Brain Cancer and Fighting Against the Odds
A lifesaving clinical trial called ONC201 extended Bryan Fevold’s life when no other treatments worked. Diagnosed in 2022 with stage 4 diffuse midline glioma (DMG), Bryan and his wife, Lynn, embarked on a journey from Colorado to California, a transition they describe as “incredibly difficult.”
Lynn was thrust into a whirlwind of insurance battles, mountains of paperwork, and waivers—all while providing care for her critically ill husband.
The Onset of Devastating Symptoms
In early 2022, Bryan’s condition worsened. He lost sensation in his hands and legs, but the most unsettling symptoms were the gradual loss of speech and vision—a terrifying ordeal that plunged them into quiet panic and desperation.
Determined to find a solution, Lynn sought every possible option. With less than one year of average survival for DMG patients, the race against time was critical.
The Science Behind Bryan’s Tumor
Bryan had a rare and aggressive H3K27M gene mutation, affecting the histone protein responsible for regulating gene expression. This mutation fuels the tumor’s rapid growth, making it highly resistant to traditional treatments. Such was the case with Bryan when both chemotherapy and radiation treatments showed no effect on slowing progression.
Hope Found in ONC201
Miraculously, Bryan has been in the trial for two years, far exceeding his initial prognosis.
A Profound Emotional Toll
By the time Bryan arrived in California and met Dr. Akansha Sharma, his situation was dire. Yet Lynn recalls their meeting with gratitude and admiration: “She was like an angel. She easily saved Bryan’s life—and mine.”
“The anticipatory grief that people experience with a diagnosis like this is absolutely crushing.”
– Lynn Welker-Fevold
A Journey of Courage and Resilience
Bryan’s story is one of persistence, love, and medical breakthroughs—a testament to the power of science, advocacy, and sheer determination in the face of overwhelming odds.
Listen to Bryan and Lynn Discuss Living with Terminal Brain Cancer
Bryan and Lynn speak to SJCI about living with stage 4 diffuse midline glioma
What is Diffuse Midline Glioma?
Diffuse Midline Glioma (DMG) is a rare and aggressive brain tumor that primarily affects children but can also occur in adults. It is classified as a Grade 4 tumor, meaning it is malignant and fast-growing. These tumors typically form in the thalamus, spinal cord, cerebellum, and the pons in the brainstem.
- DMGs are astrocytomas that spread along the midline of the brain and body.
- They often contain mutations in the H3F3A gene, specifically the H3 K27M mutation, which is linked to their aggressive nature.
- Diagnosis usually involves MRI scans and molecular testing to confirm genetic markers.
Symptoms
Because DMGs grow rapidly, symptoms can appear suddenly and worsen quickly. Common symptoms include:
- Difficulty with balance and coordination
- Weakness in limbs
- Changes in vision or speech
- Difficulty swallowing
- Altered breathing and heart rate
The life expectancy for Diffuse Midline Glioma (DMG) is, unfortunately, very poor. The average survival time after diagnosis is typically less than one year, with most patients living between 8 to 11 months.
However, some factors can influence survival:
- Age: Patients younger than 3 years or older than 10 years may have slightly better outcomes.
- Tumor Size & Spread: Smaller tumors with less spread outside the brainstem tend to have a better prognosis.
- Genetic Mutations: The H3K27M mutation is associated with worse outcomes, while the HIST1H3B mutation may respond better to treatment.
Only about 10% of patients survive beyond two years, and 2% survive five years or more. While these numbers are discouraging, ongoing clinical trials and experimental therapies offer hope for improving survival rates.
What is ONC201 Clinical Trial?
The ONC201 clinical trial has shown promising results for treating Diffuse Midline Glioma (DMG), particularly in patients with the H3K27M mutation.
Key Findings
- ONC201 is a drug that was originally designed to target dopamine receptors, but researchers discovered it crosses the blood-brain barrier, making it effective for brain tumors.
- In two clinical trials involving 71 patients, the median overall survival was nearly 22 months for those who had not experienced tumor recurrence at enrollment.
- Almost one-third of patients lived longer than two years, which is a significant improvement compared to previous treatments.
- The drug works by disrupting metabolic and epigenetic pathways, leading to tumor regression.
Combination Therapy
Researchers are also testing ONC201 in combination with other novel agents to improve outcomes. The trial aims to assess blood-brain barrier penetration, immune response, and toxicity levels when combined with radiation therapy.
How does H3K27M3 affect Gene Expression?
The H3K27M mutation disrupts normal gene expression by altering epigenetic regulation, which controls how genes are turned on or off. Here’s how it works:
1. Loss of H3K27me3 Modification
- Normally, histone H3K27 is modified by methylation (H3K27me3), which silences genes that should not be active.
- The H3K27M mutation blocks this methylation, leading to abnormal gene activation in cells.
2. Changes in Chromatin Structure
- The mutation alters the 3D structure of chromatin, making it more open and accessible.
- This allows genes that should remain inactive to be expressed, contributing to tumor growth.
3. Increased Stem Cell-Like Behavior
- Studies show that H3K27M-mutant cells behave more like stem cells, meaning they proliferate rapidly and resist differentiation.
- This makes tumors more aggressive and more challenging to treat.
4. Impact on Tumor Growth
- The mutation promotes tumor formation by disrupting normal cell development.
- It also reduces DNA methylation, further enhancing gene misregulation.
Are Clinical Trials a First-line Treatment for Brain Cancer?
Brain cancer patients should consider clinical trials as a first-line treatment rather than a last resort because they offer cutting-edge therapies that may be more effective than standard treatments. Here’s why:
1. Access to Innovative Treatments
- Clinical trials provide new drugs, immunotherapies, and targeted treatments that may not be available through conventional care.
- Some trials focus on personalized medicine, tailoring treatments to a patient’s specific genetic profile.
2. Potential for Better Outcomes
- Standard treatments like chemotherapy and radiation may have limited success for aggressive brain cancers.
- Trials often test novel approaches that could improve survival rates and quality of life.
3. Early Intervention Matters
- Starting a clinical trial before the disease progresses may increase the chances of success.
- Some experimental treatments work best when tumors are smaller and less resistant to therapy.
4. Contribution to Medical Advancements
- Patients in trials help advance research, leading to better treatments for future patients.
- Participation can accelerate drug approvals, making breakthroughs available sooner.
5. Expanded Treatment Options
- If standard treatments fail, patients may no longer qualify for certain trials.
- Early enrollment ensures more choices and access to potentially lifesaving therapies.
“My advice to them would be to stay strong and fight with everything you have because your life is not over.”
– Bryan Fevold
Advice to Others Facing Brain Cancer Diagnosis
According to Bryan:
- Your life doesn’t stop.
- You have so much to do.
- You have so much to give.
Dr. Akansha Sharma left Saint John’s Cancer Institute (SJCI) and Pacific Neuro Institute (PNI) in early 2025. The ONC201 clinical trial is still active and enrolling and is being overseen by Dr. Wagle.
Contact Us:
If you or a loved one would like to discuss clinical trial options, please call the Saint John’s Cancer Institute at 310-582-7448 to speak with a program specialist.
Bryan’s Clinical Trial Team
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Akanksha Sharma, MD, Neuro-oncologist, Pacific Neuroscience Institute at Providence Saint John’s Health Center
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Naveed Wagle, MD, Neuro-oncologist, Pacific Neuroscience Institute at Providence Saint John’s Health Center
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