Lung Cancer: Rare Genetic Mutation Allows Patients To Survive Longer

Yale University researchers found that many non-small cell lung cancer (NSCLC) patients have cancer that has metastasized to the brain, and a handful of those patients with a rare genetic mutation are living significantly longer than patients without the mutation, according to a news release.

The metastasizing of cancer to the brain, also called secondary brain cancer, occurs when cancer cells spread to the brain from a primary cancer elsewhere in the body, forming a tumor or tumors in the brain.

NSCLC makes up about 85 percent of all lung cancer, where 30-50 percent of patients develop metastatic disease in the brain. Most patients with this diagnosis die from the disease within seven months. But the researchers found that patients with the rare ALK mutation, which makes up about 5 percent of NSCLC cases, are living an average of four years, with the disease controlled in the brain nearly a year after their initial treatment, according to Kimberly Johung M.D, the study's lead author and assistant professor of therapeutic radiology.

"This study is among the first to show that genetic information about tumors can guide decision making for the treatment of brain metastases," Johung said. "Patients with the ALK mutation respond so well to targeted systemic treatments that the brain lesions actually become the driving prognostic factor in their treatment plan."

The ALK gene rearrangement produces an abnormal ALK protein that causes the cells to grow and spread. The ALK gene is part of a group of proteins called receptor tyrosine kinases (RTKs), which transmit signals from the cell surface into the cell through a process called signal transduction.

Some of the treatment approaches include whole-brain radiation therapy, radiation for individual lesions and surgery, typically for a single metastasis, according to the researchers. Whole-brain radiation is associated with significant cognitive effects and the use of additional radiation therapy for progression is common. The Yale researchers found that patients with the ALK mutation would benefit from radiation focused on individual metastases.

"Since patients are living longer with systemic disease controlled, there is likely a benefit to intensifying treatment of their brain lesions. This is a significant change in strategy for this population," Johung said.

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