every 28 days
https://www.dovepress.com/toward-a-noncytotoxic-glioblastoma-therapy-blocking-mcp-1-with-the-mtz-peer-reviewed-fulltext-article-OTT
https://www.ncbi.nlm.nih.gov/pubmed/27175087

Since many patients with glioblastoma include in their cocktails minocycline and telmisartan (or captopril), may be necessary to think about adding an injection of zoledronic acid as non-toxic supplement, 4mg once every 28 days?

Intraarterial bevacizumab

I found information about the intra-arterial administration of bevacizumab. It looks very interesting.
Does anyone know any details?

Long-term benefit of intra-arterial bevacizumab for recurrent glioblastoma.
2017 https://www.ncbi.nlm.nih.gov/pubmed/28472567
"Standard treatment for recurrent GBM is not yet established. We present a case demonstrating the benefit of intra-arterial (IA) bevacizumab with blood brain barrier disruption (BBBD) for the treatment of recurrent GBM. A 31 year-old man diagnosed with GBM, following primary resection, received temozolomide. After a second resection, he received one dose of IA bevacizumab with BBBD using mannitol, preventing regrowth for 2.5 years. Following tumor regrowth, the patient received another dose of IA bevacizumab with BBBD, which has prevented regrowth for another year."

2012 https://www.ncbi.nlm.nih.gov/pubmed/22946342
Intra-arterial bevacizumab with blood brain barrier disruption in a glioblastoma xenograft model.

Mannitol was used to prepare the solution:
https://www.drugs.com/monograph/mannitol.html

The practice of such treatment in Ukraine:
2013 https://cyberleninka.ru/article/n/ispolzovanie-metoda-vnutriarterialnogo-vvedeniya-himiopreparatov-v-sostave-kompleksnogo-lecheniya-patsientov-s-gliomami-golovnogo
For the intra-arterial administration of drugs, the endovascular technique was used.
"It was found that the method of intra-arterial delivery of chemotherapy is effective and efficient in treatment of patients with malignant gliomas of the brain, can reduce the toxic effects of chemotherapy on the patient, to improve the quality of life for patients."

Carmofur (ASAH1 inhibitor) is more potent than TMZ in killing glioblastoma cells?

I found an interesting study published in November 2017:

https://www.ncbi.nlm.nih.gov/pubmed/29348854
http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=22637&path[]=71521

"The standard glioblastoma chemotherapy agent, temozolomide, had minimal GSC-targeted effects at comparable or even higher concentrations (IC50 > 750 μM against GSCs). ASAH1 is identified as a de novo glioblastoma drug target, and ASAH1 inhibitors, such as carmofur, are shown to be highly effective and to specifically target glioblastoma GSCs. Carmofur is an ASAH1 inhibitor that crosses the blood-brain barrier, a major bottleneck in glioblastoma treatment. It has been approved in Japan since 1981 for colorectal cancer therapy. Therefore, it is poised for repurposing and translation to glioblastoma clinical trials."

"ASAH1 inhibitors are highly more potent than temozolomide in killing GSCs and U87MG cells. Due to its high level of expression in GSCs, ASAH1 inhibition is proposed as a new anti-glioblastoma therapy that specifically targets GSCs."

2017 https://www.ncbi.nlm.nih.gov/pubmed/28765947
"inhibition of ASAH1 and Sph-1P, either with humanized monoclonal antibodies, small molecule drugs (i.e. carmofur), or a combination of both, led to suppression of GBM cell growth. These results suggest that ASAH1 and Sph-1P may be excellent targets for the treatment of new GBMs and recurrent GBMs, especially since the latter overexpresses ASAH1."

https://www.drugs.com/international/carmofur.html
Unfortunately, I did not find any trials with carmofur (or mifurol) at https://clinicaltrials.gov

https://en.wikipedia.org/wiki/Carmofur
"Carmofur has also been used as adjuvant chemotherapy for curatively resected colorectal cancer patients in China, Japan, and Finland for many years. Trials and meta-analyses have confirmed that the drug is effective on patients with this cancer type, extending their survival.
A clinical trial for small hepatocellular carcinoma was stopped prematurely because 56% of the treated patients had unacceptable side effects. Moreover, the treatment had no survival advantage for stage 1 and 2 cancer patients. This may be a reason why carmofur was never pursued for FDA-approval in the US."

Maybe there are more modern and safe ASAH1 inhibitors crossing the blood-brain barrier?

Need suggestions to incorporate supplements in my mom's cocktail(GBM Patient)

Hi folks,

My mother(Age 47) was diagnosed with glioblastoma(IDH1/2 -ve, Methylated) in September 2017, and it has left me devastated ever since. She has completed her 6 weeks of radiation/chemo and her first cycle of 5/23 temozolomide. Her next cycle of temozolomide starts 5 days from now. I stumbled upon this blog just a week back, and have found this to be immensely helpful and resourceful.

I need help from you guys on what else should I incorporate in my mom's cocktail. Following are the supplements that are present in her cocktail per day already:

Metformin: 500 mg
Boswellia Serratta: 4000 mg
Resveratrol: 400 mg
Fish Oil: 3600 mg DHA+EPA + 400 mg of other omega 3 fatty acids
Curcumin with piperine: 5000 mg
Longvida: 400 mg
Quercetin: 5000 mg
Melatonin: 20 mg
Selinium: 200 mcg
Vitamin ADK supplement with 5000 IU Vitamin D3
Ashwagandha: 500 mg
Garlic: 6 cloves
Ginger: 6 cloves
Dendritic cell therapy: On the cards
Cannabis oil: Dropped because it was suppressing her WBCs

She is also on ketogenic diet and has done about 2 weeks of hyperbaric oxygen. We are looking at two more weeks of hyperbaric oxygen.

I'm looking for more supplements that are good adjuvants to temozolomide/standalone good adjuvants that I should definitely include in my mom's cocktail. It'd be great if you guys could help out in more supplements that I should include, I'm finding it very hard to self medicate my mom. Basis Ben Williams' book and reading several blogs, the following supplements have repeatedly been catching my attention:

1. DCA
2. Chloroquine
3. Care oncology clinic protocol(Metformin + Doxycline + Mobendezole + Atorvastatin)
4. Ruta 6 + Calceria Phos(Not sure if it is a good idea to use while on chemo)
5. Methadone
6. Veramapil
7. Low Dose Naltrexone
8. Disulfiram
9. Perilyl Alcohol
10. Methadone
11. Celebrex

She is already taking a total of 50 meds per day and I think she can take only 10-15 more. Would be great if you can help me from above list/any other supplement that should definitely be a part of her cocktail.

Thank you in advance!

The importance of re-testing IDH status in IDH "wild-type" low grade gliomas

PATH-36. REPEATING TESTING IN IDH WILD TYPE LGG CASES. THE IMPORTANCE OF NEXT GENERATION SEQUENCING
Link to abstract

"the observation of a particularly favorable outcome in a group of 42 patients with IDH wild type LGG (OS=93.7 months) led us to assess IDH mutation with a more sensitive technique. Next Generation Sequencing (NGS) was used to evaluate IDH status in these tumor samples, and the results of NGS assay were compared with previous findings"

"Twenty-one (50%) of the 42 initial IDH wild type LGGs were found to present IDH mutation when tested with NGS. Four patients had R132H mutation and 17 cases showed other IDH mutations (4 patients with IDH2 mutation, 5 patients with IDH1 R132C mutation, 5 patients with IDH1 R132G mutation and 3 patients with IDH1 R132S mutation)."

"Repeating testing in IDH wild type LGG cases is crucial, as well as the technique used to assess this mutation. NGS is able to find IDH mutations in 50% of patients previously misdiagnosed"

Increased expression of androgen receptor (AR) in GBM. Enzalutamide (androgen receptor inhibitor)

SNO 2016 abstract: CSIG-13 ANDROGEN RECEPTOR IS INVOLVED IN GLIOBLASTOMA AND PRESENTS A POTENTIAL THERAPEUTIC TARGET

SNO 2017 abstract: CSIG-24. ANDROGEN RECEPTOR IS A POTENTIAL THERAPEUTIC TARGET IN GLIOBLASTOMA

"Enzalutamide given orally (20 mg/kg three time per week) to nude mice bearing human gliomas (U78MG) resulted in reduction of 72% in tumor volume (p=0.0027) as compared to mice treated with vehicle. We hope that the results of this study together with continued laboratory efforts will lead to a new approach for the treatment of human glioblastoma."

Enzalutamide is an androgen receptor inhibitor approved by the FDA in 2012 for treatment of prostate cancer.

PARP inhibitors for PTEN-mutant cancer cells

Most GBM tumors (IDH1 wild-type) have a loss of one copy of chromosome 10.  Additionally, about 30% will also have a deactivating mutation in the remaining copy of PTEN, leaving no functional PTEN in these tumors.

In these tumors, PARP inhibitors may be an effective therapeutic option, based on a study showing therapeutic effects of olaparib in PTEN-negative HCT116 colon cancer xenografts, while HCT116 xenografts with restored PTEN didn't respond to olaparib.

These results are not necessarily generally applicable, as the HCT116 line is also known to have mismatch repair defect (loss of MLH1), so there may have been some interaction between loss of both mismatch repair and PTEN that sensitized cells to olaparib.

Study title:
Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors
Full study available here

Chloroquine has therapeutic effect in IDH-mutant U87 mouse model

This was an orthotopic mouse model: U87 GBM cells with either wild-type IDH or genetically engineered to contain the IDH1 R132H mutation were injected into brains of nude (immunodeficient) mice. Chloroquine was injected intraperitoneally.

According to this study, 2-hydroxyglutarate produced by the mutant IDH1 enzyme leads to endoplasmic reticulum (ER) stress, autophagy of the endoplasmic reticulum, and reduced biosynthesis of membrane phospholipids (as the ER is the site of phospholipid synthesis). Inhibiting autophagy with chloroquine triggered apoptosis (programmed cell death).

Chloroquine-treated IDH1-mutant U87 tumors had increased caspase activity (a marker of apoptosis), while the IDH1 wild-type U87 tumors had no increase in caspase activity with chloroquine treatment.

Study title:
2-hydroxyglutarate-mediated autophagy of the endoplasmic reticulum leads to an unusual downregulation of phospholipid biosynthesis in mutant IDH1 gliomas
Pubmed link

I've uploaded the full study to the Library (Folder 2 Therapies - preclinical -> Chloroquine)

Best place for dendritic cell therapy for my mom(GBM Patient)

Hi folks,

My mother is a grade 4 brain cancer patient, who was diagnosed on 17 September 2017. She has completed her 6 weeks of radio/chemotherapy and her 1st 5/23 cycle of temozolomide. I'm looking for immunotherapy(dendritic cell therapy), and where to get it done from is something that I'm terribly confused about. I shortlisted the following: 

1. IOZK(They say they will do hyperthermia) while my mom is on chemo, and will do the DC after my mom is done with the Chemo. They say they won't be able to use the tumor block because it is stored in paraffin. They tell me they have their own set of GBM antigens that they shall use.

2. Dr Nesselhut: They say they will give 4-6 vaccines of dendritic cells and can be given while on chemotherapy(1 week before or after). But they say that they can use the tumor block for making the antigens, despite the fact that the block is in paraffin. They say they can 'de-parafinise' it. I'm not sure if they really are true with their claims, but they were the only place that said they can use the block to make the antigens

3. Verita Life, Bangkok: They say that they can give the dendritic cell therapy while on chemotherapy with their own set of antigens, but can't use the tumor block. They shall couple the treatment with a lot of herbal IVs like quercetin, curcumin, resveratrol, Vitamin C etc.

4. Dr Robert Godner: They've asked me to wait for another MRI since the recent one came out clean, but with choline elevation(which is either a sign of radiation injury or residual tumor/recurrence).

I wish to know what shall be the best place to get the immunotherapy done from? Would love objective inputs from you guys. I would also want to know how many times you were made to travel to these places, if you've experienced the dendritic cell therapy from them.

PS: My personal preferential order is the order in which I've placed the above places, but IOZK and Dr Nesselhut, I foresee will easily call us to Germany about 8-10 times, which I'm not very sure my mom will be able to go. So, travel for a GBM patient a few months from now is a concern. 

Improvement of the ketogenic diet

In many studies, it has been shown that a ketogenic diet can be a useful supplement in the treatment of glioblastoma. I would like to discuss the improvement of this diet on the basis of recent research.

1. Ketogenic diet + α-lipoic acid and hydroxycitrate
2017 https://www.ncbi.nlm.nih.gov/pubmed/28122260
"To decrease anabolism, glucose uptake should be reduced (ketogenic diet). To increase catabolism, the oxidative phosphorylation should be restored. Treatment with a combination of α-lipoic acid and hydroxycitrate has been shown to be effective in multiple animal models."

2016 http://crescopublications.org/pdf/CROOA/CROOA-2-019.pdf
"Combination of Metabolic Treatment of Aggressive Primary Brain Tumour
and Multiple Metastases of the Brain"
"We report the cases of 12 patients with advanced brain tumor. They were all treated with
conventional treatment and a combination of sodium R lipoate (800 mgbid), hydroxycitrate at 500 mg tid and low-dose naltrexone at 5 mg at bedtime. Eight patients had primary brain tumour (n=8 including five glioblastomas) four patients had multiple brain metastases."

2. Ketogenic diet + Fenofibrate ?
2016 https://www.ncbi.nlm.nih.gov/pubmed/26869992
"Our results reveal a new, intriguing aspect of cancer cell biology and highlight the benefits of fenofibrate as a supplement to both canonical and dietary (ketogenic) therapeutic approaches against glioblastoma."
2015 https://www.ncbi.nlm.nih.gov/pubmed/26172294
"Given that fenofibrate is a widely used non-toxic drug, we suggest its use in patients with glioblastoma multiforme (GBM)."
2017 https://www.ncbi.nlm.nih.gov/pubmed/28459367
"...the lipid-lowering agent fenofibrate...have potential to lower synthesis or effects of G(M)-CSF and thus deprive a glioblastoma of some of the growth promoting contributions of bone marrow and G(M)-CSF.
It's strange, but in this blog I did not find any information about Fenofibrate. So is it necessary to add it to the ketogenic diet?

3. Ketogenic diet + Inhibition of glutamine metabolism ?
2017 https://www.ncbi.nlm.nih.gov/pubmed/28720668
"Inhibition of glutamine metabolism slows the in vitro and in vivo growth of GLNHigh GBM cultures despite metabolic adaptation to nutrient availability, in particular by increasing pyruvate shuttling into mitochondria."
"...the pleiotropic metabolic inhibitor EGCG, targeting glutamine metabolism, specifically reduces tumor proliferation, in vitro and in vivo, of mesenchymal GLNHigh cells."
How can the findings of this study be used? Only EGCG can not inhibit glutamine metabolism. Maybe there are more options?

4. Ketogenic diet + Specialized medium-chain triglycerides (MCT) ?
2016 http://clincancerres.aacrjournals.org/content/22/10/2482
"MCTs were specifically chosen based on carbon chain lengths (C8:C10::97%:3%), which allow them to rapidly diffuse from the gastrointestinal tract into the hepatic portal system and travel directly to the liver where they are converted into ketone bodies."

5. What other ideas can you offer to enhance the effect of a ketogenic diet?

Total resection followed by multimodal immunotherapy: 15+ months remission without RT/TMZ

HGG-05  Can Multimodal Immunotherapy Replace Radiochemotherapy in Completely Resected Adult GBM?

4th Biennial Conference on Pediatric Neuro-Oncology Basic and Translational Research, June 15-16, 2017, New York City
Link to complete abstracts
Link to abstract HGG-05

While this is only a single case, the long duration of remission in the absence of radiation and chemotherapy is intriguing.  This patient was also IDH wild-type, and was in EORTC recursive partitioning analysis (RPA) class IV, as are the majority of GBM patients in phase 3 trials.

The patient was treated at IOZK in Germany with "multimodal immunotherapy consisting of 2 cycles of 6 days Newcastle Disease Virus (NDV) infusions and local modulated electrohyperthermia (mEHT) sessions plus an autologous DC vaccine loaded with serum-derived NDV/mEHT-induced antigenic microparticles + NDV, and additionally four more treatments with NDV infusions + mEHT"

More detailed information on IOZK's methods can be found in this publication.
http://www.iozk.de/aktuelles/iozk_austin_oncology_case_reports_2017.pdf

In addition, a technique has been developed at IOZK to use blood serum-derived antigenic microparticles, where no fresh or frozen tumor tissue to produce a tumor lysate is available. This latter method was used in the case report above.