80

Management of patients with lung cancer

A national clinical guideline

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Introduction Presentation and referral Smoking cessation Diagnostic investigations Staging Surgery Radiotherapy Chemotherapy Combined modalities Endobronchial and vascular therapies Complementary therapies Multidisciplinary teams, follow up and communication Supportive and palliative care Implementation and further research Information for discussion with patients and carers Development of the guideline Abbreviations Annexes References

1 3 6 7 11 16 21 24 28 31 34 35 37 39 41 45 48 50 56

February 2005
COPIES OF ALL SIGN GUIDELINES ARE AVAILABLE ONLINE AT WWW.SIGN.AC.UK

KEY TO EVIDENCE STATEMENTS AND GRADES OF RECOMMENDATIONS

LEVELS OF EVIDENCE 1++ 1+ 12
++

High quality meta-analyses, systematic reviews of randomised controlled trials (RCTs), or RCTs with a very low risk of bias Well conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias High quality systematic reviews of case control or cohort studies High quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal Well conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal Non-analytic studies, eg case reports, case series Expert opinion

2+ 23 4

GRADES OF RECOMMENDATION Note: The grade of recommendation relates to the strength of the evidence on which the recommendation is based. It does not reflect the clinical importance of the recommendation. A At least one meta-analysis, systematic review of RCTs, or RCT rated as 1++ and directly applicable to the target population; or A body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results B A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or Extrapolated evidence from studies rated as 1++ or 1+ C A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or Extrapolated evidence from studies rated as 2++ D Evidence level 3 or 4; or Extrapolated evidence from studies rated as 2+ GOOD PRACTICE POINTS Recommended best practice based on the clinical experience of the guideline development group

Scottish Intercollegiate Guidelines Network

ISBN 1 899893 19 9 First published 2005 SIGN consents to the photocopying of this guideline for the purpose of implementation in NHSScotland Scottish Intercollegiate Guidelines Network Royal College of Physicians 9 Queen Street, Edinburgh EH2 1JQ www.sign.ac.uk
This document is produced from elemental chlorine-free material and is sourced from sustainable forests

1 INTRODUCTION

1
1.1

Introduction
THE NEED FOR A GUIDELINE
Lung cancer is the second most common cancer in Scotland after non-melanoma skin cancer.1 There are approximately 4,400 new cases and 4,000 deaths each year. Eighty five per cent of cases occur in patients over 60 years. Less than 10% of patients are alive five years after diagnosis and survival prospects have changed very little in the last 25 years.2 Incidence is higher, and survival is poorer, in people of lower socioeconomic status.3 A number of risk factors for lung cancer have been identified,4 but the overwhelmingly dominant one is exposure to tobacco smoke, with about 90% of patients being smokers or ex-smokers.1 Consequently, measures aimed at controlling tobacco use offer the best prospect for reducing the risk of, and mortality from, the disease. Reductions in the prevalence of smoking over the last 40 years have prevented an estimated 1.6 million premature deaths in the United Kingdom, many of these from lung cancer.5 Although the ideal must be to discourage people from taking up smoking in the first place, evidence suggests that the benefits of giving up smoking before middle age are substantial in terms of reducing the risk of lung cancer.6,7 Even after lung cancer has been diagnosed, the prognosis may be improved for some patients if they stop smoking (see section 3). ASH Scotland and NHS Health Scotland have published joint, evidence based guidelines on smoking cessation.8 Many specialties and professions are involved in the management of patients with lung cancer, requiring a well coordinated, multidisciplinary approach. This guideline provides advice for all stages of the patients pathway of care, from early recognition to treatment and follow up.

1.2

DEVELOPMENT AND REVIEW OF THE GUIDELINE

The first SIGN guideline on the management of lung cancer was published in February 1998. 9 This revision of that guideline includes evidence published between 1998 and April 2004, and updates practitioners on the role of chemotherapy in non-small cell lung cancer and the role of concurrent chemoradiotherapy in small cell lung cancer. The review of this guideline coincided with the development of a lung cancer guideline for England and Wales by the National Institute of Clinical Excellence (NICE). To minimise duplication of effort, elements of the systematic review of this guideline were shared between the SIGN development group and the guideline development group working on the NICE guideline.

1.3

REMIT OF THE GUIDELINE

The guideline is intended for use by chest physicians, surgeons, radiologists, pathologists, medical and clinical oncologists, pharmacists, public health practitioners, nurses, general practitioners, palliative care teams and allied health professionals. The guideline covers all aspects of the management of patients with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), and provides information for discussion with patients and carers. The guideline does not address other thoracic malignant disease such as mesothelioma, carcinoma in situ or secondary cancers that have spread to the lungs. Strategies for primary prevention or screening are also outwith the remit of the guideline. The guideline does not address the public health issues associated with smoking. Further information is available in a report from the NHS Health Development Agency.10

MANAGEMENT OF PATIENTS WITH LUNG CANCER

1.4

STATEMENT OF INTENT
This guideline is not intended to be construed or to serve as a standard of care. Standards of care are determined on the basis of all clinical data available for an individual case and are subject to change as scientific knowledge and technology advance and patterns of care evolve. Adherence to guideline recommendations will not ensure a successful outcome in every case, nor should they be construed as including all proper methods of care or excluding other acceptable methods of care aimed at the same results. The ultimate judgement regarding a particular clinical procedure or treatment plan must be made by the appropriate healthcare professional(s) in light of the clinical data presented by the patient and the diagnostic and treatment options available. It is advised, however, that significant departures from the national guideline or any local guidelines derived from it should be fully documented in the patients case notes at the time the relevant decision is taken.

1.5

REVIEW AND UPDATING

This guideline was issued in 2005 and will be considered for review in three years. Any updates to the guideline in the interim period will be noted on the SIGN website: www.sign.ac.uk

2 PRESENTATION AND REFERRAL

2
2.1

Presentation and referral

INTRODUCTION
Patients with lung cancer present with symptoms as diverse as cough, sputum, haemoptysis, breathlessness, wheeze, tiredness and weight loss.11 As some of these symptoms are common in the general population, delayed presentation and referral are a concern.

2.2

SYMPTOMS AND SIGNS

In the absence of high quality evidence derived from UK community settings, the guideline development group have based their recommendations on the Scottish Executive Health Departments Referral Guidelines for Suspected Cancer.1 Common symptoms of lung cancer are also available from case series.11 Table 1: Predominant symptoms at presentation Sign or symptom Cough Dyspnoea Haemoptysis Weight loss Chest/shoulder pain Hoarseness Fatigue No evidence was identified regarding the possible predictive value of combinations of symptoms. D D Patients should be referred urgently for a chest X-ray if they have experienced unexplained or persistent haemoptysis. Patients should be referred for a chest X-ray if any of the following symptoms persist for more than three weeks without an obvious cause: n cough n chest/shoulder pain n dyspnoea n weight loss n chest signs n hoarseness n finger clubbing n features suggestive of metastases from lung cancer (eg brain, bone, liver or skin) n persistent cervical/supraclavicular lymphadenopathy.

2.2.1

DIAGNOSIS IN PATIENTS WITH COPD There is significant overlap between symptoms of lung cancer and chronic obstructive pulmonary disease (COPD). COPD affects 1.5% of the general population and 7% of men aged over 75.12 A prospective population based study in the Netherlands found that 22% of patients diagnosed with lung cancer had coexistent COPD,13 but no evidence was identified on when to consider a diagnosis of lung cancer in patients with COPD. A chest X-ray should be performed in patients with COPD who develop new symptoms (especially weight loss) that might be attributable to lung cancer.

MANAGEMENT OF PATIENTS WITH LUNG CANCER

2.3

REFERRAL TO A RESPIRATORY PHYSICIAN

Patients who have presented to their primary care physician with respiratory symptoms and who have a subsequent abnormal chest X-ray are usually referred to a respiratory physician for confirmation of the diagnosis (see section 4) and staging of the disease (see section 5).1 Referral to a chest physician is associated with increased likelihood of receiving active treatment and of improved survival. At present approximately 25% of patients with lung cancer never see a chest physician.14 D Patients should be referred urgently to a chest physician if they have any of the following: n persistent haemoptysis in smokers or ex-smokers over 40 years of age n a chest X-ray suggestive or suspicious of lung cancer (including pleural effusion and slowly resolving or recurrent consolidation) n signs of superior vena caval obstruction (swelling of the face and or neck with fixed elevation of jugular venous pressure) n stridor (emergency referral). Even with a normal chest X-ray, patients who have experienced unexplained, nonspecific symptoms, eg fatigue potentially attributable to lung cancer, for more than six weeks should be referred urgently to a respiratory physician.

2.4

DELAYS IN PRESENTATION AND REFERRAL

Two Swedish cohort studies investigated the implications of the time interval between first symptoms, presentation and referral to hospital.15,16 One study found no association between tumour stage at diagnosis and the time elapsed from first symptoms to presentation in primary care and to the first secondary care consultation.15 The other study found that shorter time intervals were associated with a poorer prognosis.16 This apparent paradox is likely to reflect the fact that patients with severe symptoms and signs will present, and be referred, quickly. There may be a group of patients with potentially radically treatable tumours for whom delays have a negative impact on prognosis.17 Delays may cause distress to patients and carers even if they do not affect prognosis directly.18 Although there is insufficient evidence to make a recommendation on specific time scales for seeing patients, the guideline development group recommends that patients be seen promptly. Patients referred to a respiratory physician should be seen promptly, ideally within two weeks.

2.5

FAST TRACK SYSTEMS

Fast track models have emerged in an attempt to shorten the interval between presentation and treatment. One pilot randomised controlled trial (RCT) which looked at the benefits of a fast track system for diagnosis, staging and planning compared to standard practice showed higher rates of treatment and increased patient satisfaction in the intervention group.19 An observational study explored the effect of a two stop investigation service.20 The fast track service reduced waiting times for diagnosis and treatment and increased the resection rate. A subsequent abstract reporting on the same service suggested that survival is better in the fast track group after adjustment for age, sex, socioeconomic status and tumour type, but not for other important prognostic variables such as stage of disease, performance status and comorbidity.21 D Pathways for patients with suspected or confirmed lung cancer should be reviewed by Managed Clinical Networks with a view to implementing fast track models for assessing these patients.
1+

2 PRESENTATION AND REFERRAL

2.6

INFORMATION AND SUPPORT AT PRESENTATION AND REFERRAL

One systematic review and two small observational studies were identified that explore the role of information giving and support to patients at the time of presentation and referral.22-24 Only one focuses exclusively on patients with lung cancer 24 and all are set in hospital outpatient clinics rather than primary care. The studies underline the importance of enabling patients to make informed choices and that accurate information reduces patient anxiety, even when the news is bad. 22 The vast majority of cancer patients want basic information on diagnosis and treatment but not all patients want to receive all this information at once.23 There is a need for clear verbal and written information, tailored to each patients situation.24 Patients should be offered tailored, clear and accurate information, including an indication of the expected time scale of the referral process. Verbal and written communication between health professionals should include information regarding what the patient has been told about their diagnosis, investigation, treatment and prognosis. Clinicians should consider using different approaches for conveying information depending upon patients preferences eg: n verbal (from different healthcare professionals) n written (high quality information sheets and leaflets) n details of appropriate websites n recorded audio tapes of the consultation and discussion.

1+ 3+

MANAGEMENT OF PATIENTS WITH LUNG CANCER

Smoking cessation
Although patients who smoke may believe that quitting is futile following a cancer diagnosis there are proven benefits for smoking cessation for the cohort of patients where treatment results in prolonged survival.25 Continued smoking following a cancer diagnosis may:26
n n n n n

reduce survival time increase the risk of a recurrence, or a secondary primary tumour reduce treatment efficacy affect quality of life exacerbate and prolong treatment induced complications such as mucositis, dry mouth, loss of taste and voice, impaired pulmonary function, wound healing, and tissue and bone necrosis.

In patients being considered for surgery there is evidence that smoking cessation preoperatively has the potential to reduce:27,28
n n n

postoperative pulmonary complications length of stay in specialised units and overall stay in hospital demand on resources.

Discussing smoking cessation, particularly around the time of initial presentation provides a powerful window of opportunity, as patients and their families and carers are often receptive at this time to consider cessation. Without additional treatment support, 95% of those who try to give up smoking will be smoking again within six months.8 Effective pharmacological therapies and several behavioural approaches exist to help smokers quit, ranging from brief opportunistic interventions to more intense programmes provided by local specialist cessation services. Evidence based guidelines on smoking cessation are available from ASH Scotland and NHS Health Scotland at www.hebs.com/services/pubs/pdf/SmokingCes2004.pdf8 Cancer patients, and particularly those with lung cancer, usually suffer from weight loss, anorexia, breathlessness, and cough. The benefits of smoking cessation often include increased appetite, improved sense of smell and taste, weight gain, less sputum production, and an increase in oxygen intake and energy.25,29,30 See section 15.2 for sources of support for people who would like to stop smoking.

3.1

NICOTINE WITHDRAWAL
Symptoms of nicotine withdrawal can occur very rapidly, within hours of smoking the last cigarette. Integrating a patients smoking status, (eg how many a day), into their assessment provides the opportunity to recognise and manage nicotine withdrawal, as well as help to alleviate symptoms. Healthcare professionals should be aware that patients who are smokers may have enforced cessation due to incapacity to smoke. Symptoms associated with nicotine withdrawal are:30
n n n n n n n

lightheadedness sleep disturbance poor concentration irritability or aggression depression restlessness increased appetite.

Most of these symptoms can be quickly alleviated with nicotine replacement therapy.

4 DIAGNOSTIC INVESTIGATIONS

4
4.1

Diagnostic investigations
INTRODUCTION
Lung cancer is frequently suggested from chest X-ray findings: eg a solitary pulmonary nodule, pulmonary or hilar mass, poorly resolving pneumonia or pleural effusion. Histological or cytological confirmation of the diagnosis is desirable, though not always possible, and can be achieved by a variety of methods: image guided percutaneous biopsy, bronchoscopy, mediastinoscopy or thoracoscopy. Tissue diagnosis should be followed by subtyping of the cancer according to the current WHO classification.31 It may not be possible to use this classification fully if biopsy specimens or cytology samples are small, and in most instances designation as SCLC or NSCLC is sufficient for planning further management. The management of patients with an incomplete diagnosis should be discussed by the multidisciplinary team. No evidence was identified supporting the use of blood tests, eg tumour markers, in the diagnosis of lung cancer. Sometimes in patients of poor performance status (see annex 3) with major comorbidity, it is neither safe nor necessary to pursue investigations invasively towards a tissue diagnosis. Clinicians must act sensibly, sensitively and with compassion in such circumstances and proceed to non-surgical treatment or palliative care, usually after discussion in the multidisciplinary team setting. Similarly, where patients do not wish to be investigated, their preferences must be respected; refusal to undergo invasive investigation should not prejudice continuing care. Following diagnosis and initial staging investigations (see section 5) the care of patients newly diagnosed with lung cancer should be discussed in a multidisciplinary meeting for a review of clinical history, radiology and histology/cytology prior to development of a management plan.

4.2
4.2.1

IMAGING
CHEST X-RAY Lung cancer patients rarely present with a normal chest X-ray (only 2% in one study).32 Patients with lung cancer often have obstructive features (37%) and pleural effusions (22%). These indicate the need for further investigation even in the absence of a visible mass lesion. D A chest X-ray should be performed on all patients being investigated for the possibility of lung cancer.
3

4.2.2

CT SCANNING The role of computed tomography (CT) scanning of the chest in the diagnosis of lung cancer has been investigated in studies of the differential diagnosis of a solitary pulmonary nodule, where cases were reported by two independent experienced radiologists.33-35 This does not necessarily reflect typical practice. In an RCT designed to evaluate the impact of an early CT on management choices, 171 patients had CT scans reviewed before fibre optic bronchoscopy (FOB), allowing cancellation or a change to an alternative invasive procedure if appropriate. The trial included patients with distal collapse and visible tumours larger than 5 cm. Patients with peripheral lesions were excluded. CT scanning at an early stage in the patients journey allowed selection of the most appropriate investigation for confirmation of diagnosis and stage.36 The generalisability of these conclusions is not clear, given the patient selection criteria. Results from CT scanning are subject to variation caused by different scanning techniques, but suggest that CT scanning of the chest has a high sensitivity (89 to 100%) but a relatively low specificity (56 to 63%) and a poor negative predictive value (60 to 100%). This may be improved by serial scans. 35
3

1+

MANAGEMENT OF PATIENTS WITH LUNG CANCER

These results suggest that CT scanning alone should not be used to confirm a diagnosis of lung cancer and that histological and cytological confirmation of the diagnosis will be required in most cases. The same scan is often used for both diagnostic and staging purposes (see section 5.2.1). D D D Contrast enhanced CT scanning of the chest and abdomen is recommended in all patients with suspected lung cancer, regardless of chest X-ray results. A tissue diagnosis should not be inferred from CT appearances alone. CT scanning should be performed prior to further diagnostic investigations, including bronchoscopy, and the results used to guide the investigation that is most likely to provide both a diagnosis and stage the disease to the highest level.

4.2.3

NeoSPECT SCANNING Limited evidence is available on the role of NeoSPECT scanning in the investigation of patients presenting with solitary pulmonary nodules. Prospective diagnostic studies indicate that NeoSPECT scanning may be a useful adjunct to other imaging methods, but histological and cytological confirmation of the diagnosis will still be required.37-39 D NeoSPECT scanning should be considered as an investigation in patients presenting with solitary pulmonary nodules but histological confirmation will usually be required.
3

4.2.4

PET SCANNING Positron emission tomography (PET) scanning has been investigated as a diagnostic tool in the differential diagnosis of lung cancer and benign lesions presenting in the lung as a solitary nodule. At the time of publication there is a single PET scanning facility in Scotland, but PET should be available for patients with lung cancer for whom there is evidence of clinical benefit.40 A meta-analysis, a systematic review and 12 diagnostic studies were identified.41-54 The metaanalysis suggests that PET scanning has a diagnostic sensitivity of 96% and a specificity of 78% but there is considerable variation within the studies included. 41 The diagnostic studies indicate negative predictive values as low as 47%. Most of the published series are from North America where the incidence of granulomatous lung lesions is higher than in Scotland, making it unclear how these figures might relate to a Scottish population. C PET scanning may be used to investigate patients presenting with solitary lung lesions but histological/cytological confirmation of results will still be required.
2+

4.3

BRONCHOSCOPY
The value of bronchoscopy depends on the location of the primary tumour. Peripheral tumours in subsegmental bronchi may not be visible. The evidence base for the role of bronchoscopy in both central and peripheral tumours comes from two large systematic reviews.55,56
2++

4 DIAGNOSTIC INVESTIGATIONS

4.3.1

CENTRAL TUMOURS Flexible bronchoscopy has good diagnostic sensitivity (83% to 88%) for central lesions. 55,56 Sampling using multiple techniques gives the highest diagnostic yield. As a single procedure, bronchial biopsy is the most reliable. Table 2 shows the variation in sensitivity for each method. Table 2: Percentage diagnostic sensitivity in central tumours Technique Biopsy Brushings Washings All three modalities B B % Sensitivity Detterbeck55 83 64 48 83 Schreiber56 74 59 48 88
2++

Patients with central lesions who are otherwise fit should undergo flexible bronchoscopy in order to establish a histological or cytological diagnosis. Visible tumours should be sampled using more than one technique to optimise sensitivity.

4.3.2

PERIPHERAL TUMOURS Flexible bronchoscopy has a lower diagnostic sensitivity for peripheral lesions compared with central lesions (see Tables 2 and 3 ). Although fluoroscopy may improve the diagnostic yield of bronchoscopy in sampling peripheral lesions, results still compare poorly with percutaneous fine needle aspiration (FNA)/biopsy (see section 4.4).55,56 Table 3: Percentage diagnostic sensitivity in peripheral tumours Technique Biopsy Brushings Washings All three modalities B %Sensitivity Detterbeck55 60 48 37 66 Schreiber56 46 52 43 69
2++

Bronchoscopy may provide a diagnosis for peripheral lesions, although percutaneous FNA/biopsy is the preferred approach.

4.4

PERCUTANEOUS FNA/BIOPSY
Percutaneous FNA/biopsy is a highly sensitive technique for diagnosing lung cancer (sensitivity of 88% to 92%).56,57 Fine needle aspirations can be done as blind percutaneous biopsy or guided by fluoroscopy, ultrasound, CT or magnetic resonance imaging (MRI). Larger cutting needles can also be used to obtain biopsy cores of intact tissue for histology. Sensitivity is greater for peripheral lung lesions than fibre optic bronchoscopy.57 There is a high false negative rate (25%) resulting in limited ability to confirm a benign diagnosis. This may be improved by using core biopsies for histology rather than aspirates for cytology.57 Potential complications include bleeding and pneumothorax (chest drain 10%, haemoptysis 3%, mortality 0.04%). B Percutaneous FNA/biopsy should be considered as the preferred diagnostic technique in patients with peripheral lesions. Core biopsy rather than FNA may have the added advantage that specific benign diagnoses are more often possible.

2++

MANAGEMENT OF PATIENTS WITH LUNG CANCER

4.5

SPUTUM CYTOLOGY
There is a wide variation (10% to 97%) in the sensitivity of sputum cytology in the diagnosis of lung cancer.43,56,58 High sensitivity is only achieved by the use of specific and carefully controlled protocols for sample collection. In routine practice the diagnostic yield appears to be at the lower end of the range, suggesting that this technique is best reserved for cases with large central lesions where bronchoscopy or other diagnostic tests are contraindicated. D Sputum cytology should only be used in patients with large central lesions, where bronchoscopy or other diagnostic tests are deemed unsafe.
3

4.6

VIDEO-ASSISTED THORACOSCOPY
Video-assisted thoracic surgery (VATS) provides a highly sensitive (97% to 100%) method of obtaining histological and cytological material for confirmation of the diagnosis of lung cancer in patients where it has not been possible to achieve this by other less invasive means or intraoperatively prior to definitive resection.59,60 It has a low complication rate (0.8% open conversion rate). D Thoracoscopy should be considered for patients with suspected lung cancer where less invasive means have not achieved histological and cytological confirmation of diagnosis.
3

4.7

ANTERIOR MEDIASTINOTOMY/ MEDIASTINOSCOPY

Anterior mediastinotomy/mediastinoscopy may be used to establish a tissue diagnosis in selected patients presenting with mediastinal or hilar masses where this has not been achieved by other less invasive means.61 Anterior mediastinotomy/mediastinoscopy should be considered in patients with lung cancer presenting with hilar and mediastinal masses where histological or cytological confirmation has not been achieved by less invasive means.
3

4.8

GOOD PRACTICE IN PATHOLOGICAL REPORTING

The first priority in reporting histology and cytology specimens is to establish a diagnosis. Primary malignancies should then be classified as SCLC or NSCLC. NSCLC tumours should be subtyped where possible. All histology and cytology specimens should be reported by a consultant pathologist, who is a member of the Royal College of Pathologists continuous professional development (CPD) programme, who participates in relevant external quality assurance (EQA) schemes and works in a pathology laboratory with clinical pathology accreditation (CPA). Tissue from biopsies and resection specimens should be archived in the pathology department in a manner consistent with current legislation on consent and stored in line with the recommendations of the Royal College of Pathologists. The material should be available for review if required for the further management of the patient and for audit, teaching and research, as permitted by appropriate consent.

10

5 STAGING

5
5.1

Staging
INTRODUCTION
Staging is the assessment of the extent of disease and is performed for prognostic and therapeutic purposes. Lung cancer is staged using the revised International Staging System (ISS; see Annex 1), first published in 1986 by the American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer (UICC). The system has two major components: the anatomical extent of the disease (TNM; tumour, nodes, metastases) and the cell type.62 Clinical staging (c) relies on information obtained from imaging studies and biopsies. Pathological staging (p) is determined following surgical resection. This classification is used in the management of patients with NSCLC. Patients with SCLC are staged as either limited or extensive disease (see Annex 1). Accurate staging also allows more valid comparisons of outcomes to be made across hospitals and managed clinical networks. The imaging tools most commonly used to stage lung cancer are CT, MRI, ultrasound (US), PET and integrated PET-CT. Mediastinoscopy is the most commonly performed invasive procedure. The reliability of each of these tests, and the implications for the interpretation of results, is determined from the false negative (FN) and the false positive (FP) rates. These are listed in Annex 2.

5.2

T STAGE IN NSCLC
Radiographic differentiation of T1 and T2 disease does not significantly alter the choice of therapy. It is much more important to be able to predict T3 and T4 involvement if surgical resection is being considered.

5.2.1

CT SCANNING In Western countries a staging contrast enhanced CT of the thorax and upper abdomen is the standard method for assessing operability in lung cancer patients. The reliability of CT in predicting T3 or T4 disease is poor. 63 CT is equally poor at predicting chest wall invasion63 and mediastinal involvement.63 B Patients with suspected T3 or T4 disease who are otherwise fit for surgery should not be denied surgical exploration on the basis of a CT alone.
2++

5.2.2

MRI SCANNING With the exception of superior sulcus tumours, there is no benefit of MRI over CT in the assessment of patients with chest wall and mediastinal involvement.64-68 Looking specifically at mediastinal invasion, particularly invasion of blood vessels, some studies have shown an advantage of MRI over CT.67 B MRI is not recommended in the routine assessment of the T stage except in patients with superior sulcus tumours. It may be of value in selected patients with suspected mediastinal invasion.
2++

5.2.3

THORACOSCOPY Thoracoscopy may be beneficial in correctly determining the T stage in patients with T3 or T4 disease when less invasive methods have been inconclusive.69 C Thoracoscopy may be considered for more accurate determination of the T stage in patients with suspected mediastinal or chest wall invasion when less invasive techniques have been inconclusive.
2+

11

MANAGEMENT OF PATIENTS WITH LUNG CANCER

5.2.4

PLEURAL EFFUSION Spread of lung cancer to the pleural space with the development of an effusion indicates T4 disease. Pleural aspiration is essential for accurate staging in patients with a pleural effusion. A pleural biopsy should be undertaken in patients with negative fluid cytology.70 Some patients may require VATS biopsy to confirm pleural malignancy as aspiration and closed biopsy alone may be insufficient. D
n

2+

In patients being considered for curative therapy, pleural effusion should be investigated with pleural aspiration and/or pleural biopsy. The presence of malignant cells is required to categorise the lesion as T4.

In patients suitable for curative therapy VATS should be considered if aspiration and closed biopsy are negative.

5.3

N STAGE IN NSCLC
The most important aspect of intrathoracic staging is accurate determination of nodal involvement. CT and MRI scans rely solely on lymph node size to predict malignant involvement. A 1cm node size is the usual cut-off, having an average sensitivity and specificity of 75% and 76% respectively.71

5.3.1

HILAR NODES (N1) The reliability of CT,72 MRI73 and thoracoscopy74,75 in staging N1 nodes is poor. This may be a concern if radical radiotherapy is being considered and the primary tumour is distant from the hilum. Integrated PET-CT is more accurate and could have a role to play in this context.
2++

5.3.2

CT SCANNING OF MEDIASTINAL NODES (N2/3) For all categories of patients with lung cancer, the reliability of CT in the assessment of mediastinal nodes is poor with average false positive and negative rates of 45% and 13% respectively.76 The FN rate is higher with central tumours and adenocarcinomas (22% and 19%). B A positive CT scan result for mediastinal lymphadenopathy indicates the need for surgical biopsy of the enlarged nodes, regardless of size or site (with the exception of extensive infiltrating disease). Patients with small peripheral tumours and a negative CT scan of the mediastinum require no further investigation. Otherwise it is reasonable to further investigate the mediastinum with mediastinoscopy or PET prior to performing a thoracotomy.
2++

5.3.3

MRI SCANNING OF MEDIASTINAL NODES (N2/3) Conventional MRI is not superior to CT in the assessment of mediastinal nodes. 64,65,67,77,78 Data are not yet available on the reliability of new MRI contrast agents such as super paramagnetic iron oxide. B MRI has no role in the routine staging of mediastinal lymphadenopathy.
2++

12

5 STAGING

5.3.4

MEDIASTINOSCOPY AND OTHER INVASIVE TECHNIQUES FOR MEDIASTINAL NODES (N2/3) Mediastinoscopy is the gold standard for staging the mediastinum (paratracheal, pretracheal and anterior subcarinal nodes are accessible),79 with minimal morbidity, (2.3%), and mortality, (0.05%).80 Lymph node stations that cannot be reached by mediastinoscopy (aortopulmonary window, pre-aortic, paraoesophageal, inferior pulmonary ligament and posterior subcarinal) can be staged by thoracoscopy,69 endoscopic ultrasound guided FNA (EUS FNA), 81,82 endobronchial ultrasound guided FNA (EBUS FNA), percutaneous CT guided biopsy, 83-85 anterior mediastinotomy 86-88 and, less commonly, extended cervical mediastinoscopy.89 Transoesophageal and endobronchial ultrasound guided FNA are both relatively new techniques for which early experience suggests that they may prove reliable in assisting accurate staging of the mediastinum, and in some cases, in providing a primary diagnosis of more central lesions. C
n n

2+

Mediastinoscopy should be used to stage the mediastinum where possible. Inaccessible nodal stations can be staged using thoracoscopy, EUS FNA, EBUS FNA, percutaneous CT guided biopsy, extended cervical mediastinoscopy or parasternal mediastinotomy, as appropriate to the patients circumstances.

5.3.5

PET SCANNING OF MEDIASTINAL NODES (N2/3) PET scanning is more accurate than CT or MRI in detecting mediastinal lymphadenopathy. 90-92 Given a relatively high false positive rate (16%), patients should not be refused exploratory surgery on the basis of a positive PET scan. The poor anatomical localisation of PET scanning is largely overcome by integrated PET-CT.92 C
n

2+

Patients with a negative CT scan result for mediastinal adenopathy should proceed to PET, except for those with small peripheral tumours. Patients with a negative PET scan result for mediastinal adenopathy should proceed to thoracotomy. Patients with a positive PET scan result for mediastinal adenopathy require histological confirmation.

5.4

M STAGE IN NSCLC
Approximately 40% of patients with NSCLC present with distant metastases 93 and of these around 90% have clinical symptoms.94 The most common sites of metastases are brain, bone, liver, adrenal glands and lung.

5.4.1

CLINICAL EVALUATION The most important part of staging for distant metastases is the clinical evaluation utilising the patients history (especially if there has been weight loss), complemented by physical examination along with haematological and biochemical tests. Advancing imaging techniques are most useful when correlated with the findings of a clinical evaluation. Occult distant metastases are present in 15-30% of patients with cIII disease.95 C C Patients staged as cI-II on the basis of a chest CT and a negative clinical evaluation do not require further investigation to look for extrathoracic metastases. Patients staged as cIII following clinical evaluation may require further investigation for distant metastases.

2+

13

MANAGEMENT OF PATIENTS WITH LUNG CANCER

5.4.2

PET SCANNING AND DETECTION OF DISTANT METASTASES PET has been shown to identify unsuspected metastases in 10 to 15% of patients with NSCLC. When the scan is positive the lesion should be biopsied or followed up. 91,92,96 PET allows more accurate classification of the stage of the disease, and although it has not been shown whether this improves survival, it does reduce unnecessary surgical procedures.91,92 This suggests that it would be of most benefit in patients with NSCLC who are candidates for surgery or radical radiotherapy. One of the main limitations of PET scanning is that high glucose metabolism in the brain and kidney makes evaluation of metastases at these sites difficult. The drawback of limited anatomical resolution is largely overcome by integrated PET-CT.
2+

5.4.3

BRAIN METASTASES Contrast enhanced CT is the most commonly used imaging study to detect brain metastases and is as reliable as non-contrast enhanced MRI.97-104 Contrast enhanced MRI will detect more metastases than contrast enhanced CT but does not detect metastases in a greater number of patients. CT of the head is not warranted in asymptomatic patients initially staged as cI-II.98,99 In patients with N2 disease who are still being considered for curative treatment, a CT scan of the head is warranted.98 C Contrast enhanced head CT or MRI in patients with cI-II disease is not recommended. Contrast enhanced head CT or MRI is warranted in patients with N2 disease who are being considered for curative treatment.

2+

5.4.4

BONE METASTASES Bone scanning has a high false positive rate (30 to 60%) and should only be carried out where patients have symptoms suggestive of metastatic bone disease.105 A positive bone scan must be confirmed by additional studies (eg X-ray, MRI and biopsy). Compared to conventional isotope bone scanning, PET has the advantage of a much lower false positive rate, although the false negative rate is slightly higher.105 B A positive bone scan in patients with otherwise potentially curable disease must be confirmed by other studies (eg plain X-rays, MRI or biopsy).

2++

5.4.5

LIVER METASTASES Liver metastases are found in approximately 2% of asymptomatic patients initially staged as cIIII on the basis of a chest CT. 106 Benign hepatic lesions are common in the general population and the presence of a liver abnormality >1cm in an asymptomatic patient with lung cancer requires further characterisation by CT, US or MRI.107-109 Definitive confirmation of a suspected liver metastasis is best accomplished by needle biopsy which has a diagnostic accuracy of 90%.105 Complications are rare (1-2%) and consist mainly of haemorrhage.110 C
n

2+

n n

US, CT or MRI can be used to characterise most benign focal hepatic abnormalities >1cm. A definitive confirmation of a liver metastasis can only be made by needle biopsy. The management of patients with lesions too small to characterise by imaging and not amenable to biopsy is best guided by an estimation of the chance of metastatic disease given the clinical stage and symptoms.

5.4.6

ADRENAL GLAND METASTASES Incidental adrenal masses are seen in approximately 0.6% of all abdominal CTs. 70 to 95% will be benign non-functioning adenomas.111,112 In stage cI-III patients the frequency of adrenal enlargement is similar to the normal population, although approximately half of patients will have metastases on biopsy.113
2++

14

5 STAGING

The incidence of adrenal enlargement in lung cancer patients increases with higher stage disease. Adrenal glands less than 2 cm have a 10% chance of being malignant increasing to 75% for glands more than 4 cm.114-116 An adrenal adenoma can be reliably diagnosed by chemical shift MRI, enhanced CT and delayed contrast enhanced CT, making these suitable techniques for excluding metastases.114, 115 Percutaneous needle biopsy has an overall complication rate of 8-9% with 3-4% having major complications (eg pneumothorax or significant haemorrhage).117 At less than 5%, PET scanning appears to have the lowest FP and FN rates for adrenal metastases.114 B
n

2++

It may be reasonable to forego further investigation of adrenal glands <2 cm, in patients who are stage cI-II and who have a negative clinical evaluation Patients having adrenal gland nodules >2 cm, should proceed to further imaging studies and biopsy as necessary.

5.4.7

LUNG METASTASES Small pulmonary lesions are frequently seen in addition to the primary tumour on chest CT. These lesions are usually benign.118,119 C Patients with small pulmonary nodules should not be denied a curative approach without a definitive diagnosis (by biopsy, FNA or wedge resection).
2+

5.5

STAGING SCLC
The TNM system is generally not used for staging small cell lung cancer as approximately two thirds of patients present with distant metastases.95 Patients are classified as having either limited or extensive disease (see Annex 1 for definitions). Clinical evaluation can identify most patients who either have extensive disease or who are unsuitable for thoracic radiotherapy. Patients who are felt to be at high risk of having distant metastases and who are being considered for intensive treatment should undergo further staging investigations in a sequential manner.120 Useful investigations include head CT, biopsy of any palpable masses or nodes and an isotope bone scan. Bone marrow is the only site of extrathoracic disease in less than 5% of cases, and bone marrow aspiration should only be considered in patients who have no other sites of metastases.121 A pragmatic strategy is to stage patients by clinical evaluation and CT of the chest and abdomen and only proceed to further investigations if clinically indicated. B Investigation for distant metastases is recommended when intensive treatment is being considered for patients with SCLC who are considered to be at high risk of having distant metastases. Patients with SCLC should be staged by clinical evaluation and CT of the chest and abdomen. If the CT does not demonstrate extensive disease and the clinical examination is negative, management should proceed on the assumption of limited stage disease.

2++

15

MANAGEMENT OF PATIENTS WITH LUNG CANCER

6
6.1

Surgery
INTRODUCTION
Cures in lung cancer are almost always associated with surgical resection. Cure rates in Scotland and Britain are lower than in other countries in the western world. At present the British resection rate of 11%, compares unfavourably with rates of 17% throughout the rest of Europe and 21% in North America. Any increase in resection rates should be achieved without decreasing patient safety or significantly increasing unnecessary thoracotomies. 122 There is increasing evidence that adjuvant chemotherapy may be of benefit (see section 9). Very few randomised controlled trials on the surgical treatment of lung cancer were identified. The evidence base comes mainly from case series exploring different surgical techniques in different patient groups. Lung cancer patients present as a very heterogeneous group and the practice of tailoring all management decisions, including suitability for surgery, 123 on the basis of a multidisciplinary team meeting is to be recommended. The thoracic surgeon is a key member of the multidisciplinary team. The potential effects of smoking cessation on surgical outcome are described in section 3. Palliative management of endobronchial disease is discussed in section 10.

6.1.1

INFLUENCE OF SURGICAL EXPERIENCE/PRACTICE The link between individual surgeons operative mortality and case volume is unclear.124,125 Larger units offer significant advantages in terms of practice outcomes, training and resource availability.126,127

6.2
6.2.1

NON-SMALL CELL LUNG CANCER

RADICAL SURGERY (STAGE I AND II) Three retrospective studies,128-130 two prospective studies 131,132 and nine case series 133-141 covering 8,037 patients were identified. No indication of the operation type (eg lobectomy or pneumonectomy) or performance status data was given in the studies. Radical surgery confers a five year survival of between 54-80% for patients with stage 1A lung cancer and 38-65% for patients with stage 1B lung cancer. Surgery gives the highest chance of cure for patients with stage I and II lung cancer. D Patients with stage I and II lung cancer should be considered for curative surgery whenever possible.

6.2.2

REDUCTION OF SURGICAL MORBIDITY AND MORTALITY A number of observational studies comparing 30-day postoperative mortality for different surgical interventions (eg wedge resection, lobectomy and pneumonectomy) were identified.125,128,142-145 Patient characteristics varied considerably across the different studies and none of the studies described performance status and how this affects the choice of operation. Limiting the scope of the operation lowers mortality at 30 days; wedge resection has the lowest mortality rate, followed by lobectomy, pneumonectomy and extended resection in that order. Lobectomy is preferred to wedge resection on the basis of a reduced recurrence rate,146 except in patients who are unfit for surgery. Sleeve lobectomy may be a preferable option to pneumonectomy in suitable cases.

16

6 SURGERY

Six observational studies were identified that report on the 30-day mortality rate for inoperable lesions at thoracotomy.147-152 A significant mortality is associated with futile thoracotomies. D D 6.2.3 Lung resection should be as limited as possible without compromising cancer clearance. Lobectomy remains the procedure of choice for fit patients. Every effort should be made to avoid a futile thoracotomy.

VIDEO-ASSISTED THORACIC SURGERY (STAGE I AND II) Seven retrospective case series were identified incorporating a total of 969 patients with a mixture of stage I, II and IIIA lung cancer.153-159 None of the studies gave information on performance status. Not all of the studies provide information on survival by stage and the inclusion of patients at different stages will have affected survival rates across the studies. Follow up mechanisms also vary between studies. VATS for lung cancer is effective for resection of stage I and II with similar three and five year survival to that for open surgery. Patients may experience reduced pain and require shorter hospital stay than those undergoing conventional surgery.158,160-164 In 7-17% of VATS procedures conversion was required and complication rates reached 22%, similar to the rates for open surgery. There was also reasonable consistency between VATS and open surgery with regard to levels of intraoperative bleeding and hospital mortality. No evidence was identified on whether VATS is more appropriate for patients with lower performance status. Not all centres in Scotland can offer VATS. D VATS resection, undertaken by an appropriately skilled surgeon, may be offered to selected patients with clinical stage I lung cancer.
3

6.2.4

PROPHYLACTIC AND THERAPEUTIC MEDIASTINAL LYMPH NODE DISSECTION FOR STAGING AND TREATMENT OF NSCLC PATIENTS The options for mediastinal lymph node management are: Discretionary nodal sampling - enlarged or otherwise suspect nodes seen at surgery are taken for histological examination Systematic node dissection - samples are taken from each accessible mediastinal lymph node station for histological examination Radical mediastinal lymphadenectomy - all nodes in each accessible lymph node station are removed, often together with any associated connective tissue. The evidence from two randomised controlled trials 165,166 and one case series 167 suggests that five year survival increases when a radical mediastinal lymph node dissection is performed as opposed to a lymph node sampling strategy, but these studies all suffer from methodological problems. As more nodes are sampled staging is refined and this stage migration improves the apparent survival of those who remain within each group. Although there is no doubt that extensive node sampling/resection will improve the accuracy of staging it remains a matter for debate as to whether or not radical lymph node resection improves true survival. Conversely, there are concerns that radical mediastinal lymph node dissection may increase postoperative morbidity.168,169 B Systematic mediastinal lymph node dissection is recommended as offering the best compromise between accuracy of staging and containment of morbidity.

1+ 3

17

MANAGEMENT OF PATIENTS WITH LUNG CANCER

6.2.5

RESECTION IN PATIENTS WITH STAGE IIIA NSCLC A number of retrospective case series with relatively small numbers (30100 cases) have been published detailing the clinical outcomes achieved following surgery in selected patients with stage IIIA disease.170 Patients were managed using a multimodality approach that included preoperative chemotherapy and occasionally radiotherapy. Most studies suggested a survival benefit with a chemotherapy plus surgical resection protocol, compared with contemporary non-surgical management. Evidence from the few RCTs regarding preoperative chemotherapy does not support its routine use at present (see section 9.1). Patients who are suitable for surgery should have early (single station intracapsular) disease as determined by mediastinoscopy, the ability to tolerate induction treatment, evidence of response to this treatment and the reserves to subsequently tolerate major surgery. It is likely that few patients will meet these criteria. Patients with proven early N2 NSCLC may be considered for neoadjuvant chemotherapy, followed by surgery if there is CT evidence of response.

6.2.6

SUPERIOR SULCUS TUMOURS In several case series with carefully selected patient groups, postoperative survival for patients with this uncommon condition is reported as 20-40% at five years, usually in association with induction chemoradiotherapy.171-173 Review of the case volumes reported and the time periods involved suggests that only one or two such cases might be eligible for resection in Scotland each year. Exclusion of mediastinal node involvement by mediastinoscopy is generally included in the surgical assessment for operability.172 Although extended resection including excision of vertebral elements is described, such cases are extremely rare and resection is generally contraindicated in T4 tumours.174,175 D Patients with superior sulcus tumours not involving the brachial plexus and with negative mediastinoscopy may be considered for resection.

6.2.7

SURGICAL RESECTION OF BRAIN METASTASES (STAGE IV) Two small RCTs, including patients with NSCLC, have shown that surgical resection of a solitary metastasis combined with postoperative whole brain radiotherapy is superior to treatment with radiotherapy alone in terms of survival time, neurological function and quality of life.176,177 A third trial found no benefit from the addition of surgery to radiotherapy.178 An RCT comparing the effectiveness of surgery plus postoperative radiotherapy with that of surgery alone demonstrated that patients treated with combined modalities had fewer recurrences of cancer in the brain and were less likely to die of neurological causes. There was no statistically significant difference in median survival time between the groups.176,179 B Patients with a solitary synchronous or metachronous brain metastasis and otherwise potentially curative lung cancer: n may be considered for resection of the metastasis n should be given adjuvant brain radiotherapy to reduce the risk of local recurrences.

1+

6.2.8

SURGICAL RESECTION OF ADRENAL METASTASES No randomised trial data were identified to assess the efficacy of resection of adrenal metastases in non-small cell lung cancer. Only retrospective case reports concerning long term survivors following lung and adrenal resection were identified. Concerns about the probability of associated diffuse metastases present at the time of presentation have limited surgical treatment of adrenal metastases.180-182

18

6 SURGERY

6.3
6.3.1

SMALL CELL LUNG CANCER

EFFECTIVENESS OF SURGERY In general, routine surgery for limited stage SCLC is not recommended. An RCT examining the role of surgery in patients who had responded to five cycles of cyclophosphamide, doxorubicin and vincristine (CAV) chemotherapy failed to show any benefit for the surgical arm.183 There are two specific situations in which surgery may be beneficial: 1. Patients with clinical stage T1-2 N0 SCLC should be evaluated for potential surgical resection. They should be investigated thoroughly with CT chest and abdomen, radionuclide bone scan, CT brain and bone marrow biopsies. On confirmation of localised disease, surgery should be considered. Case series examining chemotherapy following resection of early stage SCLC suggest that adjuvant chemotherapy may confer a survival advantage.184-186 2. Occasionally a peripheral mass with no preoperative histology is found to be SCLC following resection. This tends to occur in patients at an early stage of the disease, who have operable cancer according to the standard criteria for NSCLC. Adjuvant chemotherapy may confer a survival advantage.184-186 A D Routine surgery for limited disease SCLC is not recommended. Patients with early stage SCLC may be considered for resection following extensive staging investigation. Adjuvant chemotherapy should be considered following resection of early stage SCLC.
1++

6.4

MANAGEMENT OF MALIGNANT PLEURAL EFFUSION

The optimal technique for pleurodesis in malignant pleural effusion has been investigated in a Cochrane review.187 The main agents used in the UK for pleurodesis are talc, tetracycline and bleomycin. Talc appears to be the most effective sclerosant, with a relative risk for successful pleurodesis of 1.26 (95% CI) compared with bleomycin or tetracycline. Adult respiratory distress syndrome following talc pleurodesis has been reported as a complication in case reports but not in RCTs. Meta-analysis indicates there is no evidence of excess mortality with talc pleurodesis compared with other sclerosants.Thoracoscopic pleurodesis was found to be more effective than medical thoracostomy pleurodesis, with a relative risk of non-recurrence of an effusion of 1.19 (95% CI) in favour of thoracoscopic pleurodesis. There was no evidence for increased mortality following thoracoscopic pleurodesis. More detailed guidelines on recurrent malignant pleural effusion have been produced by the British Thoracic Society pleural disease group.188 A A Achieving complete lung re-expansion prior to pleurodesis remains the most important prerequisite for success. Talc is the optimal sclerosant for thoracoscopic pleurodesis in patients with a malignant pleural effusion who are fit enough to undergo sedation or general anaesthesia. In patients who are unfit for a thoracoscopic procedure, tube thoracostomy pleurodesis using talc slurry should be performed.

1++

19

MANAGEMENT OF PATIENTS WITH LUNG CANCER

6.5

GOOD PRACTICE IN LUNG CANCER SURGERY

Lung cancer surgery should be practised in high volume thoracic surgery centres by surgeons trained in thoracic surgery who undertake this surgery as a major component of their clinical commitment. The thoracic surgery unit should have appropriate specialist support available pre- and postoperatively, including chest physicians, anaesthetists, radiologists, specialist nurses and pathologists with an interest in pulmonary diseases. Thoracic surgery centres should: n have a thoracic High Dependency Unit with dedicated staff and adequate monitoring facilities n have ready access to Intensive Care support n be efficiently linked to oncology specialties and geographically distant referring physicians. Treatment plans should be formulated following case review in fully serviced multidisciplinary team meetings. Lung cancer resection specimens should be reported by pathologists with reference to the WHO classification of lung and pleural tumours and the Royal College of Pathologists minimum dataset for lung cancer histopathology reports.31,189

20

7 RADIOTHERAPY

Radiotherapy
Radiotherapy has an established role in the management of patients with lung cancer, both on its own or in combination with chemotherapy. Radiotherapy has a well documented effect in palliating thoracic symptoms and, in selected patients with non-small cell lung cancer, it may be curative. It can also be useful in treating locally symptomatic metastases.

7.1
7.1.1

NON-SMALL CELL LUNG CANCER

RADICAL RADIOTHERAPY FOR STAGE I AND II PATIENTS There are no RCTs comparing radical radiotherapy with low-dose palliative radiotherapy or no active treatment. A Cochrane review190 and a systematic review191 of the non-randomised evidence identified 44 retrospective case series including a total of 3,683 patients treated with regimens of radiotherapy with doses of more than 50Gy/25F or its radiobiological equivalent. The studies are difficult to compare because of unknown variation in entry criteria or pretreatment prognostic criteria. Study results are inconsistent, with three and five year survival rates ranging from 0% to 55%. It is not clear whether the inconsistencies are due to variations in patient selection, treatment techniques or completeness of follow up. The evidence does suggest that radical radiotherapy is effective in prolonging survival in patients with NSCLC stage I and II (medically inoperable or refusing surgery). One RCT has shown that Continuous Hyperfractionated Accelerated Radiation Therapy (CHART) is more effective than 60Gy/6W in stage II patients.192 B Patients with NSCLC stage I and II who are medically inoperable or who do not consent to surgery should be offered radical radiotherapy.
2++

7.1.2

RADICAL RADIOTHERAPY IN STAGE III PATIENTS No trials were identified that compared radical radiotherapy to no treatment for stage III disease (some trials also included patients with stage I and II disease). Eight RCTs were identified using conventional radical radiotherapy (>55Gy) in one arm. Two year survival rates varied from 719%. Good prognostic factors included performance status, stage IIIA disease and use of higher radiation doses.193-200 There is no evidence to define the degree of lung function required to tolerate radical radiotherapy. B Patients meeting the following criteria should be offered radical radiotherapy: n IIIA or IIIB disease, as long as the tumour can be safely encompassed within a radical radiotherapy volume n WHO performance status (PS) 0 or 1 n less than 10% weight loss. Radical radiotherapy for patients with lung cancer should be delivered in an oncology centre equipped with 3-dimensional CT planning, facilities for conformal blocking and on-treatment verification. A recognised external quality assurance programme should be in place.

1+

21

MANAGEMENT OF PATIENTS WITH LUNG CANCER

7.1.3

HYPERFRACTIONATED AND/OR ACCELERATED RADIOTHERAPY IN STAGE III PATIENTS A meta-analysis201 and two RCTs were identified 195,202 that suggest a survival benefit for accelerated and hyperfractionated radical radiation therapy compared with conventional radiotherapy. No benefit was observed for hyperfractionated radical radiation therapy of standard time length over conventional radiotherapy. A Patients having radical radiotherapy should be given CHART (54Gy/36F/12 days) in preference to 60Gy/30F/6W.
1+ 1++

7.1.4

RADIOTHERAPY-RELATED MORBIDITY There is a paucity of data from randomised controlled trials looking at how radiation-related morbidity can be reduced, either by altering the radiation technique or by adding in other agents. Trials looking at ways of reducing radiation morbidity should be supported.

7.2
7.2.1

SMALL CELL AND NON-SMALL CELL LUNG CANCER

PALLIATIVE THORACIC RADIOTHERAPY IN PATIENTS WITH SYMPTOMATIC, LOCALLY ADVANCED LUNG CANCER No RCTs comparing palliative thoracic radiotherapy with active symptom control or chemotherapy in patients with chest symptoms were identified. In RCTs comparing different radiotherapy regimens, the majority of patients with locally advanced lung cancer obtain symptomatic benefit from palliative radiotherapy. Chest pain improves in 50-88%, haemoptysis in 73-98%, cough in 52-72%, and dyspnoea in 32-37% of patients. Palliative thoracic radiotherapy was effective in improving local chest symptoms for the majority of patients with NSCLC for at least half of their remaining life.203-205 There is no evidence that longer, more fractionated regimens of palliative thoracic radiotherapy give better or more durable symptom control than lower dose regimens of one or two fractions. Higher dose regimens of palliative thoracic radiotherapy result in increased toxicity, especially radiation oesophagitis. There is evidence that patients with good performance status live longer after more fractionated higher dose regimens of palliative thoracic radiotherapy, such as 39Gy/13F.203-205 No RCTs specifically including patients with SCLC were identified, resulting in uncertainty regarding the effectiveness of palliative radiotherapy for this group of patients. The experience of the guideline development group is that SCLC is a radio-responsive tumour and so palliative radiotherapy should be at least as effective in this group as it is for patients with NSCLC. A Patients with thoracic symptoms and good performance status not suitable for radical radiotherapy should be considered for more fractionated, higher dose regimens of palliative radiotherapy, such as 39Gy/13F. Patients with thoracic symptoms and poor performance status not suitable for radical radiotherapy should receive palliative radiotherapy with regimens of 10Gy/1F or 16Gy/2F. Patients with SCLC should be considered for palliative thoracic radiotherapy if they have significant chest symptoms and other treatments have been ineffective or are considered inappropriate.

1+

22

7 RADIOTHERAPY

7.2.2

RADIOTHERAPY IN PATIENTS WITH ISOLATED BRAIN METASTASES Two RCTs exploring the role of radiotherapy and surgery in the treatment of single metastases to the brain demonstrate a survival benefit for surgical resection of solitary brain metastases followed by whole brain radiotherapy compared to whole brain radiotherapy alone, in patients who have controlled extracranial disease.176,177 The American Society for Clinical Oncology (ASCO) lung cancer guideline on unresectable NSCLC supports the use of radiotherapy following resection.206 B Patients with single brain metastases should be offered resection followed by whole brain radiotherapy.
1+

7.2.3

PALLIATIVE RADIOTHERAPY IN PATIENTS WITH SYMPTOMATIC METASTASES Many patients with lung cancer develop symptomatic metastases that can be treated using radiotherapy. A systematic review207 and one RCT208 on palliative radiotherapy for bone metastases were identified. The RCTs were not restricted to patients with lung cancer, although a significant proportion of the patients did have lung cancer. The systematic review identified 11 trials involving 3,435 patients. There was no difference in overall or complete pain response rates between single fraction (usually 8Gy) or multifraction radiotherapy, although patients treated with a single fraction had a significantly higher re-treatment rate and were at greater risk of developing a pathological fracture ( 3.0% vs 1.6%). The remaining RCT is an interim analysis of single fraction versus multifraction radiotherapy in treating neuropathic bone pain and suggests radiotherapy may have a positive role to play in treating such pain. For patients with brain metastases, 20Gy/5F is as effective as more prolonged regimens.209 For patients with a good prognosis, 30Gy/10F is more effective in terms of survival than 12Gy/2F.210 No RCTs investigating the role of radiotherapy on skin metastases were identified. The guideline development group suggests that palliative radiotherapy regimens of 8Gy in one fraction are effective for palliation of skin metastases. A A Patients with lung cancer and symptomatic bone metastases should be treated with a single 8Gy fraction of palliative radiotherapy. Selected patients with unresectable and/or multiple brain metastases and good performance status should be considered for fractionated palliative radiotherapy (eg 20Gy/5F). Patients with symptomatic skin metastases should be considered for palliative radiotherapy with single fractions of 8Gy.

1+

23

MANAGEMENT OF PATIENTS WITH LUNG CANCER

Chemotherapy
The greatest change in the management of lung cancer since the publication of the original SIGN guideline in 1998,9 has been the increased use of chemotherapy in patients with NSCLC. There is now evidence from meta-analyses and RCTs of the potential benefit to patients. Progress in the treatment of SCLC with chemotherapy has been less marked, but changes in recommended therapy are detailed.

8.1

CHEMOTHERAPY FOR PATIENTS WITH STAGE IIIB AND IV NSCLC

A meta-analysis evaluating the benefit of chemotherapy in patients with NSCLC concluded that there is a median survival improvement of around six weeks and a 10% increase in one year survival with cisplatin-based regimens.211 The trials pre-dated introduction of the newer agents. These survival results were replicated in two large UK randomised trials, without disadvantage to quality of life.212,213 Modern chemotherapy regimens Four randomised trials of single agent modern chemotherapy (gemcitabine,214 paclitaxel,215 docetaxel216 and vinorelbine217) versus best supportive care (including radiotherapy) reveal a trend to improved quality of life with increased survival in three of the four studies. No particular combination of these agents in regimens with platinum has been shown to be more effective.218-220 Chemotherapy for NSCLC patients who are PS2 does not result in significant benefit in life expectancy,221,222 although their quality of life may be improved.213 Any treatment should be at the discretion of the clinician and should take into account any significant comorbidity or whether the poor performance status is tumour-related. A Chemotherapy with a platinum-based combination doublet regimen should be considered in all patients who are not suitable for curative resection or radical radiotherapy and are fit enough to receive it. Chemotherapy is not generally recommended for NSCLC patients who are PS3 or 4.
1+ 1+ 1++

8.1.1

CHEMOTHERAPY IN OLDER PATIENTS Age in itself does not predict tumour response but older patients may be more susceptible to the side effects of chemotherapy.213 In older patients, chemotherapy can improve quality of life and survival compared to active symptom control.217,223 A Selected older patients with stage III/IV NSCLC should be offered chemotherapy.
1+

8.1.2

DURATION OF CHEMOTHERAPY A comparison of three versus six cycles of mitomycin, vinblastine, cisplatin (MVP) demonstrated no benefit in response rate, symptom improvement, duration of response or median survival in the patients treated beyond three cycles.224 Similarly a comparison of four cycles of carboplatin and paclitaxel versus continuation of chemotherapy to progressive disease concluded that four cycles were as effective in terms of median survival and quality of life.225 A comparison of gemcitabine versus cisplatin and vindesine in a total of 169 patients demonstrated no further benefit beyond three cycles of treatment.226 A For patients with advanced NSCLC the number of chemotherapy cycles should not exceed four.

1+

24

8 CHEMOTHERAPY

8.1.3

SECOND LINE CHEMOTHERAPY In patients who are fit at the time of progression of their advanced NSCLC, second line treatment with docetaxel (75 mg/m2) can improve time to progression, survival and quality of life.227-229 At present there are no clear data on which patients are most likely to respond and it is not known if duration of initial response is important. A Second line chemotherapy with docetaxel 75 mg/m2 (three weekly) should be considered for stage IIIB/IV NSCLC patients with good performance status.
1+

8.1.4

TARGETED THERAPIES Newer approaches to chemotherapy have involved blocking specific tumour growth factor receptors. Current evidence does not support the routine use of targeted therapies in patients with stage IIIB/IV NSCLC outwith a clinical trial.230-233

8.2

CHEMOTHERAPY FOR PATIENTS WITH SCLC

Limited disease SCLC The role of chemotherapy in the treatment of patients with limited disease SCLC has been discussed in previous evidence based guidelines.234,235 Both symptom control and median survival are increased with combination, as opposed to single agent, chemotherapy, with objective response rates around 90%, but even with optimal combination therapy (see section 9), two year survival is only around 25% in the UK.236 There are no studies of chemotherapy versus best supportive care as chemotherapy has been the standard first line therapy in SCLC since the 1970s. Extensive disease SCLC Patients with extensive disease SCLC are not curable and, in the UK, have a two year survival rate of less than 5%. Patients have a high objective response rate to chemotherapy with useful symptomatic improvement.237 Careful patient selection is crucial to avoid unnecessary toxicity. Combination chemotherapy has been shown to be less toxic and more effective than single agent treatment with oral etoposide.237

8.2.1

CHEMOTHERAPY IN OLDER PATIENTS When considering the suitability of a patient for chemotherapy, age and poor performance status should be seen as separate factors. A systematic review of 168 studies and a review of 21 studies in SCLC concluded that standard chemotherapy should not be denied on the basis of age alone.234,238 Fit older patients should be offered combination chemotherapy, as this has better survival rates than single agent chemotherapy. The benefits of any kind of chemotherapy for patients who are PS3 or 4 are unclear. A Combination intravenous chemotherapy should be considered for SCLC patients over 70 years of age with performance status 0-2.

1++

8.2.2

STANDARD REGIMENS RCTs have shown that a platinum combination regimen results in improved survival when compared with anthracycline-based combinations in SCLC patients. 239,240 A regimen based on platinum agents and etoposide has proven efficacy and is one of the most commonly prescribed treatments in limited and extensive disease SCLC.241,242 The role of newer chemotherapeutic agents243 in the treatment of SCLC remains to be established. Irinotecan in combination is one of the most active new drugs but is not currently licensed for use in lung cancer. A A regimen containing a platinum agent and etoposide is recommended for first line treatment of patients with SCLC.
1+

25

MANAGEMENT OF PATIENTS WITH LUNG CANCER

8.2.3

ALTERNATING REGIMENS There is evidence that alternating regimens provide no additional benefit in terms of progressionfree or overall survival, compared with standard chemotherapy regimens.244,245

8.2.4

HIGH DOSE/INTENSIFICATION OF CHEMOTHERAPY High dose/intensification of chemotherapy has been studied in both limited and extensive disease SCLC. A review of the major studies published since 1980 concluded that there was no evidence of benefit beyond six cycles of chemotherapy, nor was there benefit from early or late dose intensification, but that shortening the treatment interval with the use of GCSF could improve median and two year survival. 246 Higher response rates have been obtained but at the expense of significant toxicity.239

8.2.5

DURATION OF CHEMOTHERAPY In patients with limited disease SCLC no survival benefit is gained from extending induction chemotherapy beyond six cycles.247 A In patients with SCLC the recommended number of chemotherapy cycles is three to six.
1+

8.2.6

SECOND LINE CHEMOTHERAPY Patients who respond to first line chemotherapy and who have had at least six months diseasefree survival are most likely to benefit from second line treatment.239 B Second line chemotherapy in patients with SCLC should be considered depending on the duration of response to first line chemotherapy and on patients performance status and wishes.
1++

8.2.7

MAINTENANCE The evidence does not support the use of continued induction therapy, oral etoposide, interferon or matrix metalloproteinase inhibitors as maintenance treatment following response to first line chemotherapy.247-249 B Maintenance chemotherapy following first line treatment is not recommended.
1+

8.3

REDUCING TOXICITY IN NSCLC AND SCLC

In one systematic review of 65 trials, the use of a haematopoietic growth factor did not improve overall survival, but did increase the rate of recovery from chemotherapy and may have reduced the number of infective episodes.250 A second systematic review of 12 studies with 2,107 patients did not support the use of growth factors to support chemotherapy in SCLC.251 In an RCT with 300 patients, granulocyte-macrophage colony-stimulating factor (GMCSF) had no effect on the ability to deliver higher dose intensities of chemotherapy nor did it reduce the rate of infectious complications.252 A The routine use of growth factors in supporting patients during chemotherapy is not recommended.
1++ 4

1+

In an RCT with 84 patients, amifostine had no significant effect on the degree of myelosuppression or other toxicities.253 A guideline based on a systematic review of the use of amifostine did not recommend its use in the curative or adjuvant setting outwith a clinical trial.254 A Amifostine should not be used with cisplatin (80 mg/m2 ) outwith clinical trials.

The use of human recombinant erythropoietin in patients receiving cisplatin-based chemotherapy reduces the need for blood transfusion, but has no other proven benefits.255,256 The benefits of smoking cessation in this context are discussed in section 3.

1++

26

8 CHEMOTHERAPY

8.4

ADMINISTRATION OF CHEMOTHERAPY
It is the responsibility of the thoracic oncology cancer team to ensure that chemotherapy is prescribed, supplied and administered according to published guidelines and national standards.257-259 D Staff should be experienced and trained in safe prescribing, preparation and administration of chemotherapy and be involved in ongoing continuous professional development and reappraisal. Hospital based administration of chemotherapy should take place during the working day in designated areas equipped to deal with any medical emergencies. Chemotherapy should be administered in environments that meet the standards set out in national guidance.
4

27

MANAGEMENT OF PATIENTS WITH LUNG CANCER

Combined modalities
There is increasing evidence that combining modalities of treatment (surgery, radiotherapy and chemotherapy) may improve outcome in both small cell and non-small cell lung cancer.This is often at the expense of increased acute, and sometimes late, toxicity.The challenge is to define the optimal combination and schedule of therapy, while balancing the benefits in disease control against the risk of toxicity.This section summarises the evidence to date on the effectiveness of combining modalities of treatment for different clinical scenarios.

9.1

PREOPERATIVE (NEOADJUVANT) CHEMOTHERAPY IN NSCLC PATIENTS UNDERGOING CURATIVE SURGERY

Neoadjuvant chemotherapy is used in patients who have resectable disease at presentation (stages I, II and limited IIIA NSCLC) and in patients in whom downstaging by chemotherapy is required prior to surgery. There is insufficient and conflicting evidence260,261 with regard to the benefits of preoperative chemotherapy in resectable lung cancer, with three published RCTs reporting conflicting results.262-264 Two studies recruiting stage III patients closed early because of disparity in survival between the two arms in favour of chemotherapy, with the surgery alone arm faring much worse than would normally be expected.263,264 Conversely, the larger trial demonstrated no benefit from chemotherapy in stage III disease, but detected a survival advantage in stages I and II.262 All three studies had confounding factors in the variable addition of radiotherapy. Preoperative chemotherapy is not recommended for patients with operable early stage lung cancer, outwith clinical trials. Studies of preoperative chemotherapy should be supported.

1-

9.2

PREOPERATIVE (NEOADJUVANT) CHEMOTHERAPY IN NSCLC PATIENTS UNDERGOING CURATIVE SURGERY PLUS RADIOTHERAPY
No randomised studies that addressed the role of preoperative chemoradiation were identified. There are a number of phase II studies. Expert consensus is that chemoradiation should not be regarded as standard practice.265 D There is no role for preoperative chemoradiation outside clinical trials.
4

9.3

POSTOPERATIVE (ADJUVANT) CHEMOTHERAPY IN NSCLC PATIENTS UNDERGOING CURATIVE SURGERY

The balance of evidence is consistent with a survival benefit from adjuvant chemotherapy at the expense of associated toxicity.266-269 A meta-analysis and two subsequent RCTs found some benefit from chemotherapy (hazard ratio less than 1.0), although this did not achieve statistical significance.266-268 The largest RCT, with 1,867 patients, demonstrated a small statistically significant survival benefit of 4% at five years. Chemotherapy-related mortality was reported at 0.8% and 23% of patients had at least one episode of life threatening adverse effects from chemotherapy, largely attributable to myelotoxicity.269 A Adjuvant chemotherapy should be considered for resected NSCLC, but discussed fully given the small margin of benefit, risk of toxicity and uncertainty as to which group of patients are most likely to benefit.

1++

28

9 COMBINED MODALITIES

9.4

POSTOPERATIVE (ADJUVANT) RADIOTHERAPY IN NSCLC PATIENTS UNDERGOING CURATIVE SURGERY

Postoperative radiotherapy (PORT) has been shown to reduce local recurrence in the radiotherapy arm.201,270,271 The PORT meta-analysis suggests an adverse effect of radiotherapy on survival with a hazard ratio of 1.21 (95% CI 1.08-1.34), favouring surgery; two year survival with adjuvant radiotherapy was 48% v 50% in the surgery alone group.270 A subsequent RCT examined the effect of postoperative radiotherapy in pathological stage I patients and demonstrated a significant survival advantage in favour of radiotherapy; five year survival 67% versus 58% (P=0.048).271 It is not clear whether the adverse effect of PORT on survival applies to postoperative radiotherapy using modern planning techniques and treatment technology. Postoperative radiotherapy has traditionally been considered for those patients with incomplete resection of the primary tumour and for those patients requiring chest wall resection to remove the tumour. There is little evidence addressing these specific indications. A Patients with NSCLC who have had complete tumour resection should not receive postoperative radiotherapy, except as part of a randomised trial. Postoperative radiotherapy may be considered in patients with incomplete resection.

1++ 4

9.5

NEOADJUVANT AND ADJUVANT CHEMOTHERAPY IN NSCLC PATIENTS UNDERGOING RADICAL RADIOTHERAPY

The evidence suggests a small survival benefit from the addition of platinum-based chemotherapy to radical radiotherapy given at standard fractionation (eg 60Gy/30F/6W). The evidence is based largely on trials involving stage III NSCLC, good performance status patients. There is no evidence relating to whether the addition of chemotherapy to CHART radical radiotherapy might improve outcomes.193-198,272,273 A Platinum-based combination chemotherapy should be considered for good performance status patients with locally advanced disease who are to be treated with radical radiotherapy at standard fractionation (eg 60Gy/30F/6W). Trials investigating the role of chemotherapy in conjunction with CHART should be supported. Clinical trials addressing the issue of timing of chemotherapy should be promoted.

1++

9.6

CONCURRENT CHEMOTHERAPY IN NSCLC PATIENTS UNDERGOING RADICAL RADIOTHERAPY

There is evidence of a small survival benefit from the addition of chemotherapy to conventionally fractionated radical radiotherapy in patients with locally advanced disease and of good performance status.274,275 It is unclear how much additional benefit is gained from giving chemotherapy concurrently rather than sequentially and how this relates to the increased risk of toxicity. There are also unresolved issues regarding the choice of drugs and whether chemotherapy should be given daily, weekly or three weekly if administered with radiotherapy. None of the studies randomising between sequential and concurrent chemoradiotherapy have yet been published in full. Clinical trials addressing the issues of optimal scheduling should be supported.

1++

29

MANAGEMENT OF PATIENTS WITH LUNG CANCER

9.7

CONSOLIDATION THORACIC RADIOTHERAPY IN PATIENTS WITH LIMITED SCLC DISEASE

Consolidation thoracic radiotherapy improves survival in patients with limited disease SCLC who have achieved complete response or partial response following combination chemotherapy.276,277 A Consolidation thoracic radiotherapy should be considered for patients with limited disease SCLC who have achieved complete response or partial response following chemotherapy.
1++

9.8

CONCURRENT RADIOTHERAPY AND CHEMOTHERAPY IN PATIENTS WITH LIMITED DISEASE SCLC

The current evidence is conflicting with regard to the benefit of concurrent radiotherapy in limited disease SCLC.278-285 Although the RCTs are good quality, the number of confounding variables and different outcome measures makes it difficult to reach a clear conclusion. There are positive studies showing benefit for early radiotherapy. Many of the studies looked at early versus late with early and late being concurrent in some studies. The definition of early varied between studies. From this work it appears that the overall treatment time for radiotherapy, as well as the timing of the start date, is a factor in outcomes. There is some evidence that concurrent chemoradiation increases toxicity. Clinical trials addressing the issue of timing of radiation should be supported.

1+ 1-

9.9

HYPERFRACTIONATED RADIOTHERAPY REGIMENS IN PATIENTS WITH LIMITED DISEASE SCLC

Two RCTs of minimal clinical relevance were identified.286,287 One used split-course radiotherapy in the control arm while the other used 45Gy/25F/5W as control. Such a protracted regimen would not be standard in the UK. Hyperfractionated, accelerated, concurrent chemoradiotherapy was more effective than daily concurrent chemoradiotherapy at this protracted radiotherapy schedule.287 It is unclear how much this difference was influenced by the different overall treatment times of the two regimens. The benefit of hyperfractionated accelerated radiotherapy relative to a standard three week course of radiotherapy remains undefined. Patients should be entered into trials of novel dose/fractionation schedules in the treatment of limited disease SCLC.

1+

9.10

PROPHYLACTIC CRANIAL RADIOTHERAPY IN SCLC PATIENTS WITH LIMITED DISEASE

Two systematic reviews and one meta-analysis were identified. Patients in remission following chemotherapy were randomised between no further treatment or prophylactic cranial irradiation.288-290 Patients receiving radiation demonstrated a reduction in brain metastases (relative risk 0.46, CI 0.38-0.57) with improved overall survival (relative risk 0.84, CI 0.73-0.97). No high quality evidence for late neuropsychological sequelae was identified. The optimal dose and fractionation for prophylactic cranial radiotherapy are uncertain. Toxicity concerns suggest it should be given following chemotherapy rather than concurrently. There may be benefit for prophylactic cranial radiotherapy in extensive disease patients who have achieved remission but this requires further study. A Prophylactic cranial radiotherapy should be offered to patients with limited disease SCLC achieving remission after chemotherapy. European Organisation for the Research and Treatment of Cancer (EORTC) studies of optimal dose/fractionation and use of prophylactic cranial radiotherapy in extensive disease SCLC should be supported.
1++

30

10 ENDOBRONCHIAL AND VASCULAR THERAPIES

10
10.1

Endobronchial and vascular therapies

INTRODUCTION
There is very little high quality evidence regarding the role of endobronchial and vascular interventions. The majority of the literature is comprised of non-randomised and descriptive studies. Interventional bronchoscopy is a highly specialised area requiring specialised resources and currently performed by few respiratory physicians in Scotland. Improvements in equipment design and techniques should lead to an increase in the application and utility of this technique.

10.2

ENDOBRONCHIAL TREATMENTS
Photodynamic therapy (PDT), brachytherapy, electrocautery, cryotherapy, stents and Nd-YAG laser therapy are therapeutic options available for the management of endobronchial malignancies. They may be used in the curative treatment of early stage lung cancers or, more commonly, in the palliative management of tumours causing airway obstruction. Much of the evidence about the use of endobronchial treatments comes from retrospective case series. Due to heterogeneity in histology (many case series include patients with nonmalignant conditions) and the stage of patients treated, the incidence of additional treatments and different methods of reporting results, these studies are very difficult to compare. Most suggest subjectively measured improvement of dyspnoea in about 70% of patients, although the duration of improvement is often not reported and many patients require repeated interventions.291-295 The only trial to adequately report quality of life compared external beam radiotherapy with high-dose rate brachytherapy. Although this trial closed early due to poor accrual, it suggested a rate of relief of dyspnoea of about 30% in both arms at four months.296

10.2.1

BRACHYTHERAPY VERSUS EXTERNAL BEAM RADIOTHERAPY Two randomised trials comparing endobronchial radiotherapy and external beam radiotherapy in patients with advanced disease were identified.297,298 The first study randomised 99 patients to either high-dose rate (HDR) brachytherapy or external beam radiotherapy. Although external beam gave better palliation, dysphagia was significantly worse. Median survival was modestly improved in the external beam group.297 The second trial compared external beam to external beam plus HDR-brachytherapy. Although there was no significant difference between patients in the two arms in terms of relief from dyspnoea, a higher rate of lung re-expansion was reported with endobronchial treatment. There were no differences in any other quality of life issues or in median survival. 298 At present the evidence suggests that external beam radiotherapy provides better palliation of symptoms in NSCLC than HDR-brachytherapy. The addition of brachytherapy to standard external beam does not improve survival or quality of life. Standard external beam radiotherapy alone is preferred to endobronchial brachytherapy in the initial palliative treatment of NSCLC.

1-

10.2.2

BRACHYTHERAPY VERSUS Nd-YAG LASER One small randomised trial (29 patients) comparing treatment of endobronchial tumours with Nd-YAG laser alone with combined Nd-YAG laser and HDR-brachytherapy was identified. A significant benefit in favour of the combined modality arm was identified in terms of the need for further endobronchial treatment, time to progression and symptom free period.299 The role of brachytherapy compared to other endobronchial treatments is uncertain and further clinical trials are required in this area.

31

MANAGEMENT OF PATIENTS WITH LUNG CANCER

10.2.3

PHOTODYNAMIC THERAPY One systematic review examining the role of PDT in the management of early stage lung cancer and locally advanced lung cancer was identified.300 Early stage lung cancer The review included 10 non-controlled studies and one summary paper reporting the use of PDT in 444 early stage lung cancer patients. Response rates varied between 31% and 85%. The method of response assessment varied between studies making comparisons difficult. Five year survival rates ranged from 43% (in patients who were not candidates for surgery) to 72% (in patients who were eligible for surgery). The rates are difficult to interpret and may have been influenced by the use of other treatment modalities.300 Locally advanced lung cancer The review included three RCTs and four non-controlled trials which demonstrated that PDT can contribute to the palliation of local cancer-related symptoms. Two RCTs compared PDT with Nd-YAG laser therapy and one compared PDT plus external beam radiotherapy with external beam radiotherapy alone. No trial showed a survival advantage for PDT but there was a significant improvement in the control of haemoptysis and the relief of dyspnoea for patients receiving PDT plus radiotherapy compared with those receiving radiotherapy alone. 300 D
n

2+

PDT may be useful as a treatment option for early stage lung cancer in patients who are inoperable for medical reasons. PDT may contribute to the control of pulmonary symptoms in patients with locally advanced disease.

Endobronchial treatments such as brachytherapy, electrocautery, cryosurgery, NdYAG laser therapy and stents, may be useful in relieving malignant airway obstruction where standard treatments (eg external beam radiotherapy) have failed.

10.3

MANAGEMENT OF SUPERIOR VENA CAVA OBSTRUCTION

One systematic review of the management of superior vena cava obstruction (SVCO) covering two randomised and 45 non-randomised studies was identified.301 The poor quality of these studies and their heterogeneity meant that only a narrative breakdown could be performed, rather than a formal statistical analysis.

10.3.1

CHEMOTHERAPY AND RADIOTHERAPY Chemotherapy or radiotherapy can provide relief of SVCO in 77% of patients with SCLC. In patients with NSCLC, SVCO was relieved in 63% following radiotherapy and in 59% following chemotherapy. No specific chemotherapy regimen was identified as being more effective than any other. Recurrence of SVCO following treatment was 17% in SCLC and 19% in NSCLC. Relapse occurred 1-16 months after initial treatment and median survival in chemotherapy/ radiotherapy studies ranged from 2-9.5 months. 301

1+

32

10 ENDOBRONCHIAL AND VASCULAR THERAPIES

10.3.2

STENTING Endovascular stenting relieved symptoms of SVCO in 95% of patients, with recurrence in 11%. The median time to relapse was 1-2 months. Recanalisation was possible in the majority of patients, leading to a long term patency rate of 92%. Stent insertion appeared to provide faster relief from symptoms of SVCO than chemotherapy or radiotherapy. It is unclear whether post-stenting anticoagulation prevents stent thromboses. Relapse of SVCO was higher in patients who had received thrombolysis prior to stent insertion (16% compared with 7%). Median survival in stent studies was 1.5-6.5 months, shorter than for chemotherapy/radiotherapy studies, although stenting is often used in patients failing to respond to, or relapsing following initial treatment.301 B In patients with SVCO due to SCLC, chemotherapy/radiotherapy is recommended as initial treatment, but stenting may be considered for relapse or persistent SVCO. In patients with SVCO due to NSCLC, stenting may be considered as a primary treatment.

1+

10.3.3

STEROIDS It is not clear whether steroids have a role to play in the management of the acute presentation of SVCO. At present they are frequently used to manage radiation-induced oedema in thoracic radiotherapy despite the absence of evidence to support their use.

33

MANAGEMENT OF PATIENTS WITH LUNG CANCER

11

Complementary therapies
Up to a third of patients with cancer in the UK use complementary or alternative therapies in the management of their condition.302 Complementary treatments are usually aimed at symptom relief, often through emotional and psychological support, and are used alongside conventional cancer therapies. Complementary therapies offer an alternative approach to established orthodox treatments. A wide variety of interventions is available in conventional health service settings as well as in the voluntary and independent sectors. These include self help approaches such as meditation and relaxation; touch therapies such as massage, reflexology and aromatherapy, and the more established techniques of homeopathy and acupuncture. There is little published RCT evidence for the efficacy of these therapies for symptom control in cancer patients in general and in lung cancer patients in particular. A Cochrane review in patients with various cancers has shown limited effectiveness of some complementary therapies although evaluations were, in general, not rigorous.303 Cancer patients will continue to seek help outside conventional medicine and will access complementary medicine services in increasing numbers. Guidance for patients regarding this area is summarised in a recent publication from the National Institute of Clinical Excellence (NICE: www.nice.org.uk/pdf/csgspmanual.pdf).302

34

12 MULTIDISCIPLINARY TEAMS, FOLLOW UP AND COMMUNICATION

12
12.1

Multidisciplinary teams, follow up and communication

INTRODUCTION
The burden of lung cancer, its treatments and their related toxicities influence all aspects of quality of life for patients and their carers. UK Government policy, Cancer in Scotland304 and the Calman-Hine report305 all emphasise the importance of multidisciplinary team working to meet the needs of this patient group. Follow up should be modified throughout the patients pathway of care to ensure a smooth progression of care and service provision. With up to 40% of patients reporting severe communication problems at the end of life, 306 and the recognised need for a patient-centred approach, effective communication throughout the cancer journey is now accepted to be an essential component of care.

12.2

ROLE OF THE MULTIDISCIPLINARY TEAM

Multidisciplinary teams (MDTs) have been defined as a group of health and social care professionals from a range of disciplines who meet regularly to discuss and agree plans of treatment and care for people with a particular type of cancer or problem, or in a particular location.302 This definition implies the inclusion of primary care teams, site-specific cancer teams, therapy teams and specialist palliative care teams. The quantity of evidence evaluating the role of the MDT is generally poor, as there are ethical considerations surrounding comparative studies in this area. Studies are also hindered by a lack of clarity when defining the MDT. The Scottish Executive has promoted the development of Managed Clinical Networks (MCNs) which will guide the formation and networking of appropriate teams (see section 14.3).307 Two cohort studies were identified.19,324 One identified the importance of the MDT in providing a fast track model to reduce waiting times. The second demonstrated the positive impact of nursing interventions. Two surveys were also identified which highlight the importance of the MDT in the assessment of patient needs, both physical and psychosocial. 308,309 The report An Assessment of Need by The Allied Health Professions Palliative Care Project states that Allied Health Professionals (AHPS) contribute positively to the quality of life of patients with oncology related palliative care needs, through rehabilitative and supportive interventions, and identifies a large number of patients for whom this need is not met.310 D D All patients with a diagnosis of lung cancer should have their treatment and management planned and directed by a multidisciplinary team. Allied health professional services should be offered to all patients with lung cancer.
n

Following diagnosis and staging all new cases of lung cancer should be discussed in a multidisciplinary team meeting, attended if possible, by the respiratory physician, radiologist, pathologist, thoracic surgeon, oncologists, site-specific lung cancer nurses, allied healthcare professionals and pharmacists, with the aim of formulating a management plan for each patient. The diagnosis, staging and management plan should be explained by the physician and the nurse to the patient at the earliest opportunity, clearly and unambiguously, so that the patient is in full possession of all necessary information. A carer should be involved when appropriate. Provision of written as well as verbal information is best.

Healthcare professionals have a responsibility to: n provide and promote rapid access to an MDT n respond sympathetically to emotional, physical, psychosocial and spiritual problems n communicate and collaborate with primary, secondary and tertiary care settings. 35

MANAGEMENT OF PATIENTS WITH LUNG CANCER

12.3

FOLLOW UP
There is a paucity of good quality research in this area. One RCT was identified which addressed nurse- versus physician-led follow up of patients with lung cancer who had completed their initial + 1 treatment and were expected to survive at least three months. Clinical nurse specialist-led follow up was as effective and led to greater patient satisfaction than physician-led follow up.311 A cohort study and two surveys exploring follow up also suggest that specialist nurse-led follow up can be as effective and lead to greater patient satisfaction than physician-led follow up.312,313,328 Further research is required to substantiate these findings, as the benefits potentially relate to more open or improved access. The British Thoracic Society Lung Cancer Working Party recommends that respiratory physicians should develop with their colleagues an explicit follow up policy within their cancer units, which 4 is appropriate to local needs and resources and takes particular note of the wishes and interests of 314 patients and their GPs. It should be clear to patients who their supervising consultant is. B D Follow up by clinical nurse specialists should complement conventional arrangements. The development of clinical nurse specialist posts should be encouraged, through resourcing and training, to facilitate best practice.
n

Hospital follow up should be continued where hospital treatment or specialist advice is still required, or whilst clinical trials are ongoing. After surgery, the surgeon should follow up all patients initially: later follow up should be according to local policy. After palliative therapy is completed, follow up should be agreed between the oncologist, respiratory physician, GP and palliative care team.

Written and verbal information on follow up should be shared between primary, secondary and tertiary care in keeping with best practice and MCN guidelines.

12.4

COMMUNICATION
A Cochrane review,315 an RCT,316 three cohort studies309,317,318 and a survey328 were identified that cover a wide range of issues related to communication skills, all demonstrating strongly that communication skills training for healthcare professionals is of lasting benefit. The following have all been shown to be potentially effective communication tools or strategies:
n n n n n n n n

1+ 2+ 3

health related quality of life measurements needs assessment tools taped consultation general information tape summary letter as follow up presence of support person actively encouraging questions and a question prompt list patient-held record. A Communication skills training should be provided across the MDT. Information needs should be resourced and provided using a variety of media, to meet individual patient/carer needs.

36

13 SUPPORTIVE AND PALLIATIVE CARE

13
13.1

Supportive and palliative care

INTRODUCTION
Supportive care is defined as care that helps the patient and their family to cope with cancer and treatment of it from pre-diagnosis, through the process of diagnosis and treatment, to cure, continuing illness or death and into bereavement. It helps the patient to maximise the benefits of treatment and to live as well as possible with the effects of the disease. It is given equal priority alongside diagnosis and treatment.319 Palliative care is defined as the active holistic care of patients with advanced, progressive illness. Management of pain and other symptoms and provision of psychological, social and spiritual support is paramount. The goal of palliative care is achievement of the best quality of life for patients and their families. Many aspects of palliative care are also applicable earlier in the course of the illness in conjunction with other treatments.319 Specialist palliative care is defined as the active total care of patients with progressive, far advanced disease and limited prognosis and their families, by a multiprofessional team who have undergone recognised specialist palliative care training. It provides physical, psychological, social and spiritual support, and will involve practitioners with a broad mix of skills.320 Specialist palliative care is an integral component of the care of patients with advanced malignancy, required at varying times during their illness. The General Medical Council has stated that every member of the medical profession requires generic palliative care skills.321 NHS Quality Improvement Scotland has set standards for the provision of both basic and specialist palliative care.320 The National Institute of Clinical Excellence also offers guidance.302

13.2

SPECIALIST PALLIATIVE CARE SERVICES

Three good quality systematic reviews, two RCTs, two cohort studies and a postal survey were identified.322-329 The studies demonstrate that the involvement of palliative care teams results in improved quality of life, improved symptom control and a reduction in hospital readmission rates. Additional reported benefits include a reduction in the number of inpatient hospital days, patients spending more time at home, greater satisfaction amongst patients and carers, a reduction in overall cost and an increase in the number of patients dying where they wished.329 B All patients with lung cancer should have access to a specialist palliative care team.

1+

There is currently no evidence comparing different palliative care team models, for example: home care compared with hospice or hospital care settings. Specialist palliative care services should be available in the community setting to support patients who wish to die at home.

37

MANAGEMENT OF PATIENTS WITH LUNG CANCER

13.3

SYMPTOM MANAGEMENT
Patients with lung cancer experience more symptom distress than other types of cancer patient.322 Patients with lung cancer frequently have comorbidities and multiple symptoms. Symptom distress scoring at the time of diagnosis allows clinical interventions for symptom management to be tailored appropriately.330 Increased symptom distress is strongly associated with greater psychological distress and poorer quality of life.331 As symptom distress can impact on a patients ability to perform activities of daily living, regular assessment of symptoms and needs, with timely referral to AHPs, will assist patients in achieving the highest functional status and maintaining quality of life.310 There is now a wealth of information relating to identification and management of symptoms.302,310,332,333 The role of smoking cessation is discussed in section 3. D Symptoms should be assessed regularly and appropriate interventions initiated by the full multidisciplinary team.

13.3.1

PAIN Pain is one of the greatest sources of suffering in patients with lung cancer. A national audit found that 58% of cancer patients in the acute hospital setting recorded their pain as either moderate or severe.304 The assessment and management of pain in patients with cancer is addressed in SIGN guideline number 44: Control of Pain in Patients with Cancer.334

13.3.2

FATIGUE Cancer and many of its treatments can cause significant fatigue, impacting on patients quality of life.335,336 An essential component of managing fatigue is its recognition by healthcare professionals and the correction of known causal factors such as a poor sleep pattern, anaemia, drug reactions and depression. Guidelines on fatigue evaluation and management can be accessed via the Fatigue Coalition.337 Regular MDT assessment of fatigue should be made and interventions initiated.

13.3.3

ANXIETY AND DEPRESSION Significant psychological distress has been reported in 43% of patients with lung cancer.338 Counselling interventions may be effective in helping patients cope more effectively with the emotional symptoms associated with their disease but the most appropriate way of delivering these remains unclear.339 All patients should undergo psychosocial assessment and have access to appropriate psychosocial and spiritual support.

13.3.4

BREATHLESSNESS AND COUGH Studies have demonstrated improved management of dyspnoea following nursing or physiotherapy intervention.329,334,340 Further guidance on the assessment and management of cough is available from www.prodigy.nhs.uk Breathlessness clinics led by nurses or physiotherapists should be made available to all lung cancer patients.

13.3.5

NUTRITIONAL ISSUES Between 46 and 61% of patients with lung cancer have experienced weight loss by the time of diagnosis or the beginning of treatment.341 Disease or treatment related nutritional issues should be managed by the appropriate professionals from the multidisciplinary team. Increasing oral nutritional intake in this group of patients has not been shown to improve weight gain, tumour response or survival.325,342

38

14 IMPLEMENTATION AND FURTHER RESEARCH

14
14.1

Implementation and further research

LOCAL IMPLEMENTATION
Implementation of national clinical guidelines is the responsibility of local NHS organisations and is an essential part of clinical governance. It is acknowledged that not every guideline can be implemented immediately on publication, but mechanisms should be in place to ensure that the care provided is reviewed against the guideline recommendations and the reasons for any differences assessed and, where appropriate, addressed. These discussions should involve both clinical staff and management. Local arrangements may then be made to implement the national guideline in individual hospitals, units and practices, and to monitor compliance. This may be done by a variety of means including patient-specific reminders, continuing education and training, and clinical audit.

14.2

RESOURCE IMPLICATIONS
Recommendations likely to be associated with additional resource use for NHSScotland are highlighted in Annex 4.

14.3

MANAGED CLINICAL NETWORKS

In Scotland the organisation and delivery of lung cancer management is still the responsibility of local NHS Boards. In the last three years three Managed Clinical Networks (MCNs) have been established to oversee and monitor lung cancer services. MCNs are defined as: linked groups of health professionals and organisations from primary, secondary and tertiary care, working in a coordinated manner, unconstrained by existing professional and Health Board boundaries, to ensure equitable provision of high quality clinically effective services throughout Scotland. 307 MCNs require an administrative infrastructure. In the case of lung cancer the core members of the MCN might include respiratory physicians, medical and clinical oncologists, GPs, surgeons, specialist nurses, managers, patients and their representatives, pathologists, radiologists, palliative care specialists, pharmacists, clinical nurse specialists, occupational therapists, physiotherapists, dietitians, speech and language therapists, audit staff, and may also include other specialties. There is no clear evidence yet to show that organising cancer services through MCNs delivers improves outcomes for lung cancer patients.

14.4
14.4.1

RECOMMENDATIONS FOR RESEARCH

PRESENTATION AND REFERRAL Investigation of the predictive values of symptoms n Identification of the benefits of patient education in the early detection of lung cancer n Measurement of the effectiveness of fast track clinics.
n

14.4.2

DIAGNOSIS AND STAGING Assessment of comorbidity in newly presenting lung cancer patients and its influence on treatment decisions n Efficacy of EUS and EBUS as an alternative to mediastinoscopy in staging mediastinal lymph nodes n Assessment of the role of PET scanning in the staging and management of patients with lung cancer.
n

39

MANAGEMENT OF PATIENTS WITH LUNG CANCER

14.4.3

SURGERY The effect of hospital and surgeon case volume on lung cancer survival n Randomised trials comparing the efficacy of VATS versus conventional surgery in early stage NSCLC n Optimal management of the patient with solitary brain metastasis with otherwise resectable NSCLC n Further randomised trials comparing the effect of mediastinal lymph node sampling versus radical lymph node dissection on survival.
n

14.4.4 14.4.5

RADIOTHERAPY Investigation of the role of postoperative radiotherapy in patients with NSCLC.

CHEMOTHERAPY Comparison of the effectiveness of carboplatin and cisplatin n Impact of cisplatin on outcomes in advanced NSCLC n Investigation of the role of chemotherapy in performance status 2 patients with NSCLC n Investigation of the role of novel targeted therapies in lung cancer (early versus late stages).
n

14.4.6

COMBINED MODALITIES Investigation of the risk and benefits of interventions with respect to quality of life.

NSCLC n Comparison of the relative benefits of adjuvant and neoadjuvant chemotherapy in patients with operable lung cancer n Identification of the optimal scheduling of chemotherapy with radical radiotherapy in patients with NSCLC. SCLC n Comparison of palliative chemotherapy and chest radiotherapy in poor performance status patients with SCLC and local chest symptoms n Assessment of the optimal timing and fractionation of thoracic radiotherapy with chemotherapy in patients with limited stage SCLC n Assessment of the optimal dose and fractionation for prophylactic cranial irradiation in patients with SCLC n Investigation of the role of PCI in patients with extensive stage SCLC in remission following chemotherapy. 14.4.7 ENDOBRONCHIAL AND VASCULAR THERAPIES The role of PDT in early stage lung cancer patients who are inoperable for medical reasons n Randomised trials comparing the effectiveness of different forms of endobronchial therapy (cryotherapy, brachytherapy, electrocautery and Nd-YAG) laser on survival in lung cancer.
n

14.4.8

SUPPORTIVE AND PALLIATIVE CARE Comparison of the different models of specialist palliative care n Identification of the causes and treatment of fatigue with respect to symptom management n Demonstration of the effect of nutritional assessment and intervention in the lung cancer population n Assessment of the role of exercise and activity.
n

14.4.9

SERVICE ORGANISATION Identification of reasons for delays in presentation n Assessment of the effect of delays on diagnosis and management n Assessment of the optimal delivery method of communications training for staff n Assessment of the role of cancer site-specific nurses n Comparison of primary and secondary care pathways n Identification of the optimal follow up practice for patients with lung cancer.
n

40

15 INFORMATION FOR DISCUSSION WITH PATIENTS AND CARERS

15
15.1

Information for discussion with patients and carers

FREQUENTLY ASKED QUESTIONS
Patients and their families need information to help them understand and cope with the diagnosis of lung cancer, the treatment options and possible outcomes. The following points are based on the types of question most commonly asked by lung cancer patients. These notes may be of use to health professionals when discussing lung cancer with patients and carers. They may also be useful in guiding the production of local patient information materials. The advice is divided into sections to highlight the issues that patients and carers might wish to discuss at each stage of care.

15.1.1

UNDERSTANDING LUNG CANCER What is lung cancer? n Is there a cure for lung cancer? n How do I find out more? n What causes lung cancer? n Are there different types of lung cancer? n What is small cell lung cancer? n What are the different types of non-small cell lung cancer? n Can other cancers occur in the lungs? n Is it an advantage to know what type of lung cancer I have? n Does lung cancer spread? n How long have I had lung cancer?
n

15.1.2

TESTS FOR LUNG CANCER What are the different tests for lung cancer? n How accurate are the test results? n Are the tests painful?
n

15.1.3

DIAGNOSIS I have just been told that I have lung cancer how will I cope? n How long will it take me to come to terms with my diagnosis? n What if I feel that I cannot cope with my diagnosis? n How do I tell the children? n How will family members and friends cope with the diagnosis? n Will treatment be painful? n How long do I have left? n Am I going to die?
n

15.1.4

TREATMENTS FOR LUNG CANCER What kinds of treatment are available to me? n How do doctors decide what type of treatment will be best for me? n How can doctors tell if my cancer is curable or not? n I am a smoker. Is it worthwhile trying to quit before I start treatment? n If I decide to stop is help available? n How will I cope with treatment?
n

41

MANAGEMENT OF PATIENTS WITH LUNG CANCER

15.1.5

SURGERY How will it be decided if I am suitable for surgery? n Are there different types of surgery? n How long will I have to wait to have my surgery? n What happens after surgery? n Will I be in pain after surgery? n What will happen on the first and second days after my operation? n When will I know how successful my operation was? n When will I be able to go home? n What happens after I am discharged from hospital? n What should I do when I get home?
n

15.1.6

CHEMOTHERAPY My doctor has told me that I need chemotherapy. What does this mean? n I have read that chemotherapy for lung cancer is not very effective - is this true? n I am frightened of needles and feel sick at the thought of treatment. What should I do? n What actually happens when I get my chemotherapy? n What are the main side effects of chemotherapy? n What can be done to alleviate these side effects? n Do the side effects ease with time? n Should I change my diet while Im having chemotherapy? n How do the doctors know if the chemotherapy is working?
n

15.1.7

RADIOTHERAPY I have been told that I need radiotherapy. What does this mean? n Why is radiotherapy used to treat lung cancer? n How will the doctors know how many treatments I need? n Is radiotherapy painful? n Are there any side effects of radiotherapy? n Should I change my diet during radiotherapy? n How do the doctors know if the radiotherapy is working? n How will I feel after the treatment ends?
n

15.1.8

PALLIATIVE CARE Ive been told that my cancer cant be treated. How will I cope? n My doctor has referred me to the palliative care team. What does this mean? n Will the palliative care nurse come to visit me at home? n Is there any help available if I need nursing during the night? n Will I become very short of breath? n Am I going to have a lot of pain? n Will I have to take morphine? n Should I plan for the future? n How do I find out how much time I have left? n Can I choose where I die?
n

42

15 INFORMATION FOR DISCUSSION WITH PATIENTS AND CARERS

15.1.9

GENERAL ISSUES I have been asked by my doctor to take part in a clinical trial. What does this mean? n Are clinical trials safe? n Where do clinical trials take place? n Im not happy with my care, how do I complain? n Who might be involved in my treatment and care? n How can I make sure that Im seeing the doctor who will give me the best treatment? n Will tiredness affect my ability to carry out everyday activities? n What kind of changes might I need to make? n Will I still be able to get out and about? n Will my sexual feelings be affected? n What will life be like after treatment?
n

15.2

SOURCES OF FURTHER INFORMATION

ASH Scotland 8 Frederick Street, Edinburgh EH2 2HB Tel: 0131 225 4725 Fax: 0131 220 6604 Email: ashscotland@ashscotland.org.uk ASH Scotland is the leading voluntary organisation campaigning for effective tobacco control legislation and providing an expert information service. CancerBACUP Scotland Suite 2, Third Floor, Cranston House, 104/114 Argyle Street, Glasgow G2 8BH Tel: 0141 223 7676 Freephone Helpline: 0808 800 1234 Fax: 0141 248 8422 www.cancerbacup.org.uk Aims to help people live with cancer. Experienced and qualified cancer nurses staff the information service. DIPex (Database of individual experiences) www.dipex.org/main.asp DIPex is a website that reports on a wide variety of personal experiences of health and illness. People can watch, listen to or read interviews, find reliable information on treatment choices and where to find support. The site includes lung cancer. Macmillan Cancer Relief (Scotland) Osborne House, 1-5 Osborne Terrace, Edinburgh EH1 2DP Tel: 0131 346 5346 Fax: 0131 346 5347 www.macmillan.org.uk The Scottish office of the UK charity, which supports people with cancer and their families with specialist information, treatment and care. Maggies Centres Scotland n The Stables, Western General Hospital, Edinburgh EH4 2XU Tel: 0131 537 3131 Fax: 0131 537 3130 n Maggies Centre Glasgow The Gatehouse, Western Infirmary, 10 Dumbarton Road, Glasgow G11 6PA Tel: 0141 330 3311 Fax: 0141 330 3363 n Maggies Centre Dundee Ninewells Hospital, Tom McDonald Avenue, Dundee, DD2 1ZV Tel: 01382 632 999 www.maggies.ed.ac.uk Email: maggies.centre@ed.ac.uk Maggies centres aim to help people with all kinds of cancer, their families and friends, to address all aspects of living with cancer, to share their experiences and to become more informed about their disease.

43

MANAGEMENT OF PATIENTS WITH LUNG CANCER

Marie Curie Cancer Care (Scotland) 29 Albany Street, Edinburgh EH1 3QN Tel: 0131 456 3700 www.mariecurie.org.uk This charity is dedicated to the care of people affected by cancer and to the enhancement of their quality of life through its caring services, research and education. Roy Castle Lung Cancer Foundation Rothesay House, 134 Douglas Street, Glasgow G2 4HF Tel: 0871 220 5434 Freephone Helpline: 0800 358 7200 www.roycastle.org Provides a comprehensive support, information and advocacy service for people affected by lung cancer. Smokeline and Tobacco unwrapped Tel: 0800 848484 www.hebs.com/tobacco/ For advice and support on giving up smoking Tak Tent Cancer Support Scotland Flat 5, 30 Shelley Court, Gartnavel Complex, Glasgow G12 0YN Tel: 0141 211 0122 Fax: 0141 211 3988 www.taktent.org.uk Email: tak.tent@care4free.net Promotes the care of cancer patients, their families and friends. It provides practical and emotional support, information and counselling as required.

44

16 DEVELOPMENT OF THE GUIDELINE

16
16.1

Development of the guideline

INTRODUCTION
SIGN is a collaborative network of clinicians, other healthcare professionals and patient organisations and is part of NHS Quality Improvement Scotland. SIGN guidelines are developed by multidisciplinary groups using a standard methodology based on a systematic review of the evidence. Further details about SIGN and the guideline development methodology are contained in SIGN 50: A guideline developers handbook, available at www.sign.ac.uk

16.2

THE GUIDELINE DEVELOPMENT GROUP

Dr Ron Fergusson (Chair) Dr Robert Rintoul (Secretary) Dr David Brewster Ms Iona Brisbane Ms Jenni Brockie Ms Jennifer Dickson Mrs Nancy Docherty Dr John Dorward Mrs Linda Gray Dr Joe Legge Dr Felicity Little Dr Fergus Macbeth Ms Fiona MacLean Mrs Audrey Melville Dr Robert Milroy Mrs Patricia Murray Dr Marianne Nicolson Dr Noelle ORourke Mr Dhru Prakash Professor Elaine Rankin Dr Safia Qureshi Dr James Rodgers Ms Allison Smith Dr Mike Sproule Consultant in Respiratory Medicine, Western General Hospital, Edinburgh Consultant Respiratory Physician, Papworth Hospital, Cambridge Director of Cancer Registration in Scotland, Information and Statistics Division, Edinburgh Lung Cancer Clinical Nurse Specialist, Beatson Oncology Centre, Western Infirmary, Glasgow Information Officer, SIGN Executive Patient Network Manager, Roy Castle Lung Cancer Foundation, Glasgow Smoking Cessation Coordinator, Blantyre Health Partnership, Hamilton and Blantyre LHCC General Practitioner, Eyemouth Superintendent Physiotherapist, Borders General Hospital, Melrose Consultant Physician, Aberdeen Royal Infirmary Consultant Clinical Oncologist, Edinburgh Cancer Centre, Western General Hospital Consultant Oncologist, Velindre Hospital, Cardiff Principal Pharmacist, Southern General Hospital, Glasgow Lay Representative, Larbert Consultant Physician, Stobhill General Hospital, Glasgow Community Nurse, Ardach Health Centre, Buckie Consultant in Medical Oncology, Aberdeen Royal Infirmary Consultant in Oncology, Beatson Oncology Unit, Western Infirmary, Glasgow Consultant Thoracic Surgeon, Hairmyres Hospital, East Kilbride Medical Oncologist, Department of Cancer Medicine, Ninewells Hospital, Dundee Programme Director, SIGN Executive Lead Cancer Physician, Borders General Hospital, Melrose Clinical Nurse Specialist, Gartnavel General Hospital, Glasgow Consultant Radiologist, Gartnavel General Hospital, Glasgow

45

MANAGEMENT OF PATIENTS WITH LUNG CANCER

Ms Joanne Topalian Mr Bill Walker Dr William Wallace Mrs Lorraine Webster

Programme Manager, SIGN Executive Consultant Cardiothoracic Surgeon, Royal Infirmary of Edinburgh Consultant Pathologist, Royal Infirmary of Edinburgh Macmillan Information Radiographer, Beatson Oncology Unit, Western Infirmary, Glasgow

The membership of the guideline development group was confirmed following consultation with the member organisations of SIGN. Declarations of interests were made by all members of the guideline development group. Further details are available from the SIGN Executive.

16.3

SYSTEMATIC LITERATURE REVIEW

The evidence base for this guideline was synthesised in accordance with SIGN methodology. A systematic review of the literature was carried out using an explicit search strategy devised by a SIGN Information Officer in collaboration with Information Scientists from the National Collaborating Centre for Acute Care. Databases searched include Medline, Embase, CINAHL, PsychINFO, and the Cochrane Library. The year range covered was 1998 to April 2004. Internet searches were carried out on various websites including the New Zealand Guidelines Programme, NELH Guidelines Finder, and the US National Guidelines Clearinghouse. The Medline version of the main search strategies can be found on the SIGN website, in the section covering supplementary guideline material. The main searches were supplemented by material identified by individual members of the development group. All selected papers were evaluated by either at least two members of the group or by systematic reviewers from the Collaborating Centre, using standard SIGN methodological checklists before conclusions were considered as evidence.

16.4
16.4.1

CONSULTATION AND PEER REVIEW

NATIONAL OPEN MEETING The national open meeting is the main consultative phase of SIGN guideline development, at which the guideline development group presents the draft recommendations for the first time. The national open meeting for this guideline was held in February 2004 and was attended by all of the key specialties relevant to the guideline. The draft guideline was also available on the SIGN website for one month to allow those unable to attend the meeting to contribute to the development of the guideline.

16.4.2

SPECIALIST REVIEW The guideline was also reviewed in draft form by a panel of independent expert referees, who were asked to comment primarily on the comprehensiveness and accuracy of interpretation of the evidence base supporting the recommendations in the guideline. SIGN is very grateful to all of these experts for their contribution to this guideline. Mr Sheikh Ahmed Dr Malcolm Campbell Dr Michael Cornbleet Dr Tim Eisen Ms Rhona Else Mr Peter Goldstraw Dr James Jett Professor Nora Kearney Chairman, Canserve Lung Cancer Patients and Carers Group General Practitioner, Southbank Surgery, Kirkintilloch Senior Medical Officer, Scottish Executive Health Department, Edinburgh Consultant Clinical Oncologist, The Institute of Cancer Research, London Physiotherapist, St Columbas Hospice, Edinburgh Thoracic Surgeon, Brompton Hospital, London Professor of Respiratory Medicine, Mayo Clinic, Rochester, USA Professor of Cancer Care, Stirling University

46

16 DEVELOPMENT OF THE GUIDELINE

Dr Keith Kerr Dr Harpreet Kohli Dr Lesley Macdonald Dr John McKay Mrs Cathy Meredith Professor Allan Price Dr Giles Roditi Professor Stephen Spiro Dr Ann Maree Wallace Mr David Waller Ms Susan Watt Ms Fiona Wilson 16.4.3 SIGN EDITORIAL GROUP

Consultant Pathologist, Aberdeen Royal Infirmary Medical Advisor, NHS Quality Improvement Scotland, Glasgow Director of Public Health, Fife NHS Board Associate Adviser (Audit), NHS Education for Scotland, Edinburgh Senior Lecturer in Radiography, Glasgow Caledonian University Consultant Clinical Oncologist, Western General Hospital, Edinburgh Consultant Radiologist, Glasgow Royal Infirmary Consultant in Respiratory Medicine, Middlesex Hospital, London Acting Director of Public Health, Lothian NHS Board Consultant Thoracic Surgeon, Glenfield General Hospital, Leicester Education and Clinical Effectiveness Advisor, Royal College of Nursing, Edinburgh Senior Occupational Therapist, Scottish Occupational Therapy Network in Oncology and Palliative Care

As a final quality control check, the guideline is reviewed by an Editorial Group comprising the relevant specialty representatives on SIGN Council to ensure that the peer reviewers comments have been addressed adequately and that any risk of bias in the guideline development process as a whole has been minimised. The Editorial Group for this guideline was as follows: Dr Bill Reith Dr Hugh Gilmour Mr Douglas Harper Dr Grahame Howard Professor Gordon Lowe Dr Sara Twaddle Dr Christine Walker Academy of Royal Colleges Royal College of Pathologists Royal College of Surgeons of Edinburgh Royal College of Radiologists Chairman of SIGN Director of SIGN Royal College of Radiologists, Faculty of Radiology

Each member of the guideline development group then approved the final guideline for publication.

16.5

ACKNOWLEDGEMENTS
SIGN is grateful to the following former members of the guideline development group and others who have contributed to the development of this guideline: Miss Gemma Healy Information Specialist, NeLH, Oxford Dr Peter Kiehlmann General Practitioner, Aberdeen Mr Carsten Mandt Information Officer, Gartnavel Hospital, Glasgow Dr John McKay General Practitioner, Kirkintilloch Dr Michael Scullion General Practitioner, Alexandria The staff and lung cancer guideline development group at the National Collaborating Centre for Acute Care, London.

47

MANAGEMENT OF PATIENTS WITH LUNG CANCER

Abbreviations
AJCC ARDS ASCO CAV CCG CCI CEV CHART CI CODE COPD CPA CPD CT DC EBUS EORTC EQA EUS F FNA GMCSF Gy HDR HDU IG IP MCN MDT MRI NeoSPECT NHSQIS NICE NSCLC PDT PE American Joint Committee on Cancer Acute respiratory distress syndrome American Society of Clinical Oncology Cyclophosphamide, doxorubicin and vincristine Cisplatin plus carboplatin plus gemcitabine Cisplatin plus carboplatin plus ifosfamide Cyclophosphamide, epirubicin and vincristine Continuous hyperfractionated accelerated radiation therapy Confidence intervals Cisplatin, vincristine, doxorubicin and etoposide Chronic obstructive pulmonary disease Clinical pathology accreditation Continuous professional development Computed tomography Docetaxel plus cisplatin Endobronchial ultrasound European Organisation for the Research and Treatment of Cancer External quality assurance Endoscopic ultrasound Fractions Fine needle aspiration Granulocyte-macrophage colony-stimulating factor Gray High-dose rate High dependency unit Ifosfamide plus gemcitabine Irinotecan and cisplatin Managed clinical network Multidisciplinary team Magnetic resonance imaging Tc-99m depreotide, an imaging agent which binds to somatostatin receptors on malignant tumours NHS Quality Improvement Scotland National Institute for Clinical Excellence Non-small cell lung cancer Photodynamic therapy Cisplatin and etoposide

48

ABBREVIATIONS

PET PORT PS RCT SCLC SIGN SVCO TNM UICC US VATS W WHO

Positron emission tomography Postoperative radiotherapy Performance status Randomised controlled trial Small cell lung cancer Scottish Intercollegiate Guidelines Network Superior vena cava obstruction Tumour, nodes, metastases Union Internationale Contre le Cancer Ultrasound Video-assisted thorascopic surgery Weeks World Health Organisation

49

MANAGEMENT OF PATIENTS WITH LUNG CANCER

Annex 1 Staging
Staging of cancers applies a set of rules to express the extent of the disease and is used for prognostic and therapeutic purposes. Staging can be clinical (based on the results of clinical examination and radiological imaging) or pathological (based on histopathological findings following surgical resection of the tumour). In non-small cell lung cancer two staging systems are widely used. The first, the TNM (tumour, nodes, metastases) was developed by the American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer (UICC) and is widely used for both clinical and pathological staging of lung cancer.62 The second classification, first proposed by Mountain in 1986, uses the TNM system to classify patients into four stages (I IV) according to prognosis.343 TNM Classification for Lung Cancer Tx T0 Tis T1 T2 Size of tumour cannot be assessed No evidence of primary tumour Carcinoma in situ only Primary tumour = 3cm Primary tumour > 3cm or Involving main bronchus >2 cm from main carina or Invades visceral pleura or Associated with partial atelectasis extending up to the hilum Tumour of any size invading chest wall, diaphragm, mediastinal pleura or parietal pericardium or Tumour in the main bronchus not involving the main carina but extending to within < 2cm or Atelectasis of an entire lung Tumour of any size invading mediastinum, heart, great vessels, trachea, oesophagus, vertebral body or main carina or Separate tumour nodules in the same lobe or Presence of a confirmed malignant pleural effusion Lymph node status cannot be assessed No lymph node metastases Metastatic carcinoma in intrapulmonary, ipsilateral hilar and peribronchial lymph nodes (including those involved by direct extension) Metastatic carcinoma in ipsilateral mediastinal or subcarinal nodes Metastatic carcinoma in contralateral mediastinal or hilar nodes or Ipsilateral or contralateral scalene nodes or Supraclavicular nodes Distant metastases cannot be assessed No distant metastases Distant metastases or Separate tumour nodules in a different lobe (ipsilateral or contralateral)

T3

T4

Nx N0 N1 N2 N3

Mx M0 M1

50

ANNEXES

Annex 1 (contd.) Staging

Mountain Classification of Lung Cancer Occult carcinoma Stage 0 Stage 1A Stage 1B Stage IIA Stage IIB Stage IIIA Tx Tis T1 T2 T1 T2 T3 T1 T2 T3 Any T T4 Any T N0 N0 N0 N0 N1 N1 N0 N2 N2 N1/N2 N3 Any N Any N M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M1

Stage IIIB Stage IV In small cell lung cancer:

limited stage disease is defined as disease that is confined to a hemithorax and regional lymph nodes and that can be encompassed into a reasonable radiation port. extensive stage disease is defined as disease that exists beyond these limits.

51

MANAGEMENT OF PATIENTS WITH LUNG CANCER

Annex 2 Reliability of staging techniques

Technique
CT for T3/4 CT for chest wall invasion CT for mediastinal involvement CT for N1 CT for N2/3 Mediastinoscopy for N2/3 PET for mediastinal lymphadenopathy Clinical evaluation Cranial CT in cI-III Isotope bone scans Chemical shift MRI for adrenal metastases Percutaneous needle biopsy for adrenal metastases PET for adrenal metastases PET for distant metastases

344

False positive (%)

32 44 33 38 45 16 60-70 5-10 30-60 10 <5 >10

False negative (%)

18 9 14 16 13 9 7 30 5-10 10-20 <5 5

52

ANNEXES

Annex 3 WHO/ECOG Performance Status

0 1 2 3 4 Fully active. Able to carry on all pre-disease performance without restriction. Restricted in physically strenuous activities but ambulatory and able to carry out work of a light and sedentary nature. Ambulatory and capable of all self care but unable to carry out many work activities; up and about more than 50% waking hours. Capable of only limited self care; confined to bed or a chair for more than 50% of waking hours. Completely disabled; unable to carry out any self care; totally confined to bed or a chair.

www.ecog.org/general/perf_stat.html

53

MANAGEMENT OF PATIENTS WITH LUNG CANCER

54
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
 UVCVGF VJCV CTTCPIGOGPVU UJQWNF DG OCFG HQT CRRTQRTKCVG RCVKGPVU VQ JCXG CEEGUU VQ VJG 2'6 UECPPKPI HCEKNKV[ KP #DGTFGGP QT TGHGTTCN VQ 2'6 HCEKNKVKGU KP 'PINCPF 6JKU TGEQOOGPFCVKQP YKNN VJGTGHQTG TGSWKTG CTTCPIGOGPVU VQ DG OCFG HQT RCVKGPVU VQ DG UGGP KP GKVJGT #DGTFGGP QT KP 'PINCPF 6JKU OC[ JCXG CUUQEKCVGF MPQEM QP GHHGEVU QP QVJGT RCVKGPVU ITQWRU TGSWKTKPI CEEGUU VQ 2'6 HCEKNKVKGU %NKPKECN CPF EQUV GHHGEVKXGPGUU FCVC KU CXCKNCDNG KP C JGCNVJ VGEJPQNQI[ CRRTCKUCN EQORNGVGF D[ 0*5 3+5

#PPGZ  4GUQWTEG KORNKECVKQPU QH TGEQOOGPFCVKQPU

6JKU UGEVKQP KU DCUGF QP FKUEWUUKQPU YKVJ VJG IWKFGNKPG FGXGNQROGPV ITQWR TGICTFKPI EWTTGPV TGUQWTEG WUG KP 5EQVNCPF CPF VJG NKMGN[ KORCEV QH KORNGOGPVCVKQP QH VJG TGEQOOGPFCVKQPU QH VJG IWKFGNKPG 9JGTG EWTTGPV RTCEVKEG YKNN PQV EJCPIG CU C TGUWNV QH VJG TGEQOOGPFCVKQPU KV KU WPNKMGN[ VJCV VJGTG YKNN DG TGUQWTEG KORNKECVKQPU

6JG HQNNQYKPI VCDNG UJQYU TGEQOOGPFCVKQPU VJCV CTG NKMGN[ VQ JCXG UKIPKHKECPV TGUQWTEG KORNKECVKQPU KH KORNGOGPVGF CETQUU 5EQVNCPF 6JG TGUQWTEG KORNKECVKQPU CUUQEKCVGF YKVJ IQQF RTCEVKEG RQKPVU JCXG PQV DGGP EQPUKFGTGF

)WKFGNKPG UGEVKQP

4GEQOOGPFCVKQP



&

2CVJYC[U HQT RCVKGPVU YKVJ UWURGEVGF QT EQPHKTOGF NWPI ECPEGT UJQWNF DG TGXKGYGF D[ /%0U YKVJ C XKGY VQ KORNGOGPVKPI HCUV VTCEM OQFGNU HQT CUUGUUKPI VJGUG RCVKGPVU



&

%QPVTCUV GPJCPEGF %6 UECPPKPI QH VJG EJGUV CPF CDFQOGP KU TGEQOOGPFGF KP CNN RCVKGPVU YKVJ UWURGEVGF NWPI ECPEGT TGICTFNGUU QH EJGUV :TC[ TGUWNVU



05%.% RCVKGPVU YKVJ C PGICVKXG %6 UECP TGUWNV HQT OGFKCUVKPCN CFGPQRCVJ[ UJQWNF RTQEGGF VQ 2'6



2CVKGPVU JCXKPI TCFKECN TCFKQVJGTCR[ UJQWNF DG IKXGP %*#46

)[( FC[U KP RTGHGTGPEG VQ )[(9



5GNGEVGF QNFGT RCVKGPVU YKVJ UVCIG ++++8 05%.% UJQWNF DG QHHGTGF EJGOQVJGTCR[



5GEQPF NKPG EJGOQVJGTCR[ YKVJ FQEGVCZGN  OIO

VJTGG YGGMN[ UJQWNF DG EQPUKFGTGF HQT UVCIG +++$+8 05%.% YKVJ IQQF RGTHQTOCPEG UVCVWU

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



#FLWXCPV EJGOQVJGTCR[ UJQWNF DG EQPUKFGTGF HQT TGUGEVGF 05%.% DWV FKUEWUUGF HWNN[ IKXGP VJG UOCNN OCTIKP QH DGPGHKV TKUM QH VQZKEKV[ CPF WPEGTVCKPV[ CU VQ YJKEJ ITQWR QH RCVKGPVU CTG OQUV NKMGN[ VQ DGPGHKV



&

#NN RCVKGPVU YKVJ C FKCIPQUKU QH NWPI ECPEGT UJQWNF JCXG VJGKT VTGCVOGPV CPF OCPCIGOGPV RNCPPGF CPF FKTGEVGF D[ C OWNVKFKUEKRNKPCT[ VGCO



(QNNQY WR D[ ENKPKECN PWTUG URGEKCNKUVU UJQWNF EQORNGOGPV EQPXGPVKQPCN CTTCPIGOGPVU



%QOOWPKECVKQP UMKNNU VTCKPKPI UJQWNF DG RTQXKFGF CETQUU VJG /&6

5GXGTCN

#XCKNCDKNKV[ QH CRRTQRTKCVG KPHQTOCVKQP HQT RCVKGPVU CPF ECTGTU

ANNEXES

55

6JGTG KU XCTKCVKQP KP VJG CXCKNCDKNKV[ QH TGUQWTEG OCVGTKCNU 6Q GPUWTG CNN RCVKGPVU CPF ECTGTU JCXG CEEGUU VQ JKIJ SWCNKV[ OCVGTKCNU TGSWKTGU EQQTFKPCVKQP DGVYGGP CNN VJG CIGPEKGU KPXQNXGF

MANAGEMENT OF PATIENTS WITH LUNG CANCER

References
1 Scottish Executive Health Department. Scottish Referral Guidelines for Suspected Cancer. Edinburgh: The Department; 2002 [cited 11 Nov 2004]. Available from url: http://www.show.scot.nhs.uk/sehd/ cancerinscotland/ ISD Scotland. Information and Statistics. Health & Care. Cancer. Information. Lung cancer and mesothelioma. [cited 11 Nov 2004]. Available from url: http://www.isdscotland.org/cancer_information Kogevinas M, Pearce N, Susser M, Boffetta P, editors. Social Inequalities and Cancer. Lyon: International Agency for Research on Cancer; 1997. (IARC Scientific Publications No. 138). Rivera MP, Detterbeck FC, Loomis DP. Epidemiology and classification of lung cancer. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 25-44. Action on Smoking and Health, Royal College of Physicians. Forty Fatal Years: a review of the 40 years since the publication of the 1962 report of the Royal College of Physicians on smoking and health. London: ASH, The College; 2002. [cited 11 Nov 2004]. Available from url: http://www.rcplondon.ac.uk/pubs/books/ash/ Peto R, Darby S, Deo H, Silcocks P, Whitley E, Doll R. Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies. BMJ 2000;321(7257):323-9. Crispo A, Brennan P, Jockel KH, Schaffrath-Rosario A, Wichmann HE, Nyberg F, et al. The cumulative risk of lung cancer among current, ex- and never-smokers in European men. Br J Cancer 2004;91(7):1280-6. NHS Health Scotland, Action on Smoking and Health. Smoking cessation guidelines for Scotland: 2004 update. Edinburgh: NHS Health Scotland; 2004. [cited 11 Nov 2004]. Available from url: http:/ /www.hebs.com/services/pubs/pdf/SmokingCes2004.pdf Scottish Intercollegiate Guidelines Network (SIGN). Management of lung cancer. Edinburgh: SIGN; 1998. (SIGN publication no. 23). Naidoo B, Warm D, Quigley R, Taylor L. Smoking and public health: a review of reviews of interventions to increase smoking cessation, reduce smoking initiation and prevent further uptake of smoking: evidence briefing. London: NHS Health Development Agency; 2004. [cited 11 Nov 2004]. Available from url: http://www.hda.nhs.uk/ documents/smoking_evidence_briefing.pdf Detterbeck FC, Rivera MP. Table 4-4. Prevalence of symptoms at presentation in 446 patients with non-small cell lung cancer [table]. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 48. National Institute for Clinical Excellence. Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care. London: NICE; 2004. (NICE Clinical Guideline 12). [cited 11 Nov 2004]. Available from url: http://www.nice.org.uk/pdf/CG012_niceguideline.pdf Janssen-Heijnen ML, Schipper RM, Razenberg PP, Crommelin MA, Coebergh JW. Prevalence of co-morbidity in lung cancer patients and its relationship with treatment: a population-based study. Lung Cancer 1998;21(2):105-13. Fergusson RJ, Thomson CS, Brewster DH, Brown PH, Milroy R; Scottish Cancer Trials Lung Group; Scottish Cancer Therapy Network. Lung cancer: the importance of seeing a respiratory physician. Eur Resp J 2003;21(4):606-10. Koyi H, Hillerdal G, Branden E. Patients and doctors delays in the diagnosis of chest tumors. Lung Cancer 2002;35(1):53-7. Myrdal G, Lambe M, Hillerdal G, Lamberg K, Agustsson T, Stahle E. Effect of delays on prognosis in patients with non-small cell lung cancer. Thorax 2004;59(1):45-9. Moody A, Muers M, Forman D. Delays in managing lung cancer. Thorax 2004;59(1):1-3. Cancer Guidance Group. Guidance on commissioning cancer services: improving outcomes in lung cancer: the manual. London: NHS Executive; 1998. p. 26. [cited 11 Nov 2004]. Available from url: http://www.dh.gov.uk/assetRoot/04/08/04/97/04080497.pdf Murray PV, OBrien MER, Sayer R, Cooke N, Knowles G, Miller AC, et al. The pathway study: results of a pilot feasibility study in patients suspected of having lung carcinoma investigated in a conventional chest clinic setting compared to a centralised two-stop pathway. Lung Cancer 2003;42(3):283-290. Laroche C, Wells F, Coulden R, Stewart S, Goddard M, Lowry E, et al. Improving surgical resection rate in lung cancer. Thorax 1998;53(6):445-9.

21 22 23 24 25 26

2 3 4

27

28

29

30 31 32

9 10

33

34 35 36

11

12

37 38 39 40

13

14

15 16 17 18

41

42

19

43 44

20

Magee LRA, Godward S, Roberts LA, Gilligan D. Specialist lung cancer service - who gets access? [abstract]. Lung Cancer 2003;41 Suppl 2:S57. Melville A, Eastwood A. Management of lung cancer. Qual Health Care 1998;7(3):170-7. Leydon GM, Boulton M, Moynihan C, Jones A, Mossman J, Boudioni M, et al. Cancer patients information needs and information seeking behaviour: in depth interview study. BMJ 2000;320(7239):909-13. Yardley SJ, Davis CL, Sheldon F. Receiving a diagnosis of lung cancer: patients interpretations, perceptions and perspectives. Palliat Med 2001;15(5):379-86. Given CW, Given B, Champion VL, Kozachik S, DeVoss DN, editors. Evidence-based cancer care and prevention: behavioural interventions. New York: Springer Publishing Company; 2003. Schnoll RA, Zhang B, Rue M, Krook JE, Spears WT, Marcus AC, et al. Brief physician-initiated quit smoking strategies for clinical oncology settings: a trial co-ordinated by the Eastern Co-operative Oncology Group. J Clin Oncol 2003;21(2):355-65. Nagagawa, M; Tanaka, H; Tsukuma, H; Kishi,Y. Relationship between the duration of the preoperative smoke-free period and the incidence of postoperative pulmonary complications after pulmonary surgery. Chest 2001;120(3):705-10. Vaporciyan AA, Merriman KW, Ece F, Roth JA, Smythe WR, Swisher SG, et al. Incidence of major pulmonary morbidity after pneumonectomy: association with timing of smoking cessation. Ann Thorac Surg 2002;73(2):420-6. British Thoracic Society. Recommendations for hospital-based smoking cessation services. London: The Society; 2004 [cited 25 Nov 2004]. Available from url: http://www.brit-thoracic.org.uk/docs/ HospitalReportJAN04.pdf Jarvis MJ. Why people smoke. BMJ 2004;328(7434):277-9. Travis WD, Sobin LH, et al. Histological typing of lung cancer and pleural tumours. 3rd ed. Berlin: Springer-Verlag; 1999. (International histological classification of tumours; no.1). Detterbeck FC, Rivera MP. Table 4-5. Findings on chest radiograph at presentation in 345 patients with lung cancer [table]. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 48. Seemann MD, Seemann O, Luboldt W, Bonel H, Sittek H, Dienemann H, et al. Differentiation of malignant from benign solitary pulmonary lesions using chest radiography, spiral CT and HRCT. Lung Cancer 2000;29(2):105-24. Siegelman SS, Khouri NF, Leo FP, Fishman EK, Braverman RM, Zerhouni EA. Solitary pulmonary nodules: CT assessment. Radiology 1986;160(2):307-12. Yankelevitz DF, Gupta R, Zhao B, Henschke CI. Small pulmonary nodules: evaluation with repeat CT preliminary experience. Radiology 1999;212(2):561-6. Laroche C, Fairbairn I, Moss H, Pepke-Zaba J, Sharples L, Flower C, et al. Role of computed tomographic scanning of the thorax prior to bronchoscopy in the investigation of suspected lung cancer. Thorax 2000;55(5):359-63. Blum J, Handmaker H, Lister-James J, Rinne N. A multicenter trial with a somatostatin analog (99m)Tc depreotide in the evaluation of solitary pulmonary nodules. Chest 2000;117(5):1232-8. Blum JE, Handmaker H, Rinne NA. The utility of a somatostatin-type receptor binding peptide radiopharmaceutical (P829) in the evaluation of solitary pulmonary nodules. Chest 1999;115(1):224-32. Grewal RK, Dadparvar S, Yu JQ, Babaria CJ, Cavanaugh T, Sherman M, et al. Efficacy of Tc-99m depreotide scintigraphy in the evaluation of solitary pulmonary nodules. Cancer J 2002;8(5):400-4. Scottish Executive. Positron emission tomography (PET) scanning: implementation within Scotland. (NHS HDL (2003) 63). [cited 11 Nov 2004]. Available from url: http://www.show.scot.nhs.uk/sehd/mels/ HDL2003_63.pdf Gould MK, Maclean CC, Kuschner WG, Rydzak CE, Owens DK. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA 2001;285(7):914-24. Detterbeck FC, Rivera MP. Table 4-10. Detection of primary lung cancers by positron-emission tomography scanning [table]. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 58. Dunagan D, Chin R Jr, McCain T, Case L, Harkness B, Oaks T, et al. Staging by positron emission tomography predicts survival in patients with non-small cell lung cancer. Chest 2001;119(2):333-9. Hain SF, Curran KM, Beggs AD, Fogelman I, ODoherty MJ, Maisey MN. FDG-PET as a metabolic biopsy tool in thoracic lesions with indeterminate biopsy. Eur J Nucl Med 2001;28(9):1336-40.

56

REFERENCES

45

46

47

48

49 50 51

52

53

54

55

56 57

58 59 60

61

62 63

64

65 66

Hickeson M, Yun M, Matthies A, Zhuang H, Adam L-E, Lacorte L, et al. Use of a corrected standardized uptake value based on the lesion size on CT permits accurate characterization of lung nodules on FDGPET. Eur J Nucl Med Mol Imaging 2002;29(12):1639-47. Imdahl A, Jenkner S, Brink I, Nitzsche E, Stoelben E, Moser E, et al. Validation of FDG positron emission tomography for differentiation of unknown pulmonary lesions. Eur J Cardiothorac Surg 2001;20(2):324-9. Keith CJ, Miles KA, Griffiths MR, Wong D, Pitman AG, Hicks RJ. Solitary pulmonary nodules: accuracy and cost-effectiveness of sodium iodide FDG-PET using Australian data. Eur J Nucl Med Mol Imaging 2002;29(8):1016-23. Lee J, Aronchick JM, Alavi A. Accuracy of F-18 fluorodeoxyglucose positron emission tomography for the evaluation of malignancy in patients presenting with new lung abnormalities: a retrospective review. Chest 2001;120(6):1791-7. Marom EM, Sarvis S, Herndon JE 2nd, Patz EF Jr. T1 lung cancers: sensitivity of diagnosis with fluorodeoxyglucose PET. Radiology 2002;223(2):453-9. Matthies A, Hickeson M, Cuchiara A, Alavi A. Dual time point 18FFDG PET for the evaluation of pulmonary nodules. J Nucl Med 2002;43(7):871-5. Pitman AG, Hicks RJ, Binns DS, Ware RE, Kalff V, McKenzie AF, et al. Performance of sodium iodide based (18)F-fluorodeoxyglucose positron emission tomography in the characterization of indeterminate pulmonary nodules or masses. Br J Radiol 2002;75(890):114-21. Pitman AG, Hicks RJ, Kalff V, Binns DS, Ware RE, McKenzie AF, et al. Positron emission tomography in pulmonary masses where tissue diagnosis is unhelpful or not possible. Med J Aust 2001;175(6):303-7. Sasaki M, Kuwabara Y, Yoshida T, Nakagawa M, Koga H, Hayashi K, et al. Comparison of MET-PET and FDG-PET for differentiation between benign lesions and malignant tumors of the lung. Ann Nucl Med 2001;15(5):425-31. Willkomm P, Bangard M, Guhlke S, Sartor J, Bender H, Gallkowski U, et al. Comparison of [18F]FDG-PET and L-3[123I]-iodo-alphamethyl tyrosine (I-123 IMT)-SPECT in primary lung cancer. Ann Nucl Med 2002;16(7):503-6. Detterbeck FC, Rivera MP. Table 4-8. Sensitivity of bronchoscopy in diagnosing lung cancer [table]. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 54. Schreiber G, McCrory DC. Performance characteristics of different modalities for diagnosis of suspected lung cancer: summary of published evidence. Chest 2003;123(1 Suppl):115S-28S. Detterbeck FC, Rivera MP. Table 4-9. Reliability of needle biopsy of pulmonary nodules to assess the presence of cancer [table]. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 57. Agusti C, Xaubet A, Monton C, Sole M, Soler N, Carrion M, et al. Induced sputum in the diagnosis of peripheral lung cancer not visible endoscopically. Respir Med 2001;95(10):822-8. Mack MJ, Hazelrigg SR, Landreneau RJ, Acuff TE. Thoracoscopy for the diagnosis of the indeterminate solitary pulmonary nodule. Ann Thorac Surg 1993;56(4):825-32. Mitruka S, Landreneau RJ, Mack MJ, Fetterman LS, Gammie J, Bartley S, et al. Diagnosing the indeterminate pulmonary nodule: percutaneous biopsy versus thoracoscopy. Surgery 1995;118(4):676-84. Best LA, Munichor M, Ben-Shakhar M, Lemer J, Lichtig C, Peleg H. The contribution of anterior mediastinotomy in the diagnosis and evaluation of diseases of the mediastinum and lung. Ann Thorac Surg 1987;43(1):78-81. Lung and pleural tumours. In: Sobin LH, Wittekind Ch, editors. TNM classification of malignant tumours. 6th ed. New York: Wiley-Liss; 2002. p. 99-103. Detterbeck FC, Jones DR, Alden Parker L Jnr. Table 5-3. Reliability of computed tomography prediction of T3,4 status [table]. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 75. Webb WR, Gatsonis C, Zerhouni EA, Heelan RT, Glazer GM, Francis IR, et al. CT and MR imaging in staging non-small cell bronchogenic carcinoma: report of the Radiologic Diagnostic Oncology Group. Radiology 1991;178(3):705-13. Musset D, Grenier P, Carette MF, Frija G, Hauuy MP, Desbleds MT, et al. Primary lung cancer staging: prospective comparative study of MR imaging with CT. Radiology 1986;160(3):607-11. Padovani B, Mouroux J, Seksik L, Chanalet S, Sedat J, Rotomondo C, et al. Chest wall invasion by bronchogenic carcinoma: evaluation with MR imaging. Radiology 1993;187(1):33-8.

67 68 69

70 71 72

73 74 75

76

77

78

79

80

81

82

83 84 85 86 87

88

Laurent F, Drouillard J, Dorcier F, Velly JF, Barat JL, Grelet P, et al. Bronchogenic carcinoma staging: CT versus MR imaging. Assessment with surgery. Eur J Cardiothorac Surg 1988;2(1):31-6. Heelan RT, Demas BE, Caravelli JF, Martini N, Bains MS, McCormack PM, et al. Superior sulcus tumors: CT and MR imaging. Radiology 1989;170(3 Pt 1):637-41. Roberts JR, Blum MG, Arildsen R, Drinkwater DC Jr, Christian KR, Powers TA, et al. Prospective comparison of radiologic, thoracoscopic, and pathologic staging in patients with early non-small cell lung cancer. Ann Thorac Surg 1999;68(4):1154-8. Walshe AD, Douglas JG, Kerr KM, McKean ME, Godden DJ. An audit of the clinical investigation of pleural effusion. Thorax 1992;47(9):734-7. Dales RE, Stark RM, Raman S. Computed tomography to stage lung cancer. Approaching a controversy using meta-analysis. Am Rev Respir Dis 1990;141(5 Pt 1):1096-101. Detterbeck FC, Jones DR, Alden Parker L Jr. Table 5-5. Reliability of computed tomography staging of N1 (hilar) node involvement [table]. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 79. Glazer GM, Gross BH, Aisen AM, Quint LE, Francis IR, Orringer MB. Imaging of the pulmonary hilum: a prospective comparative study in patients with lung cancer. AJR Am J Roentgenol 1985;145(2):245-8. Wain JC. Video-assisted thorascopy and the staging of lung cancer. Ann Thorac Surg 1993;56(3):776-8. Roberts JR, Blum MG, Arildsen R, Drinkwater DC Jr, Christian KR, Powers TA, et al. Prospective comparison of radiologic, thoracoscopic, and pathologic staging in patients with early non-small cell lung cancer. Ann Thorac Surg 1999;68(4):1154-8. Detterbeck FC, Jones DR, Alden Parker L Jr. Table 5-6. Reliability of computed tomography assessment of mediastinal nodes [table]. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 80. Heelan RT, Martini N, Westcott JW, Bains MS, Watson RC, Caravelli JF, et al. Carcinomatous involvement of the hilum and mediastinum: computed tomographic and magnetic resonance evaluation. Radiology 1985;156(1):111-5. Patterson GA, Ginsberg RJ, Poon PY, Cooper JD, Goldberg M, Jones D, et al. A prospective evaluation of magnetic resonance imaging, computed tomography, and mediastinoscopy in the preoperative assessment of mediastinal node status in bronchogenic carcinoma. J Thorac Cardiovasc Surg 1987;94(5):679-84. Detterbeck FC, Jones DR, Alden Parker L Jr. Table 5-11. Reliability of mediastinoscopy to assess N2,3 node involvement [table]. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 85. National Collaborating Centre for Acute Care. Table 16. Accuracy of anterior mediastinoscopy in the diagnosis of lung cancer [table]. In: National Collaborating Centre for Acute Care. The diagnosis and treatment of lung cancer - Appendices. London: NCC-AC; 2005. Wallace MB, Silvestri GA, Sahai AV, Hawes RH, Hoffman BJ, Durkalski V, et al. Endoscopic ultrasound-guided fine needle aspiration for staging patients with carcinoma of the lung. Ann Thorac Surg 2001;72(6):1861-7. Wiersema MJ, Harada N, Daiehagh P, Beltz HF, Pfeiffer M, Allen K, et al. Evaluation of mediastinal lymphadenopathy with transesophageal endosonography guided fine needle aspiration biopsy. Acta Endoscopica 1998;28(1):7-20. Westcott JL. Percutaneous transthoracic needle biopsy. Radiology 1988;169(3):593-601. van Sonnenberg E, Casola G, Ho M, Neff CC, Varney RR, Wittich GR, et al. Difficult thoracic lesions: CT-guided biopsy experience in 150 cases. Radiology 1988;167(2): 457-61. Protopapas Z, Westcott JL. Transthoracic needle biopsy of mediastinal lymph nodes for staging lung and other cancers. Radiology 1996;199(2):489-96. Jolly PC, Li W, Anderson RP. Anterior and cervical mediastinoscopy for determining operability and predicting resectability in lung cancer. J Thorac Cardiovasc Surg 1980;79(3):366-71. Schreinemakers HH, Joosten HJ, Mravunac M, Lacquet LK. Parasternal mediastinoscopy. Assessment of operability in left upper lobe lung cancer: a prospective analysis. J Thorac Cardiovasc Surg 1988;95(2):298-302. Best LA, Munichor M, Ben-Shakhar M, Lemer J, Lichtig C, Peleg H. The contribution of anterior mediastinotomy in the diagnosis and evaluation of diseases of the mediastinum and lung. Ann Thorac Surg 1987;43(1):78-81.

57

MANAGEMENT OF PATIENTS WITH LUNG CANCER

89

90

91

92

93

94 95

96

97 98 99

100 101

102

103 104 105

106 107 108 109

110

Ginsberg RJ, Rice TW, Goldberg M, Waters PF, Schmocker BJ. Extended cervical mediastinoscopy. A single staging procedure for bronchogenic carcinoma of the left upper lobe. J Thorac Cardiovasc Surg 1987;94(5):673-8. Detterbeck FC, Jones DR, Alden Parker L Jr. Table 5-8. Accuracy of positron-emission tomography scanning: mediastinal nodes [table]. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 83. Pieterman RM, van Putten JW, Meuzelaar JJ, Mooyaart EL, Vaalburg W, Koeter GH, et al. Preoperative staging of non-small-cell lung cancer with positron-emission tomography. N Engl J Med 2000;343(4):254-61. Lardinois D, Weder W, Hany TF, Kamel EM , Korom S, Seifert B, et al. Staging of non-small-cell lung cancer with integrated positronemission tomography and computed tomography. N Engl J Med 2003;348(25):2500-7. Bulzebruck H, Bopp R, Drings P, Bauer E, Krysa S, Probst G, et al. New aspects in the staging of lung cancer. Prospective validation of the International Union Against Cancer TNM classification. Cancer 1992;70(5):1102-10. Quinn DL, Ostrow LB, Porter DK, Shelton DK Jr, Jackson DE Jr. Staging of non-small cell bronchogenic carcinoma: relationship of the clinical evaluation to organ scans. Chest 1986;89(2):270-5. Detterbeck FC, Jones DR, Molina PL. Table 6-1. Frequency of distant metastases at presentation in patients with lung cancer [table]. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 96. Detterbeck FC, Jones DR, Molina PL. Table 6-12. Reliability of positron-emission tomography scanning to identify distant metastases [table]. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 106. Hatter J, Kohman LJ, Mosca RS, Graziano SL, Veit LJ, Coleman M. Preoperative evaluation of stage I and stage II non-small cell lung cancer. Ann Thorac Surg 1994;58(6):1738-41. Kormas P, Bradshaw JR, Jeyasingham K. Preoperative computed tomography of the brain in non-small cell bronchogenic carcinoma. Thorax 1992;47(2):106-8. Ichinose Y, Hara N, Ohta M, Motohiro A, Maeda T, Nobe T, et al. Preoperative examination to detect distant metastasis is not advocated for asymptomatic patients with stages 1 and 2 non-small cell lung cancer. Preoperative examination for lung cancer. Chest 1989;96(5):1104-9. Ferrigno D, Buccheri G. Cranial computed tomography as a part of the initial staging procedures for patients with non-small cell lung cancer. Chest 1994; 106(4):1025-29. Akeson P, Larsson EM, Kristoffersen DT, Jonsson E, Holtas S. Brain metastases - comparison of gadodiamide injection-enhanced MR imaging at standard and high dose, contrast-enhanced CT and noncontrast-enhanced MR imaging. Acta Radiol 1995;36(3):300-6. Taphoorn MJ, Heimans JJ, Kaiser MC, de Slegte RG, Crezee FC, Valk J. Imaging of brain metastases. Comparison of computerized tomography (CT) and magnetic resonance imaging (MRI). Neuroradiology 1989;31(5):391-5. Sze G, Shin J, Krol G, Johnson C, Liu D, Deck MD. Intraparenchymal brain metastases: MR imaging versus contrast-enhanced CT. Radiology 1988;168(1):187-94. Davis PC, Hudgins PA, Peterman SB, Hoffman JC Jr. Diagnosis of cerebral metastases: double-dose delayed CT vs contrast-enhanced MR imaging. AJNR Am J Neuroradiol 1991;12(2):293-300. Detterbeck FC, Jones DR, Molina PL. Table 6-6. Reliability of imaging studies to detect metastases in non-small cell lung cancer [table]. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 101. Hillers TK, Sauve MD, Guyatt GH. Analysis of published studies on the detection of extrathoracic metastases in patients presumed to have operable non-small cell lung cancer. Thorax 1994;49(1):14-9. Karhunen PJ. Benign hepatic tumours and tumour like conditions in men. J Clin Pathol 1986;39(2):183-8. Jones EC, Chezmar JL, Nelson RC, Bernardino ME. The frequency and significance of small (less than or equal to 15 mm) hepatic lesions detected by CT. AJR Am J Roentgenol 1992;158(3):535-9. Wernecke K, Rummeny E, Bongartz G, Vassallo P, Kivelitz D, Wiesmann W, et al. Detection of hepatic masses in patients with carcinoma: comparative sensitivities of sonography, CT, and MR imaging. AJR Am J Roentgenol 1991;157(4):731-9. Martino CR, Haaga JR, Bryan PJ, LiPuma JP, El Yousef SJ, Alfidi RJ. CT-guided liver biopsies: eight years experience. Work in progress. Radiology 1984;152(3):755-7.

111 112 113

114

115

116

117 118 119 120

121

122 123

124 125 126 127

128

129 130 131 132

133

Kloos RT, Gross MD, Francis IR, Korobkin M, Shapiro B. Incidentally discovered adrenal masses. Endocr Rev 1995;16(4):460-84. Herrera MF, Grant CS, van Heerden JA, Sheedy PF, Ilstrup DM. Incidentally discovered adrenal tumors: an institutional perspective. Surgery 1991;110(6):1014-21. Detterbeck FC, Jones DR, Molina PL. Table 6-7. Incidence of an abnormal adrenal gland in lung cancer patients [table]. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 103. Detterbeck FC, Jones DR, Molina PL. Table 6-9. Confirmatory tests for suspected adrenal metastases in cancer patients [table]. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 104. Detterbeck FC, Jones DR, Molina PL. Table 6-10. Confirmatory tests for benign adrenal adenoma [table]. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 105. Detterbeck FC, Jones DR, Molina PL. Table 6-11. Nuclear medicine scans for extrathoracic staging [table]. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 106. Welch TJ, Sheedy PF 2nd, Stephens DH, Johnson CM, Swensen SJ. Percutaneous adrenal biopsy: review of a 10-year experience. Radiology 1994;193(2):341-4. Keogan MT, Tung KT, Kaplan DK, Goldstraw PJ, Hansell DM. The significance of pulmonary nodules detected on CT staging for lung cancer. Clin Radiol 1993;48(2):94-6. Kunitoh H, Eguchi K, Yamada K, Tsuchiya R, Kaneko M, Moriyama N, et al. Intrapulmonary sublesions detected before surgery in patients with lung cancer. Cancer 1992;70(7):1876-9. Richardson GE, Venzon DJ, Edison M, Brown M, Frame JN, Ihde DC, et al. Application of an algorithm for staging small-cell lung cancer can save one third of the initial evaluation costs. Arch Intern Med 1993;153(3):329-37. Detterbeck FC, Jones DR, Molina PL. Figure 6-2. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 100. Fry WA, Menck HR, Winchester DP. The National Cancer Data Base report on lung cancer. Cancer 1996;77(9):1947-55. British Thoracic Society, Society of Cardiothoracic Surgeons of Great Britain, Ireland Working Party. BTS guidelines: guidelines on the selection of patients with lung cancer for surgery. Thorax 2001;56(2):89-108. Treasure T, Utley M, Bailey A. Assessment of whether in-hospital mortality for lobectomy is a useful standard for the quality of lung cancer surgery: retrospective study. BMJ 2003;327(7406):73. Silvestri GA, Handy J, Lackland D, Corley E, Reed CE. Specialists achieve better outcomes than generalists for lung cancer surgery. Chest 1998;114:675-80. Klepetko W, Aberg TH, Lerut AE, Grodzki T, Velly JF, Walker WS, et al. Structure of general thoracic surgery in Europe. Eur J Cardiothorac Surg 2001;20(4):663-8. Hannan EL, Radzyner M, Rubin D, Dougherty J, Brennan MF. The influence of hospital and surgeon volume on in-hospital mortality for colectomy, gastrectomy, and lung lobectomy in patients with cancer. Surgery 2002;131(1):6-15. van Rens MT, de la Riviere AB, Elbers HR, van Den Bosch JM. Prognostic assessment of 2,361 patients who underwent pulmonary resection for non-small cell lung cancer, stage I, II, and IIIA. Chest 2000;117(2):374-9. Adebonojo SA, Bowser AN, Moritz DM, Corcoran PC. Impact of revised stage classification of lung cancer on survival: a military experience. Chest 1999;115(6):1507-13. Suzuki K, Nagai K, Yoshida J, Moriyama E, Nishimura M, Takahashi K, et al. Prognostic factors in clinical stage I non-small cell lung cancer. Ann Thorac Surg 1999;67(4):927-32. Makitaro R, Paakko P, Huhti E, Bloigu R, Kinnula VL. Prospective population-based study on the survival of patients with lung cancer. Eur Respir J 2002;19(6):1087-92. Inoue K, Sato M, Fujimura S, Sakurada A, Takahashi S, Usuda K, et al. Prognostic assessment of 1310 patients with non-small-cell lung cancer who underwent complete resection from 1980 to 1993. J Thorac Cardiovasc Surg 1998;116(3):407-11. Myrdal G, Lambe M, Gustafsson G, Nilsson K, Stahle E. Survival in primary lung cancer potentially cured by operation: influence of tumor stage and clinical characteristics. Ann Thorac Surg 2003;75(2):356-63.

58

REFERENCES

134 135 136 137 138 139

140 141 142 143

144

145 146 147 148

149 150 151 152 153 154 155 156 157 158 159

Pastorino U, Andreola S, Tagliabue E, Pezzella F, Incarbone M, Sozzi G, et al. Immunocytochemical markers in stage I lung cancer: relevance to prognosis. J Clin Oncol 1997;15(8):2858-65. Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest 1997;111(6):1710-7. Kotlyarov EV, Rukosuyev AA. Long-term results and patterns of disease recurrence after radical operations for lung cancer. J Thorac Cardiovasc Surg 1991;102(1):24-8. Read RC, Schaefer R, North N, Walls R. Diameter, cell type, and survival in stage I primary non-small-cell lung cancer. Arch Surg 1988;123(4):446-9. Naruke T, Goya T, Tsuchiya R, Suemasu K. Prognosis and survival in resected lung carcinoma based on the new international staging system. J Thorac Cardiovasc Surg 1988;96(3):440-7. Mountain CF, Lukeman JM, Hammar SP, Chamberlain DW, Coulson WF, Page DL, et al. Lung cancer classification: the relationship of disease extent and cell type to survival in a clinical trials population. J Surg Oncol 1987;35(3):147-56. Pairolero PC, Williams DE, Bergstralh EJ, Piehler JM, Bernatz PE, Payne WS. Postsurgical stage I bronchogenic carcinoma: morbid implications of recurrent disease. Ann Thorac Surg 1984;38(4):331-8. Williams DE, Pairolero PC, Davis CS, Bernatz PE, Payne WS, Taylor WF, et al. Survival of patients surgically treated for stage I lung cancer. J Thorac Cardiovasc Surg 1981;82(1):70-6. Bernard A, Ferrand L, Hagry O, Benoit L, Cheynel N, Favre J-P. Identification of prognostic factors determining risk groups for lung resection. Ann Thorac Surg 2000;70(4):1161-7. Thomas P, Piraux M, Jacques LF, Gregoire J, Bedard P, Deslauriers J. Clinical patterns and trends of outcome of elderly patients with bronchogenic carcinoma. Eur J Cardiothorac Surg 1998;13(3):266-74. Harpole DH Jr, DeCamp MM Jr, Daley J, Hur K, Oprian CA, Henderson WG, et al. Prognostic models of thirty-day mortality and morbidity after major pulmonary resection. J Thorac Cardiovasc Surg 1999;117(5):969-79. Kruger M, Uschinsky K, Hassler K, Engelmann C. Postoperative complications after bronchoplastic procedures in the treatment of bronchial malignancies. Eur J Cardiothorac Surg 1998;14(1):46-53. Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg 1995;60(3):615-23. Deneffe G, Lacquet LM, Verbeken E, Vermaut G. Surgical treatment of bronchogenic carcinoma: a retrospective study of 720 thoracotomies. Ann Thorac Surg 1988;45(4):380-3. Duque JL, Ramos G, Castrodeza J, Cerezal J, Castanedo M, Yuste MG, et al. Early complications in surgical treatment of lung cancer: a prospective, multicenter study. Grupo Cooperativo de Carcinoma Broncogenico de la Sociedad Espanola de Neumologia y Cirugia Toracica. Ann Thorac Surg 1997;63(4):944-50. Kohman LJ, Meyer JA, Ikins PM, Oates RP. Random versus predictable risks of mortality after thoracotomy for lung cancer. J Thorac Cardiovasc Surg 1986;91(4):551-4. Massard G, Moog R, Wihlm JM, Kessler R, Dabbagh A, Lesage A, et al. Bronchogenic cancer in the elderly: operative risk and long-term prognosis. Thorac Cardiovasc Surg 1996;44(1):40-5. Van Den Bosch JM, Gelissen HJ, Wagenaar SS. Exploratory thoracotomy in bronchial carcinoma. Journal of J Thorac Cardiovasc Surg 1983;85(5):733-7. Van Meerbeeck JP, Damhuis RA, Vos de Wael ML. High postoperative risk after pneumonectomy in elderly patients with right-sided lung cancer. Eur Respir J 2002;19(1):141-5. Brown WT. Video-assisted thoracic surgery: the Miami experience. Semin Thorac Cardiovasc Surg 1998;10(4):305-12. Kaseda S, Aoki T, Hangai N. Video-assisted thoracic surgery (VATS) lobectomy: the Japanese experience. Semin Thorac Cardiovasc Surg 1998;10(4):300-4. Lewis RJ, Caccavale RJ. Video-assisted thoracic surgical non-rib spreading simultaneously stapled lobectomy (VATS(n)SSL). Semin Thorac Cardiovasc Surg 1998;10(4):332-9. McKenna RJ Jr, Fischel RJ, Wolf R, Wurnig P. Video-assisted thoracic surgery (VATS) lobectomy for bronchogenic carcinoma. Semin Thorac Cardiovasc Surg 1998;10(4):321-5. Roviaro G, Varoli F, Vergani C, Maciocco M. Video-assisted thoracoscopic surgery (VATS) major pulmonary resections: the Italian experience. Semin Thorac Cardiovasc Surg 1998;10(4):313-20. Walker WS. Video-assisted thoracic surgery (VATS) lobectomy: the Edinburgh experience. Semin Thorac Cardiovasc Surg 1998;10(4):291-9. Yim AP, Izzat MB, Liu HP, Ma CC. Thoracoscopic major lung resections: an Asian perspective. Semin Thorac Cardiovasc Surg 1998;10(4):326-31.

160

161 162 163

164

165

166 167

168 169

170

171 172

173

174 175 176 177

178

179

180 181 182

Nomori H, Ohtsuka T, Horio H, Naruke T, Suemasu K. Difference in the impairment of vital capacity and 6-minute walking after a lobectomy performed by thoracoscopic surgery, an anterior limited thoracotomy, an anteroaxillary thoracotomy, and a posterolateral thoracotomy. Surg Today 2003;33(1):7-12. Kaseda S, Aoki, T, Hangai, N, Shimizu, K. Better pulmonary function and prognosis with video-assisted thoracic surgery than with thoracotomy. Ann Thorac Surg 2000;70(5):1644-6. Nakata M, Saeki H, Yokoyama N, Kurita A, Takiyama W, Takashima S. Pulmonary function after lobectomy: video-assisted thoracic surgery versus thoracotomy. Ann Thorac Surg 2000;70(3):938-41. Sugiura H, Morikawa T, Kaji M, Sasamura Y, Kondo S, Katoh H. Longterm benefits for the quality of life after video-assisted thoracoscopic lobectomy in patients with lung cancer. Surg Laparosc Endosc Percutan Tech 1999;9(6):403-8. Giudicelli R, Thomas P, Lonjon T, Ragni J, Morati N, Ottomani R, et al. Video-assisted minithoracotomy versus muscle-sparing thoracotomy for performing lobectomy. Ann Thorac Surg 1994;58(3):712-7. Passlick B, Kubuschock B, Sienel W, Thetter O, Pantel K, Izbicki JR. Mediastinal lymphadenectomy in non-small cell lung cancer: effectiveness in patients with or without nodal micrometastases - results of a preliminary study. Eur J Cardiothorac Surg 2002;21(3):520-6. Wu Y, Huang ZF, Wang SY, Yang XN, Ou W. A randomized trial of systematic nodal dissection in resectable non-small cell lung cancer. Lung Cancer 2002;36(1):1-6. Keller SM, Adak S, Wagner H, Johnson DH. Mediastinal lymph node dissection improves survival in patients with stages II and IIIa nonsmall cell lung cancer. Eastern Cooperative Oncology Group. Ann Thorac Surg 2000;70(2):358-66. Izbicki JR, Passlick B, Karg O, Bloechle C, Pantel K, Knoefel WT, et al. Impact of radical systematic mediastinal lymphadenectomy on tumour staging in lung cancer. Ann Thorac Surg 1995;59(1):209-14. Sugi K, Nawata K, Fujita N, Ueda K, Tanaka T, Matsuoka T, et al. Systematic lymph node dissection for clinically diagnosed peripheral non-small-cell lung cancer less than 2 cm in diameter. World J Surg 1998;22(3):290-5. Detterbeck FC, Jones DR. Surgical treatment of stage IIIA(N2) nonsmall cell lung cancer. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 244-56. Alifano M, DAiuto M, Magdeleinat P, Poupardin E, Chafik A, Strano S, et al. Surgical treatment of superior sulcus tumors: results and prognostic factors. Chest 2003;124(3):996-1003. Komaki R, Roth JA, Walsh GL, Putnam JB, Vaporciyan A, Lee JS, et al. Outcome predictors for 143 patients with superior sulcus tumors treated by multidisciplinary approach at the University of Texas M.D. Anderson Cancer Center. Int J Radiat Oncol Biol Phys 2000;48(2):347-54. Martinod E, DAudiffret A, Thomas P, Wurtz AJ, Dahan M, Riquet M, et al. Management of superior sulcus tumors: experience with 139 cases treated by surgical resection. Ann Thorac Surg 2002;73(5):1534-40. Gandhi S, Walsh GL, Komaki R, Gokaslan ZL, Nesbitt JC, Putnam JB Jr, et al. A multidisciplinary surgical approach to superior sulcus tumors with vertebral invasion. Ann Thorac Surg. 1999;68(5):1778-85. Detterbeck FC, Jones DR, Kernstine KH, Naunheim KS. Lung cancer. Special treatment issues. Chest 2003; 123(1 Suppl):244S-58S. Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 1990;322(8):494-500. Vecht CJ, Haaxma-Reiche H, Noordijk EM, Padberg GW, Voormolen JH, Hoekstra FH, et al. Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery? Ann Neurol 1993;33(6):583-90. Mintz AH, Kestle J, Rathbone MP, Gaspar L, Hugenholtz H, Fisher B, et al. A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis. Cancer 1996;78(7):1470-6. Patchell RA, Tibbs PA, Regine WF, Dempsey RJ, Mohiuddin M, Kryscio RJ, et al. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA 1998;280(17):1485-9. Porte HL, Roumilhac D, Graziana JP, Eraldi L, Cordonier C, Puech P, et al. Adrenalectomy for a solitary adrenal metastasis from lung cancer. Ann Thorac Surg. 1998;65(2):331-5. Kim SH, Brennan MF, Russo P, Burt ME, Coit DG. The role of surgery in the treatment of clinically isolated adrenal metastasis. Cancer 1998;82(2):389-94. Luketich JD, Burt ME. Does resection of adrenal metastases from nonsmall cell lung cancer improve survival? Ann Thorac Surg 1996;62(6):1614-6.

59

MANAGEMENT OF PATIENTS WITH LUNG CANCER

183

184 185

186

187 188 189

190

191 192

193 194 195

196

197 198 199

200

201

202

203

Lad T, Piantadosi S, Thomas P, Payne D, Ruckdeschel J, Giaccone G. A prospective randomized trial to determine the benefit of surgical resection of residual disease following response of small cell lung cancer to combination chemotherapy. Chest 1994;106(6 Suppl):320S-3S. Fujimori K, Yokoyama A, Kurita Y, Terashima M. A pilot phase 2 study of surgical treatment after induction chemotherapy for resectable stage I to IIIA small cell lung cancer. Chest 1997;111(4):1089-93. Shepherd FA, Ginsberg RJ, Patterson GA, Evans WK, Feld R. A prospective study of adjuvant surgical resection after chemotherapy for limited small cell lung cancer. A University of Toronto Lung Oncology Group study. J Thorac Cardiovasc Surg 1989;97(2):177-86. Davis S, Crino L, Tonato M, Darwish S, Pelicci PG, Grignani F. A prospective analysis of chemotherapy following surgical resection of clinical stage I-II small-cell lung cancer. Am J Clin Oncol 1993;16(2):93-5. Shaw P, Agarwal P, Pleurodesis for malignant pleural effusion (Cochrane Review). In: The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley & Sons, Ltd. Antunes G, Neville E, Duffy J, Ali N. BTS guidelines for the management of malignant pleural effusions. Thorax 2003;58(Suppl II):ii29-ii38. The Royal College of Pathologists. Minimum data set for lung cancer histopathology reports. London: The College; 1998. [cited 16 Nov 2004]. Available from url: http://www.rcpath.org/ index.asp?PageID=254 Rowell NP, Williams CJ. Radical radiotherapy for stage I/II non-small cell lung cancer in patients not sufficiently fit for or declining surgery (medically inoperable) (Cochrane Review). In: The Cochrane Library, Issue 2, 2004. Chichester, UK: John Wiley & Sons, Ltd. Qiao X, Tullgren O, Lax I, Sirzen F, Lewensohn R. The role of radiotherapy in treatment of Stage 1 non-small cell lung cancer. Lung Cancer 2003;41(1):1-11. Saunders M, Dische S, Barrett A, Harvey A, Gibson D, Parmar M. Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small-cell lung cancer: a randomised multicentre trial. CHART Steering Committee. Lancet 1997;350(9072):161-5. Sharma S, Sharma R, Bhowmik KT. Sequential chemoradiotherapy versus radiotherapy in the management of locally advanced non-smallcell lung cancer. Adv Ther 2003;20(1):14-9. Kim TE, Murren JR. Therapy for stage IIIB and stage IV non-small cell lung cancer. Clin Chest Med 2002;23(1):209-24. Sause W, Kolesar P, Taylor S IV, Johnson D, Livingston R, Komaki R, et al. Final results of phase III trial in regionally advanced unresectable non-small cell lung cancer: Radiation Therapy Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. Chest 2000;117(2):358-64. Dillman RO, Seagren SL, Propert KJ, Guerra J, Eaton WL, Perry MC, et al. A randomised trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer. N Engl J Med 1990;323(14):940-5. Miller TP, Crowley JJ, Mira J. A randomized trial of chemotherapy and radiotherapy for stage III non-small cell lung cancer. Cancer Therapeutics 1998;1:229-36. Mattson K, Holsti LR, Holsti P, Jakobsson M, Kajanti M, Liippo K, et al. Inoperable non-small cell lung cancer: radiation with or without chemotherapy. Eur J Cancer Clin Oncol 1988;24(3):477-82. Morton RF, Jett JR, McGinnis WL, Earle JD, Therneau TM, Krook JE, et al. Thoracic radiation therapy alone compared with combined chemoradiotherapy for locally unresectable non-small cell lung cancer: a randomized, phase III trial. Ann Intern Med 1991;115(9):681-6. Johnson DH, Einhorn LH, Bartolucci A, Birch R, Omura G, Perez CA, et al. Thoracic radiotherapy does not prolong survival in patients with locally advanced, unresectable non-small cell lung cancer. Ann Intern Med 1990;113(1):33-8. Lung Cancer Disease Site Group. Altered fractionation of radical radiation therapy in the management of unresectable non-small cell lung cancer. Ontario: Cancer Care Ontario Practice Guidelines Initiative; 2000. (Practice Guideline Report #7-12). [cited 16 Nov 2004]. Available from url: http://www.cancercare.on.ca/pdf/ full7_12.pdf Saunders M, Dische S, Barrett A, Harvey A, Griffiths G, Palmar M. Continuous, hyperfractionated, accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small cell lung cancer: mature data from the randomised multicentre trial. CHART Steering committee. Radiother Oncol 1999;52(2):137-48. Macbeth F, Toy E, Coles B, Melville A, Eastwood A. Palliative radiotherapy regimens for non-small cell lung cancer (Cochrane Review). In: The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley & Sons, Ltd.

204

205

206 207

208

209

210

211

212

213

214

215

216

217

218

219

220

221 222

Bezjak A, Dixon P, Brundage M, Tu DS, Palmer MJ, Blood P, et al. Randomized phase III trial of single versus fractionated thoracic radiation in the palliation of patients with lung cancer (NCIC CTG SC.15). Int J Radiat Oncol Biol Phys 2002;54(3):719-28. Sundstrom S, Bremnes R, Aasebo U, Aamdal S, Hatlevoll R, Brunsvig P, et al. Hypofractionated palliative radiotherapy (17 Gy per two fractions) in advanced non-small-cell lung carcinoma is comparable to standard fractionation for symptom control and survival: a national phase III trial. J Clin Oncol 2004;22(5):801-10. Clinical Practice Guidelines for the treatment of unresectable nonsmall-cell lung cancer. Adopted on May 16, 1997 by the American Society of Clinical Oncology. J Clin Oncol 1997;15(8):2996-3018. Sze WM, Shelley MD, Held I, Wilt TJ, Mason MD. Palliation of metastatic bone pain; single fraction versus multifraction radiotherapy - a systematic review of randomised trials. Clin Oncol (R Coll Radiol) 2003;15(6):345-52. Roos DE, OBrien PC, Smith JG, Spry NA, Hoskin PJ, Burmeister BH, et al. A role for radiotherapy in neuropathic bone pain: preliminary response rates from a prospective trial (Trans-tasman radiation oncology group, TROG 96.05). Int J Radiat Oncol Biol Phys 2000;46(4):975-81. Borgelt B, Gelber R, Kramer S, Brady LW, Chang CH, Davis LW, et al. The palliation of brain metastases: final results of the first two studies by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 1980;6(1):1-9. Priestman TJ, Dunn J, Brada M, Rampling R, Baker PG. Final results of the Royal College of Radiologists trial comparing two different radiotherapy schedules in the treatment of cerebral metastases. Clin Oncol (R Coll Radiol) 1996;8(5):308-15. Hopwood P, Stephens RJ. Symptoms at presentation for treatment in patients with lung cancer: implications for the evaluation of palliative treatment. The Medical Research Council (MRC) Lung Cancer Working Party. Br J Cancer 1995;71(3):633-6. Spiro SG, Rudd RM, Souhami RL, Brown J, Fairlamb DJ, Gower NH, et al. Chemotherapy versus supportive care in advanced non-small cell lung cancer: improved survival without detriment to quality of life. Thorax 2004;59(10):828-36. Cullen MH, Billingham LJ, Woodroffe CM, Chetiyawardana AD, Gower NH, Joshi R, et al. Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life. J Clin Oncol 1999;17(10):3188-94. Anderson H, Hopwood P, Stephens RJ, Thatcher N, Cottier B, Nicholson M, et al. Gemcitabine plus best supportive care (BSC) vs BSC in inoperable non-small cell lung cancer - a randomized trial with quality of life as the primary outcome. UK NSCLC Gemcitabine Group. Non-Small Cell Lung Cancer. Br J Cancer 2000;83(4):447-53. Ranson M, Davidson N, Nicolson M, Falk S, Carmichael J, Lopez P, et al. Randomized trial of paclitaxel plus supportive care versus supportive care for patients with advanced non-small-cell lung cancer. J Natl Cancer Inst 2000;92(13):1074-80. Roszkowski K, Pluzanska A, Krzakowski M, Smith AP, Saigi E, Aasebo U, et al. A multicenter, randomized, phase III study of docetaxel plus best supportive care versus best supportive care in chemotherapynaive patients with metastatic or non-resectable localized non-small cell lung cancer (NSCLC). Lung Cancer 2000;27(3):145-57. Gridelli C. The ELVIS trial: a phase III study of single-agent vinorelbine as first-line treatment in elderly patients with advanced non-small cell lung cancer. Elderly Lung Cancer Vinorelbine Italian Study. Oncologist 2001;6 Suppl 1:4-7. Le Chevalier T, Pujol JL, Douillard JY, Alberola V, Monnier A, Riviere A, et al. A three-arm trial of vinorelbine (Navelbine) plus cisplatin, vindesine plus cisplatin, and single-agent vinorelbine in the treatment of non-small cell lung cancer: an expanded analysis. Semin Oncol 1994;21(5 Suppl 10):28-34. Perol M, Guerin JC, Thomas P, Poirier R, Carles P, Robinet G, et al. Multicenter randomized trial comparing cisplatin-mitomycinvinorelbine versus cisplatin-mitomycin-vindesine in advanced nonsmall cell lung cancer. Groupe Francais de Pneumo-Cancerologie. Lung Cancer 1996;14(1):119-34. Bonomi P, Kim K, Fairclough D, Cella D, Kugler J, Rowinsky E, et al. Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial. J Clin Oncol 2000;18(3):623-31. Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, et al. Comparison of four chemotherapy regimens for advanced nonsmall-cell lung cancer. N Engl J Med 2002;346(2):92-8. Kosmidis P, Mylonakis N, Nicolaides C, Kalophonos C, Samantas E, Boukovinas J, et al. Paclitaxel plus carboplatin versus gemcitabine plus paclitaxel in advanced non-small-cell lung cancer: a phase III randomized trial. J Clin Oncol 2002;20(17):3578-85.

60

REFERENCES

223

224

225

226

227

228

229

230

231

232

233

234

235 236

237

238 239

240

241

Gridelli C, Perrone F, Gallo C, Cigolari S, Rossi A, Piantedosi F, et al. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst. 2003;95(5):362-72. Smith IE, OBrien ME, Talbot DC, Nicolson MC, Mansi JL, Hickish TF, et al. Duration of chemotherapy in advanced non-small-cell lung cancer: a randomized trial of three versus six courses of mitomycin, vinblastine, and cisplatin. J Clin Oncol 2001;19(5):1336-43. Socinski MA, Schell MJ, Peterman A, Bakri K, Yates S, Gitten R, et al. Phase III trial comparing a defined duration of therapy versus continuous therapy followed by second-line therapy in advanced-stage IIIB/IV nonsmall-cell lung cancer. J Clin Oncol 2002;20(5):1335-43. Vansteenkiste J, Vandebroek J, Nackaerts K, Dooms C, Galdermans D, Bosquee L, et al. Influence of cisplatin-use, age, performance status and duration of chemotherapy on symptom control in advanced nonsmall cell lung cancer: detailed symptom analysis of a randomised study comparing cisplatin-vindesine to gemcitabine. Lung Cancer 2003; 40(2):191-9. Shepherd FA, Dancey J, Ramlau R, Mattson K, Gralla R, ORourke M, et al. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol 2000;18(10):2095-103. Fossella FV, DeVore R, Kerr RN, Crawford J, Natale RR, Dunphy F, et al. Randomised phase III trial of docetaxel versus vinorelbine or ifosfamide inpatients with advanced non-small cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group. J Clin Oncol 2000;18(12):2354-62. Dancey J, Shepherd FA, Gralla RJ, Kim YS. Quality of life assessment of second-line docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy: results of a prospective, randomized phase III trial. Lung Cancer 2004;43(2):183-94. Kris MG, Natale RB, Herbst RS, Lynch TJ Jr, Prager D, Belani CP, et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA 2003;290(16):2149-58. Giaccone G, Herbst RS, Manegold C, Scagliotti G, Rosell R, Miller V, et al. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial INTACT 1. J Clin Oncol 2004;22(5):777-84. Herbst RS, Giaccone G, Schiller JH, Natale RB, Miller V, Manegold C, et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial INTACT 2. J Clin Oncol 2004;22(5):785-94. Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard JY, et al. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer. J Clin Oncol 2003;21(12):2237-46. Gillenwater HH, Socinski MA. Extensive stage small cell lung cancer. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 360-75. Simon GR, Wagner H. Small cell lung cancer. Chest 2003;123(1 Suppl):259S-71S. Lowenbraun S, Bartolucci A, Smalley RV, Lynn M, Krauss S, Durant JR. The superiority of combination chemotherapy over single agent chemotherapy in small cell lung carcinoma. Cancer 1979;44(2):406-13. Girling DJ. Comparison of oral etoposide and standard intravenous multidrug chemotherapy for small-cell lung cancer: a stopped multicentre randomised trial. Medical Research Council Lung Cancer Working Party. Lancet 1996;348(9027):563-6. Frasci G, On behalf of the Southern Italy Cooperative Oncology Group (SICOG). Chemotherapy of lung cancer in the elderly. Crit Rev Oncol Hematol 2002;41(3):349-61. Elias AD, Skarin AT, Richardson P, Ibrahim J, McCauley M, Frei E 3rd. Dose-intensive therapy for extensive-stage small cell lung cancer and extrapulmonary small cell carcinoma: long-term outcome. Biol Blood Marrow Transplant 2002;8(6):326-33. Pujol JL, Carestia L, Daures JP. Is there a case for cisplatin in the treatment of small-cell lung cancer? A meta-analysis of randomized trials of a cisplatin-containing regimen versus a regimen without this alkylating agent. Br J Cancer 2000;83(1):8-15. Sundstrom S, Bremnes RM, Kaasa S, Aasebo U, Hatlevoll R, Dahle R, et al. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years follow-up. J Clin Oncol 2002;20(24):4665-72.

242

243 244

245

246 247

248

249

250 251

252

253

254

255

256

257 258

259

Mavroudis D, Papadakis E, Veslemes M, Tsiafaki X, Stavrakakis J, Kouroussis C, et al. A multicenter randomized clinical trial comparing paclitaxel-cisplatin- etoposide versus cisplatin-etoposide as first-line treatment in patients with small-cell lung cancer. Ann Oncol 2001;12(4):463-70. Edelman MJ, Gandara DR. Small cell lung cancer: Current status of new chemotherapeutic agents. Crit Rev Oncol Hematol 1998;27(3):211-20. Murray N, Livingston RB, Shepherd FA, James K, Zee B, Langleben A, et al. Randomized study of CODE versus alternating CAV/EP for extensive-stage small-cell lung cancer: an intergroup study of the National Cancer Institute of Canada Clinical Trials Group and the Southwest Oncology Group. J Clin Oncol 1999;17(8):2300-8. Ueoka H, Kiura K, Tabata M, Kamei H, Gemba K, Sakae K, et al. A randomized trial of hybrid administration of cyclophosphamide, doxorubicin, and vincristine (CAV)/cisplatin and etoposide (PVP) versus sequential administration of CAV-PVP for the treatment of patients with small cell lung carcinoma: results of long term followup. Cancer 1998;83(2):283-90. Tjan-Heijnen VC, Wagener DJ, Postmus PE. An analysis of chemotherapy dose and dose-intensity in small-cell lung cancer: lessons to be drawn. Ann Oncol 2002;13(10):1519-30. Morris DE, Socinski MA, Detterbeck FC. Table 24-3. Randomized trials of maintenance chemotherapy versus observation in limited stage small cell lung cancer [table]. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 346. Kelly K, Crowley JJ, Bunn PA Jr, Hazuka MB, Beasley K, Upchurch C, et al. Role of recombinant interferon alpha-2 maintenance in patients with limited stage small cell lung cancer responding to concurrent chemoradiation: a Southwest Oncology Study Group. J Clin Oncol 1995;13(12):2924-30. Jett JR, Maksymiuk AW, Su JQ, Mailliard JA, Krook JE, Tschetter LK, et al. Phase III trial of recombinant interferon gamma in complete responders with small cell lung cancer. J Clin Oncol 1994;12(11):2321-6. Dunn CJ, Goa KL. Lenograstim: an update of its pharmacological properties and use in chemotherapy-induced neutropenia and related clinical settings. Drugs 2000;59(3):681-717. Berghmans T, Paesmans M, Lafitte JJ, Mascaux C, Meert AP, Sculier JP. Role of granulocyte and granulocyte-macrophage colonystimulating factors in the treatment of small-cell lung cancer: a systematic review of the literature with methodological assessment and meta-analysis. Lung Cancer 2002;37(2):115-23. Steward WP, Von Pawel J, Gatzemeier U, Woll P, Thatcher N, Koschel G, et al. Effects of granulocyte-macrophage colony-stimulating factor and dose intensification of V-ICE chemotherapy in small-cell lung cancer: a prospective randomized study of 300 patients. J Clin Oncol 1998;16(2):642-50. Johnson PW, Muers MF, Peake MD, Poulter KM, Gurney EM, Napp VV, et al. A randomized trial of amifostine as a cytoprotective agent in patients receiving chemotherapy for small cell lung cancer. Br J Cancer 2001;84(1):19-24. Vincent M, Bramwell V, Moran LA, Anderson D, Anderson E, Andriano J, et al. Use of amifostine to ameliorate the toxic effects of chemotherapy in the treatment of cancer. Curr Oncol 2000;7(3):149-61. Mantovani G, Ghiani M, Curreli L, Maccio A, Massa D, Succu G, et al. Assessment of the efficacy of two dosages and schedules of human recombinant erythropoietin in the prevention and correction of cisplatin-induced anemia in cancer patients. Oncol Rep 1999;6:421-6. Vansteenkiste J, Pirker R, Massuti B, Barata F, Font A, Fiegl M, et al. Double-blind, placebo-controlled, randomized phase III trial of darbepoetin alfa in lung cancer patients receiving chemotherapy. J Natl Cancer Inst 2002;94(16):1211-20. Joint Council for Clinical Oncology. Quality control in cancer chemotherapy: managerial and procedural aspects. London: Royal College of Physicians, Royal College of Radiologists; 1994. Royal College of Radiologists Clinical Oncology Information Network. Guidelines for cytotoxic chemotherapy in adults. A document for local expert groups in the United Kingdom preparing chemotherapy policy documents. Clin Oncol (R Coll Radiol) 2001;13(1):s209-48. Scottish Executive. Guidelines for the use of cytotoxic chemotherapy in the clinical environment. Edinburgh: The Executive; 2001. (NHS HDL (2001) 13). [cited 17 Nov 2004]. Available from url: http:// www.show.scot.nhs.uk/indexsearch.htm

61

MANAGEMENT OF PATIENTS WITH LUNG CANCER

260

261

262

263

264

265 266

267

268

269

270 271

272

273

274

275 276 277 278 279

Detterbeck FC, Socinski MA. Induction therapy and surgery for I-IIIA, B non-small cell lung cancer. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 267-82. Lung Cancer Disease Site Group. Use of preoperative chemotherapy with or without postoperative radiotherapy in technically resectable stage IIIA non-small cell lung cancer. Ontario: Cancer Care Ontario Practice Guidelines Initiative; 2002. (Practice Guideline Report #74). [cited 17 Nov 2004]. Available from url: http:// www.cancercare.on.ca/pdf/pebc7-4f.pdf Depierre A, Milleron B, Moro-Sibilot D, Chevret S, Quoix E, Lebeau B, et al. Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer. J Clin Oncol 2002;20(1):247-53. Rosell R, Gomez-Codina J, Camps C, Javier Sanchez J, Maestre J, Padilla J, et al. Preresectional chemotherapy in stage IIIA non-smallcell lung cancer: a 7-year assessment of a randomized controlled trial. Lung Cancer 1999;26(1):7-14. Roth JA, Atkinson EN, Fossella F, Komaki R, Bernadette Ryan M, Putnam JB Jr, et al. Long-term follow-up of patients enrolled in a randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA non-small-cell lung cancer. Lung Cancer 1998;21(1):1-6. Eberhardt WE, Albain KS, Pass H, Putnam JB, Gregor A, Assamura H, et al. Induction treatment before surgery for non-small cell lung cancer. Lung Cancer 2003;42 Suppl 1:S9-14. Non-small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. BMJ 1995;311(7010):899-909. Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 2004;350(4):351-60. Tonato M. Final report of the Adjuvant Lung Project Italy (ALPI): an Italian/EORTC-LCG randomised trial of adjuvant chemotherapy in completely resected non-small cell lung cancer (NSCLC) [abstract]. ASCO Abstracts 2002;Abstract 1157. Keller SM, Adak S, Wagner H, Herskovic A, Komaki R, Brooks BJ, et al. A randomized trial of postoperative adjuvant therapy in patients with completely resected stage II or IIIA non-small-cell lung cancer. Eastern Cooperative Oncology Group. N Engl J Med 2000;343(17):1217-22. PORT Meta-analysis Trialists Group. Postoperative radiotherapy for non-small cell lung cancer (Cochrane Review). In: The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley & Sons, Ltd. Trodella L, Granone P, Valente S, Valentini V, Balducci M, Mantini G, et al. Adjuvant radiotherapy in non-small cell lung cancer with pathological stage I: definitive results of a phase III randomized trial. Radiother Oncol 2002;62(1):11-9. Johnson DH, Einhorn LH, Bartolucci A, Birch R, Omura G, Perez CA, et al. Thoracic radiotherapy does not prolong survival in patients with locally advanced, unresectable non-small cell lung cancer. Ann Intern Med 1990;113(1):33-8. Morton RF, Jett JR, McGinnis WL, Earle JD, Therneau TM, Krook JE, et al. Thoracic radiation therapy alone compared with combined chemoradiotherapy for locally unresectable non-small cell lung cancer. A randomized, phase III trial. Ann Intern Med 1991;115(9):681-6. Auperin A, Le Pechoux C. Meta-analysis of randomised trials evaluating cisplatin or carboplatin-based concomitant chemoradiotation versus radiotherpay alone in locally advanced nonsmall cell lung cancer cancer (NSCLC) [abstract]. Lung Cancer 2003;41 Suppl 2:S69-70. Rowell N, ORouke N. Concomitant chemoradiotherapy in non-small cell lung cancer: a systematic review [abstract]. Lung Cancer 2003;41 Suppl 2:S70. Pignon JP, Arriagada R, Ihde DC, Johnson DH, Perry MC, Souhami RL, et al. A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med 1992;327(23):1618-24. Warde P, Payne D. Does thoracic irradiation improve survival and local control in limited-stage small-cell carcinoma of the lung? A metaanalysis. J Clin Oncol 1992;10(6):890-5. De Ruysscher D, Vansteenkiste J. Chest radiotherapy in limited-stage small cell lung cancer: facts, questions, prospects. Radiother Oncol 2000;55(1):1-9. Perry MC, Herndon JE 3rd, Eaton WL, Green MR. Thoracic radiation therapy added to chemotherapy for small-cell lung cancer: an update of Cancer and Leukemia Group B Study 8083. J Clin Oncol 1998;16(7):2466-7.

280

281

282

283

284

285 286

287

288

289

290

291

292 293 294 295 296

297

298

299

Takada M, Fukuoka M, Kawahara M, Sugiura T, Yokoyama A, Yokota S, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limitedstage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol 2002;20(14):3054-60. Murray N, Coy P, Pater JL, Hodson I, Arnold A, Zee BC, et al. Importance of timing for thoracic irradiation in the combined modality treatment of limited-stage small-cell lung cancer. The National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1993;11(2):336-44. Work E, Nielsen OS, Bentzen SM, Fode K, Palshof T. Randomized study of initial versus late chest irradiation combined with chemotherapy in limited-stage small-cell lung cancer. Aarhus Lung Cancer Group. J Clin Oncol 1997;15(9):3030-7. Jeremic B, Shibamoto Y, Acimovic L, Milisavljevic S. Initial versus delayed accelerated hyperfractionated radiation therapy and concurrent chemotherapy in limited-stage small cell lung cancer: a randomized study. J Clin Oncol 1997;15(3):893-900. Gregor A, Drings P, Burghouts J, Postmus PE, Morgan D, Sahmoud T, et al. Randomized trial of alternating versus sequential radiotherapy/ chemotherapy in limited-disease patients with small-cell lung cancer: a European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group Study. J Clin Oncol 1997;15(8):2840-9. James L, Spiro S, ODonnell KM, Rudd RM, Clarke P, Trask C, et al. A randomised study of timing of thoracic irradiation in small cell lung cancer (SCLC) - study 8 [abstract]. Lung Cancer 2003;41 Suppl 2:S23. Bonner JA, Sloan JA, Shanahan TG, Brooks BJ, Marks RS, Krook JE, et al. Phase III comparison of twice-daily split-course irradiation versus once-daily irradiation for patients with limited stage small-cell lung carcinoma. J Clin Oncol 1999;17(9):2681-91. Turrisi AT 3rd, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, et al. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 1999;340(4):265-71. Arriagada R, Le Chevalier T, Riviere A, Chomy P, Monnet I, Bardet E, et al. Patterns of failure after prophylactic cranial irradiation in smallcell lung cancer: analysis of 505 randomized patients. Ann Oncol 2002;13(5):748-54. Kotalik J, Yu E, Markman BR, Evans WK; Cancer Ontario Practice Guidelines Initiative Lung Cancer Disease Site Group. Practice guideline on prophylactic cranial irradiation in small-cell lung cancer. Int J Radiat Oncol Biol Phys 2001;50(2):309-16. Auperin A, Arriagada R, Pignon JP, Le Pechoux C, Gregor A, Stephens RJ, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med 1999;341(7):476-84. Diaz-Jimenez JP, Martinez-Ballarin JE, Llunell A, Farrero E, Rodriguez A, Castro MJ. Efficacy and safety of photodynamic therapy versus Nd-YAG laser resection in NSCLC with airway obstruction. Eur Respir J 1999;14(4):800-5. Boxem T, Muller M, Venmans B, Postmus P, Sutedja T. Nd-YAG laser vs bronchoscopic electrocautery for palliation of symptomatic airway obstruction: a cost-effectiveness study. Chest 1999;116(4):1108-12. Morris CD, Budde JM, Godette KD, Kerwin TL, Miller JI Jr. Palliative management of malignant airway obstruction. Ann Thorac Surg 2002;74(6):1928-33. Maiwand MO. The role of cryosurgery in palliation of tracheobronchial carcinoma. Eur J Cardiothorac Surg 1999;15(6):764-8. Antypas G, Baltayiannis N, Bolanos N, Anagnostopoulos D, Tsourelis L, Kavoukas J. Nd: YAG laser in the palliative treatment of tracheal diseases. Journal of B.U.On. 2000;5(3):293-7. Moghissi K, Bond MG, Sambrook RJ, Stephens RJ, Hopwood P, Girling DJ. Treatment of endotracheal or endobronchial obstruction by nonsmall cell lung cancer: lack of patients in an MRC randomized trial leaves key questions unanswered. Medical Research Council Lung Cancer Working Party. Clin Oncol (R Coll Radiol) 1999;11(3):179-83. Stout R, Barber P, Burt P, Hopwood P, Swindell R, Hodgetts J, et al. Clinical and quality of life outcomes in the first United Kingdom randomized trial of endobronchial brachytherapy (intraluminal radiotherapy) vs. external beam radiotherapy in the palliative treatment of inoperable non-small cell lung cancer. Radiother Oncol 2000;56(3):323-7. Langendijk H, de Jong J, Tjwa M, Muller M, ten Velde G, Aaronson N, et al. External irradiation versus external irradiation plus endobronchial brachytherapy in inoperable non-small cell lung cancer: a prospective randomized study. Radiother Oncol 2001;58(3):257-68. Chella A, Ambrogi MC, Ribechini A, Mussi A, Fabrini MG, Silvano G, et al. Combined Nd-YAG laser/HDR brachytherapy versus NdYAG laser only in malignant central airway involvement: a prospective randomized study. Lung Cancer 2000;27(3):169-75.

62

REFERENCES

300

301

302

303

304

305

306 307

308 309 310

311

312 313

314

315

316

317 318

319 320

321

Maziak DE, Markman BR, MacKay JA, Evans WK; Cancer Care Ontario Practice Guidelines Initiative Lung Cancer Disease Site Group. Photodynamic therapy in nonsmall cell lung cancer: a systematic review. Ann Thorac Surg 2004;77(4):1484-91. Rowell NP, Gleeson FV. Steroids, radiotherapy, chemotherapy and stents for superior vena caval obstruction in carcinoma of the bronchus (Cochrane Review). In: The Cochrane Library, Issue 2, 2003. Oxford: Update Software. National Institute for Clinical Excellence. Guidance on cancer services: improving supportive and palliative care for adults with cancer: the manual. London: NICE; 2004. p. 148-154. [cited 17 Nov 2004]. Available from url: http://www.nice.org.uk/pdf/csgspmanual.pdf Fellowes D, Barnes K, Wilkinson S. Aromatherapy and massage for symptom relief in patients with cancer (Cochrane Review). In: The Cochrane Library, Issue 3, 2004. Chichester, UK: John Wiley & Sons, Ltd. Scottish Executive Health Department. Scottish national audit of the prevalence of pain in patients with active cancers recognised to cause pain. Edinburgh; Cancer in Scotland; 2003. [cited 6 Mar 2003]. Available from url: http://www.show.scot.nhs.uk/sehd/ cancerinscotland Expert Advisory Group on Cancer. A Policy Framework for Commissioning Cancer Services: a report to the chief medical officers of England and Wales: guidance for purchasers and providers of cancer services (The Calman-Hine Report). London: Department of Health, 1995. [cited 17 Nov 2004]. Available from url: http://www.dh.gov.uk/ assetRoot/04/01/43/66/04014366.pdf Higginson IJ, Costantini M. Communication in end-of-life cancer care: a comparison of team assessments in three European countries. J Clin Oncol 2002;20(17):3674-82. Scottish Executive. Introduction of managed clinical networks within the NHS in Scotland. Edinburgh: The Executive; 1999. (NHS MEL(1999)10). [cited 17 Nov 2004]. Available from url: http:// www.show.scot.nhs.uk/sehd/mels/1999_10.htm Moore S, National Lung Cancer Forum for Nurses. A survey of nurse specialists working with patients with lung cancer. Eur J Oncol Nurs 2002;6(3):169-75. Wright EP, Kiely MA, Lynch P, Cull A, Selby PJ. Social problems in oncology. Br J Cancer 2002;87(10):1099-104. Allied Health Professions Palliative Care Project Team. Allied health professional services for cancer related palliative care: an assessment of need. Glasgow: The Team; 2004. [cited 17 Nov 2004]. Available from url: http://www.palliativecareglasgow.info/pages/ahpproj.asp Moore S, Corner J, Haviland J, Wells M, Salmon E, Normand C, et al. Nurse led follow up and conventional medical follow up in management of patients with lung cancer: randomised trial. BMJ 2002;325(7373):1145-51. Chang CH, Cella D, Masters GA, Laliberte N, OBrien P, Peterman A, et al. Real-time clinical application of quality-of-life assessment in advanced lung cancer. Clin Lung Cancer 2002:4(2);104-9. Newell S, Sanson-Fisher RW, Girgis A, Bonaventura A. How well do medical oncologists perceptions reflect their patients reported physical and psychosocial problems? Data from a survey of five oncologists. Cancer 1998;83(8):1640-51. British Thoracic Society Standards of Care Committee Lung Cancer Working Party. BTS recommendations to respiratory physicians for organising the care of patients with lung cancer. Thorax 1998;53 Suppl 1: S1-8. Fellowes D, Wilkinson S, Moore P. Communication skills training for health care professionals working with cancer patients, their families and/or carers (Cochrane Review). In: The Cochrane Library, Issue 3, 2003. Oxford: Update Software. Bruera E, Pituskin E, Calder K, Neumann CM, Hanson J. The addition of an audiocassette recording of a consultation to written recommendations for patients with advanced cancer: A randomized, controlled trial. Cancer 1999;86(11):2420-5. Hinton J. An assessment of open communication between people with terminal cancer, caring relatives, and others during home care. J Palliat Care 1998;14(3):15-23. Smeenk FW, de Witte LP, van Haastregt JC, Schipper RM, Biezemans HP, Crebolder HF. Transmural care. A new approach in the care for terminal cancer patients: its effects on re-hospitalization and quality of life. Patient Educ Couns 1998;35(3):189-99. National Council for Hospice and Specialist Palliative Care Services. Definitions of Supportive and Palliative Care. London: The Council; 2002. (Briefing paper 11). Clinical Standards Board for Scotland. Clinical standards: specialist palliative care. Revised ed. Edinburgh: The Board; 2002. [cited 17 Nov 2004]. Available from url: http://www.clinicalstandards.org/pdf/ finalstand/SPC.pdf General Medical Council. Tomorrows doctors. Recommendations on undergraduate medical education. London: The Council; 2003. [cited 17 Nov 2004]. Available from url: http://www.gmc-uk.org/ med_ed/tomdoc.htm

322 323

324 325 326 327 328

329 330 331 332

333 334

335 336

337 338 339

340

341

342 343 344

345

Cooley, M. E. Symptoms in adults with lung cancer. A systematic research review. J Pain Symptom Manage 2000;19(2):137-153. Higginson IJ, Finlay IG, Goodwin DM, Hood K, Edwards AG, Cook A, et al. Is there evidence that palliative care teams alter end-of-life experiences of patients and their caregivers?. J Pain Symptom Manage 2003;25(2):150-68. Benor DE, Delbar V, Krulik T. Measuring impact of nursing intervention on cancer patients ability to control symptoms. Cancer Nurs 1998;21(5):320-34. Bredin M, Corner J, Krishnasamy M, Plant H, Bailey C, AHern R. Multicentre randomised controlled trial of nursing intervention for breathlessness in patients with lung cancer. BMJ 1999;318(7188):901-4. Edmonds P, Higginson I, Altmann D, Sen-Gupta G, McDonnell M. Is the presence of dyspnea a risk factor for morbidity in cancer patients? J Pain Symptom Manage 2000;19(1):15-22. Sarna L. Effectiveness of structured nursing assessment of symptom distress in advanced lung cancer. Oncol Nurs Forum 1998;25(6):1041-8. Lecouturier J, Jacoby A, Bradshaw C, Lovel T, Eccles M. Lay carers satisfaction with community palliative care: results of a postal survey. South Tyneside MAAG Palliative Care Study Group. Palliat Med 1999;13(4):275-83. Hearn J, Higginson IJ. Do specialist palliative care teams improve outcomes for cancer patients? A systematic literature review. Palliat Med 1998;12(5):317-32. Cooley ME, Short TH, Moriarty HJ. Patterns of symptom distress in adults receiving treatment for lung cancer. J Palliat Care 2002;18(3):150-9. Portenoy RK, Thaler HT, Kornblith AB, Lepore JM, Friedlander-Klar H, Coyle N, et al. Symptom prevalence, characteristics and distress in a cancer population. Qual Life Res 1994;3(3):183-9. Australian Cancer Network. Clinical practice guidelines for the prevention, diagnosis and management of lung cancer. Sydney: The Network; 2004. [cited 25 Nov 2004]. Available from url: http:// www.nhmrc.gov.au/publications/pdf/cp97.pdf South East Scotland Cancer Network (SCAN). [cited 25 Nov 2003]. Available from url: http://www.scan.scot.nhs.uk/ Scottish Intercollegiate Guidelines Network (SIGN). Control of pain in patients with cancer. Edinburgh: SIGN; 2000. (SIGN publication no. 44). [cited 17 Nov 2004]. Available from url: http:// www.sign.ac.uk/guidelines/fulltext/44/index.html Borthwick D, Knowles G, McNamara, ODea, Stroner P. Assessing fatigue and self-care strategies in patients receiving radiotherapy for non-small cell lung cancer. Eur J Oncol Nurs 2003;7(4):231-41. Stone P, Richardson A, Ream E, Smith G, Kerr DJ, Kearney N. Cancerrelated fatigue: inevitable, unimportant and untreatable? Results of a multi-centre patient survey. Cancer Fatigue Forum. Ann Oncol 2000;11(8):971-5. Portenoy RK, Itri LM. Cancer-related fatigue: guidelines for evaluation and management. Oncologist 1999;4(1):1-10. Zabora J, BrintzenhofeSzoc K, Curbow B, Hooker C, Piantadosi S. The prevalence of psychological distress by cancer site. Psychooncology 2001;10(1):19-28. Sol I, Thompson E, Subirana M, Lpez C, Pascual A. Non-invasive interventions for improving well-being and quality of life in patients with lung cancer (Cochrane Review). In: The Cochrane Library, Issue 4, 2004. Chichester, UK: John Wiley & Sons, Ltd. Hately J, Laurence V, Scott A, Baker R, Thomas P. Breathlessness clinics within specialist palliative care settings can imrove the quality of life and functional capacity of patients with lung cancer. Palliat Med 2003;17(5):410-7. Chute CG, Greenberg ER, Baron J, Korson R, Baker J, Yates J. Presenting conditions of 1539 population-based lung cancer patients by cell type and stage in New Hampshire and Vermont. Cancer 1985;56(8):2107-11. British Dietetic Association Scottish Forum. Dietitians delivering change. [cited 17 Nov 2004]. Available from url: http:// www.bda.uk.com/Downloads/dietitiansdeliveringchange.pdf Mountain CF. A new international staging system for lung cancer. Chest 1986;89(4 Suppl):225S-33S. Detterbeck FC, Jones DR, Alden Parker L Jr. Intrathoracic staging. In: Detterbeck FC, Rivera MP, Socinski MA, Rosenman JG, editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders; 2001. p. 73-93. Bradbury I, Bonell E, Boynton J, Cummins E, Facey K, Iqbal K, et al. Positron emission tomography (PET) imaging in cancer management. Glasgow: Health Technology Board for Scotland; 2002. (Health Technology Assessment Report 2). [cited 17 Nov 2004]. Available from url: http://docs.scottishmedicines.org/docs/pdf

63

80

MANAGEMENT OF PATIENTS WITH LUNG CANCER

Scottish Intercollegiate Guidelines Network Royal College of Physicians 9 Queen Street, Edinburgh EH2 1JQ www.sign.ac.uk