When a cancer metastasizes to a patient’s brain, the region of the brain it spreads to may depend on what type of cancer it arises from and where it originated in the body. These findings, published in the Journal of Neurosurgery, could help researchers further understand how certain brain tumors grow and work as a predictive diagnostic tool.
Study author Dr. Gabriel Zada, professor of neurosurgery at Keck Medicine of USC and director of the USC Brain Tumor Center, explained that the reason the researchers have seen these patterns of cancer type and spatial distribution could be attributed not only to where the cancer originates but also to activity in the local microenvironment of the brain that either convinces or prevents tumors from growing.
“If we can understand that interaction, we can use it to our advantage to prevent brain tumors from arising in those areas of the brain,” Zada said. “It's a matter of understanding what those kind of red light green light signals are, and how to harness them. And if we can find any targets, chemical compounds, or signaling features, we can use those and turn them back against this process to prevent seeding or growth of metastasis.”
To reach their findings, researchers examined retrospectively collected data of about 973 patients with metastatic brain cancer who were treated with single-fraction Gamma Knife radiosurgery (GKRS) at Keck Medical Center of USC between 1994 and 2015. The patients had a total of 3,196 unique brain metastatic lesions that arose from the five most common cancer types – melanoma, lung, breast, renal and colorectal.
“(GKRS) is a single day procedure where patients come in, and a frame is placed on their head to treat them with the Gamma Knife machine,” Zada explained. “It's kind of like going in an MRI machine, and it targets their tumors with a high degree of accuracy. It's a very safe procedure that we conduct all the time. When the frame is applied, it provides X, Y and Z coordinates for each metastatic tumor. We were the first to leverage data from the GKRS procedure to study this question, and that's where I think the novelty really is.”
The researchers analyzed the coordinate data derived from GKRS using spatial generalized additive models (GAMs), which can be used to characterize spatial processes and interpolate geostatistical data, according to the authors. They then developed a regional brain metastasis echelon model (RBMEM) to test whether a certain cancer subtype showed predilection for metastasis, and a brain region susceptibility model (BRSM) to determine whether a certain cancer type would metastasize to certain brain regions.
The findings showed that lung cancer and melanoma were more likely to metastasize to the frontal and temporal lobes, while breast, renal and colon cancers tended to metastasize to the hindbrain regions – most notably the cerebellum and brainstem.
Understanding the cancer-specific topographic patterns within the central nervous system may also help determine how the metastatic cells adapt to microenvironments in the brain and establish brain metastasis. The findings open up more doors for brain metastases to be further examined to determine the best ways to help patients with cancer – 20% to 45% of whom experience a lifetime incidence of brain metastasis. Zada said that he and the other researchers are now teaming up with multiple institutions with larger data sets.
“When we combine all that data, we can really leverage it and it gives us more statistical power to really get closer and closer to what the truth is,” Zada said. “So the next steps are to validate this with a much bigger team and a lot more data from a consortium or multicenter study. And then at the same time, we're looking at the at the science a little deeper by trying to understand these patterns in animal studies as well.”
The findings provide a glimpse into potential future avenues of treatment, Zada said.
“This is one of the first studies to suggest that there is some method to the madness of how brain metastases occur.”
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