How an Expert Would Treat His Own Glioblastoma: An Update

When facing a new cancer diagnosis, some people ask their doctors, “What would you do if you were me?” Here, our Curious Dr. George asks Al Musella, DPM, how he would handle his own case of glioblastoma, a type of brain tumor. Dr. Musella is President of the Musella Foundation For Brain Tumor Research & Information, Inc., a partner of Cancer Commons (Note: This is an updated version of a piece that originally appeared in October 2020; now, Dr. Musella provides new information on his preferred treatments for glioblastoma.)

Curious Dr. George: You direct an established foundation that supports research and information about brain tumors. What would you do if you yourself were diagnosed with glioblastoma?

Al Musella, DPM: If I were diagnosed with glioblastoma, the first thing I would do is seek help by joining the patient navigation program that my foundation operates in partnership with Cancer Commons and Head For The Cure. After registration, our team of experts evaluates each case and gives a personalized list of suggestions to look into. Below are some options that I would consider for my own hypothetical case.

Surgery: My first treatment would be surgery. It would be important to me to choose an experienced surgeon who has a better chance of removing more of the tumor with less damage. The American Brain Tumor Association has a list of experienced teams that I would consider.

I would also consider using the drug Gleolan (also known as 5-ALA) to increase the chances of a complete resection during surgery. A clinical trial is currently exploring Gleolan as part of photodynamic therapy at the time of surgery (see more below), and while it is too early to tell how much this might help, it does show promise, and I may consider enrolling.

Lastly, when considering surgical options, I would look into Gamma Tiles, which the U.S. Food and Drug Administration (FDA) has approved for both newly diagnosed and recurrent glioblastoma. These are radioactive implants placed near the tumor at the time of surgery, where they deliver a high dose of radiation precisely where it is needed and at the optimal time—immediately after tumor removal, before regrowth begins. This procedure might add, on average, about 8 months of progression-free survival, buying time for other treatments to work. However, Gamma Tiles may disqualify a patient from participating in certain clinical trials, so I would want to consider that possibility when deciding whether to use them myself.

Tumor sample for personalized vaccines and advanced testing: After surgery, I would consider sending part of the removed tumor to make a vaccine custom-designed to fight my glioblastoma, such as DCVax. This vaccine is not yet approved in the U.S. but is available in the U.K. under a special access program—although it can be expensive. I would send the rest of the tumor for advanced testing to further clarify which treatments might work best for me.

Scans: Standard MRIs may sometimes be unclear, as they can’t always differentiate between various tissue types (tumor, necrosis, swelling, normal brain tissue, or scar tissue). This can lead to misinterpretations, such as pseudo-progression, where the tumor appears to be growing when it is not, potentially leading to unnecessary changes in treatment.

Newer techniques can provide clearer results. Among the more easily available options, my current favorite is fractional tumor burden mapping. This type of scan is better than MRI (but not perfect) at discerning how much of the abnormality is an active, live tumor. I would insist on such an option for all of my scans, as comparing them over time would be the best way to tell how  treatment is going.

Radiation: There are many types of radiation, and the choice of which approach is best should be left to each patient’s medical team. Typically, the drug temozolomide is used alongside radiation to enhance its effects. Using the aforementioned Gamma Tiles at the time of surgery might allow a patient to delay standard radiation until after other treatments, or possibly replace standard radiation altogether.

FDA-approved treatments: These are the standard and FDA-approved treatments I would consider to treat my glioblastoma:

  • Temozolomide is a standard, FDA-approved treatment. A biomarker called MGMT can predict how well a patient might respond to temozolomide. If tumor testing returns the result “MGMT unmethylated,” there’s a lower chance of temozolomide being effective— not a zero chance, but lower than if MGMT is “methylated.” Temozolomide treatment typically lasts for 6 to 12 months after radiation treatment ends. In my case, I would probably choose to use temozolomide if my MGMT was methylated but might avoid it otherwise.
  • Gleostine is a drug also known as CCNU or lomustine. There is some evidence that adding Gleostine to temozolomide has better results than temozolomide alone—especially if MGMT is methylated. However, it also increases the chances of side effects. The combination may be best for younger, stronger patients, and I would consider it for myself, unless I was adding other drugs and did not want to risk needing to stop all drugs because of side effects.
  • Optune is an FDA-approved device applied to the skull using adhesive arrays that delivers tumor-treating fields. Optune has the best-reported outcomes of any FDA-approved treatments for glioblastomas. Suggested usage is at least 75% of the time, but using it over 90% of the time significantly improves outcomes. Adding a checkpoint inhibitor drug may increase the effectiveness of Optune.

Some doctors do not recommend Optune, as it can be a hassle to use or make some patients ineligible for certain clinical trials. However, as always, each patient should make their own decision based on information about their choices and their personal values. I would definitely try Optune, most likely alongside a checkpoint inhibitor. I would also be careful not to stop treatment too early. The first scan after starting Optune may show worsening (pseudo-progression), but advanced scans can clarify the situation.

  • Avastin: This is a type of drug known as a VEGF inhibitor. By itself, it has not been shown to significantly improve overall survival, but it does work well to reduce swelling, like a “super steroid.” It could be a helpful addition because some of the aforementioned treatments can cause potentially life-threatening swelling, which Avastin may be able to reverse or prevent. In addition, steroids are detrimental to the action of all immunotherapies and to Optune, so Avastin might be useful to reduce or eliminate the use of steroids.

Experimental and off-label treatments: I would also consider treatments that have shown promise but have not yet been approved by the FDA. Our patient navigation program would be especially helpful for identifying these treatments. Among my favorites, below,  I would choose the ones that I could most easily access. I would follow up with advanced imaging and change my approach at the first sign of treatment failure.

  • Onc-201: If my tumor was in the midline structures of my brain, especially the thalamus or brainstem, I would consider testing it for an H3K27M mutation or low EGFR levels. This approach is also prudent for younger patients. If either abnormality was present, I would consider treatment with Onc-201. This drug is currently available through a clinical trial and potentially through expanded access.
  • Gleolan, or 5-ALA: The concept behind this drug—introduced above as an option to use during surgery—is elegant. When exposed to a special frequency of light, it causes tumor cells to glow, helping the surgeon identify any remaining tumor tissue. Then, when the surgeon applies a laser, the dye-absorbed cells are destroyed. This is the essence of photodynamic therapy.

It should be noted that photodynamic therapy with 5-ALA has some limitations, as the laser cannot penetrate deeply into the brain or pass through the skull, making the procedure invasive. It is currently experimental, but if the surgeon I chose to remove my tumor was willing, I would consider trying it. However, I wouldn’t have surgery purely to use this treatment.

I might also consider a non-invasive approach to targeting cells that absorb 5-ALA called sonodynamic therapy. In this method, focused ultrasound is directed at the tumor through the skull. When 5-ALA is excited by the ultrasound, tumor cells are selectively destroyed, while normal cells are spared. This technique can be repeated as needed, either to treat new areas of growth or prophylactically in regions where recurrence is anticipated. I would likely opt for sonodynamic therapy once a month for my first year after diagnosis, then as needed thereafter. While sonodynamic therapy for glioblastoma is not yet FDA-approved, it is currently in clinical trials. The components of this treatment are already approved, which might expedite its pathway to full approval.

  • Niraparib is a type of drug known as a PARP inhibitor. It is already FDA-approved for other types of cancers and should be accessible off label. Niraparib stops cancer calls from repairing DNA damage, which could make most other treatments work better. The best combination of niraparib with other treatments has not yet been determined, but I would consider it for myself, especially if my glioblastoma was MGMT unmethylated.
  • Gallium maltolate is an experimental oral drug that also has an elegant mechanism of action and early promise. It is available through clinical trials and via an expanded access program.
  • MDNA55 is a drug that targets a protein called IL4R, with impressive preliminary evidence for treating glioblastoma.
  • SurVaxM, CeGaT, Gliovac, the Jaime Leandro Foundation vaccine, Imvax, the PanAm VAX vaccine, CMV vaccine, and other vaccines: I like the concept of vaccines for cancer treatment and would choose to use at least one for myself. My top choice would be DCVaxor Gliovac because they would be custom-made for my tumor and therefore designed to attack all of the known targets in my tumor. If those were not available, I would choose one of the other vaccines. Evidence has not yet conclusively shown which is best, so I would select whichever was easiest to access. None are yet FDA-approved, so access would likely be challenging and expensive.
  • CAR T-cells and viral therapies: There is a lot of excitement about CAR T-cell therapies, which modify a patient’s own T cells to fight cancer. The CAR T-cell approach can cure certain types of cancer for some patients, but it has not yet been shown to cure glioblastoma. However, every generation of CAR T-cell therapy gets better, and we are getting closer to a version that could potentially be curative for glioblastoma.

Meanwhile, many viral therapies—which use viruses to destroy tumor cells—are currently in development, and they show some early promise. For instance, the viral therapy lerapolturev (previously known as PVSRIPO) has shown enough promise that a new clinical trial recently launched to continue testing it. Delytact is another viral therapy with impressive results; it is approved in Japan but not easily accessible for Americans.

  • Some antidepressant drugs are thought to help treat tumors and can also help treat the depression that often follows a brain tumor diagnosis.
  • Combining off-label drugs is another approach I would consider. Two specific protocols for this strategy appeal to me. The first is the Care Oncology Protocol, which combines several off-label drugs with temozolomide in an attempt to target a tumor from several different angles. CUSP9v3 is another protocol that has caught my eye. Both are worth considering, but it is not yet clear which combination is best, and it is possible that a subset of the drugs combined in CUSP9v3 might work just as well with less side effects and a lower cost.
  • Checkpoint inhibitors: Cancer cells are tricky. They often manage to avoid being attacked by the immune system by generating signals called checkpoints that block immune attack—as though the tumor cells have put up a “do not disturb” sign. Drugs known as checkpoint inhibitors—many of which are FDA-approved for other cancer types and can easily be used off label—essentially remove that “do not disturb” sign, allowing the immune system to attack the tumor.

Many clinical trials have shown that, on their own, checkpoint inhibitors are not very effective (except in a small trial showing that using them before surgery may help). The reason for this lack of effectiveness is that there are not enough immune cells near the tumor to fight it. I believe an effective solution would be to apply another strategy to trigger an immune response that would get the immune cells in place, then apply a checkpoint inhibitor to unleash their response. Such a strategy could be anything that causes tumor cells to die, such as a cancer vaccine, a viral therapy, or even Optune, which would trigger an immune response.

In all, I would consider one or more of the options outlined above, especially those that can be combined with each other. And for anyone dealing with their own glioblastoma case, I highly recommend signing up for our powerful patient navigation program.

Dr. Musella can be reached at musella@virtualtrials.com.

Disclosure: The following companies are or have been sponsors of the Musella Foundation: Novocure Ltd (Optune), GT Medical (Gamma Tiles), Chimerix (Onc-201), Genentech (Avastin).

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A message from Curious Dr. George:

The goal of Cancer Commons is to help patients identify and access their best possible treatments, one patient at a time, while moving the field forward. If you have advanced cancer, let our molecular oncology scientists provide personalized information about your options.

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