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Note: The comments under each article title are the opinion of our president, Al Musella, DPM, and do not reflect official policy of the Musella Foundation!

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01/21/20 Multimodal Surgical Treatment of High-Grade Gliomas in the Motor Area: The Impact of the Combination of Navigated Transcranial Magnetic Stimulation and Fluorescein-Guided Resection.        

 This study shows a way to increase the chances of a gross total resection and at the same time getting less neurologic damage, by combining methods that were previously used by themselves! Great work!

01/21/20 Discovering the anti-cancer potential of non-oncology drugs by systematic viability profiling        

 This is a new public resource for cancer researchers.. These people tested 4,518 approved drugs to see which had anti cancer properties.  Their data is available free on their website.

01/21/20 Novocure Announces National Reimbursement in Israel for Optune® in Combination with Temozolomide for the Treatment of Newly Diagnosed Glioblastoma        

 Good news for brain tumor patients in Israel - Optune is now covered by your national health insurance!

01/21/20 Genome-wide CRISPR–Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1        

 This is very early work and we need to see how it works in people but it has the potential to be a single treatment that can treat all types of cancer without hurting the normal cells at all. This is not directly about brain tumors  - I added it to the news blast because it might turn out to be a major breakthrough in the treatment of all cancer!  I will keep an eye on it and let you know how it works out!

01/15/20 Musella Foundation Brain Tumor Copay program is now open!        

 The program might not be open too long so if you think you can use it - apply now!

01/15/20 Scientists breach brain barriers to attack tumors        

I love this kind of research - shows they are thinking through the problem and looking for new avenues of attack. This is way too early to say if it will help people, as they only tried it in mice.  Will keep an eye on it as they move into humans!

01/13/20 Medicenna Vaults on Brain Cancer Study        

 They do not give many details except to say they doubled the survival compared to matched control group. That is a major advance!

01/10/20 Optimal adjuvant therapy in elderly glioblastoma: results from a systematic review and network meta-analysis        

 In this study, they found that shortening the radiation duration from the usual 6 weeks to 3 weeks and using Temodar during and after radiation was the best option for elderly patients with a Glioblastoma.  Unfortunately they did not look at adding Optune so from this article we can not tell where Optune would fit in. This is from India and I do not know if Optune is available in India.

01/10/20 Surgery may add months or years of survival for adults with rare and deadly brain cancers        

 This report says it may now be possible to safely surgically remove high grade brainstem gliomas. This could almost double the expected average survival, which buys time for other treatments to work!  

01/09/20 Survival analysis of patients with glioblastoma treated by long-term administration of temozolomide.        

 This is the reason why we like to see prospective trials.  In this retrospective study, they looked at people who used Temodar for 6 months or less versus people who received more than 6 months of Temodar.  The progression free survival was a little better but the overall survival was more than double (47 vs 20 months) in the long term group vs. the short term group. That would be very impressive except they did not give one group 6 months of Temodar and the other group more than 6. They just looked back to see how long patients used it.  It is possible that the patients who used it longer were the ones in good shape and who were responding to it and the ones who stopped at or before 6 months did so because they were having problems, in which case you would expect the group doing well to live longer than the group not doing well.

01/08/20 New book takes a humorous look at brain cancer        

 Very well written book describes what happens from the first symptoms of a brain tumor through the surgery, radiation, chemo and all of the problems that arise. Worth the read.

01/08/20 Identification of a transient state during the acquisition of temozolomide resistance in glioblastoma.        

 I love this type of research.  They looked at how Temozolomide effects tumor cells over time. We already knew most GBM cells will become resistent to Temozolomide eventually, but they identified a stage that the cells go through where they change to slow growing and change shape.  They identified a drug which interferes with the cell. Sounds like it is worth a try in clinical trials.

01/07/20 DIPG Advocacy Group Announces Congressional Briefing for Pediatric Brain Cancer        

You can help. Follow the instructions in the article to ask your representatives to cosponsor and vote for this bill!

01/06/20 Musella Foundation Awards $250,000 Brain Tumor Research Grant        

 This is the 3rd of the 4 payments of $250K that we pledged toward this $1 million project. I still need help raising the final $250K! If anyone is interested in helping, contact me! (Al Musella, DPM


01/05/20 Mount Sinai Receives More Than $10 Million in Grant Funding for Brain Tumor Research        

 Congratulations to one of my favorite brain tumor centers!

01/04/20 Complete radiological response following subtotal resection in three glioblastoma patients under treatment with Tumor Treating Fields.        

 This is a relatively small trial but shows a huge effect supporting the use of Optune for Glioblastoma.  

In the big EF-14 phase 3 trial for newly diagnosed glioblastoma, the trial was stopped at the first interim analysis because it was obvious the Optune arm was doing so much better than the control group that it was unethical to continue withholding Optune from newly diagnosed patients.    The people running this study did not do that - they allowed it to go on for 5 years - knowing that they were withholding the best treatment.  Doesn't sound fair to me.

01/04/20 Regorafenib in glioblastoma recurrence: how to deal with conflicting ‘real-life’ experiences?        

 Very interesting question.  The clinical trial for Regorafenib in recurrent gbm showed a small benefit over Lomustine. However, the control group of Lomustine did terrible compared to the large trial testing Lomustine.  In the Regorafenib trial, the control group of Lomustine had 5.6 months of overall survival.  In the Lomustine trial, the same type of patients had a median overall survival of 8.6–9.8  months.  The Regorafenin group had 7.4 months.  So although Regorafenib did better than the randomized control group it did not do as well as the Lomustine in the Lomustine trial.  

 However, reports from real world use of the drug  came in that said almost all patients get severe side effects and they did not see the benefit seen in the trial.  So what do you do?

 Obviously more research needs to be done hopefully to find if there are biomarkers that would push you toward Lomustine, Regorafenib or the combination.  Perhaps the best way would be for having all patients be followed in a registry so we can see how it works in the real world and correlate with biomarkers.  As in our brain tumor virtual trial project or our new Excelsior registry

01/04/20 Cost-effectiveness analysis of the addition of bevacizumab to temozolomide therapy for the treatment of unresected glioblastoma.        

 This is one of the biggest problems we have - the high cost of treatments.  This analysis found a small benefit to adding bevacizumab (Avastin) to Temodar for people with inoperable Glioblastomas.  However, because of the high cost of the drug, it was determined that is not cost effective.  They set the acceptability bar at $26,500 to add 1 year of life. This treatment worked out to $171,638 for each year of life added. Not even close.  

 This is a societal problem. I do not blame the drug companies, as the cost to develop a drug under our system is so high that to recoup their investment, the prices have to be high.  Without high prices, there would not be new drugs getting approved.  We need to change the system so that any researcher with a good idea could afford to bring a drug through the system to get approval - which not only will drastically lower the cost of new drugs but gives us a wider range of treatments to use.

12/25/19 Safety and efficacy of VB-111, an anti-cancer gene-therapy, in patients with recurrent glioblastoma: results of a phase I/II study        

 VB-111 is an experimental gene therapy.   Two papers came out at the same time with conflicting results.  This phase 1/2 study had very good results but was not as large or well designed as the phase 3 trial. mentioned in the next article.  They used the treatment in a few different ways with the best being using the VB-111 alone until progression, then continue VB-111 and add Avastin.      My thoughts are that most of the immunotherapy trials fail because they stop the treatment too soon. These treatments take time to work, and sometimes the tumor looks worse before it gets better.

12/25/19 A randomized controlled phase III study of VB-111 combined with bevacizumab vs. bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE).        

 VB-111 is an experimental gene therapy being tested for use in recurrent Glioblastoma.  As I mentioned in the previous article, the results for the phase 1/2 trial came out on the same day as the results of the phase 3 trial. I do not think I ever saw that happen before.  The Phase 1/2 trial came out very good however, this failed to show any improvement of VB-111 plus Avastin randomized against Avastin alone in recurrent GBM.   If they had the results of the phase1/2 trial before they designed this phase 3 trial, they might have designed it differently as the phase 1/2 trial showed that using VB-111 alone until recurrence, then continuing vb-111 and adding avastin did much better than starting with VB-111 and Avastin at the same time.  This shows that adding combinations doesn't always improve the outcome. Everything needs to be tested and timing is very important.

I am still a fan of VB-111 but think it needs more work to find the optimal way to use it.  

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