the time from diagnosis to death has been 4 to 12 ( median 9 ) months . almost 90% of male cases of mpm have reportedly been related to asbestos exposure . although remote metastases are found in the liver , adrenal gland , kidney and lung there have been many reports of brain metastasis with verification by autopsy , in which only 7 cases were symptomatic before death , and surgical removal was done . the results of surgical removal with or without chemotherapy and/or radiation therapy have not been very effective . the life expectancy of mpm was limited by the shortage of new treatments for mpm . recently , new chemotherapeutic drugs and boron neutron caputure therapy ( bnct ) have been effective for primary mpm . gkr was chosen for its effectiveness and less invasivenesss in the treatment of brain metastases . we experienced two symptomatic and one asymptomatic brain metastases from mpm , which were treated by gkr and followed - up while the patients were alive as shown in table 1 . three cases underwent gkr at nagoya radiosurgery center using the leksell gamma knife model 4c ( elekta instrument ab ) . after the treatment , patients were evaluated by head mri and neurological changes every two months . summary of three cases of brain metastases from mpm treated by gamma knife radiosugery f = female , m = male , y = year , m = month , t.=tumor , gkr = gamma knife radiosurgery ,   rt = right , lt = left , mets.=metastasis , exp.=exposure , gk = gamma knife   v.=ventricular , front.=frontal , temp.=temporal , cbll.=cerebellum , abdom.=abdominal a single large lesion decreased markedly at 3 months with improvement of symptoms after the treatment in case 1 ( fig 1a ) and three lesions disappeared in 4 months in case 3 ( fig . no follow - up study was available in case 2 because of early death of the patient . the response of metastatic lesions of mpm to gkr seemed similar to those of other malignant tumors , however two patients died by progression of primary lesions four and one month ( case 1,2 ) after gkr . another died of new brain metastases and periventricular dissemination seven months after gkr ( case 3 ) . it was also found that mri and pathological study revealed complete disappearance of the metastatic lesions in case 3 which were treated by gkr . the time from diagnosis of mpm to death in 3 patients was 3 years , one year 4 months and 2 years 4 months , respectively , of which the mean survival time was 26.7 months . follow - up mri of case 1 and case 3 after gamma knife radiosurgery : ( a ) rt - frontoparietal metastatic lesion ( left mris ) showed marked reduction 3 months after gkr ( right mri ) in case 1 . ( b ) three metastatic lesions ( circles , upper mris ) were disappeared at 4 months after gkr ( lower mris ) in case 3 . a 71-year - old man had cough , sputum and left thoracic pain since middle of 2008 . the patient had been working at a company with asbestos exposure for ten years since 1970 . he showed weight loss of 5 kg in a month of summer and also had hemorrhagic pleural fluid accumulation in a month later , when a chest x - ray showed narrowing of left pleural cavity with pleural mass . diagnosis of mpm was obtained by needle biopsy of pleura and cytology of the pleural fluid . three courses of chemotherapy with carboplatin plus pemetrexed were undertaken in 2009 , followed by 5 courses of pemetrexed alone and 4 courses of vinorelbine . the patient complained of headache , in the early 2010 , and brain mri showed three round enhanced lesions 1 cm in diameter at the right and left frontal , and temporal lobe with perifocal edema ( fig . 1b , upper ) . additional three courses of chemotherapy with carboplatin and gemcitabine were continued for the following 6 months . no further follow - up by brain mri was made and the patient showed gradual deterioration of sensorial level at 7 months after gkr . periventricular dissemination of the lateral ventricles and new multiple brain metastases are shown on t1 enhanced axial ( a ) and coronal mri images ( b ) . coresponding lesions are shown in the coronal cerebral ( c ) and cerebellar ( d ) sections of autopsy brain . mpm occupied the left intrapleural cavity and extended into the pleural diaphragma , mediastinum and the lung . 3a ) changed to a more aggressive form by the metastasis to the brain ( fig . new metastases in the cerebrum and cerebellum with periventricular disseminated lesions were verified at autopsy ( fig . immunohistochemcal studies of metastatic brain and lung lesions from autopsy revealed they were highly positive for calretinin , focally positive for d2 - 40 and ae1/ae2 , negative for cea . a sign of tentorial herniation was found at the tectum of midbrain , which was thought to be the cause of death . pathological findings of the pleural tumor and metastatic brain tumor hx - e stain show epithelial - type arrangement of pleural tumor ( a ) , whch is changed to sarcomatous arrangement in the metastatic brain tumor ( b ) . 200 asbestos exposure was initially found to be closely related to mesothelioma in 1960 , and patients with asbestos - related mesothelioma have increased in numbers over the last few decades . a case control study had indicated that almost 90% of males with mpm have reported prior exposure to asbestos . one of our patients worked in a factory with asbestos exposure for 10 years and had been observed as a patient of pneumonopathy ( case 3 ) . case 2 had short - time asbestos exposure before diagnosis of mpm , and asbestos exposure was not confirmed in case 1 . it has been recently found that the malignant change of asbestos exposure cells originated from excessive iron particles which accumulated in the cells . prophylactic procedure to remove iron particles from the cells will be a preventive therapy for mpm . mpm is classified into four pathological types ; fibrous or sarcomatous , epithelial , undifferentiated , and mixed . epithelial type is the most common and the sarcomatous type is the rarest but this type appears to be predominant in brain metastasis . it was confirmed that case 3 had already been diagnosed as the epithelial type of mpm by biopsy , and a sarcomatous component was predominant in the brain metastasis at autopsy ( figure 3 ) . a review of 172 autopsy cases of mpm revealed that the most frequently involved organs were the liver(55.9% ) , adrenal glands ( 31.3% ) , kidney ( 30.1% ) , and the contralateral lung ( 26.8% ) . the majority of brain metastases of mpm were reported as autopsy cases and only 9 patients had antemortem diagnosis , in which 7 cases undergone surgical removal . regarding the treatment method , four of them were combined with radiotherapy and three were treated by surgery alone . two of four patients of combined treatment survived more than 36 months and the other two survived 6 and 8 months after surgery ( mean of 21.5 months ) . the results of radiotherapy alone were also poor , but the present 3 cases survived a mean of 4.3 months after gkr ( table 1 ) . mpm had a poor prognosis with a median survival time of 9 ( 412 ) months , but long - term survival can be expected by the application of new multimodal approaches such as new chemotherapy or boron neutron capture therapy for primary lesion . the mean survival of the present three patients was 26.7 months from diagnosis , two of which died of original tumor and one by brain metastases . , this will be the first report of effectiveness of gkr for brain metastasis of mpm with combination of chemotherapy . many opportunities for treating brain metastasis with mpm will emerge in the future not only by stereotactic radiosurgery but also by stereotactic radiotherapy . this paper was presented at the 21th annual meeting of the japanese society for stereotactic radiosurgery at maebashi on june 1st , 2012 and the 4th annual meeting of the japan radiosurgery society on january 19 th , 2013 . the authors have no personal , financial or institutional interest in any of the drugs , materials or divices in this article .
abstractthe median survival time of malignant pleural mesothelioma ( mpm ) has been 9 months . given the short survival , 
 there have been only few cases in which brain metastases have been diagnosed and treated before death . 
 three cases of brain metastases treated by gamma knife radiosurgery ( gkr ) are reported . 
 case 1 showed a metastatic lesion in the right frontal lobe which was treated by gkr two years after diagnosis of mpm . 
 the lesion markedly reduced and the symptoms were improved , but the patient died of progression of pleural tumor four months after gkr . a year and three months after the diagnosis , asymptomatic bifrontal lesions were treated with gkr . however , case 2 died of abdominal mass a month after . 
 case 3 showed headache one and half year after the diagnosis . 
 three brain lesions were treated by gkr , which disappeared in 4 months . 
 the patient died of new multiple brain metastases and periventricular dissemination seven months after . 
 the autopsy revealed a mpm occupying the left pleural cavity . 
 no neoplastic lesion was found in gamma knife - treated sites . 
 the cause of death was the mass effect by new metastatic lesions . 
 gkr was found effective also for the treatment of brain metastasis of mpm .