Denise Bernhardt1,2,3, Sebastian Adeberg4,5,6,7, Farastuk Bozorgmehr8,9, Nils Opfermann4,5, Juliane Hörner-Rieber4,5, Laila König4,5,7, Jutta Kappes10, Michael Thomas8,9, Andreas Unterberg11, Felix Herth10,9, Claus Peter Heußel9,12,13, Arne Warth9,14, Jürgen Debus4,5,6,7, Martin Steins8,9, Stefan Rieken4,5. 1. Department of Radiation Oncology, INF 400, University Hospital Heidelberg, 69120, Heidelberg, Germany. denise.bernhardt@med.uni-heidelberg.de. 2. Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany. denise.bernhardt@med.uni-heidelberg.de. 3. Heidelberg Ion-Beam Therapy Center (HIT), Im Neuenheimer Feld 450, 69120, Heidelberg, Germany. denise.bernhardt@med.uni-heidelberg.de. 4. Department of Radiation Oncology, INF 400, University Hospital Heidelberg, 69120, Heidelberg, Germany. 5. Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany. 6. Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. 7. Heidelberg Ion-Beam Therapy Center (HIT), Im Neuenheimer Feld 450, 69120, Heidelberg, Germany. 8. Department of Thoracic Oncology, Thoraxklinik, Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg University, Heidelberg, Germany. 9. Translational Lung Research Centre Heidelberg (TLRC-H), German Centre for Lung Research (DZL), Heidelberg, Germany. 10. Department of Pneumology, Thoraxklinik, Heidelberg University, Heidelberg, Germany. 11. Department of Neurosurgery, INF 400, University Hospital Heidelberg, 69120, Heidelberg, Germany. 12. Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik, University of Heidelberg, Heidelberg, Germany. 13. Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany. 14. Institute of Pathology, Heidelberg University, Heidelberg, Germany.
Abstract
PURPOSE: Whole brain radiation therapy (WBRT) is historically the standard of care for patients with brain metastases (BM) from small-cell lung cancer (SCLC), although locally ablative treatments are the standard of care for patients with 1-4 BM from other solid tumors. The objective of this analysis was to find prognostic factors influencing overall survival (OS) and intracranial progression-free survival (iPFS) in SCLC patients with single BM (SBM) treated with WBRT. METHODS: A total of 52 patients were identified in the authors' cancer center database with histologically confirmed SCLC and contrast-enhanced magnet resonance imaging (MRI) or computed tomography (CT), which confirmed SBM between 2006 and 2015 and were therefore treated with WBRT. A Kaplan-Meier survival analysis was performed for OS analyses. The log-rank (Mantel-Cox) test was used to compare survival curves. Univariate Cox proportional-hazards ratios (HRs) were used to assess the influence of cofactors on OS and iPFS. RESULTS: The median OS after WBRT was 5 months and the median iPFS after WBRT 16 months. Patients that received surgery prior to WBRT had a significantly longer median OS of 19 months compared to 5 months in the group receiving only WBRT (p = 0.03; HR 2.24; 95% confidence interval [CI] 1.06-4.73). Patients with synchronous disease had a significantly longer OS compared to patients with metachronous BM (6 months vs. 3 months, p = 0.005; HR 0.27; 95% CI 0.11-0.68). Univariate analysis for OS revealed a statistically significant effect for metachronous disease (HR 2.25; 95% CI 1.14-4.46; p = 0.019), initial response to first-line chemotherapy (HR 0.58; 95% CI 0.35-0.97; p = 0.04), and surgical resection (HR 0.36; 95% CI 0.15-0.88; p = 0.026). OS was significantly affected by metachronous disease in multivariate analysis (HR 2.20; 95% CI 1.09-4.45; p = 0.028). CONCLUSIONS: Univariate analysis revealed that surgery followed by WBRT can improve OS in patients with SBM in SCLC. Furthermore, synchronous disease and response to initial chemotherapy appeared to be major prognostic factors. Multivariate analysis revealed metachronous disease as a significantly negative prognostic factor on OS. The value of WBRT, stereotactic radiosurgery (SRS), or surgery alone or in combination for patients with a limited number of BM in SCLC should be evaluated in further prospective clinical trials.
PURPOSE: Whole brain radiation therapy (WBRT) is historically the standard of care for patients with brain metastases (BM) from small-cell lung cancer (SCLC), although locally ablative treatments are the standard of care for patients with 1-4 BM from other solid tumors. The objective of this analysis was to find prognostic factors influencing overall survival (OS) and intracranial progression-free survival (iPFS) in SCLCpatients with single BM (SBM) treated with WBRT. METHODS: A total of 52 patients were identified in the authors' cancer center database with histologically confirmed SCLC and contrast-enhanced magnet resonance imaging (MRI) or computed tomography (CT), which confirmed SBM between 2006 and 2015 and were therefore treated with WBRT. A Kaplan-Meier survival analysis was performed for OS analyses. The log-rank (Mantel-Cox) test was used to compare survival curves. Univariate Cox proportional-hazards ratios (HRs) were used to assess the influence of cofactors on OS and iPFS. RESULTS: The median OS after WBRT was 5 months and the median iPFS after WBRT 16 months. Patients that received surgery prior to WBRT had a significantly longer median OS of 19 months compared to 5 months in the group receiving only WBRT (p = 0.03; HR 2.24; 95% confidence interval [CI] 1.06-4.73). Patients with synchronous disease had a significantly longer OS compared to patients with metachronous BM (6 months vs. 3 months, p = 0.005; HR 0.27; 95% CI 0.11-0.68). Univariate analysis for OS revealed a statistically significant effect for metachronous disease (HR 2.25; 95% CI 1.14-4.46; p = 0.019), initial response to first-line chemotherapy (HR 0.58; 95% CI 0.35-0.97; p = 0.04), and surgical resection (HR 0.36; 95% CI 0.15-0.88; p = 0.026). OS was significantly affected by metachronous disease in multivariate analysis (HR 2.20; 95% CI 1.09-4.45; p = 0.028). CONCLUSIONS: Univariate analysis revealed that surgery followed by WBRT can improve OS in patients with SBM in SCLC. Furthermore, synchronous disease and response to initial chemotherapy appeared to be major prognostic factors. Multivariate analysis revealed metachronous disease as a significantly negative prognostic factor on OS. The value of WBRT, stereotactic radiosurgery (SRS), or surgery alone or in combination for patients with a limited number of BM in SCLC should be evaluated in further prospective clinical trials.
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