Out of the box
Standard treatments for glioblastoma include surgery, radiotherapy, and chemotherapy, and many patients cannot tolerate some of these, Dr. Baskin noted. Hence, there is a great need for a different therapeutic approach that yields better outcomes with lower toxicity.
“We didn’t want to develop another chemotherapeutic agent that would help you live another 2 months,” he said in an interview. “We were trying to think out of the box.
“If you want to do something that will really make a difference in an aggressive tumor like glioblastoma, you have to attack something so basic that the tumor can’t evade it,” he said. “For example, with temozolomide, if it is unmethylated, the tumor can repair the DNA damage from the chemotherapy. Even if you’re sensitive to begin with, over time, the tumor will eventually become resistant.”
The new device stems from work by Dr. Baskin and colleagues on mitochondria, which he describes as the powerhouse of the cell. “Mitochondrial DNA can’t repair itself, so if you damage the mitochondria, you will damage the cell, and theoretically, it cannot repair itself,” he said.
In preclinical models, the oscillating magnetic fields generated by the new device were shown to kill patient-derived glioblastoma cells in cell culture without having cytotoxic effects on cortical neurons and normal human astrocytes. Animal studies also showed that it was effective and nontoxic, explained Dr. Baskin.
However, getting the device to human clinical trials has been slow going. “We wanted to start an early-phase trial for an investigational device, but the FDA is overwhelmed with COVID-related applications,” he said. “That has taken priority, and we understand that. So we were able to evaluate it on a patient through compassionate use via the [Food and Drug Administration]–approved Expanded Access Program.”
Exciting possibilities
The patient was a 53-year-old man who had undergone radiotherapy and chemotherapy, and the tumor was progressing. Imaging revealed the presence of leptomeningeal disease, which is associated with a poor outcome and a median survival of 3.5-3.9 months.
The patient was fitted with the helmet device and wore it under supervision for the first 3 days of treatment, during which time the strength of the oscillating magnetic fields was escalated. After this initial supervised phase, the treatment continued at home without supervision, using the same regimen as on the third day.
Treatment was first administered for 2 hours while under supervision and was then gradually increased to a maximum of 6 hours per day. The patient was evaluated clinically on days 7, 16, 30, and 44 after initiation of treatment. No serious adverse events were reported during treatment. The patient’s wife reported subjective improvement in speech and cognitive function.
Dr. Baskin noted that the patient had been experiencing falls for the past year and a half before treatment was initiated. “And then he tripped and fell and sustained a head injury that he subsequently died from,” he said.
Autopsy results confirmed the rapid response to treatment, and tumor shrinkage appeared to correlate with the treatment dose.
“Our results in the laboratory and with this patient open a new world of noninvasive and nontoxic therapy for brain cancer, with many exciting possibilities for the future,” Dr. Baskin commented.
He said his team has experimented with this approach with other tumor types in the laboratory, including triple-negative breast cancer and lung cancer. “We’ve only tried it in a culture so far, but it seems to melt the cancer cells,” he said.
The work was supported by a grant from the Translational Research Initiative of the Houston Methodist Research Institute and several foundations. Dr. Baskin and two coauthors are listed as inventors on a U.S. patent application filed by Houston Methodist Hospital for the device used in this report.
A version of this article first appeared on Medscape.com.