Advice for a 8 year-old boy with diffuse midline glioma, BRAFV600E and H3K27M mutation

Dear Stephen, dear all,

Anatole, my 8 year-old son has been diagnosed in May 2018 with a diffuse midline glioma on the right thalamus. We are French and based in Stockholm, Sweden. We followed the proposed protocol with the local medical team who works in partnership with Gustave Roussy institute in France but we want to go further now, and we need your advice. The local medical team is not very aware of alternative medication but is willing to help.

Molecular status of the tumour:

BRAFV600E and H3K27M mutation

NF1 and MLH1 mutation

We have little chance to find new targetable alterations by a deeper sequencing. It is possible now that the V600E BRAF mutation is lost in the resistant cells but anyway we do not think it is wise to treat with a V600E BRAF inhibitor which in our experience could speed up tumor growth.  

History:

18/05/09 Diagnosis: MRI tumour size 3.3x3.7x3.7cm, unusual calcification

18/05/16 Biopsy, leading to light hemiparesis

Proton-therapy 18/07/02-18/08/13, 1.8Gy x 30 = 54Gy. Almost fully recovered from hemiparesis

18/09/07 Headaches

18/09/07 MRI tumour size about 4cm

18/09/12 Ventriculostomy

18/09/19 Beginning og Dasatinib (100+70mg/day), after 18/11/06 alternating with Everolimus (5mg/day) every 2 weeks (Biomede protocol)

18/09/22 Beginning of hemiparesis

18/10/03 Wheelchair for walks more than 20m

18/10/12 MRI tumour size 5 to 6cm unsure if pseudoprogession

18/10/22 Beginning of Bevacizumab then once every 2 weeks

18/11/06 Beginning of Everolimus  

18/12/03 MRI tumour size 4 to 5cm unsure if pseudoprogession

18/12/17 Crook for walks less than 20m

19/01/14 MRI tumour size 5x6x5cm

19/01/22 Stop all current chemo (Dasatinib and Everolimus, last Bevacizumab 19/01/02)

24/01/24 PET scan (methyonine)

New plan established by Gustave Roussy Institute: Mebendazol, investigation for debulking of calcification before re-irradiation, eventually ONC201
Any comment on this plan?

Supplements:

Anatole is 30kg 132cm  

D3 vitamin since 18/12/24: escalading from 40µg/d to 100µg/d now

Fish oil since 18/12/24: 1g

Melatonin since 19/01/10: escalading from 2mg/d to 5mg/d now

Turkey tail since 19/01/25: 500mg/d

We plan to add soon:

Longvida Curcumin: 800mg/d

Milk thistle: which dose would you recommend? 

Green tea extract: which dose would you recommend? 

Broccoli sprouts: which dose would you recommend? 

Metformin: Is it worth considering for a child?

Anything else you would find suitable considering his condition (celebrex, chloroquine, clomipramine, berberine, selenium, probiotics, etc?

Diet:

We follow a light low carb diet now (no refined sugar or flour, very limited sugar, no processed food, only bio food). We are planning to begin a ketogenic diet soon, we are ready to change all our habits. We will contact a dietetician specialist in this diet. Anybody else with an experience of ketogenic diet with children?

Thanks to all of you for your precious help, any contribution could help.

Fabrice

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.