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Malignant pleural mesothelioma: Staging systems
Lung Cancer (2005) 49S1, S45—S48
Malignant pleural mesothelioma: Staging systems P. Van Schil ∗ Department of Thoracic and Vascular Surgery, University Hospital of Antwerp, Wilrijkstraat 10, B-2650 Edegem, Antwerp, Belgium KEYWORDS Mesothelioma; Pleura; Staging; TNM classification; Induction therapy; Restaging; PET scan
Summary Malignant pleural mesothelioma has a very specific growth pattern invading the pleural surfaces and neighboring structures. For this reason precise estimation of tumor volume and description of local extension are particularly difficult. Different staging systems have been introduced, and the most widely used are discussed. Restaging of mesothelioma after induction therapy is even more complicated and still controversial. The recently described, modified response evaluation criteria in solid tumors (RECIST) criteria are presently the most accurate for response evaluation. © 2005 Elsevier Ireland Ltd. All rights reserved.
1. Introduction
2. Staging of mesothelioma
Malignant pleural mesothelioma is a highly lethal neoplasm arising from the surface serosal cells of the pleural cavity. It has a peculiar growth pattern extending along the pleural surface, invading the visceral and parietal pleura with further expansion into the lung and surrounding organs. For this reason, it has a non-spherical extension, which makes estimation of precise tumor volume extremely difficult. However, correct staging is extremely important to make comparative studies and determine treatment and prognosis. Response evaluation after chemo- or chemoradiotherapy is even more difficult and classical response criteria are insufficient. These topics are discussed separately.
At least five staging systems of malignant pleural mesothelioma exist. Butchart introduced a classification into four stages, which became widely used [1]. These are described in Table 1. A classification based on a multimodality approach, including extrapleural pneumonectomy in 52 patients, was proposed by Sugarbaker, and is listed in Table 2 [2]. Most of the earlier staging systems, including those of Butchart and Sugarbaker, do not use the T, N and M descriptors as used in the classical TNM-classifications for tumors. For this reason, the International Mesothelioma Interest Group (IMIG) introduced a new staging system in 1995, based on these parameters [3]. TNM-staging and stage grouping are given in Tables 3 and 4. This staging system was adopted by the American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer (UICC) [4]. It reconciles previous staging systems, and is similar to those for other solid tumors and especially non-small cell lung cancer.
* Tel.: +32 38214360; fax: +32 38214396.
E-mail address: [email protected].
0169-5002/$ — see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.lungcan.2005.03.008
S46
Table 1
P.V. Schil
Staging system by Butchart [1]
Stage
Description
I
Tumor confined within the ‘‘capsule’’ of the parietal pleura, i.e., involving only ipsilateral pleura, lung, pericardium, and diaphragm Tumor invading chest wall or involving mediastinal structures, e.g., esophagus, heart, opposite pleura. Lymph node involvement within the chest Tumor penetrating diaphragm to involve peritoneum; involvement of opposite pleura. Lymph node involvement outside the chest Distant blood-borne metastases
II III IV
Reproduced from [3] with permission of Chest.
It also incorporates data on the natural history and influence of TN status on overall survival. However, it relies mostly on surgical pathology, and even with modern staging techniques differentiation of early stages and precise invasion in locally advanced disease remains difficult. Regarding the T status, T3 implies locally advanced but potentially resectable mesothelioma, whereas T4 means an irresectable tumor, as in lung cancer patients. T1 indicates that there is usually a free pleural space, and these patients often present with a large pleural effusion. However, the presence of pleural fluid has no effect on staging. Staging is usually done by computed tomographic (CT) scanning, but magnetic resonance imaging also has an important role regarding extension along the diaphragm, the mediastinum and the apical part of the chest. Positron emission tomography has a specific value to detect distant metastases, but is less sensitive in the evaluation of locoregional extension [5]. By non-invasive staging, it is rather difficult to make a distinction between T1a, T1b and T2 disease. Correct estimation of the extent of disease is only possible during thoracotomy. In case of T1b disease, pleurectomy and decortication are usually feasible. In case of a T2 tumor there is more extensive involvement of the visceral pleura and lung, often necessitating a pleuropneumonectomy. The prognosis of a T4 tumor is rather similar to M1 disease, and for this reason it is included in stage IV.
Table 2
In the IMIG system lymph node staging is the same as for non-small cell lung cancer. The regional lymph nodes include the hilar, mediastinal and internal mammary nodes, as well as the scalene and supraclavicular lymph nodes. N2 disease includes invasion of the ipsilateral mediastinal, subcarinal or the ipsilateral internal mammary nodes; and N3 disease includes the contralateral hilar, mediastinal, internal mammary nodes and/or the ipsilateral or contralateral supraclavicular or scalene lymph nodes. As the pattern of spread involves the mediastinal lymph nodes from the beginning, bypassing the hilum, there is probably not a large survival difference between N1 and N2 involvement. Therefore, all patients with nodal involvement are classified as stage III (N1, N2) or stage IV (N3 disease), in contrast to non-small cell lung cancer where N1 usually belongs to stage II, and N3 disease to stage IIIB. Precise evaluation of the superior mediastinal lymph nodes requires a cervical mediastinoscopy. In a recent study, chest CT scan revealed enlarged lymph nodes in 39% of the patients [6]. Lymph node metastases were detected by mediastinoscopy in 26% of the patients. Overall accuracy was 67 and 93% of CT and mediastinoscopy, respectively [6]. Not only for mediastinal nodal involvement but also in the case of early mesothelioma tumors, there is a discrepancy between non-invasive and surgical staging. The IMIG classification presumes that early tumors are evaluated surgically to determine the
Staging system by Sugarbaker [2]
Stage
Description
I
Disease confined to within capsule of the parietal pleura: ipsilateral pleura, lung, pericardium, diaphragm, or chest-wall disease limited to previous biopsy sites All of stage I with positive intrathoracic (N1 or N2) lymph nodes Local extension of disease into chest wall or mediastinum; heart, or through diaphragm, peritoneum, with or without extrathoracic or contralateral (N3) lymph node involvement Distant metastatic disease
II III IV
Reproduced from [3] with permission of Chest.
Malignant pleural mesothelioma
Table 3
S47
IMIG staging system [3,4]
Primary tumor (T) TX T0
Primary tumor cannot be assessed No evidence of primary tumor
T1 T1a
Tumor involves ipsilateral parietal pleura, with or without focal involvement of visceral pleura Tumor involves ipsilateral parietal (mediastinal, diaphragmatic) pleura. No involvement of the visceral pleura Tumor involves ipsilateral parietal (mediastinal, diaphragmatic) pleura, with focal involvement of the visceral pleura
T1b T2
Tumor involves any of the ipsilateral pleural surfaces, with at least one of the following Confluent visceral pleural tumor (including fissure) Invasion of diaphragmatic muscle Invasion of lung parenchyma
T3
Tumor involves any of the ipsilateral pleural surfaces, with at least one of the following Invasion of the endothoracic fascia Invasion into mediastinal fat Solitary focus of tumor invading the soft tissues of the chest wall Non-transmural involvement of the pericardium
T4
Tumor involves any of the ipsilateral pleural surfaces, with at least one of the following Diffuse or multifocal invasion of soft tissues of the chest wall Any involvement of rib Invasion through the diaphragm to the peritoneum Invasion of any mediastinal organ(s) Direct extension to the contralateral pleura Invasion into the spine Extension to the internal surface of the pericardium Pericardial effusion with positive cytology Invasion of the myocardium Invasion of the brachial plexus
Regional lymph nodes (N) NX N0 N1 N2 N3
Regional lymph nodes cannot be assessed No regional lymph node metastases Metastases in the ipsilateral bronchopulmonary and/or hilar lymph node(s) Metastases in the subcarinal lymph node(s) and/or the ipsilateral internal mammary or mediastinal lymph node(s) Metastases in the contralateral mediastinal, internal mammary, or hilar lymph node(s) and/or the ipsilateral or contralateral supraclavicular or scalene lymph node(s)
Distant metastasis (M) MX M0 M1
Distant metastases cannot be assessed No distant metastasis Distant metastasis
Reproduced from [3] with permission of Chest.
local extension and subsequent treatment. It should also be stated that within a specific TN subset differences in tumor biology are possible, resulting in a variable prognosis within the same group.
3. Response evaluation Precise evaluation of response after chemo- or chemoradiotherapy is important, especially when
induction therapy is applied. With the introduction of neoadjuvant chemotherapy for mesothelioma patients, surgical treatment depends on response. Response evaluation is usually based on subsequent CT scans. The precise role of PET scanning in this setting has not been determined yet. For response evaluation the WHO and response evaluation criteria in solid tumors (RECIST criteria) are commonly used. Recent articles point out that as the WHO, the RECIST criteria are inadequate for response
S48
Table 4 Stage
P.V. Schil
IMIG staging system—–stage grouping [3,4] T1
N0
M0
T1a T1b
N0 N0
M0 M0
II
T2
N0
M0
III
T1, T2 T1, T2 T3
N1 N2 N0, N1, N2
M0 M0 M0
IV
T4 Any T Any T
Any N N3 Any N
M0 M0 M1
I
IA IB
Reproduced from [3] with permission of Chest.
evaluation in mesothelioma [7,8]. The WHO criteria are difficult to apply as they require measurements of perpendicular diameters of tumor nodules. The RECIST criteria include multiple measurements of single diameter or tumor thickness, which assumes that tumors are spherical. However mesotheliomas predominantly change in their perpendicular axis to the chest wall without major changes in the broader basis. For this reason, modified RECIST criteria were recently introduced [9]. These include measurements perpendicular to the chest wall or mediastinum. Tumor thickness is measured in two positions at three separate levels on transverse images of CT scan. The sum of six measurements defines a pleural unidimensional measure. Nodal, subcutaneous and other bidimensionally measurable lesions are measured unidimensionally as in the usual RECIST criteria. Unidimensional measurements are added to obtain the total tumor measurement. Complete response is defined as the disappearance of all target lesions with no evidence of tumor elsewhere. Partial response requires at least a 30% reduction in total tumor measurement. A confirmed response requires a repeat observation on two occasions, 4 weeks apart. Progressive disease is defined as an increase of at least 20% in the total tumor measurement over the nadir measurement or the appearance of new lesions. Stable disease is present when neither the criteria for partial response nor progressive disease are met.
In a recent study of 34 mesothelioma patients the agreement between WHO and RECIST response evaluation was very poor, and the RECIST criteria were found to underscore the tumor response [7]. The modified RECIST criteria perform much better than the standard WHO response, and were more sensitive to detect pleural tumor response or progression. Recommendation of this study was to use the WHO criteria for bidimensional measurable lesions, RECIST for unidimensional measurable lesions and the modified RECIST criteria for response evaluation, in which the short axis perpendicular to the chest wall is used for thickened pleural rind disease [7].
References [1] Butchart EG, Ashcroft T, Barnsley WC, Holden MP. Pleuropneumonectomy in the management of diffuse malignant mesothelioma of the pleura. Experience with 29 patients. Thorax 1976;31:15—24. [2] Sugarbaker DJ, Strauss GM, Lynch TJ, Richards W, Mentzer SJ, Lee TH, et al. Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelioma. J Clin Oncol 1993;11:1172—8. [3] International Mesothelioma Interest Group. A proposed new international TNM-staging system for malignant pleural mesothelioma. Chest 1995;108:1122—1128. [4] American Joint Committee on Cancer. Pleural mesothelioma. AJCC Cancer Staging Handbook. Springer—Verlag, New York, 2002:205—209 (Chapter 20). [5] Flores M, Akhurst T, Gonen M, Larson SM, Rusch VW. Positron emission tomography defines metastatic disease but not locoregional disease in patients with malignant pleural mesothelioma. J Thorac Cardiovasc Surg 2003;126:11—6. [6] Schouwink JH, Kool LS, Rutgers EJ, Zoetmulder FA, van Zandwijk N, v d Vijver MJ, et al. The value of chest computer tomography and cervical mediastinoscopy in the preoperative assessment of patients with malignant pleural mesothelioma. Ann Thorac Surg 2003;75:1715—8. [7] Van Klaveren RJ, Aerts JG, de Bruin H, Giaccone G, Manegold C, Van Meerbeeck JP. Inadequacy of the RECIST criteria for response evaluation in patients with malignant pleural mesothelioma. Lung Cancer 2004;43:63—9. [8] Monetti F, Casanova S, Grasso A, Cafferata MA, Ardizzoni A, Neumaier CE. Inadequacy of the new response evaluation criteria in solid tumors (RECIST) in patients with malignant pleural mesothelioma: report of four cases. Lung Cancer 2004;43:71—4. [9] Byrne MJ, Nowak AK. Modified RECIST criteria for assessment of response in malignant pleural mesothelioma. Ann Oncol 2004;15:257—60.
Malignant pleural mesothelioma: Staging systems P. Van Schil ∗ Department of Thoracic and Vascular Surgery, University Hospital of Antwerp, Wilrijkstraat 10, B-2650 Edegem, Antwerp, Belgium KEYWORDS Mesothelioma; Pleura; Staging; TNM classification; Induction therapy; Restaging; PET scan
Summary Malignant pleural mesothelioma has a very specific growth pattern invading the pleural surfaces and neighboring structures. For this reason precise estimation of tumor volume and description of local extension are particularly difficult. Different staging systems have been introduced, and the most widely used are discussed. Restaging of mesothelioma after induction therapy is even more complicated and still controversial. The recently described, modified response evaluation criteria in solid tumors (RECIST) criteria are presently the most accurate for response evaluation. © 2005 Elsevier Ireland Ltd. All rights reserved.
1. Introduction
2. Staging of mesothelioma
Malignant pleural mesothelioma is a highly lethal neoplasm arising from the surface serosal cells of the pleural cavity. It has a peculiar growth pattern extending along the pleural surface, invading the visceral and parietal pleura with further expansion into the lung and surrounding organs. For this reason, it has a non-spherical extension, which makes estimation of precise tumor volume extremely difficult. However, correct staging is extremely important to make comparative studies and determine treatment and prognosis. Response evaluation after chemo- or chemoradiotherapy is even more difficult and classical response criteria are insufficient. These topics are discussed separately.
At least five staging systems of malignant pleural mesothelioma exist. Butchart introduced a classification into four stages, which became widely used [1]. These are described in Table 1. A classification based on a multimodality approach, including extrapleural pneumonectomy in 52 patients, was proposed by Sugarbaker, and is listed in Table 2 [2]. Most of the earlier staging systems, including those of Butchart and Sugarbaker, do not use the T, N and M descriptors as used in the classical TNM-classifications for tumors. For this reason, the International Mesothelioma Interest Group (IMIG) introduced a new staging system in 1995, based on these parameters [3]. TNM-staging and stage grouping are given in Tables 3 and 4. This staging system was adopted by the American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer (UICC) [4]. It reconciles previous staging systems, and is similar to those for other solid tumors and especially non-small cell lung cancer.
* Tel.: +32 38214360; fax: +32 38214396.
E-mail address: [email protected].
0169-5002/$ — see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.lungcan.2005.03.008
S46
Table 1
P.V. Schil
Staging system by Butchart [1]
Stage
Description
I
Tumor confined within the ‘‘capsule’’ of the parietal pleura, i.e., involving only ipsilateral pleura, lung, pericardium, and diaphragm Tumor invading chest wall or involving mediastinal structures, e.g., esophagus, heart, opposite pleura. Lymph node involvement within the chest Tumor penetrating diaphragm to involve peritoneum; involvement of opposite pleura. Lymph node involvement outside the chest Distant blood-borne metastases
II III IV
Reproduced from [3] with permission of Chest.
It also incorporates data on the natural history and influence of TN status on overall survival. However, it relies mostly on surgical pathology, and even with modern staging techniques differentiation of early stages and precise invasion in locally advanced disease remains difficult. Regarding the T status, T3 implies locally advanced but potentially resectable mesothelioma, whereas T4 means an irresectable tumor, as in lung cancer patients. T1 indicates that there is usually a free pleural space, and these patients often present with a large pleural effusion. However, the presence of pleural fluid has no effect on staging. Staging is usually done by computed tomographic (CT) scanning, but magnetic resonance imaging also has an important role regarding extension along the diaphragm, the mediastinum and the apical part of the chest. Positron emission tomography has a specific value to detect distant metastases, but is less sensitive in the evaluation of locoregional extension [5]. By non-invasive staging, it is rather difficult to make a distinction between T1a, T1b and T2 disease. Correct estimation of the extent of disease is only possible during thoracotomy. In case of T1b disease, pleurectomy and decortication are usually feasible. In case of a T2 tumor there is more extensive involvement of the visceral pleura and lung, often necessitating a pleuropneumonectomy. The prognosis of a T4 tumor is rather similar to M1 disease, and for this reason it is included in stage IV.
Table 2
In the IMIG system lymph node staging is the same as for non-small cell lung cancer. The regional lymph nodes include the hilar, mediastinal and internal mammary nodes, as well as the scalene and supraclavicular lymph nodes. N2 disease includes invasion of the ipsilateral mediastinal, subcarinal or the ipsilateral internal mammary nodes; and N3 disease includes the contralateral hilar, mediastinal, internal mammary nodes and/or the ipsilateral or contralateral supraclavicular or scalene lymph nodes. As the pattern of spread involves the mediastinal lymph nodes from the beginning, bypassing the hilum, there is probably not a large survival difference between N1 and N2 involvement. Therefore, all patients with nodal involvement are classified as stage III (N1, N2) or stage IV (N3 disease), in contrast to non-small cell lung cancer where N1 usually belongs to stage II, and N3 disease to stage IIIB. Precise evaluation of the superior mediastinal lymph nodes requires a cervical mediastinoscopy. In a recent study, chest CT scan revealed enlarged lymph nodes in 39% of the patients [6]. Lymph node metastases were detected by mediastinoscopy in 26% of the patients. Overall accuracy was 67 and 93% of CT and mediastinoscopy, respectively [6]. Not only for mediastinal nodal involvement but also in the case of early mesothelioma tumors, there is a discrepancy between non-invasive and surgical staging. The IMIG classification presumes that early tumors are evaluated surgically to determine the
Staging system by Sugarbaker [2]
Stage
Description
I
Disease confined to within capsule of the parietal pleura: ipsilateral pleura, lung, pericardium, diaphragm, or chest-wall disease limited to previous biopsy sites All of stage I with positive intrathoracic (N1 or N2) lymph nodes Local extension of disease into chest wall or mediastinum; heart, or through diaphragm, peritoneum, with or without extrathoracic or contralateral (N3) lymph node involvement Distant metastatic disease
II III IV
Reproduced from [3] with permission of Chest.
Malignant pleural mesothelioma
Table 3
S47
IMIG staging system [3,4]
Primary tumor (T) TX T0
Primary tumor cannot be assessed No evidence of primary tumor
T1 T1a
Tumor involves ipsilateral parietal pleura, with or without focal involvement of visceral pleura Tumor involves ipsilateral parietal (mediastinal, diaphragmatic) pleura. No involvement of the visceral pleura Tumor involves ipsilateral parietal (mediastinal, diaphragmatic) pleura, with focal involvement of the visceral pleura
T1b T2
Tumor involves any of the ipsilateral pleural surfaces, with at least one of the following Confluent visceral pleural tumor (including fissure) Invasion of diaphragmatic muscle Invasion of lung parenchyma
T3
Tumor involves any of the ipsilateral pleural surfaces, with at least one of the following Invasion of the endothoracic fascia Invasion into mediastinal fat Solitary focus of tumor invading the soft tissues of the chest wall Non-transmural involvement of the pericardium
T4
Tumor involves any of the ipsilateral pleural surfaces, with at least one of the following Diffuse or multifocal invasion of soft tissues of the chest wall Any involvement of rib Invasion through the diaphragm to the peritoneum Invasion of any mediastinal organ(s) Direct extension to the contralateral pleura Invasion into the spine Extension to the internal surface of the pericardium Pericardial effusion with positive cytology Invasion of the myocardium Invasion of the brachial plexus
Regional lymph nodes (N) NX N0 N1 N2 N3
Regional lymph nodes cannot be assessed No regional lymph node metastases Metastases in the ipsilateral bronchopulmonary and/or hilar lymph node(s) Metastases in the subcarinal lymph node(s) and/or the ipsilateral internal mammary or mediastinal lymph node(s) Metastases in the contralateral mediastinal, internal mammary, or hilar lymph node(s) and/or the ipsilateral or contralateral supraclavicular or scalene lymph node(s)
Distant metastasis (M) MX M0 M1
Distant metastases cannot be assessed No distant metastasis Distant metastasis
Reproduced from [3] with permission of Chest.
local extension and subsequent treatment. It should also be stated that within a specific TN subset differences in tumor biology are possible, resulting in a variable prognosis within the same group.
3. Response evaluation Precise evaluation of response after chemo- or chemoradiotherapy is important, especially when
induction therapy is applied. With the introduction of neoadjuvant chemotherapy for mesothelioma patients, surgical treatment depends on response. Response evaluation is usually based on subsequent CT scans. The precise role of PET scanning in this setting has not been determined yet. For response evaluation the WHO and response evaluation criteria in solid tumors (RECIST criteria) are commonly used. Recent articles point out that as the WHO, the RECIST criteria are inadequate for response
S48
Table 4 Stage
P.V. Schil
IMIG staging system—–stage grouping [3,4] T1
N0
M0
T1a T1b
N0 N0
M0 M0
II
T2
N0
M0
III
T1, T2 T1, T2 T3
N1 N2 N0, N1, N2
M0 M0 M0
IV
T4 Any T Any T
Any N N3 Any N
M0 M0 M1
I
IA IB
Reproduced from [3] with permission of Chest.
evaluation in mesothelioma [7,8]. The WHO criteria are difficult to apply as they require measurements of perpendicular diameters of tumor nodules. The RECIST criteria include multiple measurements of single diameter or tumor thickness, which assumes that tumors are spherical. However mesotheliomas predominantly change in their perpendicular axis to the chest wall without major changes in the broader basis. For this reason, modified RECIST criteria were recently introduced [9]. These include measurements perpendicular to the chest wall or mediastinum. Tumor thickness is measured in two positions at three separate levels on transverse images of CT scan. The sum of six measurements defines a pleural unidimensional measure. Nodal, subcutaneous and other bidimensionally measurable lesions are measured unidimensionally as in the usual RECIST criteria. Unidimensional measurements are added to obtain the total tumor measurement. Complete response is defined as the disappearance of all target lesions with no evidence of tumor elsewhere. Partial response requires at least a 30% reduction in total tumor measurement. A confirmed response requires a repeat observation on two occasions, 4 weeks apart. Progressive disease is defined as an increase of at least 20% in the total tumor measurement over the nadir measurement or the appearance of new lesions. Stable disease is present when neither the criteria for partial response nor progressive disease are met.
In a recent study of 34 mesothelioma patients the agreement between WHO and RECIST response evaluation was very poor, and the RECIST criteria were found to underscore the tumor response [7]. The modified RECIST criteria perform much better than the standard WHO response, and were more sensitive to detect pleural tumor response or progression. Recommendation of this study was to use the WHO criteria for bidimensional measurable lesions, RECIST for unidimensional measurable lesions and the modified RECIST criteria for response evaluation, in which the short axis perpendicular to the chest wall is used for thickened pleural rind disease [7].
References [1] Butchart EG, Ashcroft T, Barnsley WC, Holden MP. Pleuropneumonectomy in the management of diffuse malignant mesothelioma of the pleura. Experience with 29 patients. Thorax 1976;31:15—24. [2] Sugarbaker DJ, Strauss GM, Lynch TJ, Richards W, Mentzer SJ, Lee TH, et al. Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelioma. J Clin Oncol 1993;11:1172—8. [3] International Mesothelioma Interest Group. A proposed new international TNM-staging system for malignant pleural mesothelioma. Chest 1995;108:1122—1128. [4] American Joint Committee on Cancer. Pleural mesothelioma. AJCC Cancer Staging Handbook. Springer—Verlag, New York, 2002:205—209 (Chapter 20). [5] Flores M, Akhurst T, Gonen M, Larson SM, Rusch VW. Positron emission tomography defines metastatic disease but not locoregional disease in patients with malignant pleural mesothelioma. J Thorac Cardiovasc Surg 2003;126:11—6. [6] Schouwink JH, Kool LS, Rutgers EJ, Zoetmulder FA, van Zandwijk N, v d Vijver MJ, et al. The value of chest computer tomography and cervical mediastinoscopy in the preoperative assessment of patients with malignant pleural mesothelioma. Ann Thorac Surg 2003;75:1715—8. [7] Van Klaveren RJ, Aerts JG, de Bruin H, Giaccone G, Manegold C, Van Meerbeeck JP. Inadequacy of the RECIST criteria for response evaluation in patients with malignant pleural mesothelioma. Lung Cancer 2004;43:63—9. [8] Monetti F, Casanova S, Grasso A, Cafferata MA, Ardizzoni A, Neumaier CE. Inadequacy of the new response evaluation criteria in solid tumors (RECIST) in patients with malignant pleural mesothelioma: report of four cases. Lung Cancer 2004;43:71—4. [9] Byrne MJ, Nowak AK. Modified RECIST criteria for assessment of response in malignant pleural mesothelioma. Ann Oncol 2004;15:257—60.