Monitoring of chemotherapy response in malignant pleural mesothelioma using fluorodeoxyglucose positron emission tomography.

We report a 56-year-old man who underwent monitoring of the response to chemotherapy of malignant pleural mesothelioma (MPM). (8)F-fluoro-2-deoxy-(D)-glucose positron emission tomography (FDG-PET) and computed tomography (CT) were performed prior to chemotherapy and after the first and second courses of chemotherapy. The tumor lesion exhibited shrinkage on CT and a decrease in the standardized uptake value (SUV) max after the first course of chemotherapy, but exhibited size enlargement and an increase in SUV max after the second course of chemotherapy. These findings suggest that results of quantification of metabolic response by FDG-PET are related to the objective response as determined by CT in patients with MPM.


Introduction
Malignant pleural mesothelioma (MPM) is an insidious neoplasm usually associated with asbestos exposure, with findings of malignant unilateral pleural effusion or increase in pleural thickness (1,2). Currently, imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) are widely used for the evaluation of the effects of chemotherapy on thoracic tumors. However, it is sometimes difficult to evaluate the clinical response of MPM, since it exhibits a non-spherical growth pattern with irregular edges. On positron emission tomography (PET), altered glucose metabolism is visualized by the radiolabeled glucose analogue 18 F-fluoro-2-deoxy-D-glucose (FDG). Evaluation of glucose metabolism using FDG-PET plays a critical role in early tumor diagnosis, staging, therapeutic strategy, and prediction of prognosis (3-6). FDG-PET imaging of responses to chemotherapy or irradiation has been found to be useful for patients with a variety of types of carcinomas (7,8). However, few studies of MPM patients

CT a n d P E T mo n i t o r i n g p r i o r t o c h e mo t h e r a p y ( a ) , a f t e r t h e f i r s t c o u r s e o f c h e mo t h e r a p y ( b ) , a n d a f t e r t h e s e c o n d c o u r s e o f c h e mo t h e r a p y ( c ) . Ar r o ws s h o w t h e t a r g e t l e s i o n s .
markers CEA, NSE, and pro-GRP were all within normal ranges, while CYFRA 21-1 was elevated to 6.7 ng/mL. A biopsy specimen obtained at admission from the chest wall revealed biphasic-type MPM. Thoracic drainage of pleural effusion was performed, and pleurodesis with OK-432 was performed. Pleural thickening was noted in the upper right hemithorax on chest computed tomography (Fig. 1a).
FDG-PET scanning was performed as a part of a study of the usefulness of functional imaging of MPM at Osaka City University Hospital (Osaka, Japan) (11) FDG-PET imaging and CT scanning were performed prior to chemotherapy, as well as after the first and second courses of chemotherapy, with written informed consent. FDG-PET images were compared with the corresponding CT images, permitting accurate identification of tumors by anatomical landmarks. For quantitative evaluation, a region of interest (ROI) (circle 6 mm in diameter) was placed on the area of maximum FDG uptake within the lesion. A background ROI was then placed on a non-tumorous region of the lung. The standardized uptake value (SUV), a quantitative measurement of activity in the ROI, was determined using the following formula:

Injected dose (Bq)/body weight (g)
He received chemotherapy with cisplatin and irinotecan. Severe diarrhea then developed due to irinotecan, and he received a different chemotherapy regimen including cisplatin and docetaxel as a second course. The tumor lesion exhibited shrinkage on CT and a decrease in SUV max after the first course of chemotherapy (Fig. 1b), but size enlargement and an increase in SUV max after the second course of chemotherapy (Fig. 1c). The progression-free survival and the overall survival were 90 days and 320 days, respectively.

Discussion
This case shows some technical problems to measure sizes of tumors in determining the response to chemotherapy. Cross-sectional CT or MR images seem to be inappropriate to measure the size of these nonspherical tumors such as mesothelioma. Response evaluation criteria in solid tumor (RECIST) criteria determine the method of measuring the longest diameter of tumor (12), but it has not been determined whether these methods are appropriate or not. Recently, modified RECIST criteria were reported (13). Modified RECIST criteria determine the method of measuring tumor thickness perpendicular to the chest wall or mediastinum in these nonspherical tumors. The present findings suggest that the results of quantification of metabolic response by FDG-PET may be related to objective response as determined by modified RECIST in patients with MPM. In conclusion, we have presented the use of FDG-PET for the monitoring of the response to chemotherapy in a patient with MPM. These findings suggest that FDG avidity, which reflects tumor activity, is related to the chemotherapy response determined by CT in patients with MPM.