Many recent study series on patients with various pathologies report survival times of 7-10.5 months for single or multiple newly-diagnosed or recurrent brain metastases9,12,15)
. Such patients with brain metastases from lung cancer have median survival time of 10-12 months3,8,18)
. Aoyama et al.1)
reported patients with 1-4 brain metastases undergoing stereotactic radiosurgery (SRS) treatment alone had median survival times of 8 months, while patients receiving SRS plus WBRT survived 7.5 months. This result confirms the efficacy of SRS alone, even for patients with 1-4 brain metastases1,2)
. Hoffman's group reported 10 month survival for patients with recurrent brain metastases after SRS10)
. Karlsson et al.13)
presented no statistically significant relationship between number of brain metastases upon first treatment and total number of GKRS treatments. They found long-term survivors among patients with 4 or more cerebral metastases who underwent GKRS. Among patients with 4 or more metastases, 21% of patients survived for 1 year after treatment, 10% survived for 27 months, and 5% survived for 43 months. Bhatnagar et al.5)
reported the median overall survival time after SRS for all patients having 4 or more intracranial metastases was 8 months. They concluded radiosurgery seems to provide a survival benefit for patients having 4 or more lesions, and total treatment volume is the most significant survival predictor. Chang et al.6)
analyzed GKRS's effectiveness for multiple metastatic brain tumors. They presented a median patient survival time of 10 months (range of 8.7-11.4 months), and they concluded GKRS might be a good treatment option for local metastatic lesion control and for improving survival time in patients with multiple metastatic brain lesions, even in those patients harboring more than 15 metastatic brain lesions.
Our patients with multiple GKRS showed an average of 15.6 lesions (range 3-38 lesions) each and received an average of 3.3 times (range 3-6 times) of GKRS. Median survival time of patients with multiple GKRS after their first GKRS was 18 months (range 6-50 months). It is almost three folds of survival time rather than that of patients with a single GKRS plus WBRT. This result supports that multiple GKRS treatments for metachronous multiple lesions are of necessity for treatment strategy for patients with metastatic brain tumors with regard to extending survival time and avoiding delayed adverse effects after WBRT. Furthermore, maintenance of good general condition of patients was of importance to endure chemotherapy and other advanced treatments, and it provided the opportunities of extension of survival.
Three class I studies demonstrate that WBRT significantly lowers the risk of a distant recurrence comparing to local tumor therapies (SRS or surgical resection) used in isolation1,14,16)
. However, four of 10 retrospective cohort studies revealed no significant differences in distant recurrence rates between these two treatment strategies7,11,17,19)
. Our results revealed that median time to recurrence was 7.1 months (range 1.5-16 months, the average frequency of GKRS treatments per patient was 3.3 times) in patients with multiple GKRS and 6.8 months (range 2-16 months) in patients with a single GKRS plus WBRT. These data implicated that GKRS made a longer average progression-free time, in comparison to the other reports on progression-free time of WBRT which was 4.6-6 months7)
. This result supports that GKRS alone may be an effective modality for controlling metastatic brain tumors as much as upfront WBRT.
Cox proportional hazard analysis showed that the proportional hazard of the number of the lesions, the average volume of lesions in each patients, the repeated number of GKRS, and the interval of development of new lesions were 1.1559, 1.0005, 0.08943, and 0.5970, in each. From these results we can implicate that patients with the every additional number of the lesions are more risky in 1.1559 times in the number of the lesions, when other variables are controlled. In the aspect of the average volume of lesions in each patient, the proportional hazard can be understood that patients with every additional unit volume (additional 1 cc) are more risky in 1.0005 times. With respect to the repeated number of GKRS, the proportional hazard of 0.08943 means that patients with the lesser number of GKRS are more risky. The proportional hazard (0.5970) for the interval of development of new lesions between the times of each GKRS means that the shorter the recurrence duration is, the higher the risk is in patients.
Even though our study had some limitations in the small number of patients and the heterogeneous histopathologic findings of lung cancer, this result showed that multiple GKRS is valuable treatment in extending the survival time in patients with multiple metachronous brain metastases of lung cancer.