“Navigating Brain Cancer”

“Navigating Brain Cancer” (Al Musella) [#80] Brad Power January 3, 2024 “Everybody asks me, if I had a glioblastoma, what would I do? This is if access was not a problem. There's no way that anybody is going to get this treatment plan right now. Some of these are impossible to get, and you'll never find oncologists willing to prescribe this for you.

But this is how I would approach it if I happened to have a glioblastoma right now.” – Al Musella “For us as patients and caregivers, it's a very frustrating chess game. Right now, we don't have access to a lot of these things concurrently. You have to pick and choose which ones you're going to pursue. If you do pursue one, and it doesn't work, you have to pivot really quickly to the next one.

” – Vanessa Hugo “The Promising Pathway Act … creates a conditional approval pathway for the FDA, where after you see that drug is pretty safe, and it has the effect you want it to have, it gets a conditional approval where any doctor could prescribe it, and insurance will handle it like any other approved drug.

But any patient who uses these drugs has to be followed as if they're in a clinical trial. We learn from every patient. You continue the research. The only difference from the standard pathway is it's more flexible, where you can do combinations if you like.

And any patient could get access, whereas in clinical trials, it's only a very select few, like 5% of the population, who can get into clinical trials.” - Al Musella Meeting Summary Navigating brain cancer is a daunting challenge for patients and their loved ones, marked by shock, overwhelming choices, and the urgency to make informed decisions about treatment options.

The medical team provides initial guidance, but the plethora of choices in doctors, treatment locations, tests, and clinical trials demands that patients quickly educate themselves to make rational decisions. Understanding the landscape of brain tumors, including information on medical experts, treatment options, and support sources, becomes crucial for navigating this difficult journey.

In response to this need, the Musella Foundation offers comprehensive resources including videos, written information, discussion forums, patient navigation services, and advocating for change in the system. They have been conducting a study on brain tumor patients since 1993, focusing on the treatments received and the outcomes, with the aim of identifying more effective treatment combinations.

Al Musella, the founder of the foundation, was personally motivated by his family's experience with brain cancer and has been instrumental in creating an online database of clinical trials.

The foundation also encourages participation in their brain tumor Virtual Trial, which tracks patient outcomes, and seeks support through updates on treatment options, spreading the word, advocating for change and donations to sustain these vital projects.

ls. The foundation also encourages participation in their brain tumor Virtual Trial, which tracks patient outcomes, and seeks support through updates on treatment options, spreading the word, advocating for change and donations to sustain these vital projects. What are the treatments that patients and caregivers should consider for brain cancer?

“Navigating Brain Cancer” (Al Musella) [#80] 1.Pick the most experienced surgeon . More experienced surgeons could get the tumor out with less damage to you. 2.Insert GammaTiles. These are bioresorbable tiles implanted at the time of surgery that release radiation. 3.Get DCVax (autologous tumor lysate-loaded dendritic cell vaccination) from the surgery tissue. 4.

Get advanced genomic testing on the tissue. If the genomic analysis finds a good targeted drug, take it. 5.Defer external beam radiation. External beam radiation is the standard, but there are long-term negative side effects, such as strokes. 6.Start Optune. Try for over 90% compliance with the new high power arrays. 7.

Start Keytruda (checkpoint inhibitor immunotherapy) and poly-ICLC (an immunotherapy targeted at glioblastoma). 8.Take temozolomide (the standard chemotherapy for glioblastoma) IF your cancer is MGMT methylated (a test of the MGMT enzyme, which affects the DNA-repair function, which makes tumors more susceptible to temozolomide). 9.

Start sonodynamic therapy (low intensity ultrasound combined with sonosensitizer selectively taken up in tumor cells). 10.Get advanced imaging , such as fractional tumor burden mapping . For more information on each of these options, please see the meeting transcript here. What are the challenges that patients with brain cancer and their caregivers face?

●There are many promising new therapies, but you can’t access a lot of them in a combination. You have to pick and choose which ones you're going to pursue. ●If a treatment doesn't work, you have to pivot really quickly to the next one because the disease is very aggressive. ●The current drug development process is too slow and costly for rare diseases like glioblastoma.

●Only a very select few, like 5% of the population, can access clinical trials. How can we overcome the regulatory hurdles to accessing treatments and accelerate treatment development? You should support “The Promising Pathway Act”, pending legislation which will create a conditional approval pathway for the FDA.

After you see that a drug is pretty safe, and it has the effect you want it to have, it would get a conditional approval. Any doctor could prescribe it, and insurance would handle it like any other approved drug. Any patient who uses these drugs would be followed as if they're in a clinical trial. We would learn from every patient. We would continue the research.

The only difference from the standard pathway is that it's more flexible, where you can do combinations if you like, and any patient could get access.

followed as if they're in a clinical trial. We would learn from every patient. We would continue the research. The only difference from the standard pathway is that it's more flexible, where you can do combinations if you like, and any patient could get access.

“Navigating Brain Cancer” (Al Musella) [#80] medical treatment, product, or course of action. You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health.

“Navigating Brain Cancer” (Al Musella) [#80] Meeting Notes SUMMARY KEYWORDS glioblastoma, patient, clinical trial, tumor, people, drug, treatment, cells, years, vaccine, good, radiation, talk, GBM, call, trial, pathway, question, working, vanessa SPEAKERS Al Musella (72%), Brad Power (12%), Vanessa Hugo (7%), Brian McCloskey (5%), Adrienne Nugent (2%), Ebrahim Nana (1%), Lisa Collman (1%), David Plunkett (1%) OUTLINE 1.

Brain cancer treatment and patient advocacy. (0:03) 2.Developing a platform for glioblastoma treatment. (2:18) 3.Glioblastoma treatment options and research. (8:16) 4.Personalized cancer treatment options. (14:29) 5.New brain tumor treatments with promising results. (18:55) 6.Personal journey with glioblastoma and treatment options. (23:27) 7.Cancer treatment options and advocacy. (28:11) 8.

Genetic testing for glioblastoma. (34:02) 9.Optune mechanism of action and potential for other cancers. (39:25) 10.Cancer treatment options and clinical trials. (43:56) 11.Brain cancer treatments and advocacy. (48:54) SUMMARY ●Brain cancer treatment and patient advocacy.

0:03 ○Co-founder of Cancer Patient Lab Brad Power introduces webinar on brain cancer, with guest speaker Al Musella sharing insights after decades of advocacy. ●Developing a platform for glioblastoma treatment.

2:18 ○Al Musella, president of the Musella Foundation, discusses the organization's vision for speeding up the search for a cure for glioblastoma, which involves collecting medical records, using AI to structure the data, and presenting treatment options to patients and doctors.

○The organization's virtual tumor boards bring together world experts to suggest treatment plans for patients, and the registry records the rationales for these suggestions to feed back into the AI loop.

○Al Musella proposes the "Promising Pathway Act" to provide easy access to experimental treatments for patients, including a conditional approval pathway for the FDA to approve drugs after they've shown safety and effectiveness in a smaller group of patients.

sy access to experimental treatments for patients, including a conditional approval pathway for the FDA to approve drugs after they've shown safety and effectiveness in a smaller group of patients. ○He believes that this approach would allow for more flexible combinations of drugs to be tried, and would provide valuable learning opportunities for doctors and researchers.

“Navigating Brain Cancer” (Al Musella) [#80] ●Glioblastoma treatment options and research. 8:16 ○The current drug development process is too slow and costly for rare diseases like glioblastoma. ○Al Musella prioritizes experienced surgeons for glioblastoma surgery and advanced genomic testing.

○He discusses the use of gamma tiles for glioblastoma treatment, including their effectiveness in recurrent cases and potential for combination with other therapies. ○He also mentions the importance of advanced imaging modalities, such as fractional tumor burden mapping, for identifying effective treatment targets and monitoring patient response. ●Personalized cancer treatment options.

14:29 ○Vanessa Hugo discusses the challenges of accessing personalized cancer treatments, including the need for fresh dendritic cells for the DC-Vax vaccine and the requirement for the Compassionate Use program in the UK. ○Al Musella provides updates on the availability of the vaccine under the Special Access Program in the UK and the potential for importation from the UK once approved.

○Combining DC-Vax with Keytruda shows promising survival results for glioblastoma patients, with potential for further improvement with additional therapies. ●New brain tumor treatments with promising results. 18:55 ○Al Musella presents research on Optune therapy for brain tumors, showing doubled 5-year survival in a randomized phase 3 trial.

○Combining Optune, with the new arrays and frequent use, and Keytruda, we may be able to get in the range of 50% 5-year survival, comparable to DCVax with a different mechanism. ○Al Musella discusses a new technology (sonodynamic therapy) using FDA- approved dye and ultrasound to kill cancer cells in the brain with minimal side effects.

○The technology involves repeating the treatment over time to target cells far away from the main tumor, with potential to treat glioblastoma. ●Personal journey with glioblastoma and treatment options. 23:27 ○Al Musella shared his family’s experience with brain cancer, and the importance of serial MRI scans to monitor tumor growth or shrinkage.

○Al Musella's personal journey with brain tumors began when his sister-in-law was diagnosed in 1992, and he has since dedicated himself to advocating for patients and creating resources for them. ○He has learned that the key to success in advocacy is to be proactive, persistent, and adaptable, and to be willing to take risks and challenge the status quo. ●Cancer treatment options and advocacy.

sister-in-law was diagnosed in 1992, and he has since dedicated himself to advocating for patients and creating resources for them. ○He has learned that the key to success in advocacy is to be proactive, persistent, and adaptable, and to be willing to take risks and challenge the status quo. ●Cancer treatment options and advocacy.

28:11 ○Al Musella discusses the challenges of clinical trials for rare diseases, including the risk of receiving a placebo instead of the actual drug. ○He discusses the need for legislation to help patients access treatments outside of clinical trials.

○Brian McCloskey discusses proton therapy for tricky places to treat, including glioblastoma, and the potential benefits and limitations of using radioligands for cancer treatment. ○Brian McCloskey shares his personal experience with glioblastoma running in his family and asks for insights on proton therapy and radioligands. ●Genetic testing for glioblastoma.

“Navigating Brain Cancer” (Al Musella) [#80] ○Brian McCloskey asks if glioblastoma is a germline-based cancer, citing his aunt and son who also had the disease. ○Al Musella explains that sequencing is important for diagnosis and treatment, but there are different types of sequencing and only a small percentage of patients have actionable results.

○Vanessa Hugo mentions that xCures has a registry of 140,000 total patients, including over 1000 GBM patients. ○Brian McCloskey asks if liquid biopsies are relevant in the brain cancer space, and Vanessa Hugo replies that tissue-based biopsies are more common. ●Optune mechanism of action and potential for other cancers.

39:25 ○Al Musella explains the mechanism of action for Optune, including how it disrupts cell division and exposes new antigens to the immune system. ○He highlights the importance of using immune checkpoint inhibitors in combination with Optune to enhance the immune response. ○Optune and sonodynamic therapy have potential to treat various cancers beyond GBM, including lung and pancreatic cancer.

●Cancer treatment options and clinical trials. 43:56 ○Lisa Collman asks about a new tumor treating field device called Voyager, which is in clinical trials but not yet available. ○Al Musella discusses a magnetic device in Texas that is more promising but still early in development.

○He expresses frustration with the clinical trial system and the lack of progress in developing a vaccine for cancer. ●Brain cancer treatments and advocacy. 48:54 ○Adrienne Nugent and Vanessa Hugo discuss the latest research on glioblastoma, including a Stanford study on familial GBM and a patient navigation program at Cancer Commons.

○Lisa Collman shares insights on hyper-mutated TMZ and glioblastoma, and the group discusses how to stay informed and learn from each other. ○Brad Power mentions the launch of an online discussion forum for a continuing conversation on brain cancer treatment ideas and questions.

or them. ○He has learned that the key to success in advocacy is to be proactive, persistent, and adaptable, and to be willing to take risks and challenge the status quo. ●Cancer treatment options and advocacy. 28:11 ○Al Musella discusses the challenges of clinical trials for rare diseases, including the risk of receiving a placebo instead of the actual drug.

○He discusses the need for legislation to help patients access treatments outside of clinical trials. ○Brian McCloskey discusses proton therapy for tricky places to treat, including glioblastoma, and the potential benefits and limitations of using radioligands for cancer treatment.

○Brian McCloskey shares his personal experience with glioblastoma running in his family and asks for insights on proton therapy and radioligands. ●Genetic testing for glioblastoma.

“Navigating Brain Cancer” (Al Musella) [#80] ○Brian McCloskey asks if glioblastoma is a germline-based cancer, citing his aunt and son who also had the disease. ○Al Musella explains that sequencing is important for diagnosis and treatment, but there are different types of sequencing and only a small percentage of patients have actionable results.

○Vanessa Hugo mentions that xCures has a registry of 140,000 total patients, including over 1000 GBM patients. ○Brian McCloskey asks if liquid biopsies are relevant in the brain cancer space, and Vanessa Hugo replies that tissue-based biopsies are more common. ●Optune mechanism of action and potential for other cancers.

39:25 ○Al Musella explains the mechanism of action for Optune, including how it disrupts cell division and exposes new antigens to the immune system. ○He highlights the importance of using immune checkpoint inhibitors in combination with Optune to enhance the immune response. ○Optune and sonodynamic therapy have potential to treat various cancers beyond GBM, including lung and pancreatic cancer.

●Cancer treatment options and clinical trials. 43:56 ○Lisa Collman asks about a new tumor treating field device called Voyager, which is in clinical trials but not yet available. ○Al Musella discusses a magnetic device in Texas that is more promising but still early in development.

○He expresses frustration with the clinical trial system and the lack of progress in developing a vaccine for cancer. ●Brain cancer treatments and advocacy. 48:54 ○Adrienne Nugent and Vanessa Hugo discuss the latest research on glioblastoma, including a Stanford study on familial GBM and a patient navigation program at Cancer Commons.

○Lisa Collman shares insights on hyper-mutated TMZ and glioblastoma, and the group discusses how to stay informed and learn from each other. ○Brad Power mentions the launch of an online discussion forum for a continuing conversation on brain cancer treatment ideas and questions.