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Cagney DN, Martin AM, Catalano PJ, et al. Implications of Screening for Brain Metastases in Patients With Breast Cancer and Non–Small Cell Lung Cancer. JAMA Oncol. 2018;4(7):1001–1003. doi:10.1001/jamaoncol.2018.0813
Brain metastases affect many patients with cancer.1 Given the limited intracranial penetration of most systemic therapies, the size and number of brain metastases at diagnosis determines management, with more invasive or toxic therapies such as neurosurgical resection and whole brain radiation therapy (WBRT) used for bulky and multifocal disease, respectively. Consequently, consensus guidelines from the National Comprehensive Cancer Network recommend screening magnetic resonance imaging (MRI) of the brain for patients with stage II to IV non–small cell lung cancer (NSCLC), small cell lung cancer of any stage, and stage IIIC to IV melanoma—all cancers that frequently metastasize to the brain.2
Brain metastases are common in select patients with breast cancer as well: 8% to 11% of patients with de novo metastatic human epidermal growth factor receptor 2 (ERBB2/HER2)–positive or triple negative breast cancer harbor brain metastases,3 and 46% to 53% of such patients develop brain metastases during their clinical course.4,5 Yet, the National Comprehensive Cancer Network does not recommend brain-directed screening for any patients with breast cancer,2 a recommendation that is based only on expert consensus given the lack of definitive or prospective studies on this issue. To identify the potential value of brain-directed MRI screening to select patients with breast cancer, we compared the presentation, management, and outcome of patients with breast cancer and brain metastases (which are largely unscreened with brain MRI) with those of patients with NSCLC and brain metastases (which are largely screened with brain MRI at diagnosis of systemic malignant neoplasm).
We identified patients treated for newly diagnosed brain metastases between January 1, 2000, and December 31, 2015, at Dana-Farber/Brigham and Women's Cancer Center. We then compared intracranial disease burden at presentation, intracranial management, and intracranial outcomes between patients with breast cancer and patients with NSCLC. Using SAS, version 9.4 (SAS Institute Inc), we compared continuous outcome measures using the 2-tailed unpaired t test or Wilcoxon rank sum test with categorical outcome measures using Fisher exact test; we performed a multivariable Cox regression analysis for time-to-event outcomes, except for neurologic death, which was assessed using the Fine and Gray competing risks regression. A 2-sided P < .05 defined statistical significance. Proportional hazards were verified. This study was approved by the Dana-Farber/Harvard Cancer Center institutional review board, which waived the need for written or oral patient informed consent.
Table 1 compares the baseline characteristics between 349 patients with breast cancer and 659 patients with NSCLC. Patients with breast cancer, compared with patients with NSCLC, presented with larger (median [interquartile range (IQR)] diameter, 17 [10-29] mm vs 14 [8-23] mm; P < .001) and more numerous (median [IQR], 3 [1-8] vs 2 [1-4]; P < .001) brain metastases. Patients with breast cancer were also more likely than patients with NSCLC to be symptomatic at presentation (265 [75.9%] vs 399 [60.5%]; P < .001), present with seizures (59 [16.9%] vs 75 [11.4%]; P = .01), harbor brainstem involvement (28 [8.0%] vs 28 [4.2%]; P = .02), have leptomeningeal disease at diagnosis (40 [11.5%] vs 14 [2.1%]; P < .001), and receive WBRT as initial management (209 [59.9%] vs 283 [42.9%]; P < .001;Table 1). After initial brain-directed therapy, no significant differences in recurrence or treatment-based intracranial outcomes were found between the 2 groups. However, neurological death was more common in patients with breast cancer than patients with NSCLC, both as a percentage of total deaths (103 [37.3%] vs 98 [19.9%]; P < .001; Table 1) and as a time-to-event based outcome (hazard ratio, 1.54; 95% CI, 1.10-2.17; P = .01; Table 2).
Patients with breast cancer presented with more advanced intracranial disease than did patients with NSCLC and more frequently required WBRT as initial management. However, after initial brain-directed therapy, no differences in recurrence or salvage therapy–based outcomes between the 2 cohorts were noted. This finding suggests that intracranial disease in patients with breast cancer was not more aggressive or resistant to treatment but rather was diagnosed at a later stage.
Brain-directed MRI screening for patients who harbor malignant neoplasms with potential for intracranial involvement is important given the impact of neurological compromise on quality of life. In addition, early identification of intracranial disease facilitates less invasive or less toxic approaches, such as stereotactic radiosurgery or careful use of promising systemic agents rather than WBRT or neurosurgical resection.
The limitations of our study include its retrospective nature, inherent selection bias, and potential clinical confounders. In addition, 84 patients with breast cancer (24.0%) were screened for brain metastases (eg, patient/provider preference, clinical trial)—representing a higher percentage than in previous studies, which screened less frequently5—whereas some patients with NSCLC were not, including patients diagnosed with NSCLC due to symptomatic brain metastases. Our results are, therefore, biased toward the null. Despite these limitations, this study strongly supports further investigation into MRI screening of the brain among select patients with metastatic breast cancer.
Accepted for Publication: February 19, 2018.
Corresponding Author: Daniel N. Cagney, MD, Department of Radiation Oncology, Dana-Farber/Brigham and Women’s Cancer Center, 75 Francis St, Boston, MA 02115 (email@example.com).
Published Online: May 17, 2018. doi:10.1001/jamaoncol.2018.0813
Author Contributions: Drs Cagney and Aizer had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Lin and Aizer contributed equally to this study.
Study concept and design: Cagney, Martin, Lin, Aizer.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Cagney, Lin, Aizer.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Cagney, Martin, Catalano, Lin, Aizer.
Obtained funding: Alexander, Lin.
Administrative, technical, or material support: Alexander.
Study supervision: Alexander, Lin, Aizer.
Conflict of Interest Disclosures: None reported.
Meeting Presentation: This study was presented in abstract form at the Annual Meeting of the American Society for Radiation Oncology; September 24-27, 2017; San Diego, California.
Additional Contributions: We acknowledge the contribution to this work of the following people: Rachel H. Brigell, MPH; Puyao C. Li, MD; Gabrielle A. Mezochow, BS; Luke Besse, BS; Shyam K. Tanguturi, MD; and Daphne A. Haas-Kogan, MD, all of whom are from the Department of Radiation Oncology, Dana-Farber/Brigham and Women’s Cancer Center, Harvard Medical School; Eudocia Q. Lee, MD, MPH, and Patrick Y. Wen, MD, Center for Neuro-Oncology, Dana-Farber/Brigham and Women’s Cancer Center, Harvard Medical School; Stephanie E. Weiss, MD, Department of Radiation Oncology, Fox Chase Cancer Center; Nils D. Arvold, MD, Department of Radiation Oncology, St. Luke's Radiation Oncology Associates; and Amanda J. Redig MD, PhD, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School. These contributors received no compensation for their work.
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