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Third Consensus Conference on Malignant Pleural Mesothelioma: State-of-the-art and recommendations

INTRODUCTION

Here we are once again to discuss scientific information and to disclose news about Malignant Pleural Mesothelioma (MPM).
At this time, we deem it useful to involve the readers in a new consensus conference, in other words in a meeting of experts which resulted in the drafting an update of the state-of-the-art of this topic and in the collection of recommendations on how to deal with this disease.
We are talking about the Third Italian Consensus Conference that took place in Bari back in January 2015, with the support of AIOM (Italian Association of Medical Oncology).
The resulting publication, the tangible output of the work carried out by experts on MPM, is available online at the following link: http://www.ncbi.nlm.nih.gov/pubmed/?term=Mezzapelle+et+al%2C+Sci+Rep+6%3A+22850.
This article is organised into nine different chapters: Introduction, Methods, Epidemiology, Diagnosis, Radiological Check-ups, Surgery, Radiotherapy, Chemotherapy, Psycho-social and legal aspects and future prospects.
This review contains a collection of the main references and an outline summary of the main concepts of this Consensus Conference. For more in-depth information and more specific details, please refer to the full text. 
State-of-the-art and recommendations for Malignant Pleural Mesothelioma, according to Italian experts

Epidemiological data

In 2011, the incidence of MPM in Italy was 3.49 and 1.25 cases every 100,000 people/year, respectively, for men and women. A total of 1428 cases were reported: 1035 men and 393 women (Anon, 2015). The national incidence and mortality are currently stable, and there seems to be a one-plateau trend. However, it is believed that a peak will take place in 2020-2025, especially in industrialised countries.
As everyone knows, exposure to asbestos is strictly related to the incidence of MPM, and there is a veritable dose-response relationship (Prince, 2005; Mastrangelo, 2014).
Cumulative exposure to asbestos is an indicator that takes into account the sum of the exposure and is used in various research fields. However, it fails to consider important data such as the duration or intensity of the exposure itself (Thomas, 2013; Lubin, 2006; Vlandereen, 2013; Richardson, 2012).
Nevertheless, we can safely say that, with regards to cumulative exposure to asbestos, there does not seem to be a large difference compared to the previously published Consensus Conferences (Pinto, 2011; Pinto, 2013).
Exposure to asbestos can be of the occupational type, in other words tied to the work which the patient carries out or has carried out in the past, or non-occupational, tied above all to atmospheric and domestic pollution. In Italy, it is estimated that non-occupational exposure takes place in about 10.2% of the cases (National Mesothelioma Register 2012). 
Asbestos can also spread through the air under the form of fibres. The WHO (World Health Organisation) has estimated that continuous exposure to 0.4-1 fibre/l can lead to the risk of becoming ill with MPM in 0.4-0.5 cases out of 100,000 people (World Health Organisation Regional Office for Europe, 2000).
Moreover, asbestos can also be found in water; however, there is no evidence of cases of mesothelioma caused by the ingestion of fibres.
There are documented cases of asbestos-containing talc, although this has never happened on Italian soil (Finkelstein, 2012).
Other carcinogenic substances tied to asbestos that have been the cause of MPM in Italy are fluoro-edenite, as in the area of Biancavilla (CT). These cases are similar to those described in Japan, in volcanic areas.
Although there is data of cancerogenesis only in test animals and no cases of MPM were ever described in man, silica carbide is also a carcinogenic agent that can potential cause this disease (Grosse, 2014).
There are also hereditary cases of MPM, associated with genetic alterations such as, for example, the mutations of BAP1 (Klerk, 2013; Betti, 2015. Some of these have also been described in Italy (Ascoli, 2007; Ascoli, 2014).

Diagnosis

Oftentimes, MPM manifests itself with a pleural effusion; however, this collection of fluid in the pleural cavity can also be a secondary effect of different medical conditions. Therefore, it is important to first of all proceed with a differential diagnosis between primitive tumour of the pleura, MPM, and other neoplasias that may metastasize at the pleural level, the most common ones being lung, breast and kidney neoplasias (Smith, 2014). Moreover, it is important to remember that many non-neoplastic pathologies are included within the differential diagnosis which may however cause pleural effusion: for example, infectious or inflammatory pleurisies, cardiac failure, parapneumonic effusion.
The diagnosis of MPM is carried out above all through the analysis of a pleural biopsy, which is often obtained by means of a thoracoscopy or, more rarely, by means of an eco or TC guided percutaneous biopsy (Pinto, 2013; Scherpereel, 2010; van Zandwijk, 2013).
In addition to the histological analysis carried out on the tissue obtained through a biopsy, it is also possibly to conduct a cytological analysis, evaluating the cells found in the pleural fluid. In some cases, this may allow the diagnosis to be made; however, this is exam is not as sensitive as histology (Kawai, 2014; Paintal, 2013; Hjerpe, 2015, Henderson, 2013).
In accordance with WHO, a histological classification of MPM has been defined, according to which tMPM can be subdivided into the epithelioid, sarcomatoid and biphasic histotype (Larsen, 2013).
Different markers are used to better define these tumour characteristics and, in particular to differentiate pleural metastasis from adenocarcinoma and primitive lesions caused by MPM (Ordonez, 2013; Betta, 2012).
The following markers are more commonly used to differentiate epithelioid MPM from adenocarcinomas: calretinin, D2-40 (anti-podoplanin antibody), the protein of Wilms-1 tumour, cytokeratin 5 and 6, mesothelin and thrombomodulin. Markers which are considered negative are; CEA, BerEP4, MOC-31, claudin-4 and CD155 (Henderson, 2013b; Lonardi, 2011, Jo, 2014). Napsin A, TTF1, CDX2, PAX-8, apocrine markers and hormonal receptors are instead useful for differentiating MPM from other localised metastasis at the pleural level. The marker BAP1 has been recently tested to differentiate benign mesothelial lesions from malignant ones (Cigognetti, 2015).
Sarcomatoid MPM expresses above all markers such as pan-cytokeratin, vimentin, smooth muscle differentiation markers, D2-40, calretinin (Pinto, 2013; Ordonez, 2013; Scherpereel, 2010; Churg, 2015; Henderson, 2013b).
Other useful markers for the diagnosis of MPM are mesothelin-related peptides (SMRP), osteopontin, and fibulin-3 (Lao, 2014; Creaney, 2011; Hollevoet 2011; Hollevoet, 2010; Luo, 2010; Wheatley-Price, 2010; Creaney 2014a; Franceschini, 2014).

Radiological tests

There are different radiological methods mainly used to diagnose MPM (Hallifax, 2015). The first approach usually takes place through a chest X-ray, which normally allows to identify the presence of a pleural or pericardial effusion or even very extended pleural lesions.
The chest TC, on the other hand, is considered a second-choice exam that allows one to obtain much more detailed morphological information compared to the chest X-ray.
The ultrasound scan can be useful to visualise some specific pleural anomalies, in addition to being used as a guide for conducting a thoracentecis procedure and, if necessary, as a guide for pleural biopsies.
The PET scan can be applied above all to evaluate the metabolism of some lesions; no changes have occurred since the previous Consensus Conference (Pinto, 2013).
As regards invasive diagnostic procedures, there are no changes in indications and recommendations compared to the ones described in the previous experts’ review (Pinto, 2013).
Thoracentesis is still the first minimally invasive diagnostic approach, and cytological analysis can be useful to diagnose the presence of malignant cells in about 60% of the cases. The thoracentesis procedure applied under ultrasound guidance can be useful to minimise any complications that may arise (Hooper, 2010).
Ultrasound and CT-guided biopsy have permanently replaced biopsies done blindly, and they are useful for performing accurate biopsies of lesions, irregularities or pleural thickening (Maskell, 2003; Qureshi, 2006; Adamset, 2001; Metintas, 2010a).
Thoracoscopy is the “gold standard” invasive diagnostic technique, and allows to obtain a diagnosis in 90% of the cases (Churg, 2014; Boutin, 1993; Hansen, 1998; Galbis, 2011; Brimset, 2012).
The Endo-Bronchial UltraSound (EBUS) technique, used to analyses lymph nodes that drain neoplastic cells deriving from MPM, can offer certain advantages with respect to the mediastinoscopy (Rice, 2009; Tournoy, 2008; Zielinski, 2010; Richards, 2010).
All of the radiological techniques used for diagnostic purposes also play a crucial role in establishing the stage the disease is in, thus allowing, in addition to the determination of the prognosis, a definition of the therapeutic approaches, which obviously change depending on the stage of the disease.
The methods mostly used for this purpose are still the CT scan and the PET scan (Truong, 2013a; Nickellet, 2014; Basu, 2011; Erasmus, 2005; Rice, 2009; Flores, 2003; Sørensen, 2008; Truong, 2013b; Armato, 2013; Frauenfelder, 2011; Labby, 2013a; Labby, 2013b; Byrne, 2004).

Therapeutic approaches

Surgery 

Surgery plays a role in the diagnostic approach since, through invasive methods, including the ones described above, it can be extremely useful for obtaining histological material (Greillier, 2007; Buenoet, 2004; Attanoos, 2008 ).
Surgery is also employed in the treatment of malignant pleural effusion. In fact, in addition to being used for diagnostic purposes, thoracoscopy can also be for medical purposes since it allows the intrapleural administration of talc for the purpose of obtaining a pleurodesis. In the same way, specific surgical drainage methods can be applied for each clinical case (Waller, 1995; Halstead 2005; Martin-Ucar, 2001; Nakas, 2008).
Of course, the role of surgery in the treatment of MPM aims at the complete resection of the disease. It is important to remember that this is possible only in those cases where the MPM is resectable and, consequently, it can only be used in the earlier stages (Rice, 2011 Aug; Gomez, 2014; Treasure, 2014; Flores Pass, 2008; Lang-Lazdunski, 2012; Taioli, 2015; (Cao, 2014; Sugarbaker, 2014; Nakas, 2012 ). 
(For specific recommendations and detailed indications of surgery in MPM, please refer to the full text of the Consensus Conference.) 

Radiotherapy 

In the past, radiotherapy was used to treat the progress of the section used for access of thoracoscopy or pleural drainages. In fact, it was believed that irradiating this tract would decrease the possibility of developing metastasis along the anatomical course of the optic instrument or of the drainage used during invasive procedures. However, studies are contradictory and, as of today, there is no evidence such as to suggest stopping the use of radiotherapy (Boutin, 1995; Bydder, 2004; O’Rourke, 2007).
There is no random data in support of the usefulness of adjuvant therapy for MPM. Nevertheless, it is believed that a total dosage of 54 Gy may be associated to a reduced failure of the local treatment (Rusch, 2001). Different studies have compared radiotherapy technique with modulated intensity with standard radiotherapy. However, effective radiotherapy would seem to be the one applied to the entire hemi-thorax concerned by the disease (Forster, 2003; Rice, 2007; Stahel, 2014). At present, there is some preliminary data available on the potential use of radiotherapy with modulated intensity, used to spare the lung contained in the hemi-thorax affected by MPM (Rosenzweig, 2012; Minatel, 2014; Chance, 2015).
Palliative radiotherapy is certainly crucial for controlling the symptoms and, in particular, for pain management (Bissett, 1991; Lindén, 1996; MacLeod, 2015).
(For specific recommendations and detailed indications of radiotherapy in MPM, please refer to the full text of the Consensus Conference.)

Chemotherapy 

Standard chemotherapy indications were widely described in the previous Consensus Conference (Pinto, 2013).
Nevertheless, please remember that the first therapeutic line of this disease is based on the administration of a combination of platinum salts and third-generation antifolates (Fennell, 2008; Muers, 2008; Vogelzang, 2003; Van Meerbeeck, 2005; Santoro, 2008; van den Bogaert, 2006; Buikhuisen, 2013, Anon, 2016; Ceresoli, 2008; Ceresoli 2014).
New knowledge aimed at understanding the pathogenic ways of this disease have allowed the identification of new therapeutic targets, including of the biological type (Kindler, 2012; Zalcman, 2010, Zalcman, 2015; Hassan, 2014). 
The second-line therapy has not allowed a clear improvement in terms of survival compared to the support therapy only, although certain standard drugs, such as Pemetrexed, have contributed favourable data in terms of better objective response and control of the disease rate (Jassem, 2008; Ceresoli, 2014). There are no pharmaceutical agents approved for second-line therapy, consequently the possibility to enrol patients in clinical studies may be considered a good treatment opportunity.
There is still no confirmed scientific evidence concerning the use of second-line biological drugs (Ceresoli, 2014; Krug, 2015; Calabrò, 2013; Anon, 2016; Alley, 2015; Ceresoli, 2011; Bearz, 2012; Zucali, 2012).

Conclusions

Unfortunately, the efficacy of current therapies for MPM is still quite limited, and the prognosis of this disease remains regrettably negative.
New therapeutic approaches are needed, and the research conducted in this area is offering interesting results that require confirming, randomised, multicentric and reproducible studies.
In the meantime, it is useful to continue with a strict surveillance of the subjects at risks and, consequently, there is some advice that can be easily applied.
In fact, the surveillance programmes being implemented are aimed at different objectives, such as:

  • informing subjects exposed to asbestos of the possible risks associated with it, both in terms of present exposure and past exposure;
  • informing the relatives of subjects exposed to asbestos and the possible risk for these individuals, even though they may have not been directly exposed;
  • carefully reconstructing the patient’s work history, especially entering into details of exposure to carcinogenic substances, its duration and intensity;
  • arranging for spreading information concerning diagnostic and therapeutic instruments and the medical prospects available abroad as well;
  • providing support for claims in order to obtain payments and compensations;
  • conduct proper counselling aimed at getting people to stop smoking cigarettes and follow a proper and healthy lifestyle.

Future therapeutic prospects are just around the corner, and a series of research projects underway offer new hope for the treatment of this pathology.

References

1. Adams, R.F., Gray, W., Davies, R.J., Gleeson, F.V. Percutaneous image-guided cutting needle biopsy of the pleura in the diagnosis of malignant mesothelioma. Chest. 2001;120:1798–1802.
2. Alley, E.W., Molife, L.R., Santoro, A. et al, Clinical safety and efficacy of pembrolizumab (MK-3475) in patients with malignant pleural mesothelioma: preliminary results from KEYNOTE-028. Proc AACR Annual Meeting. 2015; (abstract CT103).
3. American Joint Committee on Cancer. Pleural Mesothelioma. AJCC Cancer Staging Manual. 7th ed. Springer, New York (NY); 2010:271–274.
4. V ReNaM Report, 2015 (in press)
5. Anon, 2016. www.clinicaltrials.gov. Pemetrexed disodium or observation in treating patients with malignant pleural mesothelioma without progressive disease after first-line ClinicalTrials.gov Identifier NCT01085630.
6. Anon, 2016. www.clinicaltrials.gov. Placebo controlled study of VS-6063 in subjects with malignant pleural mesothelioma (COMMAND) ClinicalTrials.gov Identifier NCT01870609.
7. Anon, 2016 www.clinicaltrials.gov. Randomized, double-blind study comparing tremelimumab to placebo in subjects with unresectable malignant mesothelioma ClinicalTrials.gov Identifier Brozek.
8. Anon, 2016. IOM documento di consenso sulle cure simultanee at www.aiom.it.
9. Armato, S.G. 3rd, Labby, Z.E., Coolen, J., Klabatsa, A., Feigen, M., Persigehl, T., Gill, R.R. Imaging in pleural mesothelioma: a review of the 11th International Conference of the International Mesothelioma Interest Group. Lung Cancer. 2013;82:190–196.
10. Ascoli, V., Cavone, D., Merler, E. et al, Mesothelioma in blood related subjects: report of 11 clusters among 1954 Italy cases and review of the literature. Am. J. Ind. Med. 2007;50:357–369.
11. Ascoli, V., Romeo, E., Carnovale Scalzo, C. et al, Familial malignant mesothelioma: a population-based study in Central Italy (1980–2012). Cancer Epidemiol. 2014;38:273–278.
12. Attanoos, R.L., Gibbs, A.R. The comparative accuracy of different pleural biopsy techniques in the diagnosis of malignant mesothelioma. Histopathology. 2008;53:340–344.
13. Barnes, G., Baxter, J., Litva, A., Staples, B. The social and psychological impact of the chemical contamination incident in Weston Village, UK: a qualitative analysis. Soc. Sci. Med. 2002;55:2227–2241.
14. Basu, S., Saboury, B., Torigian, D.A., Alavi, A. Current evidence base of FDG-PET/CT imaging in the clinical management of malignant pleural mesothelioma: emerging significance of image segmentation and global disease assessment. Mol. Imaging Biol. 2011;13:801–811.
15. Baum, A. Implications of psychological research on stress and technological accidents. Am. Psychol. 1993;48:665.
16. Bearz, A., Talamini, R., Rossoni, G. et al, Re-challenge with pemetrexed in advanced mesothelioma: a multi-institutional experience. BMC Res. Notes. 2012;5:482.
17. Berry, G. Relative risk and acceleration in lung cancer. Stat. Med. 2007;26:3511–3517.
18. Betta, P.G., Magnani, C., Bensi, T., Trincheri, N.F., Orecchia, S. Immunohistochemistry and molecular diagnostics of pleural malignant mesothelioma. Arch. Pathol. Lab. Med. 2012;136:253–261.
19. Betti, M., Casalone, E., Ferrante, D. et al, Inference in germline BAP1 mutations and asbestos exposure from the analysis of familial and sporadic mesothelioma in a high-risk area. Genes. Chromosomes Cancer. 2015;54:51–62.
20. Bissett, D., Macbeth, F.R., Cram, I. The role of palliative radiotherapy in malignant mesothelioma. Clin. Oncol. (R. Coll. Radiol.). 1991;3:315–317.
21. Boardman, J.D., Downey, L., Jackson, J.S., Merrill, J.B., Saint Onge, J.M., Williams, D.R. Proximate industrial activity and psychological distress. Popul. Environ. 2008;2008:3–25.
22. Boutin, C., Rey, F. Thoracoscopy in pleural malignant mesothelioma: a prospective study of 188 consecutive patients. Part 1: diagnosis. Cancer. 1993;72:389–393.
23. Boutin, C., Rey, F., Viallat, J.R. Prevention of malignant seeding after invasive diagnostic procedures in patients with pleural mesothelioma. A randomized trial of local radiotherapy. Chest. 1995;108:754–758.
24. Brims, F.J.H., Arif, M., Chauhan, A.J. et al, Outcomes and complications following medical thoracoscopy. Clin. Respir. J. 2012;6:144–149.
25. British Lung Foundation. An unnatural death. A report into investigations of mesothelioma death and their impact on bereaved families. ; 2007 (Retrieved online at)http://www.blf.org.uk/Files/fa7128ca-3269-438d-9661-a06200e1303c/An-unnatural-death-final-report.pdf-..
26. British Lung Foundation. Survey of people affected by mesothelioma 2013. ; 2013 (Retrieved online at)http://www.blf.org.uk/Files/87d9e3ee-3056-4e4d-af16-a21f011cb06b/BLF-mesothelioma-survey-report.pdf..
27. Bueno, R., Reblando, J., Glickman, J. et al, Pleural biopsy: a reliable method for determining the diagnosis but not subtype in mesothelioma. Ann. Thorac. Surg. 2004;78:1774–1776.
28. Buikhuisen, W.A., Burgers, J.A., Vincent, A.D. et al, Thalidomide versus active supportive care for maintenance in patients with malignant mesothelioma after first-line chemotherapy (NVALT 5): an open-label, multicentre, randomised phase 3 study. Lancet Oncol. 2013;14:543–551.
29. Bydder, S., Phillips, M., Joseph, D.J., Cameron, F., Spry, N.A., DeMelker, Y., Musk, A.W. A randomised trial of single-dose radiotherapy to prevent procedure tract metastasis by malignant mesothelioma. Br. J. Cancer. 2004;91:9–10.
30. Byrne, M.J., Nowak, A.K. Modified RECIST criteria for assessment of response in malignant pleural mesothelioma. Ann. Oncol. 2004;15:257–260.
31. Calabrò, L., Morra, A., Fonsatti, E. et al, Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma: an open-label, single-arm, phase 2 trial. Lancet Oncol. 2013;14:1104–1111.
32. Cao, C., Tian, D., Park, J., Allan, J., Pataky, K.A., Yan, T.D. A systematic review and meta-analysis of surgical treatments for malignant pleural mesothelioma. Lung Cancer. 2014;83:240–245.
33. Ceresoli, G.L., Castagneto, B., Zucali, P.A. et al, Pemetrexed plus carboplatin in elderly patients with malignant pleural mesothelioma: combined analysis of two phase II trials. Br. J. Cancer. 2008;99:51–56.
34. Ceresoli, G.L., Zucali, P.A., De Vincenzo, F. et al, Retreatment with pemetrexed-based chemotherapy in patients with malignant pleural mesothelioma. Lung Cancer. 2011;72:73–77.
35. Ceresoli, G.L., Grosso, F., Zucali, P.A. et al, Prognostic factors in elderly patients with malignant pleural mesothelioma: results of a multicenter survey. Br. J. Cancer. 2014;111:220–226.
36. Ceresoli, G.L. Second line treatment in malignant pleural mesothelioma: translating the evidence into clinical practice. Lung Cancer Manage. 2014;3:263–271.
37. Chance, W.W., Rice, D.R., Allen, P.K., Tsao, A.S., Fontanilla, H.P., Liao, X.Z., Chang, J.Y., Tang, C., Pan, H.Y., Welsh, J.W., Mehran, R.J., Gomez, D.R. Hemithoracic intensity modulated radiation therapy after pleurectomy/decortication for malignant pleural mesothelioma: toxicity, patterns of failure, and a matched survival analysis. Int. J. Radiat. Oncol. Biol. Phys. 2015;91:149–156.
38. Checkoway, H., Pearce, N., Kriebel, D. Research Methods in Occupational Epidemiology. second ed. University Press, Oxford; 2004:163–167.
39. Cherny, N., Catane, R., Schrijvers, D. et al, European society of medical oncology (ESMO) program for the integration of oncology and palliative care: a 5-year review of the designated centers’ incentive program. Ann. Oncol. 2010;21:362–369.
40. Cheung, M., Talarchek, J., Schindeler, K. et al, Further evidence for germline BAP1 mutations predisposing to melanoma and malignant mesothelioma. Cancer Genet. 2013;206:206–210.
41. Churg, A., Roggli, V., Galateau-Salle, F. Mesothelioma. in: W.D. Travis, E. Brambilla, H.K. Muller-Hermelink et al, (Eds.) Pathology & Genetics: Tumours of the Lung Pleura, Thymus and Heart. IARC Press, Lyon; 2004:128–136.
42. Churg, A., Allen, T., Borczuk, A.C. et al, Well-differentiated papillary mesothelioma with invasive foci. Am. J. Surg. Pathol. 2014;38:990–998.
43. Churg, A., Roggli, V.L., Galateau-Salle, F. Tumours of the pleura: mesothelial tumours. in: W.D. Travis, E. Brambilla, A.P. Burke, A. Marx, A.G. Nicholson (Eds.) WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. IARC Press, Lyon; 2015.
44. Cigognetti, M., Lonardi, S., Fisogni, S., Balzarini, P., Pellegrini, V., Tironi, A., Bercich, L., Bugatti, M., Rossi, G., Murer, B., Barbareschi, M., Giuliani, S., Cavazza, A., Marchetti, G., Vermi, W., Facchetti, F. BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations. Mod. Pathol. 2015; (Epub ahead of print).
45. Couch, S.R., Coles, C.J. Community stress, psychosocial hazards, and EPA decision-Making in communities impacted by chronic technological disasters. Am. J. Public Health. 2011;101:S140–S148.
46. Creaney, J., Francis, R.J., Dick, I.M. et al, Serum soluble mesothelin concentrations in malignant pleural mesothelioma: relationship to tumor volume, clinical stage and changes in tumor burden. Clin. Cancer Res. 2011;17:1181–1189.
47. Creaney, J., Segal, A., Olsen, N. et al, Pleural fluid mesothelin as an adjunct to the diagnosis of pleural malignant mesothelioma. Dis. Markers. 2014;2014:413946.
48. Creaney, J., Dick, I.M., Meniawy, T.M. et al, Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma. Thorax. 2014;69:895–902.
49. Crighton, E.J., Elliott, S.J., van der Meer, J., Small, I., Upshur, R. Impacts of an environmental disaster on psychosocial health and well-being in Karakalpakstan. Soc. Sci. Med. 2003;2003:551–567.
50. Downey, L., Willigen, M.V. Environmental stressors the mental health impacts of living near industrial activity. J. Health Soc. Behav. 2005;46:289–305.
51. Drescher, C.F., Schulenberg, S.E., Smith, C.V. The deepwater horizon oil spill and the Mississippi Gulf coast: mental health in the context of a technological disaster. Am. J. Orthopsychiatry. 2014;84:142–151.
52. de Assis, L.V., Locatelli, J., Isoldi, M.C. The role of key genes and pathways involved in the tumorigenesis of malignant mesothelioma. Biochim. Biophys. Acta. 2014;1845:232–247.
53. de Klerk, N., Alfonso, H., Olsen, N. et al, Familial aggregation of malignant mesothelioma in former workers and residents of Wittenoom, Western Australia. Int. J. Cancer. 2013;132:1423–1428.
54. Erasmus, J.J., Truong, M.T., Smythe, W.R., Munden, R.F., Marom, E.M., Rice, D.C., Vaporciyan, A.A., Walsh, G.L., Sabloff, B.S., Broemeling, L.D., Stevens, C.W., Pisters, K.M., Podoloff, D.A., Macapinlac, H.A. Integrated computed tomography-positron emission tomography in patients with potentially resectable malignant pleural mesothelioma: staging implications. J. Thorac. Cardiovasc. Surg. 2005;129:1364–1370.
55. Fennell, D.A., Gaudino, G., O'Byrne, K.J. et al, Advances in the systemic therapy of malignant pleural mesothelioma. Nat. Clin. Pract. Oncol. 2008;5:136–147.
56. Finkelstein, M.M. Malignant mesothelioma incidence among talc miners and millers in New York State. Am. J. Ind. Med. 2012;55:863–868.
57. Flores Pass, H.I., Seshan, V.E. et al, Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: results in 663 patients. J. Thorac. Cardiovasc. Surg. 2008;135:620–626.
58. Flores, R.M., Akhurst, T., Gonen, M., Larson, S.M., Rusch, V.W. Positron emission tomography defines metastatic disease but not locoregional disease in patients with malignant pleural mesothelioma. J. Thorac. Cardiovasc. Surg. 2003;126:11–16.
59. Forster, K.M., Smythe, W.R., Starkshall, G. Intensity modulated radiotherapy following extrapleural pneumonectomy for the treatment of malignant mesothelioma: clinical implementation. Int. J. Radiat. Oncol. Biol. Phys. 2003;55:606–616.
60. Foster, R.P., Goldstein, M.F. Chernobyl disaster sequelae in recent immigrants to the United States from the former Soviet Union (FSU). J. Immigr. Minor. Health. 2007;9:115–124.
61. Franceschini, M.C., Ferro, P., Canessa, P.A. et al, Mesothelin in serum and pleural effusion in the diagnosis of malignant pleural mesothelioma with non-positive cytology. Anticancer Res. 2014;34:7425–7429.
62. Frauenfelder, T., Tutic, M., Weder, W., Götti, R.P., Stahel, R.A., Seifert, B., Opitz, I. Volumetry: an alternative to assess therapy response for malignant pleural mesothelioma. Eur. Respir. J. 2011;38:162–168.
63. Galbis, J.M., Mata, M., Guijarro, R. et al, Clinical-therapeutic management of thoracoscopy in pleural effusion: a groundbreaking technique in the twentyfirst century. Clin. Transl. Oncol. 2011;13:57–60.
64. Glik, D.C. Risk communication for public health emergencies. Annu. Rev. Public Health. 2007;28:33–54.
65. Gomez, D., Tsao, A.S. Local and systemic therapies for malignant pleural mesothelioma. Curr. Treat. Options Oncol. 2014;4:683–699.
66. Granieri, A., Tamburello, S., Tamburello, A., Casale, S., Cont, C., Guglielmucci, F., Innamorati, M. Quality of life and personality traits in patients with malignant pleural mesothelioma and their first-degree caregivers. Neuropsychiatr. Dis. Treat. J. 2013;9:1193–1202.
67. Grattan, L.M., Roberts, S., Mahan, W.T., McLaughlin, P.K., Otwell, W.S., Morris, J.G. The early psychological impacts of the Deepwater Horizon oil spill on Florida and Alabama communities. Environ. Health Perspect. 2011;119:838–843.
68. Greillier, L., Cavailles, A., Fraticelli, A. et al, Accuracy of pleural biopsy using thoracoscopy for the diagnosis of histologic subtype in patients with malignant pleural mesothelioma. Cancer. 2007;110:2248–2252.
69. Grosse, Y., Loomis, D., Guyton, K.Z. et al, Carcinogenicity of fluoro-edenite, silicon carbide fibres and whiskers, and carbon nanotubes. Lancet Oncol. 2014;15:1427–1428.
70. Guglielmucci, F., Franzoi, I.G., Barbasio, C.P., Borgogno, F.V., Granieri, A. Helping traumatized people survive: a psychoanalytic intervention in a contaminated site. Front. Psychol. 2014;5:1419.
71. Hallifax, R.J., Haris, M., Corcoran, J.P., Leyakathalikhan, S., Brown, E., Srikantharaja, D., Manuel, A., Gleeson, F.V., Munavvar, M., Rahman, N.M. Role of CT in assessing pleural malignancy prior to thoracoscopy. Thorax. 2015;70:192–193.
72. Halstead, J.C., Lim, E., Venkateswaran, R.M. et al, Improved survival with VATS pleurectomy—decortication in advanced malignant mesothelioma. Eur. J. Surg. Oncol. 2005;31:314–320.
73. Hansen, M., Faurschou, P., Clementsen, P. Medical thoracoscopy, results and complications in 146 patients: a retrospective study. Respir. Med. 1998;92:228–232.
74. Hassan, R., Kindler, H.L., Jahan, T. et al, Phase II clinical trial of amatuximab, a chimeric antimesothelin antibody with pemetrexed and cisplatin in advanced unresectable pleural mesothelioma. Clin. Cancer Res. 2014;20:5927–5936.
75. Henderson, D.W., Reid, G., Kao, S.C., van Zandwijk, N., Klebe, S. Challenges and controversies in the diagnosis of mesothelioma: part 1. Cytology-only diagnosis, biopsies, immunohistochemistry, discrimination between mesothelioma and reactive mesothelial hyperplasia, and biomarkers. J. Clin. Pathol. 2013;66:847–853.
76. Henderson, D.W., Reid, G., Kao, S.C., van Zandwijk, N., Klebe, S. Challenges and controversies in the diagnosis of malignant mesothelioma: part 2. Malignant mesothelioma subtypes, pleural synovial sarcoma, molecular and prognostic aspects of mesothelioma, BAP1, aquaporin-1 and microRNA. J. Clin. Pathol. 2013;66:854–861.
77. Hjerpe, A., Ascoli, V., Bedrossian, C.W.M., Boon, M.E., Creaney, J., Davidson, B., Dejmek, A., Dobra, K., Fassina, A., Field, A., Firat, P., Kamei, T., Kobayashi, T., Michael, C.W., Önder, S., Segal, A., Vielh, P. Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma. Complementary statement from the International Mesothelioma Interest Group, also endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology. Acta Cytol. 2015;59:2–16.
78. Hollevoet, K., Nackaerts, K., Thimpont, J. et al, Diagnostic performance of soluble mesothelin and megakaryocyte potentiating factor in mesothelioma. Am. J. Respir. Crit. Care Med. 2010;181:620–625.
79. Hollevoet, K., Nackaerts, K., Gosselin, R. et al, Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma. J. Thorac. Oncol. 2011;6:1930–1937.
80. Hooper, C., Lee, Y.C., BTS Pleural Guideline Group. Investigation of a unilateral pleural effusion in adults: british thoracic society pleural disease guideline 2010. Thorax. 2010;65:ii4–ii17.
81. Hui, D., Kim, Y.J., Park, J.C. et al, Integration of Oncology and palliative care: a systematic review. Oncologist. 2015;20:1–7.
82. IARC International Agency for Research on Cancer (IARC). Arsenic, metals, fibres, and dusts. IARC working group on the evaluation of carcinogenic risks to humans. IARC Monogr. Eval. Carcinog. Risks Hum. 2012;100:11–465.
83. Iavicoli, S., Buresti, G., Colonna, F. et al, Economic burden of Mesothelioma in Italy. in: Communication at International Conference on Monitoring and Surveillance of Asbestos-related Diseases Proceedings Book 2014. ; 2014.
84. Jassem, J., Ramlau, R., Santoro, A. et al, Phase III trial of pemetrexed plus best supportive care compared with best supportive care in previously treated patients with advanced malignant pleural mesothelioma. J. Clin. Oncol. 2008;26:1698–1704.
85. Jo, V.Y., Cibas, E.S., Pinkus, G.S. Claudin-4 immunohistochemistry is highly effective in distinguishing adenocarcinoma from malignant mesothelioma in effusion cytology. Cancer Cytopathol. 2014;122:299–306.
86. Kao, S.C., Yan, T.D., Lee, K., Burn, J. et al, Accuracy of diagnostic biopsy for the histological subtype of malignant pleural mesothelioma. J. Thorac. Oncol. 2011;6:602–605.
87. Kawai, T., Hiroshima, K., Kamei, T. Pulmonary pathology: SY22-2 diagnosis of mesothelioma using japanese criteria. Pathology (Phila.). 2014;46:S39.
88. Kindler, H.L., Karrison, T., Gandara, D.R. et al, Multi-center, double-blind, placebo- controlled, randomized phase II trial of gemcitabine/cisplatin plus bevacizumab or placebo in patients with malignant mesothelioma. J. Clin. Oncol. 2012;30:2509–2515.
89. Krug, L.M., Kindler, H.L., Calvert, H. et al, Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Oncol. 2015;16:447–456.
90. Labby, Z.E., Nowak, A.K., Dignam, J.J., Straus, C., Kindler, H.L. Armato SG 3rd: disease volumes as a marker for patient response in malignant pleural mesothelioma. Ann. Oncol. 2013;24:999–1005.
91. Labby, Z.E., Armato, S.G. 3rd, Dignam, J.J., Straus, C., Kindler, H.L., Nowak, A.K. Lung volume measurements as a surrogate marker for patient response in malignant pleural mesothelioma. J. Thorac. Oncol. 2013;8:478–486.
92. Ladanyi, M., Zauderer, M.G., Krug, L.M. et al: new strategies in pleural mesothelioma: BAP1 and NF2 as novel targets for therapeutic development and risk assessment. Clin. Cancer Res. 2012;18:4485–4490.
93. Lang-Lazdunski, L., Bille, A., Lal, R. et al, Pleurectomy/decortication is superior to extrapleural pneumonectomy in the multimodality management of patients with malignant pleural mesothelioma. J. Thorac. Oncol. 2012;7:737–743.
94. Langholz, B., Thomas, D., Xiang, A., Stram, D. Latency analysis in epidemiologic studies of occupational exposures: application to the Colorado Plateau uranium miners cohort. Am. J. Ind. Med. 1999;35:246–256.
95. Lao, I., Chen, Q., Yu, L., Wang, J. Sarcomatoid malignant mesothelioma: a clinicopathologic and immunohistochemical analysis of 22 cases. Zhonghua Bing Li Xue Za Zhi. 2014;43:364–369.
96. Larsen, B.T., Klein, J.R., Hornychová, H. et al, Diffuse intrapulmonary malignant mesothelioma masquerading as interstitial lung disease: a distinctive variant of mesothelioma. Am. J. Surg. Pathol. 2013;37:1555–1564.
97. Lindén, C.J., Mercke, C., Albrechtsson, U., Johansson, L., Ewers, S.B. Effect of hemithorax irradiation alone or combined with doxorubicin and cyclophosphamide in 47 pleural mesotheliomas: a nonrandomized phase II study. Eur. Respir. J. 1996;9:2565–2572.
98. Lonardi, S., Manera, C., Marucci, R., Santoro, A., Lorenzi, L., Facchetti, F. Usefulness of claudin 4 in the cytologic al diagnosis of serosal effusions. Diagn. Cytopathol. 2011;39:313–317.
99. Lubin, J.H., Caporaso, N.E. Cigarette smoking and lung cancer: modeling total exposure and intensity. Cancer Epidemiol. Biomarkers Prev. 2006;15:517–523.
100. Luo, L., Shi, H.Z., Liang, Q.L. et al, Diagnostic value of soluble mesothelin-related peptides for malignant mesothelioma: a meta-analysis. Respir. Med. 2010;104:149–156.
101. MacLeod, N., Chalmers, A., O'Rourke, N., Moore, K., Sheridan, J., McMahon, L., Bray, C., Stobo, J., Price, A., Fallon, M., Laird, B.J. Is radiotherapy useful for treating pain in mesothelioma?: a phase II trial. J. Thorac. Oncol. 2015;10:944–950.
102. Martin-Ucar, A.E., Edwards, J.G., Rengajaran, A. et al, Palliative surgical debulking in malignant mesothelioma: predictors of survival and symptom control. Eur. J. Cardiothorac. Surg. 2001;20:1117–1121.
103. Maskell, N.A., Gleeson, F.V., Davies, R.J. Standard pleural biopsy versus CT guided cutting-needle biopsy for diagnosis of malignant disease in pleural effusions: a randomised controlled trial. Lancet. 2003;361:1326–1330.
104. Mastrangelo, G., Fadda, E., Comiati, V. et al, A rare occupation causing mesothelioma: mechanisms and differential etiology. Med. Lav. 2014;105:337–347.
105. Metintas, M., Ak, G., Dundar, E. et al, Medical thoracoscopy vs CT scan-guided Abrams pleural needle biopsy for diagnosis of patients with pleural effusions: a randomized, controlled trial. Chest. 2010;137:1362–1368.
106. Metintas, M., Ak, G., Dundar, E. et al, Medical thoracoscopy vs CT scan-guided Abrams pleural needle biopsy for diagnosis of patients with pleural effusions: a randomized, controlled trial. Chest. 2010;137:1362–1368.
107. Minatel, E., Trovo, M., Polesel, J., Baresic, T., Bearz, A., Franchin, G., Gobitti, C., Rumeileh, I.A., Drigo, A., Fontana, P., Pagan, V., Trovo, M.G. Radical pleurectomy/decortication followed by high dose of radiation therapy for malignant pleural mesothelioma. Final results with long-term follow-up. Lung Cancer. 2014;83:78–82.
108. Muers, M.F., Stephens, R.J., Fisher, P. et al, Active symptom control with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma (MS01): a multicentre randomised trial. Lancet. 2008;17:1685–1694.
109. Nakas, A., Martin-Ucar, A.E., Edwards, J.G. et al, The role of video-assisted thoracoscopic pleurectomy/decortication in the therapeutic management of malignant pleural mesothelioma. Eur. J. Cardiothorac. Surg. 2008;33:83–88.
110. Nakas, A., Waller, D., Lau, K., Richards, C., Muller, S. The new case for cervical mediastinoscopy in selection for radical surgery for malignant pleural mesothelioma. Eur. J. Cardiothorac. Surg. 2012;42:72–76.
111. Nickell, L.T. Jr., Lichtenberger, J.P. 3rd, Khorashadi, L., Abbott, G.F., Carter, B.W. Multimodality imaging for characterization, classification, and staging of malignant pleural mesothelioma. Radiographics. 2014;34:1692–1706.
112. O’Leary, J., Covell, K. The Tar Ponds kids: toxic environments and adolescent well-being. Can. J. Behav. Sci. 2002;34:34–43.
113. O'Rourke, N., Garcia, J.C., Paul, J., Lawless, C., McMenemin, R., Hill, J. A randomised controlled trial of intervention site radiotherapy in malignant pleural mesothelioma. Radiother. Oncol. 2007;84:18–22.
114. Ordóñez, N.G. Deciduoid mesothelioma: report of 21 cases with review of the literature. Mod. Pathol. 2012;25:1481–1495.
115. Ordóñez, N.G. Mesotheliomas with small cell features: report of eight cases. Mod. Pathol. 2012;25:689–698.
116. Ordóñez, N.G. Pleomorphic mesothelioma: report of 10 cases. Mod. Pathol. 2012;25:1011–1022.
117. Ordóñez, N.G. Mesothelioma with signet-ring cell features: report of 23 cases. Mod. Pathol. 2013;26:370–384.
118. Ordóñez, N.G. Application of immunohistochemistry in the diagnosis of epithelioid mesothelioma: a review and update. Hum. Pathol. 2013;44:1–19.
119. Paintal, A., Raparia, K., Zakowski, M.F., Nayar, R. The diagnosis of malignant mesothelioma in effusion cytology: a reappraisal and results of a multi-institution survey. Cancer Cytopathol. 2013;121:703–707.
120. Palinkas, L.A. A conceptual framework for understanding the mental health impacts of oil spills: lessons from the Exxon Valdez oil spill. Psychiatry. 2012;75:203–222.
121. Partridge, A.H., Seah, D.S., King, T. Developing a service model that integrates palliative care throughout cancer care: the time is now. J. Clin. Oncol. 2014;32:3330–3367.
122. Pike, M.C., Doll, R. Age at onset of lung cancer: significance in relation to effect of smoking. Lancet. 1965;1:665–668.
123. Pinto, C., Ardizzoni, A., Betta, P.G. et al, Expert opinions of the first Italian consensus conference on the management of malignant pleural mesothelioma. Am. J. Clin. Oncol. 2011;34:99–109.
124. Pinto, C., Novello, S., Torri, V. et al, Second Italian consensus conference on malignant pleural mesothelioma: state of the art and recommendations. Cancer Treat. Rev. 2013;39:328–339.
125. Price, B., Ware, A. Mesothelioma: risk apportionment among asbestos exposure sources. Risk Anal. 2005;25:937–943.
126. Qureshi, N.R., Gleeson, F.V. Imaging of pleural disease. Clin. Chest Med. 2006;27:193–213.
127. Registro Nazionale Mesoteliomi (ReNaM), 2012 Quarto Rapporto Edizioni INAIL Roma.
128. Reid, A., de Klerk, N.H., Magnani, C. et al, Mesothelioma risk after 40 years since first exposure to asbestos: a pooled analysis. Thorax. 2014;69:843–850.
129. Rice, D.C., Smythe, W.R., Liao, Z. et al, Dose-dependent pulmonary toxicity after postoperative intensity-modulated radiotherapy for malignant pleural mesothelioma. Int. J. Radiat. Oncol. Biol. Phys. 2007;69:350–357.
130. Rice, D.C., Steliga, M.A., Stewart, J. et al, Endoscopic ultrasound-guided fine needle aspiration for staging of malignant pleural mesothelioma. Ann. Thorac. Surg. 2009;88:862–868.
131. Rice, D., Rusch, V., Pass, H. et al, Recommendations for uniform definitions of surgical techniques for malignant pleural mesothelioma: a consensus report of the international association for the study of lung cancer international staging committee and the international mesothelioma interest group. J. Thorac. Oncol. 2011 Aug;6:1304–1312.
132. Richards, W.G., Godleski, J.J., Yeap, B.Y. et al, Proposed adjustments to pathologic staging of epithelial malignant pleural mesothelioma based on analysis of 354 cases. Cancer. 2010;116:1510–1517.
133. Richardson, D.B., Cole, S.R., Langholz, B. Regression models for the effects of exposure rate and cumulative exposure. Epidemiology. 2012;23:892–898.
134. Rosenzweig, K.E., Zauderer, M.G., Laser, B. et al, Pleural intensity modulated radiotherapy for malignant pleural mesothelioma. Int. J. Radiat. Oncol. Biol. Phys. 2012;83:1278–1283.
135. Rusch, V.W., Rosenzweig, K., Venkatraman, E. et al, A phase II trial of surgical resection and adjuvant high-dose hemothoracic radiation for malignant pleural mesothelioma. J. Thorac. Cardiovasc. Surg. 2001;122:788–795.
136. Sørensen, J.B., Ravn, J., Loft, A., Brenøe, J., Berthelsen AK for the Nordic Mesothelioma Group. Preoperative staging of mesothelioma by 18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography fused imaging and mediastinoscopy compared to pathological findings after extrapleural pneumonectomy. Eur. J. Cardiothorac. Surg. 2008;34:1090–1096.
137. Santoro, A., O’Brien, M.E., Stahel, R.A. et al, Pemetrexed plus cisplatin or pemetrexed plus carboplatin for chemonaive patients with malignant pleural mesothelioma: results of the international expanded access program. J. Thorac. Oncol. 2008;3:756–763.
138. Sartori, S., Postorivo, S., Vece, F.D., Ermili, F., Tassinari, D., Tombesi, P. Contrast-enhanced ultrasonography in peripheral lung consolidations: what's its actual role. World J. Radiol. 2013;5:372–380.
139. Scherpereel, A., Astoul, P., Baas, P. et al, Guidelines of the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma. Eur. Respir. J. 2010;35:479–495.
140. Schu¨nemann, H.J., Oxman, A.D., Brozek, J. et al, GRADE: grading quality of evidence and strength of recommendations for diagnostic tests and strategies. Br. Med. J. 2008;336:1106–1110.
141. Smith, M., Colby, T. The Diagnosis of thoracic malignant mesothelioma: practical considerations and recent developments. Turk. Patoloji Derg. 2014;30:1–10.
142. Smith, T.J., Temin, S., Alesi, E.R. American Society of Clinical Oncology provisional clinical opinion: the integration of palliative care into standard oncology care. J. Clin. Oncol. 2012;30:880–887.
143. Stahel, R.A., Riesterer, O., Alexandros, X., Opitz, I., Beyeler, M., Ochsenbein, A. et al, Neoadjuvant chemotherapy and extrapleural pneumonectomy (EPP) of malignant pleural mesothelioma (MPM) with or without hemithoracic radiotherapy: final results of the randomized multicenter phase II trial SAKK17/04. Ann. Oncol. 2014;25:v1–v41.
144. Stahel, R.A., Weder, W., Felley-Bosco, E. et al, Searching for targets for the systemic therapy of mesothelioma. Ann. Oncol. 2015; (Epub ahead of print).
145. Sugarbaker, D.J., Richards, W.G., Bueno, R. Extrapleural pneumonectomy in the treatment of epithelioid malignant pleural mesothelioma: novel prognostic implications of combined N1 and N2 nodal involvement based on experience in 529 patients. Ann. Surg. 2014;260:577–580.
146. Sureka, B., Thukral, B.B., Mittal, M.K., Mittal, A., Sinha, M. Radiological review of pleural tumors. Indian J. Radiol. Imaging. 2013;23:313–320.
147. Taioli, E., Wolf, A.S., Flores, R.M. Meta-analysis of survival after pleurectomy decortication versus extrapleural pneumonectomy in mesothelioma. Ann. Thorac. Surg. 2015;99:472–480.
148. Testa, J.R., Cheung, M., Pei, J. et al, Germline BAP1 mutations predispose to malignant mesothelioma. Nat. Genet. 2011;43:1022–1025.
149. Thomas, D.C. Invited commentary is it time to retire the pack-years variable? Maybe Not!. Am. J. Epidemiol. 2013;179:299–302.
150. Tournoy, K.G., Burgers, S.A., Annema, J.T. et al, Transesophageal endoscopic ultrasound with fine needle aspiration in the preoperative staging of malignant pleural mesothelioma. Clin. Cancer Res. 2008;14:6259–6263.
151. Treasure, T., Dusmet, M., Fiorentino, F. et al, Surgery for malignant pleural mesothelioma: why we need controlled trials. Eur. J. Cardiothorac. Surg. 2014;45:591–592.
152. Truong, M.T., Viswanathan, C., Godoy, M.B., Carter, B.W., Marom, E.M. Malignant pleural mesothelioma: role of CT, MRI, and PET/CT in staging evaluation and treatment considerations. Semin. Roentgenol. 2013;48:323–334.
153. Truong, M.T., Viswanathan, C., Godoy, M.B., Carter, B.W., Marom, E.M. Malignant pleural mesothelioma: role of CT, MRI, and PET/CT in staging evaluation and treatment considerations. Semin. Roentgenol. 2013;48:323–334.
154. Van Meerbeeck, J.P., Gaafar, R., Manegold, C. et al, Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European organisation for research and treatment of cancer lung cancer group and the national cancer institute of Canada. J. Clin. Oncol. 2005;23:6881–6889.
155. Vlandereen, J., Portengen, L., Shuz, J. et al, Effect modification of the association of cumulative exposure and cancer risk by intensity of exposure and time since exposure cessation: a flexible method applied to cigarette smoking and lung cancer in the SYNERGY study. Am J. Epidemiol. 2013;179:290–298.
156. Vogelzang, N.J., Rusthoven, J.J., 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;21:2636–2644.
157. van den Bogaert, D.P., Pouw, E.M., van Wijhe, G. et al, Pemetrexed maintenance therapy in patients with malignant pleural mesothelioma. J. Thorac. Oncol. 2006;1:25–30.
158. Waller, D.A., Morritt, G.N., Forty, J. Video-assisted thoracoscopic pleurectomy in the management of malignant pleural effusion. Chest. 1995;107:1454–1456.
159. Weber, D.G., Casjens, S., Johnen, G. et al, Combination of MiR-103a-3p and mesothelin improves the biomarker performance of malignant mesothelioma diagnosis. PLoS One. 2014;9:e114483.
160. Wheatley-Price, P., Yang, B., Patsios, D. et al, Soluble mesothelin-related peptide and osteopontin as markers of response in malignant mesothelioma. J. Clin. Oncol. 2010;28:3316–3322.
161. World Health Organization Regional Office for Europe. Air Quality Guidelines for Europe Copenhagen 2000. WHO Regional Publications, ; 2000 (European Series, No. 9).
162. Yoshikawa, Y., Sato, A., Tsujimura, T. et al, Frequent inactivation of the BAP1 gene in epithelioid-type malignant mesothelioma. Cancer Sci. 2012;103:868–874.
163. Zahid, I., Sharif, S., Routledge, T., Scarci, M. What is the best way to diagnose and stage malignant pleural mesothelioma. Interact Cardiovasc. Thorac. Surg. 2011;12:254–259.
164. Zalcman, G., Margery, J., Scherpereel, A. et al, IFCT-GFPC-0701 MAPS trial, a multicenter randomized phase II/III trial of pemetrexed-cisplatin with or without bevacizumab in patients with malignant pleural mesothelioma. J. Clin. Oncol. 2010;28 (abstract 7020).
165. Zalcman, G., Mazieres, J., Margery, J. et al, Bevacizumab 15 mg/kg plus cisplatin-pemetrexed (CP) triplet versus CP doublet in malignant pleural mesothelioma (MPM): results of the IFCT-GFPC-0701 MAPS randomized phase 3 trial. J. Clin. Oncol. 2015;33 (abstract 7500).
166. Zielinski, M., Hauer, J., Hauer, L. et al, Staging algorithm for diffuse malignant pleural mesotelioma. Interact Cardiovasc. Thorac. Surg. 2010;10:185–189.
167. Zucali, P.A., Simonelli, M., Michetti, G. et al, Second-line chemotherapy in malignant pleural mesothelioma: results of a retrospective multicenter survey. Lung Cancer. 2012;75:360–367.
168. van Zandwijk, N., Clarke, C., Henderson, D. et al, Guidelines for the diagnosis and treatment of malignant pleural mesothelioma. J. Thorac. Dis. 2013;5:E254–E307.