Prognosis in ALK-Rearranged NSCLC With Brain Metastases Better Than Thought

By Megan Brooks

October 09, 2015

NEW YORK (Reuters Health) - Tumor genetic information can provide valuable additional prognostic information in patients with non-small-cell lung cancer (NSCLC) and brain metastases, according to a new study.

"In this work, we found that patients whose tumors harbor mutation and rearrangement of the ALK gene comprise a previously unrecognized subgroup that has the longest survival," said Dr. Joseph Contessa of Yale University School of Medicine in New Haven, Connecticut.

"This study shows for the first time that genetic information from tumors provides important prognostic information that can guide decision making for the treatment of brain metastases," he told Reuters Health by email. "Brain metastases are a common and significant challenge in taking care of patients with NSCLC."

The prognosis for these patients is typically based on clinical factors such as patient age, Karnofsky performance status (KPS), disease status at other sites in the body, and the number of brain metastases.

The researchers studied 90 patients with brain metastases from ALK-rearranged NSCLC from six centers; 84 received stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT) and 86 received tyrosine kinase inhibitor (TKI) therapy.

"NSCLC brain metastasis is often considered a final stage of advanced disease and an ominous sign of disease progression and death," Dr. Contessa and colleagues note in the Journal of Clinical Oncology online October 5. But in their cohort of NSCLC with ALK rearrangement and brain metastases, median overall survival following the development of brain metastases was greater than four years and intracranial progression-free survival was nearly one year.

These "favorable survival outcomes" were noted despite roughly three-quarters of patients presenting with multiple brain metastases, nearly half with at least four metastases, the researchers point out.

Clinical factors associated with improved survival included absence of extracranial metastases (ECM) (p=0.003), KPS of at least 90 (p<0.001), and no history of TKI therapy before development of brain metastases (p<0.001). These factors "will be useful for stratifying patients into risk groups in the setting of a clinical trial or for guiding decision making between the use of SRS or WBRT," the team says.

Because patients with ALK-rearranged NSCLC with brain metastases have a "relatively long" survival, SRS and deferred WBRT "should be strongly considered," the researchers say.

Dr. Contessa added, "Patients with ALK rearranged tumors and brain metastasis should be evaluated for treatment with stereotactic radiosurgery and whole brain radiation should be avoided or delayed when possible. Due to the extended survival, brain recurrence at new sites requiring a second or third round of SRS is also common and these patients therefore require close follow-up with surveillance imaging."

"These findings establish a role for the use of molecularly defined prognostic indices to tailor treatment for patients with CNS metastases from NSCLC," the authors conclude in their paper.


J Clin Oncol 2015.