Multiple GKRS versus a Single GKRS Plus WBRT for Multiple Metachronous Brain Metastases | HS Kim, et al. of lesions in each patient, 2) the average volume of lesions in each patient, 3) the number of repeated GKRS, and 4) the inter- val of development of new lesions, respectively. MATERIALS AND METHODS Patients Between May 2006 and July 2010, 112 patients with brain metastases from lung cancer underwent GKRS. Metastatic brain lesions were identified with 3.0 Tesla MRI (Verio, Sie- mens, Erlangen, Germany). This study included 31 patients who had multiple metachronous metastases. Twenty out of 31 patients underwent multiple GKRS (group A) and the remain- ing 11 patients underwent a single GKRS plus WBRT (group B). Inclusion criteria were as follows : 1) only intracranial metas- tases in additional positron emission tomography at the time of their first GKRS treatment to eliminate the effect of systemic condition, 2) the Karnofsky Performance Scale (KPS) at each GKRS scored 70 or more, 3) patients who did not underwent WBRT prior to GKRS. Patients in group B were the patients who did not want repeated GKRS due to economic problem and they showed 70 or more score of KPS and only intracranial metastases at time of WBRT. The patients continued receiving chemotherapy until they or their family refused further treat- ment. Chemotherapy regimens were different according to his- topathologic types of the lung cancer. GKRS technique and dosage of WBRT The Leksell Gamma Knife, C-type (Elekta Instruments, Inc.) was used for all patients’ treatments. We obtained T1-weighted, high-dose gadolinium (Gd) enhanced images, with an injected Gd volume of 0.4 mmol/kg. Furthermore, we used multiple iso- centers to insure a highly conformal dose distribution and de- fined a prescription dose as a dose covering at least 93% of the target volume. To irradiate the tumor margins, we used the 50% or 48% isodose line, with an average marginal dose of 20 Gy (range 14-22). WBRT was performed by radiation oncologist. Irradiated dosage was total 20 Gy for 10 days (200 cGy per day). Follow-up and evaluation of treatment response The follow-up schedule was the same in all patients. Patients underwent brain MRI with a 3.0 Tesla MRI (Verio, Siemens, Erlangen, Germany) every 3 months after GKRS treatment and received clinical and neurological examinations every month. In patients with severe headache or neurological deterioration, we obtained brain MRI every month. Statistical analysis We analyzed cumulative survival between two groups of mul- tiple GKRS (group A) and a single GKRS plus WBRT (group B) by Kaplan-Meier method. In group A, we used the Kaplan- Meier and Cox proportional hazards method to analyze rela- tionship between survival and 1) the number of lesions in each patient, 2) the average volume of lesions in each patient, 3) the number of repeated GKRS, and 4) the interval of development of new lesions, respectively. Total volume of lesions of individu- al patients was calculated. However, it was not statistically ana- lyzed because of the diversity in volumetric measurement in each patient and each lesion. In group A, four factors were analyzed as followed standards : 1) the number of lesions in each patient : above 10 and below 10, 2) the average volume of lesions in each patient : above 10 cc and below 10 cc, 3) number of repeated GKRS : above 3 times and below 3 times, and 4) the interval of development of new lesions : above 7 months and below 7 months. RESULTS Result of 20 patients with multiple GKRS (group A) The patients’ male to female ratio was 13 : 7, and their mean age was 58.2 years (range 36-77 years). Mean tumor volume was 1.97 cc (range 0.01-27.5 cc) and mean lesion number per patients was 15.6 lesions (range 3-38 lesions). Total treated le- sion volume was average 23.7 cc (range 0.15-79 cc). Average frequency of GKRS treatments was 3.3 times (range 3-6 times). Median time for development of new lesions was 7.1 months (range 1.5-16 months). Histopathological findings regarding lung cancers revealed adenocarcinoma in 13 patients, large cell neuroendocrine tumor in three, small cell lung cancer in two, large cell undifferentiated carcinoma in one, and squamous cell cancer in one (Table 1). Median survival time after first GKRS was 18 months (range 6-50 months). Three patients had been survived for quite a long time : 47, 48, and 50 months after their first GKRS, respectively. Patients did not suffer from any radia- tion-induced adverse effects. From the neurological perspec- tive, two patients with large, centrally-located lesions showed temporary motor weakness after GKRS. Causes of death were medical problems that included aggravation of the primary lung cancer, pneumonia, and cachexia. Neurological deteriora- tion was not a cause of patient death. The mean follow-up dura- tion was 18 months (range 6-60 months). Result of 11 patients with single GKRS plus WBRT (group B) Male to female ratio was 6 : 5, and their mean age was 61.4 years (range 36-70 years). Mean tumor volume was 3.2 cc (range 0.05-6.7 cc) and mean lesion number per patient was 14.3 lesions (range 4-38 lesions). Total treated lesion volume was average 25 cc (range 0.3-60 cc). Median time for develop- ment of new lesions was 6.8 months (range 2-16 months). His- topathological findings regarding lung cancer revealed adeno- carcinoma in 8 patients, small cell lung cancer in 3 (Table 1). Median survival time after first GKRS was 6 months (range 3-18 months). Causes of death were medical problems in 8 patients that in- cluded aggravation of the primary lung cancer, pneumonia, and 335