Over the past 30 years, many developments in brain cancer and brain metastases have continued, with recent discoveries – at the U.Va. Cancer Center and beyond – aiming to unify all therapies to promote patient survival and reduce the side effects of more invasive treatments.
The U.Va. The Cancer Center is owned by a national organization known as the American Society for Clinical Oncology, which asked a panel of medical professionals to reassess the pre-existing protocol for treating brain cancer as part of an effort joint with the Society for Neuro-Oncology and the American Society for Radiation Oncology. This two-year process – designed to update guidelines on how to treat patients with brain cancer based on evaluation of previous clinical trials and analysis of the effectiveness of methods existing ones – is now complete for 2022.
Brain cancer is a particularly devastating disease that tends to weaken a large part of the body because most tumors do not originate in the brain, but rather elsewhere, such as the lungs or melanoma skin. Brain metastases – tumors away from the original site – occur when another organ gives rise to a tumor that spreads to the brain.
It is also particularly widespread. On 200,000 people in the United States are diagnosed with a brain tumor each year. In the 1970s and 1980s, brain metastases were considered a death sentence, and the average survival rate for a patient diagnosed with one was around four months.
David Schiff of the U.Va. Cancer Center and Michael Vogelbaum of Moffitt Cancer Center are both neuro-oncologists and members of the ASCO panel. The two are committed to researching ways to advance currently available treatments for brain tumors to support the development of this technology.
“Over the past 30 years or so there has been a series of advancements,” Schiff said. “In the 1990s, it was recognized that in some cases surgical removal of a single brain metastasis, particularly if it was causing symptoms, could improve survival and quality of life.”
From the late 1990s to the early 2000s, the use of localized radiation became more widespread.
“It all started with a study that showed that if someone has just one brain metastasis, it can be removed with surgery,” Vogelbaum said. “If you take it out and then treat it with the whole brain radiation, patients actually live longer than if you just did the whole brain radiation.”
Known as stereotactic radiation therapy, machines such as the gamma knife, a targeted beam of radiation used to treat tumors, helped control brain metastases better than whole-brain radiation therapy, which was the industry standard at the time. Whole-brain irradiation has many drawbacks, including cognitive neurotoxicity, which is an overall decline in brain function.
“Because it treated areas of the brain that did not have tumors, radiation was not uncommonly associated with cognitive side effects,” Schiff said. “If people survived more than a few months, it was sometimes noticed that their memory and concentration weren’t what they used to be.”
The purpose of these new guidelines was to bring together experts from neurosurgery, radiation therapy, oncology and other specialties to review recent medical literature from clinical trials and large clinical series to determine the necessary circumstances surgery or other appropriate therapies.
“It was understood that treatment of brain metastases is a type of multidisciplinary approach,” Vogelbaum said. “That’s why [ASCO] wanted us to bring together a very diverse panel, so we could review the latest evidence and start putting new drugs into perspective.
Research studies and evidence have been compiled to weigh each treatment in terms of suitability to determine the strength and relevance of each medical recommendation.
“Anytime someone developed a brain metastasis, they came to see a neurosurgeon and a radiation oncologist,” Vogelbaum said. “And we would decide whether it was a combination, surgery or radiosurgery.”
Whole-brain radiation therapy was rarely used as a primary treatment method, as combination therapies had become the norm over the past 20 years.
“There are safer ways to deliver radiation therapy to the whole brain, by blocking the memory structures from the radiation fields, what we call hippocampal avoidance or brain radiation therapy, and using certain drugs during whole-brain radiation also to help protect memory,” Schiff said.
The hippocampus region of the brain is associated with the formation and storage of new memories. Hippocampal avoidance is an advance in whole-brain radiation that uses intensity-modulated radiation therapy – a technique to identify certain brain regions while avoiding others – to help preserve cognition in patients.
In recent years, targeted immunotherapy drugs have shown positive results in tumors caused by melanoma, lung cancer and kidney cancer. Immunotherapy drugs use checkpoint inhibitors that block checkpoint proteins that regulate immune responses against binding with their partner proteins. By doing so, an ‘off’ signal is prevented from being sent, allowing T cells, which protect against infection, to kill cancer cells.
“Recent studies have shown that in certain circumstances with specific types of tumors, if brain metastases are not symptomatic and not particularly prominent, these smart drugs or immunotherapies may also help control brain metastases,” Schiff said. . “In some cases, [the drug] saves patients from needing radiation therapy, radiosurgery or surgery for the treatment of their brain metastases.
The new guidelines emphasize reducing toxicity while increasing efficacy. For example, although surgery may seem invasive, for some patients it leads to better functional and cognitive outcomes than whole-brain radiation therapy. The main goals of alternative therapies are to improve longevity and quality of life.
“Now it’s a small minority of patients who actually die from brain metastases,” Schiff said. “In most patients, we are able to control what is happening in the brain.”
In terms of improving standards of care at the patient level, ASCO makes immense educational efforts, such as weekly reviews, seminars, huge annual meetings, and smaller subspecialty meetings for physicians. .
Compiling the necessary information in one place is convenient for radiation oncologists around the world who are on the front line treating cancer patients who develop brain metastases. This treatment protocol is designed as a framework which 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 progress that has been made over the past few decades.” said Vogelbaum.