www.jkns.or.kr http://dx.doi.org/10.3340/jkns.2012.52.3.193 J Korean Neurosurg Soc 52 : 193-199, 2012 Print ISSN 2005-3711 On-line ISSN 1598-7876 Copyright © 2012 The Korean Neurosurgical Society Clinical Article Incidence and Risk Factors for Leptomeningeal Carcinomatosis in Breast Cancer Patients with Parenchymal Brain Metastases Jong-myung Jung, M.D.,1 Sohee Kim, M.S.,2 Jungnam Joo, Ph.D.,2 Kyung Hwan Shin, M.D., Ph.D.,3 Ho-Shin Gwak, M.D., Ph.D.,4 Seung Hoon Lee, M.D., Ph.D.4 Department of Neurosurgery,1 Seoul National University College of Medicine, Cancer Biostatistics Branch,2 Seoul, Korea Department of Radiation Oncology,3 Neuro-Oncology Clinic,4 National Cancer Center, Goyang, Korea Objective : The objective of study is to evaluate the incidence of leptomeningeal carcinomatosis (LMC) in breast cancer patients with parenchymal brain metastases (PBM) and clinical risk factors for the development of LMC. Methods : We retrospectively analyzed 27 patients who had undergone surgical resection (SR) and 156 patients with whole brain radiation therapy (WBRT) as an initial treatment for their PBM from breast cancer in our institution and compared the difference of incidence of LMC according to clinical factors. The diagnosis of LMC was made by cerebrospinal fluid cytology and/or magnetic resonance imaging. Results : A total of 27 patients (14%) in the study population developed LMC at a median of 6.0 months (range, 1.0-50). Ten of 27 patients (37%) developed LMC after SR, whereas 17 of 156 (11%) patients who received WBRT were diagnosed with LMC after the index procedure. The inci- dence of LMC was significantly higher in the SR group compared with the WBRT group and the hazard ratio was 2.95 (95% confidence interval; 1.33-6.54, p<0.01). Three additional factors were identified in the multivariable analysis : the younger age group (<40 years old), the progressing systemic disease showed significantly increased incidence of LMC, whereas the adjuvant chemotherapy reduce the incidence. Conclusion : There is an increased risk of LMC after SR for PBM from breast cancer compared with WBRT. The young age (<40) and systemic bur- den of cancer in terms of progressing systemic disease without adjuvant chemotherapy could be additional risk factors for the development of LMC. Key Words : Brain metastasis · Breast cancer · Leptomeningeal carcinomatosis · Surgery · Whole brain radiation therapy. INTRODUCTION The incidence of parenchymal brain metastasis (PBM) from primary systemic cancer has been increasing along with pro- longed survival of the patients with cancer. Recent report showed that up to 30% of cancer patients can be expected to develop PBM according to the types of primary cancer6,12). A popula- tion-based estimate of the incidence proportion of PBM was highest for lung cancer followed by melanoma, renal-, and breast cancer3). However, leptomeningeal carcinomatosis (LMC), which is one of terminal manifestations of central nervous system (CNS) me- tastasis from systemic malignancy, remains incurable without a discernible advance in treatment over the past decades. LMC also has been diagnosed more frequently with the advancement of neuroimaging and prolonged survival of cancer patients8,13,29). Among the pathogenesis of LMC, spread of cancer cells fol- lowed by surgical resection (SR) has been suggested from sev- eral clinical observations of solid tumors including malignant brain tumors2,11,16,22,23,34). Although the overall incidence of LMC is difficult to estimate according to PBM status, it is apparent that the primary cancer showing a high incidence of PBM, such as lung cancer, breast cancer or melanoma, develops into a high proportion of LMC among those cancer patients5,35). Several reports suggested that the risk for development of LMC may increase in patients with PBM who underwent SR compared with non-surgical treatment, and at the same time, the risk may also be affected by factors such as location of the tu- • Received : January 10, 2012 • Revised : June 14, 2012 • Accepted : September 17, 2012 • Address for reprints : Ho-Shin Gwak, M.D., Ph.D. Neuro-Oncology Clinic, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 410-769, Korea Tel : +82-31-920-1666, Fax : +82-31-920-2798, E-mail : nsghs@ncc.re.kr • This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 193