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Sorry - I did not notice the date on the article! That was old news! At least I know people read this newsletter as a few people pointed out the error!
This edition of the Brain Tumor Guide For The Newly Diagnosed is a huge upgrade from prior version! Only the electronic edition is available now. We will be sending the files to the printer to get a soft cover version in a few days! Please let me know if you spot any problems in the guide! We have a few days to correct it before it goes to printer! IF you order the printed version, we will be sending the old 11th edition of the guide until the new edition is available!
Sitoiganap is a therapeutic vaccine which used to be called Gliovac or ERC1671. This paper presents the results of the expanded access program for the vaccine on patients with recurrent glioblastoma. Expanded access programs are not as controlled as a traditional randomized controlled trial, in that they usually allow any patient to enter - whereas the traditional trials cherry pick those patients who would be expected to do well on the treatment. So these patients would be expected to do worse than the historical clinical trial statistics. Although this is a small study, the results are very exciting. The vaccine more than doubled the median survival to 19.6 months. Other trials are reporting a median survival of about 8 months for recurrent glioblastoma. The 2 year survival rate was 45% which is excellent.
With this data, they asked the European Medicines Agency (EMA) to approve the vaccine for the treatment of Glioblastoma. Strangely the EMA refused and wants more data. Seeing how there were minimal side effects and had very good results in a small group, I feel they should have received approval. Probably the same thing would happen here with our FDA. This is outrageous and we should fight to get the regulations changed. Our Promising Pathway Act is designed just for these types of treatments - it really is too early to tell how well it works, but with no side effects and early indication of success, how could a regulatory agency tell us that they will not allow us access to treatments like this. As with all previously approved brain tumor treatments, we never really find out how they work until after approval and they are used in combinations and on average patients.
This is one of the most important papers of the year. They look at the mechanisms of action of Optune and come up with ideas to improve the effectiveness of Optune. My favorite is where they talk about 5-ala. 5 ala is a dye, approved as Gleolan to be used during brain tumor surgery to help the surgeon tell the difference between tumor and normal brain. The dye accumulates in tumor only. Optune increased the concentration of the dye in the tumor but not in the normal brain, so to start with - combining Optune and Gleolan for a surgery would seem helpful. However, there are new clinical trials going on now where 5-ala is used in a new way called sonodynamic therapy. They give the 5-ala then wait for the tumor to take up the dye, then they treat the tumor noninvasively with focused ultrasound. The focused ultrasound excites the dye causing it to kill the tumor cells. Too early to tell how good it is by itself but imagine the possibility of easily increasing it's effectiveness just by using Optune while waiting for the dye to be taken up by the tumor? They also talk about Optune opening the blood brain barrier letting chemotherapies in that couldn't pass the blood brain barrier by themselves. This opens up a lot of possibilities. They also talk about the immune effects - possibly adding a checkpoint inhibitor may help with that. They talk about the effect Optune has on migration and movement of cancer cells. It slows them down. The problem we have with drugs like Avastin is they cut off the blood supply to the tumor, which causes the tumor cells to migrate towards a better oxygen supply. Imagine if we add Optune - to stop that migration. Perhaps the combination (which is being tested now in trials) could be a home run by starving the tumor cells and stopping them from invading the normal brain.
The best part of all of this is that all of the components are FDA approved and could possibly be used off label. Our patient navigation program is probably the best way to screen all of the possibilities!
This is early research but interesting. If it is true, I doubt it is a major cause as then we would see a geographic distribution of brain tumors that mimics the distribution of Lyme disease cases which we do not see. However, if there is a link, that may be the reason Doxycycline might help brain tumors. Doxycycline is an old oral antibiotic - very safe - that is used in the treatment of Lyme disease which is caused by a bacteria. It is also part of the Care Oncology Glioblastoma Protocol, which is a cocktail of repurposed drugs used to treat Glioblastoma - and which has reported some success!
The NCCN is the most trusted source for treatment information about all types of cancers. They just published their recommendations for pediatric brain tumors. They basically recommend clinical trials for all brain tumors. In an ideal world, I would disagree and try for a cocktail approach with unapproved drugs, but that is impossible for most patients, so the best course of treatment now for pediatric brain tumors is clinical trials. Even for those "curable" tumors - there are clinical trials going on that try to eliminate the long term side effects of treatments.
This is another form of Sonodynamic Therapy - as I mentioned recently, this is one of the most promising new therapies for brain tumors. It is noninvasive, and can be repeated if needed. This trial is https://clinicaltrials.gov/ct2/show/NCT05362409 which is "Study to Evaluate 5-ALA Combined With CV01 Delivery of Ultrasound in Recurrent High Grade Glioma". Eligible patients have recurrent grade 3 or 4 brain tumors including Oligodendroglioma, anaplastic astrocytoma and Glioblastoma! this trial excludes DIPG but the other sonodynamic therapy trial I recently mentioned does allow DIPG.
This article talks about using electric field delivery via implanted electrodes. Interesting to think about the best way to approach these therapies - implant electrodes and a battery, or noninvasively, with arrays. Most patients have to make the decision about Optune early in their journey before they realize how serious their glioblastoma is and at first do not like the idea of shaving their heads and wearing arrays - some refuse to use it at first only to accept it when they realize that their lives are at stake but by then it is too late to even bother trying. Compare that to having electrodes implanted into the brain with possible short or long term complications. Hard decisions.
We awarded 3 more exciting brain tumor research grants today!
The first grant is to help fund a phase 1 trial of a new drug for Glioblastomas (and eventually other brain tumors). It targets Olig2 which is a transcription factor that is used in early brain development then turns off when the brain matures and it is no longer needed. In brain cancers, Oligo2 is turned back on in cancer stem cells and causes the initiation of tumors as well as driving tumor growth, promoting resistance to radiation and chemotherapy and drives invasion into the healthy brain. The theory is that this new experimental drug, CT-179, can inhibit Olig2, and hopefully lead to significantly improved outcomes. It is an oral drug that crosses the blood brain barrier and early lab work was impressive.
The next grant is to help fund a learning health system for brain cancer. xCures created an amazing system that we use for our patient navigation program. It combines artificial intelligence with expert opinions, tumor boards, a regulatory grade registry as well as medical literature to create the learning system. The goal of the learning system is to find the best treatment options for each patient, and to accelerate the development of promising therapies and combinations of therapies. Our grant will help them analyze the effectiveness of the process and improve it. Disclaimer: I own stock in and am a paid consultant to xCures and recused myself from evaluating this grant application. Our entire medical advisory board as well as executive board approved this grant which covers only a small part of the project. We will raise more money for it in the future.
The third grant was to the DIPG / DMG collaborative. We are a foundational partner of the collaborative and I am on their grants committee, so I have a say where our funds go. They have about 24 partner organizations who each chip in money that we use to fund much larger grants than we could each do alone. They have given out a total of over $13 million in grants so far! Although they are limited funding research for pediatric DIPG and Diffuse Midline Gliomas, most of it will also apply to most other adult malignant brain tumors.
This makes a total of 10 brain tumor research grants totaling $405,000 that we (the Musella Foundation) gave out for 2022! We are close to matching last year's total of $427,000, but not yet close to the pre-covid $625,000 we awarded in 2018. Our annual fundraisers have each not done as well as pre-covid yet but we are adding a lot of smaller events. One of our volunteers is hosting a fishing fundraiser on Long Island July 9-17, 2022, in memory of his son, Michael Vincent Clapps, who died of a glioblastoma. For details or to donate - go to https://virtualtrials.org/Claps Please consider hosting a fundraiser for us so we can give out more grants! We have one more very special grant that we approved but are waiting to save up the funds to pay it! And we get frequent requests for more grants - which we have been turning down for now until we can build up our grants fund again.
This was a small, 12 patient study of an experimental treatment which had remarkable results. For DIPG, survival is usually about 8-12 months. With this treatment, average survival was 17 months, with acceptable side effects. This could be a big advance. Of course it is not good enough by itself, but opens up possibilities of combinations with other treatments to be a part of the ultimate cocktail cure. We need to fight for the promising pathway act to get access to these treatments now and to have the technology in place to figure out how best to use these treatments!
This is one of my favorite new treatments. Very elegant. You get a dye injected IV which preferentially concentrates in the tumor. Then focused ultrasound is applied using a helmet like device for a few minutes. This activates the dye which kills the tumor cells. It is noninvasive (other than the injection into the arm) and can be repeated if needed. The Clinical trial for DIPG is now open, and the trial for recurrent Glioblastoma will open soon. I will be watching this closely and wish them luck.
Pinpoint Patient Recruiting is doing another survey of Glioblastoma patients (or caregivers). They pay you $75 for your time to take a 30 minute online survey! They also are a sponsor of our organization. See details below!
We (the Musella Foundation) are also looking for long term survivors (over 2 years for Glioblastoma or DIPG / DMG patients or 3 years for other tumor types!) to post their survivor stories on Virtualtrials.org. Reply to this email for details!
This may affect you - so read this! Brain tumor patients are usually given a drug to help prevent stomach problems from the steroids they use. Most commonly it is a proton pump inhibitor such as
This letter to the editor to Neuro-Oncology practice raises a very serious issue. These drugs may cause resistance to Temodar (Temozolomide) by increasing the levels of an enzyme called ALDH1A1. If this enzyme is high, the average survival for a patient with a methylated MGMT GBM is 14.6 months compared to 32.9 months if the enzyme is low. For Unmethylated MGMT, the numbers are 12.6 vs 21.4 months. This is a HUGE difference.
This has not been tested in a GBM trial, but it raises a red flag when considering these drugs, especially when there are easy alternatives. Instead of the drugs listed above, H3 blockers, such as
These 5k runs / walk are a lot of fund and raise money for our brain tumor grants program!
Diffuse midline gliomas with the H3K27M mutation are among the worst of the worst brain tumors, even if the diagnosis is not glioblastoma.. In this meta analysis, they found that these patients only have a median overall survival of 10 months and although radiation helps, no chemotherapies they tested helped at all. This is a huge unmet need.
This article talks about the combination of Onc-201 and paxalisib for DIPG. It says that Onc-201 works by itself for DIPG but usually the tumor develops resistance to it through the P13K pathway. Paxalisib targets this P13K pathway so it makes sense to try the combination. They treated 2 patients under compassionate use and both had dramatic reductions in tumor volume, complete resolution of symptoms and extended survival. So they started a trial https://clinicaltrials.gov/ct2/show/NCT05009992 for the combination to use in DIPG and DMG. I will be watching this trial closely.
Impressive results: 64% overall response rate and 91% clinical benefit rate for pediatric low grade gliomas. What makes this even more impressive is that there is very little research for this tumor type, which is the most common pediatric brain tumor type, and there are no approved treatments or even a standard of care for this type of tumor. Best yet - it is an oral drug and reasonable toxicity profile.
I think focused ultrasound is going to make a major breakthrough in the treatment of not only brain tumors but many brain diseases. There are many different ways to use it. We have video in our video library about focused ultrasound and the many ways it can be used. There is a new clinical trial that may be one of my new favorites for Glioblastoma and DIPG involving 5-ALA and focused ultrasound to kill the tumor.
