Researchers Find that Lung Cancer Patients with Brain Metastases and Rare Genetic Mutations Have Extended Survival

Researchers Find that Lung Cancer Patients with Brain Metastases and Rare Genetic Mutations Have Extended Survival

A study published in Journal of Clinical Oncology entitled Extended Survival and Prognostic Factors for Patients With ALK-Rearranged Non-Small-Cell Lung Cancer and Brain Metastasis,” finds that patients with lung cancer associated with rare genetic mutation showed extended life expectancy when compared to those without the mutation.

Lung cancer is a fatal disease identified by abnormal cell growth in the lung tissues. These tissues form malignant tumors with the ability to spread to other parts of the body in a process called metastasis. Signs and symptoms of patients with lung cancer include shortness of breath, severe coughing often with blood, fatigue, weight loss, chest pain, and difficulties in swallowing among others. Lung cancer is caused by combination of genetic and environmental factors like cigarette smoking, exposure to Radon gas, asbestos and air pollution. It is worth noting that lung cancer is the most common cancer among men, which represents about one in five of all deaths from cancer.

There are two primary types of lung cancer: 1) small-cell lung carcinoma (SCLC), and 2) non-small-cell lung carcinoma (NSCLC). Compared to SCLC, NSCLC comprises 85% of all lung cancers, and metastatic disease to the brain occurs in 30%–50% of patients. In general, life expectancy of patients diagnosed with NSCLC is short but could be extended if the patients possess a genetic mutation in anaplastic lymphoma kinase (ALK) enzyme, a rare mutation found in only 5% of NSCLC cases. In order to determine the prognostic factors as well as outcomes of patients suffering from NSCLC-induced brain metastasis associated ALK mutation, the researchers screened six institutions and identified a total of 90 suitable patients. Afterwards, 84 of the 90 were subjected to radiotherapy of the brain using stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT), and 86 of the 90 patients were treated with therapy-based tyrosine kinase inhibitor (TKI).

The results suggested that the average overall survival of patients after formation of brain metastases was about 49.5 months. However, patients with free intracranial progression had only an average survival of 11.9 months. Follow-up diagnostics illustrated that the patients had constant interventions for brain metastases, and about 45% of them were found to have progressive brain metastases at death. Factors like absence of extracranial metastases, no treatment with TKIs prior to brain metastases, and well-being of the patients improved overall survival. By contrast, other factors such as single brain metastasis or prior treatment with SRS instead of WBRT decreased overall survival of the patients.

In summary, these findings highlight the importance of therapeutic interventions as a means of controlling intracranial disease. Overall, patients with NSCLC-induced brain metastases associated ALK mutation showed extended life expectancy when treated by means of various therapies (SRS and/or WBRT, and TKIs). Further details of the findings will be presented on Oct. 19 at the 56th Annual Meeting of the American Society for Radiation Oncology (ASTRO).

“This study is among the first to show that genetic information about tumors can guide decision making for the treatment of brain metastases,” study lead author Dr. Kimberly Johung, assistant professor of therapeutic radiology at Yale University, 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.”

“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 added.

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