A barrage against brain tumors

Leading-edge surgery and innovative vaccines offer more hope than ever

Brain cancer survivor James R. Green

One morning in January 2012, James R. Green, a retired Veterans Affairs medical technician, stepped into the shower as usual in his Carmichael, Calif., home. When he raised his arm to pull the shower curtain, however, Green knew something was amiss. “I kept trying to pull the curtain shut, but my hand wouldn’t go where it was supposed to and my fingertips were numb.”

Green called for his wife, Donna, who was employed as executive chief of nurses for the VA in Northern California. “I told her I thought I was having a stroke,” he says. But within minutes his functioning returned, and he felt fine.

“I think a lot of people would’ve just waited for something else to happen at that point,” Green says. “But my wife, being a nurse, wouldn’t let me do that.” They headed to the emergency room, where he had a CT scan and MRI. Despite working in healthcare, neither was prepared for the diagnosis. “The doctor told us I had a large mass on the right side of my brain, near the motor strip, which is extremely dangerous. I was totally shocked. I went from one day being fine to the next hearing that I would need brain surgery,” says Green, now 70.

Donna Green was adamant that her husband have the best care, which meant a trip south to UCI Health. The news, however, got worse. “Once I had the tumor biopsied, I learned I had a glioblastoma. My wife and her nurse friend who accompanied us to the appointment burst into tears when we got the news. I guess that’s when I knew I was up against something daunting.”

Glioblastoma is a rare and notoriously difficult cancer. Most patients survive less than a year. Green underwent a 10-hour surgery at UC Irvine Medical Center in February 2012. That was followed by 31 days of radiation and chemotherapy at the UCI Health Chao Family Comprehensive Cancer Center. Today he continues treatment as part of an innovative clinical trial. Dr. Daniela Bota, a neuro-oncologist and national authority onemerging treatments for glioblastoma, oversees Green’s care.

Since 2012, treatment of glioblastomas has made tremendous strides. With newer techniques, UCI Health doctors are able to resect only the affected area, without harming normal brain tissue around the tumor, says Dr. Frank P.K. Hsu, chair of the UCI Health Department of Neurological Surgery. Hsu has pioneered many neurosurgical techniques that reduce patient risk and produce better outcomes.

An advanced navigation and brain mapping technology called BrainPath helps surgeons get in and out through the safest route and even allows them to remove previously inoperable tumors seated deep within the brain. Some tumors can now be removed through the nose (called nasal-endoscopic surgery) with use of a guided scope and imaging technology or through much smaller openings in the cranium than previously imaginable (called keyhole surgery).

Other advances, such as intraoperative imaging (imaging done on the spot during surgery rather than after), robot-assisted surgery and biopsy, and use of special fluorescent dyes to more easily identify cancer cells, all place the UCI Health Comprehensive Brain Tumor Program on the leading edge. “But no matter how advanced we are, treating a brain tumor is never routine,” Hsu says. Much depends on surgical skill, technology, radiation, chemotherapy and access to innovative clinical trials.

Glioblastoma is a particularly formidable opponent. It’s impossible to remove it entirely because the tumor is surrounded by a zone of migrating cancer cells, which infiltrate surrounding tissue. Traditionally chemotherapy and radiation have been the best bets to stave off new tumors. Unfortunately, the odds have never been tipped in the patient’s favor: The recurrence rate for glioblastoma is almost 100 percent, with an average time of recurrence between six and seven months.

Even more challenging, Bota determined that Green is EGFRvIII-positive. This means he has a particular gene mutation, shared by only 33 percent of glioblastoma patients, which causes him to be more prone to tumor regrowth. “Patients who express the EGFRvIII mutation have had even worse long-term survival rates than patients who do not have this mutation,” she says.

UCI Health, though, is home to the only National Cancer Institute-designated comprehensive cancer center in Orange County, with access to the latest postsurgical brain tumor drug and immunotherapy treatments.

“Many of our patients, like Mr. Green, participate in clinical trials. We’re really out there leading the fight for breakthroughs,” says Bota, who is the primary investigator for many of the trials.

Clinical trials must adhere to Food and Drug Administration protocols and progress in phases. Phase 1 trials test new drugs or treatments on small groups of patients to evaluate safety, efficacy and side effects. If successful, the treatments advance to Phase 2 with larger groups to further test efficacy and monitor side effects. Phase 3 trials use even larger groups to confirm effectiveness before the treatment is finally approved for the general public.

Following surgery, Green joined the ReACT study, a Phase 2 trial that hinges on using the patient’s own immune system to fight cancer. In the ReAct study, Green was injected with rindopepimut, a medication that imitates the EGFRvII protein and stimulates the patient’s immune system to recognize and fight tumor cells that express the gene mutation.

Rindopepimut was administered in the form of an injection every two weeks in the beginning, and then monthly, which Green had along with a chemotherapy infusion. The therapy is intended to boost his immune system to fight off cancer recurrence.

Another clinical trial led by Bota is called the ERC1671 study. It combines samples of a patient’s tumor cells with those of three other patients and mixes them with reagents so that the patient’s immune system will recognize them as foreign. These cell extracts are then injected to prime the patient’s immune system to fight the tumor and possible recurrences.

“The same cancer can take different pathways, and the concept to the ERC1671 study is to prompt the body to fight cancer not only in the way that the patient already had it—stimulated by the patient’s own tumor cells—but in several different ways by introducing the cells of other patients,” Bota says. “It’s exciting to be working in cancer immunotherapy right now. We see so much potential for hope.”

Green believes participating in his trial, which is now heading into Phase 3, has extended his life even under the worst circumstances. Shortly after surgery his wife, Donna, who suffered from a chronic illness, took a turn for the worse and passed away.

“Donna’s death is the reason I’m here,” he says. “She wanted me to move near Irvine to take part in this trial. So I did. I’m convinced the top-notch surgery, the care from everyone here and the vaccines are why I’m alive and feeling well now, more than three years later.”  

Hsu says there’s nothing better than hearing that. “We have the very best technology, many promising clinical trials and a world-class team of experts in neuro-oncology, neurosurgery, radiation therapy, clinical trials, nursing and more. But, ultimately, this is all about the patient. Our dream is to help patients reclaim their lives.”

That’s exactly what Green hopes to do. Green’s first career and abiding love is photography. He worked in Southern California for the Gardena Valley News newspaper. “I’m looking forward to getting back to photography and maybe moving full-time to a vacation home we own in Las Vegas,” he says. “A few years ago I thought I had zero chance at a future, but now I see one. That’s pretty amazing.”