J Korean Neurosurg Soc 52 | September 2012 mor, treatment modality and the histology of primary can- cer21,23,24,30-33). However, to our knowledge, neither a controlled- prospective study nor any study which attempted to adjust these variables to evaluate the significant risk factors for LMC has been reported. Breast cancer is known to be the second most common can- cer associated with PBM and is also, one of the most common primary cancers that causes LMC5,6,38). Thus, we retrospectively collected data on patients with PBM from one primary histolo- gy of breast cancer. The primary objective of the study was to estimate the incidence of LMC after SR or whole brain radia- tion therapy (WBRT) as the initial treatment in a cohort of breast cancer patients with PBM. Further, we examined if SR confers a higher risk for the development of LMC than WBRT in these patients, and also, analyzed the influence of the above men- tioned clinical factors on the development of LMC. MATERIALS AND METHODS Study population From our institutional medical record database, we identified 274 cases of SR or WBRT as the initial treatment for PBM from breast cancer between August, 2001 and December, 2010. Elev- en breast cancer patients, who received radiosurgery as the ini- tial treatment for their PBM, were not included in this cohort. Patients were excluded if they were diagnosed with LMC be- fore the index procedure (12 patients), did not have a MRI fol- low-up at our institution after the index procedure (76 patients), or had incomplete data (3 patients) on entities under study. A total 183 patients met the eligibility criteria and are included in this analysis. Twenty-seven patients (15%) underwent SR of their tumors, and the remaining 156 patients (85%) received WBRT. Among 27 SR group, 11 patients underwent WBRT within one month after SR as an adjuvant treatment, 10 patients received WBRT after local or distant recurrence of their brain metastasis, and the remaining 6 patients were observed without WBRT. Patients were followed up with MRI every 3 to 6 months, until the patients died or no longer returned to our hospital. Evaluation of clinical factors We reviewed the following factors from medical records and conventionally categorized them for the analysis : type of index procedure (SR or WBRT), age, time from diagnosis to brain me- tastasis, volume of tumor, number of brain metastatic lesions (single or multiple), location (supratentorial or infratentorial) of the brain metastatic lesion, adjuvant chemotherapy, Karnofsky Performance Status (KPS) scale and systemic disease status (no evidence of disease, stable, or progressing). Outcome evaluation The primary outcome was the incidence of LMC, as diag- nosed by cytological CSF analysis or neuroimaging findings such as “clear leptomeningeal enhancement extending into the cerebral sulci or into the folia of the cerebellum, spinal cord, cauda equina or subependyma”13). All patients were evaluated by brain MRI at least once for monitoring local or cerebral re- currence. Spinal MRI and CSF cytology was examined only if the patient had symptoms of LMC. Time to event (LMC) was defined as the time from the index procedure to the diagnosis of LMC or the last follow-up image. WBRT group patients were censored when they received SR for the management of recur- rent tumor to avoid overlapped exposure to higher risk. Statistics The differences in the distributions of categorical variables for SR and WBRT groups as well as the incidence of LMC were an- alyzed using the chi-square test or Fisher exact test, as appropri- ate. Continuous variables were tested using Student’s t-test or Wilcoxon test. A p-value of 0.05 or less was considered statisti- cally significant. For the analysis of the cumulative incidences of LMC, patients were censored at the end of observation or lost to follow-up. In the univariable analysis, the Cox propor- tional hazard model was used to estimate the hazard and corre- sponding 95% confidence interval (CI) of developing LMC for each of the risk factors. Factors that showed at least marginal significance from the univariable analysis (p-value <0.2) were included in the multivariable analysis to account interrelation- ships among the variables. RESULTS Characteristics of the patients Characteristics of patients who underwent SR or WBRT for their PBM are presented in Table 1. The median follow-up (of im- age) after index procedure was 6.0 months (range, 1-51 months), and the follow-up periods were not different according to the treatment modality with a median of 5.8 months for the WBRT group and 8.0 months for the SR group. The median survival of SR group was 14.5 months (95% CI; 10.5-28.7) and that of WBRT only was 9.4 months (95% CI; 7.4-11.9). However, this apparent difference of median survival between SR group and WBRT group was not statistically significant (p>0.05). The median age of the patients at the time of the index proce- dure was 52 years (range, 28-80 years), and the median time from diagnosis of the primary cancer to brain metastasis was 41 months (range, 1-271 months). The median tumor volume was 4.0 cm³ (range, 0.01-105.0 cm³), and it was significantly differ- ent between two modes of treatment : the median tumor vol- ume of the SR group was 10.9 cm³ while that of the WBRT group was 3.1 cm³ (p<0.001). Fifty-eight patients (32%) had a single lesion at the time of index procedure while the remaining 125 patients (68%) had multiple metastases. Patients with a sin- gle lesion were more frequently treated by SR than those with multiple lesions (p<0.001). Supratentorial lesions constituted 28% of the patients, and an infratentorial lesion occurred in 72% of the patient. Infratentorial lesion includes the case with 194