When modern surgery to resect brain tumors first began at Johns Hopkins in the early 1900s, the focus was simply to help patients stay alive as long as possible. While extending survival is still a key part of most brain tumor research programs, say Johns Hopkins neurosurgeons Chetan Bettegowda and Raj Mukherjee, an increasing number of studies are now focused on improving patients’ quality of life.
“The impact of a brain tumor is like almost nothing else in medicine because it may affect the core of our consciousness, the ability to move, speak, sense and interact — much of who we are as people,” Mukherjee says. “Living longer after diagnosis is very important, but living as well as possible is equally significant.”
“We’re optimistic that these lines of investigation could lead to significant advances in survival.” –Chetan Bettegowda
Toward these ends, both physician-scientists are leading studies that may change the way patients with brain tumors are treated. This research will gradually be supported by funding from Johns Hopkins’ new Reza Khatib, M.D., Brain Tumor Research Center, founded in May 2021 through a generous gift from retired neurosurgeon Reza Khatib and his wife, Georgiana Clifford Khatib. During Khatib’s medical career, he battled on the front lines against the aggressive brain cancer glioblastoma.
Bettegowda, the center’s inaugural director, says the variety of clinical trials taking place at Johns Hopkins — in collaboration with specialists from the Johns Hopkins Neuro-Oncology Program — suggests the promise of new therapies for patients with different brain cancers or secondary tumors that metastasize to the brain.
One approach he and his colleagues study is using biological engineering mechanisms to force cancer cells to produce neoantigens that are recognized by antibodies or CAR-T cells — which can prompt the immune system to more effectively attack these tumors. Other clinical trials include new targeted drug therapies for gliomas and novel protocols for radiation, as well as surgery-based trials to look for different markers of successful drug delivery.
“We’re optimistic that these lines of investigation could lead to significant advances in survival,” Bettegowda says.
Mukherjee’s research focuses on developing and validating new techniques and tools that improve quality of life for people with brain tumors. For example, in one recent study, he and his colleagues reported a novel online calculator to predict short-term postoperative outcomes in patients with metastatic brain tumors. This open-source tool can help neurosurgeons decide whether surgery is the best option for patients, or whether they might have better quality of life with nonsurgical outcomes.
In another recent study, Mukherjee and his colleagues crowd-sourced a definition of supratotal resection for anatomically distinct gliomas, a consensus that sets the stage for prospective studies to compare this type of surgery with gross resection. Although supratotal resection can extend quantity of life, Mukherjee explains, it can affect quality of life. Other research he’s led has tested the use of tubular retractors in brain tumor resections, integrating resting state functional MRI into guided imaging during resections, and using a five-factor frailty index to predict mortality in patients with brain tumors.
“As we make progress toward improving quantity and quality of life,” says Bettegowda, “the closer we come to changing brain tumors from terminal illnesses to chronic ones, or even diseases that may eventually be curable in a large number of people.”