Incidence of brain metastases from lung cancer varies by sex, age

The incidence of brain metastases among patients with nonmetastatic lung cancer varies according to patient characteristics such as age, sex and histology, according to results of an observational study.

Brain metastases also appeared associated with worse survival among patients with non–small cell lung cancer, but not among those with small cell lung cancer.

“Brain metastases are a significant cause of morbidity and mortality in patients with cancer, leading to neurologic symptoms and function and emotional impairment along with a significant burden to caregivers and society,” Shirish M. Gadgeel, MD, a thoracic oncologist in the department of oncology at Karmanos Cancer Institute of Wayne State University in Detroit, and colleagues wrote. “The presence of brain metastases also can limit an individual’s therapeutic options and enrollment in clinical trials. Conversely, the early diagnosis and treatment of brain metastases may increase overall survival and independent functionality.”

Although lung cancer is the most common tumor that metastasizes to the brain, there is a lack of significant data surrounding incidence of brain metastases in patients with nonmetastatic primary lung cancer, according to the researchers.

Gadgeel and colleagues used data from the Metropolitan Detroit SEER registry to evaluate 34,681 patients who were diagnosed with a first primary nonmetastatic lung cancer when aged 20 years or older between 1973 and 2011. In the cohort, 30,445 patients had NSCLC and 4,235 patients had small cell lung cancer (SCLC).

Researchers categorized patients by age at diagnosis (20-39, 40-59, 60-79, or 80 years or older), race (black or white), and sex.

Because the study spanned 39 years, researchers divided patients into three diagnosis periods each lasting 13 years (1973-1985, 1986-1998, 1999-2011) for analysis of temporal trends.

Overall, 2,712 patients with NSCLC developed brain metastases (incidence rate, 9%) and 760 patients with SCLC developed brain metastases (incidence rate, 18%).

Among patients with NSCLC, brain metastases were more common in women than men (10% vs. 8%), patients aged 20 to 39 years compared with the patients aged 80 years or older (19% vs. 3%) and in patients with regional vs. local disease at diagnosis (11% vs. 7%; P < .0001 for all).

A greater proportion of black patients vs. white patients developed brain metastases, but the difference was not significant (10% vs. 9%).

Among patients with SCLC, researchers found no statistically significant difference in the incidence rate in women vs. men (19% vs. 17%) and in black patients vs. white patients (20% vs. 18%).

Researchers observed temporal trends in brain metastases incidence that were statistically different; however, according to the researchers, these data were not clinically informative. For patients with NSCLC, there was a statistically significant decreasing trend of brain metastases over the 13-year periods analyzed. For patients with SCLC, the incidence fluctuated over the 3 time periods, with the highest incidence occurring in 1968 to 1998 (23%).

Among patients with NSCLC, those with brain metastases experienced shorter median survival (16 months vs. 21 months), whereas patients with SCLC and brain metastases had insignificantly longer median survival (14 months vs. 11 months).

Results of Cox proportional hazards models adjusted for covariates showed patients with NSCLC who developed brain metastases were at increased risk for death across disease histologies, including adenocarcinoma (HR = 1.53, 95% CI, 1.44-1.63) squamous (HR = 1.39; 95% CI, 1.29-1.5) large cell (HR = 1.37; 95% CI, 1.19-1.58) and other (HR = 1.42; 95% CI, 1.3-1.56).

This association did not persist among patients with SCLC (HR = 1.05; 95% CI, 0.97-1.14)

Researchers noted that the incidence of brain metastases identified among patients with nonmetastatic lung cancer may be lower than their actual occurrence in patients with lung cancer because the results may be impacted by variability and changing patterns in the assessment of metastases in hospital registries.

“The current study data provide updated estimates of the occurrence of brain metastases in a large, population-based sample,” researchers wrote. “Further work is needed to develop a prediction tool that can be applied prospectively toward the prediction of BM in patients with lung cancer.” – by Nick Andrews

Disclosure: Gadgeel reports advisory board roles with Ariad Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer and Roche. Please see the full study for a list of all other researchers’ relevant financial disclosures.