European Respiratory Society
Thoracic Malignancies (out of print)

This book has been superseded by a newer edition.

Lung cancer is estimated to be the fifth most common cause of death in the world and the most commonly diagnosed cancer. This book covers the huge advances that have been made in understanding the biology of lung cancer, the improvements in diagnostic staging and the introduction of new molecularly targeted therapies. An essential reference guide for respiratory physicians dealing with all aspects of thoracic malignancies.

  • European Respiratory Society Monographs
  1. Page vii
  2. Page viii
  3. Page ix
  4. Page 1
    Correspondence: N. van Zandwijk, Asbestos Diseases Research Institute, Bernie Banton Centre, University of Sydney, Hospital Road, Concord NSW 2139, Australia. E-mail:

    Lung cancer is the leading cause of cancer mortality for males and females, and has grown into a worldwide problem over the last 50 yrs.

    Cigarette smoking elicits >80% of all lung cancers. Although the prevalence of smoking is declining, the risk of lung cancer after smoking cessation persists and remains elevated in comparison to never-smokers.

    Despite a rapid increase in insight into carcinogenesis, the accurate identification of high-risk groups has remained difficult; attempts to decrease lung cancer risk by preventive measures other than smoking cessation have so far been unsuccessful.

    However, strategies to slow, halt or even reverse the carcinogenic process continue to gain great interest. It is very likely that further identification of the different molecular steps of carcinogenesis will finally translate into effective preventive strategies.

  5. Page 15
    Correspondence: E. Brambilla, CHU Albert Michallon, Dept of Pathology, BP 217, 38043 Grenoble Cedex 0933 476765949, France. E-mail:

    Lung cancer is the most commonly diagnosed cancer and the first cause of mortality worldwide. The clinical importance of a standard international classification is increasing, since therapeutic decisions and treatment response are more than ever based on histological typing. The international standard for histological classification of lung tumours is that proposed by the World Health Organization in 1999, revised with further molecular characteristics in 2004. The four major histological classes, squamous cell carcinoma, adenocarcinoma (the highest in frequency), small cell carcinoma and large cell carcinoma, are distinguished by objective criteria on surgical samples and rarely by immunohistochemical markers. However, differentiation signs required for classification may not be present in small biopsies in the context of extended late-stage nonsurgical disease and classification will then rely on a panel of immunohistochemical markers, in order to keep minimal the diagnosis of nonsmall cell or large cell carcinoma, which is of no help in the specific or targeted therapy indications.

    Histological heterogeneity is an important feature of lung cancer, as is the strong distribution bias of histology, with smokers developing all categories and nonsmokers presenting mostly with adenocarcinoma.

  6. Page 36
    Correspondence: F.R. Hirsch, University of Colorado Cancer Center, P.O. Box 6511, Mail Stop 8117, Aurora, CO 80045, USA. E-mail:

    Bronchial dysplasia, atypical adenomatous hyperplasia and diffuse idiopathic pulmonary neuroendocrine hyperplasia are putative pre-invasive lesions for squamous cell carcinoma, adenocarcinoma and carcinoid tumours of the lung, respectively.

    Recent improvements in our ability to detect and sample these lesions along with detailed histological classification schemes have led to numerous advances in our understanding of their natural history. Importantly, many molecular and genetic alterations can now be associated with the development of these lesions and, in some instances, are being related to their progression. These findings are leading to the description of biomarkers that will have applications in the early detection of pre-invasive lung lesions and can be used as indicators of their malignant potential.

    In addition, new techniques and therapies are being developed for the prevention of lung cancer. The evaluation of these potential therapeutic strategies are being tested in increasingly relevant pre-clinical models of pre-invasive disease, and the findings from these studies are being used to efficiently evaluate potential preventive therapies in ongoing clinical trials.

    In the present chapter, we present new findings related to the detection, molecular characterisation and evaluation of diagnostic and therapeutic intervention for pre-invasive lesions of the lung.

  7. Page 57
    Correspondence: J.R. Jett, Mayo Clinic, Rochester, MN 55905, USA. E-mail:

    Currently, the diagnosis of lung cancer is made primarily in the pursuit of symptoms. Screening is not being widely applied in patients at risk for lung cancer because no screening test (chest radiography, sputum cytology or computed tomography (CT)) has been shown to reduce mortality from lung cancer.

    The most sensitive image modality currently available for detecting pulmonary nodules is CT. Conventional chest CT requires radiation dosage and image-acquisition time that is impractical for screening purposes. However, the development of low-dose, fast-spiral CT has greatly reduced the radiation dose and the scan time, making screening feasible.

    Prospective, single-arm observational studies have shown that screening with CT detects a large percentage of lung cancer in early stage and with favourable prognosis for those cancers detected, but the apparent survival improvement may be due to the biases inherent with screening. Screening introduces inherent biases of lead time, length time and overdiagnosis; it is not clear if the calculated survival is true improvement or just apparent improvement due to bias.

    Randomised controlled trials of CT screening are currently under way in the USA and Europe that will hopefully definitively show mortality reduction with CT screening.

  8. Page 71
    Correspondence: N. Navani, Centre for Respiratory Research, University College London, Rayne Building, 5 University Street, London, WC1E 6JJ, UK. E-mail:

    Lung cancer presents late in its natural history and its symptoms and signs are often nonspecific. Spread of the disease within the chest may result in pleural effusion and mediastinal involvement. Extrathoracic metastases commonly occur to bone, brain and liver. Distant effects of lung cancer, termed paraneoplastic syndromes, produce a varied constellation of symptoms and signs with musculoskeletal, endocrine and neurological abnormalities predominating. Paraneoplastic syndromes do not imply metastatic spread and may manifest prior to the discovery of the underlying tumour.

  9. Page 88
    Correspondence: T. Eisen, Dept of Oncology, University of Cambridge and Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. E-mail:

    Lung cancer is largely a smoking-induced tumour. Understanding of genetic predisposition to smoking dependency and lung cancer is increasing as powerful genomic technologies are developed. Whole genome microarray expression analysis has led to further subclassification of lung cancer, particularly adenocarcinoma, and the development of new prognostication methods.

    Dissection of the genetic and morphological features of dysplastic and early malignant cells together with advances in our understanding of stem cell biology and the role of cancer stem cells may lead to the development of new strategies to detect and treat early lung cancers and prevent the development of chemoresistance.

    As the cell biology of lung cancer becomes clearer, so new therapeutic targets become available. These therapeutic possibilities range from selection of the most appropriate chemotherapies, through inhibition of growth factors, angiogenesis and drug resistance to activation of the anti-tumour host immune response. The importance of tumour stroma interactions in determining cancer behaviour is also a new avenue that may bring improvements in treatment outcome through avoidance of chemoresistance to conventional drugs and through the development of new drugs to stromal targets.

    The bewildering biological variety of superficially similar tumours underlines the future directions of the management of lung cancer. Interventions at all levels from prevention to chemotherapy for advanced disease will be increasingly influenced by genetic and cell biological analysis of individual patients and their tumours.

    However, so far, this rapid progress has not translated to rapid clinical improvements. As this translational gap is bridged over time, significant improvements will result.

  10. Page 106
    Correspondence: P. Shaw, Dept of Radiology, University College Hospital, 235 Euston Road, London NW1 2BU44 02073809068, UK. E-mail:

    Lung cancer is the most common cancer worldwide, and remains the leading cause of death from cancer in the UK. Despite its prevalence, screening is not currently recommended, although large scale trials using computed tomography (CT) are ongoing.

    Chest radiographs remain the first line of imaging investigation usually. With the advent of multislice CT scans, image acquisition times and resolution have improved. Nodule detection has been ameliorated and high quality coronal and sagittal reformats can now be constructed. Positron emission tomography (PET) scanning has revolutionised staging and has a negative predictive value for N3 disease, which is equal to that of gold standard mediastinoscopy. In the UK, the National Institute of Clinical Excellence (London, UK) has recommended that when a PET scan is negative for N2/3 disease, then biopsy is not required even if the nodes are enlarged by CT criteria. Dual modality PET-CT images are increasingly performed, which overcome the poor spatial resolution of using PET alone. Magnetic resonance imaging is still recommended for the assessment of superior sulcus tumours, and research into its value for nodal staging is ongoing at present.

    Lung cancer is divided into small cell lung cancer and nonsmall cell lung cancer (NSCLC). The imaging characteristics of the different tumours vary. At present the tumour, node, metastasis staging system only applies to NSCLC.

    In addition to characterising and staging lung cancer, imaging is used to guide the best site for tissue sampling. This may involve computed tomography guided percutaneous transthoracic biopsies or ultrasound guided percutaneous nodal sampling. A co-axial system is increasingly used to perform radiologically guided biopsies.

  11. Page 136
    Correspondence: N. Navani, Centre for Respiratory Research, University College London, Rayne Building, 5 University Street, London WC1E 6JJ44 2073809476, UK. E-mail:

    A tissue diagnosis of lung cancer is crucial to differentiate nonsmall cell lung cancer (NSCLC) from small cell lung cancer. In patients with intra-thoracic disease, bronchoscopy remains a standard, routinely performed procedure that can provide important diagnostic as well as staging information. Surgical biopsy and mediastinoscopy are still considered to be gold standard investigations. However, rapid advances in technology have allowed the bronchoscopist's role to be expanded considerably. Autofluorescence bronchoscopy aids in the diagnosis of pre-invasive lesions and early lung cancers, while endobronchial and endoscopic ultrasound have become established for the mediastinal staging of NSCLC. In the current epidemic of lung cancer, these techniques are at the forefront of establishing a diagnosis and disease stage and are central to the multidisciplinary management of lung cancer.

  12. Page 150
    Correspondence: J-P. Sculier, Dept of Critical Care and Thoracic Oncology, Institut Jules Bordet, Université Libre Bruxelles (ULB), 1, rue Héger-Bordet, B-1000 Brussels, Belgium

    The stage of lung cancer has a key role in the management of the patient. The system classifying lung cancer based on the status of primary tumour (T), regional lymph nodes (N) and metastatic involvement (M) was originally proposed in 1946, and has been the subject of many modifications to improve its prognostic and operational roles.

    In the present chapter, the 1997 classification is described, as well as the various problems reported in the literature concerning its application.

    In order to improve the staging system, an international initiative, International Association for the Study of Lung Cancer staging project, was undertaken to make a huge databases and to propose a revision of the 1997 system. The proposal, which will be used as official staging classification in 2009, is presented and discussed, as well as the role of stage in prognosis. Indeed, stage is so far the main prognostic factor in lung cancer.

    In the future, proposals for further TNM revisions should be based on a prospective international multicentric databases where the details of the T, N and M descriptors should be available.

  13. Page 169
    Correspondence: C.F.N. Koegelenberg, Dept of Medicine, Faculty of Health Sciences, University of Stellenbosch and Tygerberg Academic Hospital, P.O. Box 19063, Tygerberg, 7505, Cape Town, South Africa. E-mail:

    Pulmonary resection remains the only curative intervention for bronchogenic carcinoma, but is considered to be a high-risk surgical procedure. Furthermore, pulmonary resection candidates often suffer from concomitant chronic obstructive lung disease or ischaemic heart disease. Pulmonary resection candidates therefore should undergo a structured pre-operative evaluation while they are at their personal best. The clinical assessment should focus on respiratory, cardiovascular and other general clinical parameters, including the smoking status. A resting ECG should be performed on all candidates. Serious cardiovascular pathology should be diagnosed and corrected prior to continuing with the stepwise approach.

    The initial pulmonary function evaluation should at least include forced expiratory volume in 1 s (FEV1), forced vital capacity and diffusing capacity of the lung for carbon monoxide (DL,CO). Values > 80% of predicted for FEV1 and DL,CO are associated with an uncomplicated surgical course for resection up to a pneumonectomy. Patients with impaired pulmonary functions warrant formal cardiopulmonary exercise testing. A maximal oxygen uptake (V′O2,max) value of >20 mL·kg−1·min−1 or >75% predicted qualifies for resection up to pneumonectomy, whereas a value <10 mL·kg−1·min−1 (or <40% predicted) is generally prohibitive for any resection. The cut-off value for a lobectomy is 15 mL·kg−1·min−1.

    Intermediate cases (V′O2,max 10–20 mL·kg−1·min−1 or 40–75%) require some form of assessment of their regional lung functions in order to predict post-operative values. This should be done by means of anatomical calculations, with either radionucleotide perfusion scanning or quantitative computed tomography scanning reserved for borderline or indeterminate cases. Patients with predicted post-operative FEV1 and DL,CO >40% or &SetFont Italic="1";V&SetFont Italic="0";′O2,max >10 mL·kg−1·min−1 may still have a resection up to a calculated extent.

    Lung volume reduction surgery may be combined with lung cancer surgery in selected individuals, who may otherwise have been deemed inoperable.

  14. Page 187
    Correspondence: S.G. Spiro, 66 Grange Gardens, Pinner, Middlesex, HA55QF, UK. E-mail:

    Surgery remains the best option for cure in nonsmall cell lung cancer (NSCLC) and for the occasional small cell tumour. About 10–15% of NSCLC cases go to pulmonary resection, although the resection rate varies across different countries and within countries. Staging is paramount with regard to case selection for resection, and the introduction of positron emission tomography scanning and endoscopic mediastinal lymph node sampling will further refine this. The new International Association for the Study of Lung Cancer staging classification, based on a very large number of cases, has further defined prognosis by stage, and will influence selection of patients for surgery. The mortality of resection is falling and in large centres is now about 1% for lobectomy and 3–4% for pneumonectomy. Sublobar resections are becoming increasingly common as more patients are found to have stage I disease following computed tomography screening or more intensive investigation for chronic obstructive pulmonary disease. Segmentectomy appears as successful as lobectomy of patients below 71 yrs of age, with better preservation of lung function. However the non-anatomic wedge resection carries a worse long-term survival than both segmentectomy and lobectomy. Following careful case selection, older patients fare no worse than their younger counterparts. While patients presenting with stage I and II disease are suitable for curative surgery, stage IIA remains a complex constellation of presentations. Those with N1 disease can do relatively well, but for presentations such as superior sulcus tumours and chest wall tumours, if there is nodal involvement and the stage is worse than T3N0, the prognosis is much worse. The evidence for surgery after chemoradiation induction for locally advanced stage IIIA or IIIB has not yet been made, and chemoradiotherapy alone may be the treatment of choice. Trial results are awaited. In addition to age (half of lung cancer patients present aged ≥70 yrs), comorbidity remains a major reason for inoperability. For small cell lung cancer, there are only small series of patients who have undergone resection. Each case should be reviewed on its merits and if at a truly early stage after the best possible staging, resection must be considered.

  15. Page 207
    Correspondence: M. Hatton, Dept of Clinical Oncology, Weston Park Hospital, Whitham Rd, Sheffield, S10 2SJ, UK

    There is a well established role for radiation treatment in the management of nonsmall cell lung cancer. As a single modality it is indicated as a radical treatment option for patients with loco-regional disease that is unresectable disease (or for patients who decline surgery) and deemed unsuitable for chemotherapy. For these patients the evidence points towards some advantages for accelerated treatment regimes such as continuous hyperfractionated accelerated radiotherapy, and the research effort should be directed towards dose escalation and the application of the new technologies. As a single modality, radiotherapy also maintains an important role, in combination with all other aspects of palliative care, in the control of symptoms and maintenance of quality of life.

    A multimodality approach is now the standard for the management of most presentations of lung cancer and the combination of chemoradiotherapy is established in the radical treatment of nonsmall cell lung cancer. How best these two modalities are combined in palliative treatment is an area for further research. The benefits of the combination of radiotherapy and surgery are less clear-cut, as are any benefits from a trimodality approach with input from all three treatment disciplines.

  16. Page 244
    Correspondence: D. Gilligan, Oncology Centre, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Trust, Cambridge, CB2 0QQ, UK. E-mail:

    Lung cancer is the leading cause of cancer death in the western world. Surgical resection remains the treatment of choice for operable nonsmall cell lung cancer (NSCLC). Even after complete resection, systemic relapse is common and hence there is a role for adjuvant and neoadjuvant treatment.

    Adjuvant chemotherapy is feasible and improves overall survival in completely resected NSCLC, with cisplatin chemotherapy offering survival advantage of 5% at 5 yrs. Use of alkylating agents is not recommended as they are detrimental to survival. There is a small increase in noncancer-related death with cisplatin chemotherapy; hence, only patients at high risk of systemic relapse should be offered adjuvant treatment. At present, adjuvant chemotherapy is not recommended for stage IA patients and its benefits in stage IB patients are debatable. Adjuvant uracil-tegafur has no confirmatory trials in the western population and, thus, it is not recommended outside the context of a clinical trial. There has been an ongoing debate about neoadjuvant versus adjuvant chemotherapy. Neoadjuvant chemotherapy is feasible, with no increase in post-operative complications. It has so far failed to show improvement in overall survival and it is likely that the standard of care is towards adjuvant chemotherapy.

    In the adjuvant setting, where the aim is cure, cisplatin-based regimes are preferred over carboplatin-based regimes. One of the main toxicities of cisplatin is nausea and vomiting but, with the use of new anti-emetics, this may be less of an issue. There should be no scepticism about chemotherapy in elderly patients. Patients under the age of 70 yrs with a good performance status benefit from adjuvant chemotherapy, but there is paucity of data for those over 70.

    New knowledge of mechanisms of oncogenesis has allowed us to identify new molecular targets for cancer treatment. So far, no molecular targets have been shown conclusively to have a significant relationship with clinical outcome, particularly survival in NSCLC. Newer targeted agents, including including epidermal growth factor receptor and vascular endothelial growth factor inhibitors, are still under evaluation in phase III clinical trials.

  17. Page 260
    Correspondence: R.M. Huber, Division of Respiratory Medicine, Medizinische Klinik Innenstadt, University of Munich, Ziemssenstraße 1, D-80336 Munich49 8951604905, Germany. E-mail:

    In nonsmall cell lung cancers (NSCLC), up to 40% of patients present with locally advanced disease with involvement of the hilar and mediastinal lymph nodes. The term locally advanced includes tumours at stage IIIB and inoperable tumours at stage IIIA. The primary intention in these patients is curative treatment with multimodality therapy, including chemotherapy and thoracic radiotherapy. However, the benefit of combined radiochemotherapy must be weighed against the potential for increased toxicity. If the individual patient and tumour characteristics allow an intense treatment approach, simultaneous radiotherapy/chemotherapy is the probable standard of care. Biological agents such as tyrosine-kinase inhibitors and the importance of subtypes of NSCLC are being evaluated for integration into the management of these tumours.

  18. Page 271
    Correspondence: E. Quoix, Service de Pneumologie, Nouvel Hôpital Civil, Hôpitaux universitaires de Strasbourg, 1, Place de l’hôpital, 67091 Strasbourg cedex, France. E-mail:

    There is no dispute that chemotherapy is the standard treatment for advanced stage (IIIB (wet) and IV) nonsmall cell lung cancer.

    The best chemotherapy regimen for patients with performance status (PS) 0–1, no renal or cardiac insufficiency is a platin-based doublet. The drug combined with platin salt maybe any of the new generation drugs (vinorelbine, taxotere, taxol, gemcitabine, pemetrexed) with similar results regarding survival benefit, the differences being essentially the toxicity profiles. Carboplatin, which is less toxic than cisplatin, may be used instead of cisplatin, with a slightly less efficacy (probably not clinically important). Tailored treatment approach is a new concept with adaptation of platin-based doublets to the histology of the tumour (gemcitabine is no more recommended for adenocarcinoma and pemetrexed is not recommended for squamous cell carcinoma). Also gene expression (ERCC1, RRM1, β-tubulin class III, etc.) might become of primary importance for customised chemotherapy.

    The recommended number of cycles is four to six for stable or responding patients. At the current time there is no indication in favour of any maintenance therapy.

    For patients with PS 2, a combination of carboplatin and paclitaxel is feasible, but there is no direct comparison with single agent therapy and thus no clear-cut recommendation.

    In elderly patients the recommended first-line chemotherapy is a single agent, the most extensively studied being vinorelbine and gemcitabine.

    Second-line therapy is now well established, with docetaxel or pemetrexed being the recommended choices. Targeted therapies can be used either as second-line therapy (female, nonsmokers, adenocarcinomas) or third-line therapy.

    There is no recommendation beyond third-line regarding any chemotherapy/targeted therapy scheme and this remains an unmet need.

  19. Page 284
    Correspondence: D.F. Heigener, Dept of Thoracic Oncology, Krankenhaus Grosshansdorf, Woehrendamm 80, 22927 Grosshansdorf, Germany. E-mail:

    There are numerous targeted approaches under investigation, and mentioning them all is beyond the scope of this chapter. The only approved substances are erlotinib, bevacizumab and gefitinib; the latter not in Europe. Cetuximab has proven to be effective as additional treatment in the first-line setting of advanced disease and is awaiting approval. Beyond that, we have to await many phase III trials for further effective drugs. Combination trials of agents with different targets (e.g. epidermal growth factor receptor and vascular endothelial growth factor receptor) are under way.

  20. Page 299
    Correspondence: D. De Ruysscher, Dept of Radiation Oncology (Maastro Clinic), University Medical Center Maastricht, GROW Research Institute, Dr. Tanslaan 12, NL-6229 ET Maastricht31 884455773, The Netherlands. E-mail:

    Limited disease small cell lung cancer (LD-SCLC) is a heterogeneous disease, not only for its clinical behaviour, but also for its anatomical extension. In very rare, early cases, LD-SCLC might be treated with surgery and chemotherapy, but as the overwhelming majority of patients present with locally advanced disease, the standard of care is concurrent chest radiotherapy with cisplatin and etoposide chemotherapy followed by prophylactic cranial irradiation (PCI). Newer chemotherapeutic drugs as well as targeted agents have not improved the outcome thus far.

    Given concurrently with chest irradiation, cisplatin combined with etoposide, administered every 21 days for 4–5 cycles, have frequently been used.

    Thoracic radiotherapy should begin as early as possible during the first chemotherapy cycle. A total radiation dose of 45 Gy is recommended, delivered in a short overall treatment time (<4 weeks). Accelerated therapy increases absolute 5-yr survival rates by 10% compared with longer treatment times, at the expense of an incidence of severe oesophagitis of ∼30% that is reversible within a few weeks. Haematological complications and late pulmonary damage may occur but are not more frequent than with less intensive schedules yielding inferior long-term survival. Obviously, only fit patients (World Health Organisation performance status 0–2) with adequate organ function can tolerate this treatment.

    As the tumour remission status is difficult to assess due to radiographic changes induced by chemoradiation therapy, patients that show no tumour progression are suitable for PCI. The recommended dose is 25 Gy, given in 10 daily fractions of 2.5 Gy. PCI reduces the risk of brain metastases by ∼50%. When delivered after chemotherapy and at the recommended doses and fractionation, PCI did not lead to persistent neurocognitive function decline.

    With this treatment strategy, 5-yr survival rates of 25% can be achieved in patients with LD-SCLC.

  21. Page 310
    Correspondence: P.E. Postmus, Dept of Pulmonary Diseases, Vrije Universiteit University Medical Centre, Amsterdam, The Netherlands. E-mail:

    Treatment outcome of extensive disease small cell lung cancer has reached a plateau during the last two decades. The only relevant and recent improvement has come from adding cranial irradiation to patients responding to chemotherapy. New drugs have either not been tested yet in small cell lung cancer or failed to demonstrate any promising result.

  22. Page 318
    Correspondence: Y.C.G. Lee, University Dept of Medicine, 4/F, G Block, Queen Elizabeth II Medical Centre, Perth WA 600961 893462816, Australia. E-mail:

    Malignant pleural disease is common in patients with lung cancer. Establishing malignant pleural involvement in lung cancer patients often alters management and significantly impacts on staging and prognosis.

    Histocytological confirmation should be obtained for suspected malignant pleural effusions to differentiate them from paramalignant effusions. If cytology is negative, imaging-guided biopsy or thoracoscopy should be considered.

    Relieving dyspnoea and improving quality of life are the goals of management of malignant effusions. Pleurodesis should be considered in suitable patients. Long-term indwelling pleural catheters are recommended in patients with trapped lung or in whom pleurodesis has failed.

  23. Page 336
    Correspondence: F.J.F. Herth, Dept of Pneumology and Critical Care Medicine, Thoraxklinik am Universitätsklinikum, Amalienstr. 5, D-69126 Heidelberg49 62213961202, Germany. E-mail:

    The field of interventional pulmonary medicine is a relatively new area in pulmonary medicine, resulting from technological advances as well as the increasing need for palliative and curative treatment modalities for patients with tracheobronchial, parenchymal and pleural disease. This chapter reviews the advances in endoscopic techniques aimed at the tracheobronchial tree, laser photoresection, electrosurgery, argon plasma coagulation, stent placement, brachytherapy and others, in patients suffering from lung cancer.

  24. Page 349
    Correspondence: J.M. Samet, Dept of Preventive Medicine, Keck School of Medicine, Institute for Global Health, University of Southern California, 1441 Eastlake Ave, Room 4436, MC 9175, Los Angeles, CA 900891 3238650127, USA. E-mail:

    In the USA, lung cancer remains the leading cause of cancer death in both males and females, even though an extensive list of modifiable risk factors has long been identified. The predominant cause of lung cancer is exposure to tobacco smoke, with active smoking causing most cases but passive smoking also contributing to the lung cancer burden. The reductions in smoking prevalence in males that occurred in the late 1960s until the 1980s will continue to drive lung cancer mortality rates downward in males during the first portion of this century, but rates in females have not yet begun to decrease. Asbestos has been identified as responsible for the great majority of mesothelioma cases. Fortunately, exposures to major occupational respiratory carcinogens have largely been controlled, but the population is still exposed to environmental causes of lung cancer, including radon, the second leading cause of lung cancer death. Mesothelioma incidence has begun to reflect limitations on use of asbestos implemented decades ago and should continue to fall if asbestos use is limited and workers are protected.

  25. Page 392
    Correspondence: A. Scherpereel, Service. de Pneumologie et d’Oncologie Thoracique, Hôpital Calmette, CHRU de Lille, 59037 Lille Cedex, 33 320445611, France. E-mail:

    Malignant pleural mesothelioma (MPM) is a previously rare cancer with an increasing incidence worldwide linked to asbestos, its main aetiological factor. Moreover, MPM patients have a poor prognosis despite recent improvements in disease management. Most patients are diagnosed late in the course of the disease when radical treatment is no longer an option. Therefore, an earlier diagnosis of MPM is needed to potentially increase the survival of patients.

    To date, a firm and reliable diagnosis of mesothelioma is based on histology, usually obtained by biopsies during a thoracoscopy, the key procedure for MPM, and using international 2004 World Health Organization classification and guidelines from pathologists. Several soluble markers assessed in blood or pleural effusions, including soluble mesothelin and osteopontin, have been previously proposed for MPM diagnosis but none has been validated yet. Soluble mesothelin, the most promising candidate, has good diagnostic and prognostic values but is quite specific for the epithelioid subtype, the most frequent type of mesothelioma, thus restraining its usefulness in practice. Other potential markers, such as osteopontin, are of little interest for MPM diagnosis because of their low specificity.

    Imaging, such as computed tomography (CT) scanning and positron emission tomography, separately or better when coupled, may help MPM diagnosis and staging, but present data do not justify their use for MPM screening among asbestos-exposed subjects. Current international “tumour, node, metastasis” classification for MPM staging is of limited use in routine practice, because it is based on CT scans and has only been validated with patients who have been surgically treated, quite rare in clinical practice.

    Optimising early diagnosis and staging of MPM, along with developing new treatments for patients through large and randomised clinical trials, must be our main goals in improving the outcome of patients.

  26. Page 407
    Correspondence: W. Weder, Division of Thoracic Surgery, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland. E-mail:

    Over the past 10 yrs, there have been several achievements in the management of malignant pleural mesothelioma (MPM), including a better insight into the tumour biology, more effective chemotherapy with pemetrexed or gemcitabine in combination with cisplatin, and extrapleural pneumonectomy (EPP) within a multimodality treatment. Nevertheless, the choice of the best treatment remains a matter of debate. A systematic review of the value of surgery remains highly critical as to the quality of the studies and the lack of randomised studies. Pleurectomy/decortication (P/D) has proven its effectiveness as a palliative procedure for symptom control such as relief of dyspnoea due to control of pleural effusion and freeing a tumour-entrapped lung but it is limited to good performance status patients. P/D provides the advantage of avoiding a pneumonectomy and may be indicated for patients with reduced cardiopulmonary capacity or mesotheliomas located mainly at the parietal pleura. However, P/D is, by intent, less radical than EPP. Furthermore, the application of full adjuvant hemithoracic radiotherapy is not possible because of the risk of damage to the remaining lung. The best long-term results may be achieved by multidisciplinary concepts including EPP together with neo- or adjuvant chemotherapy and a median survival time of about 2 yrs has been reported by several studies. Hemithoracic radiotherapy after EPP has been suggested to decrease the rate of local relapse; however, it is a complex procedure associated with additional morbidity and mortality.

    Diagnosis and treatment of MPM remains a challenge and is best performed in a specialised centre by a multidisciplinary team, in order to balance treatment related morbidity with potential treatment benefit. Proper randomised trials are still needed to answer these basic questions.

  27. Page 419
    Correspondence: R.M. Rudd, London Lung Cancer Group, Barts Mesothelioma Research, 54 New Cavendish Street, London, UK. E-mail:

    Systemic chemotherapy is the only type of treatment for malignant pleural mesothelioma, which has been demonstrated by randomised trial to confer prolongation of survival without detrimental effect on quality of life. The combination of pemetrexed with cisplatin prolongs survival by a median of ∼3 months. Carboplatin can probably be substituted for cisplatin for greater tolerability without significant loss of efficacy. Pemetrexed with a platinum agent should be regarded as first choice therapy in the current state of knowledge. The combination of gemcitabine with a platinum agent and single agent vinorelbine are other regimes which have useful antitumour activity, although they have not been demonstrated by randomised trial to prolong survival. The optimal timing and duration of chemotherapy have not yet been determined. There is some evidence to support the use of second-line chemotherapy in selected patients. Patients who are fit enough to receive chemotherapy should be given full information about it by a clinician experienced in treating mesothelioma with chemotherapy, so they can decide whether they wish to receive it. It is no longer acceptable for respiratory physicians to tell patients that there is no treatment available for mesothelioma. Many new targeted agents have been utilised for treatment of mesothelioma. Epithelial growth factor receptor inhibitors have proved to be of no value. Additionally, to date, results with angiogenesis inhibitors have been disappointing although trials of various agents of this type and other cell-cycle pathway inhibitors are in progress.