talc pleurodesis ( tp ) is a procedure first described by bethune 1 in 1935 as a means to anchor the lung during lobectomy 2 . ever since then , tp has been employed worldwide in the management of recurrent pneumothorax and malignant pleural effusion , with a success rate in excess of 90% 3 - 5 .
tp is performed by instillation of sterile talc into the pleural cavity ( chemical pleurodesis ) , with chemical irritation leading to pleuritis , and ultimately to pleural fibrosis .
computed tomography ( ct ) and f - fluorodeoxy - glucose ( fdg ) positron - emission tomography ( pet ) are important imaging techniques for the detection and staging of cancers that , used together , may provide a more accurate tumor staging tool 6 . however , tp treatment has been reported to increase fdg uptake in thickened pleura , making it difficult to distinguish between benign inflammatory processes and malignancies , with the potential for false positive results 7 - 16 .
malignant pleural mesothelioma ( mpm ) is a thoracic neoplasm originating from the pleural lining , where an increased fdg uptake has been observed 17 , and several studies have reported on the use of pet to monitor chemotherapeutic response 18 - 21 . in this setting ,
the concomitant presence of a disease such as mpm , and the application of a procedure like tp , may produce an increase in suv that underestimates the tumor response to chemotherapy . in clinical practice
, the distinction of responding patients by those with stable or progressive disease has a prognostic implications and this is confirmed by some reports 22 , 23 .
the distinction of these two categories of disease may allow to recognize patients with better prognosis which may benefit by trimodality therapy by those with a resistant disease where it may be suggested a conservative approach .
the aim of this retrospective mpm case series was to analyze tp - induced pleural changes by fdg pet / ct and to verify the concordance between metabolic and radiologic response after chemotherapy .
inclusion criteria was biopsy confirmed mpm performed during tp , followed by fdg pet / ct staging .
all patients subsequently underwent three or four courses of pemetrexed based chemotherapy before fdg pet / ct restaging . written informed routinary consent was obtained from each patient before each examination , as standard quality of our institution require .
all data were acquired on a combined pet / ct in - line system ( biograph sensation 16 , siemens ) .
patients were instructed to fast for at least 6 h prior to scanning , which started 50 - 60 min after injection of 5.18 mbq fdg per kilogram body weight .
the glucose level was checked before radiotracer injection and it always was lower than 160 mg / dl .
all patients received a non - enhanced ct scan with 80ma , 120 kv parameters .
scans were acquired in the head and neck area , the thorax and the lower abdomen during shallow breathing , and the upper abdomen during non - forced expiration .
immediately after ct , the pet scan was performed using an acquisition time of 3 min per bed position .
the patient remained in the same supine position on the pet / ct table throughout the procedure , and acquisition times ranged from 18 to 24 min .
ct data were used for attenuation correction , and pet images were reconstructed by standard 2d - iterative algorithm ( ordered subset expectation maximization ) .
images were derived from an isocontour volume of interest ( voi ) drawn over the corresponding hemithorax region using a commercially available workstation ( siemens esoft 2004 ) .
voi margins were checked to cover the whole area of interest in all three planes .
the kidneys and the myocardium were spared from analysis by tracing a second voi positioned over the heart or kidneys .
the minimal suv within the first voi was set to a level of 2.5 to eliminate any physiological liver uptake , that may have influenced mpm measurements .
an example of pet / ct scan with recognized voi is represented in figure 1 .
all patients were radiologically staged according to brigham and women 's hospital 's revised mpm surgical staging system which considers tumor histology , resectability and nodal status 24 .
pleural biopsies obtained during tp procedures were analyzed to determine the histologic mpm subtypes 25 .
ct scans were assessed by a thoracic radiologist , experienced in mpm measurement and unaware of patient outcome ; radiologic response to chemotherapy was assessed using the modified mpm recist criteria 26 .
qualitative and semiquantitative evaluations of pet / ct images were performed by drawing a voi around the pleural thickness ; suvmax and suvmean depended on the initial dose administered and the body mass index .
criteria for therapeutic response assessment were according to the european organization for research and treatment of cancer ( eortc ) that defined guidelines for the use of pet using fdg .
these guidelines stated a 25% reduction in the maximum standardized uptake value ( suvmax ) as threshold for definition of partial response 27 .
all analyses were carried out by sas statistical software for windows version 9.1 ( sas institute inc . , cary , nc , usa ) .
inclusion criteria was biopsy confirmed mpm performed during tp , followed by fdg pet / ct staging .
all patients subsequently underwent three or four courses of pemetrexed based chemotherapy before fdg pet / ct restaging . written informed routinary consent was obtained from each patient before each examination , as standard quality of our institution require .
all data were acquired on a combined pet / ct in - line system ( biograph sensation 16 , siemens ) .
patients were instructed to fast for at least 6 h prior to scanning , which started 50 - 60 min after injection of 5.18 mbq fdg per kilogram body weight .
the glucose level was checked before radiotracer injection and it always was lower than 160 mg / dl .
all patients received a non - enhanced ct scan with 80ma , 120 kv parameters .
scans were acquired in the head and neck area , the thorax and the lower abdomen during shallow breathing , and the upper abdomen during non - forced expiration .
immediately after ct , the pet scan was performed using an acquisition time of 3 min per bed position .
the patient remained in the same supine position on the pet / ct table throughout the procedure , and acquisition times ranged from 18 to 24 min .
ct data were used for attenuation correction , and pet images were reconstructed by standard 2d - iterative algorithm ( ordered subset expectation maximization ) .
images were derived from an isocontour volume of interest ( voi ) drawn over the corresponding hemithorax region using a commercially available workstation ( siemens esoft 2004 ) .
voi margins were checked to cover the whole area of interest in all three planes .
the kidneys and the myocardium were spared from analysis by tracing a second voi positioned over the heart or kidneys .
the minimal suv within the first voi was set to a level of 2.5 to eliminate any physiological liver uptake , that may have influenced mpm measurements .
an example of pet / ct scan with recognized voi is represented in figure 1 .
all patients were radiologically staged according to brigham and women 's hospital 's revised mpm surgical staging system which considers tumor histology , resectability and nodal status 24 .
pleural biopsies obtained during tp procedures were analyzed to determine the histologic mpm subtypes 25 .
ct scans were assessed by a thoracic radiologist , experienced in mpm measurement and unaware of patient outcome ; radiologic response to chemotherapy was assessed using the modified mpm recist criteria 26 .
qualitative and semiquantitative evaluations of pet / ct images were performed by drawing a voi around the pleural thickness ; suvmax and suvmean depended on the initial dose administered and the body mass index .
criteria for therapeutic response assessment were according to the european organization for research and treatment of cancer ( eortc ) that defined guidelines for the use of pet using fdg .
these guidelines stated a 25% reduction in the maximum standardized uptake value ( suvmax ) as threshold for definition of partial response 27 .
all analyses were carried out by sas statistical software for windows version 9.1 ( sas institute inc . , cary , nc , usa ) .
eight patients were included in our study , 6 ( 75% ) males and 2 ( 25% ) females , with a median age of 65 years ( range : 54 - 77 ) .
histologic examination revealed an epitheliod subtype in 7 ( 88% ) cases and a mixed subtype in 1 ( 12% ) , 5 ( 63% ) of which were located on the left side and 3 ( 37% ) on the right .
overall , 7 ( 88% ) stage i and 1 ( 12% ) stage ii diseases were reported .
all patients underwent pemetrexed - based chemotherapy ( 3 patients in combination with carboplatin , 4 with cisplatin , and 1 with pemetrexed only ) with a median of 3.5 courses ( range : 3 - 4 ) before restaging .
after tp treatment , there was a mean interval of 14 days ( range : 9 - 22 ) and 125 days ( range : 76 - 162 ) between fdg pet / ct staging and restaging , respectively , and , on average , 26 days ( range : 6 - 46 ) between the last course of chemotherapy and the fdg pet / ct restaging .
suv mean and suv max before and after treatment is summarized in the table 2 .
the concordance between two kinds of responses was respectively 37.5% ( 3 out of 8 patients ) and 75% ( 6 out of 8 patients ) . comparing radiologic and metabolic response , expressed as suvmax and suvmean ( see table 2 and table 3 ) , the concordance was 37.5% ( 3 out of 8 patients ) and 75% ( 6 out of 8 patients ) , respectively .
talc pleurodesis is used to treat patients with persistent pleural effusions or pneumothorax not amenable to other therapies 1 - 5 .
pathologic studies have shown that granulomatous inflammation occurs in the visceral and parietal pleural immediately after tp , resulting in pleural inflammation . for several years , this has been presumed to be the cause of increased fdg activity , leading to the difficulty in distinguishing between benign and malignant disease 7 , 8 , 10 .
mpm is a malignancy arising from the pleural sierosa with an fdg - avidity 17 , and this characteristic has been proposed to evaluate chemotherapeutic response 18 - 21 .
pleural inflammation , induced by tp and mpm , produces pleural thickening or nodularity detected by radiologic examination , and the resulting increase in suv uptake leads to biases in the post - chemotherapy evaluation .
increased fdg uptake , with an associated increase in the thickness of non calcified pleural lesions , or new fdg - avid pleural lesions without associated calcification , are suspicious for malignancy , whereas fdg uptake in calcified pleural lesions suggests benign tp - induced changes .
currently , little clinical data is available on which is the best metabolic index to reduce chemotherapy evaluation bias in mpm patients previously treated with tp . in our experience , considering that morphologic changes shown by ct - scan predict response to chemotherapy 26 , we observed that the metabolic response measured by suvmean seems to be in better agreement with the radiologic evaluation compared to the suvmax , but without reaching statistical significance .
this may probably be due to the relatively small number of cases in our study , and therefore a larger prospective study is required to confirm our hypothesis .
 purpose : talc pleurodesis ( tp ) is employed worldwide for the management of persistent pneumothorax or pleural effusion , particularly of malignant origin . however , there are very little available data on 18f - fluorodeoxyglucose positron - emission tomography / computed tomography ( 18f fdg pet / ct ) response evaluation in malignant pleural mesothelioma ( mpm ) patients treated with tp and chemotherapy.methods : patients with histologically confirmed mpm underwent tp and fdg pet / ct staging and restaging after 3 - 4 courses of chemotherapy . 
 all patients fasted and received a dose of 5.18 mbq 18f - fdg per kilogram of body weight . 
 whole - body emission scans were acquired with and without ordered subset expectation maximization ( osem ) iterative reconstruction algorithm.results : from january 2004 to march 2010 , 8 patients with biopsy confirmed mpm ( 7 epithelial , 1 biphasic ) , with a median age of 65 years ( range : 54 - 77 ) , were evaluated . 
 median follow - up was 31 months ( range : 4 - 44 ) . 
 after tp treatment , there was a mean interval of 14 days ( range : 9 - 22 ) and 125 days ( range : 76 - 162 ) between fdg pet / ct staging and restaging . according to modified recist and eortc criteria 
 , there was a concordance between the radiologic and metabolic suvmean and suvmax responses in 6 ( 75% ) and 3 ( 37.5% ) patients , respectively.conclusion : tp produces an increased fdg pet uptake which may interfere with the post - chemotherapy disease evaluation . in our case series , the metabolic response measured by suvmean seems to be in better agreement with the radiologic response compared to the suvmax . 
Introduction
Subjects and Methods
Clinical data
FDG PET/CT evaluation
Image and response evaluations
Statistical analysis
Results
Discussion