soft - tissue sarcomas are rare cancers that account for 1% of all adult cancers . pazopanib , a multitargeting tyrosine kinase inhibitor , was approved for patients with advanced soft - tissue sarcoma . although the frequency of this complication was low , many questions remain regarding the causal relationship between the two as well as regarding the mechanism . in this study , we reviewed 2 cases of pneumothorax that occurred in patients with soft - tissue sarcoma during pazopanib treatment . a 63-year - old male presented with malignant fibrous histiocytoma originating from the left femur . one year after the operation , multiple lung metastases and a metastasis to the right pleura emerged . however , multiple lung metastases and the metastasis to the right pleura progressed , and multiple liver metastases and peritoneum dissemination emerged . he was started on pazopanib treatment . after approximately 4.5 months of pazopanib treatment ( 132 days ) , a left hemopneumothorax was found by chest x - ray ( fig . thoracic cavity drainage and pleurodesis with autologous blood were performed ; however , the patient did not recover from the pneumothorax and died from disease progression 34 days after occurrence . an 81-year - old female presented with a spindle cell and pleomorphic sarcoma from the left femur . . however , the sarcoma recurred with multiple lung metastases and she was started on pazopanib treatment ( 600 mg / day ) . on the fourth day of pazopanib treatment , hemosputum and dyspnea were noted , and bilateral pneumothorax was found by chest x - ray ( fig . pazopanib treatment was stopped , and thoracic cavity drainage was performed for the left and right pneumothorax without any treatment . a 63-year - old male presented with malignant fibrous histiocytoma originating from the left femur . one year after the operation , multiple lung metastases and a metastasis to the right pleura emerged . however , multiple lung metastases and the metastasis to the right pleura progressed , and multiple liver metastases and peritoneum dissemination emerged . he was started on pazopanib treatment . after approximately 4.5 months of pazopanib treatment ( 132 days ) , a left hemopneumothorax was found by chest x - ray ( fig . thoracic cavity drainage and pleurodesis with autologous blood were performed ; however , the patient did not recover from the pneumothorax and died from disease progression 34 days after occurrence . an 81-year - old female presented with a spindle cell and pleomorphic sarcoma from the left femur . the sarcoma was resected and she was treated with postoperative radiation therapy . however , the sarcoma recurred with multiple lung metastases and she was started on pazopanib treatment ( 600 mg / day ) . on the fourth day of pazopanib treatment , hemosputum and dyspnea were noted , and bilateral pneumothorax was found by chest x - ray ( fig . pazopanib treatment was stopped , and thoracic cavity drainage was performed for the left and right pneumothorax without any treatment . we have described 2 cases of pneumothorax that occurred in patients with soft - tissue sarcoma during pazopanib treatment . in the preapproval clinical trial of pazopanib for metastatic soft - tissue sarcoma , the frequency of pneumothorax during pazopanib treatment .   demonstrated that pneumothorax sometimes occurs in patients with sarcoma as part of the natural history of the disease . moreover , no pneumothorax was reported in the clinical trial of pazopanib for renal cell carcinoma treatment [ 4 , 5 ] . the mechanism of secondary pneumothorax from lung metastases is unclear , although several theories have been proposed , including tumor necrosis , check valve , and tumor embolus . angiogenesis inhibitors are known to cause tumor necrosis and cavitations in lung lesions , which may possibly be the cause of pneumothorax during pazopanib treatment . pneumothorax during bevacizumab treatment , another angiogenesis inhibitor , is a frequent occurrence [ 8 , 9 ] . moreover , pneumothorax during sunitinib , another multitargeting tyrosine kinase inhibitor treatment , has also been reported . we have treated 16 patients with soft - tissue sarcoma with pazopanib , and 2 of these patients ( 12.5% ) experienced pneumothorax complications . similarly , nakano et al .   reported that the frequency of pneumothorax in patients with soft - tissue sarcoma during pazopanib treatment was 9.4% . these frequencies are higher than that reported in the preapproval clinical trial of pazopanib . the above - mentioned case series reported by hoag et al .   also found chest radiograph findings in patients with sarcoma who experienced pneumothorax . multiple nodules ( in 48.4% of cases ) and cavitary or cystic lesions ( in 25.8% of cases ) were the most common radiographic findings , with pleural abnormalities seen in 11.7% of cases . moreover , 2 of 4 patients ( 50% ) in our institute with multiple lung metastases were complicated by pneumothorax . because pazopanib treatment is recommended for treatment of more advanced disease ( e.g. , multiple lung metastases ) , it might be expected that the frequency of pneumothorax in our institute may be higher than in previous reports . the pneumothorax in case 2 was bilateral , and the above - mentioned case series also reported that 41.6% of the cases of pneumothoraxes in patients with sarcoma were bilateral on initial presentation . according to that case series , 45.7% of the pneumothoraxes in patients with sarcoma recurred , and the outcomes of these patients were not positive ; the 1-year mortality after pneumothorax was 75% . in the present study , case 1 did not recover from the pneumothorax and died 34 days after occurrence . in conclusion , herein we report 2 cases of pneumothorax that occurred during pazopanib treatment in patients with soft - tissue sarcoma . although a causal relationship is uncertain , it is possible that the pneumothorax occurred as a result of the pazopanib treatment . according to a previous report   and our experience , the risk of pneumothorax may be higher in patients with multiple lung metastases , and the prognosis of patients with sarcoma who experience pneumothorax is poor .
pazopanib , a multitargeting tyrosine kinase inhibitor , has single - agent activity in patients with advanced soft - tissue sarcoma . 
 herein , we describe 2 cases of pneumothorax that occurred during pazopanib treatment in patients with soft - tissue sarcoma . 
 these 2 patients had multiple lung metastases . according to previous reports and our past experience 
 , the risk of pneumothorax may be higher in patients with multiple lung metastases . although a causal relationship is uncertain , the risk of pneumothorax when prescribing pazopanib for these patients should be considered .