Lung Cancer by Sujal R. Desai


8157410f44a8e89.jpg Author Sujal R. Desai
Isbn 9780521872027
File size 3.5 MB
Year 2015
Pages 166
Language English
File format PDF
Category medicine



 

Lung Cancer Despite the worldwide drive to increase awareness of the risks of smoking, lung cancer remains a global problem. A multidisciplinary team approach is now considered the most effective way to manage lung cancer. Imaging plays a central role in this multidisciplinary approach; this is reflected in the present volume. Individual chapters focus on imaging (including screening, diagnosis of symptomatic cases and staging) pathology and treatment options in lung cancer. Due to recent interest in the potential role of PET for a variety of malignancies, a separate chapter is devoted to this technique. Each volume in Contemporary Issues in Cancer Imaging is coordinated by an expert guest editor with contributions from all members of the multidisciplinary team, bringing together expertise from many specialties to promote the understanding and application of modern imaging in patient management. Sujal R. Desai is a Consultant Radiologist at King’s College Hospital, London. Contemporary Issues in Cancer Imaging A Multidisciplinary Approach Series Editors Rodney Reznek Cancer Imaging, St Bartholomew’s Hospital, London Janet Husband Diagnostic Radiology, Royal Marsden Hospital, Surrey Lung Cancer Sujal R. Desai CAMBRIDGE UNIVERSITY PRESS Cambridge, New York, Melbourne, Madrid, Cape Town, Singapore, São Paulo Cambridge University Press The Edinburgh Building, Cambridge CB2 8RU, UK Published in the United States of America by Cambridge University Press, New York www.cambridge.org Information on this title: www.cambridge.org/9780521872027 © Cambridge University Press 2007 This publication is in copyright. Subject to statutory exception and to the provision of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of Cambridge University Press. First published in print format 2006 ISBN-13 ISBN-10 978-0-511-27042-0 eBook (NetLibrary) 0-511-27042-9 eBook (NetLibrary) ISBN-13 ISBN-10 978-0-521-87202-7 hardback 0-521-87202-2 hardback Cambridge University Press has no responsibility for the persistence or accuracy of urls for external or third-party internet websites referred to in this publication, and does not guarantee that any content on such websites is, or will remain, accurate or appropriate. Contents Contributors Series Foreword Introduction 1 Clinical Considerations in Lung Cancer page vii ix xi 1 Pallav Shah 2 Pathology of Lung Cancer 12 Sabine Pomplun 3 Imaging of Lung Cancer 27 Sayed A. H. Z. Jafri and Sarah J. Copley 4 Screening for Lung Cancer 46 Thomas E. Hartman 5 Staging of Lung Cancer 57 Zelena A. Aziz 6 Positron Emmision Tomography in Lung Cancer 84 Thomas B. Lynch and Gary J. R. Cook 7 Contemporary Issues in the Systemic Treatment of Lung Cancer 99 Alistair Ring and Joseph Prendiville 8 Radiotherapy in Lung Cancer 120 Shahreen Ahmad 9 Surgery for Lung Cancer 136 Andrew Chukwuemeka and Michael T. Marrinan Index 143 Colour plate section appears between pages 20 and 21 v Contributors Shahreen Ahmad, b.sc., m.b.b.s., m.r.c.p., f.r.c.r. Guy’s, King’s and St Thomas’ Joint Cancer Centre Department of Clinical Oncology St Thomas’ Hospital London, UK Zelena A. Aziz, Department of Radiology St Bartholomew’s and the Royal London Hospital London, UK Andrew Chukwuemeka, m.d., f.r.c.s. SELCN Lead for Lung Cancer Research Guy’s, King’s and St Thomas’ Cancer Centre London, UK Gary. J. R. Cook, f.r.c.r., f.r.c.p. Department of Nuclear Medicine and PET Royal Marsden Hospital Sutton Surrey, UK Sarah. J. Copley, m.d., m.r.c.p., f.r.c.r. Department of Radiology Hammersmith Hospital London, UK Thomas E. Hartman, m.d. Department of Radiology Mayo Clinic Rochester, MN, USA Sayed A. M. Z. Jafri, m.b.b.s., m.r.c.s. Department of Radiology Hammersmith Hospital London, UK Thomas. B. Lynch, f.r.c.p. Department of Nuclear Medicine and PET Royal Marsden Hospital Sutton Surrey, UK Michael T. Marrinan, f.r.c.s.ed. SELCN Lead for Lung Cancer Research Guy’s, King’s and St Thomas’ Cancer Centre London, UK Sabine Pomplun, m.sc., m.d., m.r.c. path Department of Histopathology King’s College Hospital London, UK Joseph Prendiville, ph.d., mb., b.c., b.a.o., f.r.c.p. SELCN Lead for Lung Cancer Research Guy’s, King’s and St Thomas’ Cancer Centre London, UK vii viii Contributors Alistair Ring, m.a., b.m., b.cl., m.r.c.p., m.d. SELCN Lead for Lung Cancer Research Guy’s, King’s and St Thomas’ Cancer Centre London, UK Pallav Shah, m.d., f.r.c.p. Royal Brompton Hospital London, UK Series Foreword Imaging has become pivotal in all aspects of the management of patients with cancer. At the same time it is acknowledged that optimal patient care is best achieved by a multidisciplinary team approach. The explosion of technological developments in imaging over the past years has meant that all members of the multidisciplinary team should understand the potential applications, limitations and advantages of all the evolving and exciting imaging techniques. Equally, to understand the significance of the imaging findings and to contribute actively to management decisions and to the development of new clinical applications for imaging, it is critical that the radiologist should have sufficient background knowledge of different tumours. Thus the radiologist should understand the pathology, the clinical background, the therapeutic options and prognostic indicators of malignancy. Contemporary Issues in Cancer Imaging  A Multidisciplinary Approach aims to meet the growing requirement for radiologists to have detailed knowledge of the individual tumours in which they are involved in making management decisions. A series of single subject issues, each of which will be dedicated to a single tumour site, edited by recognized expert guest editors, will include contributions from basic scientists, pathologists, surgeons, oncologists, radiologists and others. While the series is written predominantly for the radiologist, it is hoped that individual issues will contain sufficient varied information to be of interest to all medical disciplines and to other health professionals managing patients with cancer. As with imaging, advances have occurred in all these disciplines related to cancer management and it is our fervent hope that this series, bringing together expertise from such a range of related specialities, will not only promote the understanding and rational application of modern imaging but will also help to achieve the ultimate goal of improving outcomes of patients with cancer. Rodney Reznek London Janet Husband London ix Introduction In the United Kingdom well over 30,000 new cases of lung cancer are diagnosed each year and there are a roughly similar number of deaths attibutable to the disease annually. In recent years there has been a paradigm shift in emphasis in the management of patients with lung cancer: a ‘team approach’ is now considered most appropriate and most institutions now have dedicated groups of multidisciplinary specialists who contribute to clinical management. This multidisciplinary approach is reflected in the present volume dedicated to lung cancer. Individual chapters focus on the clinical aspects, pathology, radiology (including screening, diagnosis of symptomatic cases and staging) and treatment options in lung cancer. Because of the recent interest in the potential role of positron emission tomography for a variety of malignancies, a separate chapter is devoted to this technique. Whilst the volume is primarily directed at radiologists, it is hoped that the volume will also be of value to other medical specialists who regularly manage patients with lung cancer. Sujal R. Desai xi 1 Clinical Considerations in Lung Cancer Pallav Shah Royal Brompton Hospital, London, UK Introduction Lung cancer remains one of the commonest malignancies, accounting for 20% of all cancers in men with a lifetime risk of 1 in 13 and 12% of all cancers in women with a lifetime risk of 1 in 23 [1]. In the United Kingdom roughly 40,000 new cases are recorded each year. The estimated incidence for lung cancer in males in 2005 in the United States was 92,305 with approximately 91,537 males expected to die from the disease [2]. The risk of lung cancer is about fourfold greater in men than in women and this increases with age: in the European Union the incidence of lung cancer is 7 per 100,000 for men and 3 per 100,000 for women at the age of 35 years, but in patients aged over 75, the rates are 440 and 72 in men and women respectively [3]. Wide geographical variations in the incidence of lung cancer are also reported and this is primarily related to worldwide variations in smoking behaviour. Aetiology Smoking cigarettes is far and away the dominant risk factor in patients with lung cancer, accounting for 90% of lung cancers in men and almost 80% of cases in women. The relationship between smoking and lung cancer mortality was first established by Doll and Hill [4]. In their study, newly admitted patients with suspected lung, liver or bowel cancers were questioned. The results demonstrated conclusively that patients with a final diagnosis of lung cancer were more likely to be smokers than those without a final diagnosis of lung cancer. The critical study was a prospective study from a cohort of doctors on the medical register who were recruited via a letter in the British Medical Journal; there were 40,000 respondents. Over the subsequent two and half years there were 789 patient deaths, 36 of whom had lung cancer. Doll and Hill found a significant increase in the risk of lung cancer 1 2 Pallav Shah with tobacco consumption [5]. A recent update has also published the 50-year results of this landmark investigation [6]. Occupational asbestos exposure has also been shown to increase the risk of lung cancer, particularly with amphibolic froms of asbestos [7]. The effect is significantly increased in individuals who smoke (up to 16-fold) [8]. Radon, which is a decay product of uranium 238 and radon 226, can also accumulate in homes and some studies have demonstrated an increased risk of lung cancer [9]. Exposure to the following carcinogens has also been associated with an increased risk from lung cancer: arsenic, beryllium, bis-choromethyl ether, cadmium, chromium, nickel, polycyclic aromatic hydrocarbons and vinyl chloride. Consequently, a greater incidence of lung cancer has been observed in industries such as coal-gas, metal refining and smelting processes. Natural History Assuming the hypothesis that lung cancer grows from a single cell, it usually takes approximately 40 volume-doublings for the tumour to reach a diameter of 10 cm, which is the average size of the tumour at death (Table 1.1) [10]. The average size at which tumours are diagnosed is 3 cm and they have usually undergone 33 volume doublings. Small cell cancers are the most rapidly dividing cancers and double in volume approximately every 29 days. Thus, small cell cancers have been present, on average, for about 2 years 4 months before becoming detectable. In contrast, adenocarcinomas of the lung are slow growing, doubling in volume every 161 days. Squamous cell carcinomas and poorly differentiated carcinomas tend to be somewhere in between, doubling in volume every 88 days. Table 1.1. Natural history of untreated lung cancer (adapted from Geddes, 1979 [10]) Cell type Small cell Poorly differentiated Squamous Adenocarcinoma Volume doubling time (days) Tumour size 29 86 88 161 Time from malignant change (in years) Earliest diagnosis Usual diagnosis death 1 cm 2.4 7.1 7.1 13.2 3 cm 2.8 8.2 8.4 15.4 10 cm 3.2 9.4 9.6 17.6 Clinical Considerations in Lung Cancer The growth rate of lung cancer also illustrates (Table 1.1) that the disease is usually diagnosed late in its natural history. Against this, it is noteworthy that most tumours are capable of metastasizing after about 20 volume doublings but not detectable until after 30 volume doublings. Hence the majority of patients have advanced disease by the time of presentation. Clinical Features Symptoms and Signs due to Local Disease The majority of patients who are diagnosed with lung cancer have symptoms at presentation [11]. The most common symptoms are chronic cough with or without sputum production (Table 1.2). Excessive sputum production is an occasional feature of bronchoalveolar cell carcinoma. Haemoptysis is a symptom that frequently prompts patients to seek medical attention and is a presenting feature in up to 50% of cases. Chest pain is a common feature and may vary from dull vague pain on the side of the tumour or more severe pain due to chest wall or mediastinal invasion. Local invasion of adjacent structures such as ribs and vertebral bodies by the tumour may also cause severe persistent pain. Table 1.2. Clinical features of lung cancer Local disease Intra-thoracic spread Symptoms Cough Productive sputum Haemoptysis Chest pain Weight loss Symptoms Chest wall pain Shoulder tip pain Weakness in the hand Hoarse voice Headaches Facial swelling Clinical signs Clubbing of finger nails Monophonic wheeze Focal wheezing Stridor Clinical signs Dilated neck veins Facial plethora Horner’s syndrome Wasting of the small muscles of the hand 3 4 Pallav Shah Recurrent focal pneumonia and segmental pneumonia should raise the possibility of an obstructive lesion in the airways and should prompt further investigation. Unilateral and monophonic wheezes are less common features of an obstructive bronchial tumour. Stridor may occur where there is tracheal involvement. Symptoms and Signs due to Intra-thoracic Extension Extension of lung cancer to adjacent structures may also lead to clinical symptoms and signs. Breathlessness and chest pain may be caused by pleural involvement or pericardial involvement. The subsequent pleural or pericardial effusions may cause breathlessness, and in the case of pericardial involvement may also lead to cardiovascular compromise. Right upper lobe tumours or adjacent mediastinal nodes may invade or externally compress the superior vena cava (SVC). Such patients then present with a relatively classical SVC syndrome comprising headaches, facial fullness or plethora and oedema with congested neck and chest veins. The SVC syndrome is a presenting feature in about 10% of patients with small cell lung cancer. Apical tumours may also extend to involve the superior sympathetic chain leading to a Horner’s syndrome, and brachial plexus involvement causes shoulder and neck pain with atrophy of the small muscles of the hand. Left-sided tumours may compress the recurrent laryngeal nerve as it courses above the aortic arch leading to a hoarse voice and left vocal cord paralysis. Direct tumour invasion or enlarged mediastinal nodes may cause oesophageal compression and hence dysphagia. Symptoms and Signs due to Distant Spread Weight loss is a relative common complaint in patients with lung cancer, which is usually associated with a poor outcome; indeed a decrease of weight exceeding 20% of baseline body weight, in the preceding month, is often indicative of metastatic disease. Patients with liver metastases often present with weight loss. Lung cancer also frequently spreads to the adrenal glands, bone, brain and skin. Involvement of these sites may cause localized pain. Bone metastases can occur at any site but tend to occur in the ribs, vertebrae, humeral and femoral bones. With brain metastases there may also be neurological symptoms, such as confusion, personality changes and epileptic seizures. Supraclavicular and anterior cervical lymph nodes may be involved in up to 25% of patients and should be routinely assessed in the evaluation of patients with lung cancer. Clinical Considerations in Lung Cancer Symptoms and Signs due to Para-neoplastic Syndromes Para-neoplastic syndromes are present in 1020% of patients with lung cancers. Some of the typical syndromes are displayed in Table 1.3 and are usually due to the ectopic production of hormones or peptides. These patients can present with vague symptoms such as tiredness, nausea, abdominal pain or confusion, or more specific symptoms such as galactorrhoea. Ectopic hormone production is more common in small cell lung cancer and some of the cells show neuro-endocrine characteristics. Table 1.3. Paraneoplastic syndromes Common Rare General Anorexia, Cachexia Weight loss Clubbing of finger nails HPOA General Fever Marantic endocarditis Connective Tissue/vasculitis Dermatomyositis/Polymyositis Systemic Lupus Erythematosus Hypercalcitoninemia Hypoglycemia Hypophosphatemia Lactic acidosis Haematological Endocrine Amyloidosis Hypercalcemia Cutaneous Eosinophilia SIADH Acanthosis nigricans Leucocytosis Acquired ichthyosis Leukoerythroblastic reaction Haematological Acquired palmoplantar keratoderma Polycythemia Anaemia Dermatomyositis Thrombocytopenia Polycythemia Erythema annulare Exfoliative dermatitis Neurological Neurological Pemphigus Autonomic neuropathy Lambert-Eaton Pruritis Cerebellar degeneration Limbic encephalitis myasthenia syndrome Peripheral neuropathy Endocrine Pontine myelinosis Acromegaly Retinopathy Carcinoid Syndrome Cushings Syndrome Renal Gynaecomastia Glomeronephritis Tubulointerstitial Key: HPOA is hypertrophic pulmonary osteo-arthropathy. SIADH is syndrome of inappropriate antidiuretic hormone secretion. 5 6 Pallav Shah The range of peptides secreted includes adrenocorticotrophic hormone (ACTH), antidiuretic hormone (ADH), calcitonin, oxytocin and parathyroid hormone. Although elevated levels of these peptides are found in patients with lung cancer only about 5% of patients develop the clinical syndromes. Digital clubbing with hypertrophic pulmonary osteo-arthropathy (HPOA) is considered a nonmetastatic manifestation of lung cancer. Peripheral neuropathy and neurological syndromes such as Lambert-Eaton myasthenic syndrome may also be associated with lung cancer. Diagnosis of Lung Cancer Histopathological and cytological confirmation of the diagnosis is an essential step in the management of patients with lung cancer. Diagnosis and staging can be approached together to provide better prognostic information and more appropriately planned treatment. A computed tomography (CT) scan of the thorax and abdomen should be the initial diagnostic test after chest radiography (Fig. 1.1). The CT study will not only provide information about the location of the primary lesion but also about possible involvement of adjacent structures and provisional staging information (note that the issue of the imaging diagnosis and staging of lung cancer are the subjects of separate chapters in this volume). In addition to CT scanning, many patients with suspected lung cancer will be referred for fibreoptic bronchoscopy. This is discussed in the following section. Fibroptic Bronchoscopy Bronchoscopy is one of the key investigations in the assessment of patients with suspected lung cancer since the procedure not only permits visual examination of the major airways down to subsegmental level, but also provides a variety of methods of sampling abnormal tissue for cytological or histopathological diagnosis. Central tumours vary in appearance from extrinsic polypoid lesions through diffuse plaque-like infiltrations to subtle mucosal irregularity (Fig. 1.2). Large tumour masses and enlarged lymph nodes may also cause extrinsic narrowing of the airways. With central lesions, a number of sampling techniques such as bronchial washings, bronchial biopsy and bronchial brushings may be utilized. With washings, Clinical Considerations in Lung Cancer Figure 1.1 (a) Chest radiograph and (b) CT scan demonstrating a right upper lobe mass approximately 20 ml of saline is instilled around the area of abnormality and the aspirate sent for cytological analysis. Bronchial biopsy is the most useful test for polypoid lesions. Forceps can be inserted through the instrument channel of the bronchoscope to pinch biopsies of the lesion under direct vision. A cytological brush can also be used to scrape some cells from the abnormal area. A combination of these techniques should provide a spot-on diagnosis in up to 90% of patients where the lesion is located in the larger central airways [12]. Where the lesion is peripheral, techniques such as segmental lavage, selective brushings and fluoroscopic transbronchial fine needle aspiration may be utilized. However, the yield is usually lower at around 40% [13, 14]. Hence, CT guided biopsy is the usual technique for obtaining a diagnosis in peripherally located lesions. New techniques have been developed which facilitate bronchoscopic sampling of peripheral lesions including magnetic navigation guided bronchoscopy. A spiral CT with 1.53 mm slice thickness is required and specific landmarks marked at virtual bronchoscopy. A catheter with a magnetic tracking device is then inserted through the instrument channel (Super Dimensions BronchusTM) and the catheter tip is positioned at the same landmarks and calibrated with the CT scan. This allows the CT data to be overlayed on the patient and the system can then be used to guide the catheter with the magnetic tracking device to the target lesion. Once the target is reached, the tracking device is removed, the biopsy forceps or 7 8 Pallav Shah Figure 1.2 Videobronchoscopy appearance of: (a) normal endobronchial airway at segmental level (b) polypoid exophytic tumour; (c) submucosal lesion (for a colour version of this figure please see the colour plate section) needle is inserted through the catheter and appropriate samples obtained for diagnosis. Transbronchial fine needle aspiration (TBNA) is a technique that is being incorporated into the routine clinical assessment of patients with suspected lung cancer [15, 16]. It enables sampling of mediastinal and hilar lymph nodes and provides both diagnostic and staging information. The procedure should be planned according to data provided by a recent CT study. The TBNA needle is inserted through the bronchoscopic channel then inserted at the appropriate point through the airway (Fig. 1.3). The needle is pushed all the way through and suction is applied to the other end with a 20 ml syringe. A jabbing action during the procedure allows cytological material to be aspirated into the needle. The sample obtained is then spread on slides or injected into a liquid media and Clinical Considerations in Lung Cancer Figure 1.3 (a) CT scan of a patient with right upper lobe tumour and enlarged right paratracheal lymph node and (b) videobronchoscopy appearance of the trachea demonstrating transbronchial fine needle aspiration of the right paratracheal lymph node (for a colour version of this figure please see the colour plate section) sent for cytological analysis. TBNA should be performed before inspection of the airways so as not to contaminate the samples and minimize the risk of false positive results. This is important as TBNA in this context provides both diagnostic and staging information. On site cytological analysis appears to enhance the diagnostic yield of TBNA and reduces the number of samples that have to be obtained for diagnosis [17]. It must be remembered that TBNA results do not exclude neoplastic disease and should be followed up by further investigations, such as mediastinoscopy, in appropriate cases. TBNA is a safe and effective technique. Complications are rare and consist of pneumothorax, pneumomediastinum and bleeding [15, 16]. Puncture bronchoscopes have been developed which integrate video bronchoscopes with a linear array ultrasound probe to improve the diagnostic yield from TBNA. This integrated bronchoscope can be used to assess the mediastinum accurately, which significantly improves the diagnosis and staging of patients with suspected lung cancer. The bronchoscope has a dedicated needle, which can be inserted through the instrument channel of the bronchoscope so TBNA can be performed with real time ultrasound imaging. A preliminary study in 70 patients has demonstrated a high sensitivity (95.7%) and accuracy (97.1%) in patients with suspected malignancy [18]. 9 10 Pallav Shah Prognosis The three main prognostic factors for bronchogenic carcinoma are cell type, disease staging or extent and treatment modality. Small cell lung cancer carries the worst prognosis and untreated median survival is only around three months. With chemotherapy this improves to around nine months. In contrast, survival of non-small cell lung cancer is better. Disease stage strongly influences treatment and survival. Patients with Stage I disease who are amenable to surgery have a five-year survival rate  over 60%  whereas patients with stage III or IV disease who are only amenable to palliative treatment have a five-year survival rate of less than 10%. The EUROCARE data demonstrate marked variations in survival between European countries [19]. For example, one-year and five-year survival rates in Finland were 43% and 16%, respectively, compared to 23% and 6% in the United Kingdom. Other prognostic factors are age. The EUROCARE data demonstrate a poorer prognosis with increasing age [19]. This relationship is maintained with cell type and disease stage. Summary Smoking is the main aetiological factor in the pathogenesis of lung cancer. Despite this knowledge, the incidence and mortality for lung cancer remains high. Symptoms occur late in the natural history of lung cancer and hence the majority of lung cancers present late with advanced disease. Accurate diagnosis and staging are an essential guide to treatment and prognosis. REFERENCES 1. Quinn, M., Babb, P., Brock, A., Kibly, L., Jones, J. (2001). Cancer Trends in England & Wales 19501999. London: Office for National Statistics. 2. Stat Bite (2005). US death rates for selected cancers in men, 19692002. J Natl Cancer Inst., 97(18), 1328. 3. Ferley, J., Bjalk, R. J., Pisani, P., et al. (1996). Eucan90: Cancer in the European Union. IARC Cancer base ND 1. lyon: IARc. 4. Doll, R., Hill, A. B. (1950). Smoking and cancer of the lung; preliminary report. Br Med J, 2, 739. 5. Doll, R., Hill, A. B. (1954). The mortality of doctors in relation to their smoking habits. A preliminary report. Br Med J, 4877, 1451.

Author Sujal R. Desai Isbn 9780521872027 File size 3.5 MB Year 2015 Pages 166 Language English File format PDF Category Medicine Book Description: FacebookTwitterGoogle+TumblrDiggMySpaceShare Despite the world-wide drive to increase awareness of the risks of smoking, lung cancer remains a global problem. A multidisciplinary team approach is now considered the most effective way to manage lung cancer. Imaging plays a central role in this multidisciplinary approach; this is reflected in the present volume. Individual chapters focus on imaging (including screening, diagnosis of symptomatic cases and staging), pathology and treatment options in lung cancer. Due to recent interest in the potential role of PET for a variety of malignancies, a separate chapter is devoted to this technique. Each volume in Contemporary Issues in Cancer Imaging is co-ordinated by an expert guest editor with contributions from all members of the multidisciplinary team, bringing together expertise from many specialities to promote the understanding and application of modern imaging in patient management.     Download (3.5 MB) Image Processing in Radiation Therapy Case Studies In Pain Management Lung Cancer: Translational And Emerging Therapies Case-Based Interventional Neuroradiology Atlas Of Fiberoptic Bronchoscopy Load more posts

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