Mesothelioma and radical multimodality therapy: who benefits? [Review]

Curative resection of a well-differentiated papillary mesothelioma of the pericardium.

Trials in malignant mesothelioma. LCSG 851 and 882. [Review]

Operation and intracavitary photodynamic therapy for malignant pleural mesothelioma: a phase II study.

Prognostic factors and survival in malignant pleural mesothelioma.

Malignant pleural mesothelioma. Extrapleural pneumonectomy and pleurectomy. [Review]

A phase II trial of pleurectomy/decortication followed by intrapleural and systemic chemotherapy for malignant pleural mesothelioma.

Prognostic factors of malignant mesothelioma of the pleura.

Malignant pleural mesothelioma. Multivariate analysis of prognostic factors on 113 patients.

Pleurectomy/decortication and adjuvant therapy for malignant mesothelioma.

Extrapleural pneumonectomy in the setting of a multimodality approach to malignant mesothelioma.

Survival of asbestos insulation workers with mesothelioma.

Diagnostic and therapeutic strategy in malignant pleural mesothelioma.

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

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

Pleurectomy for mesothelioma.

Year: 1995

Mesothelioma and radical multimodality therapy: who benefits? [Review]
Chest. 107(6 Suppl.):345S-350S, 1995 Jun. United States
Sugarbaker DJ. Jaklitsch MT. Liptay MJ.
Division of Thoracic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Abstract
The incidence of malignant pleural mesothelioma is increasing. Untreated, patients with this disease experience a rapid and horrendous clinical decline. Surgery plays a role in the diagnosis, staging, and treatment of this malignancy. Surgery, chemotherapy, and radiotherapy alone have been unable to achieve major improvements in survival for most patients. More recent phase II trials suggest that surgery, at one time a purely palliative approach, may have a potentially curative role when used in combination with chemotherapy and radiotherapy.

Year: 1995

Curative resection of a well-differentiated papillary mesothelioma of the pericardium
Archives of Pathology & Laboratory Medicine. 119(3):266-7, 1995 Mar. United States
Sane AC. Roggli VL
Department of Pulmonary/Critical Care Medicine, Duke University Medical Center, Durham, NC 27710.

Abstract
A 27-year-old woman presented with fatigue and dyspnea and was found to have a 2 x 4-cm mass in the pericardium, which was resected. Histologic examination demonstrated a well-differentiated papillary mesothelioma of the pericardium. Postoperatively, she received radiation therapy and had no evidence of recurrence 28 years later. It is extremely rare for this indolent variant of mesothelioma to arise in the pericardium.

Year: 1994

Trials in malignant mesothelioma. LCSG 851 and 882. [Review]
Chest. 106(6 Suppl.):359S-362S, 1994 Dec. United States
Rusch VW.
Thoracic Surgery Service, Memorial Sloan-Kettering Cancer Center, New York 10021.

Abstract
In 1985 the Lung Cancer Study Group (LCSG) initiated clinical trials in malignant pleural mesothelioma because LCSG member institutions had access to large numbers of patients and had significant experience treating this uncommon cancer. The first trial, LCSG 851, defined the patient population seen by the LCSG, and the feasibility of performing surgical resection by extrapleural pneumonectomy in a multi-institutional setting. Of 83 patients entered on this study from September 1985 to June 1988, only 20 could undergo an extrapleural pneumonectomy, and 3 of 20 patients died postoperatively. This experience prompted the LCSG to explore combining a potentially less morbid operation, pleurectomy/decortication, with adjuvant therapy. The results of another LCSG trial (LCSG 861) and of a small single institutional pilot study demonstrated the feasibility of intrapleural cisplatin-based chemotherapy, and led to the development of LCSG 882, which combined pleurectomy/decortication with postoperative intrapleural, and subsequent systemic, cisplatin-based chemotherapy. This study was not completed because of discontinuation of funding for the LCSG. However, a single-institution phase 2 trial of very similar design has subsequently shown the feasibility of this combined modality approach.

Year: 1994

Operation and intracavitary photodynamic therapy for malignant pleural mesothelioma: a phase II study.
Annals of Thoracic Surgery. 58(4):995-8, 1994 Oct. United States
Takita H. Mang TS. Loewen GM. Antkowiak JG. Raghavan D. Grajek JR. Dougherty TJ.
Division of Thoracic Surgery and Oncology (Department of Surgical Oncology), New York State Department of Health, Roswell Park Cancer Institute, Buffalo.

Abstract
From April 1991 to May 1993, 23 patients entered a phase II clinical study of surgical resection and adjuvant intracavitary photodynamic therapy for malignant pleural mesothelioma. Two days preoperatively, patients received an intravenous injection of 2 mg/kg of the photosensitizer Photofrin. Six patients underwent a pleuro-pneumonectomy, and 15 patients a pleurectomy, after which intracavitary photodynamic therapy was administered. A total light energy dose of 20 to 25 J/cm2 was given. In 2 patients the tumor was unresectable due to intrapericardial invasion. Postoperative complications were noted in more than 50 percent of patients; 2 patients died of postoperative complications. Postoperative survival was analyzed according to intraoperative staging proposed by the American Joint Committee for Cancer Staging, published in 1992. The overall estimated median survival is 12 months; that of stage III and IV patients is 7 months. Five patients with stage I and II diseases (who had grossly complete resection by pleurectomy) are alive, disease-free, for 11, 17, 18, 21, and 33 postoperative months. Intraoperative staging is important in carrying out further clinical studies of malignant pleural mesothelioma.

Year: 1994

Prognostic factors and survival in malignant pleural mesothelioma.
European Respiratory Journal. 7(6):1035-8, 1994 Jun. Denmark
Van Gelder T. Damhuis RA. Hoogsteden HC.
Dept of Internal Medicine I, University Hospital Rotterdam, The Netherlands.

Abstract
Malignant pleural mesothelioma is a lethal disease and little is known about prognostic factors. The prognostic significance of age, stage of disease, gender and histological subtype was studied in 167 new cases of cytologically (15%) or histologically (85%) proven malignant pleural mesothelioma in the Rotterdam area, during the period 1987-1989. Median survival of all patients was 242 days. Univariate analysis identified age, stage and histopathological subtype as significant prognostic factors, which was confirmed in multivariate analysis. Median survival rates for patients < 65, 65-74 and > or = 75 yrs were 359, 242 and 131 days, respectively. Patients with Stage I disease had a median survival of 359 days compared to 147 and 112 days, respectively, for patients with Stage II and the combination of Stages III and IV. Mixed histopathological subtype (190 days) was less favorable than sarcomatous (207 days) and epithelial (252 days) subtypes. Using a Cox proportional hazard model in patients with malignant pleural mesothelioma, age, histological subtype and stage were identified as independent prognostic factors. These prognostic factors should be taken into account when starting or evaluating treatment studies.

Year: 1994

Malignant pleural mesothelioma. Extrapleural pneumonectomy and pleurectomy. [Review]
Chest Surgery Clinics of North America. 4(1):113-26, 1994 Feb. United States
Allen KB. Faber LP. Warren WH.
Department of Surgery, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois.

Abstract
Diffuse malignant pleural mesothelioma is an uncommon, uniformly fatal malignancy. Controversy continues to surround the optimal surgical procedure, both extrapleural pneumonectomy or pleurectomy, which should be utilized in conjunction with post-operative chemotherapy and/or radiotherapy. This retrospective study reviews a single institution's experience with extrapleural pneumonectomy and pleurectomy in the multimodality treatment of diffuse malignant pleural mesothelioma.

Year: 1994

Journal of Clinical Oncology. 12(6):1156-63, 1994 Jun. United States
A phase II trial of pleurectomy/decortication followed by intrapleural and systemic chemotherapy for malignant pleural mesothelioma.
Rusch V. Saltz L. Venkatraman E. Ginsberg R. McCormack. P. Burt M. Markman M. Kelsen D.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.

Abstract
PURPOSE: This study investigated the feasibility of a novel approach to the treatment of malignant pleural mesothelioma by combining surgical resection with immediate postoperative intrapleural chemotherapy and subsequent systemic chemotherapy.
PATIENTS AND METHODS: Patients with biopsy-proven, resectable malignant pleural mesothelioma underwent pleurectomy/decortication immediately followed by intrapleural chemotherapy with cisplatin 100 mg/m2 and mitomycin 8 mg/m2. Systemic chemotherapy was started 3 to 5 weeks postoperatively and included cisplatin 50 mg/m2 on days 1, 8, 15, 22, 36, 43, 50, and 57, and mitomycin 8 mg/m2 on days 1 and 36. Patients were then monitored by serial chest and abdominal computed tomographic (CT) scans every 3 months until death or for a minimum of 18 months, whichever occurred first.
RESULTS: Of 36 patients entered onto the study, 28 had pleurectomy/decortication and intrapleural chemotherapy. There was one postoperative death, and two episodes of grade 4 renal toxicity after intrapleural chemotherapy. The 23 patients who also had systemic chemotherapy received a median of 80% and 87% of the planned total cisplatin and mitomycin doses, respectively. No grade 3 or 4 toxicities were observed. The overall survival rate of the 27 patients who were originally candidates for systemic chemotherapy was 68% at 1 year and 40% at 2 years, with a median survival duration of 17 months. Locoregional disease was the most common form of relapse (16 of 20 patients).
CONCLUSION: This short but aggressive combined modality regimen was generally well tolerated, but should not be used outside of a protocol setting because of the potential for serious toxicity. Overall survival was as good or better than with previously reported multimodality approaches, but other strategies are needed to improve local control.

Year: 1993

Prognostic factors of malignant mesothelioma of the pleura
Comment in: Cancer 1994 Feb 1;73(3):755 Cancer. 72(2):410-7, 1993 Jul 15. United States
De Pangher Manzini V. Brollo A. Franceschi S. De Matthaeis M. Talamini R. Bianchi C.
Department of General Medicine, Hospital of Monfalcone, Italy.

Abstract
BACKGROUND. Pleural mesothelioma is a rare condition with a poor prognosis. The area of Monfalcone, North East Italy, provided a unique opportunity to study the disease because of its past heavy exposure to asbestos in local harbors and shipyards and its high necropsy rates.
METHODS. The effects of various patient and tumor characteristics on survival were evaluated in 80 patients (73 males and 7 females; median age, 69) of histologically or cytologically confirmed malignant mesothelioma of the pleura. These patients were examined between October 1979 and October 1991 at the General Hospital of Monfalcone in the Friuli-Venezia Giulia region. Substantial exposures to asbestos were identified in 79 patients.
RESULTS. Median survival rate was 13 months (range, 2-44 months), and overall 2- and 5-year survival rates were 23% and 0%, respectively. The factors that exerted a significant favorable influence on survival were as follows: (1) age younger than 65; (2) performance status less than or equal to one; (3) lack of less than or equal to 10% weight loss at any time; (4) Stages I and II; (5) epithelial or mixed histologic type; and (6) presence of pleural fluid with mesothelial cells but without neoplastic cells. When these factors were introduced in a Cox proportional hazard model, age, stage, and histologic type were the only independent prognostic factors. The increased hazards for patients, ages 65-74 (as compared to < 65), and for patients with sarcomatous histologic type (as compared to epithelial type) were 2.6 (95% confidence interval [CI], 1.2-5.7) and 4.5 (95% CI, 1.6-12.8).
CONCLUSIONS. Survival rate in 24 untreated patients (median, 10 months) and 56 patients variously treated (median, 15 months) did not differ significantly. The availability of large portions of tumor specimens for histologic examinations in 77 of 80 patients, chiefly from high necropsy rate, strengthens the value of the present analysis of prognostic factors.

Year: 1993

Malignant pleural mesothelioma. Multivariate analysis of prognostic factors on 113 patients.
Anticancer Research. 13(3):683-9, 1993 May-Jun. Greece
Fusco V. Ardizzoni A. Merlo F. Cinquegrana A. Faravelli B. De Palma M. Chessa L. Nicolo G. Serra M. Capaccio A. et al.
Division of Medical Oncology, Istituto Nazionale per la Ricera sul Sancro, Genoa, Italy.

Abstract
We report on clinical features of 113 cases of pathologically confirmed Malignant Pleural Mesothelioma, observed in Genoa (Italy) between 1979 and 1985. Overall median survival was 10 months. Among the pretreatment variables studied (age, sex, asbestos exposure, pathological type, chest pain and dyspnea at the time of diagnosis), the only one of prognostic value in the univariate analysis was the histological subtype: median survivals were 12, 7 and 4 months for the patients in the epithelial, mixed, and fibrosarcomatous groups, respectively (p = 0.0012). A multivariate analysis confirmed the independent predictive power of the histotype (p = 0.0022). A review of literature data concerning prognostic factors in Malignant Pleural Mesothelioma is presented.

Year: 1993

Pleurectomy/decortication and adjuvant therapy for malignant mesothelioma
Chest. 103(4 Suppl.):382S-384S, 1993 Apr. United States
Rusch VW.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York.

Abstract
Malignant mesothelioma is an uncommon and usually fatal cancer, for which there is no standard treatment. However, surgical resection remains the mainstay of treatment because of the inability to treat the entire hemithorax effectively with radiation and the lack of effective chemotherapy drugs. Extrapleural pneumonectomy is the only technically feasible operation for patients who have bulky local tumor and chronic entrapment of the lung, but pleurectomy/decortication is associated with a lower operative morbidity and mortality, and seems to lead to an equally good survival in patients who have early-stage disease. Because of the high risk of local recurrence after surgical resection by either extrapleural pneumonectomy or pleurectomy/decortication, efforts have been directed at developing effective adjuvant treatment. Radiation given postoperatively after pleurectomy/decortication has led to a minimal improvement in survival and to significant side effects. Adjuvant chemotherapy is considered investigational but is currently being evaluated in a clinical trial using high-dose intrapleural and systemic chemotherapy after pleurectomy/decortication. Additional well-designed prospective trials are needed to alter the dismal outcome of this disease.

Year: 1993

Extrapleural pneumonectomy in the setting of a multimodality approach to malignant mesothelioma.
Chest. 103(4 Suppl.):377S-381S, 1993 Apr. United States
Sugarbaker DJ. Mentzer SJ. DeCamp M. Lynch TJ Jr. Strauss GM.
Harvard Medical School, Brigham and Women's Hospital, Boston 02115.

Abstract
The use of extrapleural pneumonectomy in a multimodality treatment setting for malignant pleural mesothelioma is described, presenting first the right-sided approach and then the left-sided. This technique used in a multimodality approach with CAP chemotherapy (cyclophosphamide 600 mg/m2, doxorubicin 60 mg/m2, cisplatin 75 mg/m2) 5 cycles at 3-week intervals, and radiotherapy (55 Gy radiation to sites of previous bulky disease or residual disease) to treat 44 patients with malignant pleural mesothelioma resulted in improved operative mortality and decreased length of hospital stay.

Year: 1992

Survival of asbestos insulation workers with mesothelioma.
British Journal of Industrial Medicine. 49(10):732-5, 1992 Oct. England
Ribak J. Selikoff IJ.
Environmental Sciences Laboratory, Mount Sinai School of Medicine, City University of New York.

Abstract
Malignant mesothelioma is a lethal disease. It is rare in the general population; however, workers exposed to asbestos suffer significant burdens of the neoplasm. The survival time of 457 consecutive fatal cases of pleural and peritoneal mesothelioma that occurred among 17,800 asbestos insulation workers observed prospectively from 1 January 1967 to 1 January 1987 was studied. Mean survival time from initial presentation of the disease to death was 11.4 months for the pleural mesothelioma patients compared with 7.4 months for the peritoneal group. This difference was statistically significant. Mean survival time from diagnosis to death was shorter for both groups of patients: 8.4 months for pleural mesothelioma v 5.8 months for the peritoneal cases. In conclusion, survival time in mesothelioma patients is short; most die within a year from the onset of the initial symptoms. No effective therapy is yet available.

Year: 1992

Diagnostic and therapeutic strategy in malignant pleural mesothelioma
Comment in: Eur J Cardiothorac Surg 1992; 6(3):164 European Journal of Cardio-Thoracic Surgery. 5(9):466-72; discussion 473, 1991. Germany
Branscheid D. Krysa S. Bauer E. Bulzebruck H. Schirren J.
Department of Thoracic Surgery, Rohrbach Hospital, Heidelberg, FRG.

Abstract
We retrospectively analyzed 301 patients with diffuse malignant pleural mesothelioma (235 male, 66 female; median age 59 years). Prognosis depended significantly on patient age, evidence of pain, loss of weight, tumor cell type, stage, local and distant metastasis, involvement of peritoneum and surgical treatment. The overall median survival rate was 238 days, after extended pleuropneumonectomy 284 days, and after decortication 315 days - significantly better than the prognosis in patients without surgical treatment or exploratory thoracotomy. Pleuropneumonectomy should only be considered in young patients with an epithelial cell-type tumor (possibly with adjuvant chemotherapy). Decortication seems nowadays to be the treatment of choice.

Year: 1993

Extrapleural pneumonectomy, chemotherapy, and radiotherapy in the treatment of diffuse malignant pleural mesothelioma.
Comment in: J Thorac Cardiovasc Surg 1993 May; 105(5):943-4 Journal of Thoracic & Cardiovascular Surgery. 102(1):10-4; discussion 14-5, 1991 Jul. United States
Sugarbaker DJ. Hewer EC. Lee TH. Couper G. Mentzer S. Corson JM. Collins JJ Jr. Shemin R. Pugatch R. Weissman L. et al.
Division of Thoracic Surgery, Brigham & Women's Hospital, Boston, MA 02115

Abstract
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 cisplatinum 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.

Year: 1991

The role of extrapleural pneumonectomy in malignant pleural mesothelioma. A Lung Cancer Study Group trial
Comment in: J Thorac Cardiovasc Surg 1991 Jul; 102(1):153, Comment in: J Thorac Cardiovasc Surg 1993 May; 105(5):943-4 Journal of Thoracic & Cardiovascular Surgery. 102(1):1-9, 1991 Jul. United States
Rusch VW. Piantadosi S. Holmes EC.
Memorial Sloan-Kettering Cancer Center, New York, N.Y.

Abstract
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 multi-institutional 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 post-resection 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 non-surgical 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 non-surgical 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.

Year: 1991

Pleurectomy for mesothelioma.
Comment in: Med J Aust 1991 Jun 3;154(11):783-4, Comment in: Med J Aust 1991 Dec 2-16;155(11- 12):855 Medical Journal of Australia. 154(7):455-7, 460, 1991 Apr 1. Australia
Brancatisano RP. Joseph MG. McCaughan BC.
Department of Surgery, Repatriation General Hospital Concord, NSW.

Abstract
OBJECTIVE: To assess the effectiveness and safety of parietal pleurectomy in establishing a tissue diagnosis and controlling pleural fluid accumulation in patients with pleural mesothelioma, and to assess the success of this procedure in effecting palliation.
DESIGN AND SETTING: Fifty consecutive patients with pleural mesothelioma who underwent thoracotomy at the cardiothoracic units at Concord and Royal Prince Alfred Hospital were reviewed retrospectively. The male:female ratio was 4:1 and the mean age was 63 years. In only 11 of the 50 patients was a tissue diagnosis of mesothelioma made before surgery.
INTERVENTIONS: At thoracotomy, subtotal parietal pleurectomy was performed in 45 of the 50 patients. In two patients biopsy alone was performed and three patients were treated by a chemical pleurodesis only, as pleurectomy was not technically possible. Pulmonary decortication was required in 28 patients to allow full expansion of the underlying lung for effective pleurodesis.
RESULTS: There was one postoperative death. The morbidity rate was 16%. Excluding the patient who died in the postoperative period, the median survival was 16 months, and ranged from three to 54 months, with 21% of patients surviving for more than two years. Only one patient developed a re-accumulation of pleural fluid.
CONCLUSIONS: Pleurectomy, with decortication when required, provides both a tissue diagnosis and effective control of pleural fluid accumulation and therefore excellent palliation in patients with pleural mesothelioma. We advocate early thoracotomy in these patients.