Clinical Investigation
Gender, Race, and Survival: A Study in Non–Small-Cell Lung Cancer Brain Metastases Patients Utilizing the Radiation Therapy Oncology Group Recursive Partitioning Analysis Classification

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Purpose

To explore whether gender and race influence survival in non–small-cell lung cancer (NSCLC) in patients with brain metastases, using our large single-institution brain tumor database and the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) brain metastases classification.

Methods and materials

A retrospective review of a single-institution brain metastasis database for the interval January 1982 to September 2004 yielded 835 NSCLC patients with brain metastases for analysis. Patient subsets based on combinations of gender, race, and RPA class were then analyzed for survival differences.

Results

Median follow-up was 5.4 months (range, 0–122.9 months). There were 485 male patients (M) (58.4%) and 346 female patients (F) (41.6%). Of the 828 evaluable patients (99%), 143 (17%) were black/African American (B) and 685 (83%) were white/Caucasian (W). Median survival time (MST) from time of brain metastasis diagnosis for all patients was 5.8 months. Median survival time by gender (F vs. M) and race (W vs. B) was 6.3 months vs. 5.5 months (p = 0.013) and 6.0 months vs. 5.2 months (p = 0.08), respectively. For patients stratified by RPA class, gender, and race, MST significantly favored BFs over BMs in Class II: 11.2 months vs. 4.6 months (p = 0.021). On multivariable analysis, significant variables were gender (p = 0.041, relative risk [RR] 0.83) and RPA class (p < 0.0001, RR 0.28 for I vs. III; p < 0.0001, RR 0.51 for II vs. III) but not race.

Conclusions

Gender significantly influences NSCLC brain metastasis survival. Race trended to significance in overall survival but was not significant on multivariable analysis. Multivariable analysis identified gender and RPA classification as significant variables with respect to survival.

Introduction

In 1997, the Radiation Therapy Oncology Group (RTOG) published a prognostic classification for brain metastases patients after carrying out a recursive partitioning analysis (RPA) of the pretreatment characteristics of 1200 patients enrolled in three completed randomized trials (1). This analysis was prompted by questions regarding the impact of patient selection on benefits of new treatment interventions for brain metastases beyond standard whole-brain radiotherapy. The resulting three prognostic classes included Karnofsky Performance Status (KPS), status of the primary tumor, presence of extracranial disease, and age, and stratified patients into homogeneous survival groups (Table 1). Since its publication, a number of studies have validated the reliability and generalizability of these RPA classes in the setting of brain metastases research 2, 3, 4, 5, 6. In the original RTOG analysis, however, neither patient sex nor race/ethnicity was included as a prognostic variable.

Recent data emerging from clinical experience with the use of epidermal growth factor receptor–tyrosine kinase inhibitors in non–small-cell lung cancer (NSCLC) suggest a benefit to these agents as a function of ethnicity and gender (i.e., Asian ethnicity and female gender are predictors of response) (7). The basis for this selectivity remains conjectural. These findings are intriguing given that gender has been recognized as having a strong prognostic association with lung cancer outcomes (8). The influence of race or ethnicity on outcomes, however, is historically more controversial (9).

Because the RTOG brain metastases recursive analysis did not include gender or race, the question of the potential influence of these factors on survival for NSCLC patients with brain metastases prompted a retrospective analysis of our large, single-institution, brain tumor database. In that regard, we used the RTOG RPA brain metastases classification to create otherwise homogeneous prognostic cohorts. Establishing the validity of gender and/or race for prognosis could permit improvements in clinical trial design by including them as stratification factors in future brain metastases trials.

Section snippets

Study population

For the interval January 1982 to September 2004, 835 patients with brain metastases from NSCLC (see Table 1) were identified from the comprehensive Cleveland Clinic brain tumor database, an institutional review board–approved registry of more than 1200 patients with brain metastases. Patients recorded in this database were either diagnosed and treated for primary and secondary tumors at our institution as well as at outside hospitals, or referred to the Cleveland Clinic for treatment of brain

Results

For 835 patients, the median follow-up was 5.4 months (range, 0–122.9 months). The median age was 62.4 years (range, 25–90 years). The median KPS was 80 (range, 20–100). There were 485 male patients (M) (58.4%) and 346 female patients (F) (41.6%). The present analysis involved 828 patients (99%) who self-identified as either black/African American (B; n = 143 [17%]) or white/Caucasian (W; n = 685 [83%]); 7 patients had neither ethnic/racial designation and were therefore excluded. By gender and

Discussion

The results of the present analysis support an association between gender and survival in NSCLC brain metastases patients. To date, there are a large number of publications suggesting that women diagnosed with NSCLC 10, 11, 12, 13, 14 or small-cell lung cancer 15, 16, 17, 18, 19, 20, 21 have a better prognosis than men. With specific reference to brain metastases and NSCLC, there are retrospective studies suggesting that female gender may have a positive impact on outcomes 22, 23, 24, 25. Two

Conclusions

Gender significantly influences NSCLC brain metastasis survival, supporting an association between gender and lung cancer in all stages of the disease. Our data also replicate the utility of the RTOG RPA classification for prognosis in this population. There is a suggestion that race may influence overall survival, but this was absent on multivariable analysis. Although a significant interaction between gender, race, and survival was seen in only one RPA class, further characterization of these

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    Presented in part at the 13th European Cancer Conference, October 30–November 3, 2005, Paris, France; and at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2–6, 2006, Atlanta, GA.

    Conflict of interest: none.

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