PNIBLOG

A Journey to New Frontiers

Brain tumors sometimes make themselves known in baffling ways. For Redmond “Rusty” Doms, 77, the odyssey of symptoms began when people he was looking at—people he knew well—morphed into faces he could no longer recognize. “I was starting to look at people, and all of a sudden their appearance would change,” he recalls. “I knew who they were, but I’d look at them and didn’t know who they were. I’d lose my train of thought. I’d get a little disoriented.”

Doms—a longtime, cherished trustee of the Saint John’s Health Center Foundation—is often on the hospital campus. One day as he walked by his primary care doctor’s office, he mentioned the strange sensations. The doctor ordered a brain scan. The next day Doms’ phone rang, and he answered to find Pacific Neuroscience Institute director and neurosurgeon Daniel F. Kelly, MD on the phone.

Doms was diagnosed with late-stage glioblastoma, an aggressive brain cancer.

Achal Singh Achrol, MD and Santosh Kesari, MD PhD

Achal Singh Achrol MD & Santosh Kesari MD PhD

Today, however, Doms is fighting back against the cancer with the help of a trio of neurosurgeons and neuro-oncologists who are bringing to bear the best possible weapons. Dr. Kelly performed surgery in May 2016 to remove as much of the tumor as possible. Post-surgery, neuro-oncologist, Santosh Kesari, MD, PhD, treated him with chemotherapy, radiation therapy, and Optune, a device worn on the head to deliver electromagnetic radiation to the tumor. PNI co-founder Dr. Kesari is director of neuro-oncology at PNI and professor of neurosciences and chair of the department of translational neurosciences and neurotherapeutics at John Wayne Cancer Institute.

But the tumor progressed and, earlier this year, Doms became only the second person in the nation to receive an intratumoral investigational therapy that features a “trojan horse” technique to deliver a bioengineered fusion protein that specifically targets the tumor. The MDNA55 Medicenna Trial is led by PNI neurosurgeon Achal Singh Achrol, MD, who serves as principal investigator for the clinical trial in collaboration with Dr. Kesari. Dr. Achrol is chief of the glioma surgery program and director of neurovascular surgery and neurocritical care at PNI.

Now Doms is looking forward to getting back to his regular activities which include paddleboarding at the beach. “I’ve got challenges, but overall I’m a happy patient,” Doms says. “Dr. Kelly saved my life, and Dr. Kesari gave me a chance at a normal life.”

This unique treatment exemplifies the philosophy behind neurological care at PNI: Find the best treatment for each individual patient, and if one doesn’t exist, innovate.

Brain cancer care is highly specialized, says Dr. Achrol. Pacific Neuroscience Institute physicians Dr. Kelly, Dr. Kesari and Dr. Achrol practice at Providence Saint John’s Health Center in Santa Monica and Providence Little Company of Mary Medical Center Torrance. PNI provides state-of-the-art care for patients with all types of brain tumors, as well as stroke, movement disorders such as Parkinson’s disease and other neurological conditions.

“This is the purpose of the Pacific Neuroscience Institute and the John Wayne Cancer Institute,” Dr. Achrol says. “We accept even the most complex cases, and specialize in advanced precision therapies not yet available at other health centers.”

Patients have access to more than a dozen clinical trials at PNI, and about 10 other clinical trials are in the planning stages, says Dr. Kesari. These trials are particularly important for patients with extremely challenging diseases, such as glioblastoma or metastatic brain cancers from lung, breast and melanoma.

“The standard-of-care treatments can only take you so far in terms of survival,” Dr. Kesari says. “That’s why innovations and clinical trials are the only way to make a difference and improve the outcomes for these deadly diseases. We offer patients hope. That’s really what clinical trials are all about.”

Daniel F. Kelly, MD

Daniel F. Kelly, MD

PNI neurosurgeons and neuro-oncologists also strive to make treatments more tolerable and precise. Dr. Kelly and Dr. Achrol, for example, are experts in minimally invasive neurosurgery. Minimally invasive techniques use smaller, more precise openings to minimize brain, scalp and muscle manipulation and lead to quicker recovery times for patients.

An advanced level of surgical and technical expertise is needed to provide the treatment Doms received. For the administration of the investigational drug, Dr. Achrol mapped his specific tumor through 3D imaging using specialized computer software to determine its mass and optimal placement sites for treatment catheters that deliver therapy to the entire tumor, a process called “convection-enhanced delivery.” Then, using real-time MRI, Dr. Achrol made small holes in the skull to insert tiny catheters into the tumor along computationally-planned trajectories to deliver the bioengineered fusion protein, which features a “trojan horse” delivery system.

Dr Kelly and Dr KesariThe bio-engineered fusion protein, called MDNA55, binds to specific cell receptors, called IL4 receptors, that are only found on tumor cells—not normal brain tissue. Once attached to those cells, the protein delivers its payload: a toxin that is absorbed and kills the cells while leaving surrounding healthy tissue unharmed. While chemotherapy only kills dividing cancer cells, the toxin kills both dividing and quiet, or slow-growing, cancer cells, thus increasing the odds that more of the cancer will be destroyed.

“While it’s technologically challenging, the concept itself is relatively straight-forward in that you want to get the drug to every tumor cell,” Dr. Achrol says. “We are one of only two sites on the West Coast that offer this clinical trial and we’re currently the leading enrollment site nationally of only a handful across the United States.”

It’s fitting that physicians at Pacific Neuroscience Institute are leading the trial enrollment because the treatment grew from research pioneered in the 1990s by Robert W. Rand, MD, PhD—a neurosurgeon associated with the John Wayne Cancer Institute. The idea of injecting a toxin directly into a tumor was a promising concept, but surgeons two decades ago lacked the technology to refine the treatment.

“We are using a more sophisticated delivery system—injecting the toxin directly into the tumor at the time of surgery,” Dr. Kesari says. “We inject it through a catheter over many hours to get as much drug as possible into the entire tumor area, and we monitor it in real-time with the MRI machine.”

There are broader applications as well. The concept of engineering a toxic component to be delivered to the tumor without affecting the surrounding tissue can be applied to other types of cancers, Dr. Achrol says.

“I have a world of confidence with my doctors,” Doms says. “I couldn’t be in a better place. I think Saint John’s and PNI have created a world-class neuroscience team here that cannot be found anywhere else.”

Rusty Doms and his paddleboard

Rusty Doms with his paddleboard

As a trustee of the Saint John’s Health Center Foundation, Doms has provided support for many decades and continues to lead the way through his philanthropy. He serves as an advocate for the innovative work being done at PNI and its ongoing benefits to patients and their families. Generous support for neuroscience research pioneered at PNI is a key component to finding successful treatments and innovative cures for neurological and cranial diseases.

“Results from clinical trials like MDNA55 give patients tremendous hope,” says Dr. Kesari. “It gives us even more motivation to move the field forward as much as possible and as quickly as possible to get these innovative treatments to our patients.” People don’t realize how much support goes into developing clinical trials and bringing them to the clinical setting, he adds. “Someone had to do it for the first time at some point. Philanthropy is really needed to help get a trial like this to the stage it’s at now.”

 

For more information about supporting Pacific Neuroscience Institute, please contact Karter White, PNI Foundation Administrative Director at 310-829-8271.

To find out more about our brain tumor clinical trials program, please contact us at 310-829-8265 or neuro.oncology@jwci.org.

Pioneers of Innovation from Saint John’s Foundation on Vimeo.

Adapted from original article written by SHARI ROAN and photographed by MONICA OROZCO in FALL 2017 issue of BREAKTHROUGHS Magazine published by Providence Saint John’s Health Center.