Second recurrence

Treatment options available for second recurrence

Hi everyone,

Has anyone here or perhaps Stephen that would have any recommendations for a second recurrence?

My sister just had her third resection (second recurrence) and we are now looking for options for methyled:

wild-type/ATRX not in favour of mutation 

IDH1 absent not in favour mutation

anti-GFAP positive

September 2020, after being diagnosed,  She had her resection #1 (followed by temodal and radiation). Temodal for about 18 months 

August 2022  Recurrence #1 followed by temodal for a month then rapid growth.

October 2022 Resection #2  followed with 1 month with PCV 

Jan 2023         Recurrence #2 

Feb 2023         Resection #3

She’s 47 and lives in Montreal. 

Is 1 month enough to say temodal isn’t working anymore? And PCV for just one cycle ?

Is there anyone here who also have had multiple recurrences? 

Thank you so much for your help.

Hi everyone! Thank you for your advice, guidance and experience. I wish everyone a complete recovery!

My name is Kirill, age 33. I am looking for help and advice. On May 20, 2020, I had surgery to partially remove the neoplasm in the left temporo-insula.

Analysis results: A diffuse glioma with infiltrative growth into the brain tissue is revealed. The tumor is represented mainly by the astrocytic component, also a little oligodendrocytic and hemistocytic. Mitotic figures are noted. Cellular density is increased. Reactive endothelium is found in the vessels.

1. Anaplastic astrocytoma, WHO Grade 3
2. IDH1 R132 H - mutant
3. MGMT - unmethylated
4. Ki-67 up to 15%

There is no exact information, but surgeons estimate about 80-90% removal of the neoplasm. 

I had the following treatment:

1. Proton therapy course 6 weeks. Radiation quantity 60 GyE. Finished 08/25/2020. At the time, I had no information about additional treatment that you discuss on the forum, so I have not used the means for increasing the sensitivity of the tumor in radiation therapy.
2. Temozolomide 200 mg/m2 (in my case 350 mg). Standard schedule 5/28.

10/09/2020 – start of 1^st course

04/23/2020 – 8 course.

During chemotherapy, I ate large amounts of antioxidant foods (broccoli, berries, green tea, garlic, onions, parsley, etc.). I have a simple diet: whole grains, refusal of meat in favor of fish, refusal of sugars and simple carbohydrates, a lot of vegetables and fruits, greens. I also took: curcumine, boswellia, omega-3, lycopene, resveratrol. Daily walking at least 1 hour.

At the moment, a fairly large cyst has formed at the place of the surgery. MRI 03/09/2021 shows stable results, no positive nor negative changes. PET/СT 04/02/2021 shows relapse. The doctors asked for a second MRI to check. The doctors, as usual, are conservative and treat according to the protocol.

After such news, I immediately bought medicines and dietary supplements, which are recommended on the forum.

Medicines:

1. Levetiracetam
2. Fluoxetine
3. Mifepristone
4. Hydroxychloroquine
5. Metformin
6. Valaciclovir
7. Disulfiram
8. Minocycline
9. Atorvastatin
10. Mebendazole
11. Tamoxifen
12. DCA
13. Celecoxib

I would be grateful for your help, whether they suit me and how to combine them all.

Dietary supplements:

1. Berberine
2. Fungi Perfecti, Stamets 7
3. Fungi Perfecti, Host Defense Turkey Tail
4. Now Foods, EGCg, green tea extract, 400 mg,
5. Life Extension, optimized resveratrol
6. Life Extension Boswellia serrata
7. Curcumin SLCP
8. Now Foods, silymarin
9. Solgar, vitamin D3 5000 ME
10. Now Foods, ultra omega-3
11. Life Extension, Mega Lycopene

I really want the tumor to shrink. Thanks to your forum, I plan to:

1. Switching to the metronomic schedule Temozolomide, dose 70-80 mg / kg2. 3 weeks taking, 1 week off. Or without interruption if I have enough strength.
2. Add Levetiracetam, Fluoxetine, Disulfiram, Valproic Acid to reduce the effect of MGMT
3. Add Metformin for blood glucose control.

Thank you for your opinion and advice:

1. What medications can be added (or removed), in what dose and for how long should I take it?
2. Is it a good idea to add Agomelatine before taking Temozolomide on a metronomic schedule?
3. How do Levetiracetam and Fluoxetine interact, how and in what quantities is it better to take them together?
4. What do you think about Temozolomide + Tamoxifen at this stage? I am thinking about Tamoxifen, because for a year now I have a very high level of estradiol, always the very upper limits. I heard that it could somehow relate to a tumor. I also know that Ben Williams has been taking Tamoxifen on a regular basis. I know that Tamoxifen is not very friendly with Fluoxetine...
5. Please suggest a different scheme if you have different opinion.

If such a scheme does not bring the desired result, then I plan to take Lomustine. Since I heard that Lomustine may be useful in the case of Astrocytoma-Secondary glioblastoma independent of MGMT.

Thank you for your opinion and advice:

1. Do I need to add drugs that reduce the effect of MGMT? Maybe there is a better combination of Lomustine with other drugs? Or is Lomustine not the best option / combination?
2. What medications can be added (or removed), in what dose and for how long to take?
3. Please suggest a different scheme if you have different opinion.

What are your thoughts on having several different short courses of chemotherapy? Ben Williams drastically changed his schemes so that cells did not have time to mutate, adapt and survive.

• Maybe TMZ + Tamoxifen
• Then BCNU (Carmustine)
• Then Procarbazine, oral Lomustine (CCNU). This regimen is known as PC
• Then TMZ + ??? or Avastin + ???
• + Dietary supplements
• + in my case reduce the effect of unmethylated MGMT …

What combinations can fit in my case?

If there will be a second operation, what is the best way to build a more effective treatment with the information already available?

I think there may be several options:

A) Radiation therapy may be prescribed.

I will do the following:

1) Adjuvant therapy Temozolomide + reducing the effect of unmethylated MGMT (Levetiracetam, Fluoxetine, Valproic Acid + ???)

2) I will add drugs that will increase the tumor sensibilization to radiation therapy.

What exactly to add and in what doses in my case?

 

B) They may refuse the radiation therapy and prescribe chemotherapy.

What is the best way to start chemotherapy? Should I continue Temozolomide on the metronomic schedule or change something?

I have a great need to find a specialist, an experienced person with whom there could be a personal connection during treatment. Can you help with this, Stephen?

Also, I really want to help in the development of the project, how can I donate?

Thank you very much for your opinion and support.

P-Selectin Study

 A study that caught my attention with impressive results in vivo albeit mice. They inhibited the p-P-Selectin protein to achieve the results. I found many supplements in my research reducing P-Selectin (EGCG, Melatonin, Lipitor, Resveratrol, Boswellia, etc). What was interesting I found is all the drugs tied with P-Selectin all dealt with inflammation. Sure enough, I found diets such as the Paleo, Low Fat, and Mediterranean diets reduced P-Selectin. I also found a study that correlates P-Selectin to cholesterol levels (LDL) as well as inflammatory responses to exercise.

Study:

https://www.timesofisrael.com/israeli-scientists-stop-brain-tumors-in-mice-say-may-cure-a-deadly-cancer/?fbclid=IwAR0mxsbykw5w5mE33zAgUCO1x3cn6BRXAQjZ5Jb_F3w255JltJ60FcEhQNw

Diet impact:

https://pubmed.ncbi.nlm.nih.gov/11412051/

Impact of Edema:

https://pubmed.ncbi.nlm.nih.gov/10670575/

Exercise and LDL correlation of P-Selectin:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590908/

Chloroquine supplies - help please

 Hello friends,

It seems to be that supplies of Chloroquine have now completely dried up in the UK (I'm not sure whether it is beause there is no international travel, Brexit is causing problems, or it has been bought up by those believing it offers COVID-19 protection). Can anyone please help me source it somehow? Happy to message privately. I have a grade III anaplastic astrocytoma, currently showing no growth following resection 18 months ago. I have been taking it continuously until the wholesaler told our pharmacy that they didn't have any more and didn't know when it was next due to arrive.

Any help would be HUGELY appreciated.

Stuart

doctorsjgf@gmail.com

Green tea differences ?

 Not sure whether there is any research looking into this but until recently I have been using Teavigo Green Tea Extract 90% EGCG, 30 Veg Capsules by Swanson but these have been out of stock. I have started taking a different preparation (which has higher EGCG): https://www.british-supplements.net/products/clean-green-tea-extract-polyphenols-916mg-catechins-748mg-egcg-420mg

But I wondered whether there was anything particular about the TeaVigo preparation that made it better for accessing the brain?

Best wishes all,

Our story/ 4years OS

 My husband was diagnosed in  September 2016 at 38 years with GBM IV in frontal lobe, 8cm diameter size. He lived 4 years and 2 months from diagnosis.

I remember over 4years ago I was desperatly looking for the cure for him, some knowledge and hope.

With my medical background I felt that we have to take risks, that with standard care we will get standard results  - this website was an incredible source of knowledge plus Ben Williams, plus Mustella fundation, plus Inspire forum. I want to share our story.

Subtotal resection on October 2016. GBM IV, Wild type, methylated. Then standard protocol temodal and radio for  6 weeks. 

Before radiotheraphy he was put on valproic acid 1g twice daily (without epilepsy). Right before radio he was in ketosis (not eating for 36h) and during Stupp protocol on very strict keto diet. During this time we add some repurposed drugs - metformin, chloroqinine, disulfiram, keppra, cimetidine, celecoxibum, alfadiol tried to decrease dexamethazone as much as possible. Boswellia, curcumin, green team from the very begining. 3 months after completing this protocol he had huge pseudoprogression - maybe due to all this stuff. But our oncology departament kept him on TMZ.

He also had immunotheraphy from Jan2017 - hypothermia and NCV then DCVax and later also Keytruda.

A lot of tiny steps. For example I was trying to find studies for which types of bateria types in gut microbiome the response for Keytruda is better and we were suplementing them. 

During first year he also started nasal inhalations with perillyl alcohol. Also ECCG hat. He tried DCA, Sativex.

He had over three years without signs of disease. He got back to his work.

Then Dec 19 progression- second surgery, stereotacitic radio, temodal rechallange, lomustine without good results.

I want to thank Stephen for his commitment and energy he put into this site and all of you who share experiences with this disease. 

I am in awe what human can bare and what a gift life is.

Thank you. 

Patricia

Mebendazole + temozolomide phase 1 trial results

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817892/

Mebendazole and temozolomide in patients with newly diagnosed high-grade gliomas: results of a phase 1 clinical trial

This was a phase 1 safety and dose finding trial rather than an efficacy trial, but could be some useful info here.

Intranasal perillyl alcohol + low carbohydrate diet

 Adjuvant effect of low-carbohydrate diet on outcomes of patients with recurrent glioblastoma under intranasal perillyl alcohol therapy

"Results:

In the 1-year follow-up, the POH/LCD group showed a 4.4-fold decrease in the proportion of patients who needed treatment with corticosteroids, as well as a reduction in tumor size and peritumoral edema, as compared to the POH group. While 75% of patients undergoing POH treatment experienced seizures, this fraction was reduced to 56% in the POH/LCD group. A 2.07-fold increase in the proportion of patients with stable disease, along with a 2.8-fold decrease in the proportion of patients with TP, was seen in the POH/LCD group."

POH = intranasal perillyl alcohol

LCD = low carbohydrate diet

TP = tumor progression.

View full study here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710475/

Dexamethasone limits benefit of Immune checkpoint blockade

 New study published in clinical cancer research:

Concurrent Dexamethasone Limits the Clinical Benefit of Immune Checkpoint Blockade in Glioblastoma

https://pubmed.ncbi.nlm.nih.gov/33239433/

from the abstract:

Results: Despite the inherent responsiveness of GL261 to immune checkpoint blockade, concurrent dexamethasone administration with anti-PD-1 therapy reduced survival in a dose-dependent manner. Concurrent dexamethasone also abrogated survival following anti-PD-1 therapy with or without radiotherapy in immune-resistant CT-2A models. Dexamethasone decreased T-lymphocyte numbers by increasing apoptosis, in addition to decreasing lymphocyte functional capacity. Myeloid and natural killer cell populations were also generally reduced by dexamethasone. Thus, dexamethasone appears to negatively affect both adaptive and innate immune responses. As a clinical correlate, a retrospective analysis of 181 consecutive patients with IDH wild-type GBM treated with PD-(L)1 blockade revealed poorer survival among those on baseline dexamethasone. Upon multivariable adjustment with relevant prognostic factors, baseline dexamethasone administration was the strongest predictor of poor survival 

Conclusions: Our preclinical and clinical data indicate that concurrent dexamethasone therapy may be detrimental to immunotherapeutic approaches for patients with GBM.

The GL261 referred to is a mouse model of glioma.

Blockade Strategy Feedback

 Hello, everyone!

I was diagnosed in May 2019 with GBM and I have completed SOC in Apr. 2020 (Total resection, 42days Chemo/Radiation, and 6 months maintenance chemo). I have done a lot of research on supplements and medications as well as reviewing many promising techniques to stop GBM. One, in particular, had caught my eye which is the CUSP9 protocol. I like this protocol because it attempts to stop GBM in its tracks not just slow or delay things until a recurrence. In addition, I find the results from this study to be one of the best and I believe the strategy used to attack a recurrence is very logical by blocking all the known survival pathways of GBM. I feel that current strategies only partially attack GBM and because of its adaptive characteristics only delays or slows down the inevitable. Cutting off survival paths seems the best strategy until something more profound is developed for people with GBM.

I devised this because it is a helpless feeling treatment is over without much to prevent a recurrence, cocktails are either partially attempting to stop GBM or there is no rhyme or reason to them, dosing strategies do not follow the research, and posted research used in cocktails does not come from peer-reviewed information.

I do not have access to prescription drugs like some people to be able to copy the CUSP9 protocol if I ever have a recurrence or for the newly diagnosed protocol. So I tried researching supplements to see if I could find a supplement-based comparable solution. Unfortunately, when supplements are tested in studies, there is little information on the survival pathways impacted by supplements in the study. I had to reassess my strategy at this point.

I did notice supplements did have common terms in the studies such as proliferation, apoptosis, etc. So I went through many studies and found 9 common mechanisms referenced in the studies as shown.

So I went through studies (NCBI) on many popular supplements used in many "cocktails" and identified the mechanisms impacted by the supplements. I came up with this:

I chose a list of supplements which should provide a blockade to all the mechanisms. I also chose redundancies of each mechanism as I suspect there are many pathways behind these mechanisms. To give a validation to my blockage strategy, I researched Ben Williams protocol he uses to see what mechanisms his protocol covers. I was surprised to find this

His protocol impacts all the mechanisms I found and he also has redundancies in each mechanism of the blockade.

Another argument for this is my oncologist informed me in March of 2020 I had a tumor remnant leftover from surgery 2.5cm in size at the largest diameter with no metabolic activity(contrast and spectroscopy). He thought it was swelling but the MRI with spectroscopy verified as a tumor remnant. This was a shock because I was told by the surgeon I had a complete resection. I was told the only way to get rid of it was removal during any additional surgeries I may experience and since there was no metabolic activity, it would be monitored. In my July MRI, the remnant was 1.8cm in size with a "significant" reduction in blood flow to the original tumor area. In my last October MRI, it was at 1.0cm with more "significant" reduction in blood flow (no metabolic activity). 

So my questions are these:

1. My oncologist attributes the reductions to SOC. However, he admits never seeing such a positive result as this. Could this be the result of SOC, my blockade, or something else?

2. Does anyone see limitations in this or recommend improvements?

Thank you for your feedback.

Regards,

Eric

Questions for newly diagnosted (Melatonin, Chloroquine, Celebrex and NO)

 Hi everyone,

I'm so grateful to have found this blog to give me hope for my sister.  Thank you so much Stephen to have create this. 

She's been diagnosed recently with glioblastoma (Methyled). She's starting her treatment in a couple of days and I have some question:

Melatonin:

My sister is set to have 6 weeks of radio/chemo (TMZ). Melatonin needs to be taken at night but will there be enough in her system to have an effect during the day when She's receiving the radio/chemo? 

Open mind NO or doctor: 

Also, is there anyone who had good luck to find an open mind about supplements and medications that we want to add to her protocol? We are in Canada (Montreal).

Chloroquine: 

If I can't find any doctor willing to prescribe it, is Artemisinin a good plan B? If so, what dosage would be best?

Celebrex:

If for the same reason I'm not able to find a doctor, is Boswellia extract a good plan B?

thanks a lot for your help.

frederique

Lomustine hair loss (alopecia) experience

Hi all

Wondering if anyone who has taken lomustine or CCNU experienced hair loss or low-grade alopecia as a result. If so, could you share the experience, how much loss, how long did it take for hair to grow back, etc.

Thanks!

Expanded Access Protocol for PVS-RIPO (modified poliovirus) treatment for GBM

 This just posted on clinicaltrials.gov on Oct 23:

https://clinicaltrials.gov/ct2/show/NCT04599647

EAP for the Treatment of Glioblastoma With PVSRIPO

scroll down to bottom of the above link for contact info

Treatment options for a first recurrence of GBM

Hi everyone,

Few questions regarding my mother, who unfortunately has had a recurrence of her Glioblastoma. 

BACKGROUND

In August 2019, the Neurological Institute of McGill University (Montreal, Canada) discovered the tumor. My mother had a full resection in September 2019. Pathology : Glioblastoma grade 4, IDH1 wild type - MGMT unmethylated.

After the surgery, the Neuro team has put her on their M-HARTT STUDY https://clinicaltrials.gov/ct2/show/NCT02780024 - which means having condensed radiotherapy (4 weeks) with TMZ, then TMZ for 6 months and Metformin (850) on a daily basis. 

My mother and myself have been very inspired by Ben Williams, this blog, the Surviving Terminal Cancer documentary and Stephen/Ben Williams documents https://virtualtrials.com/pdf2017/treatment_options_gbm_2017.pdf

We've added repurposed drugs and supplements to her diet, which I've listed below.

My mother recovered well from the operation of September 2019, being back to her 100% during the summer and having a clean MRI in July. 

Her MRI of September showed a mass of 2.5cm appeared in her brain. Neither the neurosurgeon, nor the oncologist knew whether it was radio-necrosis or a recurrence. We decided to wait for a month to see how it progressed, adding 4mg decadron to her medications. October 2020, the mass had grown 8mm, so we decided to go into surgery. 

My mother was operated 2 days ago, the surgery was done using 5-aminolevulinic acid (ALA) - which has only very recently been approved in Canada. She's well recovered from it thus far, she's still in the hospital. It seems they've removed most of the tumor, although the 5-ALA technology showed there were small cancer cells left.

We're currently waiting for the pathology from the lab and we'll also send the tumor to Foundation One. I know the results from both these analysis will guide us for the next steps, but I wanted to turn to this blog community - which I highly respect and estimate - to get all the knowledge to navigate through the next steps for this fight against GBM. 

Here are my questions:

1) What are the treatment options for this first recurrence and which one would you recommend?

2) Are there specific questions I should ask regarding the pathology and the results from Foundation One ?

3) From the list of repurpused drugs below, any of them you'd recommend we cut out or we add ?

4) Do you think CUSP9 would be appropriated in this situation and/or any other repurposed drugs? 

5) Would it be a good idea to consider Ben William's approach to chemo, i.e. BCNU chemotherapy with tamoxifen, verapamil, Accutane ? 

LIST OF MEDICATIONS AND SUPPLEMENTS

- Temozolomide (from Octobre 2019 to May 2020)

- Celebrex (from October 2019 until now)

- Melatonin (from October 2019 until now)

- Vitamin D (from October 2019 until now)

- Metformin (from October 2019 until now)

- Keppra (from October 2019 until now)

- Pantoprazole (from October 2019 until now)

- Atorvastatin (Summer 2020 until now) 

- Silibinin extract (Spring 2020 until now) 

- Selenium  (Spring 2020 until now) 

- Omega-3 Fish Oil Extract (Spring 2020 until now) 

- Coriolus versicolor extract PSK (Spring 2020 until now) 

- Curcumin with Peper - longvida (Spring 2020 until now) 

- Maitake-D mushroom extract (Spring 2020 until now) 

- Reishi mushroom extract (Spring 2020 until now) 

- Green Tea Extract (Spring 2020 until now) 

- Soy Isoflavones (Spring 2020 until now) 

- Resveratrol (Spring 2020 until now) 

- Boswellia Serrata (September 2020 until now)

- Tumeric with peper (October 2019 until now) 

- Green Tea (October 2019 until now) 

Many thanks for taking the time to read this,

Bertrand 

P.S. For the French speakers/Canadians out there, there was a Radio-Canada (CBC) news piece about McGill's research for a new treatment against GBM - the  ZR2002 molecule - where my mother was featured (we've been encouraging their research):

https://ici.radio-canada.ca/nouvelle/1469050/maladie-orpheline-meurtriere-interesse-pharmaceutiques

https://pubmed.ncbi.nlm.nih.gov/31540977/

Lab study points to ketogenic diet as not effective for slowing glioblastoma growth?

 I spotted this, and wondered whether there are any implications for the theory that ketogenic diets can help stop glioblastoma tumours growing?

Although it's only on cells and mice, it doesn't look good for the ketogenic diet...

Glioblastoma Utilizes Fatty Acids and Ketone Bodies for Growth Allowing Progression during Ketogenic Diet Therapy

Thoughts?

18 year old APXA 2nd recurrence after treatment, immunotherapy optivo with radiation next week

 Hello and thank you for creating and adding me to this blog. Sorry for the long post.

My 18 year old son is battling a recurrence of APXA a rare high-grade brain tumor. He just had his 3rd brain surgery on August 27. This one they had to leave tumor behind due to location. This week has been tough, he is having lots of issues with spelling and writing and word finding and is frustrated, also right hand shaking when using it a lot and also very tired. The tumor came back only a little over a year after last surgery on Feb 14, 2019. He had proton radiation with TMZ and later a Mek inhibitor. Stopped TMZ as things looked good and blood counts were low.

His first surgery was for seizures as his tumor was stable for many years. It was total resection and path ganglioglima grade 1. We did not even have mri for 7 months, but when we did there was a new tumor, this one also total resection came back as APXA. EML4-Braf fusion (have not found anybody with this one) CDKN2a/2b deletion and tert mutation(this was new) When we found the recurrance on June 9, we swtiched from Mek inhibitor to a trial for 2nd generation Braf inhibitor TAK-580 but while he felt great on it the tumor grew like crazy. We went from nothing on March 9, to 1cm by 8 mm on June 9 and 3 by 4 cm August 26 day before surgery.

They want him to start PD-1 inhibitor immunotherapy along with stereotactic radiation next week. We are looking at also doing custom peptide vaccine, being offered a company in Mexico, they take tumor tissue to tempus they run genetic sequencing and then created a vaccine to be given along with immunotherapy.

He is clearly suffering from inflamation post surgery as he is having lots of issues he did not have before. He is super weak, especially right side( hand shaking on and off ) sleeping a ton. Started to have headaches this week, never had them before. I am scared on inflation immunotherapy causes.

I had him on 

longvida curcumin 400 mg tab curcubrain, boswellia extract 65% 500 mg amandean, nordic naturals ultra omega 3, papay for platelets, B complex 2 times a week his pee was neon, D3 gels 5000 but only 1 a week and probiotics daily. He also eats waffles made from flax and chia egg with lentil flour, buckwheat flour and quinoa flour with manuka honey and crackers with home made raw almond, brazil nut, pumpkin seed and hemp seeds and peanut butter. Sprouted bread toasted with garlic. Smoothie one a day cup of wild blueberry with brocolli sprouts, avocado and cacao and turkey tail mushroom powder.

I think I need higher dosages of these things from what I am reading

4 caps of longvida, should I switch brands? and on empty stomach

8 caps of boswellia not 1 like before

2 caps of rans-pterostilbene, we did not do this before I got the relentless improvement 100 mg

ultimate omega2x will give him 2150 mg omega3 and 1000iu D3, should I do more than 1 serving?

I got trans-pterostilbene and started him on it this week, i also have ashwagandha but not sure if that is needed. 

I really want to do cannabis we are in California right now and he has a card, San Francisco, if anybody can advise, would be great. We are here for another week.

Has anybody seen this type of tumor and success treating it when this aggressive?

Has anybody done neoantigen vaccine or know of someone who has we are looking at this https://clinicaltrials.gov/ct2/show/NCT04509167?term=tijuana+and+neoantigen&draw=2&rank=1

We are working with Dr. Kesari on this has anybody here worked with him.

He is also advising we do metformin, statin with all of this and then also add CDK inhibitor and mTor or Mek inhibitor. I am not sure how much his body can handle. He is 5ft 9 and 120lb now was down to 109 while on TMZ.

I welcome all advice, trying to find the right balance of what to do. He can swallow anything so pill number size not an issue. But hates trying new foods and is a super picky eater especially with healthy things and veggies, he loves hamburgers and cheetos and corn chips. I do give him grass fed 93% burgers, whole wheat buns and organic everything.

If you were able to do immunotherapy with supplements/repurposed drugs/any kind of other treatment and had success please share what you did.

Thank you again to everybody here and forgive me if some of this is confusing.

Julia

Urgent help needed - Butterfly Glioblastoma

September 12, 2020

Hi Stephen & All,

Seeking your help relating to my Mothers Brain Tumor treatment, please help with the treatments, procedures and medicines. We are in India and we have very limited access to new and emerging treatments and hardly in trails for Glioblastoma.

My mother (Age in 60's) diagnosed with Brain Tumor on April 2020, had first surgery in last week of April 2020, didn't receive any biopsy report till July and no other(Radiation & Chemo) treatment due to COVID lock down in India, July biopsy report after first surgery just mentioned possible high grade glioma, She recovered well after first surgery but in July she started having seizures and MRI in July showed recurrence and she had second surgery in first week of August but this time shes having issues after surgery due CSF leak and till now we trying to get it fixed before going for radiation, in the mean time we are looking for options we have to stop tumor growth, I think we are getting late in radiation treatment, I think if we can start chemo before radiation it may help.

As per her CT scan today her tumor is growing very fast.

Biopsy details from last month below

On IHC - The tumor cells are positive for GFAP, IDH-1 and p53, Ki67 index very high (30%).

Impression - Histological features are suggestive of  Glioblastoma, IDH-1 mutant, WHO grade IV, Corpus callosum.

August MRI - Recurrent parietal butterfly Glioma.

Please help.

Thank you

Vins

Managing skin side effects of Optune

 Prevention and Management of Dermatologic Adverse Events Associated With Tumor Treating Fields in Patients With Glioblastoma

PDF available for free download here:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399624/pdf/fonc-10-01045.pdf

Chloroquine phase 1 trial

 Chloroquine combined with concurrent radiotherapy and temozolomide for newly diagnosed glioblastoma: a phase IB trial

Abstract

Treatment of glioblastoma xenografts with chloroquine results in macroautophagy/autophagy inhibition, resulting in a reduction of tumor hypoxia and sensitization to radiation. Preclinical data show that EGFRvIII-expressing glioblastoma may benefit most from chloroquine because of autophagy dependency. This study is the first to explore the safety, pharmacokinetics and maximum tolerated dose of chloroquine in combination with radiotherapy and concurrent daily temozolomide in patients with a newly diagnosed glioblastoma. This study is a single-center, open-label, dose-finding phase I trial. Patients received oral chloroquine daily starting one week before the course of chemoradiation (temozolomide 75 mg/m2/d) until the end of radiotherapy (59.4 Gy/33 fractions). Thirteen patients were included in the study (n = 6: 200 mg, n = 3: 300 mg, n = 4: 400 mg chloroquine). A total of 44 adverse events, possibly related to chloroquine, were registered including electrocardiogram QTc prolongation, irreversible blurred vision and nausea/vomiting resulting in cessation of temozolomide or delay of adjuvant cycles. The maximum tolerated dose was 200 mg chloroquine. Median overall survival was 16 months (range 2 - 32). Median survival was 11.5 months for EGFRvIII- patients and 20 months for EGFRvIII+ patients. A daily dose of 200 mg chloroquine was determined to be the maximum tolerated dose when combined with radiotherapy and concurrent temozolomide for newly diagnosed glioblastoma. Favorable toxicity and promising overall survival support further clinical studies.

https://pubmed.ncbi.nlm.nih.gov/32866424/

Promising Pathway Act: The most important bill ever introduced into congress for brain tumor patients needs your support!

Quote from Musella Foundation website:

This bill - if passed - will allow you to get access to many treatments quickly! It will increase the amount of research - particularly of combination cocktails, and may even help keep the prices of new drugs down!

Please visit https://virtualtrials.com/activism.cfm to find out more.

You can follow status updates here.

Unfortunately, I'm not a US resident so I can't contribute directly to get this bill passed but I hope I can contribute by sharing. 

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."

Recurrence: VAL-083 or CCNU? Keytruda?

Hello all,

A few questions for my friend who is unfortunately having a recurrence.

1) Following surgery, is it better to go with VAL-083 since he is unmethylated or stick with CCNU since that is more the standard protocol for recurrent GBM? Any experiences with VAL-083 out there? 

2) Is the tumor genetic sequencing provided by the University of Pittsburgh considered the best, or should he request a Caris report?

3) Have any of you or your loved ones tried Keytruda pre-operatively to activate the immune system? How did you feel about it? Any significant side effects? 

For background purposes:

My friend was diagnosed in August 2018 - age 48. He had a total resection followed by SOC, Optune, supplements and 11 months of TMZ. A second tumor developed slowly  in the occipital area and was removed in November 2019. Unfortunately, the tumor recurred at the second site shortly after the surgery. However, following a second course of radiation and TMZ, it remained stable for six months. Avastin was used to control swelling and reduce tumor growth. In addition, a PARP inhibitor, Olaparib(Lynparza), was added after SOC as indicated by the genetic analysis. The tumor was unmethylated and IDH mutated.

The second tumor location recently started showing activity again. So a third surgery is planned in the next couple of weeks. We are looking at which chemotherapy to pursue afterwards and whether to use Keytruda before or after, as well. We have a friend that had a very positive response following a recurrence on the VAL-083 MD Anderson trial. He was unmethylated, as well, and has had clear scans for six months since completing VAl-083.

My friend was advised to stop using Avastin, although we have seen some studies that continued to use it in combination with CCNU. He is now age 50 with no deficits. He continues to use Optune. Any thoughts, experiences or pertinent studies relating to the chemo options for recurrence, VAL-083 and Keytruda would be greatly appreciated. We are grateful for the combined wisdom of Stephen and this community.

Best, 

Evelyn

Questions on my mom's drug cocktail(GBM Patient)

Hi folks/Stephen,

My mom was diagnosed with Glioblastoma(GBM) in September 2017. Following is the details of her GBM:

Her last scan was 6 months back and showed no growth, choline elevation or perfusion. We're yet to get another scan done in a few days from now.

She has been on the following supplements for almost the past three years. She started Chloroquine and Valganciclovir a year back. I had the following questions to ask, would be great if you can help me with the answers:

1. Is it safe to take these supplements for such a long duration? Are there any supplements that you would suggest that need to be stopped/paused? My concern is specifically with supplements like Valgancyclovir and Chloroquine, given the fact that they are not naturopathic/nutritional supplements?

2. Is there any supplement that you would suggest adding to my mom's drug cocktail? I've shared details of my mom's biopsy/genetic mutation below my mom's supplement list.

3. Are there any doctors/integrative oncologists that you would suggest consulting? I have been consulting Patrice Surley so far for my mom's treatment beyond the standard of care.

Supplements

Supplement	Cap count per day
Boswellia Serrata 500 mg	8
Keppra 500 mg	2
Chloroquine Phosphate 250 mg	1
Valganciclovir 450 mg	1
Curcumin + Piperine 1 g	4
Longvida 400 mg	2
Metformin 500 mg	3
Quercetin 865 mg	4
Resveratrol 200 mg	2
Bromelain 500 mg	6
Reishi 1g	2
Artemisia 1 g	2
Ashwagandha 500 mg	1
Selenium 200 mcg	1
Vitamin A + D + K2 - 5000 IU	1
Molybdenum Glycinate 1g	1
Celebrex 200 mg	2
Green tea extract 500 mg 40% EGCG	2
Juice from 5g of Ginger	1
Garlic 2 cloves	3

Details of the genetic mutation of my mom's tumour

Following are the details from her biopsy

IDH1 and IDH2: Not detected
CHR 1p and CHR 19q: Negative for CHR 1p and CHR 19q codeletion
Methylation: Detected
Ki67 labelling index is 15-20%

Following is her FoundationOne report:

Genomic Alterations Identified
EGFR A289V – subclonal, amplification, EGFRvIII
PTEN I67T
CDKN2A/B loss
TERT promoter -124C>T

Additional Findings
Microsatellite status MS-Stable
Tumor Mutational Burden TMB-Low; 3 Muts/Mb

Additional Disease-relevant Genes with No Reportable Alterations Identified†
IDH1(-ve)
PDGFRA

Following is the diet and supplements that my mom is taking:

Diet: Ketogenic Diet/Low Carb high-fat diet

I look forward to hearing from you all!

Reirradiation + ketogenic diet + intermittent fasting, randomized trial

ERGO2: A prospective randomized trial of calorie restricted ketogenic diet and fasting in addition to re-irradiation for malignant glioma
https://sci-hub.tw/https://www.redjournal.org/article/S0360-3016(20)31308-0/pdf    (full PDF from sci-hub)

https://www.redjournal.org/article/S0360-3016(20)31308-0/pdf   (link to journal abstract, full PDF requires a payment)

Half the patients were randomized to re-irradiation plus standard diet (SD), the other half were randomized to re-irradiation plus ketogenic diet plus intermittent fasting (KD-IF).

• PFS6 was not significantly different between the two groups (KD-IF: 20%, SD: 16%). 
• Similarly, no difference in PFS, local PFS6 and OS was observable.
• Explorative analysis revealed that patients of the KD-IF group who had a glucose of less than the median (83.5 mg/dl) on day 6 had a significantly longer PFS and OS compared to those above the median

Grade II Astrocytoma (IDH1 Mutant) treatment plan

Hi Stephen and all,

Thank you for allowing me to create this thread. I am a 31 years old male from Australia.

I recently got diagnosed with a Grade II Astrocytoma with histopathology report as follow;

Clinical Notes: Incidentally found left Insular region glioma

Mitoses: 0/HPF

Immunohistochemical Stains: Block 1

Ki67: 1%

How estimated: Visually and IDH1, Ki67 dual stain

IDH1 R132H: Positive

ATRX:  Lost

P53:  10%(moderate/strong staining)

EGFR:  Negative

Other Positive:  GFAP, PHH3 highlights 2 mitotic figures, however, it remains possible that these cells are not tumor cells hence it shouldn't be used in grading

MGMT promoter Methylation: If clinically indicated. Block 1 Tumor 60%. Patient Agreement required.

I had Gross Total Resection and according to my neurosurgeon, there is no residual tumor left. Size upon diagnosis was around (14mm x 13mm x 10mm).

I had a few questions regarding Histopathology, wondering if you all can help, please?

1) Should I push for a more thorough genetic study on this tumor? Is it worth it at this point in time to get PTEN, MGMT (as it looks like they haven't performed this test) & Ip/19q codeletions? I know it is unlikely for it to be 1p/19q codeleted since it has p53 staining & ATRX loss.

  

2) Why does it mention mitotic figure: 0/10HPF, then goes on to mention PHH3 highlights 2 mitotic figures but 'possibly' nontumor cells? How do they know that they were nontumor cells?

3) Does Ki67 index & P53 values mean much?

My neurosurgeon has advised holding off any chemo/radiation for the time being and adopt a 'watch and wait' approach. I am happy to hold off chemo/radiation too but I do want to start taking supplements and other medication to possibly delay the recurrence. I plan on taking the following supplements and medication (Please tell if I am mental for doing it).

Supplements:

Curcumin (Longvida)

Vit D (4000IU)

Fish Oil

Vit C (4g)

Magnesium

Resveratrol

Green Tea Extract

Selenium

Milk Thistle

Sulforaphane (From broccoli sprouts)

ZINC: Should I add this? I read on this forum somewhere that it is not really beneficial for people who have enough Zinc levels in their blood. 

Medication:

Aspirin daily 100mg daily (COX 2 Inhibitor) or should I consider Celebrex?

Melatonin (10g - 15g daily)

Metformin 1000mg daily (Keeping the blood sugar level down)

I am thinking of using;

Metformin 1000mg daily (Keeping the blood sugar level down)

Betablocker (Propanolol)

Low dose Mebendazole (Cycle off every after a month use)

Angiogenesis Receptor blocker

DCA

Clomipramine

Thank you for pointing out Isosidenib and Vorasidenib Steph!

- I am really worried about my glioma acquiring hypermutation, is it possible that Agios inhibitors can turn IDH1 into Wildtype by how they operate? 

- I know no one knows for sure, but is it normal to adopt watch and wait approach for Grade II astrocytoma? 

- Are there any clinical trials I should consider? I can't seem to find any trials on LGGs at the moment.

Thank you so much for taking out the time to read this.

Regards

Ruki

Levetiracetam (Keppra) + standard of care, single-arm phase 2

A pilot study of levetiracetam as a sensitizer of temozolomide for newly diagnosed glioblastoma: A prospective, open-label, phase II study (KBTS-1601 study).
https://meetinglibrary.asco.org/record/189964/abstract

This was reported at the recent ASCO virtual conference.

• Eligible patients were aged 18 years or older and had newly diagnosed glioblastoma with an ECOG performance status of 0-2
• The first dose of levetiracetam was given just after the surgery at 250mg orally twice a day and increased up to 500mg twice a day prior to radiation
• Forty-six patients were enrolled between August 2016 and January 2019
• Median overall survival (OS) was 30.0 months, and median PFS was 15.0 months

This was a single arm trial, with outcomes compared to a historical control group. A median overall survival of 30 months and median progression-free survival of 15 months does seem to be an improvement on historical results. 

For comparison, the unblinded results of the phase 3 DCVax trial (preliminary report based on 331 patients) had a median overall survival of 23.1 months from surgery. The historical control group used by the Korean team that conducted this levetiracetam trial had median OS of 17.5 months.

Quite urgently seeking Suggestions

Hi Everyone,

I have been a long-time reader of this amazing blog that Stephen created and regularly check it for any posts about new treatments or therapies. I am really happy to see that Stephen still occasionally posts new studies and answers some questions. 

I am quite urgently seeking advice on next steps in relation to treatment for my partner (of 18 years), who is a very physically active person and despite everything that has occurred, remains very positive. She is 40 years old.

Background:

We are based in Australia and she was diagnosed in December 2011 (2 days before Christmas!) with a low grade Astrocytoma in the left Temporal Lobe. 

2012 (February): She underwent craniotomy that resulted in a subtotal resection – it was an awake craniotomy owing to the tumour’s location near important speech areas.

Histopathology of the sample was unfortunately not very detailed and only confirmed a Low Grade Astrocytoma with a very low KI67 of < 1%

2015 (February): The lesion increased in size over the years (pretty much doubled) to 55 x 34 x 49mm – so a second surgery was performed that again resulted in subtotal resection.

Histopathology results showed – Low Grade Astrocytoma, IDH1 Mutated.

A retrospective FoundationOne profile was obtained on this sample in 2017 and only showed 2 mutations: IDH1 (R132H) mutated and TP53 (R175H).

2017 (September): The tumour continued to grow and extended into the frontotemporal region and insula. Another Surgery was conducted in two sessions due to expected length, and a large portion of tumour from the temporal and frontotemporal regions was removed, as well as a small portion from the insula.

Histopathology results showed – IDH1, 1p/19q co-deletion, ATRX lost, TP53 Mutated, KI67 of 2%

A Caris profile was also obtained which also showed that the tumour was not MGMT methylated – although after asking Stephen about this at the time, he said that MGMT was a bit of a hit and miss due to the heterogeneity found in tumours – so we remained hopeful that MGMT may still be methylated in most of the tumour given it is typical of low grade gliomas.

 

* The Caris report conflicted with the histopathology and showed ATRX intact.

2018 (January): Managed to get Bayer to sponsor my partner to take part in their IDH1 Inhibitor trial (BAY1436032), went to L.A and got knocked down at the last minute due to not completely satisfying their RANO requirements!

(September) Sought out the top neurooncologist + radio oncologist team in Sydney and she started IMRT then moved on to a round of TMZ which finished in early 2019.

2019 : MRI’s showed decent shrinkage in the tumour volume for the first 6 months then stable.

2020 (January) : MRI showed slight enhancement in the original temporal lobe resection cavity + strangely an enhancing nodule on the right ventricle. These were determined by the neuro and radio oncologists to be late radiation treatment effect and thought that they would resolve.

(Late February) MRI showed the enhancing nodule in right ventricle shrinking a bit, but enhancing area in temporal lobe cavity growing a bit. Still determined to be late treatment effect.

(June) : MRI – ALL HELL HAS BROKEN LOOSE. There are now another 3 large enhancing lesions – one in the right Frontal lobe, with a small one behind it, one in the Left ventricle (looks like a cherry sitting on the ventricle wall) and a much larger enhancement of in the original temporal resection cavity.

Needle Biopsy – a needle biopsy has just (yesterday) been performed on the right frontal lesion to get a better understanding of the makeup of the new lesions. We are currently awaiting the results and will also hopefully be getting a Caris or FoundationOne genetic testing on the sample.

The surgeon mentioned that he could already see an increase in size since her last last (less that 1 week prior). So this is a very fast growing tumour/s.

Proposed Initial Treatment

Her neuro-oncologist and radio-oncologist have suggested that she begin (as soon as possible) with CCNU + Procarbazine – and possibly Avastin for the swelling.

 Current Medications (all anti-epileptics):

- Epilim (Sodium valproate)

- Fycompa (Perampanel)

- Lamictal (Lamotrigine)

- Briviact (Brivaracetam)

- Frisium (Clobazam)

Suggestions

I would be extremely grateful if anyone can:

- provide their thoughts on the proposed treatment

- make any other treatment suggestions

- suggest anything that could possibly increase the effectiveness of the   
   suggested treatment

- point out any pitfalls or things to be aware/weary of whilst on the treatment

- suggest any promising potential trials or treatments anywhere in the world

- suggest any cokctails that they have used with this treatment that have 
  resulted in better outcomes + better tolerability

The rapid change from a fairly stable low grade astrocytoma really did catch us (and her doctors) off-guard and I would be very appreciative of any advice or suggestions that anyone could kindly offer.

Thanks to you all.

Ryan.

New Note:

Just today my partner was told that she has extremely low levels of Vitamin D. Strangely enough, she has been really craving oily fish for the last 3 months and has been eating smoked trout and smoked salmon almost daily - obviously not enough to build up sufficient levels. The 3 month craving of Vitamin D strangely coincided with the new lesions showing up and their extremely fast growth.

I wonder if dramatically increasing her Vitamin D level may slow the progression? She has started taking 4000 IU and intends to keep it up every day.

Can anyone comment on this level of Vitamin D, would you up it even further? And are there any caveats with regards to Vitamin D supplementation.

Also, it there a particular way to rapidly raise the levels in the blood?