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Lung cancer and its management
Lung cancer
Lung cancer and its management
to rise slowly in females.1 These changes in incidence parallel the changes in smoking rates but with some 20–25 years delay. Around 85% of cases occur in individuals over the age of 60 years with the median age at diagnosis being 72 years (Figure 1).2 It is rare below the age of 40 years. There is a strong association between socioeconomic deprivation and the incidence of lung cancer, with wide geographical variation across the UK. Some of the highest rates are seen in Scotland and Northern England. The overall prognosis of lung cancer is poor and thus the mortality rates are not dissimilar to those for incidence. Worldwide, lung cancer is the commonest cause of cancer death, with an estimated death toll of 1.3 million in 2003.3 In the same year in the UK there were 33,465 deaths from the disease this amouned to 22% of all cancer deaths. This compares with 12,900 deaths from breast cancer and 16,200 from colorectal cancer.1 Although the incidence of lung cancer has been falling overall in recent years in this country, there has been very little improvement in the overall survival.
Michael D Peake
Abstract Lung cancer is the commonest cause of death from cancer and there are over 37,000 new cases every year in the UK. Whilst smoking is the most important aetiological factor, some 4000 of these cases occur in never smokers. Overall the prognosis is poor, largely because around 80% of patients have locally advanced or metastatic disease at diagnosis. One reason for this is the non-specific nature of many of the symptoms and clinicians need to have a low threshold for requesting chest X-rays. Patients should be referred urgently to a rapid access clinic run by a specialist lung cancer multidisciplinary team. Investigation can be complex. CT scan should usually be carried out prior to further investigation. Small-cell lung cancer is best managed with platinum-based combination chemotherapy plus radiotherapy in patients with limited disease. Good radiological and clinical response is the rule, but relapse is common and there is only a small proportion of long-term survivors. The management of non-small-cell lung cancer (NSCLC) is highly stage-dependent and no more than 20% of patients have surgically resectable tumours. Combination chemo-radiotherapy is of proven value in some patients with locally advanced NSCLC but for those with more advanced and metastatic disease of good performance status, combination chemotherapy is the first line of treatment. In this group survival benefit is modest. Newer ‘biological’ agents are showing promise in NSCLC.
Aetiology and risk factors Smoking Cigarette smoking is by far the most important aetiological factor, with around 90% of cases in males and 80–85% in females being attributable to this habit.4 There is a wide variety of carcinogenic substances in tobacco smoke, the most important of which are polycyclic aromatic hydrocarbons (PAHs) such as benzapyrene and nitrosamines. There is some evidence that a diet low in antioxidants and high in polyunsaturated fats enhances the lung cancer risk associated with smoking. Approximately 1 in 6 lifelong smokers will develop lung cancer, the risk being more strongly related to the duration of
Keywords chemo-radiotherapy; EGFR inhibitors; lung cancer; non-small-
Age distribution of lung cancer cases in England and Wales, 2006
cell lung cancer; multidisciplinary team; palliative care; platinum-based chemotherapy; screening; small-cell lung cancer; surgery
2500
The term ‘lung cancer’ covers a variety of malignant tumours arising within the lungs, most of which are pathologically classified as carcinomas. It excludes the asbestos-related malignant mesothelioma of the pleura.
2000
1500
Epidemiology 1000
Lung cancer is one of the commonest cancers in the Western world. In the UK in 2003 the crude incidence rate was 62.3 cases per 100,000, this amounting 37,127 new cases each year – 1 in 7 of all new cancer cases in the country.1 The male:female ratio has changed significantly over recent years being around 3:1 in the late 1970s but only 1.5:1 in 2005.2 This is because the incidence has been falling in males since the 1970s but continuing
500
0
Michael D Peake MBChB FRCP is a Consultant and Senior Lecturer in Respiratory Medicine, Glenfield Hospital, Leicester, UK. Competing interests: none declared.
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55–59
60–64
65–69
70–74
75–79
80–84
85+
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755
900
1,379
1,795
1,895
2,164
1,472
816
Female
600
678
883
1,123
1,242
1,407
1,087
661
(Reproduced with permission of the NHS Information Centre).2
Figure 1
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Lung cancer
smoking than the number of cigarettes smoked per day.4 Smoking cessation at almost any age significantly reduces the risk of developing lung cancer, causing the risk to stabilize, and stopping before the age of 50 results in a fairly low risk of developing lung cancer. Even stopping smoking at the age of 60 delays the risk of developing the disease by more than 10 years and significantly reduces the overall risk (Figure 2).5
Chronic obstructive pulmonary disease and interstitial lung disease The presence of chronic airflow obstruction is associated with a significant excess risk of developing lung cancer variously estimated as between two- and six-fold. This excess risk is independent of the smoking history and is higher the more severe the impairment of forced expiratory volume over one second (FEV1).8 There is also a significantly higher risk of lung cancer, particularly adenocarcinoma, in patients with interstitial lung disease.
Passive smoking There are, however, at least 4000 people in the UK who have never smoked who die of lung cancer each year. It is estimated that some 20% of these deaths can be attributed to passive smoking.
Family history A history of lung cancer in a first-degree relative is associated with an approximate doubling of risk, independent of the smoking history.9 This relative risk is as high as five-fold where the cancers develop under the age of 60 years.
Occupational factors Estimates suggest that between 3 and 17% of lung cancer cases relate directly to a variety of occupational exposures. The most important of these is asbestos, in part because it was in common use between the 1950s and 1970s, but also because it confers a multiplicative risk when combined with smoking.6
Pathology Lung cancers are epithelial tumours (i.e. carcinomas). The large majority arise in the major airways but they can also develop in the lung parenchyma. As a result of exposure to inhaled carcinogens the cells in the surface epithelium undergo a series of genetic mutations which result initially in cellular dysplasia, then metaplasia, before developing into carcinoma-in-situ and finally invasive carcinoma. The main cell types with their approximate frequency are listed in Table 1. Tumours are grouped for most clinical purposes into ‘non-small-cell lung cancer’ (NSCLC) and ‘small-cell lung cancer’ (SCLC). Over recent years the incidence of adenocarcinomas has been increasing and that of SCLC decreasing. Small-cell lung cancer usually arises in the larger airways and has the most rapid doubling time of all lung cancers. In at least three-quarters of patients metastatic spread has occurred by the time of diagnosis. Squamous cell carcinoma usually arises in the central airways and has a propensity to form large solid tumours, which sometimes cavitate. Adnenocarcinoma is less strongly associated with smoking, is more common in women, and can have a significantly slower doubling time than other lung carcinomas. It often develops from a peripheral nodule. Broncho-alveolar cell carcinoma is relatively rare, is very weakly associated with smoking and characteristically (though
Radon Radon is a naturally occurring radioactive gas that is emitted from uranium occurring naturally in surface rocks and soils. It is estimated to cause 1000 cases of lung cancer per year in the UK and there are certain areas of the country, particularly the South West, where environmental exposure is more likely.7 As with asbestos, the risk conferred by radon is much greater in smokers.
Cumulative risk (%)
Effects of stopping smoking at various ages on the cumulative risk (%) of death from lung cancer up to age of 75 years 16
14
12
Continuing cigarette smok ers Stopped age 60 Stopped age 50 Stopped age 40 Stopped age 30 Lifelong non-smokers
Men
10
8
Pathological classification of the major types of invasive lung cancer
6
4
2
0 45
55
65
75
Age (Reproduced with permission from the BMJ publishing group. Peto R, et al. BMJ 2000; 321: 323–29.)
Approximate frequency (%) 15
Non-small-cell carcinomas Squamous cell carcinoma Adenocarcinoma Large cell carcinoma Broncho-alveolar cell carcinoma Adeno-squamous carcinoma Carcinoid tumours (atypical)
40 35 5 1 1 1
Table 1
Figure 2
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Cell type Small-cell carcinoma
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not exclusively) occurs in older female patients. It is a form of adenocarcinoma that spreads along the lining of alveolar spaces and small airways and usually presents as ill-defined peripheral consolidation, often initially mis-diagnosed as infection.
Symptoms of lung cancer Primary tumour • Cough • Dyspnoea • Wheezing/stridor (large airway narrowing) • Haemoptysis • Chest pain • Fatigue/lethargy • Fever/malaise (post-obstructive pneumonia) • Weight loss
Spread Lung cancers have a very high rate of spread which can occur in the following ways: • local invasion into structures such as the pleura, mediastinum, heart and great vessels • lymphatic spread to hilar, mediastinal and supra-clavicular nodes • haematogenous spread to distant organs, the most common of which are liver, other lobes of the lung, brain, bone, adrenal glands, skin • endobronchial spread in broncho-alveolar cell carcinoma.
Regional spread • Facial swelling (superior vena caval obstruction) • Hoarseness (left recurrent laryngeal merve palsy) • Dyspnoea (pleural effusion; phrenic nerve palsy) • Dysphagia (mediastinal node enlargement) Distant metastases • Bone pain • CNS symptoms (confusion, seizures) • Abdominal pain (liver capsule)
Prognosis The overall prognosis for lung cancer is poor, with around 50% of patients not surviving beyond 6 months of diagnosis and only 20–25% being alive at one year. This relatively bleak picture is largely the result of late presentation with the majority having locally advanced, inoperable, or metastatic disease by the time they reach specialist care. The best outlook is observed in those patients with NSCLC diagnosed with early-stage disease.
Paraneoplastic syndromes ( Table 3) Table 2
Signs Physical examination in patients with lung cancer is often normal, but there a wide variety of signs can occur. • Local respiratory signs include wheeze and signs of consolidation or pleural effusion. • Stridor is uncommon, but of particular importance because it implies impending large airway obstruction. • Finger clubbing is commonest in squamous cell carcinoma and rare in SCLC. • Palpable supra-clavicular lymphadenopathy is an important finding both for diagnosis and staging. • Hoarseness may be present. • Hepatomegaly may be a sign of liver metastases. • Skin metastases are relatively common and are often multiple. • Signs of superior vena cava obstruction include fixed elevation of the external jugular venous pressure, swelling of the face, neck and upper limbs, distended veins on the chest wall.
Screening Three large studies from the 1980s using plain chest x-rays to screen for lung cancer failed to show any impact on overall death rates. This has led to more recent efforts to assess other potential screening methods, the most studied of which is low-dose CT scanning. Whilst there is no doubt that this technique can detect lung cancers significantly earlier than plain chest X-rays, there is no population-based evidence as yet of any impact on overall mortality from lung cancer. It remains the subject of intensive research.
Presentation Symptoms In its early stages, most patients with lung cancer are asymptomatic and a significant proportion of stage I and II tumours are detected incidentally when investigations such as chest Xrays are carried out for other purposes. The symptoms of lung cancer are summarized in Table 2. It will be clear that most of these are non-specific and occur commonly in smokers and the general ageing population. Even haemoptysis is, in the general population, more commonly associated with benign conditions. Often it is a subtle change in a chronic symptom, such as cough or dyspnoea, that alerts the patient or clinician that there may be a more serious underlying cause. The clinician has to maintain a very high level of alertness to the risk factors in the patient presenting with such symptoms – for example, haemoptysis is much more likely to be caused by lung cancer in a 65-year-old smoker than in a 40-year-old non-smoker. It is, therefore, vital to take a good history that includes details of smoking, occupation, the presence of other respiratory conditions and family history.
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Paraneoplastic syndromes There are many paraneoplastic syndromes associated with lung cancer, the commoner ones are listed in Table 3. The two most common in clinical practice are: • hyponatraemia – associated with inappropriate antidiuretic hormone secretion (SIADH) • hypercalcaemia – most common in squamous cell carcinoma. Multidisciplinary teams (MDTs) The investigation of lung cancer is discussed elsewhere (pages 155–161). The proper diagnosis, staging, assessment and treatment of lung cancer patients cannot be carried out by clinicians in any one specialty. The model of MDT working has, therefore, evolved in recent years and is now considered the standard of 164
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Non-small-cell lung cancer Treatment of NSCLC is primarily dependent on stage, with fitness and comorbidity being factors in a proportion of patients. At least 60% of patients with NSCLC have metastatic disease at the time of presentation and in the UK no more than 20% have resectable disease.
Commoner paraneoplastic syndromes in lung cancer • Hyponatraemia – syndrome of inappropriate antidiuretic hormone secretion • Hypercalcaemia – parathormone analogue secretion (can also result from skeletal metastases) • Hypertrophic pulmonary osteoarthropathy • Ectopic ACTH secretion (usually presenting as hypokalaemic alkalosis) • Eaton–Lambert syndrome
Stage I – IIIA NSCLC Surgery is the treatment of choice in those with stage I and II disease who are fit, and also in a proportion of those with stage IIIA tumours. Lobectomy is the optimum surgical procedure, preserving lung function and being associated with better survival than simple wedge resection of the tumour mass. Occasionally pneumonectomy is required but is associated with higher morbidity and perioperative mortality, especially in older patients. In patients with impaired lung function a variety of ‘parenchymal sparing’ surgical techniques are available, such as wedge resection and sleeve resection (to avoid pneumonectomy). Video-assisted thoracoscopic surgery (VATS) reduces trauma to the thoracic cage and probably increases the range of patients in whom surgery is feasible. Concurrent lung volume reduction surgery may also be possible in some patients in whom the tumour is sited in a region of the lung with emphysema and poor perfusion. The five-year survival rate of patients after surgery is shown in Table 5. Adjuvant (postoperative) chemotherapy has been shown to improve absolute five-year survival by up to 10% in patients with stage II and IIIA NSCLC. Postoperative radiotherapy has been demonstrated to be of no value unless the resected tumour margin is not clear or un expected mediastinal node involvement was found at the time of surgery. Radical radiotherapy is of proven value in patients with stage I and II NSCLC who are medically unfit for surgery, although the five-year survival rates are less than half those seen with surgery. Continuous hyperfractionated accelerated radiotherapy (CHART) has been shown to be superior to conventional radiotherapy.11 Radical radiotherapy is not, however, without its risks, and radiation pneumonitis has to be considered when taking into account the fitness of patients with impaired lung function. Pancoast tumours arise in the superior sulcus of the thorax and are most often squamous cell carcinomas. They are classically associated with brachial plexus involvement, which can lead to severe nerve root pain and Horner’s syndrome. There are usually treated with a combination of chemo-radiotherapy followed by surgical resection if feasible.
Table 3
care.10 The membership of a lung cancer MDT should include respiratory physicians, thoracic surgeons, radiologists, pathologists, clinical oncologists, medical oncologists, palliative care physicians and specialist nurses, all of whom contribute to the complex decision-making for each patient. Communication with the patient The time around diagnosis of cancer is hugely stressful for patients and their loved ones. Breaking the bad news is a difficult task that should ideally be carried out by a senior clinician in the controlled setting of a quiet room. It requires experience, skill and compassion and it is vital that the clinician fully understands the significance of the clinical findings and what the next step of the care pathway will be. The greatest skill is in being able to combine a realistic picture of the outcome with as positive an approach to the management as is possible.
Treatment Small-cell lung cancer Around 75% of patients with SCLC have extensive disease at the time of diagnosis and in many ways it is best considered a systemic disease. Surgery has a limited place in patients with tumours of a small size in whom every effort has been made to rule out nodal or distant metastases. Prognostic factors are very powerful in SCLC and, in addition to extensive stage disease, a poor prognosis is associated with PS of 2 or worse, hyponatraemia and elevation of the LDH or alkaline phosphatase. The mainstay of treatment is chemotherapy combined with radiotherapy in good prognosis patients. SCLC is a highly chemosensitive tumour, with response rates of approaching 90% using modern combination platinum-based chemotherapy. The most common combination in use as first-line treatment is cisplatin with etopside given in 4 to 6 cycles at three-weekly intervals. In patients with limited disease this is given in combination with thoracic radiotherapy. Cerebral metastases are common, so patients who respond well to first-line treatment are offered prophylactic cranial irradiation. Patients with extensive disease of PS 0–2 are usually managed with combination chemotherapy alone. Treatment of SCLC results in good symptomatic relief in the majority of patients and there are significant medium-term improvements in survival (Table 4). Unfortunately relapse is common and, overall, less than 5% of patients survive beyond 2 years.
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Stage IIIB – IV The vast majority of patients with stage IIIB NSCLC are considered inoperable, but there is a small proportion who have T4 tumours by virtue of satellite nodules in the same lobe as the primary, or who have central T4 tumours removable by sleeve resection who may benefit from surgery. In good PS patients with stage IIIB NSCLC where the tumour can be encompassed in a radiotherapy field, there is good evidence that a combination of chemotherapy and radiotherapy is associated with a significant improvement in mediumterm survival and a small proportion of long-term survivors.12 For those with stage IIIB disease too extensive for such radical therapy and those with stage IV (metastatic) disease, combination chemotherapy is now established as the first-line treatment in fitter 165
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Survival in small-cell lung cancer by stage and treatment Stage
Untreated median survival
Treated median survival
5 year survival (%)
Limited disease Extensive disease
3 months 6 weeks
14–20 months 8–12 months
10–20 3–5
Table 4
patients. Cisplatin or carboplatin are most commonly combined with vinorelbine, gemcitabine or paclitaxel and given for up to four cycles at three-weekly intervals. NSCLC is less chemosensitive than SCLC with response rates between 50 and 60% using modern platinum-based regimes. Many studies have confirmed a modest improvement in median survival of around 10–12 weeks on such chemotherapy, and the proportion of patients who remain alive at one year is almost doubled on treatment. There is often significant symptomatic improvement and careful studies have shown no overall detriment to quality of life with chemotherapy.13
apoptosis. The growth of small vessels (angiogenesis) is essential for a tumour to survive and both EGFR and VEGF are involved in this process and in the growth of endothelial cells. Inhibitors of both of these receptors have been developed and are showing promise in the treatment of lung cancer, particularly NSCLC where EGFR is over-expressed in the majority of cases. The first such agent to be licensed in the UK is the EGFR tyrosine-kinase inhibitor, erlotinib. It is an oral agent, the toxicity of which is largely limited to skin rashes and diarrhoea, very different from that seen with conventional chemotherapy. Erlotinib has been shown in one large multi-centre trial14 to confer a significant survival advantage in patients with advanced (stage IIIB and IV) NSCLC who have relapsed after first- or second-line chemotherapy. There is a small percentage of patients in whom the response is dramatic and there are many examples of long-term survivors in this particularly poor prognosis group. A good response is more commonly seen in patients with adenocarcinomas, those who have never smoked, are of female sex and of South Asian extraction. The EGFR inhibitors also appear to be very active in broncho-alveolar cell carcinomas. However, an overall survival benefit has been shown across all patient groups. Other agents include the VEGF inhibitor bevacizumab, which has been shown to confer a survival advantage in non-squamous NSCLC in combination with chemotherapy. There is emerging evidence that patients with particular genetic mutations in the EGFR receptor are more likely to respond to some of these agents and we are probably entering an era where therapy will become much more targeted at individual patients, based on the detailed characteristics of their tumours.
Palliative radiotherapy Palliative radiotherapy is of value in the management of multiple symptoms in all patients with lung cancer at any stage of their illness. It may be of particular value in the following situations: • pain – from bone metastases or chest wall involvement • large airway obstruction – particularly when there is extrinsic compression • persistent cough • persistent haemoptysis • spinal cord compression • superior vena caval obstruction • symptomatic cerebral metastases. ‘Biological’ agents In the last few years there have been great strides made in the understanding of tumour biology; in particular the factors controlling angiogenesis and apoptosis (programmed cell death) are becoming clearer. Central to these processes are the epidermal growth factor receptors (EGFR) and vascular endothelial growth factor (VEGF) receptors. EGFR is normally widely expressed by many cell types and its activation results in a cascade of tyrosine kinase enzyme activation that leads to the stimulation of tumour proliferation, angiogenesis, invasion, metastasis and inhibition of
Palliative care Lung cancer is a disease with a very high frequency of symptoms of a distressing nature and where the duration of survival in the majority of patients in measured in months rather than years. Whilst it is essential that every effort is made to identify those patients suitable for radical therapy, it is equally important to ensure that there is universal rapid access to high-quality specialist supportive and palliative care. It has to include both the patient and their carers and should encompass a variety of elements including: • quality of life • symptom control • support with adjustment to loss • support and guidance regarding the completion of unfinished business • dignified death in patient’s place of choice • prevention of problems in bereavement. The following are the most common symptoms to cause distress in the final months and weeks of life.
Five-year survival in non-small-cell lung cancer after surgical resection Stage Stage Stage Stage Stage Stage Stage
Survival at 5 yrs (%) IA IB IIA IIB – chest wall invasion IIB – mediastinal invasion III (N0 disease)
84 68 47 56 29 34
Table 5
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management are underpinned by NICE guidance.12 The key elements of a lung cancer service should include: • clear referral pathways to a specialist team with identification of all abnormal chest X-rays • the availability of a rapid-access lung cancer clinic • all patients should be managed by a specialist MDT comprising representatives of all the key disciplines • all patients should have access to a lung cancer nurse specialist • every service should regularly audit its activity, performance and outcomes. ◆
Dyspnoea can be caused by a variety of factors: • chest infections (often on a background of COPD): nebulized bronchodilators often give relief in this situation • large airway obstruction: this may be amenable to palliative radiotherapy, bronchial stenting or laser debulking • pleural effusion: best managed by talc pleurodesis • phrenic nerve palsy. There is good evidence that specialist breathlessness clinics are of benefit in some patients. Opioids can be of value in terminal dyspnoea and are best administered orally. Pain is particularly a problem when there is chest wall involvement or bony metastases. Careful use of appropriate analgesics based on the WHO ‘analgesic ladder’ is the mainstay of treatment, but it is important to recognize opioid-resistant pain. Occasionally nerve root block or even cordotomy are required for intractable symptoms. Palliative radiotherapy is an important component of pain management in some patients (see above). Pleural effusions are best dealt with in specialist respiratory units with experience in the use of talc pleurodesis which, when properly carried out, can provide long-term relief from recurrent effusions in over 80% of patients. Cough can be difficult to manage but palliative radiotherapy is often useful as are oral opioids and sometimes nebulized bronchodilators. Fatigue is common and often goes unrecognized by doctors. It may be the result of anaemia and correction of this may be of value. Cachexia is almost universal in the later stages of the disease and oral corticosteroids offer good, if short-term, relief in many patients. Depression is also poorly recognized and put down to a ‘normal response’ to a patient’s illness. Antidepressants are of great value in some patients.
References 1 Cancer Research UK. CancerStats: lung cancer and smoking. 2007 Available at: www.Info.cancerresearchuk.org/cancerstats (accessed 24 October 2007). 2 The Information Centre for Health and Social Care. National lung cancer audit. Second annual report. 2007. Available at: http://www. ic.nhs.uk (accessed 24 October 2007). 3 GLOBOCAN 2002. Cancer incidence, mortality and prevalence worldwide 2002 estimates, 2006. Available at: http://www-dep.iarc.fr/ (accessed 24 October 2007). 4 Peto R, Lopez A, Boreham J, et al. Mortality from smoking in developed countries 1950–2000. Available at: http://www.ctsu. ox.ac.uk/∼tobacco/ (accessed 24 October 2007). 5 Peto R, Darby S, Deo H, et al. Smoking, smoking cessation and lung cancer in the UK since 1950: combination of national statistics with two case-controlled studies. Br Med J 2000; 321: 326–69. 6 Fishwick D, Barber CM. Occupational risk factors for lung cancer. Lung Canc Pract 2007; 3: 8–10. 7 Darby S, Hill D, Auvinen A, et al. Radon in homes and risk of lung cancer: collaborative analysis of individual data from 143 European case-controlled studies. Br Med J 2005; 330: 223. 8 Purdue M, Gold L, Järvholm B, et al. Impaired lung function and lung cancer incidence in a cohort of Swedish construction workers. Thorax 2007; 62: 51–56. 9 Nitadori J, Inoue M, Iwasaki M, et al. Association between lung cancer incidence and family history of lung cancer: data from a large-scale population-based cohort study, the JPHC study. Chest 2006; 130: 968–75. 10 Department of Health. The NHS national cancer plan. London: Department of Health, 2001. 11 Saunders M, Dische S, Barrett A, et al. Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small cell lung cancer; mature data from the randomised trial. Radiother Oncol 1999; 52: 137–48. 12 National Institute for Health and Clinical Excellence. Guidelines on the diagnosis and treatment of lung cancer. London: NICE, 2005 Available at: www.nice.org.uk (accessed 24 October 2007). 13 Brown J, Fairlamb D, Gower N, et al. Assessment of quality of life in the supportive care setting of the big lung trial in non-small cell lung cancer. J Clin Oncol 2005; 23: 7417–27. 14 Shepherd F, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005; 353: 123–32. 15 Calman K, Hine D. A policy framework for commissioning cancer services. A report by the Expert Advisory Group on Cancer to the Chief Medical Officers of England and Wales. London: Department of Health, 1995.
Specialist nursing The emergence of the lung cancer nurse specialist (LCNS) has been one of the most important elements in improving the care of lung cancer patients in the last 10 years or so. With the emergence of the MDT, patients are often seen by a variety of doctors, commonly in more than one hospital. The LCNS is there with the patient and carers at the start of their ‘journey’ when they are being told the diagnosis. They are in the ideal position to form an ongoing supportive relationship with the patient and their carers and to provide a stable ‘thread’ as they move along the care pathway. They are an invaluable source of information and advice and are of proven benefit in the follow-up of many patients. Proper education and advice can help identify problems at a stage before they become emergencies and can probably avoid many an unnecessary hospital admission. They have an important role in providing a link between the hospital and primary care setting.
Service provision Cancer services in the UK have developed and improved greatly since the Calman–Hine report of 199515 and the National Cancer Plan of 2001.10 Further development will be seen following the publication of the Cancer Reform Strategy in 2007. Details of
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to rise slowly in females.1 These changes in incidence parallel the changes in smoking rates but with some 20–25 years delay. Around 85% of cases occur in individuals over the age of 60 years with the median age at diagnosis being 72 years (Figure 1).2 It is rare below the age of 40 years. There is a strong association between socioeconomic deprivation and the incidence of lung cancer, with wide geographical variation across the UK. Some of the highest rates are seen in Scotland and Northern England. The overall prognosis of lung cancer is poor and thus the mortality rates are not dissimilar to those for incidence. Worldwide, lung cancer is the commonest cause of cancer death, with an estimated death toll of 1.3 million in 2003.3 In the same year in the UK there were 33,465 deaths from the disease this amouned to 22% of all cancer deaths. This compares with 12,900 deaths from breast cancer and 16,200 from colorectal cancer.1 Although the incidence of lung cancer has been falling overall in recent years in this country, there has been very little improvement in the overall survival.
Michael D Peake
Abstract Lung cancer is the commonest cause of death from cancer and there are over 37,000 new cases every year in the UK. Whilst smoking is the most important aetiological factor, some 4000 of these cases occur in never smokers. Overall the prognosis is poor, largely because around 80% of patients have locally advanced or metastatic disease at diagnosis. One reason for this is the non-specific nature of many of the symptoms and clinicians need to have a low threshold for requesting chest X-rays. Patients should be referred urgently to a rapid access clinic run by a specialist lung cancer multidisciplinary team. Investigation can be complex. CT scan should usually be carried out prior to further investigation. Small-cell lung cancer is best managed with platinum-based combination chemotherapy plus radiotherapy in patients with limited disease. Good radiological and clinical response is the rule, but relapse is common and there is only a small proportion of long-term survivors. The management of non-small-cell lung cancer (NSCLC) is highly stage-dependent and no more than 20% of patients have surgically resectable tumours. Combination chemo-radiotherapy is of proven value in some patients with locally advanced NSCLC but for those with more advanced and metastatic disease of good performance status, combination chemotherapy is the first line of treatment. In this group survival benefit is modest. Newer ‘biological’ agents are showing promise in NSCLC.
Aetiology and risk factors Smoking Cigarette smoking is by far the most important aetiological factor, with around 90% of cases in males and 80–85% in females being attributable to this habit.4 There is a wide variety of carcinogenic substances in tobacco smoke, the most important of which are polycyclic aromatic hydrocarbons (PAHs) such as benzapyrene and nitrosamines. There is some evidence that a diet low in antioxidants and high in polyunsaturated fats enhances the lung cancer risk associated with smoking. Approximately 1 in 6 lifelong smokers will develop lung cancer, the risk being more strongly related to the duration of
Keywords chemo-radiotherapy; EGFR inhibitors; lung cancer; non-small-
Age distribution of lung cancer cases in England and Wales, 2006
cell lung cancer; multidisciplinary team; palliative care; platinum-based chemotherapy; screening; small-cell lung cancer; surgery
2500
The term ‘lung cancer’ covers a variety of malignant tumours arising within the lungs, most of which are pathologically classified as carcinomas. It excludes the asbestos-related malignant mesothelioma of the pleura.
2000
1500
Epidemiology 1000
Lung cancer is one of the commonest cancers in the Western world. In the UK in 2003 the crude incidence rate was 62.3 cases per 100,000, this amounting 37,127 new cases each year – 1 in 7 of all new cancer cases in the country.1 The male:female ratio has changed significantly over recent years being around 3:1 in the late 1970s but only 1.5:1 in 2005.2 This is because the incidence has been falling in males since the 1970s but continuing
500
0
Michael D Peake MBChB FRCP is a Consultant and Senior Lecturer in Respiratory Medicine, Glenfield Hospital, Leicester, UK. Competing interests: none declared.
MEDICINE 36:3
–54
55–59
60–64
65–69
70–74
75–79
80–84
85+
Male
755
900
1,379
1,795
1,895
2,164
1,472
816
Female
600
678
883
1,123
1,242
1,407
1,087
661
(Reproduced with permission of the NHS Information Centre).2
Figure 1
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smoking than the number of cigarettes smoked per day.4 Smoking cessation at almost any age significantly reduces the risk of developing lung cancer, causing the risk to stabilize, and stopping before the age of 50 results in a fairly low risk of developing lung cancer. Even stopping smoking at the age of 60 delays the risk of developing the disease by more than 10 years and significantly reduces the overall risk (Figure 2).5
Chronic obstructive pulmonary disease and interstitial lung disease The presence of chronic airflow obstruction is associated with a significant excess risk of developing lung cancer variously estimated as between two- and six-fold. This excess risk is independent of the smoking history and is higher the more severe the impairment of forced expiratory volume over one second (FEV1).8 There is also a significantly higher risk of lung cancer, particularly adenocarcinoma, in patients with interstitial lung disease.
Passive smoking There are, however, at least 4000 people in the UK who have never smoked who die of lung cancer each year. It is estimated that some 20% of these deaths can be attributed to passive smoking.
Family history A history of lung cancer in a first-degree relative is associated with an approximate doubling of risk, independent of the smoking history.9 This relative risk is as high as five-fold where the cancers develop under the age of 60 years.
Occupational factors Estimates suggest that between 3 and 17% of lung cancer cases relate directly to a variety of occupational exposures. The most important of these is asbestos, in part because it was in common use between the 1950s and 1970s, but also because it confers a multiplicative risk when combined with smoking.6
Pathology Lung cancers are epithelial tumours (i.e. carcinomas). The large majority arise in the major airways but they can also develop in the lung parenchyma. As a result of exposure to inhaled carcinogens the cells in the surface epithelium undergo a series of genetic mutations which result initially in cellular dysplasia, then metaplasia, before developing into carcinoma-in-situ and finally invasive carcinoma. The main cell types with their approximate frequency are listed in Table 1. Tumours are grouped for most clinical purposes into ‘non-small-cell lung cancer’ (NSCLC) and ‘small-cell lung cancer’ (SCLC). Over recent years the incidence of adenocarcinomas has been increasing and that of SCLC decreasing. Small-cell lung cancer usually arises in the larger airways and has the most rapid doubling time of all lung cancers. In at least three-quarters of patients metastatic spread has occurred by the time of diagnosis. Squamous cell carcinoma usually arises in the central airways and has a propensity to form large solid tumours, which sometimes cavitate. Adnenocarcinoma is less strongly associated with smoking, is more common in women, and can have a significantly slower doubling time than other lung carcinomas. It often develops from a peripheral nodule. Broncho-alveolar cell carcinoma is relatively rare, is very weakly associated with smoking and characteristically (though
Radon Radon is a naturally occurring radioactive gas that is emitted from uranium occurring naturally in surface rocks and soils. It is estimated to cause 1000 cases of lung cancer per year in the UK and there are certain areas of the country, particularly the South West, where environmental exposure is more likely.7 As with asbestos, the risk conferred by radon is much greater in smokers.
Cumulative risk (%)
Effects of stopping smoking at various ages on the cumulative risk (%) of death from lung cancer up to age of 75 years 16
14
12
Continuing cigarette smok ers Stopped age 60 Stopped age 50 Stopped age 40 Stopped age 30 Lifelong non-smokers
Men
10
8
Pathological classification of the major types of invasive lung cancer
6
4
2
0 45
55
65
75
Age (Reproduced with permission from the BMJ publishing group. Peto R, et al. BMJ 2000; 321: 323–29.)
Approximate frequency (%) 15
Non-small-cell carcinomas Squamous cell carcinoma Adenocarcinoma Large cell carcinoma Broncho-alveolar cell carcinoma Adeno-squamous carcinoma Carcinoid tumours (atypical)
40 35 5 1 1 1
Table 1
Figure 2
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Cell type Small-cell carcinoma
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not exclusively) occurs in older female patients. It is a form of adenocarcinoma that spreads along the lining of alveolar spaces and small airways and usually presents as ill-defined peripheral consolidation, often initially mis-diagnosed as infection.
Symptoms of lung cancer Primary tumour • Cough • Dyspnoea • Wheezing/stridor (large airway narrowing) • Haemoptysis • Chest pain • Fatigue/lethargy • Fever/malaise (post-obstructive pneumonia) • Weight loss
Spread Lung cancers have a very high rate of spread which can occur in the following ways: • local invasion into structures such as the pleura, mediastinum, heart and great vessels • lymphatic spread to hilar, mediastinal and supra-clavicular nodes • haematogenous spread to distant organs, the most common of which are liver, other lobes of the lung, brain, bone, adrenal glands, skin • endobronchial spread in broncho-alveolar cell carcinoma.
Regional spread • Facial swelling (superior vena caval obstruction) • Hoarseness (left recurrent laryngeal merve palsy) • Dyspnoea (pleural effusion; phrenic nerve palsy) • Dysphagia (mediastinal node enlargement) Distant metastases • Bone pain • CNS symptoms (confusion, seizures) • Abdominal pain (liver capsule)
Prognosis The overall prognosis for lung cancer is poor, with around 50% of patients not surviving beyond 6 months of diagnosis and only 20–25% being alive at one year. This relatively bleak picture is largely the result of late presentation with the majority having locally advanced, inoperable, or metastatic disease by the time they reach specialist care. The best outlook is observed in those patients with NSCLC diagnosed with early-stage disease.
Paraneoplastic syndromes ( Table 3) Table 2
Signs Physical examination in patients with lung cancer is often normal, but there a wide variety of signs can occur. • Local respiratory signs include wheeze and signs of consolidation or pleural effusion. • Stridor is uncommon, but of particular importance because it implies impending large airway obstruction. • Finger clubbing is commonest in squamous cell carcinoma and rare in SCLC. • Palpable supra-clavicular lymphadenopathy is an important finding both for diagnosis and staging. • Hoarseness may be present. • Hepatomegaly may be a sign of liver metastases. • Skin metastases are relatively common and are often multiple. • Signs of superior vena cava obstruction include fixed elevation of the external jugular venous pressure, swelling of the face, neck and upper limbs, distended veins on the chest wall.
Screening Three large studies from the 1980s using plain chest x-rays to screen for lung cancer failed to show any impact on overall death rates. This has led to more recent efforts to assess other potential screening methods, the most studied of which is low-dose CT scanning. Whilst there is no doubt that this technique can detect lung cancers significantly earlier than plain chest X-rays, there is no population-based evidence as yet of any impact on overall mortality from lung cancer. It remains the subject of intensive research.
Presentation Symptoms In its early stages, most patients with lung cancer are asymptomatic and a significant proportion of stage I and II tumours are detected incidentally when investigations such as chest Xrays are carried out for other purposes. The symptoms of lung cancer are summarized in Table 2. It will be clear that most of these are non-specific and occur commonly in smokers and the general ageing population. Even haemoptysis is, in the general population, more commonly associated with benign conditions. Often it is a subtle change in a chronic symptom, such as cough or dyspnoea, that alerts the patient or clinician that there may be a more serious underlying cause. The clinician has to maintain a very high level of alertness to the risk factors in the patient presenting with such symptoms – for example, haemoptysis is much more likely to be caused by lung cancer in a 65-year-old smoker than in a 40-year-old non-smoker. It is, therefore, vital to take a good history that includes details of smoking, occupation, the presence of other respiratory conditions and family history.
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Paraneoplastic syndromes There are many paraneoplastic syndromes associated with lung cancer, the commoner ones are listed in Table 3. The two most common in clinical practice are: • hyponatraemia – associated with inappropriate antidiuretic hormone secretion (SIADH) • hypercalcaemia – most common in squamous cell carcinoma. Multidisciplinary teams (MDTs) The investigation of lung cancer is discussed elsewhere (pages 155–161). The proper diagnosis, staging, assessment and treatment of lung cancer patients cannot be carried out by clinicians in any one specialty. The model of MDT working has, therefore, evolved in recent years and is now considered the standard of 164
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Non-small-cell lung cancer Treatment of NSCLC is primarily dependent on stage, with fitness and comorbidity being factors in a proportion of patients. At least 60% of patients with NSCLC have metastatic disease at the time of presentation and in the UK no more than 20% have resectable disease.
Commoner paraneoplastic syndromes in lung cancer • Hyponatraemia – syndrome of inappropriate antidiuretic hormone secretion • Hypercalcaemia – parathormone analogue secretion (can also result from skeletal metastases) • Hypertrophic pulmonary osteoarthropathy • Ectopic ACTH secretion (usually presenting as hypokalaemic alkalosis) • Eaton–Lambert syndrome
Stage I – IIIA NSCLC Surgery is the treatment of choice in those with stage I and II disease who are fit, and also in a proportion of those with stage IIIA tumours. Lobectomy is the optimum surgical procedure, preserving lung function and being associated with better survival than simple wedge resection of the tumour mass. Occasionally pneumonectomy is required but is associated with higher morbidity and perioperative mortality, especially in older patients. In patients with impaired lung function a variety of ‘parenchymal sparing’ surgical techniques are available, such as wedge resection and sleeve resection (to avoid pneumonectomy). Video-assisted thoracoscopic surgery (VATS) reduces trauma to the thoracic cage and probably increases the range of patients in whom surgery is feasible. Concurrent lung volume reduction surgery may also be possible in some patients in whom the tumour is sited in a region of the lung with emphysema and poor perfusion. The five-year survival rate of patients after surgery is shown in Table 5. Adjuvant (postoperative) chemotherapy has been shown to improve absolute five-year survival by up to 10% in patients with stage II and IIIA NSCLC. Postoperative radiotherapy has been demonstrated to be of no value unless the resected tumour margin is not clear or un expected mediastinal node involvement was found at the time of surgery. Radical radiotherapy is of proven value in patients with stage I and II NSCLC who are medically unfit for surgery, although the five-year survival rates are less than half those seen with surgery. Continuous hyperfractionated accelerated radiotherapy (CHART) has been shown to be superior to conventional radiotherapy.11 Radical radiotherapy is not, however, without its risks, and radiation pneumonitis has to be considered when taking into account the fitness of patients with impaired lung function. Pancoast tumours arise in the superior sulcus of the thorax and are most often squamous cell carcinomas. They are classically associated with brachial plexus involvement, which can lead to severe nerve root pain and Horner’s syndrome. There are usually treated with a combination of chemo-radiotherapy followed by surgical resection if feasible.
Table 3
care.10 The membership of a lung cancer MDT should include respiratory physicians, thoracic surgeons, radiologists, pathologists, clinical oncologists, medical oncologists, palliative care physicians and specialist nurses, all of whom contribute to the complex decision-making for each patient. Communication with the patient The time around diagnosis of cancer is hugely stressful for patients and their loved ones. Breaking the bad news is a difficult task that should ideally be carried out by a senior clinician in the controlled setting of a quiet room. It requires experience, skill and compassion and it is vital that the clinician fully understands the significance of the clinical findings and what the next step of the care pathway will be. The greatest skill is in being able to combine a realistic picture of the outcome with as positive an approach to the management as is possible.
Treatment Small-cell lung cancer Around 75% of patients with SCLC have extensive disease at the time of diagnosis and in many ways it is best considered a systemic disease. Surgery has a limited place in patients with tumours of a small size in whom every effort has been made to rule out nodal or distant metastases. Prognostic factors are very powerful in SCLC and, in addition to extensive stage disease, a poor prognosis is associated with PS of 2 or worse, hyponatraemia and elevation of the LDH or alkaline phosphatase. The mainstay of treatment is chemotherapy combined with radiotherapy in good prognosis patients. SCLC is a highly chemosensitive tumour, with response rates of approaching 90% using modern combination platinum-based chemotherapy. The most common combination in use as first-line treatment is cisplatin with etopside given in 4 to 6 cycles at three-weekly intervals. In patients with limited disease this is given in combination with thoracic radiotherapy. Cerebral metastases are common, so patients who respond well to first-line treatment are offered prophylactic cranial irradiation. Patients with extensive disease of PS 0–2 are usually managed with combination chemotherapy alone. Treatment of SCLC results in good symptomatic relief in the majority of patients and there are significant medium-term improvements in survival (Table 4). Unfortunately relapse is common and, overall, less than 5% of patients survive beyond 2 years.
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Stage IIIB – IV The vast majority of patients with stage IIIB NSCLC are considered inoperable, but there is a small proportion who have T4 tumours by virtue of satellite nodules in the same lobe as the primary, or who have central T4 tumours removable by sleeve resection who may benefit from surgery. In good PS patients with stage IIIB NSCLC where the tumour can be encompassed in a radiotherapy field, there is good evidence that a combination of chemotherapy and radiotherapy is associated with a significant improvement in mediumterm survival and a small proportion of long-term survivors.12 For those with stage IIIB disease too extensive for such radical therapy and those with stage IV (metastatic) disease, combination chemotherapy is now established as the first-line treatment in fitter 165
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Survival in small-cell lung cancer by stage and treatment Stage
Untreated median survival
Treated median survival
5 year survival (%)
Limited disease Extensive disease
3 months 6 weeks
14–20 months 8–12 months
10–20 3–5
Table 4
patients. Cisplatin or carboplatin are most commonly combined with vinorelbine, gemcitabine or paclitaxel and given for up to four cycles at three-weekly intervals. NSCLC is less chemosensitive than SCLC with response rates between 50 and 60% using modern platinum-based regimes. Many studies have confirmed a modest improvement in median survival of around 10–12 weeks on such chemotherapy, and the proportion of patients who remain alive at one year is almost doubled on treatment. There is often significant symptomatic improvement and careful studies have shown no overall detriment to quality of life with chemotherapy.13
apoptosis. The growth of small vessels (angiogenesis) is essential for a tumour to survive and both EGFR and VEGF are involved in this process and in the growth of endothelial cells. Inhibitors of both of these receptors have been developed and are showing promise in the treatment of lung cancer, particularly NSCLC where EGFR is over-expressed in the majority of cases. The first such agent to be licensed in the UK is the EGFR tyrosine-kinase inhibitor, erlotinib. It is an oral agent, the toxicity of which is largely limited to skin rashes and diarrhoea, very different from that seen with conventional chemotherapy. Erlotinib has been shown in one large multi-centre trial14 to confer a significant survival advantage in patients with advanced (stage IIIB and IV) NSCLC who have relapsed after first- or second-line chemotherapy. There is a small percentage of patients in whom the response is dramatic and there are many examples of long-term survivors in this particularly poor prognosis group. A good response is more commonly seen in patients with adenocarcinomas, those who have never smoked, are of female sex and of South Asian extraction. The EGFR inhibitors also appear to be very active in broncho-alveolar cell carcinomas. However, an overall survival benefit has been shown across all patient groups. Other agents include the VEGF inhibitor bevacizumab, which has been shown to confer a survival advantage in non-squamous NSCLC in combination with chemotherapy. There is emerging evidence that patients with particular genetic mutations in the EGFR receptor are more likely to respond to some of these agents and we are probably entering an era where therapy will become much more targeted at individual patients, based on the detailed characteristics of their tumours.
Palliative radiotherapy Palliative radiotherapy is of value in the management of multiple symptoms in all patients with lung cancer at any stage of their illness. It may be of particular value in the following situations: • pain – from bone metastases or chest wall involvement • large airway obstruction – particularly when there is extrinsic compression • persistent cough • persistent haemoptysis • spinal cord compression • superior vena caval obstruction • symptomatic cerebral metastases. ‘Biological’ agents In the last few years there have been great strides made in the understanding of tumour biology; in particular the factors controlling angiogenesis and apoptosis (programmed cell death) are becoming clearer. Central to these processes are the epidermal growth factor receptors (EGFR) and vascular endothelial growth factor (VEGF) receptors. EGFR is normally widely expressed by many cell types and its activation results in a cascade of tyrosine kinase enzyme activation that leads to the stimulation of tumour proliferation, angiogenesis, invasion, metastasis and inhibition of
Palliative care Lung cancer is a disease with a very high frequency of symptoms of a distressing nature and where the duration of survival in the majority of patients in measured in months rather than years. Whilst it is essential that every effort is made to identify those patients suitable for radical therapy, it is equally important to ensure that there is universal rapid access to high-quality specialist supportive and palliative care. It has to include both the patient and their carers and should encompass a variety of elements including: • quality of life • symptom control • support with adjustment to loss • support and guidance regarding the completion of unfinished business • dignified death in patient’s place of choice • prevention of problems in bereavement. The following are the most common symptoms to cause distress in the final months and weeks of life.
Five-year survival in non-small-cell lung cancer after surgical resection Stage Stage Stage Stage Stage Stage Stage
Survival at 5 yrs (%) IA IB IIA IIB – chest wall invasion IIB – mediastinal invasion III (N0 disease)
84 68 47 56 29 34
Table 5
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management are underpinned by NICE guidance.12 The key elements of a lung cancer service should include: • clear referral pathways to a specialist team with identification of all abnormal chest X-rays • the availability of a rapid-access lung cancer clinic • all patients should be managed by a specialist MDT comprising representatives of all the key disciplines • all patients should have access to a lung cancer nurse specialist • every service should regularly audit its activity, performance and outcomes. ◆
Dyspnoea can be caused by a variety of factors: • chest infections (often on a background of COPD): nebulized bronchodilators often give relief in this situation • large airway obstruction: this may be amenable to palliative radiotherapy, bronchial stenting or laser debulking • pleural effusion: best managed by talc pleurodesis • phrenic nerve palsy. There is good evidence that specialist breathlessness clinics are of benefit in some patients. Opioids can be of value in terminal dyspnoea and are best administered orally. Pain is particularly a problem when there is chest wall involvement or bony metastases. Careful use of appropriate analgesics based on the WHO ‘analgesic ladder’ is the mainstay of treatment, but it is important to recognize opioid-resistant pain. Occasionally nerve root block or even cordotomy are required for intractable symptoms. Palliative radiotherapy is an important component of pain management in some patients (see above). Pleural effusions are best dealt with in specialist respiratory units with experience in the use of talc pleurodesis which, when properly carried out, can provide long-term relief from recurrent effusions in over 80% of patients. Cough can be difficult to manage but palliative radiotherapy is often useful as are oral opioids and sometimes nebulized bronchodilators. Fatigue is common and often goes unrecognized by doctors. It may be the result of anaemia and correction of this may be of value. Cachexia is almost universal in the later stages of the disease and oral corticosteroids offer good, if short-term, relief in many patients. Depression is also poorly recognized and put down to a ‘normal response’ to a patient’s illness. Antidepressants are of great value in some patients.
References 1 Cancer Research UK. CancerStats: lung cancer and smoking. 2007 Available at: www.Info.cancerresearchuk.org/cancerstats (accessed 24 October 2007). 2 The Information Centre for Health and Social Care. National lung cancer audit. Second annual report. 2007. Available at: http://www. ic.nhs.uk (accessed 24 October 2007). 3 GLOBOCAN 2002. Cancer incidence, mortality and prevalence worldwide 2002 estimates, 2006. Available at: http://www-dep.iarc.fr/ (accessed 24 October 2007). 4 Peto R, Lopez A, Boreham J, et al. Mortality from smoking in developed countries 1950–2000. Available at: http://www.ctsu. ox.ac.uk/∼tobacco/ (accessed 24 October 2007). 5 Peto R, Darby S, Deo H, et al. Smoking, smoking cessation and lung cancer in the UK since 1950: combination of national statistics with two case-controlled studies. Br Med J 2000; 321: 326–69. 6 Fishwick D, Barber CM. Occupational risk factors for lung cancer. Lung Canc Pract 2007; 3: 8–10. 7 Darby S, Hill D, Auvinen A, et al. Radon in homes and risk of lung cancer: collaborative analysis of individual data from 143 European case-controlled studies. Br Med J 2005; 330: 223. 8 Purdue M, Gold L, Järvholm B, et al. Impaired lung function and lung cancer incidence in a cohort of Swedish construction workers. Thorax 2007; 62: 51–56. 9 Nitadori J, Inoue M, Iwasaki M, et al. Association between lung cancer incidence and family history of lung cancer: data from a large-scale population-based cohort study, the JPHC study. Chest 2006; 130: 968–75. 10 Department of Health. The NHS national cancer plan. London: Department of Health, 2001. 11 Saunders M, Dische S, Barrett A, et al. Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small cell lung cancer; mature data from the randomised trial. Radiother Oncol 1999; 52: 137–48. 12 National Institute for Health and Clinical Excellence. Guidelines on the diagnosis and treatment of lung cancer. London: NICE, 2005 Available at: www.nice.org.uk (accessed 24 October 2007). 13 Brown J, Fairlamb D, Gower N, et al. Assessment of quality of life in the supportive care setting of the big lung trial in non-small cell lung cancer. J Clin Oncol 2005; 23: 7417–27. 14 Shepherd F, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005; 353: 123–32. 15 Calman K, Hine D. A policy framework for commissioning cancer services. A report by the Expert Advisory Group on Cancer to the Chief Medical Officers of England and Wales. London: Department of Health, 1995.
Specialist nursing The emergence of the lung cancer nurse specialist (LCNS) has been one of the most important elements in improving the care of lung cancer patients in the last 10 years or so. With the emergence of the MDT, patients are often seen by a variety of doctors, commonly in more than one hospital. The LCNS is there with the patient and carers at the start of their ‘journey’ when they are being told the diagnosis. They are in the ideal position to form an ongoing supportive relationship with the patient and their carers and to provide a stable ‘thread’ as they move along the care pathway. They are an invaluable source of information and advice and are of proven benefit in the follow-up of many patients. Proper education and advice can help identify problems at a stage before they become emergencies and can probably avoid many an unnecessary hospital admission. They have an important role in providing a link between the hospital and primary care setting.
Service provision Cancer services in the UK have developed and improved greatly since the Calman–Hine report of 199515 and the National Cancer Plan of 2001.10 Further development will be seen following the publication of the Cancer Reform Strategy in 2007. Details of
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