This reports the opposite of what we thought regarding tumor mutational burden.  A high tumor mutational burden in other cancers would make the tumor more likely to respond to immunotherapy but that did not work out with Glioblastomas.  This study says that a very low tumor mutational burden for glioblastomas results in a better response with immunotherapies. They also release some new data from the PVSRIPO trial showing impressive results for recurrent Glioblastoma patients with less than the median tumor mutational burden.  Of 21 patients in the trial, 10 in the high TMB group and 11 in the Low TMB group, at the 3 years point after treatment 3 of the patients in the low TMB group were alive, while none in the High TMB group were alive.  These 3 patients were still alive at the end of the trial, one at 36 months, one at 60 months and one at 96 months!  It is a small number of patients, but I would consider this trial if I had a low TMB.  TMB is usually reported on your pathology report.

 It is difficult to interpret the results because there was a mix of anaplastic astrocytoma and glioblastoma, and they did not disclose the MGMT methylation status, the IDH status ir if they patients used Optune or any other treatment. However, they have shown that adding Mebendazole is safe, and it appears that the outcome is a little better than Temozolomide alone.  This is a pretty popular drug for Glioblastoma patients to take. It is part of the Care Oncology Protocol, which also adds 3 other repurposed approved drugs. The Care Oncology protocol has some imnpressive data behind it.

 Impressive results for a phase 1 trial.  The link to the journal article is in the press release.

 GammaTile  is an FDA approved treatment for brain tumors that is implanted at the time of surgery (both newly diagnosed or recurrent) and can double the time before the tumor grows, which buys time for other treatments to work.

It is not available everywhere just yet, visit their website to see which centers are using it now and ask your neurosurgeon about it.

This free webinar will go into detail about it.

 This may be a new way to detect recurrences sooner!

 This is a very interesting drug. It is a smart bomb. It seeks out IL13Ra2 which is a cell surface protein present on many types of cancer cells (including Glioblastomas, and DIPG), and rarely found on normal cells. It carries along a pseudomonas exotoxin that kills the cells that the drug attaches to. The net effect is that it kills tumor cells without harming the normal cells.  The Musella Foundation has given a few grants to support the creation of this drug over the last 11 years and I am so happy to see it has received orphan designation. That will make it easier and cheaper to  bring it to patients.

Outcomes and Patterns of Care in Elderly Glioblastoma Multiforme Patients: A Population-Based Study of the National Cancer Database         One of the key findings is that only 42% of the elderly patients in the USA with Glioblastoma used any chemotherapy compared to 63% of younger people. Same problem with radiation and surgery, all 3 of which were shown to increase survival time if used.   They found the average survival time was only 9.1 months. We need to figure out why these people did not receive treatment.  Cost may be a factor.  The first Temodar prescription usually costs in the neighborhood of $8,000 with a Medicare copayment of about $1,000. Many people refuse to buy the Temodar due to the cost. The manufacturer of Temodar closed their assistance program a long time ago and right now we - the Musella Foundation - are the only copayment assistance program open that can help Medicare patients with their copayment for Temodar (and Optune and Avastin). (Others open and close but none are open now).  We helped over 1,500 patients pay for the medications they need. I am sure this has helped these people live longer. Having said that, we need to change the laws so people who have health insurance do not have to go without medicines due to their cost.

This can be practice changing.  We previously reported that Temozolomide did not help patients with Glioblastoma that have unmethylated MGMT and the Wild Type IDK. This confirms it, and in the opinion of the authors, makes it Ok to not use Temozolomide on patients in this group, and try something else.  We have always been afraid of trying this because there was a small "tail" of survivors in the trials of patients with unmethylated MGMT who did do well with Temozolomide.  This article explains that the old test was not specific enough, and says they now break down the MGMT result into 3 groups, highly methylated, where Temozolomide has a good chance of helping, low (truly) unmethylated which has no chance of Temozolomide helping, and the intermediate range where there may be a small benefit. They say that those in the intermediate group were labelled as unmethylated and they account for those responders in the old trials.

The  Bridge to a Cure Foundation raises money to fund pediatric cancer research and is trying to unite the organizations working on pediatric cancer to work together to speed up the pace of research.  By joining their board, I will help them work with the pediatric brain cancer groups!   Of course, I will still run the Musella Foundation and participate in all of the other collaborations we are in. This will help raise the funds we need to implement some of the great ideas these collaborations have but were unable to fund!

 Finally good news for those of us with a weight problem.  The study is too small to prove anything but they found that obese individual had a 5 month increase in median survival compared to non obese patients. It would be interesting to check this on other databases and see if it is real.  If it is, then we have to account for BMI in clinical trials as the 5 month difference is more than the difference needed to get a drug approved. 

 This is an important study.. they looked at the mitochondria of the tumor cells, and found differences among some of the tumors that may open an Achilles heel. This subgroup might be treatable with existing approved drugs (such as Metformin).  The Musella Foundation recently awarded a grant to a different set of researchers to study this in depth.

 This is one of my favorite trials... PVSRIPO + Keytruda makes a lot of sense. The PVSRIPO is injected into the tumor and kills tumor cells.  The Keytruda ramps up the immune system so that it learns from these destroyed tumor cells and seeks out and kills tumor cells anywhere else in the brain (and maybe the entire body).  PVSRIPO by itself is a good treatment. For recurrent Glioblastoma, they reported a 3 year survival rate of 21% compared to historical controls of about 4%.  Hopefully adding Keytruda will increase that significantly.  Keytruda by itself did not really work out well with Glioblastoma, because it only revs up the immune system and there needs to be something there for the immune system to see.   The PVSRIPO kills the cells, making them into a better target for the immune system.

Disclaimer: I am on the patient advisory board of the Brain Tumor Center at Duke.

Interesting study.  They found that people who had a T. gondii infection, as determined by having antibodies against the parasite were more likely to develop a brain tumor. More research needs to be done to repeat this experiment in different groups of patients, and to  see if the parasite can really cause a tumor and / or influences the growth of the tumor.  There are other conflicting studies that did not show the association, but this one seems the best designed.

 I really like this trial.  They may have figured out why the vaccine wasn't working that well, and found a way around it. They tested it in dogs who had naturally occurring tumors and it worked pretty well. Now they are doing a clinical trial of the vaccine plus the CD200 checkpoint inhibitor in humans with recurrent glioblastoma . I will be watching this closely and wish them luck.  For details on the trial, go to https://clinicaltrials.gov/ct2/show/NCT04642937

 Hopefully this will speed up the FDA approval process for Onc-201. This drug should have been approved last year. 

 The GBM Agile trial is the next generation of clinical trials. It is an adaptive design which allows flexibility to change as circumstances dictate instead of the rigidity of the old style trials.  

Very exciting news.  As I mentioned in a few previous posts (such as https://virtualtrials.org/newsarticle.cfm?item=6750) , the G47 Delta virus did remarkably well in a phase 2 trial for recurrent or residual Glioblastoma.  They reported a 1 year survival rate of 92% compared to historical controls of 15%.  This article says they applied for the Japanese equivalent of our FDA approval for it last month.   So at least in Japan, there will hopefully be a new, effective  Glioblastoma treatment soon. We have to work on getting it here in the USA.

 Leptomeningeal spread is a serious complication.  Left untreated, average survival is only 2 months.  The article talks about a few treatments but there is an interesting clinical trial going on specifically for patients with leptomeningeal  spread: Brain Tumor-Specific Immune Cells (IL13Ralpha2-CAR T Cells) for the Treatment of Leptomeningeal Glioblastoma, Ependymoma, or Medulloblastoma  It is too early to tell how good this works, but the alternatives do not seem that good either. Car-T cells have worked miracles in other cancers. This is a new type of Car-T cell treatment that hopefully will work for brain tumors!  They picked the absolute worst situation to test it in - so if it does work we should know quickly. Unlike most immunotherapies, Car-T cells have the possibility (at least in other cancers) of working quickly. 
Disclaimer: The company running the trial, Mustang Bio, is a sponsor of the Musella Foundation.  

 This article suggests it is safe to freeze your eggs before treatment for a brain tumor, then implant them after the treatment, without risk of spreading the tumor.