Elucidating the role of incidental use of beta-blockers in patients with metastatic brain tumors in controlling tumor progression and survivability

摘要

Background: Beta-adrenergic antagonists have demonstrated beneficial effects in tumor progression and survivability in patients with various cancers by inhibiting norepinephrine-induced tumor cell migration. However, little is known about their effects on the outcomes of metastatic brain tumors (MBTs). This study was undertaken to evaluate the effects of beta-blockers, if any, on the outcome of MBTs, and their possible role in controlling tumor progression and survivability. Materials and Methods: A retrospective cohort analysis of 225 patients identified as having MBTs presenting to our institution from 2001 through 2013 was conducted by reviewing electronic patient records. Patients were categorized into three groups: Group A comprised hypertensives on beta-blockers only (40, 18%), Group B comprised hypertensive patients on antihypertensive medications other than beta-agonists (65, 29%), and Group C comprised normotensives (120, 53%). All outcomes were compared using the data on pre - and post-gamma knife radiosurgery (GKRS) for these groups. One-way analysis of variance (ANOVA) was used to compare the radiological and clinical outcomes in the patient population following beta-blockers usage in Group A versus groups B and C. Cox regression model was used to demonstrate prognostic factors for the outcome in patients having different primaries. Overall survival period was plotted on Kaplan-Meier curves. The log-rank (Mantel-Cox) test was used to analyze the survival difference in the cases. P Results: The mean age of patients was 57.34 ± 10.98 years (range: 30-87 years) and 44% were males. More than half (130/225, 58%) of patients with MBT had their primary tumor source in the lung, 16% in the breast, and 7% each in the kidneys and the rectum. Frontal lobe was the most commonly affected (80, 35.5%). Statistically significant control of tumor growth (P = 0.001), tumor progression (P = 0.0001), and higher survival outcomes (P = 0.015) were observed in Group A as compared to other groups. In comparing the different groups, breast primaries showed the strongest correlation to survival benefit (P = 0.049) from beta-blocker usage as a primary antihypertensive medication. Conclusion: Concomitant use of beta-blockers with conventional therapy may offer potential benefit to hypertensive patients developing MBTs by ameliorating tumor progression and conferring a survival advantage. This effect was most notable in patients with primary tumors originating in the breast. Prospective studies, molecular research, and randomized controlled trials are warranted to further explore this promising effect.