CMV (Cytomegalovirus) - specific dendritic cell vaccine trial summary

https://sci-hub.tw/https://clincancerres.aacrjournals.org/content/early/2020/07/25/1078-0432.CCR-20-1082.long

Once, Twice, Three Times a Finding: Reproducibility of Dendritic Cell Vaccine Trials Targeting Cytomegalovirus in Glioblastoma

"We have now observed that nearly one-third of the GBM study patient population receiving CMV-specific DC vaccines results in exceptional long-term survivors."

Deciding between Chemo and Targeted Therapies for Recurrence

I've been a longtime follower of this community and I'm hoping that others here can help me cut through all the information I'm being given to make some decisions for my husband.

Background
My husband was diagnosed at age 34 in October 2018 after having neck pain for a few weeks and then a sudden onset of extreme disorientation. He had an emergency resection (97.8% debulked). His tumor was originally located in the left parietal lobe. His tumor is unmethylated, IDH wild-type. Initially he followed SOC. Radiation concurrent with TMZ, then Stupp protocol 5/23 with Optune.

In May 2019, he had progression, stopped TMZ and Optune in preparation for surgery. Second resection in June 2019. He got a pre-surgical infusion of Keytruda (Pembrolizumab). Second surgery was MRI assisted at Memorial Sloan Kettering. Resection was successful and he followed with a short course of photon radiation and Keytruda infusions every 3 weeks. Around this time we also stopped doing a strict Keto diet because he had dropped close to 40 pounds. We now follow it in moderation.

We used Store My Tumor to preserve a tissue sample from the second surgery and used that to create an autologous dendritic cell vaccine from whole tumor lysate at Thomas Nesselhut's clinic in Germany. He was primed with an oncolytic virus, also used adjuvants of Inter-leukin 2 and Aldara cream.

Fall 2019 we continued Keytruda infusions and his dendritic cell vaccine with Tetanus adjuvant. In October 2019 he had an adverse event (possible focal seizure or pressure wave). We discontinued Keytruda (had completed 7 rounds). Started on a course of Avastin infusions and 4 mg Dexamethasone to control inflammation. We made the decision to discontinue Optune at this time. It was a quality of life decision. It was really interfering with his enjoyment and activity (we have twin toddlers). I am 100% okay with that decision and won't force him to do something he hates.

In November 2019 he was accepted into the SurVaxM clinical trial via compassionate release. He completed a priming dose (4 rounds) of the peptide vaccine SurVaxM. His most recent dose was in April 2020. In January 2019, it looked like there was further progression in the corpus callosum. We decided to continue with Avastin infusions and dendritic cell treatment and did a course of Proton Beam radiation.
His first MRI post radiation showed a modest reduction in tumor. (March 2020).
His most recent MRI in May 2020 is showing new growth. The area that got proton beam radiation continues to shrink, but there is a new tumor measuring 2.9 X 1.7 cm within the posterior medial left temporal lobe. Thankfully he has remained largely asymptomatic and stable. He has issues with leg weakness from prolonged steroid usage and his right arm and hand have lost dexterity. He has never had a seizure. He has some memory issues and lately some issues with processing.
Now we are faced with a decision about what to do next and we are getting a lot of differing opinions.
His tumor has the following markers:

x





We are deciding between adding a cytotoxic chemotherapy and a targeted therapy. One team of doctors is strongly recommending CCNU. Their other options would be Metronomic TMZ, Carboplatin, or Irinotecan.

Our vaccine team is very wary of cytotoxic chemo and believe it would negate the immunotherapies. They are okay with metronomic TMZ or metronomic Cytoxan.

A third doctor recommended Carboplatin and keeping Keytruda.

We have been offered the possibility of trying a targeted therapy to match his genetic markers. The choices there are Abemaciclib (CDK4/6 inhibitor) or Cabozantinib (MET fusion). I would like to get a PI3K/Mtor inhibitor or an MDMA inhibitor but there are next to none that are commercially available and I don't think we can get into any trials or want to wait that long. Piqray is one potential option in the PI3K/Mtor area. We don't know if we could combine them with chemo. I think we would have to see how he responds to one before adding them together.

Surgery and radiation seem unlikely though we are going to pursue consultations for surgery (we are based in NY) and gamma knife with Dr. Christopher Duma. I don't think these will pan out, but the consultations can't hurt.

I am really struggling with how to make these choices. His quality of life is fairly good. None of these options seem to have strong data behind them, but all have those small percentages of patients where things work and no one knows why.

I want to make a decision quickly. I am leaning towards Metronomic chemo (even though I know he is unmethylated and the chances of it working are small). But we can get it immediately and we know somewhat how he responds on chemo. He always tolerated it well, never had low counts and managed side effects with cannabis and IV fluids and colace. I think we could try chemo for one month and do another scan and see quickly if there is any impact.

We would have to get approval for the targeted therapies and I think perhaps it makes the most sense to hold those while we try something else.

He has been on his vaccine for almost one year and I have no idea if it has done anything, perhaps it's simply held things back.

I know this community has so much knowledge. I welcome any insight. He is 19 months past diagnosis and we have never had a long stretch of stability. We have thrown everything at this disease. Given how aggressive its been, I hope that all that we have done has given him more time than if we had just done SOC. I want to give him time, good time.

His genetic markers are:
TERT
CDKN2A
MDM2
CCND2
PTEN
FOXP1
TET2
YAP1
CCND2
BIRC3
PTPRZ1-Met Fusion

We completed EVA-PCD assay through Nagourney Cancer Institute. Tumor tissue sample allowed for testing of 5 agents. Results were:

• Dactolisib (PI3K/mTOR)--sensitive

• Palbociclib (CDK4/6)--sensitive

• Crizotinib (ALK/MET/ROS)--intermediate

• Carboplatin & Topotecan--intermediate

• Olaparib (PARP)--resistant

His medications are as follows:

Immunotherapy

Dendritic Cell Vaccine

SurVaxM vaccine

Keytruda

Tetantus adjuvant

Aldara adjuvant

Lion's Mane

Apoptosis/Autophagy 

Chloroquine 

Mebendazole 

Artemisinin 

Simvastatin 

Escozine 

Anti-Angiogenic

Avastin

EGCG 

Metabolic 

Metformin 

Anti-Inflammatory

Bromelain 

Curcumin 

Boswellia Serrata

Quercetin

Other 

Cymbalta 

Clonazepam

Valproic Acid

Melatonin

Turkey Tail

CBD (sublingual)

Cannabis (whole flower, vaporized as needed)

 

GAPVAC phase 1 trial results

GAPVAC phase 1 trial
https://www.clinicaltrials.gov/ct2/show/NCT02149225

just published results in Nature

http://sci-hub.tw/https://www.nature.com/articles/s41586-018-0810-y

ERC1671 vaccine randomized phase 2 trial results

Phase II study of ERC1671 plus bevacizumab versus bevacizumab plus placebo in recurrent glioblastoma: interim results and correlations with CD4+ T-lymphocyte counts.

Median overall survival (OS) of patients treated with ERC1671 plus bevacizumab was 12 months. In the placebo plus bevacizumab group, median OS was 7.5 months. The maximal CD4+ T-lymphocyte count correlated with OS in the ERC1671 but not in the placebo group.

CONCLUSION:

The addition of ERC1671/GM-CSF/cyclophosphamide to bevacizumab resulted in a clinically meaningful survival benefit with minimal additional toxicity.

Report on the treatment of 15 patients in the IOZK clinic.

The IOZK clinic in July 2018 published an article with information on the treatment of 15 patients.
Some of the details seemed interesting to me.

The first 10 patients (in the table) were treated using vaccines based on dendritic cells:
- Of these, 3 patients survived 18, 22 and 10 months. By the way, the patient, who survived 18 months, used the CUSP9 protocol.
- The remaining 7 patients continue treatment. However, of these 7 patients with no progression, only 2, with a result of 27 and 17 months without progression after surgery. In others, the tumor slowly progresses.

Also, we see that 3 patients out of 15 used perillol alcohol (POH).

http://www.iozk.de/aktuelles/iozk_glioblastoma_immunotherapy_austin_oncology_report_2018.pdf

"The median PFS was 13 months. Median OS was not reached with a median follow up of 17
months (rang 4-30 months). Estimated overall survival at 30 months was 58%..."
"DC vaccinations have been given after the chemotherapy. The obvious reason is that temozolomide might affect T cell proliferation and hence the anti-tumoral immune response upon DC vaccination."
Does this mean that it is better not to combine the Stupp protocol with the DC vaccine in the same period?

This just in:

medpagetoday.com

ASCO Reading Room | Addition of a Personalized Vaccine to Standard Therapy in Glioblastoma

 

Right to Try (for U.S. patients/advocates)

Hi guys,

I'm wondering if anyone here has pursued the Right to Try law here in the United States? Searching the blog, I couldn't find anything...

My brother is living in Texas where the law has been passed and I've obtained the document provided by the organization website to present to his doctors. (The document is linked here under "How do I initiate a request?" or here is a Google Doc version I uploaded which is the exact same)

James would like to try DCVax-L, if possible.

In order to produce the DCVax-L vaccine, you need to supply fresh or preserved tumor tissue. I've contacted the drug company, Northwest Biotherapeutics https://www.nwbio.com/) and was told:

"In order to manufacture DCVax-L, we usually require 2-3 grams of frozen tumor tissue, although we have worked with less in certain circumstances.  The tissue must be stored frozen without any chemicals or preservatives and not in saline or blocks of paraffin."

I've confirmed that the tissue from his previous resection has now been transferred to paraffin so is unusable.

James's doctors have already said another resection is not advisable due to the location of his tumor progression. However, assuming we could get a biopsy to have some fresh tissue, I'm wondering if this would be a block for his doctors to go ahead and pursue the Right to Try submission to the drug company.

Would they be likely to submit the document and start the legal process if we don't even have the tissue?

It would seem foolish to do a biopsy if we weren't for sure going to be a candidate for the vaccine.

(Again, I'm unsure if a biopsy is possible at the moment but should find out this week.)

Additionally, I requested more information from NWBio about the Right to Try law and she didn't address it with detail, but just assured me that without tissue, nothing could be done.

Does anyone here have experience with kickstarting this Right to Try process? Any tips or advice would be much appreciated.

Link to my first post outlining James's current condition for context.

SurVaxM - Update

https://mimivax.com/wp-content/themes/JointsWP-master/assets/pdf/download.pdf

DCVax Update

https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1507-6

Mike B

HSPPC-96 vaccine Phase 1 trial results in China

Heat shock protein peptide complex-96 vaccination for newly diagnosed glioblastoma:
a phase I, single-arm trial
https://insight.jci.org/articles/view/99145   (open access)

The survival results of this trial are worth remarking upon.

20 newly diagnosed GBM patients received standard treatments plus HSPPC-96 vaccine (also known as Prophage, under development in the USA by Agenus). All had total tumor resections, and the majority had MGMT unmethylated tumors and were IDH1 wild-type.

19 of the 20 were evaluable for efficacy. Median survival for the entire group was 31.4 months.  I've seen only a couple of other small trials (vaccine trials involving complete or near complete tumor resection) with efficacy outcomes comparable to this.

Clear efficacy of the vaccine was shown by tumor specific immune responses (TSIR) being increased on average by 2.3-fold after vaccination, and the fact that those with "high" TSIR (TSIR above the median) had not reached median survival (> 40.5 months), while those with low TSIR (below the median) had median survival of only 14.6 months, showing vaccine efficacy in only a subset of patients.  Median PFS are unremarkable (11 months median for the entire group, 12.3 months for the high TSIR group), but immune-related pseudoprogression could have been a factor in dropping PFS values.

Compared to the phase 2 trial published by Bloch et al. in 2017,  https://www.ncbi.nlm.nih.gov/pubmed/28193626
the Chinese trial had worse PFS outcomes but better survival outcomes, also suggesting that pseudoprogression may have been a factor in the Chinese trial.

Additionally, patients with MGMT-methylatated tumors had far better outcomes in the Bloch et al. trial, but in this Chinese trial, 14 out of 16 tested tumors were MGMT unmethylated.

A trial is currently underway testing pembrolizumab with or without HSPPC-96 vaccine, and I would expect the combination therapy  to improve even further on the efficacy results of the vaccine.
https://clinicaltrials.gov/ct2/show/NCT03018288

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]."

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!

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. 

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.

Treatment options post-RT/TMZ phase for IDH1 mutated, MGMT unmethylated GBM

Hi all,

I was diagnosed in late September with a GBM (frontal, left, with large cyst, IDH1 mutated, MGMT unmethylated), which was subsequently successfully operated (gross total resection) at the end of September. I guess as many/most here, I eventually stumbled across Ben William's book, the Glioblastoma Treatment options guide and ultimately this invaluable blog and community, which I have been studying and following closely since. I recently concluded the first phase of my treatment, following standard Stupp Protocol (6 weeks concomitant RT/TMZ) and am currently planning next steps (plus waiting for first post-RT MRI next week...).

While I did not get 'smart' in time to save my tumor material from being paraffined post-OP (unbelievably, this is still standard practice here in Germany in most hospitals), I did actively supplement my first phase of treatment with what I think is a reasonably aggressive 'cocktail' approach, including the following components:

--------------------------------------------------------------------------------------

Meds:
- Chloroquine, 1x 250mg
- Celebrex, 2x 200mg
- Disulfiram, 1x 250mg - 500mg (+4mg copper)
- Sativex (THC/CBD spray), ca. 3-4 sprays (approx. 15-20mg)

In general, I tolerated these medications without any major problems or side effects, with a few exceptions. Notably, towards the end of the treatment I developed some peripheral neuropathy in my left foot, which has now almost recovered, however (took around 3-4 weeks to recover). Nevertheless, it cause me to cease the Chloroquine and Disulfiram shortly before the end of my RT treatment phase. In addition, I found it a little hard to tolerate Sativex as I wasn't too keen on the psychoactive effect, which gave me some anxiety / mild panic attacks from time to time at night. As a result, I took it only for around 3 weeks or so.

Supplements:
- Berberine: 1000mg
- Boswellia Serrata: up to 4400mg (gradually increased dosage over course of RT to protect from Edema)
- CBD oil (8%), 5 drops (started after ceasing to take Sativex)
- PSP, 2100mg
- Curcumin (Longvida), 2000mg, increased to 3000mg towards end of treatment
- Green Tea Extract, 3625mg
- Lycopene, 20mg
- Matiake D-Fraction Pro, 65mg (3x 23 drops)
- Melatonin, 20mg
- Omega 3 DHA/EPA, 3528mg
- Probiotics, ca. 40bn units
- Pterstilbene, 250mg
- Resveratrol, 500mg
- Selenium, 200ug
- Silymarin, 1500mg
- Soy extract, 3750mg
- Vitamin D, 9000IU

In general, all of the above were well tolerated without side effects. I'd also like to mention I was able to avoid any kind of Edema / Cortisone use during my RT therapy, which I believe may have been at least in part facilitated by Boswellia in combination with Celebrex.


Other:
- Ketogenic diet, max 40 g Carbs per day; generally constant medium to high Ketone bodies when measuring. Started 1 week before RT, and continued to last day
- Caloric restriction, lost ca. 8 kilos in 6.5 weeks of RT, which I think equates approx. 600kcal or so in daily caloric restriction
- Daily morning smoothie, with variety of hopefully beneficial things like berries, broccoli sprouts, spirulina, tumeric powder, Matcha green tea, cocoa powder,  etc.
- Daily walks of ca. 1 hour to combat radiotherapy fatigue and keep fit

Ketogenic diet was somewhat difficult to maintain psychologically, but possible due to my partner's kind help in continuously seeking out new and often tasty dishes to keep things interesting. Caloric restriction much easier, since Temodal anyway caused me lack of appetite. I believe daily walks were very helpful to avoid RT fatigue, which affected me only in very minor way and much less than I expected.

--------------------------------------------------------------

NEXT STEPS & QUESTIONS

I am currently considering next steps, and having talked to various NOs and other Brain Tumor specialists, I am still not entirely convinced what the right way forward is. As expected, most doctors do not want to deviate from the Stupp Protocol (i.e. follow up the RT/TMZ phase with 6 months of 5/23 TMZ cycles). However, I am not convinced such a treatment would necessarily add much benefit in my case, since my tumor is MGMT unmethylated.

One of the leading specialists in Germany told me that the unmethylated MGMT status is irrelevant in the case of IDH1 mutated tumors like mine, since a study (NOA-4) showed that there was no significant difference in responsiveness  between MGMT methylated or unmethylated IDH1 tumors.

https://www.ncbi.nlm.nih.gov/pubmed/19901110

However, upon further research I stumbled across the following interesting study from China, which seems to suggest that IDH1 mutated tumors might in fact be particularly resistant to TMZ (3-10x more resistant in cell culture test). The study also notes that in China they observed relatively little additional benefit of TMZ cycles for the IDH1 mutated group of patients compared to RT alone, and the authors argue that survival benefits for IDH1 mutated tumors may simply be the result of a less invasive / more benign type of tumor relative to wildtype. It makes me wonder if the fact that MGMT doesn't seemingly play as big a role for IDH1 mutated tumors is simply the result of the fact that neither responds well to TMZ...:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747376/

I'm therefore a bit hesitant to simply go ahead with TMZ therapy hoping for the best, and would like to consider other options.
One approach I am considering is Immunotherapy at the IOZK clinic in Cologne, which is not far from my house. However, because I don't have frozen tumor material, they would have to make a personalized vaccine using a liquid biopsy approach. This, in turn, could make the treatment even more unproven than vaccines anyway are even when made from tumor lysate. An additional option which could possible materialize down the road (but not yet, as no trials are running here presently to my knowledge) is to try to get hold of an IDH1 vaccine on a compassionate use basis.


My immediate next step is to see the MRI results next week, but I'd be very grateful for any advice on how to proceed from here. Especially, I'd like to try and resolve the following questions:

1. Would it be unwise to not do any additional TMZ cycles? Are there any obvious chemotherapy alternatives perhaps?

2. Would the immunotherapy using liquid biopsy at IOZK clinic be a good alternative for ongoing chemotherapy cycles? Would it be advisable to start this right away (i.e. without any additional TMZ cycles), or should I do some TMZ cycles first just to hedge my bets?

3. Any other recommendations in terms of maintenance strategies. E.g. what medication(s) could make a good maintenance therapy, without concurrent chemotherapy?


Thanks in advance for any comments, and wish you all a very happy and most importantly healthy 2018!

Best,
John

New cytomegalovirus-directed vaccine trial for recurrent GBM

This phase 1 trial opened this month in New York, and will be opening in Virginia as well.

The vaccine is called VBI-1901 and consists of two CMV antigens (gB and pp65), delivered via enveloped virus-like particles (eVLP), plus GM-CSF as an adjuvant.

View trial outline here.

Immunotherapy at IOZK Cologne

Hello all,

My 38 year old brother has been diagnosed with a Glioblastoma six weeks ago. Since then he has had total surgical resection and is currently finishing his second week of temodar and radiation. He has also added quite an extensive amount of additional medication as a cocktail approach (I am sure that he will write a more detailed post about the drugs he is taking, when he finds the time). We have found the information in this blog to be extremely helpful. Thanks a lot to Stephen and all of you participating in this great resource.

Right now we are thinking about additional options for the time after his chemo/radiation phase. One thing that we are quite interested in is immunotherapy. Unfortunately my brother’s resected tumor tissue hasn’t been frozen but conserved in paraffin so that options are somewhat limited. We have contacted IOZK in cologne and they have said that they could produce a vaccine without the tumor tissue, using only a blood sample. Cologne is not too far from where we live.

I have read various comments, in this blog, about the IOZK clinic and I know that some of you have been, or have had family members being treated there. I would be very grateful if you could tell me about your experience with the clinic and whether you would recommend giving it a try.

Thanks!

Phil

VXM01 (VEGFR-2 DNA Vaccine) trial ?

Hello all,

I found this trial in Europe (Heidelberg Germany):
https://clinicaltrials.gov/show/NCT02718443
http://abstracts.asco.org/199/AbstView_199_191829.html 

What's your opinion, does it seem something that could work on recurrent AA3  (IDH1 mutated, MGMT methylated) (ASCO abstract goes beyond my understanding... :)

Or would it be better to go with PARP + TMZ combo?

br,
Juha

GBM treatment options with a moderate budget

My 29 years old husband was diagnosed on 3/26 with a multifocal, thalamic GBM. We are from Hungary. He has undergone surgery on the 5th of April. 80% of the walnut-sized tumor was resected from his thalamus. His other, frontomediobasal tumor seems to be inactive (although it's pretty big, too) so the surgeon didn't resect it and it didn't received radiation either. He has completed SOC and currently is on his first cycle of 5/23 TMZ monotherapy. He has no EGFR amplification. His tumor is IDH negative and indeed very aggressive. Only 3 weeks after surgery he was hospitalized because of edema which was caused by tumor regrowth. So now he has quite a few smaller tumors around his thalamus besides the remaining 20% piece. 

His first post-radiation MR is scheduled for the middle of August. Since I've not yet received the information regarding his MGMT methylation status (long story) I'm constantly worrying and seeking for opportunities in case of tumor progression since in my country there's no protocol for recurrent glioblastoma other than Avastin. I mean no PCV or other chemos, no immunotherapy, no clinical trials, no Optune device (I requested an offer from Germany and it turns out that it costs 30 000 € /months and you need a technical and medical support at home).

I'm aware that we need to manage our finances cleverly in this situation. If you had up to 20,000-30,000 USD which option or options would you go for?

- Immunotherapy in Germany (It seems to me that only Nesselhut Clinic fits into our budget but reviews are not so convincing as nothing in the world of GBM.) 

- Keytruda / Opdivo immunotherapy + TMZ 

In Hungary it's not part of the protocol but hopefully we can find a doctor who will prescribe it at our own expense. As I can see Opdivo has kind of failed; is Keytruda. better? Do we need PD-L1 testing to get it?

- We have gamma knife in Hungary and it can be paid through National Insurance (so patients who qualify don't need to pay for it) but doctors are reluctant to let GBM patients to choose this option. It's usually used for small and simple tumors and for brain metastases. If our NO will advise against it or will be not so eager to help maybe I can search for other European gamma knife possibilities although I can't find too many comments on gamma knife and GBM.

- Neuroblate Laser Ablation. As far as I know it's exactly for problematic tumors, like thalamic ones. I'm planning to send them an inquiry but I have concerns about whether it is an adequate alternative to surgery for inoperable tumors. Can it prolong life or is it just a palliative treatment? How much would be the estimated cost? Has anybody personal experiences with it? Is laser ablation superior to gamma knife? 

Our NO said my husband's thalamic tumor is no accessible for surgery anymore and considering his bad reaction to the first surgery maybe laser ablation or gamma knife wouldn't be the best option for him. What are your thoughts on it? 

- SPMF treatment in India. It's quite cheap but no statistics are available and it's so hard to believe for me that the same effect is achievable with 1-2 hours of treatment for 28 days as with the Optune cap which you need to wear almost all day long up until it works. I've read about a young patient with thalamic tumor on Inspire who had Optune and it didn't do any good for him because of the location. I suppose that the same applies for SPMF, too. 

- I sent an inquiry to Duke's polio virus trial.

My clinical trial applications have been ignored from all over the world so I was tricky enough to mention that "I'm aware that non-U.S. citizens should cover their costs on their own in case of qualifying for a clinical trial and I hope I can manage it with the help of my family. "

I got this answer from doctor Friedman personally "We would not have a trial for you at this time since the surgery was so long ago and the tumor is not growing If it ever does regrow please let us know"

Maybe it was just a polite "no" or maybe this possibility is truly open for us in case of a recurrence but the truth is that I have no idea how much a treatment like this could cost in one of the world's best institutions for cancer. Anybody has any idea about their fees?

- Ask the Brazilian doctor to come to Hungary and teach us to administer Perillyl Alcohol. I've read that the brave persons who tried to make it themselves found it unbearable to use.

Any and all help is very much appreciated. Thank you in advance and sorry for my grammar mistakes.

ERC1671 + avastin

Hi everyone, it's been awhile since I've been on here.  My husband was diagnosed 6/2016 and we are close to hitting that one year mark.  We were looking forward to it as my husband had been getting weekly infusions of MRZ (marizomib-clinical trial) for 3 weeks out of the month and it was  taking a toll on his arms/veins and he could have used a much needed break.  Unfortunately, after monthly MRI's since December, NO suggested surgery as the spot they had been tracking had doubled since the last MRI and was ~14mm.

Up to now, my husband has been doing great and people often comment on how they can't even tell that he is battling brain cancer.  The only issues he had was headaches (which never really stopped) and fatigue.  However, he still continued to work every day and come home to help me with the kids. He even got discharged from hospital after 2 days and looks great!

The pathology report came back and we were hoping that the abnormality was just necrosis, but it's now confirmed that it's indeed recurrence.  I guess the bright side is is that he can now do immunotherapy.  I was wanting him to enter the dcvax clinical trial, but apparently it's closed.  The only thing available for him at his treatment center (uc irvine) is ERC1671 in combination of avastin. Has anyone had any experience with this or can offer any feedback??  Thank you!