This type of research adds to our understanding of how Glioblastomas grow. They found that the mutated EGFR (Epidermal Growth Factor Receptor)  can not distinguish between the 7 different proteins that bind to it - the mutated EGFR sees them all as if they are Epidermal Growth Factor which causes the cell to grow and divide quickly.  Whereas a normal wild type EGFR some of the proteins that bind to the receptor inhibit growth.  This may explain why just using an EGFR inhibitor by itself doesn't really work with Glioblastomas.   It may block the growth signal, but it still doesn't allow the growth inhibitors to work normally.  So the next generation of EGFR targeting drugs have to figure out a way to not only block the growth signals but to trigger the inhibitory signals as well!  Excellent work!

This is a very interesting video about this man's battle and how he dealt with the stress of a diagnosis of a malignant brain tumor and then the recurrence of the tumor.

 These results are interesting. They had a complete response and 2 durable partial responsed out of the 30 patients in arm d of the trial (which is the highest dose arm).  It is very hard to get a complete response in recurrent glioblastoma.  The good part is this drug, Selinexor, is approved for other types of cancer, so can be used off label for brain tumors now (although cost may be a problem).  By itself it obviously is not good enough but may play a part in a rational combination therapy.  They examined the gene expressions that changed as a result of the treatment with this drug.  This opens the door to experiment with drugs that target the expressions that increased after Selinexor. All drug research should try to measure these gene expression changes.

 This is fascinating.  They found that the placement of arrays makes a huge difference. Most of the recurrences were outside of the area of the brain that got a high dose of Tumor Treating Fields.  This supports the concept that the array placement should be updated at the time of recurrence to cover the new areas or perhaps should be designed at the start of treatment to cover the most likely areas of spread as well as the current tumor.

 Very impressive results.  Although it is FDA approved, it is not yet available everywhere. If you are going to have a brain tumor surgery, ask your doctor if they think GammaTile is appropriate for your case and if they have access to it. If they do not use GammaTiles, it might be worthwhile to get an opinion from a surgeon that does use it. There is a list of participating centers at https://gammatile.com/findatreatmentcenter/

Disclaimer - GT Medical Technologies, Inc, the company that makes GammaTile, is a sponsor of the Musella Foundation.

 Take a look at this website.  https://costplusdrugs.com/ Mark Cuban created the company to sell generic drugs at his cost.  A few of the drugs are used by brain tumor patients. For example, Generic Gleevec which usually cost $2,500 for 30 tablets is being sold for $17.10 (plus shipping).  Keppra XR which usually sells for $94.65 is available for $6.30.     Zofran which is usually $160 is now $6.30.   They have 100 different medications.  They do not take insurance but this is usually way less than you would pay for a copay. Check all of your drugs. I found a few that I use and will give it a try.

I already sent a request for them to add Temozolomide and Lomustine.  I did not hear back yet - but it couldn't hurt if a LOT of people requested those drugs! Go t their website and use the contact form!

 They went back and analyzed the results of the big EF-14 clinical trial for Newly Diagnosed Glioblastoma patients of Optune plus Temozolomide vs. Temozolomide alone, broken down by extent of surgery. They divided the patients into 3 groups, those with biopsy only, those with a partial resection and those with a total resection of the tumor.   They found that in all 3 groups, there was a significant survival advantage to Optune.  The survival times I talk about are from the start of the trial, which was about 2-3 months after initial diagnosis. For the Biopsy only patients, average survival with Optune was 16.5 months compared to 11.5 months without Optune.  This is a 43% increase in survival time. This might not sound like much but now that we have so many other options to add, this 43% increase can buy the time needed to try other treatments which may synergize with Optune. 

For the patients with a partial resection, the outlook is somewhat better, 21.4 months with Optune vs. 15.1 months without - a 41% increase in survival. And finally, for those with a complete resection, the median survival with Optune was 22.6 months vs. 18.5 without Optune, for a 22% increase in survival.

 This is only a report on 3 patients and needs more research but looks promising. It makes a lot of sense to use this combination. LITT is an fda approved treatment for brain tumors that is sometimes an alternative to open surgery. It is a minimally invasive surgery where the surgeon makes a small drill hole in the skull and inserts a fiber optic cable that delivers laser energy to kill the tumor. They follow the progress inside an MRI machine. This causes the release of tumor specific antigens into the environment. Your body can then mount an immune response to the tumor and possibly stop the tumor from recurring.   

Pembrolizumab is an immune checkpoint inhibitor which takes the brakes off of the immune reponse.  By themselves, they do not do much with  glioblastoma.  However, there was an earlier report that if you start the Pembrolizumab before a surgery and continue after the surgery, it works much better than starting after surgery. The thinking is that the surgery exposes the tumor specific antigens and the Pembrolizumab revs up the immune system response to that. Without the priming of the immune system, the Pembrolizumab has nothing to work on.  This article talks about the same effect with LITT.  

In the future, we need more work on additional components of a cocktail - perhaps add Optune after the LITT which can continuously kill tumor cells slowly over time, which can prime the immune system, and add Pembrolizumab to enhance that effect.

 VT1021 is an experimental treatment for brain tumors.  Follow the link below to see the mechanism of action and the impressive results of the initial trial. The GBM AGILE trial is the most advanced clinical trial system. It is a learning system where multiple treatments are evaluated against each other.

 This study shows that (at least in the mouse model used) using high doses of steroids reduces the effectiveness of the immunotherapy.    We knew that already. This study confirms the magnitude of the effect and it is large.  This brings me back to why we need the Promising Pathway Act. I keep talking about this but can't get the help we need to get it passed.  In this case, there was a drug in trials many years ago called Xerecpt.    It was to treat swelling from brain tumors, without the side effects of steroids. Early testing looked very good but it failed it's pivotal study.  Only a few patients were able to come off steroids entirely, but all were able to greatly reduce the dosage of their steroids.  At the time, it did not seem worth pursuing it as an alternative to steroids if it still required use of a small amount of steroids. But now with this current study, we see a great value in being able to reduce the dosage of steroids. It will make the immunotherapies work better. And it will greatly reduce the side effects of steroids.  I hate to see pictures of little kids with brain tumor who get bloated from steroids - as well as problems sleeping, increased chance of infections, irritation to stomach, increase in blood sugar, muscle wasting and weakness, skin thinning, emotional problems and eye problems.  As if they did not have enough problems with the tumor. Under the Promising Pathway Act, we could get drugs like this (both Xerecept and the immunotherapy mentioned) approved and try them in combination with immunotherapies and get better results and less side effects. 

This is in adults only.  Unfortunately, the median overall survival is only 15.9 months - worse than a Glioblastoma.

 This technology is readily available in the USA and is FDA approved.  

 This is a complicated study to read.  The shocking data to me is in the supplemental materials.  These show how few patients - especially the elderly - get the standard Temodar regimen.   Over half of MGMT unmethylated patients do not even get Temodar at all. Only 26% of MGMT methylated patients complete the standard schedule of Temodar and 35% do not even get any Temodar.  They did note that if you do complete the entire course of Temodar (which they say is 6 weeks during radiation then 6 months after), you have a much higher overall survival - 24.7 months in unmethylated and 36.3 months for methylated patients.   I do not know if that means there is a benefit of Temodar to unmethylated patients, or just that patients in good enough shape 6 months after radiation to take Temodar will just do better in general. Bottom line - the old standard of Temodar and radiation (without Optune)  is not really good enough and we need to find better ways forward.

 Although this is for pediatric DIPG, if it works, it could be used for any type of brain tumors!

 We received generous donations and are able to reopen the program!  Do not feel bad about asking for help. That is what we are here for. We understand what you are going through and want to help. If you could use the help - apply!

Bevacizumab is an FDA approved treatment for Glioblastoma, which inhibits VEGF (Vascular endothelial growth factor).  By itself, for glioblastomas,  it did not increase overall survival, but it did make people feel better for a longer time - with an increased progression free survival.  It is thought that combining it with other drugs is more rational than using it by itself if the purpose is to extend life.  (It can be used by itself as a super steroid to get rid of swelling). This study reviews the medical literature and reports on which combinations did the best.  Unfortunately, the best combination they found was Bevacizumab plus Rindopepimut. I say unfortunate because Rindopepimut is no longer available.   It is a therapeutic vaccine against EGFRvIII.  It did very well in early trials, but in a large randomized trial, it did not do better than the control group - which was an immune enhancer that is also part of Rindopepimut.  Both groups did better than expected by historical controls, but the way the  trial was designed  resulted in failure and they no longer make the drug.

IF the Promising Pathway Act ever passes, there is a possibility of going back and reviving some of these treatments that "failed" even though they had good results in some patients and did what they were supposed to do. In this case, Rindopepimut was supposed to inhibit EGFRvIII and it did. It helped a little but not enough to get approved by itself. It's real strength would have been as part of a cocktail approach as mentioned in this current study where it says adding Bevacizumab to Rindopepimut resulted in the best results.  I think we need 4 or 5 drug combinations to hit the home run, but to get that far we need access to the components!

 We (The Musella Foundation with the help of our fantastic donors!) helped fund this research project.  They found that just adding a drug that inhibits the main way the Glioblastoma cells move did not really help much. In fact, they found that the cells easily and quickly used a different mechanism to move.  Combining inhibitors of both pathways did help. A lot, but not completely -  a 3rd drug might be needed to target the resistance pathway.  They did find a biomarker in the blood that may predict recurrence of Glioblastoma. More work needs to be done to validate the biomarker and to completely eliminate invasion! Good work!

 This is one of my favorite webinars. Dr Dunn explains his thoughts on how to find the best combinations of treatments for pediatric brain tumors. 

Well worth watching.  It is a little technical - it is like an entire high level college course compressed into an hour or so, so if there is anything you do not understand, we can discuss it in our facebook group (link in the article!)