Urgent help for an 11 year old girl

Dear Stephen and all,

I have a question concerning my friend’s daughter. She is a Spanish 11 year old girl. She has been diagnosed with a grade IV medular glioma. She had surgery, but the tumor could not be removed. They just took a biopsy. She has had 30 sessions of radiation and 27 days of temozolomide. Parents are desperatly looking for possible clinical trials that would fit her case. Any suggestions on specific treatments or cocktails would be of much help as well. Even though they live in Spain they would have no problem travelling overseas. We are attaching pathological report, MRI and tractography report.

Please click on the following link.  Once the link takes you to the page of the girl's medical information, click on "Visualizar el estudio" to see her images and "Descargar el informe" to read the medical report:

http://resultados.healthtime.es/PortalPaciente/OpenSharedStudyRequest/a4ac550a-19f7-4d58-99ad-6e1fb2e06ccb

The picture I am including is the report of the pathologist.  It is in Spanish, but I think it is understandable.  If you have any questions, please contact me. 

Thank you all in advance.

Isabel

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?

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

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

Immunotherapy and cannabis

Hi,

Does anyone have information on concurrent use of immunotherapy and cannabis? I read that cannabis can have anti-inflammatory effects primarily due to it suppressing the immune system. This seems worrisome if the patient is on immunotherapy. All I could find is one retrospective study on cannabis and opdivo use: http://oncologypro.esmo.org/Meeting-Resources/ESMO-2017-Congress/The-effect-of-cannabis-use-on-tumor-response-to-Nivolumab-in-patients-with-advanced-malignancies

Has anyone's doctor mentioned a possible contraindication?

Thank you.

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.

Early reccurance? please help

Good morning all,
I have posted a story of my husband last year, but now I am in a black hole and l need help.
He was diagnosed with GBM IV October last year. He had big tumor in right frontal lobe over 6cm diameter. After some time we have found out that it wasn't total resection with some tumor left in corpus callosum and lodge. Till the end of the year he had finished his 6 week course of chemo and radiotheraphy. Then he was switched to monthly TMZ.
At that time we also have started vaccination with NCV because we didn't have fresh tumor tissue for DCV. A week after each vaccine he had seizures despite the fact being on Keppra and Depakine. For the first time we thought it was time coincidance. But after second he did extra scan and yesterday we found out he has two tumors - one in the lodge 5cm and second 4cm crossing corpus callosum in left hemisphere and huge oedema.
Today neurosurgeon told me they won't operate and that the treatment is over.
He is on meds from Cusp-nd protocol from the pretty begining, his tumor was MGMT promotor methylated so I don't know what has happened and what to do.
Can vaccination have such a huge impact on scan?
I don't know if we should try
rechallange it with metronomic TMZ,
try different chemo
go on Avastin
Perillyl alcohol
Nivolumab
Any thoughts....
I thought we have a little more time together...
Pat/brainbutton

Treatment questions

I have a few questions I've been thinking about and would love your opinions. Background first, my husband is fighting an AA3 right insular brain tumor. Surgery removed 80% of the tumor and then an emergency surgery three days later removed nearly his entire right temporal lobe.  His tumor was never tested for MGMT status but it is IDH1 mutated. Surgeries were in July 2016 with TMZ and radiation following in September and October.  He is currently finishing up his 5th cycle of TMZ, been wearing Optune since the end of November and will be receiving his 5th round of NDV infusions at the IOZK clinic this coming week.  Last MRI done in early January has shown no tumor change from his original surgery.  My questions are:

1. Research has shown that patients who complete 12 rounds of TMZ often have longer periods of PFS. However, vaccinations that would begin in May at the IOZK clinic require that he discontinue TMZ or else risk them not working. We are spending all our savings to do this treatment. What I'm wondering is if we should continue on as planned with 6 cycles of TMZ and then vaccinate or try to push back vaccinations to complete 12 rounds of TMZ and then do vaccinations?

2. Seizures endured during his two week hospital stay in July required 4 different medications to calm my husbands seizures. Before being discharged, his medical team were able to get that down to two medications: Keppra and Vimpat. He was prescribed his maximum dose at 3000mg and 400mg respectively. Since learning of this website and studying different supplements and such, with all the pills he is swallowing he's slowly weaned himself down to 2000mg and the occasional 200mg if he remembers his lunch medications. His NO has never been particularly interested in bringing any of his seizure medications down, probably because of his chart notes. At our last visit our NO was questioning his moods. Asking if he seemed more agitated than usual. I lied and said no because I was worried that she'd take him off of Keppra (the medication we were discussing). My understanding is that it helps with MGMT status. So finally my question is, should I try and keep him on Keppra for its benefits or let them change his seizure medication to Gabapentin?

Thank you for any insight in advance. I'm really wondering what others might do in our situation.

CUSp9

Dear all,
We just came back from the second visit from IOZK with a list of CUSP9 drugs:
1.valdoxan
2. naproxen
3. antabuse
4. minocyclin
5. propranolol
6.spironolacton
7. Valproic acid

The only one that seems to be available over the counter is naproxen as Alive. I saw also antabuse on-line at Canadian pharmacy, but the rest are definitely prescription in the US. Does anyone have any experience getting these? Thanks!

chemo with dendritic vaccine

Dear all,
My son is finishing his second vaccine at IOZK. His tumor is astrocytoma III, H3K27m, low methylation ( our doctor still won't give us the percentage!), clean MRI ( only 4 months since surgery)
Van Gool is against any chemo for now. He wants to do another MRI in three weeks, and he added Accutane and Keytruda this time. Our US oncologist wants to do avastin and then temodar with CCNU. Another well-esteemed Russian NO who is very open- minded ( she was the one who recommended van gool to us) thinks we should continue with temodar while on vaccine since there is a good chance it worked till now. We are very confused - tend to just trust Van gool, but scared to give up chemo even for a month. Any thoughts? thank you!

Conversation with NO

Dear all,
I need some advice as to how much to share/not to share with our NO regarding my son's vaccine treatment. We just started vaccine with Van Gool  ( three weeks after the end of chemoradiation)who thinks my son should definitely not do any  chemo while on immunotherapy (except for, if we have PD1 , maybe Keytruda). He has low MGMT expression, which justifies the use of TMD, but his blood counts dropped really low the last few weeks of chemo and he generally tolerated it very poorly.  Our NO previously was talking about either doing avastin or/and maintenance or CCNU based on the post radiation MRI ( which we will have for the first time since surgery in October).
While I tend to go with Van Gool's idea, I am not sure how much I should tell our NO. I am afraid if we put it on record that my son is doing DC vaccine, that would preclude him from further clinical trials. Conversely , if we don't follow the standard procedure, maybe we could be excluded from trials as well. Our NO is a good guy ( not a brilliant professional, though), but I am not sure how much I should/should not share with him.
Thanks!

dendridic vaccine plus virus

Dear all,
we are planning on getting the vaccine with Van Gool for my 17-year old pretty soon. I know he is using  Newcastle virus with it, but I wonder if this would be the most effective/aggressive option. I have seen mixed reports on its efficacy, so I wonder if tetanus shot or Hilton would be a better option to add to the vaccine. From what I read, tetanus seems a lot more effective. As much as I trust Van Gool's expertise, I still can't fully put my faith into any one treatment if there is a possibility of something working better. I am sure Van Gool would insist on his approach, but I wonder if this is because he truly believes it is better tan others ( such as tetanus) or because this is the only protocol they use at the moment. Would anyone have an opinion on that? Thanks!

Considering treatment options for high grade diffuse midline glioma H3k27m for my 8 year old daughter

Hi all,

Thanks so much to Stephen for your in depth reply to my questions about my 8 year old daughter and invitation to this blog. We moved to Norway in July and my daughter was diagnosed in early September with high grade diffuse midline glioma with H3K27m mutation after an extended biopsy, where it was determined that the tumor was not resectable. She underwent 3 further operations to have a double valve shunt put in to relieve hydrocephalus symptoms. She finished 6 weeks of radiation and Temodal about 10 days ago. The doctors want to start her on Temodal/Lomostine 4 weeks after radiation finished. If we follow this path, we could also have a full molecular analysis done and, upon recurrence, may possibly be able to access a trial using afatinib for BI1200.120, if applicable, or another targeted agent. I would also push for using repurposed drugs in the cocktail approach if possible and our conservative doctors could be convinced. 

We are trying to explore other options, and thanks to Stephen, learned about a new phase I peptide vaccine trial opening for paediatric glioma patients with mutation H3.3K27m based in San Fransisco. It is for patients who have completed 6 weeks of radiation and have not yet started chemo again, which is exactly where we are now. https://clinicaltrials.gov/ct2/show/NCT02960230

I am finding it so difficult to determine what would be the most promising, preferably least toxic option for my daughter. Any input on how promising a peptide vaccine targeted to this kind of mutation could be? Compared with temodar/lomostine/cocktail approach?

Many thanks in advance for your input.

Jeni

IOZK clinic / NDV

Good morning Stephen and all,

Does anyone has experience with the IOZK clinic in Cologne? I can't find much data on the vaccination they use along with the NDV except in few pediatric cases. Has anyone had success with it in adult Glioblastoma?

Thanks
Noha

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

Choice of german clinic.

Hello everybody!
Can I ask for help in choosing a German clinic for immunotherapy?

At the moment, we only have histology and immunohistochemistry, the location of tumor left temple - that's all we know so far.

1.Histology.
this is a very cellular glial neoplasm consisting of pleomorphic, atypical gemistocytic astrocytes which diffusely infiltrate the cerebral cortex and subcortical white matter, forming secondary structures of Scherer. Mitotic figures, including atypical forms, are readily recognized, as well as prevascular lymphocytic infiltrates and foci of microvascular proliferation. In addition, there are large areas of confluent necrosis with early organisation and some trombotic blood vessels.2.Immunohistochemistry:ki-67 ( sp6)- positive tumor expression to 15 %Bcl-2a Ab-1 (Clone 100/D5)- tumor expression weakly positive,p53 ( clone Sp5) positive expression to 5 %/And another part of brain (left temple)/ki-67- positive expression to 5 %CD 45/T200/LCA Ab-2 ( clone PD7/26/16 +2B11)- positive expression in abscess,GFAP glial fibrillary Acidic Protein Ab-6(GFAP) positive expression.
Conclusion :Pleomorfhic glioblastoma ( ki-67- to 15 %) with a plot of abscecc.


Now we have a proposition to send blocks to clinic Hallwang to make tests ( Next generation Sequencing 3+tumor surface makers and amplification analysis 9500 euro, and Screening for tumor Associated Antigens TAA 3800 euro) to start producing of vaccines.
( From mail from clinic: It is known, that tumors show the accumulation of several genetic modifications, thus providing cancer cells with the selective growth advantage to initiate expansion. Now, sophisticated high-throughput technologies enable the identification of  these mutated genes in cancers, leading to potent targeted immunotherapy - by so called tumor-associated–antigen-multiplex-THX-Vaccination-Strategy. Particularly THX-Vaccination-Strategies against the tumor antigens or mutated antigens have shown amazing results, showing a stronger anti-tumor immune response than several dendritic cell vaccinations. In comparison to the often used single-THX-Vaccination-Strategy - "one THX against one tumor antigen" - that is limited by the so called MHC-class-match and by the fact that one THX might not be efficient to induce an immune response or can be bypassed quickly, we have established a Multiplex-THX-Vaccination-Strategy that includes all therapeutic relevant immunogenic THX’s against one tumor antigen - "Multiplex Immunogenic THX’s (50-200 THX’s) against one tumor antigen. Furthermore, we are using the Multiplex THX’s in combination with the most upfront immuno-adjuvants. Our adjuvants have been optimized in order to improve efficacy and stability of the Multiplex THX Vaccine formulations and to reduce side effects.

Besides this test we would strongly suggest one of the most upfront analytic approaches by next generation sequencing (NGS). We entered the third generation of NGS, namely NGSIII that offers the analysis of all therapeutic relevant cancer driving mutations, thus offering the chance for a targeted genetic therapy and an efficient immunotherapy.)

Another one proposal is from Dr. H. Bojar.

Vaccine design

1.       Transcriptome analysis (activity of all 20 000 human genes) including selected immunohistochemical analyses: 1 500 €

2.       Exome analysis tumor DNA versus blood DNA (mutation analysis of all 20 000 protein-coding genes):                   6 500 €

3.       HLA class I & II haplotype determination:                                                                                                                              1 000 €

Vaccine production

1.       Synthesis of 10 mutated neoantigen peptides                                                                                                             approx.. 5 000 €

2.       Production of the vaccine cocktails incl. quality control (sterility etc.)                                                                    approx.. 2 500 €

Also we are still waiting for information from another clinics from Stephen list of german clinics.

can I ask to help me understand? the price of the study of the tumor is very different if a higher price is justified? I apologize in advance for the stupid question, certainly I ask about elementary things.

 Thank you in advance!

Tania.

My Mum's story so far (GBM - trying cocktail and immunotherapy)

Hi all,

I thought it was time to share my Mums story so far. This blog has been just so helpful and I am so grateful to Stephen and all who contribute to this so thank you.

I will try to keep this as brief as possible and focus on the important and maybe interesting bits for others going through this.

My Mum, Marilyn, aged 66 was diagnosed in July with GBM. Symptoms were; getting lost on her drive home from work (a drive she has done many many times), text messages were getting muddled, trouble feeling stable when walking down stairs and some speech issues such as forgetting the word for things. The first scan showed a very large tumour in her front left temporal region and a very small one further back on the left side near her speech and communication region. She is being treated in the UK where we are from but I live in San Francisco so I am back and forth a bit (trying to not get fired from my job but be home as much as possible to offer her and my Dad support). My brother is a great support too and lives in the UK.

After diagnosis, she had keyhole surgery on the larger tumour which was a success with 99% resected. We decided to leave the smaller tumour alone as there was a risk of her speech worsening and her symptoms were so relieved after her first op. The plan was to try to hold this smaller one in place with chemo and radiation. As she is being treated by the NHS she didn't get any tumour tissue testing as a standard which absolutely boggles my mind! I had to fight hard for it. The results from the pathologist got back to us insisting there was too much necrotic tissue in her tumour to be able to test for anything.

Mum started on a cocktail during radiation mainly of supplements but towards the end of the 6 weeks had added CBD oil and a few repurposed drugs from the Care Oncology Clinic; Metformin and Mebendazole. Celebrex has been impossible to get hold of for us even with two letters of recommendations from two different oncologists to give to our GP. However I am chasing a few more options now so there is still hope here.

After radiation/chemo her symptoms worsened significantly, in particular her sentence forming and some of her movements. We were told this was just a result of the radiation and to be expected so we were hoping she might start to improve again but in mid November things got so bad she was rushed to hospital. She could not talk and her right side movement was significantly impaired. She was given a high dose of steroids (after not being on any after radiation) as they found she had severe cerebral oedema. This was unfortunately caused by the smaller tumour growing significantly since her first operation. It had grown and a new one was forming next to it and very close to Mums motorneruone center.


Thankfully surgery was an option. She ended up having to wait nearly 5 weeks for the surgery as it was a 'really busy time of year'. It was a very long 5 weeks and Mum got back onto a cocktail during some of this and had been finding the CBD oil particularly helpful. She was not keen on taking THC but is very happy to take the CBD and feels brighter after doing so. The surgery happened on Christmas Eve and went as well as possible. The surgeon was a bit amazed/stumped to find so much necrosis, he said it "was all grey" and he could not see any live tissue. Normally there is some necrosis but he was really stunned to find as much as he did and felt that whatever she has been doing she should keep on doing that! I am not sure what to think here as her original tumour was also full of necrotic tissue so it could just be the nature of this GBM. It was interesting hearing how shocked the surgeon was though and how positive he felt that something was causing it to die.

This time around with the surgery we had asked again for tumour tissue testing but had no luck again due to the necrosis. We also decided to pursue immunotherapy at IOZK in Cologne with Stefaan Van Gool. Mum's tumour was frozen and shipped off to Cologne and they seem to think they can still build a successful vaccine with the tissue so that was some good news.

Mum's NO had wanted her to switch to PCV after she progressed during radiation but we felt it was too soon to give up on Temodar for a whole lot of reasons. With the number of scans she has had in the past few months we are able to see that a tiny bit of growth from her original resected tumour has stayed static indicating something is holding that in place. She started on her first month of the high dose Temodar a few weeks ago. Between days 5-10 of the month she will go to Cologne for her treatment.

The first NDV injection was done on Tuesday. They had her on a drip of Selenium, Vitamin C and Newcastle Disease Virus at the same time as having Hyperthermia treatment. She tolerated it well. She went back the next morning for the same again. So far my Mum and Dad have found the clinic to be really pleasant and they have been well looked after. Mum had a slight fever during the night on Wednesday but is good right now. Attached a picture of Mum undergoing the IOZK treatment...

We are adding and adapting Mums cocktail gradually but this is it below for next week. We have Cimetedine and Sildenafil waiting in the wings and are working on getting Celebrex and Minocycline too. We have not added the COCs other prescribed drugs, Doxycycline and Atorvastatin as there is not enough evidence of efficacy with these. We may consider adding DCA as well -especially as it is accessible although I am concerned about the potential side effects and being so far from home so often it is hard to only hand out the instructions and not be there to manage any potential symptoms.

______________________________________________________
First thing in AM         Lanzoprazole                      (x1)        30mg
______________________________________________________
Before Breakfast          Levetiracetum                    (x1)        500mg
                                     Wild Alaskan Fish Oil          (x1)        1125mg
                                     Selenium                             (x1)        200mcg
                                     Broccoli Sprout Extract       (x2)        1000mg

During/After                 Dexamathasone                 (x1)        2mg 
Breakfast                      Metformin                          (x1)        500mg
                                     Zinc                                     (x1)         50mg
                                     Boswellia (Wokvel)             (x1)         333mg
                                     Curcumin (Longvida)           (x2)        1000mg
                                     Ashwaganda                       (x1)        125mg
                                     Coriolus PSK                      (x2)        1200mg
                                     Honokiol (HonoPure)          (x2)         500mg
________________________________________________________
Before Lunch/Mid        Wild Alaskan Fish Oil           (x1)        1125mg
Morning                        CBD oil                                              100mg
                                      Pterostilibine                       (x1)         50mg

During/After                 Vitamin D3                            (x2)         4000IU
Lunch                           Green Tea Extract                (x1)         725mg
                                     Pterostilibine                        (x2)         100mg
                                     Boswellia                             (x1)         333mg
                                     Ashwaganda                        (x1)         125mg
                                     Mebendazole                      (x2)         200mg
 _______________________________________________________
 Before Dinner/Late      Flaxseed oil                         (x1)        300mg
Afternoon                     Curcumin                             (x2)       1000mg

During/After                Levetiracetum                    (x1)        500mg
Dinner                          Metformin                          (x1)        500mg
                                     Milk Thistle                         (x3)        450 mg
                                     Coriolus PSK                      (x2)         1200mg  
                                     Vitamin D3                          (x1)        2500IU
                                     Chloroquine                      (x1)         250mg
                                     Honokiol (HonoPure)         (x2)         500mg

_______________________________________________________
Bedtime                        Melatonin                           (x1)          10mg 


Does anyone know of any reason to not take a very high dose of Vitamin D3 for extended periods?
Whilst supplement shopping today I read the label on the back of one of the Vit D3 5000 IU bottles that said to only take once every other day and to be wary of taking for continued periods. I am not sure what side effects there might be and again I am sure whatever they may be are most likely insignificant compared with the potential benefits in this case.


Has anyone got any good methods for organising supplements? Any recommendations on pill organisers? I noticed Ben Williams uses them in the survivngterminalcancer doco. There are a whole range on Amazon. It makes sense to prepare a weeks worth ahead of time.

I am so grateful for this space to share and discuss. Thanks so much Stephen -I am not sure I can say thank you enough times!

Best wishes to all.

Alison

Edited to add IOZK cost breakdown:

Hi all,

I am half way through my 4 week holiday from treatment and starting 6 months of TMZ on 23rd December. Fortunately things are on a roll with TTF and IOZK as i am aiming to do all 3 approaches (TTF, IOZK, TMZ+Cockatail) concurrently. What im a bit concerned about is continuing my cocktail while i undergo Newcastle Virus and DC immune therapy. I was wondering if anyone has any advice on what drugs i should perhaps stop/start taking in the run up to IOZK which begins on 30th December. I also thought i would use this opportunity to finally share my cocktail.
Thanks, Mark.

Details:
Male 54, primary GBM, over 90% resection on 3rd September 2015,MGMT mythelated at 36%, ATRX positive, IDH1 wild type (negative?), no P53 (only very weak focal expression), and no testing for EGFR and other indicators.

This is what im taking (dosages per day):

Vit D - 9000 IU
Longvidia Circumin - 1800mg
Echinacea - 800mg
Astragalus - 800ng
Grapeseed extract - 200mg
Selenium - 400 ug
Omega 3 - 3000mg
Pterostilbene - 250mg
Enhanced Rhodiala complex with Russian Gingseng - 2 tablets = (166mg rhodalia, 250mg ashwangandha, 320mg gingseng )
Cruciferous vegetable extract - 2 tablets
Probiotic complex - 1 tablet
CoQ 10 alpha lipoic acid - 1 tablet
Vit B12 -100 ug
Milk Thistle - 2 times 5mls
Boswellia Serrata - 2 times 5mls
Corioliolus mushroom - 3 grams
Reishi mushrooms - 2 grams
Maitake mushrooms - 9 grams
Melatonin - 20 grams
Vit B1 -500mg
THC/CBD oil -  1gram (not oral)

Metformin - 1500mg
Chloroquine - 250 mg
Celebrex - 600mg
Disulfiram (only on chemo days) - 250 mg
Keppra - 1000mg
Prozac - 20mg
DCA - Up until a week ago 20mg per kilo but experienced slight trembling and numbness , off for a week now and resuming at 10mg per kilo tomorrow