Pre-Considerations before surgery for Glioblastoma Resection
Theoretical Supplements
I am mostly a private person, but in this case I really need to reach out. I am an advocate for patients with Glioblastoma and anaplastic astrocytoma. A Phase 3 clinical trial is testing a vaccine called DCVax-L which is being used to treat brain cancer.
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All told, hospitals store tumors in paraffin wax which does not save tumor tissue in a viable state for future processing. A common misconception I have received from patients and doctors indicates that they cannot freeze tissue in a way that saves tissue in a viable way, but I know of two private tumor banks which can definetly store tumor tissue : www.storemytumor.com, and www.healthbank.com.
The last patient was enrolled in the DCVax-L clinical trial more than 3 years ago, so it could be unblinded any day. This link discusses the delay in unblinding as presented in June 2018 by the Chief Technical Officer of Northwest Biotherapeutics, manufacturer of DCVax-L.
(min 25:40).
Their will be a gap between when the trial is unblinded, and when hopefully it's approved, and hopefully we can be proactive and save their tumor tissue correctly, to at least give them an option if that's so desired.
Here is a screenshot from a Medical Journal article that illustrates the success of the trial, pre-unblinding. It was written May 30, 2018.
This is a clinical trial taking place in Canada, US, and Europe, lead by the former Sr. Editor in Chief of Journal of Neuro Oncology; Dr. Linda Liau.
Here is a graphic of midterm results from a subset of patients who decided to leave the trial (presumably they were getting the placebo) because they were progressing or pseudoprogressing. They were then given verified doses of DCVax-L.,. In other words the patients had a recurrence of the disease, were taken off the trial, and given verified versions of DCVax-L.
Related, this is an article written by UCLA, where Dr. Linda Liau works and teaches, indicating that patients who are doing well/surviving in the trial are in the mesenchyal gene expression: The implications of this development are extremely significant IMO.
Finally, hope for patients outside the mesenchymal gene expression, where I hope we can see an off label combination of keytruda or opdivo (same thing I think) and DCVax if it's approved, or via compassionate use: Hope is in the form of this chart indicating what makes mesenchymal gene expression patients so "special":
As you can see the PD1 immunosuppression is lowest in mesenchymal gene expressions,. All other types of immunosuppression, mesenchymal has the highest levels.
--------------> PD1 is a prognostic factor in lung cancer survival when treated with Keytruda, which blocks PD1. Keytruda (pembrolizumab) is now prescribed to patients who have high levels of PD1, pre-treatment
The vaccine is created by mincing the actual tumor tissue, mixing it with a lysate, and combining it with immature white blood cells that later mature into dendritic cells. After more labwork, the vaccine has been created which is injected into the patient intradermally.
In an amazing discovery via a small study, 9 patients were given the vaccine and imiquimod, an FDA approved melanoma cream. At least 5 patients were still alive 5+ years after treatment. The vaccine interacts with the increased number of white blood cells that have risen to the surface of the skin where the cream was applied, so when the vaccine is injected to that area, there is the synergistic effect of loaded dendritic cells teaching naive white blood cells to go carry out the targeted immunotherapy.
Additionally, I am well aware that their are constraints about processing approvals to children as the above clinical trial was for patients 18 and over,. However I would indicate that this same vaccine was tested on a small subset of children (3), and 2 were still alive at the time of publication. Both with High grade cancerous tumors. (glioblastoma grade 4 or anaplastric astrocytoma grade 3). I do think that their is definetly an option for children as well for this vaccine., especially given the challenging diagnosis. Here's the link to the small study of DCVax-L on children.
I wish to mention I am also a shareholder in Northwest Biotherapeutics,the company that makes/studies DCVax-L. Saving tumor tissue frozen may give a patient the opportunity to pursue tumor lysate vaccine like DCVax, given the storage process yields a viable product once thawed. A careful approach of saving tissue frozen may be warranted as perhaps cross referencing private storage techniques with hospital techniques to make sure that the correct method of storage, or consensus is followed. Parafinized tissue will allow a patient the opportunity to pursue other clinical trials perhaps if that is their wish. Its important to note that freezing tissue may not help a person redirect their treatment into a different clinical trial if the clinical trial planners are wishing for a specific look at immunostained paraffin slides.
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