Moore AJ, Parker RJ, Wiggins J.

Department of Respiratory Medicine, Wexham Park Hospital, Wexham, Slough, Berkshire, UK. a.moore@ic.ac.uk

Abstract

Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its incidence is increasing, with an expected peak in the next 10-20 years. Pleural malignant mesothelioma is the most common form of mesothelioma. Typical presenting features are those of chest pain and dyspnoea. Breathlessness due to a pleural effusion without chest pain is reported in about 30% of patients. A chest wall mass, weight loss, sweating, abdominal pain and ascites (due to peritoneal involvement) are less common presentations. Mesothelioma is directly attributable to occupational asbestos exposure with a history of exposure in over 90% of cases. There is also evidence that mesothelioma may result from both para-occupational exposure and non-occupational “environmental” exposure. Idiopathic or spontaneous mesothelioma can also occur in the absence of any exposure to asbestos, with a spontaneous rate in humans of around one per million. A combination of accurate exposure history, along with examination radiology and pathology are essential to make the diagnosis. Distinguishing malignant from benign pleural disease can be challenging. The most helpful CT findings suggesting malignant pleural disease are 1) a circumferential pleural rind, 2) nodular pleural thickening, 3) pleural thickening of > 1 cm and 4) mediastinal pleural involvement. Involvement of a multidisciplinary team is recommended to ensure prompt and appropriate management, using a framework of radiotherapy, chemotherapy, surgery and symptom palliation with end of life care. Compensation issues must also be considered. Life expectancy in malignant mesothelioma is poor, with a median survival of about one year following diagnosis.

Hesdorffer ME, Chabot J, DeRosa C, Taub R.

Mesothelioma Applied Research Foundation, Santa Barbara, CA, USA. mhesdorer@curemeso.org

Abstract

Opinion statement: Malignant peritoneal mesothelioma (MPM) is an aggressive neoplasm that rapidly spreads within the confines of the abdominal cavity to involve most accessible peritoneal and omental surfaces. Current treatment options are unsatisfactory, and new approaches are needed. Recent publications have reported improved survival with an intensive loco-regional treatment strategy including cytoreductive surgery (CRS) along with hyperthermic intraperitoneal chemotherapy (HIPEC). We have noted at our institution prolonged survival in selected patients after intensive multimodality treatment. Our most recently reported trial included initial laparatomy with omentectomy, resection of peritoneal implants, and placement of bilateral peritoneal Portacath; repeated courses of intraperitoneal chemotherapy with doxorubicin, cisplatin, and interferon gamma; second-look laparotomy; and intraoperative hyperthermic perfusion with mitomycin and cisplatin, followed by whole abdominal radiation. To date there have been no universally accepted treatments for MPM. Unless referred to a specialty center, patients are routinely treated with pemetrexed and cisplatin which has been shown to increase survival in pleural mesothelioma.

Kent M, Rice D, Flores R.

Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

Abstract

Opinion statement: The clinical presentation of malignant pleural mesothelioma (MPM) is nonspecific. The process to obtain the correct diagnosis can be challenging and requires a high index of suspicion. Once the diagnosis is made, there is no universally accepted standard of care and treatment decisions are strongly influenced by physician bias. Physicians who see few numbers of patients tend to treat based on symptoms alone by drainage of the pleural effusion and talc pleurodesis, while physicians at several tertiary referral centers tend to take an aggressive multimodality approach incorporating surgical resection, chemotherapy, and radiation. The primary goal of surgery in this setting is the resection of all gross disease. The choice of operation, extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D), depends on disease stage, pulmonary function, philosophy of the treating physician, and type of planned adjuvant therapy.

Nakas A, Trousse DS, Martin-Ucar AE, Waller DA.

Department of Thoracic Surgery, Glenfield Hospital, Groby Road, Leicester LE3 9QA, United Kingdom.

Abstract

Objective: To identify the optimal debulking procedure in patients with malignant pleural mesothelioma who are not suitable for extrapleural pneumonectomy (EPP).

Methods: We reviewed 102 consecutive patients (93 male; 9 female, mean age 63 years) who were not suitable for EPP because of either advanced tumour stage or suboptimal fitness. Patients underwent either a non-radical tumour decortication to obtain lung expansion (group NR) or latterly a radical pleurectomy/decortication to obtain macroscopic tumour clearance (group R). We analysed the comparative perioperative courses and long-term survival.

Results: The two groups were similar for age and gender distribution but epithelioid type was more predominant in group R: 78% compared to 55% epithelioid in group NR. Thirty-day mortality was similar (5.9% in group R and 9.8% in the group NR, p = 0.36) but 90-day mortality was significantly higher in the group NR (29.4% vs 9.8% in group R, p = 0.012). More patients in group R received adjuvant chemotherapy (65% vs 28%, p = 0.000) and radiotherapy (65% vs 26%, p = 0.000). Median survival for all cell types was significantly higher in group R (15.3 months vs 7.1 months, p < 0.000). Group R survival rates at 1, 2, 3 and 4 years were 53, 41, 25 and 13%, respectively while for group NR they were 32, 9.6, 2 and 0%, respectively. For epithelioid cell type there was still a significant median survival advantage in group R (25.4 months vs 10.2 months, p < 0.000), but there was no difference for sarcomatoid (9.3 months vs 3.2 months, p = 0.16) or biphasic cell types (9.4 months vs 7 months, p = 0.38).

Conclusion: If a patient with epithelioid MPM is fit enough to tolerate a thoracotomy then macroscopic clearance of the tumour is the preferred option as part of a multimodality regime including chemotherapy.

Keywords: Malignant pleural mesothelioma; Radical surgery; Pleurectomy/decortication

Hasegawa S, Tanaka F.

Department of Thoracic Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan, hasegawa@hyo-med.ac.jp.

Abstract

Malignant pleural mesothelioma (MPM) is associated with a poor prognosis; and to make things worse, its incidence is increasing throughout the world. Surgical management of MPM is comprised of two aspects: diagnosis and resection. Surgical biopsy with thoracoscopy provides a higher yield but a higher rate of tumor cell seeding than blind biopsy. In some surgical cases, extended surgical staging with mediastinoscopy, laparoscopy, and contralateral thoracoscopy is required for the preoperative evaluation for resectablity. There are two types of surgical resection for MPM. Pleurectomy/decortication (P/D) involves removal of as much of the visceral, parietal, and pericardial pleura and the tumor as possible without removing the underlying lung. Because P/D is less radical but less invasive compared to extrapleural pneumonectomy (EPP), it can be tolerated by poor-risk patients. EPP comprises en bloc resection of visceral, parietal, and pericardial pleura and adjacent components such as ipsilateral lung, pericardium, and diaphragm, without opening the pleural cavity. EPP was considred a highly dangerous procedure with a surgical mortality of more than 30% decades ago, but its current operative mortality/morbidity rates are 4%-9% and 60%, respectively. As macroscopic complete resection is the primary goal of surgery for MPM because of its diffuse intrapleural growth, surgical resection alone is associated with poor survival. In this context, combination therapy with surgery plus chemotherapy and/or radiotherapy is currently considered the standard treatment for patients with respectable MPM. A national survey of EPP was conducted recently in Japan, and a few multicenter clinical trials will start soon

Keywords: Malignant pleural mesothelioma – Pleurectomy – Extrapleural pneumonectomy – Chemotherapy – Multimodality treatment

Sienel W, Kirschbaum A, Passlick B.

Abteilung Thoraxchirurgie, Chirurgische Universitätsklinik, Universitätsklinikum Freiburg.

Abstract

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 (≤ cT3, < pN2, cM0), mediastinoscopy is recommended in addition to computed tomography of the chest and upper abdomen. Currently, neoadjuvant chemotherapy with pemetrexed and cisplatin followed by extrapleural pneumonectomy and postoperative radiotherapy is claimed to afford the best treatment results. We have treated 17 patients with such a regimen and achieved a 3-year survival rate of 76 % so far. During the follow-up duration of 23 months, 3 patients (18 %) developed distant metastasis and one (6 %) a mediastinal local recurrence. Multimodal therapy of malignant pleural mesothelioma including extrapleural pneumonectomy should only be performed in specialised centres for thoracic surgery where uncomplicated interdisciplinary communication is the rule and which provide the required expertise in patient selection, operative technique and postoperative care.

Keywords: malignant pleural mesothelioma – multimodal therapy – trimodal therapy – interdisciplinary cooperation – extrapleural pneumonectomy – pemetrexed

Batirel HF, Metintas M, Caglar HB, Yildizeli B, Lacin T, Bostanci K, Akgul AG, Evman S, Yuksel M.

Marmara University Hospital, Department of Thoracic Surgery, Istanbul, Turkey. hbatirel@marmara.edu.tr

Abstract

Introduction: Multimodality treatment has achieved significant success in local control and treatment of early-stage malignant pleural mesothelioma patients. However, its favorable effect on survival is questionable.

Methods: We have instituted a trimodality treatment protocol consisting of extrapleural pneumonectomy, adjuvant high-dose (54 Gy) hemithoracic irradiation, and platin-based chemotherapy in a multi-institutional setting. Preoperative pulmonary function tests, echocardiogram, chest computed tomography, and magnetic resonance imaging scans were performed in all patients. Twenty patients have been treated with this protocol during 2003-2007. Seventeen had a history of environmental asbestos/erionite exposure. Clinical stages were T1-3N0-2.

Results: Median age was 56 (41-70, 8 female). There was one postoperative mortality (% 5) due to ARDS. Morbidity occurred in 11 patients (% 55). Histology was epithelial in 17, mixed in 2, and sarcomatoid in 1. Sixteen patients underwent extrapleural pneumonectomy. Microscopic margin positivity was present in 14 patients with macroscopic complete resection. Twelve patients completed all three treatments. Median follow-up was 16 months (1-43). Overall median survival was 17 months (24% at 2 years). Eight patients had extrapleural lymph node involvement (internal mammary [n = 3], subcarinal [n = 2], pulmonary ligament [n = 1], diaphragmatic [n = 1], subaortic [n = 1]). There was better survival in patients without lymph node metastasis (24 versus 13 months median survival, p = 0.052). Currently, 7 patients are alive, 6 without recurrence, and 2 patients at 40 and 45 months.

Conclusions: Trimodality treatment in malignant pleural mesothelioma seems to prolong survival in patients without lymph node metastasis. Novel techniques are needed for preoperative assessment of extrapleural lymph nodes.

Ribi K, Bernhard J, Schuller JC, Weder W, Bodis S, Jörger M, Betticher D, Schmid RA, Stupp R, Ris HB, Stahel RA; for the Swiss Group for Clinical Cancer Research (SAKK).

Swiss Group for Clinical Cancer Research (SAKK) Coordinating Center, Effingerstr. 40, CH-3008 Bern, Switzerland.

Abstract

Background: In patients with malignant pleural mesothelioma undergoing a multimodality therapy, treatment toxicity may outweigh the benefit of progression-free survival. The subjective experience across different treatment phases is an important clinical outcome. This study compares a standard with an individual quality of life (QoL) measure used in a multi-center phase II trial.

Patients and methods: Sixty-one patients with stage I–III technically operable pleural mesothelioma were treated with preoperative chemotherapy, followed by pleuropneumonectomy and subsequent radiotherapy. QoL was assessed at baseline, at day 1 of cycle 3, and 1, 3 and 6 months post-surgery by using the Rotterdam Symptom Checklist (RSCL) and the Schedule for the Evaluation of Quality of Life-Direct Weighting (SEIQoL-DW), a measure that is based on five individually nominated and weighted QoL-domains.

Results: Completion rates were 98% (RSCL) and 92% (SEIQoL) at baseline and 98%/89% at cycle 3, respectively. Of the operated patients (N = 45) RSCL and SEIQoL were available from 86%/72%, 93%/74%, and 94%/76% at months 1, 3, and 6 post-surgery. Average assessment time for the SEIQoL was 24 min compared to 8 min needed for the RSCL. Median changes from baseline indicate that both RSCL QoL overall score and SEIQoL index remained stable during chemotherapy with a clinically significant deterioration (change ≥ 8 points) 1 month after surgery (median change of −66 and −14 for RSCL and SEIQoL, respectively). RSCL QoL overall scores improved thereafter, but remained beneath baseline level until 6 months after surgery. SEIQoL scores improved to baseline-level at month 3 after surgery, but worsened again at month 6. RSCL QoL overall score and SEIQoL index were moderately correlated at baseline (r = .30; p ≤ .05) and at 6-month follow-up (r = .42; p ≤ .05) but not at the other time points.

Conclusion: The SEIQoL assessment seems to be feasible within a phase II clinical trial, but may require more effort from staff. More distinctive QoL changes in accordance with clinical changes were measured with the RSCL. Our findings suggest that the two measures are not interchangeable: the RSCL is to favor when mainly information related to the course of disease- and treatment is of interest.

Keywords: Mesothelioma; Multimodal treatment; Individual quality of life; RSCL; SEIQoL-DW

Aigner C, Hoda MA, Lang G, Taghavi S, Marta G, Klepetko W.

Department of Cardio-Thoracic Surgery, Medical University of Vienna, Waehringer Guertel 18–20, 1090 Vienna, Austria.

Abstract

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.

Keywords: Malignant pleural mesothelioma; Extrapleural pneumonectomy; Pleuropneumonectomy; Multi-modal treatment; MPM; EPP

Hesdorffer ME, Chabot JA, Keohan ML, Fountain K, Talbot S, Gabay M, Valentin C, Lee SM, Taub RN.

Division of Oncology, Columbia University New York, New York, USA. mhesdorffer@curemeso.org

Abstract

Objective: We report a single-institution Phase I or II trial of surgical debulking, intraperitoneal chemotherapy, and immunotherapy followed by whole abdominal radiotherapy in patients with malignant peritoneal mesothelioma.

Methods: Between 1997 and 2000, 27 patients with malignant peritoneal mesothelioma were enrolled: 23 with epithelial subtype and 4 with sarcomatoid or mixed subtype. The treatment regimen consisted of surgical debulking followed by 4 intraperitoneal courses of cisplatin alternating with 4 courses of doxorubicin, 4 doses of intraperitoneal gamma interferon, a second laparotomy with resection of residual disease plus intraoperative intraperitoneal mitomycin and cisplatin heated to 41 degrees C, and finally whole abdominal radiotherapy.

Results: The median overall survival was 70 months with a 3-year survival of 67% (95% confidence interval, 46%-81%). Fourteen patients have died of their disease with a median time to death of 17 months (range, 0.4-71 months) after consenting to treatment. Seven patients are alive without evidence of disease with a median follow-up of 90 months (range, 71-110 months), and 6 are alive with disease with a median follow-up of 86 months (range, 70-106 months). The regimen was well tolerated. There were no patients with Grade III or IV hematological toxicities, 2 patients with Grade III ototoxicity, and 3 patients with Grade III gastrointestinal toxicity.

Conclusion: Based on the results of this study, intensive multimodality therapy appears feasible and effective in this group of patients.