Multiple GKRS versus a Single GKRS Plus WBRT for Multiple Metachronous Brain Metastases | HS Kim, et al. Table 2. Result of Cox proportional hazard cy of SRS alone, even for patients with 1-4 brain metastases1,2). Hoffman’s group Standard error Wald df p-value Exp(B) reported 10 month survival for patients Numbers of lesion 0.0607 5.6889 1 0.0171 1.1559 with recurrent brain metastases after Average volume of lesions 0.0003 3.9263 1 0.0475 1.0005 SRS10). Karlsson et al.13) presented no Repeated numbers of GKRS 0.7213 11.2021 1 0.0008 0.0894 statistically significant relationship be- Interval of development of new lesion 0.1629 10.0296 1 0.0015 0.5970 tween number of brain metastases Wald : Wald test statistic, df : degree of freedom, Exp(B) : odds ratio, GKRS : gamma knife radiosurgery upon first treatment and total number of GKRS treatments. They found long-term survivors among metastatic brain tumors as much as upfront WBRT. patients with 4 or more cerebral metastases who underwent Cox proportional hazard analysis showed that the propor- GKRS. Among patients with 4 or more metastases, 21% of pa- tional hazard of the number of the lesions, the average volume tients survived for 1 year after treatment, 10% survived for 27 of lesions in each patients, the repeated number of GKRS, and months, and 5% survived for 43 months. Bhatnagar et al.5) re- the interval of development of new lesions were 1.1559, 1.0005, ported the median overall survival time after SRS for all pa- 0.08943, and 0.5970, in each. From these results we can impli- tients having 4 or more intracranial metastases was 8 months. cate that patients with the every additional number of the le- They concluded radiosurgery seems to provide a survival bene- sions are more risky in 1.1559 times in the number of the le- fit for patients having 4 or more lesions, and total treatment vol- sions, when other variables are controlled. In the aspect of the ume is the most significant survival predictor. Chang et al.6) an- average volume of lesions in each patient, the proportional haz- alyzed GKRS’s effectiveness for multiple metastatic brain ard can be understood that patients with every additional unit tumors. They presented a median patient survival time of 10 volume (additional 1 cc) are more risky in 1.0005 times. With months (range of 8.7-11.4 months), and they concluded GKRS respect to the repeated number of GKRS, the proportional haz- might be a good treatment option for local metastatic lesion ard of 0.08943 means that patients with the lesser number of control and for improving survival time in patients with multi- GKRS are more risky. The proportional hazard (0.5970) for the ple metastatic brain lesions, even in those patients harboring interval of development of new lesions between the times of more than 15 metastatic brain lesions. each GKRS means that the shorter the recurrence duration is, Our patients with multiple GKRS showed an average of 15.6 the higher the risk is in patients. lesions (range 3-38 lesions) each and received an average of 3.3 Even though our study had some limitations in the small num- times (range 3-6 times) of GKRS. Median survival time of pa- ber of patients and the heterogeneous histopathologic findings of tients with multiple GKRS after their first GKRS was 18 months lung cancer, this result showed that multiple GKRS is valuable (range 6-50 months). It is almost three folds of survival time treatment in extending the survival time in patients with multi- rather than that of patients with a single GKRS plus WBRT. ple metachronous brain metastases of lung cancer. This result supports that multiple GKRS treatments for meta- chronous multiple lesions are of necessity for treatment strategy CONCLUSION for patients with metastatic brain tumors with regard to extend- ing survival time and avoiding delayed adverse effects after Our study reports that patients with multiple GKRS showed WBRT. Furthermore, maintenance of good general condition 18 months of median survival time after first GKRS and, on the of patients was of importance to endure chemotherapy and contrary, patients with a single GKRS plus WBRT showed 6 other advanced treatments, and it provided the opportunities of months of median survival time after first GKRS. In patients extension of survival. with multiple GKRS, the result of Kaplan-Meier analysis showed Three class I studies demonstrate that WBRT significantly that the large numbers of lesion (more than 10 lesions), the lowers the risk of a distant recurrence comparing to local tumor large repeated numbers of GKRS (more than three times) and therapies (SRS or surgical resection) used in isolation1,14,16). even the short interval of development of new lesions (shorter However, four of 10 retrospective cohort studies revealed no than 7 months) did not influence onto the limitation of the sur- significant differences in distant recurrence rates between these vival time of patients. The large volume of the lesions was only two treatment strategies7,11,17,19). Our results revealed that median related with shortening the survival time of patients. In Cox time to recurrence was 7.1 months (range 1.5-16 months, the proportional hazard method, however, the volume of the le- average frequency of GKRS treatments per patient was 3.3 times) sions was not a hazard factor of shortening the survival time. in patients with multiple GKRS and 6.8 months (range 2-16 Authors thought that multiple GKRS could improve or sustain months) in patients with a single GKRS plus WBRT. These data a general and neurological condition of patients without radia- implicated that GKRS made a longer average progression-free tion induced adverse effect and it made opportunities that pa- time, in comparison to the other reports on progression-free tients get advanced chemotherapy and other supportive treat- time of WBRT which was 4.6-6 months7). This result supports ments. In conclusion, our result supports that multiple GKRS is that GKRS alone may be an effective modality for controlling of value of treatment in extending the survival time in patients 337