Original Study Nine-year Experience: Prophylactic Cranial Irradiation in Extensive Disease Small-cell Lung Cancer Denise Bernhardt, 1,2,3 Sebastian Adeberg, 1,2,3,4 Farastuk Bozorgmehr, 5,6 Nils Opfermann, 1,2 Juliane Hoerner-Rieber, 1,2 Michael C. Repka, 7 Jutta Kappes, 8 Michael Thomas, 5,6 Helge Bischoff, 5,6 Felix Herth, 6,8 Claus Peter Heußel, 6,9,10 Jürgen Debus, 1,2,3,4 Martin Steins, 5,6 Stefan Rieken 1,2 Abstract In 2007, a European Organization for Research and Treatment of Cancer (EORTC) study demonstrated a beneficial effect on overall survival (OS) with the use of prophylactic cranial irradiation (PCI) in extensive disease small-cell lung cancer. Nevertheless, debate is ongoing regarding the role of PCI, because the patients in that trial did not undergo imaging of the brain before treatment. Also, a recent Japanese randomized trial showed a detrimental effect of PCI on OS in patients with negative pretreatment brain magnetic resonance imaging findings. Of our patients, 87% underwent brain imaging before PCI. In the present retrospective analysis, we found that PCI leads to a nearly doubled median OS compared with the irradiation arm of the EORTC trial, with a 2-month prolonged median OS compared with the irradiation arm of the Japanese trial. Background: In 2007, the European Organization for Research and Treatment of Cancer (EORTC) study (ClinicalTrials.gov identifier, NCT00016211) demonstrated a beneficial effect on overall survival (OS) with the use of prophylactic cranial irradiation (PCI) for extensive disease (ED) small-cell lung cancer (SCLC). Nevertheless, debate is ongoing regarding the role of PCI, because the patients in that trial did not undergo magnetic resonance imaging (MRI) of the brain before treatment. Also, a recent Japanese randomized trial showed a detrimental effect of PCI on OS in patients with negative pretreatment brain MRI findings. Materials and Methods: We examined the medical records of 136 patients with ED SCLC who had initially responded to chemotherapy and undergone PCI from 2007 to 2015. The outcomes, radiation toxicity, neurologic progression-free survival, and OS after PCI were analyzed. Survival and correlations were calculated using log-rank and univariate Cox proportional hazard ratio analyses. Results: The median OS and the median neurologic progression-free survival after PCI was 12 and 19 months, respectively. No significant survival difference was seen for patients who had undergone MRI before PCI compared with patients who had undergone contrast-enhanced computed tomography (P ¼ .20). Univariate analysis for OS did not show a sta- tistically significant effect for known cofactors. Conclusion: In the present cohort, PCI was associated with improved survival compared with the PCI arm of the EORTC trial, with a nearly doubled median OS period. Also, the median OS was prolonged by 2 months compared with the irradiation arm of the Japanese trial. Clinical Lung Cancer, Vol. -, No. -, --- ª 2016 Elsevier Inc. All rights reserved. Keywords: Brain metastasis, ED, PCI, SCLC, Survival 1 Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany 2 Heidelberg Institute of Radiation Oncology, Heidelberg, Germany 3 Heidelberg Ion-Beam Therapy Center, Heidelberg, Germany 4 Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center, Heidelberg, Germany 5 Department of Thoracic Oncology, Thoraxklinik, Heidelberg University, Heidelberg Translational Lung Research Centre, Heidelberg, Germany 6 German Centre for Lung Research, Heidelberg, Germany 7 Department of Radiation Medicine, Georgetown University Hospital, Washington, DC 8 Department of Pneumology, Thoraxklinik, Heidelberg University, Heidelberg, Germany 9 Diagnostic and Interventional Radiology With Nuclear Medicine, Thoraxklinik 10 Department of Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany Submitted: Sep 12, 2016; Revised: Nov 15, 2016; Accepted: Nov 22, 2016 Address for correspondence: Denise Bernhardt, MD, Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, Heidelberg 69120, Germany E-mail contact: denise.bernhardt@med.uni-heidelberg.de 1525-7304/$ - see frontmatter ª 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.cllc.2016.11.012 Clinical Lung Cancer Month 2016 - 1