For the past 30 years, numerous developments in brain cancer and brain metastases have been ongoing, with recent discoveries — at the U.Va. Cancer Center and beyond — aiming to unify all therapies to promote patient survival and reduce side effects of more invasive treatments.
The U.Va. Cancer Center belongs to a national organization known as the American Society for Clinical Oncology, which called for a panel of medical professionals to reassess the pre-existing protocol for brain cancer treatment as part of a joint effort with the Society for Neuro-Oncology and the American Society for Radiation Oncology. This two-year process — designed to update the guidelines on how to treat brain cancer patients based on assessment of previous clinical trials and analyzing the effectiveness of existing methods — is now complete for 2022.
Brain cancer is an especially devastating condition that tends to debilitate much of the body as most tumors do not originate in the brain, but rather elsewhere, such as the lungs or the skin from melanoma. Brain metastases — tumors away from the initial site — occur when another organ gives rise to a tumor that spreads to the brain.
It is also particularly prevalent. About 200,000 people in the U.S. are diagnosed with a brain tumor annually. In the 1970s and 1980s, brain metastases were thought to be a death sentence, and the average survival rate for a patient diagnosed with one was about four months.
David Schiff of the U.Va. Cancer Center and Michael Vogelbaum of the Moffitt Cancer Center are both neuro-oncologists and members of the ASCO panel. The two have been committed to researching ways to advance the currently available treatments of brain tumors to support the development of this technology.
“Over the last 30 years or so, there have been a series of advances,” Schiff said. “In the 1990s, it was recognized that in certain cases, surgical removal of a single brain metastasis, especially if it was causing symptoms, could improve survival and quality of life.”
In the late 1990s through early 2000s, the use of localized radiation became more prevalent.
“It started with a study that showed that if someone has just one brain metastasis, it can be removed by surgery,” Vogelbaum said. “If you remove it, and then treat it with the whole brain radiation, the patients actually live longer than if you just do whole brain radiation alone.”
Known as stereotactic radiotherapy, machines such as the gamma knife, a targeted beam of radiation used to treat tumors, helped control brain metastases better than whole brain radiation, which was the industry standard at the time. Whole brain radiation has many disadvantages including cognitive neurotoxicity, which is an overall decline in brain function.
“Because it treated areas of the brain that didn’t have tumors, radiation was not uncommonly associated with cognitive side effects,” Schiff said. “If people did survive more than a few months, it was sometimes noted that their memory and concentration were not what they used to be.”
The purpose of these new guidelines was to bring together experts from neurosurgery, radiation, oncology and other specialties to review recent medical literature of clinical trials and large clinical series in order to determine the circumstances necessary for surgery or other appropriate therapies.
“There was an understanding that treating brain metastases is a multidisciplinary type of approach,” Vogelbaum said. “That’s why [ASCO] wanted us to put together a very diverse panel, to be able to go through the latest evidence and start to put the new medications in perspective.”
Research studies and evidence were compiled to weigh each treatment in terms of relevance in order to determine the strength and appropriateness of each medical recommendation.
“Whenever anyone developed a brain metastasis, they would come to a neurosurgeon and a radiation oncologist,” Vogelbaum said. “And we would decide whether it was a combination or surgery or radiosurgery.”
Rarely was whole brain radiation used as a primary treatment method, as the combined therapies had become the standard for the past 20 years.
“There are safer ways to give whole brain radiation, sort of by blocking out the memory structures from the radiation fields, which we call hippocampal avoidance or brain radiation therapy, and the use of certain medications during whole brain radiation therapy as well to help protect memory.” Schiff said.
The hippocampus region of the brain is associated with new memory formation and storage. Hippocampal avoidance is an advancement in whole brain radiation which uses intensity-modulated radiotherapy – a technique to pinpoint certain regions of the brain while avoiding others – to help preserve cognition in patients.
In more current years, targeted immunotherapy drugs have shown positive results in tumors caused by melanoma, lung cancer and kidney cancer. Immunotherapy drugs use checkpoint inhibitors which block checkpoint proteins that regulate immune responses from binding with their partner proteins. By doing this, an “off” signal is prevented from being sent, thus allowing T cells, which protect from infection, to kill the cancer cells.
“Recent studies have shown that in select circumstances with specific types of tumors, if the brain metastases are not symptomatic, and are not particularly large, that these smart drugs or immunotherapies can help control the brain metastases as well,” Schiff said. “In some cases, [the drug] spares patients from needing radiation, radiosurgery or surgery for treatment of their brain metastasis.”
The new guidelines emphasize minimizing toxicity while increasing effectiveness. For instance, while surgery may sound invasive, for selected patients it leads to better functional and cognitive outcomes than whole brain radiation. The primary goals of alternative therapies are improving longevity and the quality of life.
“Now, it's a small minority of patients who actually die from the brain metastases,” Schiff said. “In most patients, we’re able to control what's happening in the brain.”
In terms of enhancing standards of care at the patient level, ASCO has immense educational efforts, such as weekly journals, seminars, huge annual meetings and smaller sub-specialty meetings for physicians.
Compiling the necessary information all in one place is convenient for radiation oncologists all over the world who are on the frontline for treating patients with cancer who go on to develop brain metastases. This treatment protocol is designed as a framework that is then individualized for each patient.
“The guidelines can point to the next questions, but really by their very nature, look back and document the advancements that have been made over the past few decades.” Vogelbaum said.