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J Thorac Cardiovasc Surg 1999;117:54-65
© 1999 Mosby, Inc.
GENERAL THORACIC SURGERY |
From the Division of Thoracic Surgery and the Department of Pathology, Brigham and Women's Hospital; Surgical Services and the Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Mass; and Hematology-Oncology, University of Massachusetts, Worcester, Mass.
Read at the Seventy-eighth Annual Meeting of The American Association for Thoracic Surgery, Boston, Mass, May 3-6, 1998.
Received for publication May 8, 1998. Revisions requested June 30, 1998. Revisions received Sept 25, 1998. Accepted for publication Sept 29, 1998. Address for reprints: David J. Sugarbaker, MD, Division of Thoracic Surgery, Brigham and Women's Hospital, Boston, MA 02115.
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Abstract |
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 Top Abstract IntroductionPatients and methodsResultsDiscussionAppendix: DiscussionReferences |
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Introduction |
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TopAbstractIntroductionPatients and methodsResultsDiscussionAppendix: DiscussionReferences |
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1-3 The natural history of malignant pleural mesothelioma includes a median survival of 4 to 12 months without intervention, 4-6 and there is no accepted standard therapy. The biologic behavior of malignant pleural mesothelioma is unique among thoracic malignant disease. It has shown a natural history of relentless local progression with rare hematogenous spread even in the late stages of untreated disease. 7 Even after aggressive local control measures, locoregional recurrence is the fate of a majority of patients. 8
Extended survival has been reported in patients undergoing multimodality therapy of radical extrapleural pneumonectomy followed by chemotherapy and radiation. 9-13 The difficulty in this management of the disease has been to differentiate patients most likely to benefit from this aggressive approach from those patients destined to die early of the disease.
Since 1980, The Brigham and Women's Hospital applied extrapleural pneumonectomy for malignant pleural mesothelioma in the context of trimodality therapy. Two earlier reports of this series have reviewed the results of 52 and 120 patients. 13,14 We now review our results with 183 consecutive patients and analyze prognostic variables among the 176 long-term survivors. These variables form the basis of a revision of our published 14 staging system. We also wish to assess the feasibility of this approach in the light of this larger patient cohort in preparation for future clinical trials and alternative treatment strategies.
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Patients and methods |
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TopAbstractIntroductionPatients and methodsResultsDiscussionAppendix: DiscussionReferences |
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All pathologic material establishing the diagnosis of malignant pleural mesothelioma was reviewed by The Brigham and Women's Hospital Pathology Department for confirmation. If a definitive diagnosis could not be made on tissue available, a pleuroscopy and biopsy under direct vision was performed. A multimodality team comprising a medical oncologist, a surgeon, and a radiation oncologist evaluated all patients with histologically proven malignant pleural mesothelioma. Patients were considered surgical candidates if they had a Karnofsky performance status of greater than 70%, a creatinine level within normal limits, liver function test results within the normal range, and tumor judged to be completely resectable on the basis of computed tomographic scan, magnetic resonance imaging (MRI), and echocardiography. Physiologic exclusion criteria included room air arterial PCO2 greater than 45 mm Hg, room air arterial PO2 less than 65 mm Hg, echocardiography demonstrating an ejection fraction of less than 45%, and a predicted postoperative forced expiratory volume in 1 second (FEV1) of less than 1 L. Patients with a preoperative FEV1 of less than 2 L underwent quantitative radionuclide ventilation-perfusion scanning to predict postoperative pulmonary function more accurately.
Trimodality treatment consisted of extrapleural pneumonectomy followed by postoperative intravenous chemotherapy and radiotherapy. Extrapleural pneumonectomy entailed resection of the pleura, lung, diaphragm, and pericardium en bloc. 15 Separate resection of prior open biopsy sites, thoracoscopy incisions, and chest tube tracks included a 1-cm margin of normal tissue.A standardized pathologic analysis was routinely undertaken for each specimen. First, a gross examination of the specimen was performed by the pathologist to determine any obvious areas of tumor remaining at the resection margins. Then, approximately 20 sections were taken through each specimen to ascertain whether positive microscopic margins remained along the chest wall. The bronchus, pericardium, and diaphragm were carefully examined for microscopic margins. A positive margin identified on the specimen was then used to direct postoperative thoracic radiation treatment.
Extrapleural pneumonectomy at our institution has always included nodal sampling of hilar, paraesophageal, inferior pulmonary ligament, peridiaphragmatic, and subcarinal nodal stations. Additionally, right extrapleural pneumonectomies had sampling of paratracheal nodes, and left extrapleural pneumonectomies included sampling of aortopulmonary window nodes. Involvement of these nodes has been determined in a standardized fashion by the same senior pathologist (J. M. Corson) throughout this series of patients.
Extrapleural nodes are defined as mediastinal lymph nodes and peridiaphragmatic lymph nodes not located within the pleural reflection. Intrapleural nodes are defined as any lymph node located within the pleural envelope. Each patient's status was staged by Butchart criteria, 9 the new international TNM mesothelioma staging system, 16 and the system previously published by this group. 14
Chemotherapy was initiated 4 to 6 weeks after convalescence from extrapleural pneumonectomy. Nine patients treated before 1985 received doxorubicin 50 to 60 mg/m2 and cyclophosphamide 600 mg/m2 for 4 to 6 cycles. Eighty patients treated from 1985 to 1994 also received cisplatin 70 mg/m2 added to the previous regimen (CAP). Ninety-four patients undergoing treatment from 1995 to 1997 received carboplatin (Paraplatin; Bristol Myers Squibb, Princeton, NJ) and paclitaxel (Taxol; Bristol Myers Squibb) at dosages of an area under the curve (AUC) of 6 and 200 mg/m2, respectively. Although chemotherapy was started between 4 and 6 weeks after extrapleural pneumonectomy, it was started up to 12 weeks after the operation if a patient had major postoperative morbidity. Patients received 2 cycles of carboplatin/ paclitaxel chemotherapy 3 weeks apart, followed by the prescribed course of radiation therapy with concurrent weekly paclitaxel. Beginning 3 to 4 weeks after completion of radiation therapy, patients received 2 additional cycles of carboplatin and paclitaxel 3 weeks apart.
External beam radiotherapy was delivered with the use of linear accelerators ranging in energy from 4 to 15 MV. The total radiation dose to the hemithorax was typically 30 Gy delivered in 1.5-Gy fractions, and the mediastinum received 40 Gy. A boost dose was given to areas of gross residual disease, localized positive resection margins, and/or localized lymph nodes. The boost dose, if given, was typically 14 Gy in 2-Gy fractions for a total cumulative dose to the boost region of 54 Gy.
Because clinical symptoms and radiographic studies are not sensitive enough to accurately diagnose early recurrence, the disease-free interval is difficult to measure. Therefore survival is the major end point of this study. The survival duration was measured from the date of extrapleural pneumonectomy until the date of the patient's last follow-up contact or death. Perioperative mortality is defined as death occurring within 30 days of the operation. Morbidity is defined as an untoward event directly resulting in prolonged hospitalization.
Statistical analysis of survival was undertaken by use of a landmark of 30 days after surgical resection. Univariate analysis was performed by means of the Kaplan-Meier life-table method to determine the effects of demographic and pathologic variables. The log rank test was used to determine statistical significance of comparisons among survival curves. Dichotomous variables included smoking history, asbestos exposure, chest pain, dyspnea, cough, age greater or less than 65 years, side of tumor, sex, cell type (epithelial versus mixed and sarcomatous), tumor at surgical margins, and metastases to extrapleural nodes. Results with a P value of less than .05 were considered significant and were included in a multivariate proportional hazards regression model. This generated an odds ratio of death for each variable associated with shortened survival.
Variables found to be significant on multivariate analysis were used to modify our previously published surgical staging system. Log rank tests were used to determine the statistical significance of survival comparisons between stage groupings.
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Results |
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Morbidity and mortality
Morbidity was divided into major and minor subtypes. Major morbidity was defined as an untoward event leading to longer hospital stay and occurred in 45 of the 183 patients (24.5%). Major cardiovascular morbidity occurred in 7 patients: cardiac arrest (n = 5), right ventricular failure (n = 1), and left ventricular failure (n = 1). Pulmonary morbidity (n = 15) included patients with aspiration (n = 5), pulmonary failure (n = 5), pulmonary embolus (n = 3), and contralateral pneumothorax (n = 2). Infectious morbidity (n = 9) causes included sepsis (n = 4), wound infection (n = 3), empyema (n = 1), and bacteremia (n = 1). Gastrointestinal morbidity (n = 7) included bleeding in the upper gastrointestinal tract (n = 2), perforated duodenal ulcer (n = 2), colectomy for Clostridium difficile colitis (n = 1), Ogilvie's syndrome (n = 1), and pancreatitis (n = 1). Technical morbidity (n = 12) included patients who underwent re-exploration for bleeding or suspected cardiac tamponade (n = 9), diaphragmatic patch rupture (n = 2), and cardiac herniation (n = 1). Other miscellaneous morbidity (n = 18) included patients with vocal cord paralysis (n = 10), deep venous thrombosis (n = 4), seizure (n = 2), and acute renal failure (n = 2).
Minor morbidity included atrial and ventricular arrhythmias, which occurred in 75 patients (41%). These arrhythmias were treated with cardioversion or pharmacologic therapy without lengthening hospital stay. Specifically, atrial fibrillation occurred in 68 patients (37%) and ventricular arrhythmias occurred in 7 patients (3.8%). Overall, some morbidity occurred in 92 patients (50%).
There were 7 perioperative (30-day) deaths (3.8%). Three patients died of pulmonary embolus, 2 died of myocardial infarction, 1 of cardiac herniation through a pericardial defect, and 1 of respiratory failure. The median postoperative length of stay was 9 days (range 5-101 days).
Long-term survival
The 30-day survival landmark was reached by 176 patients. The median survival for these patients was 19 months; 2- and 5-year survivals were 38% and 15%, respectively (Fig 1).
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Epithelial cell type (Fig. 2), negative resection margins (Fig. 3), and lack of extrapleural lymph nodal involvement (Fig. 4) were significant prognostic factors associated with prolonged survival in univariate analysis. The 103 (59%) patients with epithelial cell type tumors had 2- and 5-year survivals of 52% and 21%, respectively (Fig. 2). By contrast, the survival for the 73 patients with sarcomatous or mixed cell type was 16% at 2 years, and no patient survived 5 years (P = .0001; Fig. 2). The 66 patients with negative resection margins had a 2-year survival of 44% and a 5-year survival of 25% compared with the 110 patients with positive resection margins, who had a 2-year survival of 33% and a 5-year survival of 9% (P = .02; Fig. 3). The 136 patients with negative extrapleural nodal status had a 2-year survival of 42% and a 5-year survival of 17%; the 40 patients with positive extrapleural nodal status had a 2-year survival of 23%, and none survived 5 years (P = .004; Fig. 4). Eleven patients had metastases to the extrapleural peridiaphragmatic nodes but not to the mediastinal nodes. We considered metastases to extrapleural peridiaphragmatic nodes to act like metastases to mediastinal nodes because they lay within the same nodal drainage bed as the station 8 (periesophageal) and station 9 (inferior pulmonary ligament) nodes in the American Thoracic Society lymph node map for lung cancer.
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14 was also used to stage this cohort of patients. By this method, survival was significantly stratified by stage (P = .048). Median survival intervals for patients with stage I (n = 66), II (n = 41), and III (n = 69) disease were 25, 20, and 16 months, respectively. The identification of these predictive variables by the Cox proportional hazards model led us to revise our previous staging system to account for positive margins and extrapleural nodes (Table II). When the criterion of extrapleural nodal involvement was reassigned from stage II to stage III, survival stratification was improved (Fig. 5). This revised staging system significantly stratified long-term survival (P = .0011). This same cohort was not stratified by the new international TNM system for mesothelioma 16 (P = .31) or by the Butchart staging system 9 (P = .09).
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Discussion |
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TopAbstractIntroductionPatients and methodsResultsDiscussionAppendix: DiscussionReferences |
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14 significantly stratified survival. Finally, we propose a revision to our previously published staging system.
This study demonstrates in a large patient cohort that extrapleural pneumonectomy is a safe means of cytoreduction. In 1976, Butchart and associates 9 reported their experience with extrapleural pneumonectomy but demonstrated a prohibitively high perioperative mortality rate of 31%. The advent of improved surgical techniques, hemostasis, prosthetic reconstruction of the diaphragm and pericardium, advances in intraoperative and postoperative monitoring, and better critical care support have since improved postoperative outcome to our current rate of 7 deaths in 183 operations (3.8% mortality).
The major operative morbidity in this cohort was 24.5%, but many of the complications do not present major setbacks when treated appropriately. Atrial fibrillation occurred in 37% but was well controlled with calcium channel blockers, digoxin, procainamide, or a combination of these agents. No patient had severe consequences as a result of this complication. It is possible that rapid filling within the denuded hemithorax results in respiratory distress because the dense fluid shifts the mediastinum toward the remaining lung and compresses it. Aspiration of the fluid-filled hemithorax, as demonstrated in 6 of our patients, leads to repositioning of the mediastinum, decrease in intra-abdominal pressure, and subsequent lung re-expansion followed by resolution of hypoxia. The attendant morbidity and potential mortality from extrapleural pneumonectomy stresses the importance of performing the procedure at specialized institutions.
The current regimen of combined carboplatin-paclitaxel adjuvant chemotherapy was designed in 1995. Platinum-based chemotherapy yielded a response in 7 of 15 (47%) patients with peritoneal mesothelioma 17 and in 18% with pleural mesothelioma. 18 Paclitaxel as a single agent in advanced pleural mesothelioma produced regression in 2 of 15 (13%) and stable disease in 5 of 15 (33%) patients treated by the Cancer and Leukemia Group B (CALGB) in 1993. 19 In 1995 Herscher and colleagues 20 reported local control of advanced pleural mesothelioma with single-agent paclitaxel in 7 of 8 (88%) patients. Although there were no combination data of carboplatin-paclitaxel in malignant pleural mesothelioma, these 2 agents had recognized single-agent activity against this chemotherapy-resistant disease. Furthermore, there were published data on the use of carboplatin-paclitaxel combinations in the treatment of advanced breast, ovarian, and lung cancers with high response rates: 78% to 94% in breast cancer, 21,22 57% to 81% in ovarian cancer, 23,24 and 38% to 86% in lung cancer. 25-31 The rationale for this approach has been steadily evolving in the literature. Cisplatin and paclitaxel as single agents were each effective against some in vivo mesothelioma cell lines in athymic nude mice, but they were more effective in all cell lines when given in combination. 32
Carboplatin-paclitaxel was recognized as a better tolerated chemotherapy regimen than the CAP (cyclophosphamide-doxorubicin-platinum) regimen it replaced. Less toxicity for patients after pneumonectomy would suggest more patients will receive adjuvant therapy.
In other types of malignant disease, chemotherapy is more effective in the setting of minimal residual tumor burden, 33 although this remains unproven in pleural mesothelioma.
Extrapleural pneumonectomy combined with adjuvant chemoradiation therapy by this protocol offers improved survival for certain subgroups of patients. Specifically, patients with epithelial cell type, lack of extrapleural nodal involvement, and negative surgical margins have a median survival approaching 5 years. The patients with non-epithelial cell type (sarcomatoid and mixed cell type) have a significantly worse survival, with only 16% living for 2 years after the operation. This suggests that our current trimodality treatment plan is having a small impact within this group with unfavorable histologic features, and new strategies for local control are needed. One possibility would be to apply chemotherapy combinations currently administered in the treatment of sarcomas such as MAID (methotrexate, Adriamycin [Pharmacia & Upjohn, Kalamazoo, Mich], ifosfamide, and prednisone) instead of carboplatin-paclitaxel combinations that have demonstrated responses against epithelial tumors.
Mesothelioma, unlike lung cancer, tends to progress locally rather than systemically. Of the 54% of patients with recurrences reported by Baldini and colleagues, 8 67% had recurrences within the ipsilateral hemithorax and 50% had recurrences within abdominal regions; a majority of these recurrences appeared to result from direct extension from the ipsilateral hemithorax. Recurrences are thought to result from trauma, spillage, and residual tumor at the resection margins that subsequently are entrapped in fibrin deposits and become exposed to postoperative growth factors. 34 In this study, patients with positive resection margins had a median survival of 15 months (33% 2-year survival, 9% 5-year survival) and patients with negative resection margins had a median survival of 23 months (44% 2-year survival, 25% 5-year survival; P = .02). Our previous report on the first 120 patients did not demonstrate this finding, 13 which we attribute to the larger number of patients in the current study cohort. Taken together, these observations suggest that future investigative efforts should be directed toward more effective methods of locoregional control.
Pass and colleagues 35 have studied the role of intraoperative photodynamic therapy as a method of local control in the treatment of malignant pleural mesothelioma. They have performed a phase I trial to determine the maximally tolerated dose. However, they recently published the results of a phase III trial indicating that this treatment did not appear to prolong survival or improve local control when performed after surgical debulking. 36
Rusch and colleagues 37,38 have extensively studied pleurectomy and postoperative intrapleural chemotherapy. Their results have shown only marginal improvement in outcome without significant toxicity. In patients undergoing pleurectomy, gross residual tumor frequently remains within the hemithorax. Given the millimeter level of penetration of intracavitary chemotherapy, the amount of cytoreduction with pleurectomy may be inadequate to allow the intracavitary chemotherapy to work optimally. 39-42 In patients undergoing extrapleural pneumonectomy, residual tumor within the hemithorax is most often microscopic, presenting a smaller tumor burden to be controlled with intracavitary chemotherapy. Kodama and colleagues 43 have used hyperthermic intrathoracic chemotherapy in patients undergoing resection for adenocarcinoma with evidence of improved local control. No data exist in patients with malignant pleural mesothelioma after surgical resection.
The dismal survival of patients with extrapleural nodal involvement suggests a role for pre-resectional lymph node staging. Either mediastinoscopy or positron emission tomography (PET) scanning may play a useful role in patient selection. Although paraesophageal lymph nodes are inaccessible by mediastinoscopy, a positive finding of a diseased mediastinal node is useful nonetheless. Data on the detection of mediastinal nodes via mediastinoscopy and PET scanning are nonexistent in patients with mesothelioma. The pattern of mesothelioma tumor spread does not appear to follow an ordered lymphatic pattern like that seen in lung cancer, and studies establishing the sensitivity and specificity of mediastinoscopy in this particular disease are needed.
We recommend that patients with a histologic diagnosis of sarcomatoid or biphasic mesothelioma and comorbid disease undergo mediastinoscopy because the combination of both sarcomatoid or mixed cell types and positive extrapleural nodal status predicts a survival that mimics the natural history without surgical intervention. If pre-resectional nodal testing proves positive in high-risk patients with sarcomatoid or mixed tumors, we would not recommend proceeding with extended resection.
The proposed International TNM Staging System 16 and the Butchart staging system 9 failed to stratify survival when applied to our cohort of 176 patients. The TNM staging system placed 8% of our cohort into the stage I category, 11% into stage II, 78% into stage III, and 3% into stage IV. Since the majority of our cohort of 176 patients were categorized as stage III by TNM, it is difficult to separate patients with different tumor characteristics that are necessary to stratify survival in our patient cohort. In addition, the T descriptor alone was not a statistically significant predictor of survival, reflecting the inability of this system to describe the biologic behavior of this particular tumor.
The system proposed by Butchart similarly did not significantly stratify survival. A small number of patients were categorized as having stage III disease (n = 5, 3%). The distinction between extent of primary tumor involvement and intrathoracic nodal involvement is not appropriately taken into account by this staging system, as reflected by the majority of patients being placed in the stage II category.
The staging system proposed previously by this group 14 continued to stratify survival successfully. This is a surgical staging system based on the ability to completely remove all tumor within the pleural envelope and involved regional nodes. Observer bias may exist because this staging system originated at our institution and was based on an earlier cohort. Validation by other institutions will be required to judge the utility of this clinical staging system.
We considered peridiaphragmatic nodes to be extrapleural nodes in this analysis. Metastasis to peridiaphragmatic nodes was associated with a similar median survival as metastasis to mediastinal nodes. However, if one considers only the 29 patients with metastases to the mediastinal nodes that could be reached by mediastinoscopy, there was a highly significant difference in long-term survival of these patients compared with patients with uninvolved mediastinal nodes (P = .0026).
Because of the negative effect of extrapleural nodal disease on survival, we propose a revised staging system to predict long-term survival (Table II). This staging system differs from our previous publication 14 in that the presence of extrapleural node involvement has now been included in stage III. This represents a distinction as to the location and extent of nodal involvement based on the poorer survival of patients in this subgroup.
A median survival of 51 months in the subgroup of patients with negative extrapleural lymph nodes is a ray of hope in the treatment of this dismal disease. We believe it is no longer appropriate to offer only supportive care to all patients with mesothelioma because a subgroup of well-selected patients appears to benefit from aggressive multimodality treatment (Fig. 6
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Appendix: Discussion |
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TopAbstractIntroductionPatients and methodsResultsDiscussionAppendix: DiscussionReferences |
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The data further support the functional staging classification originally proposed by Dr Sugarbaker and his colleagues and now further revised and updated, which further adds to the risk stratification and predictive value of this classification.
I would like to expand on what Dr Sugarbaker has already stated. Using his revised staging criteria, we can make better-informed decisions regarding appropriate treatment for individual patients. Not all patients with mesothelioma are in a hopeless condition. A significant percentage of patients deserve an aggressive multimodality approach, as the Brigham group has delineated.
Dr Sugarbaker, to what do you attribute the absence of adult respiratory distress syndrome (ARDS) in this large group of patients undergoing extrapleural pneumonectomy? Are you doing something we all should be doing?
Obviously, patient selection is important. To what percentage of patients with malignant pleural mesothelioma do you offer this multimodality approach?
Do you have an arbitrary age cutoff, or is this individualized? Are you performing mediastinoscopy routinely before resection?
This is an aggressive regimen. Do you have any quality-of-life data from the first year of treatment? What percentage of patients have grade IV toxicity during the postoperative chemotherapy-radiotherapy regimen?
Did you find MRI predictive of which patients should be able to have at least a microscopically complete resection, if not a complete resection? Can you base this on MRI criteria?
Dr Sugarbaker. Thank you for your comments. I would like to start by addressing the question of ARDS. We did have some cases of ARDS, which contributed to the 25% morbidity. ARDS is seen in the same percentage that one would expect in patients undergoing pneumonectomy for non-small cell lung cancer.
However, we have selected these patients via MRI, looking for resectable disease, and by echocardiogram, and we do restrict intravenous fluids, probably not much different from our standard pneumonectomy patients. Nevertheless, I wonder what effect the screening for myocardial function would have on patients undergoing pneumonectomy in general. It may be helping, and it is an unseen benefit.
We do not have an age cutoff, but most of the patients whom we consider for this aggressive strategy are in their fifth or sixth decade. Surprisingly, we are seeing an increasing number of patients in their 40s and 50s with the disease. That does make one reconsider possible new causes, such as the simian 40 virus, but we do not have any specific age cutoff.
We seriously consider using this therapy in about one third of patients whom we see, so we see 3 or 4 for every single patient whom we consider for extrapleural pneumonectomy followed by trimodality therapy.
In terms of mediastinoscopy, PET scanning, or laparoscopy to get at retro-aortic or retro-paraesophageal nodes, these are areas that need to be studied. Dr Rusch published a study on the use of laparoscopy to detect transdiaphragmatic involvement or intraperitoneal involvement, but I think we need to move forward with an evaluation of the ability of mediastinoscopy to detect nodal disease in these patients.
Notice that we very carefully suggested that these were extrapleural nodes, and they are really a "grab bag" of mediastinal nodes, and that it is not clear how many of them would be accessible via mediastinoscopy. Nevertheless, I believe that PET will be an interesting tool for pre-resectional staging.
Patients with sarcomatous disease who have positive mediastinal nodes on mediastinoscopy should not be considered for aggressive therapy. Their survival is dismal despite an aggressive approach and the resectability rate is low.
We do not have data on the quality of life in these individuals, but it is an important point and should be studied.
I do not have data on grade IV toxicity at hand. The reason we switched from the CAP protocol (cytoxan, Adriamycin, and then platinol), which was the most active combination chemotherapy against mesothelioma, to carboplatin and paclitaxel was precisely because of the incidence of grade IV toxicity that prevented patients from completing the adjuvant regimen.
We consider MRI to be a better pre-resectional staging modality than computed tomographic scanning, and we believe this has contributed significantly to the resectability rate in our patients, which now approaches 80%. It is indeed superior for looking at mediastinal invasion or transdiaphragmatic invasion.
Dr G. Alexander Patterson (St Louis, Mo). That was a great paper, Dr Sugarbaker. However, I do not understand why you are so light on the radiation. It seems to me that when local control is the issue, you emphasize surgery over radiation. I would have thought that 3000 rad was not quite consistent with the magnitude of the local control you are trying to achieve by that sort of an operation. How did you decide on that particular radiation regimen?
Dr Sugarbaker. We arrived at that dose in a retrograde fashion. We began with 5500 rad, the maximal cytologic dose, to the ipsilateral hemithorax. When we combined that with paclitaxel (Taxol) sensitization and the chemotherapy of carboplatin and paclitaxel, we found that a significant number of patients were becoming neutropenic from the amount of marrow that was being radiated. The dose can go as high as 4000 rad, and it really depends on the patient's blood count, but a significant number of patients will become neutropenic from the amount of rib marrow that is being radiated.
Dr L. Penfield Faber (Chicago, Ill). Dr Sugarbaker, this is an outstanding surgical series with a phenomenal mortality rate of 3.8%. Surgeons who have done extrapleural pneumonectomy for mesothelioma fully realize what an achievement this is, as the earlier described mortality rates were much higher. The current mortality rate in our series at the Rush–Presbyterian–St Luke's Medical Center is 7.5%.
Having done extrapleural pneumonectomies and removed specimens that include the pleura, the pericardium, the lung, and the diaphragm, I find it difficult to understand what constitutes a negative microscopic margin. It can be technically difficult to achieve a negative margin when removing the diaphragm from the inferior aspect of the posterior sulcus or at the apex of the chest along the innominate vein and subclavian vessels. You stated that this procedure is really a technique of cytoreduction, and it was implied that there may well be residual microscopic disease. It is difficult for me to comprehend where the microscopic margins are negative and also to understand how a surgical pathologist would evaluate and dissect the specimen to identify negative microscopic margins. Please explain how negative microscopic margins are achieved with this diffuse malignant tumor.
My second question refers to the possible toxic manifestations of paclitaxel coupled with radiation. We have recently completed a pilot phase II study of neoadjuvant therapy for clinically advanced lung cancer using paclitaxel in combination with radiation. We have observed significant complications after surgical resection when pretreating these patients with paclitaxel and radiation. Because of these complications, we no longer use paclitaxel in combination with radiation for neoadjuvant therapy of lung cancer. I would appreciate hearing any comments you might have on the toxic manifestations of paclitaxel in your series.
Dr Sugarbaker. I appreciate your comments. The issue of pathologic resection margins is an important one. The frustration that you outlined—where would you take your sample, how would you approach a specimen—led Dr Joseph Corson (professor of pathology at the Harvard Medical School, and chief of surgical pathology until last year at The Brigham and Women's Hospital) to devise a systematic method some 9 years ago for assessing these specimens; his method involves systematically taking margins from 10 to 15 different points on the specimen, because trying to discern where the specimen looked positive and where it looked negative led to a nonsystematic appraisal.
Dr Corson or his fellow takes the specimen, inks it, and lets us know exactly which of the sections is positive. I would emphasize that in evaluating the survival curves we are looking at a marker of cytoreduction.
I am not suggesting that we are rendering patients disease-free. However, if you think of 10 to 15 sections and you begin to look at margins negative, margins positive, you are really looking at a quantification of how well your local control procedure accomplished what it set out to do.
The most important lesson is that patients in whom we have achieved near-complete cytoreduction appear to have a survival advantage. This directs us toward local control strategies, such as heated intrathoracic chemotherapy at the time of resection, high-dose radiotherapy, photodynamic therapy, and some of the other areas that would be used against this particular tumor in its most vulnerable and most lethal form, which is local recurrence.
Last, I share your concern regarding paclitaxel radiotherapy. We have found that it is unsuccessful as neoadjuvant therapy in mesothelioma. We have performed extensive surgery after induction therapy and have had a very high complication rate, which led us to abandon that form of treatment. Sometimes patients are referred who have already been treated. Those patients do not do well. Paclitaxel radiotherapy is still an open question. We have witnessed toxicity in conjunction with its use. As Dr Patterson elucidated, we have had to reduce our dose of radiotherapy to avoid toxicity in these patients.
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 T. Yamanaka, F. Tanaka, S. Hasegawa, M. Okada, T. Soejima, N. Kamikonya, K. Fukuoka, and T. Nakano A Feasibility Study of Induction Pemetrexed Plus Cisplatin Followed by Extrapleural Pneumonectomy and Postoperative Hemithoracic Radiation for Malignant Pleural Mesothelioma Jpn. J. Clin. Oncol., March 1, 2009; 39(3): 186 - 188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Zellos, W. G. Richards, L. Capalbo, M. T. Jaklitsch, L. R. Chirieac, B. E. Johnson, R. Bueno, and D. J. Sugarbaker A phase I study of extrapleural pneumonectomy and intracavitary intraoperative hyperthermic cisplatin with amifostine cytoprotection for malignant pleural mesothelioma. J. Thorac. Cardiovasc. Surg., February 1, 2009; 137(2): 453 - 458. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Sorensen, J. Ravn, A. Loft, J. Brenoe, A. K. Berthelsen, and on behalf of the Nordic Mesothelioma Group Preoperative staging of mesothelioma by 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography fused imaging and mediastinoscopy compared to pathological findings after extrapleural pneumonectomy Eur. J. Cardiothorac. Surg., November 1, 2008; 34(5): 1090 - 1096. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Nakas, D. S. Trousse, A. E. Martin-Ucar, and D. A. Waller Open lung-sparing surgery for malignant pleural mesothelioma: the benefits of a radical approach within multimodality therapy Eur. J. Cardiothorac. Surg., October 1, 2008; 34(4): 886 - 891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Flores, T. Routledge, V. E. Seshan, J. Dycoco, M. Zakowski, Y. Hirth, and V. W. Rusch The impact of lymph node station on survival in 348 patients with surgically resected malignant pleural mesothelioma: Implications for revision of the American Joint Committee on Cancer staging system J. Thorac. Cardiovasc. Surg., September 1, 2008; 136(3): 605 - 610. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. M. Abdel Rahman, R. M. Gaafar, H. A. Baki, H. M. El Hosieny, F. Aboulkasem, E. G. Farahat, A. M. Nouh, and K. A. Mansour Prevalence and Pattern of Lymph Node Metastasis in Malignant Pleural Mesothelioma Ann. Thorac. Surg., August 1, 2008; 86(2): 391 - 395. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Beshay, G. Carboni, B. Hoksch, M. A. Reymond, and R. A. Schmid The role of muscle flap in preventing bronchus stump insufficiency after pneumonectomy for malignant pleural mesothelioma in high-risk patients Interactive CardioVascular and Thoracic Surgery, August 1, 2008; 7(4): 621 - 625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Chamberlain, K. Fareed, A. Nakas, A. E. Martin-Ucar, and D. A. Waller Video-assisted cervical thoracoscopy: a novel approach for diagnosis, staging and pleurodesis of malignant pleural mesothelioma. Eur. J. Cardiothorac. Surg., July 1, 2008; 34(1): 200 - 203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. van Sandick, I. Kappers, P. Baas, R. L. Haas, and H. M. Klomp Surgical Treatment in the Management of Malignant Pleural Mesothelioma: A Single Institution's Experience Ann. Surg. Oncol., June 1, 2008; 15(6): 1757 - 1764. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. C. Mineo, V. Ambrogi, E. Pompeo, A. Baldi, F. Stella, P. Aurea, and M. Marino The Value of Occult Disease in Resection Margin and Lymph Node After Extrapleural Pneumonectomy for Malignant Mesothelioma Ann. Thorac. Surg., May 1, 2008; 85(5): 1740 - 1746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Anraku, K. S. Cunningham, Z. Yun, M.-S. Tsao, L. Zhang, S. Keshavjee, M. R. Johnston, and M. de Perrot Impact of tumor-infiltrating T cells on survival in patients with malignant pleural mesothelioma. J. Thorac. Cardiovasc. Surg., April 1, 2008; 135(4): 823 - 829. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H Kothmaier, F Quehenberger, I Halbwedl, P Morbini, F Demirag, H Zeren, C E Comin, B Murer, P T Cagle, R Attanoos, et al. EGFR and PDGFR differentially promote growth in malignant epithelioid mesothelioma of short and long term survivors Thorax, April 1, 2008; 63(4): 345 - 351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Flores, H. I. Pass, V. E. Seshan, J. Dycoco, M. Zakowski, M. Carbone, M. S. Bains, and V. W. Rusch Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: Results in 663 patients J. Thorac. Cardiovasc. Surg., March 1, 2008; 135(3): 620 - 626. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Shiomi, Y. Hagiwara, K. Sonoue, T. Segawa, K. Miyashita, M. Maeda, H. Izumi, K. Masuda, M. Hirabayashi, T. Moroboshi, et al. Sensitive and Specific New Enzyme-Linked Immunosorbent Assay for N-ERC/Mesothelin Increases its Potential as a Useful Serum Tumor Marker for Mesothelioma Clin. Cancer Res., March 1, 2008; 14(5): 1431 - 1437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Nakas, A. E. Martin-Ucar, J. G. Edwards, and D. A. Waller Localised malignant pleural mesothelioma: a separate clinical entity requiring aggressive local surgery Eur. J. Cardiothorac. Surg., February 1, 2008; 33(2): 303 - 306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Borasio, A. Berruti, A. Bille, P. Lausi, M. G. Levra, R. Giardino, and F. Ardissone Malignant pleural mesothelioma: clinicopathologic and survival characteristics in a consecutive series of 394 patients Eur. J. Cardiothorac. Surg., February 1, 2008; 33(2): 307 - 313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Okada, T. Mimura, C. Ohbayashi, T. Sakuma, T. Soejima, and N. Tsubota Radical surgery for malignant pleural mesothelioma: results and prognosis Interactive CardioVascular and Thoracic Surgery, February 1, 2008; 7(1): 102 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Nakas, A. E. Martin Ucar, J. G. Edwards, and D. A. Waller The role of video assisted thoracoscopic pleurectomy/decortication in the therapeutic management of malignant pleural mesothelioma Eur. J. Cardiothorac. Surg., January 1, 2008; 33(1): 83 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. L. Kindler, R. Bueno, and J. R. Testa New Biomarkers, Surgical Controversies, and Rationally Targeted Therapies for Malignant Mesothelioma ASCO Educational Book, January 1, 2008; 2008(1): 354 - 361. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
British Thoracic Society Standards of Care Committ BTS statement on malignant mesothelioma in the UK, 2007 Thorax, November 1, 2007; 62(Suppl_2): ii1 - ii19. [Full Text] [PDF]
|
|
|
|
|
|
T. Suda, Y. Kitamura, S. Hasegawa, K. Negi, and Y. Hattori Video-assisted thoracoscopic extrapleural pneumonectomy for malignant pleural mesothelioma. J. Thorac. Cardiovasc. Surg., October 1, 2007; 134(4): 1088 - 1089. [Full Text] [PDF]
|
|
|
|
 |
|
 W Weder, R. Stahel, J Bernhard, S Bodis, P Vogt, P Ballabeni, D Lardinois, D Betticher, R Schmid, R Stupp, et al. Multicenter trial of neo-adjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma Ann. Onc., July 1, 2007; 18(7): 1196 - 1202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. L. Ceresoli, C. Gridelli, and A. Santoro Multidisciplinary Treatment of Malignant Pleural Mesothelioma Oncologist, July 1, 2007; 12(7): 850 - 863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Treasure and M. Utley Ten traps for the unwary in surgical series: A case study in mesothelioma reports J. Thorac. Cardiovasc. Surg., June 1, 2007; 133(6): 1414 - 1418. [Full Text] [PDF]
|
|
|
|
|
|
B.-D. Grigoriu, A. Scherpereel, P. Devos, B. Chahine, M. Letourneux, P. Lebailly, M. Gregoire, H. Porte, M.-C. Copin, and P. Lassalle Utility of Osteopontin and Serum Mesothelin in Malignant Pleural Mesothelioma Diagnosis and Prognosis Assessment Clin. Cancer Res., May 15, 2007; 13(10): 2928 - 2935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Martin-Ucar, A. Nakas, J. G. Edwards, and D. A. Waller Case-control study between extrapleural pneumonectomy and radical pleurectomy/decortication for pathological N2 malignant pleural mesothelioma Eur. J. Cardiothorac. Surg., May 1, 2007; 31(5): 765 - 770. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Sugarbaker Editorial comment Eur. J. Cardiothorac. Surg., May 1, 2007; 31(5): 770 - 771. [Full Text] [PDF]
|
|
|
|
|
|
M. Lucchi, A. Chella, F. Melfi, P. Dini, M. Ambrogi, L. Fino, G. Fontanini, and A. Mussi A phase II study of intrapleural immuno-chemotherapy, pleurectomy/decortication, radiotherapy, systemic chemotherapy and long-term sub-cutaneous IL-2 in stage II-III malignant pleural mesothelioma Eur. J. Cardiothorac. Surg., March 1, 2007; 31(3): 529 - 534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Pilling, A. G. Nicholson, C. Harmer, and P. Goldstraw Prolonged Survival Due to Spontaneous Regression and Surgical Excision of Malignant Mesothelioma Ann. Thorac. Surg., January 1, 2007; 83(1): 314 - 315. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Rice Reply Ann. Thorac. Surg., December 1, 2006; 82(6): 2337 - 2338. [Full Text] [PDF]
|
|
|
|
|
|
P. S. Adusumilli, D. P. Eisenberg, B. M. Stiles, S. Chung, M.-K. Chan, V. W. Rusch, and Y. Fong Intraoperative localization of lymph node metastases with a replication-competent herpes simplex virus. J. Thorac. Cardiovasc. Surg., November 1, 2006; 132(5): 1179 - 1188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. P. Agarwal, J. M. Seely, F. R. Matzinger, R. M. MacRae, R. A. Peterson, D. E. Maziak, and C. J. Dennie Pleural Mesothelioma: Sensitivity and Incidence of Needle Track Seeding after Image-guided Biopsy versus Surgical Biopsy Radiology, November 1, 2006; 241(2): 589 - 594. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. L. Ceresoli, A. Chiti, P. A. Zucali, M. Rodari, R. F. Lutman, S. Salamina, M. Incarbone, M. Alloisio, and A. Santoro Early Response Evaluation in Malignant Pleural Mesothelioma by Positron Emission Tomography With [18F]Fluorodeoxyglucose J. Clin. Oncol., October 1, 2006; 24(28): 4587 - 4593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Flores, T. Akhurst, M. Gonen, M. Zakowski, J. Dycoco, S. M. Larson, and V. W. Rusch Positron emission tomography predicts survival in malignant pleural mesothelioma J. Thorac. Cardiovasc. Surg., October 1, 2006; 132(4): 763 - 768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Edwards, D.J. Stewart, A. Martin-Ucar, S. Muller, C. Richards, and D. A. Waller The pattern of lymph node involvement influences outcome after extrapleural pneumonectomy for malignant mesothelioma J. Thorac. Cardiovasc. Surg., May 1, 2006; 131(5): 981 - 987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. G. Richards, L. Zellos, R. Bueno, M. T. Jaklitsch, P. A. Janne, L. R. Chirieac, B. Y. Yeap, R. J. Dekkers, P. M. Hartigan, L. Capalbo, et al. Phase I to II Study of Pleurectomy/Decortication and Intraoperative Intracavitary Hyperthermic Cisplatin Lavage for Mesothelioma J. Clin. Oncol., April 1, 2006; 24(10): 1561 - 1567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. L. Ceresoli, P. A. Zucali, A. G. Favaretto, F. Grossi, P. Bidoli, G. Del Conte, A. Ceribelli, A. Bearz, E. Morenghi, R. Cavina, et al. Phase II Study of Pemetrexed Plus Carboplatin in Malignant Pleural Mesothelioma J. Clin. Oncol., March 20, 2006; 24(9): 1443 - 1448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Intrapleural topical application of cisplatin with the surgical carrier Vivostat increases the local drug concentration in an immune-competent rat model with malignant pleuromesothelioma. J. Thorac. Cardiovasc. Surg., March 1, 2006; 131(3): 697 - 703.e3.
|
|
|
|
|
|
T. Treasure, C. Tan, L. Lang-Lazdunski, and D. Waller The MARS trial: mesothelioma and radical surgery Interactive CardioVascular and Thoracic Surgery, February 1, 2006; 5(1): 58 - 59. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Rice, J. J. Erasmus, C. W. Stevens, A. A. Vaporciyan, J. S. Wu, A. S. Tsao, G. L. Walsh, S. G. Swisher, W. L. Hofstetter, N. G. Ordonez, et al. Extended Surgical Staging for Potentially Resectable Malignant Pleural Mesothelioma Ann. Thorac. Surg., December 1, 2005; 80(6): 1988 - 1993. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Sterman, A. Recio, A. Vachani, J. Sun, L. Cheung, P. DeLong, K. M. Amin, L. A. Litzky, J. M. Wilson, L. R. Kaiser, et al. Long-term Follow-up of Patients with Malignant Pleural Mesothelioma Receiving High-Dose Adenovirus Herpes Simplex Thymidine Kinase/Ganciclovir Suicide Gene Therapy Clin. Cancer Res., October 15, 2005; 11(20): 7444 - 7453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Tan and T. Treasure Mesothelioma: time to take stock J R Soc Med, October 1, 2005; 98(10): 455 - 458. [Full Text] [PDF]
|
|
|
|
|
|
J.M. Alvarez, T. Ha, W. Musk, P. Robins, R. Price, and M.J. Byrne Importance of mediastinoscopy, bilateral thoracoscopy, and laparoscopy in correct staging of malignant mesothelioma before extrapleural pneumonectomy J. Thorac. Cardiovasc. Surg., September 1, 2005; 130(3): 905 - 906. [Full Text] [PDF]
|
|
|
|
|
|
P. A. Rascoe, X. Cao, J. C. Daniel, S. D. Miller, and W. R. Smythe Receptor tyrosine kinase and phosphoinositide-3 kinase signaling in malignant mesothelioma J. Thorac. Cardiovasc. Surg., August 1, 2005; 130(2): 393 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Maruyama, F. Shoji, T. Okamoto, T. Miyamoto, T. Miyake, T. Nakamura, J. Ikeda, Y. Aoki, H. Wataya, H. Asoh, et al. Triplet Chemotherapy with Cisplatin, Gemcitabine and Vinorelbine for Malignant Pleural Mesothelioma Jpn. J. Clin. Oncol., August 1, 2005; 35(8): 433 - 438. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Argote-Greene, M. Y. Chang, and D. J. Sugarbaker Extrapleural pneumonectomy for malignant pleural mesothelioma MMCTS, June 28, 2005; 2005(0628): 133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Gordon, G. N. Rockwell, P. A. Godfrey, R. V. Jensen, J. N. Glickman, B. Y. Yeap, W. G. Richards, D. J. Sugarbaker, and R. Bueno Validation of Genomics-Based Prognostic Tests in Malignant Pleural Mesothelioma Clin. Cancer Res., June 15, 2005; 11(12): 4406 - 4414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Erasmus, M. T. Truong, W. R. Smythe, R. F. Munden, E. M. Marom, D. C. Rice, A. A. Vaporciyan, G. L. Walsh, B. S. Sabloff, L. D. Broemeling, et al. Integrated computed tomography-positron emission tomography in patients with potentially resectable malignant pleural mesothelioma: Staging implications J. Thorac. Cardiovasc. Surg., June 1, 2005; 129(6): 1364 - 1370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Neragi-Miandoab, S. P. Gangadharan, and D. J. Sugarbaker Cardiac Sarcoma 14 Years after Treatment for Pleural Mesothelioma N. Engl. J. Med., May 5, 2005; 352(18): 1929 - 1930. [Full Text] [PDF]
|
|
|
|
|
|
M. Hazarika, R. M. White Jr., B. P. Booth, Y.-C. Wang, D. Y. Lee Ham, C. Y. Liang, A. Rahman, J. V.S. Gobburu, N. Li, R. Sridhara, et al. Pemetrexed in Malignant Pleural Mesothelioma Clin. Cancer Res., February 1, 2005; 11(3): 982 - 992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P. Parungo, S. Ohnishi, A. M. De Grand, R. G. Laurence, E. G. Soltesz, Y. L. Colson, P. M. Kang, T. Mihaljevic, L. H. Cohn, and J. V. Frangioni In Vivo Optical Imaging of Pleural Space Drainage to Lymph Nodes of Prognostic Significance Ann. Surg. Oncol., December 1, 2004; 11(12): 1085 - 1092. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bueno, J. Reblando, J. Glickman, M. T. Jaklitsch, J. M. Lukanich, and D. J. Sugarbaker Pleural Biopsy: A Reliable Method for Determining the Diagnosis But Not Subtype in Mesothelioma Ann. Thorac. Surg., November 1, 2004; 78(5): 1774 - 1776. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Aelony Need for Further Information on Pemetrexed Study J. Clin. Oncol., October 15, 2004; 22(20): 4234 - 4235. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Pistolesi and J. Rusthoven Malignant Pleural Mesothelioma: Update, Current Management, and Newer Therapeutic Strategies Chest, October 1, 2004; 126(4): 1318 - 1329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Weder, P. Kestenholz, C. Taverna, S. Bodis, D. Lardinois, M. Jerman, and R. A. Stahel Neoadjuvant Chemotherapy Followed by Extrapleural Pneumonectomy in Malignant Pleural Mesothelioma J. Clin. Oncol., September 1, 2004; 22(17): 3451 - 3457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Andreopoulou, P. J. Ross, M. E. R. O'Brien, H. E. R. Ford, K. Priest, T. Eisen, A. Norton, S. Ashley, and I. E. Smith The palliative benefits of MVP (mitomycin C, vinblastine and cisplatin) chemotherapy in patients with malignant mesothelioma Ann. Onc., September 1, 2004; 15(9): 1406 - 1412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Stewart, A. Martin-Ucar, J. E. Pilling, J. G. Edwards, K. J. O'Byrne, and D. A. Waller The effect of extent of local resection on patterns of disease progression in malignant pleural mesothelioma Ann. Thorac. Surg., July 1, 2004; 78(1): 245 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Sugarbaker, M. T. Jaklitsch, R. Bueno, W. Richards, J. Lukanich, S. J. Mentzer, Y. Colson, P. Linden, M. Chang, L. Capalbo, et al. Prevention, early detection, and management of complications after 328 consecutive extrapleural pneumonectomies J. Thorac. Cardiovasc. Surg., July 1, 2004; 128(1): 138 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kramer, R. M. Pieterman, D.-J. Slebos, W. Timens, W. Vaalburg, G. H. Koeter, and H. J.M. Groen PET for the Evaluation of Pleural Thickening Observed on CT J. Nucl. Med., June 1, 2004; 45(6): 995 - 998. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. K. Ozvaran, X. X. Cao, S. D. Miller, B. A. Monia, W. K. Hong, and W. R. Smythe Antisense oligonucleotides directed at the bcl-xl gene product augment chemotherapy response in mesothelioma Mol. Cancer Ther., May 1, 2004; 3(5): 545 - 550. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A Baldi, D Santini, F Vasaturo, M Santini, G Vicidomini, M P. Di Marino, V Esposito, A M Groeger, G Liuzzi, B Vincenzi, et al. Prognostic significance of cyclooxygenase-2 (COX-2) and expression of cell cycle inhibitors p21 and p27 in human pleural malignant mesothelioma Thorax, May 1, 2004; 59(5): 428 - 433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.E. Pilling, D.J. Stewart, A.E. Martin-Ucar, S. Muller, K.J. O'Byrne, and D.A. Waller The case for routine cervical mediastinoscopy prior to radical surgery for malignant pleural mesothelioma Eur. J. Cardiothorac. Surg., April 1, 2004; 25(4): 497 - 501. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sharma, P. Fidias, L. A. Hayman, S. L. Loomis, K. H. Taber, and S. L. Aquino Patterns of Lymphadenopathy in Thoracic Malignancies RadioGraphics, March 1, 2004; 24(2): 419 - 434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. J. Wang, G. P. Reddy, M. B. Gotway, C. B. Higgins, D. M. Jablons, M. Ramaswamy, R. A. Hawkins, and W. R. Webb Malignant Pleural Mesothelioma: Evaluation with CT, MR Imaging, and PET RadioGraphics, January 1, 2004; 24(1): 105 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V H Gerbaudo, S Britz-Cunningham, D J Sugarbaker, and S T Treves Metabolic significance of the pattern, intensity and kinetics of 18F-FDG uptake in malignant pleural mesothelioma Thorax, December 1, 2003; 58(12): 1077 - 1082. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Edwards, D. E. B. Swinson, J. L. Jones, S. Muller, D. A. Waller, and K. J. O'Byrne Tumor Necrosis Correlates With Angiogenesis and Is a Predictor of Poor Prognosis in Malignant Mesothelioma Chest, November 1, 2003; 124(5): 1916 - 1923. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C Parker and E Neville Lung cancer * 8: Management of malignant mesothelioma Thorax, September 1, 2003; 58(9): 809 - 813. [Full Text] [PDF]
|
|
|
|
|
|
V. W. Rusch Pemetrexed and Cisplatin for Malignant Pleural Mesothelioma: A New Standard of Care? J. Clin. Oncol., July 15, 2003; 21(14): 2629 - 2630. [Full Text] [PDF]
|
|
|
|
|
|
R. M. Flores, T. Akhurst, M. Gonen, S. M. Larson, and V. W. Rusch Positron emission tomography defines metastatic disease but not locoregional disease in patients with malignant pleural mesothelioma J. Thorac. Cardiovasc. Surg., July 1, 2003; 126(1): 11 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Schouwink, L. Schultze Kool, E. J. Rutgers, F. A. N. Zoetmulder, N. van Zandwijk, M. J. v.d. Vijver, and P. Baas The value of chest computer tomography and cervical mediastinoscopy in the preoperative assessment of patients with malignant pleural mesothelioma Ann. Thorac. Surg., June 1, 2003; 75(6): 1715 - 1718. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Gordon, R. V. Jensen, L.-L. Hsiao, S. R. Gullans, J. E. Blumenstock, W. G. Richards, M. T. Jaklitsch, D. J. Sugarbaker, and R. Bueno Using Gene Expression Ratios to Predict Outcome Among Patients With Mesothelioma J Natl Cancer Inst, April 16, 2003; 95(8): 598 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
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P. G. Phillips, G. Asimakopoulos, and M. O. Maiwand Malignant pleural mesothelioma: outcome of limited surgical management Interactive CardioVascular and Thoracic Surgery, March 1, 2003; 2(1): 30 - 34. [Abstract] [Full Text] [PDF]
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S. van Ruth, P. Baas, R.L. M. Haas, E.J. Th. Rutgers, V.J. Verwaal, and F.A. N. Zoetmulder Cytoreductive Surgery Combined With Intraoperative Hyperthermic Intrathoracic Chemotherapy for Stage I Malignant Pleural Mesothelioma Ann. Surg. Oncol., March 1, 2003; 10(2): 176 - 182. [Abstract] [Full Text] [PDF]
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Y. Aelony Missing data from mesothelioma study J. Thorac. Cardiovasc. Surg., February 1, 2003; 125(2): 442 - 443. [Full Text] [PDF]
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H. I. Pass Pleural mesothelioma in 2002: Going somewhere very slowly J. Thorac. Cardiovasc. Surg., December 1, 2002; 124(6): 1074 - 1077. [Full Text]
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T. T. Lee, D. L. Everett, H.-K. G. Shu, T. M. Jahan, M. Roach III, J. L. Speight, R. B. Cameron, T. L. Phillips, A. Chan, and D. M. Jablons Radical pleurectomy/decortication and intraoperative radiotherapy followed by conformal radiation with or without chemotherapy for malignant pleural mesothelioma J. Thorac. Cardiovasc. Surg., December 1, 2002; 124(6): 1183 - 1189. [Abstract] [Full Text]
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P. Bonnette, G. B. Heckly, S. Villette, A. Fragola, J. H. Schouwink, and P. Bass Intraoperative Photodynamic Therapy After Pleuropneumonectomy for Malignant Pleural Mesothelioma Chest, November 1, 2002; 122(5): 1866 - 1867. [Full Text] [PDF]
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 P. A. Janne, M. L. Taffaro, R. Salgia, and B. E. Johnson Inhibition of Epidermal Growth Factor Receptor Signaling in Malignant Pleural Mesothelioma Cancer Res., September 15, 2002; 62(18): 5242 - 5247. [Abstract] [Full Text] [PDF]
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V. H. Gerbaudo, D. J. Sugarbaker, S. Britz-Cunningham, M. F. Di Carli, C. Mauceri, and S. T. Treves Assessment of Malignant Pleural Mesothelioma with 18F-FDG Dual-Head Gamma-Camera Coincidence Imaging: Comparison with Histopathology J. Nucl. Med., September 1, 2002; 43(9): 1144 - 1149. [Abstract] [Full Text] [PDF]
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W. R. Smythe, I. Mohuiddin, M. Ozveran, and X. X. Cao Antisense therapy for malignant mesothelioma with oligonucleotides targeting the bcl-xl gene product J. Thorac. Cardiovasc. Surg., June 1, 2002; 123(6): 1191 - 1198. [Abstract] [Full Text] [PDF]
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 G. J. Gordon, K. Appasani, J. P. Parcells, N. K. Mukhopadhyay, M. T. Jaklitsch, W. G. Richards, D. J. Sugarbaker, and R. Bueno Inhibitor of apoptosis protein-1 promotes tumor cell survival in mesothelioma Carcinogenesis, June 1, 2002; 23(6): 1017 - 1024. [Abstract] [Full Text] [PDF]
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J. G. Edwards, S. P. Faux, S. M. Plummer, K. R. Abrams, R. A. Walker, D. A. Waller, and K. J. O'Byrne Cyclooxygenase-2 Expression Is a Novel Prognostic Factor in Malignant Mesothelioma Clin. Cancer Res., June 1, 2002; 8(6): 1857 - 1862. [Abstract] [Full Text] [PDF]
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I. Mohiuddin, X. Cao, M. K. Ozvaran, L. Zumstein, S. Chada, and W. R. Smythe Phosphatase and Tensin Analog Gene Overexpression Engenders Cellular Death in Human Malignant Mesothelioma Cells via Inhibition of AKT Phosphorylation Ann. Surg. Oncol., April 1, 2002; 9(3): 310 - 316. [Abstract] [Full Text] [PDF]
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 X. X. Cao, I. Mohuiddin, F. Ece, D. J. McConkey, and W. R. Smythe Histone Deacetylase Inhibitor Downregulation of bcl-xl Gene Expression Leads to Apoptotic Cell Death in Mesothelioma Am. J. Respir. Cell Mol. Biol., November 1, 2001; 25(5): 562 - 568. [Abstract] [Full Text] [PDF]
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V. W. Rusch, K. Rosenzweig, E. Venkatraman, L. Leon, A. Raben, L. Harrison, M. S. Bains, R. J. Downey, and R. J. Ginsberg A phase II trial of surgical resection and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma J. Thorac. Cardiovasc. Surg., October 1, 2001; 122(4): 788 - 795. [Abstract] [Full Text] [PDF]
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British Thoracic Society Standards of Care Committ Statement on malignant mesothelioma in the United Kingdom Thorax, April 1, 2001; 56(4): 250 - 265. [Full Text]
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G. Maggi, C. Casadio, R. Cianci, O. Rena, and E. Ruffini Trimodality management of malignant pleural mesothelioma Eur. J. Cardiothorac. Surg., March 1, 2001; 19(3): 346 - 350. [Abstract] [Full Text] [PDF]
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S. Bandoh, J. Fujita, Y. Fukunaga, S. Ohtsuka, K. Susaki, Y. Yang, S. Kobayashi, and J. Takahara Nodular Thickening of Interlobar Fissures: an Early Manifestation of Malignant Mesothelioma: A Case Report Jpn. J. Clin. Oncol., February 1, 2001; 31(2): 82 - 85. [Abstract] [Full Text] [PDF]
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R. Bueno, K. Appasani, H. Mercer, S. Lester, and D. Sugarbaker The {{alpha}} folate receptor is highly activated in malignant pleural mesothelioma J. Thorac. Cardiovasc. Surg., February 1, 2001; 121(2): 0225 - 233. [Abstract] [Full Text] [PDF]
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