Peptide Vaccine for 5 year old with GBM

All-

Thanks to everyone for contributing to this great resource.  First a profile of our daughter's condition and then a question at the end.

Thanks!!!

Our 5 year old:

DOB 9/2/2011

Brooklyn, NY

9/9/2013 admission to:

Weill-Cornell Medical Center

Right neck abscess lanced and drained

March 18th, 2016 admission to:

Weill-Cornell Medical Center

Mass discovered in head after experiencing headaches for a few weeks

Left occipital/parietal brain tumor

Operated 3/19/2016

"Full Gross Resection"

Pathology determines Glioblastoma Multiforme "methylated" 

Transferred to Memorial Sloan Kettering

Photon Radiation treatment for 33 days (Dr. Suzanne Wolden)

Temozolomide chemotherapy for 43 days

MRI on 7/8/2016 'clear' 

'Maintenance' regime of temozolomide prescribed for 12 cycles (5 days chemo/23 days off)

Currently in 5th? cycle 

MRI on 10/5/2016 'clear'

Genetic sequencing/testing

• Cornell _ Precision Medicine

• MSK _ Methylation array

• MSK _ Impact Testing

• Caris Test

Other Diagnosis via 3rd party (non-MSK) bloodwork

• Positive (via Plasma test) for CMV antibodies

• Positive (via DNA test) for Herpes-6 active case

Other Treatments

• Cronaxal (cronaxal.com)

• Cannibas oils (THC/THCa/CBD)

• Chinese Herbs (prescription pending)

• Supplements- Vitamin B, C, D, L-Lysine, Curcumin, sodium selenite, paw paw, cayenne pepper w/garlic, green tea extract, etc.

• Ketogenic diet since appx. June 2016

We are so grateful that our daughter is NED to-date but are considering engaging in an off-label customized peptide vaccine treatment coming out of Tubingen Germany via CeGaT.  Has anyone in this community had any experiences with this?

Treatment description from their literature:

Our personalized peptide vaccination approach aims to train the immune system to recognize

specific “non-self” antigens (neoantigens) which are predicted to be specifically presented by the

patient’s tumor cells. In order to identify tumor-specific mutations, the patient’s tumor and normal

tissue sample (mostly blood) are analyzed using the modern next-generation sequencing technology.

Many of the identified tumor-specific mutations lead to alterations in proteins. Bioinformatic

prediction algorithms are subsequently applied to select those mutated peptides which are most

probably presented on the surface of the tumor cells by the patient-specific HLA molecules and

which have the potential to elicit a strong immune response. These selected peptides are synthesized

and injected as a vaccine in order to stimulate the immune system and to enhance the propagation

and activation of immune cells that specifically attack tumor cells presenting the mutated peptides.

In order to further boost the vaccine specific immune response, an immune stimulatory adjuvant (Leukine) is

co-applied at the injection site.

While they have had good results to-date they have not treated any children.  This obviously concerns us.  Does anyone have any experience with peptide vaccines in children?  The doctors say that theoretically there shouldn't be any difference beyond dosage/body mass.  What are people's thoughts on:

1) The logic of this treatment approach

2) Experiences?

3) Peptides in children

4) Experiences with FDA Personal Use Exemption program / importing off-label drugs from overseas

Again, thanks to everyone for help!

Winston
Brooklyn, NY

SPMF treatment and my husband

Dear all,

let me now just post facts.
(This is continuation of http://btcocktails.blogspot.sk/2016/08/smpf-therapy-v-novocure.html#comment-form)

Attached are two MRI descriptions right before and right after the SPMF treatment (2 hours 28 consecutive days).

Please, see for yourself.

I further should mention that:
1. My husband has ongoing immunotherapy in his body with DC vaccines. Started in August.
Takes also metronomic cyclophosphamide and MGN-3.
(Not sure how effective that is when one has 12mg of dexamethasone.)
2. Half a month before the travel to India we started Kava Kava (1-2 grams a day) and continued till mid September.
(Than we ran out of it.)
3. For three days he had Graviola leaves and twigs decoction.
4. Since we were in Ayurvedic centre, he ate in Sativic restaurant. Organic local food.
5. Was touched on his head by local person and prayed for.
6. He forgave one man who harmed him in the past.

This is all what was new and could add to the SPMF treatment. One never knows what works to which extent.

As told by Dr. Vasishta, tumor should keep shrinking and dying. (I hope it will do.)

What was not new is: Melatonin, Vitamin D, Reishi, Cordyceps, Omega 3, Curcumin, Boswelia, ...

All the best and take care,
Hana

P.S. my introductory post is: http://btcocktails.blogspot.sk/2016/07/my-husband-introduction.html

L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity

Link to article:
http://www.cell.com/cell/pdf/S0092-8674(16)31313-7.pdf

Aynone taking l-arginine and your  thoughts on supplementation?

39 y/o female - Biopsy results

Hi -

My friend was told she has GBM.  Here are the results of her biopsy:

NEUROPATHOLOGICAL DIAGNOSIS: 
Left occipital mass: stereotactic biopsy:
Integrated diagnosis: GLIOBLASTOMA, IDH WILD TYPE, WHO 
GRADE IV
Histological classification: GLIOBLASTOMA
WHO grade: WHO GRADE IV
Molecular information: 
* IDH: MUTATION NOT IDENTIFIED BY IDH1/2 SEQUENCING 
(EXON 4)
* ATRX: RETAINED NUCLEAR IMMUNOREACTIVITY
* p53: LOW IMMUNOREACTIVITY, 
<10% OF NEOPLASTIC CELLS
* 1p/19q: RETAINED BY FLUORESCENCE IN SITU 
HYBRIDIZATION
* MGMT: GENE METHYLATION NOT DETECTED

I'm out of practice on everything except MGMT.  Can someone please help me understand what else this tells us, and what drugs this may prioritize for her?  She's not as willing to take lots and lots of pills as my Dad was.  I would like to pick maybe the top 5 if we can.

Thank you!
Annie

Garlic and other veggie pills antiproliferative and antioxidant activities

hi Stephen and all,

I came across this Canadian study .. It mentions that garlic and broccoli sprouts ( sulforaphane) had almost 100% inhibition of U-87 glioma cells proliferation. Anyone here taking them? How much mg dose per day should be taken? Thanks

http://www.chrisbeatcancer.com/wp-content/uploads/2013/01/Anti-Cancer-Vegetables-Study.pdf

CCNU/TMZ

Stephen

Have you heard any results from the CCNU/TMZ combination study out of Germany?  Final completion date was supposed to be December 2015.  There must be some information floating around about the results, but I can't locate it.

Hi everyone thanks for inviting me.  My name is Martina
I have a question is someone on the blog who had or have brainstem tumor grade 3/4 and is after surgery?

Hyerbaric oxygen plus nimustine (ACNU) in a glioma xenograft model

Pubmed abstract
full study uploaded to Brain Tumor Library, folder 2 (Therapies, preclinical), Hyperbaric oxygen subfolder

The SU3 human glioma cell line was injected into the flanks of nude mice.  ACNU is a nitrosourea in the same class as CCNU (lomustine) and BCNU (carmustine).

Long term analysis of NOA-04 for anaplastic (grade 3) gliomas published today

This was a randomized phase 3 trial testing radiation therapy (followed by chemotherapy with PCV or TMZ at recurrence) versus chemotherapy (followed by radiation therapy at recurrence). Half the chemotherapy patients were randomized to PCV and the other half to temozolomide.

In this new update, patients are divided into three molecular groups:  CIMP negative, CIMP positive 1p/19q codeleted, and CIMP positive 1p/19q non-codeleleted.  CIMP positivity in this study is essentially another way of saying "IDH-mutant" as IDH mutation virtually always leads to the CpG Island Methylator Phenotype (CIMP).   The latter two subgroups correspond to molecular oligodendroglioma and molecular astrocytoma, respectively.

One of the more important findings in this study is that PCV was superior to TMZ in the molecular oligodendroglioma subgroup.  (This image shows progression-free survival, but the same trend was evident in time-to-treatment failure analysis and overall survival).

On the other hand, PCV and TMZ were more or less equivalent in efficacy for the molecular astrocytoma group (CIMP+ non-codel).

These findings support the use of the PCV regimen for molecular oligodendrogliomas, however it's still an open question whether the addition of vincristine (V) to procarbazine (P) and CCNU (C) adds any benefit.  Some retrospective evidence suggests that PC chemotherapy (without vincristine) is comparable in efficacy to PCV.

This study was published in the November 2016 edition of Neuro-Oncology, and the figures above are taken from the Supplementary figures.

http://neuro-oncology.oxfordjournals.org/content/18/11/1529.abstract?etoc

Photodynamic therapy

Hi All, anyone heard of photodynamic therapy? I read about sone Australian studies that had considerable success with it. Anyone tried it? If yes, can you please share information: where and whether it was effective?
Many thanks
Noha

Best Medication choices for Immunotherapy

Hello.  I'm relatively new to the blog and am wondering what your opinions are on the best medications to be on while doing Temodar and Immunotherapy through IOZK.  My husband will begin treatment in November and I want to start pushing his NO here for any medications that he should start taking now.

Thank you all so much!

Tumeric powder and cancer

Hello everyone

This programme was broadcast a couple of weeks ago.  No media organisation is perfect, but at least the BBC is not sponsored by commercial organisations.  Interesting to see that it re-emphasises the need for tumeric to be cooked/absorbed with fats to be effective.

http://www.ncl.ac.uk/press/news/2016/09/turmeric/

Looking for help with our cocktail

Hi everyone,
I'm new to this blog and would love to get some advice. My dad was diagnosed in December 2015 with a glioblastoma. Unfortunately it's inoperable because of it's location (corpus callosum). I've just read Ben William's book and I think it's very sensible to try the cocktail approach. He finished radiation plus Temodal and is now in his 5th cycle of Temodal. After the 6th cycle he'll be switched to metronomic Temodal. He also takes:
- dexamethadone 4mg/day
- D-L-methadone 1,75ml/2x day
- Heparine injections because of a thrombosis
- Keppra 500mg/2x day
He is also using Optune TTF. But there's more that we want to do. I'm very interested in DCA but worried if it might interact with the methadone. From what I've read online, he should start on a low dose and without caffeine as brain tumor patients can't seem to tolerate a higher dose. Do you think that we should give it a try? I think it's pretty hard to get...
Additionally we're considering the following:
- PSK
- Melatonin plus Aloe Vera (again I'm worried because of the methadone as it makes him really tired)
- Fish oil (Omega 3)
-CoQ10
It would be so helpful for us if you could give u your advice!
Thank you so much
Steffi

Medicinal Mushrooms

Hello everyone!

I currently have my husband taking three different kinds of medicinal mushrooms: Turkey Tail PSK, Maitake D fraction, and Reishi.  Originally I started him out on pills, but between all the other supplements and medications, the mere sight of his pills makes him want to gag.  He seemed to really detest the mushrooms out of them all, so I switched to extracts in a smoothie.  I have been able to get away with that for a few weeks until recently.  He swears he can taste them.  His taste for food has definitely changed these past few weeks of treatment (he is in week 5 of 6 of radiation/TMZ).  Normally never a picky eater, now he has developed extreme distaste for foods he normally loved.  So my question to you all is: If I had to give up one or two of the mushrooms, which would you remove?  Or perhaps you have another suggestion for disguising them that works particularly well for the pills you can't stand?  I hate to give them up.  I'm doing everything I can think of so far to keep his immune system healthy.  His blood work has been good each week despite the fact that I refused to give him the antibiotic his oncology team prescribed and I can't help but think that the mushrooms play a role in that.

Phase 1/2 trial in Japan: dendritic cell + glioma cell fusion immunotherapy

https://www.ncbi.nlm.nih.gov/pubmed/27688162  (the full study will be added to the Immunotherapy folder of the Library)

This trial recruited 22 newly diagnosed and 10 recurrent GBM patients.  The therapy consisted of autologous glioma cells (lethally irradiated) chemically fused with autologous dendritic cells.  The fusion cells were also transfected with poly I:C (a synthetic double-stranded RNA analog) and small interfering RNA for IL-10 (IL-10 is an immunosuppressive cytokine).  For the newly diagnosed patients this treatment was added onto standard treatments (radiation and temozolomide).

Median progression-free survival (PFS) and overall survival (OS) for the 22 newly diagnosed patients was 17 and 30 months.  Average age of these patients was 56.7 years.

Median PFS and OS (from recurrence) for the 10 recurrent GBM patients was 11 and 17 months. Average age was 50.1 years.

This is certainly one of the best phase 2 outcomes for newly diagnosed GBM yet published in a peer-reviewed journal, and the results for recurrent GBM are also impressive (though only 10 recurrent patients were treated and the average age was on the low side).

Thanks

Thank you Stephen and many others for passing on your helpful knowledge of GBM.

Unfortunately, I failed in my attempts to help make my daughter one of the longer term survivors of this dreadful disease.

So with a very heavy heart and great sadness I have to say my beautiful, very special 18yr old daughter Maddie lost her 13 month battle with GBM on Mon 26th Sept 2016.

Avastin Infusion

My husband just had his third Avastin infusion, his protocol is once every two weeks at 1/2 the usual dose. Sadly, he is that 10% of those who use Avastin that the treatment has completely kicked him in the butt. On the plus side, it seems to have done an excellent job reducing his inflammation (see MRI below). I'm checking with this group on those who have used Avastin and what were the side-effects, if any. Also, what was the upside? Just FYI, Greg's neuro-onc is recommending that he has 3 more rounds before we decide to give Greg a break.
For background, Greg is 62 yrs old, diagnosed with GBM on May 1, 2015. The tumor is in his right temporal lobe. Resection was not an option. He had 5 rounds of Temodar, his MGMT is methylated but his IDH1 is non-mutated.




The right scan is August, then yesterday's MRI, then August, then yesterday's

MRI notes... biopsy pending. What do you think it sounds like?

Hi -

My friend had her biopsy Monday which went very well.  She is now waiting on the diagnosis and advice from the tumor review board, likely next Tuesday.  I am reading her MRI notes and would love your insights.  I suspect GBM based on "high-grade" and the impression notes.  Anyone else want to take a look and weigh in?  I haven't told her that I think it will be GBM.  We are still hopeful for MS, lymphoma, <anything else>...

FINDINGS:
Redemonstration of bilateral enhancing lesions, grossly unchanged:
Subcortical enhancing lesion in the right parietal lobe measures approximately
27 x 17 mm (9/139).
Peripherally enhancing and centrally necrotic left occipital lesion measuring
20 x 17 mm (9/84). Grossly unchanged T2/FLAIR abnormality about the left
occipital lesion.

These lesions demonstrated diffusion projection on the previous MRI,
suggestive of high-grade, highly cellular tumors.

Additionally, there is masslike, T2 hyperintense cortical expansion of the
left anterior temporal pole, unchanged.

The ventricles are symmetric. Basal cisterns are patent. No midline shift. No
acute infarction. No intracranial hemorrhage. No extra-axial fluid collection.

Orbits and soft tissues are unremarkable. Visualized vascular flow voids are
maintained. The calvarium is intact. Visualized paranasal sinuses and mastoid
air cells are clear.

Impression

IMPRESSION:
Redemonstration of bilateral enhancing lesions in the left occipital and right
parietal lobes, as well as infiltrating T2 hyperintense cortical expansion of
the left anterior temporal pole. The left temporal pole lesion is worrisome
for primary malignancy, with the additional lesions possibly representing
multifocal primary glioma versus less likely metastatic disease. Presence of
some diffusion restriction involving the bilateral enhancing lesions on the
previous exam is suggestive of some high-grade, highly cellular components.

Temsirolimus in Recurrent GBM

Hi All,

Has anyone tried Temsirolimus in addition to avastin in recurrent GBM? Was it successful? Thanks!!

Effects of metformin treatment on glioma-induced brain edema

http://www.ajtr.org/files/ajtr0024896.pdf

"Finally, metformin treatment dose-dependently reduced glioma induced vascular permeability and cerebral edema in vivo in rats. Thus, our results suggested that metformin may protect endothelial cell tight junction, prevent damage to the blood brain barrier induced by brain tumor growth, and alleviate the formation of cerebral edema."

The rats were fed metformin dissolved in their daily drinking water.