Every other day, Lynn Oxenberg leans over her bathroom sink while her husband shaves the shade of auburn hair that is beginning to cover his head.
Once clean-shaven, she sticks four spots of tan onto her scalp with electrodes designed to stop aggressive cancer cells from growing in her brain.
She puts the protruding wires and a two-book battery in a mini backpack, then heads to the grocery store, the library, or lunch with friends.
This has been Oxenberg’s routine for six years. It can be arduous, but it helped keep the 73-year-old Elkins Park grandmother alive much longer than most people with glioblastoma, an aggressive brain cancer that kills in 15 months on average.
Penn doctors are currently investigating whether the treatment routine, coupled with highly sensitive MRI monitoring, could one day make Lynn’s experience – living with glioblastoma for years – less of an anomaly.
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There is no cure for glioblastoma and the disease is exceptionally difficult to treat. Glioblastoma is usually treated with a combination of surgery, radiation, and chemotherapy, then closely monitored for signs that the cancer has returned. Once cancer begins to grow back, it is almost always fatal. Surgery, chemotherapy, and radiation therapy will never be able to eliminate all of the cancer, because glioblastoma tumors burrow into brain tissue like the tentacles of an octopus.
Penn researchers are testing whether they can help glioblastoma patients, who have already undergone surgery and other treatments to shrink the size of their tumor, to live longer by combining the tumor treating field therapy (TTF) that Oxenberg uses with artificial intelligence-based MRI scans which take the “temperature” of a tumor for very precise results.
The combination deviates from the standard of care for the disease. Instead of waiting for the disease to return and treating it with more chemotherapy or radiation, TTF therapy, made by Swiss pharmaceutical company Novocure, constantly sends electric fields through the brain to prevent cancer cells from develop. Temperature-taking MRI scans can show early signs of tumor recurrence and help doctors quickly change their care plan.
Suyash Mohan, director of neuroradiology research at Penn, calls it a “whole brain” treatment that could be more effective than trying to isolate a tumor that can never be completely removed. TTF therapy controls cancer cells and highly detailed MRI scans can help make rapid changes to treatment, if necessary.
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Optune, Novocure’s FDA-approved TTF therapy device, has shown modest results in extending the lifespan of glioblastoma patients. Patients in Novocure’s phase 3 trial who wore the device 70% to 80% of the time lived an average of 21 months, compared to 15 months in patients who received standard treatment. But the device can be cumbersome: patients must shave their heads to glue the electrodes in place. Unlike medications that stay in the body for hours or days after taking, Optune only works when worn.
Some cancer experts say that while the results are promising, it can be difficult to convince patients to take such aggressive measures. The treatment is covered by Medicare and many commercial health plans, but costs $21,000 per month without insurance.
It is unclear whether this approach will ever lead to a significant change in the outlook for glioblastoma patients. But Mohan thinks Penn’s work is a glimpse into the possibility that one day one of the most aggressive cancers could be treated as a chronic disease.
“The overall survival of this disease has not changed over the last 25 years,” Mohan said. “We need to re-evaluate how we approach this tumor. »
Artificial Intelligence-Driven MRIs for Glioblastoma
Glioblastoma is a fast-growing brain cancer, more common in older people. Treatment can slow the growth of cancer and help manage symptoms, but there is no cure.
Patients can have surgery to remove most of the tumor, even if some are too deep in the brain to access. Surgeons usually cannot remove the entire tumor: its tentacles that reach down into the folds of the brain are impossible to remove safely.
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Doctors may recommend radiation or chemotherapy to kill remaining cancer cells, but because the tumor is so closely linked to the brain, it is difficult to target cancer cells without also killing healthy brain cells.
Doctors rely on MRI imaging to help them determine whether treatments are shrinking the tumor. But some treatments cause inflammation that can look like a tumor on an MRI, making it difficult for doctors to determine exactly where the tumor is.
Mohan and his colleagues developed a tool that acts like a thermometer, using artificial intelligence to give a more nuanced reading of the brain. The MRI technique uses images of the entire brain to create a real-time “temperature” that can tell doctors more precisely where a tumor is and whether it is growing or shrinking.
Patients are examined every two months, as often as they would be with a traditional MRI. But results are available immediately, which can reduce the anxiety of waiting for answers and allow doctors to make more immediate changes to patients’ treatment plans, Mohan said.
The goal is to provide more advanced MRI images that can help doctors make faster and more accurate decisions about patient care, he said.
Disrupting glioblastoma cells with electricity
Penn is currently testing the MRI technique in a clinical trial in glioblastoma patients receiving TTF treatment. While chemotherapy and radiation target specific tumor spots—with varying precision—TTF sends electrical currents throughout the brain to disrupt the growth of cancer cells.
Early clinical trials of Optune revealed a slight increase in life expectancy for patients treated with TTF therapy and a greater likelihood of survival for up to five years.
But the demands of the treatment outweigh the potential benefits for some patients, said Stephanie Weiss, chief of the division of neurological oncology at Fox Chase Cancer Center.
Patients must shave their heads every other day to ensure the electrodes stick to their skin and use glue which can be irritating.
And because the treatment only works when the device is worn, patients are supposed to wear it at least 18 hours a day for two years.
“It makes a lot of sense,” Weiss said, “but I think what we’re doing right now is rudimentary.”
Novocure executive chairman William Doyle agrees there is room for improvement. The company, which has offices in Wayne, is designing thinner skull patches and studying whether they can increase the power delivered by the patches, which would reduce the length of time patients must wear the device.
The company is also working on an app that would help patients track how long they have worn the device.
Granted, it’s not the most stylish look, Optune’s gauze headband and mini backpack may allow glioblastoma patients to survive long enough to reach important family milestones, like graduation or child marriage, Doyle said.
“You can live with this” is the message the company sends to patients and doctors, Doyle said.
Living with glioblastoma
Oxenberg was diagnosed in December 2017 and after undergoing surgery and as much chemotherapy as her body could tolerate, her doctor suggested she try Optune. Oxenberg agreed.
She began treatment in April 2018 and still wears the device 90% of her day.
She was hesitant to part with her red hair which had been her identity ever since the nurses in the maternity ward paraded her around to show off the flaming stuffed animals which stuck out from the hospital swaddling blankets.
“I realized my hair was overrated,” she said.
It’s a job she says she’s willing to do to spend more time with her husband, children and grandchildren.
Earlier this month, all ten traveled to the Outer Banks of North Carolina for their annual summer vacation. The sun and sea breeze felt different on his exposed scalp. And she soaked it up.