DÄ internationalArchive18/2013Malignant Pleural Mesothelioma

Review article

Malignant Pleural Mesothelioma

Incidence, Etiology, Diagnosis, Treatment, and Occupational Health

Dtsch Arztebl Int 2013; 110(18): 319-26. DOI: 10.3238/arztebl.2013.0319

Neumann, V; Löseke, S; Nowak, D; Herth, F J F; Tannapfel, A

Background: The incidence of malignant mesothelioma in Germany is about 20 cases per million persons per year. Its association with asbestos exposure, usually occupational, has been unequivocally demonstrated. Even though the industrial use of asbestos was forbidden many years ago, new cases of mesothelioma continue to appear because of the long latency of the disease (median, 50 years). Its diagnosis and treatment still present a major challenge for ambulatory and in-hospital care and will do so for years to come.

Methods: This article is based on a selective review of the literature, along with data from the German Mesothelioma Register.

Results: 1397 people died of mesothelioma in Germany in 2010. A plateau in the incidence of the disease is predicted between 2015 and 2030. Most mesotheliomas arise from the pleura. The histological subtype and the Karnofsky score are the main prognostic factors. Only limited data are now available to guide treatment with a combination of the available methods (chemotherapy, surgery, radiotherapy). The prognosis is still poor, with a median survival time of only 12 months. Symptom control and the preservation of the patient’s quality of life are the main aspects of care for patients with mesothelioma.

Conclusion: The incidence of mesothelioma is not expected to drop in the next few years. The available treatments are chemotherapy, surgery, and radiotherapy. Specialized treatment centers now increasingly provide multimodal therapy for treatment of mesothelioma.

LNSLNS

Malignant diffuse mesothelioma is a tumor arising from the mesothelial or submesothelial cells of the pleura, peritoneum, or pericardium. More than 80% of all mesotheliomas originate in the pleura (1), and more than 80% of patients with pleural mesothelioma are men (1, 2). This disease is much rarer than lung carcinoma: 1397 persons died of malignant mesothelioma in Germany in 2010. Mesothelioma is officially recognized as an occupational cancer and as a signal disease for occupational asbestos exposure (Figure). Its incidence has been constant in recent years and is not expected to drop until some time between 2015 and 2030. Mesothelioma remains a diagnostic and therapeutic challenge for ambulatory and in-hospital care and is likely to remain one in the years to come.

New cases of mesothelioma classified as occupational disease according to No. 4105 of the Regulation Concerning Occupational Diseases
New cases of mesothelioma classified as occupational disease according to No. 4105 of the Regulation Concerning Occupational Diseases
Figure
New cases of mesothelioma classified as occupational disease according to No. 4105 of the Regulation Concerning Occupational Diseases

Methods

The publications reviewed for this article were retrieved by a selective search of the Medline database with the same search terms that were used in the creation of the S2 guideline (3) of the European Respiratory Society and the European Society of Thoracic Surgeons. Further quantitative data on mesothelioma as an occupational disease according to No. 4105 of the German Regulation Concerning Occupational Diseases (Berufskrankheitenverordnung, BKV) were obtained from the database of the German Mesothelioma Register.

Mesothelioma and asbestos

In 1960, a path-breaking study revealed the association of mesothelioma with crocidolite asbestos (4). In 1965, mesothelioma was first designated a “signal tumor” of asbestos exposure (5). As many as 90% of cases of mesothelioma are due to asbestos exposure, and there is a clear correlation between a country’s asbestos consumption and the incidence of mesothelioma there (6) (eBox). There are no official data on the number of people occupationally exposed to asbestos in Germany; estimates range from 1.5 to 2.5 million workers since the Second World War. In 2011, the database of the Preventive Care Division (Gesundheitsvorsorge, GVS) of the German legally mandated casualty insurance carriers contained data on 561 277 persons who had handled asbestos-containing materials on the job. These data, however, do not permit any statistically valid inferences about the number of persons in this group who have mesothelioma.

The use of asbestos in Germany
The use of asbestos in Germany
eBox
The use of asbestos in Germany

Aside from occupational exposure, persons can be exposed to asbestos in any of the following ways (7):

  • private activities
  • proximity to factories where asbestos is used
  • living in areas where asbestos occurs naturally
  • faulty removal of construction elements that contain asbestos from old buildings.

Incidence and latency

Mesothelioma arises in 1 to 2 per million of the general population per year (6); its incidence among occupationally exposed persons is more than 40 times as high (1). Although asbestos processing is forbidden in many industrialized countries, the incidence of the disease is expected to rise further. A person’s risk of developing mesothelioma is age-dependent (ten times higher in persons over age 60 than in persons under age 40) and continues to rise decades after exposure (6). The incidence is currently rising (Table 1) in Europe, Japan, and Australia and falling in the United States (1). The reason for this discrepancy is currently unclear. The average latency of mesothelioma after asbestos exposure was once thought to be 30 years, but more recent data have led this figure to be revised upward to 50 years (1, 8).

Predicted peak incidence years and incidence at peak for mesothelioma in various countries
Predicted peak incidence years and incidence at peak for mesothelioma in various countries
Table 1
Predicted peak incidence years and incidence at peak for mesothelioma in various countries

Diagnostic assessment and clinical manifestations

Because the clinical manifestations of mesothelioma are usually nonspecific, the diagnosis is often not made immediately. Diagnostic delays of up to six months are common (9).

Dyspnea is the first symptom of pleural mesothelioma in 90% of cases (3). Pleural mesothelioma can cause pain by irritating intercostal nerves or by infiltrating into the chest wall. Rarer manifestations include phrenic nerve palsy, irritative cough, paraneoplastic phenomena, and spontaneous pneumothorax (10). Symptomatic metastases are unusual.

The diagnosis of mesothelioma should be considered in any patient with a unilateral pleural effusion or thickening, especially if chest pain is present (11). The differential diagnosis includes pleural effusion of inflammatory or infectious origin (e.g., due to tuberculosis, pneumonia, or chest trauma) and pleural effusion due to venous congestion.

Whenever mesothelioma is suspected, a detailed occupational history should be taken and the patient should be referred to an experienced center for pulmonary medicine. Initially, non-invasive tests such as ultrasonography, computerized tomography (CT), and magnetic resonance imaging (MRI) can be used to obtain further support for the suspected diagnosis and assess the extent of disease. The diagnosis can only be definitively established by biopsy.

Imaging methods

Transthoracic ultrasonography enables an assessment of the pleura in the presence of a pleural effusion; it is the best available means of visual guidance for pleural puncture (12).

CT is the best way to judge the extent of tumor and to detect lymph node metastases (11).

MRI is the best way to determine whether the tumor has invaded the diaphragm or the chest wall.

Positron emission tomography (PET) is now coming into wider use; its main advantage is greater sensitivity for the detection of distant metastases (11).

Pleural puncture and cytological diagnosis

Tumor cells are found in pleural effusion fluid in more than 50% of cases of pleural mesotheliomas, with the likelihood of positive cytology depending on the tumor subtype. Cytological abnormalities are found in both reactive and malignant processes, and negative cytology does not rule out mesothelioma (13). As discussed in the guidelines (3, 13), the sensitivity of cytological diagnosis is limited.

Percutaneous needle biopsy and image-guided percutaneous pleural biopsy

Studies have shown that percutaneous needle biopsy without image guidance is 7% to 47% sensitive and 100% specific (14). Malignant and benign pleural changes are unevenly distributed in the pleura; taking biopsies under image guidance (with either ultrasound or CT) raises the sensitivity to the range of 77% to 87%, still with 100% specificity (15).

Thoracoscopy and thoracotomy

In the guidelines (3), video-assisted thoracoscopic surgery (VATS) is recommended for the diagnostic assessment of pleural effusions of unclear origin. The sensitivity and specificity of VATS for the diagnosis of pleural mesothelioma are 95%–98% and 100%, respectively. VATS enables the removal of specimens under visual observation, as well as pleurodesis in the same procedure (14). The surgeon can inspect the lesion with VATS to assess its resectability (16).

Histopathological diagnosis

The histopathological appearance of mesothelioma is variable and therefore presents a diagnostic challenge. The diagnosis should be made by a specialized pulmonary pathologist (possibly in a reference center for pulmonary diseases). Close cooperation between the surgeon and the pathologist is needed (3, 13, 17).

Mesothelioma is divided into epithelioid, biphasic, and sarcomatoid subtypes on the basis of the predominant histomorphological growth pattern. Special immunohistochemical tests are obligatory (13, 17). There is no single specific marker for mesothelioma; different combinations of markers are used depending on the differential-diagnostic questions to be answered (13, 17).

Staging

The chest X-ray usually shows a unilateral pleural effusion (11). A chest CT is the best way to assess the extent of tumor and of lymph node involvement.

MRI or mediastinoscopy may be needed for the assessment of chest-wall infiltration or mediastinal involvement (affected mediastinal lymph nodes) (11). In addition, abdominal ultrasonography, bone scintigraphy, and sometimes MRI of the head may be needed to rule out distant metastases (11). The European Pneumological Society (3) recommends using the tumor-nodes-metastases (TNM) classification of the Union for International Cancer Control (UICC) (18). Mesothelioma is staged on the basis of the histopathological and intraoperative findings along with the results of clinical staging tests.

Survival time and prognostic factors

Patients with malignant pleural mesothelioma have a poor prognosis, with estimated median survival times varying from 4 to 12 months (3). Only 12% of patients with negative prognostic factors live longer than one year.

The main prognostic factors are age, sex, tumor subtype, and tumor stage. Patients with epithelioid tumors have a relatively favorable prognosis, as do women and patients who are under age 75 when the diagnosis is made.

Another clinically relevant prognostic factor (3) is the Karnofsky score, a rating of the patient’s symptom-related restriction of activities, ability to care for himself or herself, and autonomy, on a scale of 0 to 100.

Other prognostic factors are of use solely for the purposes of clinical research (low hemoglobin content, high LDH level, or high leukocyte and platelet count). Potential serum markers, e.g., soluble mesothelin or osteopontin, are now being studied but cannot currently be used for valid prognostication (3).

Treatment

Mesothelioma is a rare cancer that is best treated in specialized centers offering state-of-the-art care with either curative or palliative intent, as well as pain control. In such centers, oncologists, radiologists, and surgeons should closely cooperate and coordinate their patients’ care in regularly scheduled meetings. Specialized centers also generally participate in clinical trials and enter their patients into disease registries.

The goals of treatment for cancer are to prolong life and to improve the quality of life. The current treatments for mesothelioma are only partly successful at meeting these goals. No cure is now available.

Palliative care is appropriate in situations where the following criteria are met:

  • poor general condition and nutritional state
  • biphasic or sarcomatoid mesothelioma (any stage)
  • stage 3 or 4 epithelioid mesothelioma
  • N2 stage and/or M1 stage.

For palliative treatment, thoracoscopy with pleurodesis can be used to control symptomatic pleural effusions and lessen pain. Recurrent pleural effusions can be treated by talcum pleurodesis with 93% efficacy (19).

Multimodal strategies for treatment with curative intent are currently being pursued. Little evidence is available to date indicating which treatment combinations are best for which types of patients (3).

Treatment with curative intent is appropriate in situations where the following criteria are met:

  • the patient is under 70 years old
  • no appreciable cardiopulmonary compromise
  • no relevant accompanying disease
  • epithelioid mesothelioma (stage 1 or 2)
  • N0 situation (mediastinoscopy).

In the following sections, we will discuss only robust treatment modalities that have demonstrated their reliability and for which the available evidence from clinical trials is good enough for them to be mentioned in clinical guidelines (Table 2). There is no room here for an additional discussion of little-tested or experimental approaches.

Overview of treatment studies for malignant pleural mesothelioma
Overview of treatment studies for malignant pleural mesothelioma
Table 2
Overview of treatment studies for malignant pleural mesothelioma

Surgery

The goal of surgery is gross total resection of the tumor. As mesotheliomas tend to grow diffusely, they are usually not totally resectable; some residual tumor tissue (often microscopic) is generally left behind. Adjuvant chemotherapy is given achieve elimination of remaining tumor cells (20).

Pleurectomy/decortication

Pleurectomy and decortication with en bloc resection of the parietal and visceral pleura is an effective method of preventing pleural effusion (20). It is a suitable means of symptom control for patients who cannot benefit from pleurodesis, in particular those with a lung that cannot expand adequately (”trapped lung syndrome”) because of fibrotic changes, of either neoplastic or inflammatory origin, that restrict the mobility of the visceral pleura and can cause it to adhere to the parietal pleura. Pleurectomy/decortication has a lower mortality (1.5%–5%) than extrapleural pleuropneumectomy, and patients recover from it more rapidly. There is an increased risk of local recurrence after this procedure (2.5%–5.9%); a significant effect on median survival (10 to 17 months) has been observed, but there is no significant effect on long-term survival (21).

Extrapleural pleuropneumectomy (EPP)

This procedure involves resection of the lung, the pleura, the pericardium, and the diaphragm and should only be performed in highly specialized centers in trials of multimodal treatment. The mortality of this highly invasive procedure can be held down to 3.4%–10% in experienced centers, but its morbidity can be as high as 50%, and complications often necessitate a second procedure (20). EPP provides no advantage in terms of survival rates, even in the setting of multimodal treatment (22). The reported rates of local recurrence after EPP vary widely, from 0% to 37% (3, 23, 24).

Chemotherapy

A path-breaking publication from the year 1999 (25) and multiple studies thereafter (26, 27) showed that chemotherapy with cisplatin and pemetrexed can be effective. Randomized therapeutic trials are difficult to organize because case numbers are small. One such trial of chemotherapy versus placebo did not reveal any significant effect on survival times (28). No randomized trials of chemotherapy as a second line of treatment have been performed to date, although the available evidence to date does suggest that second-line treatment can prolong survival more than symptom control alone (29). Decisions about chemotherapy should be made individually for each patient after the physician has discussed the matter thoroughly with the patient and his or her family, who must be clearly told that the efficacy of treatment is limited. Only patients with a Karnofsky performance status above 60% are candidates for chemotherapy. Palliative chemotherapy may be indicated for patients with rapid tumor progression or severely limiting symptoms (30).

Radiotherapy

Patients with mesothelioma are given prophylactic radiotherapy at puncture sites and after surgical interventions to prevent local recurrence and to relieve pain in palliative care. Radical radiotherapy of the entire tumor is not currently feasible, because these tumors tend to grow in a complex geometrical configuration, and the resultingly high radiation load of treatment would be likely to cause collateral damage to the heart and lungs (24).

Prophylactic radiotherapy after decortication/pleurectomy is not recommended in the guidelines (3), which do, however, state that radiotherapy can be given after EPP in a clinical-trial setting. Radiotherapy for pain relief should be discussed with patients who have chest pain and infiltration of the chest wall (3).

Multimodal approaches

Multimodal treatments involve surgery combined with chemotherapy and, in some cases, radiotherapy. In one trial, neo-adjuvant chemotherapy combined with pleuropneumectomy and followed by radiotherapy led to a higher average 3-year survival rate than unimodal treatment (76 %) (31) and prolonged the median survival time (22 months for stage I) in another study (32).

Clinical trials are now underway to assess the possible benefit of combining cytoreductive pleurectomy with intraoperative hyperthermic chemotherapy, a procedure in which the temperature is raised to 42°C to increase the tissue penetration of chemotherapeutic drugs and thereby potentiate their effect.

Screening methods

Attempts to detect mesothelioma early with serum markers (33), high-resolution CT (HRCT), or PET have not yielded any clinical breakthroughs to date (34, 35). Pleural ultrasonography is less sensitive than CT and is thus unlikely to be of additional use for early detection (11, 36). Because of the low prevalence and poor prognosis of mesothelioma and the limited therapeutic options for it, as well as the less than ideal sensitivity of the putative screening methods proposed to date, there is as yet no validated method for the early detection of this disease, even if performed repeatedly at close intervals (3).

A more detailed discussion of the diagnosis and treatment of mesothelioma and of the pertinent insurance aspects can be found in the international guidelines of the ERS/EST Task Force (3) and the Mesothelioma Interest Group (37), as well as the Falkenstein recommendations of the German Social Accident Insurance (DGUV) (38) and the S2 guideline of the Association of Scientific Medical Societies in Germany (AWMF) (39).

Mesothelioma from the viewpoint of occupational health

The diagnosis of mesothelioma must always arouse the suspicion of an occupational disease. According to German law (§202 SGB VII), the physician is required to report a suspected occupational disease in such cases, even if the patient has no recollection of being exposed to asbestos in the workplace. In view of the fact that the latency of disease can be as long as 60 years, the patient’s occupational history must be taken by an appropriately trained person in a qualified and comprehensive manner. It must be borne in mind that mesothelioma can also be caused by short-term, low-level exposure (40, e1) (eBox).

Taking an occupational history from an elderly and (often) multimorbid patient can be difficult but may be facilitated by the use of a catalogue of photographs of workplaces in which workers historically received intense exposure to asbestos (Questionnaire of the Munich Tumor Center, [e2]).

Asbestos is still being used commercially in the newly industrialized countries of Asia, and the incidence of mesothelioma there can be expected to rise. Only a worldwide prohibition of asbestos use (e3) can prevent a further rise in the number of victims.

Countries that produce asbestos and/or use it for industrial purposes should be compelled by international pressure to cease these activities. In particular, attempts by industry lobbyists to cast doubt on the carcinogenicity of white asbestos (chrysotyle)—particularly with respect to lung cancer—should be contradicted in the scientific discussion (e4).

Conflict of interest statement

Dipl.-Biol. Neumann, Dr. Löseke, Prof. Nowak, and Prof. Tannapfel have served as paid medicolegal consultants for casualty insurance carriers for the pathological diagnosis of mesothelioma and the determination of a causal link to asbestos exposure in individual cases.

Prof. Herth states that he has no conflict of interest.

Manuscript submitted on 19 November 2012; revised version accepted
on 21 February 2013.

Translated from the original German by Ethan Taub, M.D.

Corresponding author
Dipl.-Biol. Volker Neumann
Deutsches Mesotheliomregister am Institut für Pathologie
der Ruhr-Universität Bochum am Berufsgenossenschaftlichen
Universitätsklinikum Bergmannsheil
Bürkle-de-la-Camp-Platz 1
44789 Bochum, Germany
Volker.Neumann@ruhr-uni-bochum.de

@For eReferences please refer to:
www.aerzteblatt-international.de/ref1813

eBox:
www.aerzteblatt-international.de/13m0319

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Nakas A, Trousse DS, Martin-Ucar AE, Waller DA: Open lung-sparing surgery for malignant pleural mesothelioma: the benefits of a radical approach within multimodal therapy. Eur J Cardiothorac Surg 2008; 34: 886–91. CrossRef MEDLINE
e19.
Halstead JC, Lim E, Venkateswaran RM, Charman SC, Goddard M, Ritchie AJ: Improved survival with VATS pleurectomy-decortication in advanced malignant mesothelioma. Eur J Surg Oncol 2005; 31: 314–20. CrossRef MEDLINE
e20.
Nakas A, von Meyenfeldt E, Lau K, Muller S, Waller D: Long-term survival after lung-sparing total pleurectomy for locally advanced (International Mesothelioma Interest Group Stage T3-T4) non-sarcomatoid malignant pleural mesothelioma. Eur J Cardiothorac Surg 2012; 41: 1031–6. CrossRef MEDLINE
e21.
Okada M, Mimura T, Ohbayashi C, Sakuma T, Soejima T, Tsubota N: Radical surgery for malignant pleural mesothelioma: results and prognosis. Intera CardioVasc and Thorac Surg 2008; 7: 102–6. CrossRef MEDLINE
e22.
Maziak DE, Gagliardi A, Haynes AE, Mackay JA, Evans WK, Cancer Care Ontario Program in Evidence-based Care Lung Cancer Disease Site Group: Surgical management of malignant pleural mesothelioma: a systematic review and evidence summary. Lung Cancer 2005; 48: 157–69. CrossRef MEDLINE
e23.
Aziz T, Jilaihawi A, Prakash D: The management of malignant pleural mesothelioma; single centre experience in 10 years. Eur J Cardiothorac Surg 2002; 22: 298–305. CrossRef MEDLINE
e24.
Ambrogi V, Baldi A, Schillaci O, Mineo TC: Clinical impact of extrapleural pneumonectomy for malignant pleural mesothelioma. Ann Surg Oncol 2012; 19: 1692–9. CrossRef MEDLINE
e25.
Flores RM, Pass HI, Seshan VE, et al.: Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: results in 663 patients. J Thorac Cardiovasc Surg 2008; 135: 620–6. CrossRef MEDLINE
e26.
Aigner C, Hoda MAR, Lang G, Taghavi, S, Marta G, Klepetko W: Outcome after extrapleural pneumonectomy for malignant pleural mesothelioma. Eur J Cardiothoracic Surg 2008; 34: 204–7. CrossRef MEDLINE
e27.
Yan TD, Boyer M, Tin MM, et al.: Extrapleural pneumonectomy for malignant pleural mesothelioma: Outcomes of treatment and prognostic factors. Gen Thorac Surg 2009; 138: 619–24. CrossRef MEDLINE
e28.
Treasure T, Lang-Lazdunski L, Waller D, et al. for the MARS trialists: Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma: clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study. Lancet Oncol 2011; 12: 763–72. CrossRef MEDLINE
e29.
Nakas A, Martin Ucar AE, Edwards JG, Waller DA: The role of video assisted thoracoscopic pleurectomy/decortication in the therapeutic management of malignant pleural mesothelioma. Eur J Cardiothorac Surg 2008; 33: 83–8. CrossRef MEDLINE
e30.
Hillerdal G, Sorensen JB, Sundström S, Riska H, Vikström A, Hjerpe A: Treatment of malignant pleural mesothelioma with Carboplatin, liposomized Doxorubicin and Gemcitabine. J Thorac Oncol 2008; 3: 1325–31. CrossRef MEDLINE
e31.
Vogelzang NJ, Rusthoven JJ, Symanowski J, et al.: Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 2003; 21: 2636–44. CrossRef MEDLINE
e32.
Metintas M, Ak G, Erginel S, Alatas F, Yildirim H, Kurt E, Metintas S: A retrospective analysis of malignant pleural mesothelioma patients treated either with chemotherapy or best supportive care between 1990 and 2005. A single institution experience. Lung Cancer 2007; 55: 379–87. CrossRef MEDLINE
e33.
van Meerbeeck JP, Gaafar R, Manegold C, et al.: European Organisation for Research and Treatment of Cancer Lung Cancer Group, National Cancer Institute of Canada: Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma. J Clinic Oncol 2005; 23: 6881–9. CrossRef MEDLINE
e34.
Knuuttila A, Salomaa ER, Saikkonen S, Hurme S, Salo J: Pemetrexed in malignant pleural mesothelioma and the clinical outcome. Clin Respir J 2012; 6: 96–103. CrossRef MEDLINE
e35.
Muers MF, Stephens RJ, Fisher P, et al.: MS01 Trail Management Group: active symptom control with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma (MS01): a multicentre randomised trail. Lancet 2008; 371: 1685–94. CrossRef MEDLINE
e36.
Rice DC, Stevens CW, Correa AM, et al.: Outcomes after extrapleural pneumonectomy and intensy-modulated radiation therapy for malignant pleural mesothelioma. Ann Thorac Surg 2007; 84: 1685–92. CrossRef MEDLINE
e37.
Rosenzweig KE, Zauderer MG, Laser B, et al.: Pleural intensity-modulated radiotherapy for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys 2012; 83: 1278–83. CrossRef MEDLINE
e38.
Rusch VW, Rosenzweig K, Venkatraman E, et al.: A phase II trail of surgical resection and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma. J Thorac Cardiovasc Surg 2001; 122: 788–95. CrossRef MEDLINE
e39.
Gupta V, Mychalczak B, Krug L, et al.: Hemithoracic radiation therapy after pleurectomy/decortication for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys 2005; 63: 1045–52. CrossRef MEDLINE
e40.
Lang-Lazdunski L, Bille A, Belcher E, et al.: Pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine followed by adjuvant chemotherapy in patients with malignant pleural mesothelioma. J Thorac Oncol 2011; 6: 1746–52. CrossRef MEDLINE
e41.
Bille A, Belcher E, Raubenheimer H, et al.: Induction chemotherapy, extrapleural pneumonectomy, and adjuvant radiotherapy for malignant pleural mesothelioma: experience of Guy`s and St Thomas` hospitals. Gen Thorac Cardiovasc Surg 2012; 60: 289–96. CrossRef MEDLINE
e42.
Sugarbaker DJ, Flores RM, Jaklitsch MT, et al.: Resection margins, extrapleural nodal status and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients. J Thorac Cardiovasc Surg 1999; 117: 54–63. CrossRef MEDLINE
e43.
Krug LM, Pass HI, Rusch VW, et al.: Multicenter phase II trail of neoadjuvant Pemetrexed plus Cisplatin followed by extrapleural pneumonectomy and radiation for malignant pleural mesothelioma. J Clinic Oncol 2009; 27: 3007–13. CrossRef MEDLINE
e44.
van Schil PE, Baas P, Gaafar R, et al. on behalf of the European Organisation for research and Treatment of Cancer (EORTC) Lung Cancer Group: Trimodal therapy for malignant pleural mesothelioma: results from an EORTC phase II multicentre trail. Eur Respir J 2010; 36: 1362–9. CrossRef MEDLINE
e45.
Weder W, Stahel RA, Bernhard J, et al. on behalf of the Swiss Group for Clinical Cancer Research. Ann Oncol 2007; 18: 1196–02. CrossRef MEDLINE
e46.
Patel PR, Yoo S, Broadwater G, et al.: Effect of increasing experience on dosimetric and clinical outcomes on the management of malignant pleural mesothelioma with intensity-modulated radiation therapy. Int J Radiat Oncol Biol Phys 2012; 83: 362–8. CrossRef MEDLINE
e47.
Bölükbas S, Manegold C, Eberlein M, Bergmann T, Fisseler-Eckhoff A, Schirren J: Survival after trimodality therapy for malignant pleural mesothelioma: Radical pleurectomy, chemotherapy with Cisplatin/Pemetrexed and radiotherapy. Lung Cancer 2011; 71: 75–81. CrossRef MEDLINE
German Mesothelioma Register at the Institute of Pathology, Ruhr-University Bochum, Bergmannsheil University Hospital: Dipl.-Biol. Neumann, Dr. rer. nat. Löseke, Prof. Dr. med. Tannapfel
Institute of Occupational, Social and Environmental Medicine, Ludwig-Maximilians-University, Munich:
Dr. med. Nowak
Pneumology and Respiratory Critical Care Medicine, Thorax Clinic at Heidelberg University Hospital:
Prof. Dr. med. Herth
Institute of Pathology, Ruhr-University Bochum, Bergmannsheil University Hospital: Prof. Dr. med. Tannapfel
New cases of mesothelioma classified as occupational disease according to No. 4105 of the Regulation Concerning Occupational Diseases
New cases of mesothelioma classified as occupational disease according to No. 4105 of the Regulation Concerning Occupational Diseases
Figure
New cases of mesothelioma classified as occupational disease according to No. 4105 of the Regulation Concerning Occupational Diseases
Key messages
Predicted peak incidence years and incidence at peak for mesothelioma in various countries
Predicted peak incidence years and incidence at peak for mesothelioma in various countries
Table 1
Predicted peak incidence years and incidence at peak for mesothelioma in various countries
Overview of treatment studies for malignant pleural mesothelioma
Overview of treatment studies for malignant pleural mesothelioma
Table 2
Overview of treatment studies for malignant pleural mesothelioma
The use of asbestos in Germany
The use of asbestos in Germany
eBox
The use of asbestos in Germany
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e17.Schipper PH, Nichols FC, Thomse KM, Deschamps C, Cassivi SD, Allen MS, Pairolero PC: Malignant pleural mesothelioma: surgical management in 285 patients. Ann Thorac Surg 2008; 85: 257–64. CrossRef MEDLINE
e18.Nakas A, Trousse DS, Martin-Ucar AE, Waller DA: Open lung-sparing surgery for malignant pleural mesothelioma: the benefits of a radical approach within multimodal therapy. Eur J Cardiothorac Surg 2008; 34: 886–91. CrossRef MEDLINE
e19.Halstead JC, Lim E, Venkateswaran RM, Charman SC, Goddard M, Ritchie AJ: Improved survival with VATS pleurectomy-decortication in advanced malignant mesothelioma. Eur J Surg Oncol 2005; 31: 314–20. CrossRef MEDLINE
e20.Nakas A, von Meyenfeldt E, Lau K, Muller S, Waller D: Long-term survival after lung-sparing total pleurectomy for locally advanced (International Mesothelioma Interest Group Stage T3-T4) non-sarcomatoid malignant pleural mesothelioma. Eur J Cardiothorac Surg 2012; 41: 1031–6. CrossRef MEDLINE
e21.Okada M, Mimura T, Ohbayashi C, Sakuma T, Soejima T, Tsubota N: Radical surgery for malignant pleural mesothelioma: results and prognosis. Intera CardioVasc and Thorac Surg 2008; 7: 102–6. CrossRef MEDLINE
e22.Maziak DE, Gagliardi A, Haynes AE, Mackay JA, Evans WK, Cancer Care Ontario Program in Evidence-based Care Lung Cancer Disease Site Group: Surgical management of malignant pleural mesothelioma: a systematic review and evidence summary. Lung Cancer 2005; 48: 157–69. CrossRef MEDLINE
e23.Aziz T, Jilaihawi A, Prakash D: The management of malignant pleural mesothelioma; single centre experience in 10 years. Eur J Cardiothorac Surg 2002; 22: 298–305. CrossRef MEDLINE
e24.Ambrogi V, Baldi A, Schillaci O, Mineo TC: Clinical impact of extrapleural pneumonectomy for malignant pleural mesothelioma. Ann Surg Oncol 2012; 19: 1692–9. CrossRef MEDLINE
e25.Flores RM, Pass HI, Seshan VE, et al.: Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: results in 663 patients. J Thorac Cardiovasc Surg 2008; 135: 620–6. CrossRef MEDLINE
e26.Aigner C, Hoda MAR, Lang G, Taghavi, S, Marta G, Klepetko W: Outcome after extrapleural pneumonectomy for malignant pleural mesothelioma. Eur J Cardiothoracic Surg 2008; 34: 204–7. CrossRef MEDLINE
e27.Yan TD, Boyer M, Tin MM, et al.: Extrapleural pneumonectomy for malignant pleural mesothelioma: Outcomes of treatment and prognostic factors. Gen Thorac Surg 2009; 138: 619–24. CrossRef MEDLINE
e28.Treasure T, Lang-Lazdunski L, Waller D, et al. for the MARS trialists: Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma: clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study. Lancet Oncol 2011; 12: 763–72. CrossRef MEDLINE
e29.Nakas A, Martin Ucar AE, Edwards JG, Waller DA: The role of video assisted thoracoscopic pleurectomy/decortication in the therapeutic management of malignant pleural mesothelioma. Eur J Cardiothorac Surg 2008; 33: 83–8. CrossRef MEDLINE
e30.Hillerdal G, Sorensen JB, Sundström S, Riska H, Vikström A, Hjerpe A: Treatment of malignant pleural mesothelioma with Carboplatin, liposomized Doxorubicin and Gemcitabine. J Thorac Oncol 2008; 3: 1325–31. CrossRef MEDLINE
e31.Vogelzang NJ, Rusthoven JJ, Symanowski J, et al.: Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 2003; 21: 2636–44. CrossRef MEDLINE
e32.Metintas M, Ak G, Erginel S, Alatas F, Yildirim H, Kurt E, Metintas S: A retrospective analysis of malignant pleural mesothelioma patients treated either with chemotherapy or best supportive care between 1990 and 2005. A single institution experience. Lung Cancer 2007; 55: 379–87. CrossRef MEDLINE
e33.van Meerbeeck JP, Gaafar R, Manegold C, et al.: European Organisation for Research and Treatment of Cancer Lung Cancer Group, National Cancer Institute of Canada: Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma. J Clinic Oncol 2005; 23: 6881–9. CrossRef MEDLINE
e34.Knuuttila A, Salomaa ER, Saikkonen S, Hurme S, Salo J: Pemetrexed in malignant pleural mesothelioma and the clinical outcome. Clin Respir J 2012; 6: 96–103. CrossRef MEDLINE
e35.Muers MF, Stephens RJ, Fisher P, et al.: MS01 Trail Management Group: active symptom control with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma (MS01): a multicentre randomised trail. Lancet 2008; 371: 1685–94. CrossRef MEDLINE
e36.Rice DC, Stevens CW, Correa AM, et al.: Outcomes after extrapleural pneumonectomy and intensy-modulated radiation therapy for malignant pleural mesothelioma. Ann Thorac Surg 2007; 84: 1685–92. CrossRef MEDLINE
e37.Rosenzweig KE, Zauderer MG, Laser B, et al.: Pleural intensity-modulated radiotherapy for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys 2012; 83: 1278–83. CrossRef MEDLINE
e38.Rusch VW, Rosenzweig K, Venkatraman E, et al.: A phase II trail of surgical resection and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma. J Thorac Cardiovasc Surg 2001; 122: 788–95. CrossRef MEDLINE
e39.Gupta V, Mychalczak B, Krug L, et al.: Hemithoracic radiation therapy after pleurectomy/decortication for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys 2005; 63: 1045–52. CrossRef MEDLINE
e40.Lang-Lazdunski L, Bille A, Belcher E, et al.: Pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine followed by adjuvant chemotherapy in patients with malignant pleural mesothelioma. J Thorac Oncol 2011; 6: 1746–52. CrossRef MEDLINE
e41.Bille A, Belcher E, Raubenheimer H, et al.: Induction chemotherapy, extrapleural pneumonectomy, and adjuvant radiotherapy for malignant pleural mesothelioma: experience of Guy`s and St Thomas` hospitals. Gen Thorac Cardiovasc Surg 2012; 60: 289–96. CrossRef MEDLINE
e42.Sugarbaker DJ, Flores RM, Jaklitsch MT, et al.: Resection margins, extrapleural nodal status and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients. J Thorac Cardiovasc Surg 1999; 117: 54–63. CrossRef MEDLINE
e43.Krug LM, Pass HI, Rusch VW, et al.: Multicenter phase II trail of neoadjuvant Pemetrexed plus Cisplatin followed by extrapleural pneumonectomy and radiation for malignant pleural mesothelioma. J Clinic Oncol 2009; 27: 3007–13. CrossRef MEDLINE
e44.van Schil PE, Baas P, Gaafar R, et al. on behalf of the European Organisation for research and Treatment of Cancer (EORTC) Lung Cancer Group: Trimodal therapy for malignant pleural mesothelioma: results from an EORTC phase II multicentre trail. Eur Respir J 2010; 36: 1362–9. CrossRef MEDLINE
e45.Weder W, Stahel RA, Bernhard J, et al. on behalf of the Swiss Group for Clinical Cancer Research. Ann Oncol 2007; 18: 1196–02. CrossRef MEDLINE
e46.Patel PR, Yoo S, Broadwater G, et al.: Effect of increasing experience on dosimetric and clinical outcomes on the management of malignant pleural mesothelioma with intensity-modulated radiation therapy. Int J Radiat Oncol Biol Phys 2012; 83: 362–8. CrossRef MEDLINE
e47.Bölükbas S, Manegold C, Eberlein M, Bergmann T, Fisseler-Eckhoff A, Schirren J: Survival after trimodality therapy for malignant pleural mesothelioma: Radical pleurectomy, chemotherapy with Cisplatin/Pemetrexed and radiotherapy. Lung Cancer 2011; 71: 75–81. CrossRef MEDLINE