The brain cancer diagnosis was so grim for Rick Miller that he says a social worker told him to “put my affairs in order.” Glioblastomas usually kill people in about 12 to 15 months.
But that wasn’t the end of Miller’s journey. He and his wife, Diana, made a trip from their Eastern Shore home to the University of Maryland Medical Center in Baltimore to hear other options and enrolled in a clinical trial.
That was three years ago.
Miller, 65, doesn’t live alone. There is no sign of cancer and he is going back to his boat maintenance. Two months ago, he and Diana traveled to their son’s wedding in Florida.
“It worked,” stated a smiling Miller, standing in front of his next boat project, his own 40-footer, on his property near Chestertown.
His doctors cannot say he is cured, nor can they guarantee that the cancer will not return, or even officially credit the treatment he received during the clinical trial for his life and health. But, they say, he and most of the 14 people who took part in the first study are still alive. After years of little progress in discovering new treatments for glioblastomas, they are in the unusual position of having hope.
Glioblastomas are the type of brain cancer that killed U.S. Senators Ted Kennedy and John McCain and President Joe Biden’s son Beau. They are normally treated with surgery, chemotherapy, and radiation, but the tumors almost always come back. Federal figures show that about 14,000 people are diagnosed each year in the United States, but only 5% survive five years, according to the Glioblastoma Foundation.
The foundation cites the method used on Miller, focused ultrasound, as one of the few avenues for promising research. Others include reusing older drugs and earlier detection.
Miller received standard care when he entered the Phase 1 trial. Such tests are intended to assess safety and demonstrate whether a process works. Surgeons on the East Coast had already removed a large, late-stage tumor from the right side of Miller’s brain in 2019.
At the Baltimore hospital, neurosurgeon Dr. Graeme F. Woodworth and medical personnel head Miller with a metal halo and screws. They put him in a magnetic resonance imaging or MRI machine and injected a bubbling agent into his arm. They then used ultrasound or high-frequency sound waves to guide the tiny bubbles to the precise location and shape of the tumor.
Woodworth viewed images of the MRI on a computer screen from a control room as the commotion of the bubbles caused temporary leaks in the protective layer around the brain known as the blood-brain barrier. The barrier of cells and blood vessels normally protects the brain from toxins, but also blocks beneficial therapies.
The openings lasted for hours, long enough for Miller to return home and follow separate instructions from his cancer doctors for taking standard chemotherapy pills.
He came back monthly for more targeted ultrasound treatments.
Woodworth has not yet submitted his findings in a peer-reviewed journal, but he is working with pharmaceutical leaders and seeking funding for more and larger studies to learn more about the technique’s efficacy and get it approved by the US Food and Drug Administration. and Drug Administration for wider uses. They also work to determine if there are more effective drugs overall or that help people with different types of glioblastomas.
“All we can say now is that we did it safely,” said Woodworth, also a professor and chair of neurosurgery at Maryland’s School of Medicine. “Today it feels promising. But we need more evidence.”
Doctors have already refined the process of forming the opening to the tumor site and eliminated that immobilizing metal halo, which Miller called the worst part of the trial.
Focused ultrasound is a growing area of research, with more than a dozen companies investing nearly $400 million last year to potentially provide better treatment for multiple cancers, not all of them in the brain, according to the Focused Ultrasound Foundation.
Woodworth is working with an Israeli medical device company, Insightec Ltd., which developed the tools for the procedure.
Three years later, the Millers couldn’t be happier with the results, whether due to the trial, his general good health before his cancer diagnosis, or a truly successful surgery performed by neurosurgeon Dr. Khalid Kurtom of the University of Maryland Shore Regional Health.
Miller’s absence of cancer has been confirmed in regular scans by Dr. Mark Mishra, director of radiation oncology clinical research at the University of Maryland School of Medicine and associate director of the Hospital System’s Cancer Network. He presented the trial option to the couple.
“As soon as I mentioned it, they were both very interested and were among the first to sign up,” Mishra said of Miller and his wife, who is a nurse. “He stands out because he’s done so well. He hasn’t had a recurrence, but more importantly, he’s maintained his quality of life and is getting back out and doing things he used to do before he was diagnosed with cancer. “
Mishra noted the “difficult conversations” they had before treatment about the diagnosis and the rarity of long-term survival. Now he said, “Mr. Miller’s case shouldn’t be unique, and the only way to raise that bar is through clinical trials.”
He said they will take place in Maryland, other universities and the National Institutes of Health, and doctors will be looking at different types of drugs for new or recurrent tumors, as well as for different subtypes of glioblastomas. Since there may be different molecular features at different stages in different patients, they may be treated uniquely in the future, towards personalized or precision medicine.
Other focused ultrasound studies unrelated to the Maryland studies are also planned, including at Johns Hopkins Medicine.
dr. Chetan Bettegowda, a Hopkins neurosurgeon scientist, is working on those trials. He said he and Woodworth are informally sharing some information about the technology to advance the research and collaborate on a separate trial in a different area.
Bettegowda said the news about Miller’s health was “truly remarkable” and said focused ultrasound had the potential to be a “paradigm shift” in the treatment of glioblastomas.
“We’ve long understood that the brain has natural mechanisms to prevent drugs from entering, and we’ve tried other ways, such as with catheters or polymers or local injection into the brain after surgery,” he said.
“Some have shown some effects, but unfortunately not enough effects to cure large numbers of people,” he said. “That’s where having something like this that’s non-invasive and can be done repeatedly and focused and tuned to individual tumors is pretty powerful. There’s a lot of enthusiasm for that.”
The area where Bettegowda and Woodworth are working together is to improve the assessment of how well the treatment is working. For now, that’s limited to the occasional MRI. That’s because tumor cell biomarkers, which could provide more information, are blocked by the blood-brain barrier from entering the body’s circulation, where they can be picked up in a blood test.
Targeted ultrasound could provide the openings for that blood test — or liquid biopsy — that shows how tumor cells respond to chemotherapy, radiation or other treatments down to their DNA.
The ability to provide better results, Bettegowda said, is what keeps him in the operating room and lab.
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Diana and Rick Miller are happy with the investigation, though they hope Rick never needs a trial again.
Diana Miller, who is being treated for breast cancer, recalled how her husband passed out several times during a previous trip to Florida, episodes she initially thought were related to his heart. After they returned home, he texted his wife gibberish during another episode. At that point, she rushed him to an emergency room, and soon after, they learned about the advanced tumor.
She is grateful to the doctors on the coast and in Baltimore, as well as their network of friends who support them. She particularly noted those who helped move their clients’ boats to and from the water for maintenance and storage.
Rick Miller plans to continue some work, but expect to sell some inventory from his shop and yard and move closer to retirement. He can’t handle 12-hour days at Miller’s Marine, the company he’s built over the decades between the Chester River and the Chesapeake Bay.
However, his mind still knows its way around a boat’s engine, HVAC unit and electrical systems. He will use that knowledge to restore the 40-foot boat he keeps in a large shed opposite his house for “when he wakes up with a little more ambition.”
For now, the couple’s journey continues on a 17-foot boat that Rick gave to Diana a while ago and taught her how to work. They often go out to enjoy the evening together and take their dog for a swim.
“It’s my wife’s boat,” he said, “but sometimes she takes me.”