Moving the Needle on Brain Tumor Treatment

arrow bisecting two hemispheres of the brain

Inspired by Family

Henry Brem’s parents were Holocaust survivors. They came to New York when they were 20 years old after every member of their respective families had been murdered by the Nazis. They had little education; the Nazis invaded their native Poland when they were both 14. And yet, “they came with a joy to this country in 1949, and a tremendous ambition,” he said.

They had a passion for learning and imbued their four children (two professors of neurosurgery, one a professor of surgery and one a periodontist) with the Jewish ethical values of tikkun olam, or making the world a better place, of love for all of mankind, and of the value of life.

Throughout his career, Brem said his love for family — especially for his wife of 46 years, breast cancer specialist and radiologist Rachel Brem, and their three daughters — has had an enormous impact on the way he thinks about his patients and their families.

In four decades on the Johns Hopkins faculty, Henry Brem has built one of the largest and most distinguished brain tumor research and treatment centers in the world. He has transformed the field of neurosurgery by pioneering the use of navigational imaging, and by inventing and developing Gliadel wafers, which use biodegradable polymers that deliver chemotherapy directly — and with more potent therapeutic impact than systemic chemotherapy — to malignant tumors in the brain.

Brem is the Harvey Cushing Professor of Neurosurgery, director of the Department of Neurosurgery and neurosurgeon-in-chief of The Johns Hopkins Hospital. He is professor of oncology, ophthalmology and biomedical engineering. He has mentored numerous neurosurgeons — at least 20 are chairs of neurosurgery departments around the country. And he resurrected and runs Harvey Cushing’s Hunterian Neurosurgery Laboratory, where he has trained researchers who have gone on to further advance the most promising approaches to treating brain cancer.

Yet, for Brem, it is all “good, but not good enough.” The median survival for glioblastoma has doubled since he joined the Johns Hopkins faculty in 1980, but today it is still less than two years.

In a moving talk he delivered recently as part of CIM’s series of seminars on humanism in medicine, “Research as an Imperative for Clinical Excellence,” the renowned neurosurgeon made a powerful case for the importance of the role of physician-scientist in humanizing medicine — for providing the best available treatment while working persistently in the lab (and sometimes even in Congress to get Medicare to pay for vital new therapies like Gliadel) to pursue the holy grail of more effective treatment.

Overcoming Emptiness

Brem said that he discovered the joys of research as an undergraduate at New York University. The summer after his freshman year, he worked in a molecular biology laboratory while also getting up at 5:30 a.m. to accompany medical residents at Columbia on rounds. He avidly read up on their cases and could often answer questions they couldn’t. So they invited him to join them in the operating room. “It was very exciting to do so,” he says.

He chose neurosurgery because he wanted to have maximum impact on patients’ lives, and he spent his years in medical training mastering neurosurgical medicine and technique. “And I was very nervous,” he said. “I’d wake up early before I operated, I’d restudy the anatomy, the technique.” Brem was delighted and relieved when he quickly built up a large practice, offering his patients “the best that was available in medicine at the time.”

Yet he felt what he described as “a huge emptiness.” Patients were coming great distances with malignant brain tumors, and “we formed these incredible bonds, and then they died.” When he apologized for letting them down, they reassured him. “‘We know that you’re working on making it better… we want to be part of that process.’” So he felt, and continues to feel, a great moral obligation to honor them by finding better treatments.

Promise on the Horizon

When Brem decided to specialize in brain tumors, at least one mentor tried to discourage him. “The FDA had not approved any new therapy for brain tumors in over 20 years, and the median survival [of 9 months] had not changed from Cushing’s time,” Brem said.

But, inspired by his patients, he worked tirelessly to pioneer new therapies and improvements in imaging and surgical techniques. Clinical research led by Brem and other physician-scientists has more than doubled median survival and increased long-term survival. “On the one hand, that’s very satisfying because it shows that with scientific approaches, we could change something that had never been changed before,” he said. “On the other hand, it’s terrible. Twenty months is still dismal.”

Yet his hope is that by persisting in the lab, “we will eventually, with incremental improvements, see this turned into a chronic, manageable disease.” Inspired, for instance, by a glioblastoma patient who has survived for decades without recurrence — possibly because a serious post-operative infection stimulated his immune system — his team at Johns Hopkins has launched clinical trials to test a promising combination of his trademark localized delivery of chemotherapy and an immunotherapy drug.

“It’s not a one-man show like it was in Harvey Cushing’s time,” said Brem as he concluded his talk with a slide emblazoned with a single word: Gratitude. Gratitude, not only for “the privilege I’ve had in working with great people, both as a student and all through my career,” but for the patients “who give me the stimulation to help move the needle forward.”