As her daughter fought a brain tumor, part of Sue’s responsibility was to help ensure that she could maintain her home and the sense of dignity that went along with it, even as her mobility and independence took a hit.
The US Food and Drug Administration (FDA) determines whether any particular drug may be prescribed by doctors. It’s normally a years-long process to get a drug approved, across multiple phases, first to ensure a drug’s safety, then to determine its efficacy, and finally to assess its effectiveness compared against existing “gold-standard” treatments. Yet in some cases, patients with brain tumors and other serious conditions can get permission to try treatments that haven’t yet gone through this process, thanks to the FDA’s Expanded Access program.
Expanded Access, which is sometimes called “compassionate use,” due to its roots in offering drug options to terminally ill patients, gives patients a way to access investigational or experimental treatments outside of the structure of a clinical trial. In the past, clinical trials were the only way to access experimental treatments. According to the FDA, Expanded Access is for patients “with an immediately life-threatening condition or serious disease or condition to gain access to an investigational medical product (drug, biologic, or medical device).”
Treatments through Expanded Access remains something that is carried out under the supervision of your doctor, and so discussing all of your options with your neuro-oncologist remains the first step. Whenever possible, your doctor will probably recommend clinical trials before expanded access, because clinical trial drugs may be better understood from the perspective of safety, dosing, side effects, and drug interactions. Furthermore, data collected in clinical trials contributes to global progress against the disease.
Nevertheless, many brain tumor patients may be in a situation where standard treatments have been exhausted and clinical trial eligibility cannot be met. In those cases, Expanded Access might be the best or only way to use a drug that could help.
The program works like this:
- A doctor asks a drug company to provide an experimental treatment.
- The doctor submits the treatment plan to an Institutional Review Board (IRB), who act as a check on patient welfare and ensure that the patient can properly give their informed consent.
- The doctor and the IRB submit the request to the FDA, who approve most requests that have gone through the appropriate steps.
One obstacle to Expanded Access is that many doctors have limited experience going through the process. To remove roadblocks, the FDA launched an initiative in 2019 to make it easier for doctors and patients to take advantage of the program. The FDA’s oncology staff now run a call center for doctors wishing to submit Expanded Access requests on behalf of their patients. FDA staffers will now help the doctor with paperwork, drug company contacts, and IRB proposals.
While no patient hopes to find themselves in a position where throwing a Hail Mary pass seems like the best option, it remains an unfortunate reality that many brain tumor patients reach that point. When other approaches seem exhausted
Brain tumors vary a lot, and those variances shape what kind of treatment is most appropriate. A typical journey for a person with a brain tumor goes like this: an MRI produces a preliminary brain tumor diagnosis, followed by surgery to remove the tumor, and then a biopsy—that is, a detailed chemical analysis—gives doctors a clear understanding of what key traits and mutations a tumor has. Only then can the rest of the treatment plan come together.
But researchers at UT Southwestern’s O’Donnell Brain Institute have developed a new AI that can determine the key mutations in a brain tumor from scans alone—no surgery necessary. They’re using a “deep learning” AI model, which is the same technique your phone’s photos app uses to identify faces. The technique classifies the mutation status of a brain tumor from 3D scans with over 97% accuracy. The researchers are planning some additional experiments but they hope that it will lead to more patients with gliomas able to be treated without resorting to surgery.
A pediatric oncologist at the University of Florida will launch the first in-human trial of a brain tumor immunotherapy treatment this summer. All immunotherapy techniques for cancer are based on the principle of teaching the immune system to recognize cancer cells as foreign invaders.
Dr. Elias Sayour has developed a technique that extracts genetic material from a patient’s own tumor, encases it in a fat-like nanoparticle, and injects the particles into patients. To the immune system, these particles look like a dangerous virus, and this triggers an immediate strike, not just on the injected particles, but on the similar-looking tumor cells.
Researchers at the Cumming School of Medicine at the University of Calgary recently published a new study that showed that combining Niacin, aka vitamin B3, with chemotherapy, helps the immune system attack glioblastoma cells, which can dramatically slow the advance of the disease.
One reason glioblastoma is so deadly is that it often hijacks the immune system, causing it to help the cancer instead of destroying it. The researchers found that this common compound can help reverse that and give drugs and the immune system the leg up it needs.
However, the lead researcher of the study, Dr. Wee Yong, cautioned that just because the findings involve a widely available compound, people shouldn’t try and dose themselves. “It’s extremely important to follow strict protocols and conduct a clinical trial first, even though this treatment involves two well-known, existing therapies. It’s important people don’t rush out and try adding niacin on their own, as we need to confirm dosage, delivery and length of time for optimum clinical results,” Yong told UCalgary News.
Diffuse intrinsic pontine glioma, or DIPG, is one of the most common and most deadly forms of pediatric brain tumors, and it is usually inoperable because it attacks the brain stem.
Researchers at the University of Michigan have found positive results in mouse models using a gene therapy that stimulates the immune system. Normally, DIPG tumors suppress immune system activity in their surrounding tumor microenvironment. But the researchers introduced a gene called TK/Flt3L, which encourages immune activity in the region. They found that introducing this gene increases immune activity around the tumor without causing adverse side effects. This looks to be a promising step in developing future clinical immune therapies for DIPG.
The mainstream, standard-of-care treatment for brain tumors consists of some combination of resection (surgery to remove the tumor), radiation (destroying cancer cells with a precision-shaped beam of energy), and chemotherapy (the use of powerful drugs that are toxic to tumor cells. These are all effective to some degree, and though none of them represent a “cure,” all are important tools to be used by oncologists. There is much ongoing research to improve techniques in all three areas.
At the same time, many researchers and firms are seeking on approaches to complement these three core techniques. Many of these have promising science behind them, and appear to be gaining a place in the toolkit as well.
A word of caution: these approaches are at various places in the clinical trial / approval pipeline, and patients should discuss with their doctors, or a team at a major brain tumor center, to identify a treatment strategy for you.
Status: FDA approved in newly diagnosed and recurrent brain tumors
GammaTile is an approach in which a neurosurgeon removed as much tumor tissue as possible, and then implants a small wafer into the tumor bed, where it delivers highly targeted doses of radiation to help prevent regrowth. The technique is for operable brain tumors, including gliomas, meningiomas, and metastases. Compared to traditional radiation therapy, GammaTile should keep localized to protect healthy brain tissue. In a clinical study, patients experienced better local control compared to previous treatments.
Status: FDA Approved in newly diagnosed and recurrent brain tumors
Optune, a device that consists of an array of electromagnetically-charged nodes worn on the scalp, is an FDA-approved adjunct therapy for brain tumors. Most patients on Optune are also receiving chemotherapy or radiation. The technique, also known as “tumor-treating fields” interferes with a tumor’s cell division, leading to longer periods of no disease progression for patients using Optune plus TMZ compared to patients who on TMZ alone. The device will generally be worn nearly 100% of the time to be maximally effective.
Status: Pre-clinical Trials
Two big problems vex doctors trying to treat brain tumors. One is the blood brain barrier and the other is targeting treatments so as to damage tumor tissue but spare healthy brain. Sonodynamic therapy (SDT) is an approach currently being explored by researchers at the Ivy Brain Tumor Center in Phoenix, AZ. With this technique, drugs are introduced into the brain that only become toxic once they’re exposed to ultrasound. So two levels of targeting are involved. First, researchers start with a drug that is selectively absorbed by tumors. Second, they aim the ultrasound so the drug only becomes activated right where it is needed, sparing nearby tissue.
BBB Drug Delivery Systems – Lipid or Polymer Nanoparticles
Status: Various clinical trials
The other problem mentioned above, the blood-brain barrier (BBB), makes drug treatment of any central nervous system disease challenging. Temozolamide (TMZ), which became FDA approved in 2005, does cross the BBB, but many newer molecules that researchers are developing do not. Fortunately, many researchers are also investigating molecules that can help future drugs cross BBB. A common theme in these approaches is the use of bio-engineered nanoparticles that are small enough or feature surface adaptations that allow passage across the BBB. Some of thee nanoparticles may even be candidates to help deliver gene therapies to tumor sites.
Fatigue is the most common side effect of brain tumor treatment. All the major forms of cancer treatment, including chemotherapy, radiation, and even surgery recovery can cause fatigue.
Fatigue is more than simple tiredness. It is a widely-recognized medical condition, marked by extreme lack of energy, which can cause inability to function in daily life. It may be acute – lasting a short time in connection with a direct cause, or chronic — becoming a long-term fact of life for someone affected.
According to the NIH, fatigue related to cancer is different than what healthy people feel. Healthy people’s fatigue is generally relieved by sleep and rest. But for someone with a brain tumor, especially if they’re undergoing treatment, it is normal to experience some fatigue all the time, and for it to become very serious from a light amount of activity.
Even compared with other cancers, brain tumors can lead to especially severe cases of fatigue. Dr. David Cachia of the Medical University of South Carolina told Cancer Network that one study found 96% of patients with high-grade gliomas to experience moderate to severe fatigue. It’s not limited to the worst brain tumors either. Another study found that 39% of patients with lower-grade gliomas, interviewed more than 3 years after finishing treatment, still reported bouts of severe fatigue.
Dr. Cachia pointed out a few other contributing factors for fatigue. Patients in active treatment are more than twice as likely to experience fatigue. Patients with many other symptoms, such as pain, distress, or weakness, were more likely to experience fatigue. This is called symptom clustering. And women are 2.5 times more likely than men to report severe fatigue.
If you’re experiencing extreme or worsening fatigue, that’s something to speak with your doctor about. You may be experiencing side effects from medication or it may be a sign of something that warrants medical attention.
Additionally, taking steps around an overall positive and healthy lifestyle can make a difference:
- eat a healthy and balanced diet.
- Take time to relax, and save your energy for when you need it. It’s OK to do less than you’re accustomed to.
- Practice good sleep habits, such as turning off the tv and limiting screens or highly stimulating activities close to bedtime.
- Stretch and do some light exercise if you’re able to.
- Get a massage. There’s actual research that massage helps with cancer-related fatigue and overall quality of life.