Multimodal therapy for malignant pleural mesothelioma including extrapleural pneumonectomy

Multimodal therapy including neoadjuvant chemotherapy with subsequent extrapleural pneumonectomy and postoperative radiotherapy has been shown to improve the survival of patients with malignant pleural mesothelioma (MPM) if they are selected carefully. Careful patient selection is required in order to administer aggressive multimodal therapy only to patients who will benefit from such a treatment. To achieve an accurate staging (相似文献   

Extrapleural pneumonectomy for malignant pleural mesothelioma

We analyzed 14 patients with malignant pleural mesothelioma (MPM) who underwent extrapleural pneumonectomy (EPP). 14 men had a mean age of 58.5 years. Preoperarive histological diagnosis was as follows: epithelial 12, biphasic 1, sarcomatous 1. Postoperative diagnosis was: 8, 5, 1, respectively. According to staging of International Mesothelioma Interest Group (IMIG), 3 patients had stage 11 disease, 8 did stage Ill and 3 did stage IV, postoperatively. The operative mortality rate was 7% (1 death), and morbidity rate was 50% (7 cases). The median survival time and 2- and 5-year survival rate were 20.2 months, 33. 8.3%, respectively. EPP for strictly selected patients has been successful in improving survival of patients with negative-node, epithelial type and negative residual tumors.     

The role of extrapleural pneumonectomy in malignant pleural mesothelioma. A Lung Cancer Study Group trial

Malignant pleural mesothelioma is usually a fatal cancer for which operation has been the mainstay of treatment because chemotherapy and radiation are relatively ineffective. The choice of operation for malignant pleural mesothelioma remains controversial. Extrapleural pneumonectomy has been advocated because it allows complete removal of gross tumor and can be associated with long-term survival. To evaluate extrapleural pneumonectomy, we conducted a prospective multiinstitutional trial in patients with biopsy-proved previously untreated malignant pleural mesothelioma. Criteria for extrapleural pneumonectomy were (1) potentially completely resectable unilateral disease by computed tomography scan, (2) predicted postresection forced expiratory volume in 1 second greater than 1 L/sec, and (3) no other major medical problems. Patients who were not candidates for extrapleural pneumonectomy had a more limited operation with or without adjuvant therapy or had nonsurgical treatment. From September 1985 to June 1988 83 eligible patients (64 male, 19 female) were entered. The mean age for all patients was 59.7 years. Only 20 of the 83 patients (24%) underwent extrapleural pneumonectomy. Three of these 20 patients (15%) died postoperatively. The recurrence-free survival was significantly longer for the patients undergoing extrapleural pneumonectomy than for the other two groups (p = 0.03), but there was no difference in overall survival among the three groups. In univariate analyses, epithelial versus sarcomatoid and mixed histologic findings and platelet count less than 400,000 were associated with a better overall survival (p = 0.02), and performance status (Karnofsky less than 80) was predictive of recurrence (p = 0.02). In a multivariate analysis, histologic findings, sex, age, extrapleural pneumonectomy, weight loss, and performance status all had no significant impact on survival. Extrapleural pneumonectomy was associated with a greater likelihood of relapse in distant sites than were limited operation and nonsurgical treatment. We conclude that (1) only a small proportion of all patients with malignant pleural mesothelioma are candidates for extrapleural pneumonectomy, (2) extrapleural pneumonectomy carries a significant operative mortality and does not seem to improve overall survival compared with more conservative forms of treatment, (3) extrapleural pneumonectomy alters the patterns of relapse, and (4) factors previously thought to have an impact on survival in other series did not affect outcome in this trial.     

Outcome after extrapleural pneumonectomy for malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma is a mainly asbestos-related neoplasm that occurs with increasing frequency and is associated with a poor prognosis. Extrapleural pneumonectomy which was initially performed as a stand-alone treatment in patients with resectable disease is now currently almost uniformly applied as part of a multi-modal approach. Its value and advantage over other therapeutic strategies remain points of discussion. We therefore analysed our experience with extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma. METHODS: We retrospectively reviewed our institutional experience with all consecutive patients undergoing extrapleural pneumonectomy for malignant pleural mesothelioma from 1994 to 2005. Patients were analysed with regard to hospital mortality and morbidity and long-term outcome. RESULTS: Forty-nine patients (10 female/39 male, mean age 58+12 years) underwent extrapleural pneumonectomy during the observation period. Median ICU stay was 1 day, median postoperative length of hospital stay was 13 days. After a mean follow-up of 2573 days, median survival was 376 days (mean 672+121 days, range 9-3384). One-year survival was 53%, 3-year survival 27% and 5-year survival 19%. CONCLUSION: Extrapleural pneumonectomy as part of a multi-modality treatment regimen is a good treatment option for selected patients with malignant pleural mesothelioma. The long-term results of this limited series compare favourably to non-surgical treatment regimens. Larger randomised prospective multi-centre trials are warranted to establish clear guidelines.     

Extrapleural pneumonectomy for thoracic malignancies

Extrapleural pneumonectomy has been used by thoracic surgeons in the treatment of malignant pleural mesothelioma as well as other pleural diseases, such as tuberculous empyema. Recently, this operative procedure has been also sporadically applied for the treatment of carcinomatous pleuritis of lung cancer and/or invasive thymoma in some institutions. We performed this operation in 24 patients with thoracic malignancy: 15 patients with carcinomatous pleuritis of primary lung adenocarcinoma (6 patients with T4N0 disease, 2 with T4N1, and 7 with T4N2), 3 patients with stage IV a thymoma, and 6 patients with malignant pleural mesothelioma (2 patients with stage II disease, 3 with stage III, and 1 with stage IV). All patients survived the operation and were discharged from the hospital. Major complications were intrathoracic hemorrhage and empyema in 2 patients each. The median survival time and 5-year survival rate of lung cancer patients were 34 months and 45.5%, respectively. All patients with thymoma are alive now without disease 9 to 133 months after operation. All patients with malignant pleural mesothelioma except 1, who lately underwent this treatment, died of disease from 15 to 27 months after surgery. Our results indicate that carefully selected patients with carcinomatous pleuritis of lung cancer and thymoma may be candidates for extrapleural pneumonectomy for cure. Nevertheless, the ultimate value of this surgical treatment should be ascertained in a prospective study with a large number of patients.     

Malignant pleural mesothelioma

Malignant pleural mesothelioma carries a poor prognosis, for which no standard therapy has been established. We report 15 cases of malignant pleural mesothelioma experienced since 2000 focusing on their clinical features. They included 14 male and 1 female aged 38 to 81 (62.8 on average) years. All patients were diagnosed by pleural biopsy under thoracoscopic guidance. Histology of the pleural biopsy specimen showed epithelial mesothelioma in 8 patients, biphasic mesothelioma in 3, sarcomatous mesothelioma in 2 and desmoplastic malignant mesothelioma (DMM) in 2. Twelve patients received chemotherapy. Of these, 3 were followed by surgery. In addition to 2 of these 3 patients, 2 underwent extrapleural pneumonectomy (EPP) without adjuvant treatment. Remaining 1 received palliative treatment only. As a result, 6 patients are surviving, 7 died of primary diseases and 2 died of other diseases. The longest survival time with chemotherapy is 41 months in a surviving patient with epithelial mesothelioma and that with EPP is 25 months in a surviving patient with DMM. The 2-year survival rate of the 14 patients was 44.4% and the median survival time in patients with epithelial mesothelioma was 30.6 months.     

Extrapleural pneumonectomy for malignant pleural mesothelioma and primary lung cancer

The extrapleural pneumonectomy for 6 patients with malignant pleural mesothelioma and 2 patients with primary lung cancer have been performed in our unit in those 10 years. Range of the age was 48-57 year-old. All of them were male and have been in occupational asbestos exposure. The mean survival time after extrapleural pneumonectomy was 620 days. In those, we experienced a case of malignant mesothelioma with excellent reduction by induction therapy of cisplatin+docetaxel hydrate, who underwent the extrapleural pneumonectomy continuously. We mentioned more over about the role of extrapleural pneumonectomy for primary lung cancer with pleural dissemination, and intrapleural perfusion hyperthermo-therapy for malignant mesothelioma.     

Integrated computed tomography-positron emission tomography in patients with potentially resectable malignant pleural mesothelioma: Staging implications

BACKGROUND: Integrated computed tomography-positron emission tomography imaging with coregistration of anatomic and functional imaging data may improve the accuracy of malignant pleural mesothelioma staging. We evaluate the use of integrated computed tomography-positron emission tomography in patients with malignant pleural mesothelioma who are being considered for extrapleural pneumonectomy. METHODS: Twenty-nine patients with malignant pleural mesothelioma who were judged to be candidates for extrapleural pneumonectomy after clinical and conventional radiologic evaluation underwent whole-body integrated computed tomography-positron emission tomography and pathologic staging. Two reviewers blinded to the results of clinical and pathologic staging retrospectively evaluated computed tomography, positron emission tomography, and coregistered computed tomography-positron emission tomography images. Staging was performed according to the International Mesothelioma Interest Group TNM staging system. Histopathology and/or results of further radiologic evaluation or follow-up served as the reference standard. RESULTS: Integrated computed tomography-positron emission tomography provided additional information in 11 of 29 patients that precluded extrapleural pneumonectomy. The overall tumor stage was correctly classified in 21 of 29 patients. The tumor stage was correctly determined in 15 of 24 patients, 6 of whom had T4 (nonresectable) disease. The node stage was accurately determined in 6 of 17 patients. Extrathoracic metastases not identified by routine clinical and conventional radiologic evaluation were detected in 7 of 29 patients and were found to be diffuse (n = 2) or solitary (n = 5). CONCLUSIONS: Integrated computed tomography-positron emission tomography increases the accuracy of malignant pleural mesothelioma staging and is important in determining the appropriate therapy in patients being considered for extrapleural pneumonectomy.     

Extrapleural pneumonectomy in the multimodality therapy of malignant pleural mesothelioma. Results in 120 consecutive patients.

OBJECTIVE: The authors examine the feasibility and efficacy of trimodality therapy in the treatment of malignant pleural mesothelioma and identify prognostic factors. BACKGROUND: Mesothelioma is a rare, uniformly fatal disease that has increased in incidence in recent decades. Single and bimodality therapies do not improve survival. METHODS: From 1980 to 1995, 120 patients underwent treatment for pathologically confirmed malignant mesothelioma at Brigham and Women's Hospital and Dana-Farber Cancer Institute (Boston, MA). Initial patient evaluation was performed by a multimodality team. Patients meeting selection criteria and with resectable disease identified by computed tomography scan or magnetic resonance imaging underwent extrapleural pneumonectomy followed by combination chemotherapy and radiotherapy. RESULTS: The cohort included 27 women and 93 men with a mean age of 56 years. Operative mortality rate was 5.0%, with a major morbidity rate of 22%. Overall survival rates were 45% at 2 years and 22% at 5 years. Two and 5-year survival rates were 65% and 27%, respectively, for patients with epithelial cell type, and 20% and 0%, respectively, for patients with sarcomatous or mixed histology tumors. Nodal involvement was a significant negative prognostic factor. Patients who were node negative with epithelial histology had 2- and 5-year survival rates of 74% and 39%, respectively. Involvement of margins at time of resection did not affect survival, except in the case of full-thickness, transdiaphragmatic invasion. Classification on the basis of a revised staging system stratified median survivals, which were 22, 17, and 11 months for stages I, II, and III, respectively (p = 0.04). CONCLUSIONS: Extrapleural pneumonectomy with adjuvant therapy is appropriate treatment for selected patients with malignant mesothelioma selected using a revised staging system.     

Preoperative assessment and surgical indication for malignant pleural mesothelioma

The standard surgical procedure for patients with malignant pleural mesothelioma (MPM) is extrapleural pneumonectomy (EPP). However, high morbidity and mortality rates have been reported in patients who received EPP, whereas survival rates after EPP remain unsatisfactory. Thus, a carefully and precise preoperative assessment to select appropriate candidates for EPP is essential in patients with MPM, and we conducted a surgical staging with laparoscopy, mediastinoscopy and contralateral thoracoscopy for potentially resectable MPM patients. Among 5 consective patients who received the preoperative surgical staging during past 10 months, 1 patient was judged not to be a surgical candidate due to the presence of contralateral pleural metastasis. In conclusion, this surgical staging is a useful preoperative evaluation to prevent an unnecessary operation.     

Pleural mesotheliomas. Current knowledge]

Pleural mesotheliomas are rare primary tumors of the pleura. Three groups are classified under the term mesothelioma: 1) benign pleural mesothelioma for which complete surgical treatment is curative with a good prognosis; 2) localized malignant mesothelioma which is a fibrosarcoma, best treated by wide en-bloc resection; 3) diffuse malignant mesothelioma which is mainly of epithelial type. The prognosis is poor in spite of all therapeutic approaches using irradiation, chemotherapy and surgery, alone or in combination, and long-term survivals are uncommon. Two surgical approaches are currently available for patients with diffuse mesothelioma: radical extrapleural pneumonectomy and pleurectomy/decortication. Rigorous combinations of multimodality therapy are needed to improve local control and survival.     

A phase II trial of surgical resection and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma

BACKGROUND: Surgical resection of malignant pleural mesothelioma is reported to have up to an 80% rate of local recurrence. We performed a phase II trial of high-dose hemithoracic radiation after complete resection to determine feasibility and to estimate rates of local recurrence and survival. METHODS: Patients were eligible if they had a resectable tumor, as determined by computed tomographic scanning, and adequate cardiopulmonary function for extrapleural pneumonectomy or pleurectomy/decortication. After complete resection, patients received hemithoracic radiation (54 Gy) and then were followed up with serial computed tomographic scanning. RESULTS: From 1995 to 1998, 88 patients (73 men and 15 women; median age, 62.5 years) were entered into the study. The operations performed included 62 extrapleural pneumonectomies (70%) and 5 pleurectomies/decortications; procedures for exploration only were performed in 21 patients. Seven (7.9%) patients died postoperatively. Adjuvant radiation administered to 57 patients (54 undergoing extrapleural pneumonectomy and 3 undergoing pleurectomy/decortication) at a median dose of 54 Gy was well tolerated (grade 0-2 fatigue, esophagitis), except for one late esophageal fistula. The median survival was 33.8 months for stage I and II tumors but only 10 months for stage III and IV tumors (P =.04). For the patients undergoing extrapleural pneumonectomy, the sites of recurrence were locoregional in 2, locoregional and distant in 5, and distant only in 30. CONCLUSION: Hemithoracic radiation after complete surgical resection at a dose not previously reported is feasible. This approach dramatically reduces local recurrence and is associated with prolonged survival for early-stage tumors. Stage III disease has a high risk of early distant relapse and should be considered for trials of systemic therapy added to this regimen of resection and radiation.     

The effect of extent of local resection on patterns of disease progression in malignant pleural mesothelioma

Background

We sought to determine whether or not there are differences in disease progression after radical or nonradical (debulking) surgical procedures for malignant pleural mesothelioma.

Methods

Over a 49-month period, 132 patients with malignant pleural mesothelioma underwent surgery. Fifty-three underwent extrapleural pneumonectomy and 79 underwent nonradical procedures. Time to evidence of clinical disease progression was recorded, as was the site(s) of that disease.

Results

One-hundred nineteen patients were evaluable, of which 59% (22 radical; 48 nonradical) had disease progression. Overall 30-day mortality was 8.5% (7.5% radical; 9% nonradical). The median time to overall disease progression was considerably longer after extrapleural pneumonectomy than debulking surgery (319 days vs 197 days, p = 0.019), as was the time to local disease progression (631 days vs 218 days, p = 0.0018). There was no preponderance of earlier stage disease in the radical surgery group. There was a trend toward prolonged survival in those undergoing radical surgery, but no significant difference between the groups (497 days vs 324 days, p = 0.079). In those who had extrapleural pneumonectomy, time-to-disease progression significantly decreased with N2 disease compared with N0/1 involvement (197 days vs 358 days, p = 0.02).

Conclusions

Extrapleural pneumonectomy may be preferable to debulking surgery in malignant pleural mesothelioma to delay disease progression and give greater control of local disease. Involvement of N2 nodes is associated with accelerated disease progression and is therefore a contraindication to extrapleural pneumonectomy.     

Extrapleural pneumonectomy, chemotherapy, and radiotherapy in the treatment of diffuse malignant pleural mesothelioma

Malignant pleural mesothelioma has been considered a uniformly fatal disease associated with a median survival of 4 to 18 months. Extrapleural pneumonectomy alone has proved disappointing in the treatment of this disease, as have chemotherapy and radiotherapy. From 1980 to 1990, 31 patients with pleural mesothelioma underwent multimodality therapy that included extrapleural pneumonectomy with resection of the pericardium and diaphragm. The age of the patients was 53.4 +/- 8.6 years; 26 were male. All patients had the pathologic diagnosis reviewed before treatment. At thoracotomy six patients had residual (unresectable) gross disease, and in 23 there was histologic evidence of disease at the resection margin. The perioperative morbidity and mortality rates were 19% and 6%, respectively. The mean length of hospital stay for the 29 patients who survived the operation was 10.9 +/- 3.5 days. Postoperatively 26 patients received cyclophosphamide, doxorubicin, and cis-platinum chemotherapy with or without radiotherapy. The survival rates were 70% at 1 year and 48% at 2 years. Trends toward improved survival in the patients with complete resections approached but did not reach statistical significance. These data suggest that this multimodality protocol can be administered with acceptable morbidity and mortality. Prospective trials are justified to further clarify the role of this approach.     

Extrapleural pneumonectomy for diffuse, malignant mesothelioma

Extrapleural pneumonectomy for malignant mesothelioma is a radical procedure that entails en bloc removal of the parietal pleura, lung, pericardium, and diaphragm. Minimal tumor remains after this procedure; palliation and occasional long-term survival may be achieved in properly selected patients. Extrapleural pneumonectomy for diffuse, malignant mesothelioma was done in 33 patients (27 male and 6 female) with 18 procedures on the left side and 15 on the right. There was a history of exposure to asbestos in 16 (48%) of the patients. Histological classification revealed that 20 tumors were epithelial, 10 were mixed, and 3 were sarcomatous. Good palliation, defined as survival for 24 months with a return to fairly normal activities, was obtained in 8 patients (24%) and survival for 36 months was achieved in 5 patients. Three patients died of the disease at 59 months, 60 months, and 82 months. There were 3 operative deaths (9.1%), and serious postoperative complications occurred in 8 patients (24%). Postoperative adjunctive therapy consisting of chemotherapy or irradiation or both was given to approximately one-half of the patients. These findings indicate that extrapleural pneumonectomy for malignant mesothelioma can be done with an acceptable morbidity and mortality. Palliation is achieved in 24% of patients, and there may be an occasional long-term survivor.     

The role of surgery in the treatment of malignant pleural mesothelioma

The role of surgery in the treatment of diffuse pleural malignant mesothelioma is controversial. The procedures proposed to date are extrapleural pneumonectomy, pleurectomy, and thoracoscopy. External radiation or intraoperative implantation of radioisotopes, chemotherapy and intrapleural treatment with various different agents are also considered as adjuvant therapy. Patient selection, postoperative morbidity and mortality and survival rates are discussed. Our personal series of 72 diffuse pleural malignant mesotheliomas is described: 29 had a palliative operation while 43 underwent radical surgery consisting in 24 extrapleural pneumonectomies and 19 pleurectomies.     

Surgical Management of Malignant Mesothelioma

The surgical management of 18 patients diagnosed as having malignant mesothelioma is reviewed. Of these patients, 7 received limited treatment—pleurectomy or biopsy. The mean survival was 10 months, and no patient was disease-free at time of death. The other 11 patients were treated by radical extrapleural pneumonectomy. There were 2 long-term, disease-free survivors at 2 and 4 years. Mean survival for the entire group was 15 months, but most patients received good palliation following tumor removal.Surgical procedures for removal of malignant mesothelioma can be accomplished safely and without major morbidity. When possible, radical extrapleural pneumonectomy affords the best palliation and the only opportunity for cure.     

Malignes Pleuramesotheliom

The role of surgical resection per se and the type of surgery in the management of multimodality treated malignant pleural mesothelioma remains controversial. Patient selection for either extrapleural pneumonectomy or radical pleurectomy depends not only on the cardiopulmonary status of the patient, tumor stage and intraoperative findings but is also strongly influenced by surgeons’ preference, experience and philosophy. The aim of this review is to compare extrapleural pneumonectomy and radical pleurectomy with regard to surgical technique, morbidity, mortality and survival.     

Pleurectomy/decortication plus chemotherapy: outcomes of 40 cases of malignant pleural mesothelioma

Malignant pleural mesothelioma still has a dismal prognosis. Despite good patient selection and a multimodality approach, local disease control remains a problem. Whether submitted to pleurectomy/decortication or to extrapleural pneumonectomy, disease progression occurred in all 40 patients in this study. The role of radio-chemotherapy remains uncertain. Between 1985 and 2002, 40 patients underwent pleurectomy/decortication in combination with intracavitary chemotherapy. Pleurectomy was performed to remove all gross tumour, or to achieve significant debulking. Partial or total pleurectomy of the visceral pleura depended on the extent of the tumour. Systemic chemotherapy was administered when disease progression occurred. All 40 patients had disease progression, due in all cases to local recurrence. The Kaplan-Meyer method was used for statistical evaluation. Treatment was relatively well tolerated and quality of life satisfactory. Until disease progression, no important chest pain, pleural effusion, or dyspnoea occurred. Overall survival was 28% at 2 years and 17% at 3 years. Histological sub-type is the only significant prognostic factor for survival. Low morbidity and mortality and good quality of life after treatment make pleurectomy/decortication with intracavitary and systemic chemotherapy not only a radical approach in early stages, but also a good palliative treatment in advanced malignant pleural mesothelioma, especially in patients who are unsuitable for extrapleural pneumonectomy.