Frontiers in Lung Cancer

This chapter comprises of 2 sections.

Section 1 (By Keyvan Moghissi): This section gives an account of the relevant anatomy of the thorax, thoracic cavity and the bronchopulmonary segments. In addition, it also provides a brief reference to the bronchoscopic morphology.

Section 2 (By Peter Tcherveniakov): This section describes thoracoscopic anatomy as viewed on the monitor used in the Visual Assisted Thoracoscopic Surgery (VATS) system.

Lung cancer is the worldwide leading cause of cancer-related deaths [1]. At a fundamental level, understanding the important molecular and cellular events that lead to lung cancer is critical for developing treatments to reverse this statistic. This chapter reviews the progress and limitations of our current understanding of lung cancer. It describes the initiation and progression of lung cancer from carcinogeninduced mutation of DNA to tumour formation and metastases.

Lung Cancer is now the commonest cause of premature death in our industrial conurbations. It presents late and tends to be investigated on prolonged pathways, often with a stage shift along the way. Survival rates are closely related to stage at diagnosis, leading to a number of approaches to early diagnosis, most of which have not been validated as population screening tools. Most early screening trials used imaging, sometimes supplemented by sputum cytology, and achieved improved survival but did not reduce overall mortality, a rigorous benchmark that avoids the pitfalls of lead-time bias and overdiagnosis. The landmark National Lung Cancer Screening Study (NLST) a targeted screening study now nearly a decade old, achieved a 20% mortality improvement but this did not lead to the clinical implementation of screening programs in Europe or in the UK, where there is still an unaccountable scepticism, despite recent confirmatory evidence that the targeted screening of highrisk populations can save many lives. The Manchester implementation pilot used community-based health-checks and CT scans to access a very deprived population, detecting one lung cancer for every 23 scans, most at early stage and nearly all suitable for curative-intent treatments, with the almost complete avoidance of inappropriate interventions for non-malignant disease. Substantial numbers of non-malignant respiratory and cardiac conditions were also identified and referred for treatment. The programme is now being rolled out across the Greater Manchester conurbation and has been incorporated into the NHS Long-term Plan. It is to be hoped that the implementation of targeted screening, together with a step-change in the pace of diagnostic and treatment pathways, will start to make a real difference, assisted by a reinvigoration of evidence-based smoking cessation programmes for this uniquely preventable disease.

(Section 1) In this section, the current practice of imaging is described. Attention has been focused on the role of radiology in the staging of lung cancer and the pulmonary nodule. New methods, such as the potential use of Nano-technology in medical imaging, are briefly referred here.

(Section 2) In this short section, the physics of fluorescence is briefly described. The application of florescence imaging in clinical practice of lung cancer are presented. Autofluorescence imaging for endobronchial cancer which is now an established method and is described in some detail.

Lung cancer is a common neoplasm. Diagnosis of lung cancer at an early stage is associated with the best prognosis. Therefore, early recognition of symptoms through increased awareness, systematic investigations and rapid diagnosis of lung cancer is of importance. Patients investigated for lung cancer would require a chest radiograph, computed tomography and Positron Emission Tomography. Imaging can provide a non-invasive approach to staging lung cancer. However, in a number of patients, more invasive methods may be required for accurate staging. Endobronchial ultrasound (EBUS) and Endoscopic ultrasound are techniques, which in conjunction with mediastinoscopy, form important techniques for mediastinal lymph node staging as well as sampling for histological diagnosis. Patients with more peripheral lesions may need biopsy using CT guidance or newer approaches such as radial EBUS or navigational bronchoscopy. Many patients with lung cancer would also require complex physiological fitness assessment, including lung function and exercise testing. A proportion of patients with lung cancer may develop pleural effusion, which would require careful assessment based on the use of systematic diagnostic protocols and understanding of the best interventional and therapeutic strategies. Therefore, investigations and management of patients with lung cancer have become complex and should be undertaken through the multidisciplinary team approach.

This chapter consists of two sections. In the first section, bronchoscopy and its contribution in diagnosis of central lung cancer are discussed. Particular emphasis is made on autofluorescence bronchoscopy and endobronchial sonography. Therapeutic bronchoscopy discusses the various methods with particular emphasis on the role of Nd Yag laser and Photodynamic Therapy.

The application of VATS (Video-Assisted Thoracic Surgery) for a variety of thoracic surgical procedures has increased the technical complexity of these procedures, especially in long-sparing oncological resections. Pre-operative assessment of procedural feasibility is imperative for these new techniques and approaches, making imaging modalities increasingly important for the diagnosis and treatment of lung cancer. Three-dimensional (3D) reconstructions of these two-dimensional images can aid in a better visuospatial understanding of thoracic anatomy. Using this method, tumors can be localized precisely with respect to their anatomical borders, possibly leading to an increase in the use of sublobar resections. Furthermore, deviant vascular anatomy can be detected pre-operatively, potentially facilitating the procedures. In order to create a tangible model, rapid prototyping (more commonly known as 3D printing) can facilitate a better understanding of pulmonary vascular anatomy and anatomical relations to the tumor. Additionally, these models can be used to improve patient counseling and result in higher patient knowledge scores. We foresee these techniques to evolve rapidly in the nearby future, with the introduction of whole-slide scanning, 3D scanning and bioprinting. For diagnosis and treatment of thoracic disease, these methods will undoubtedly prove useful for many processes.

In standard and conventional surgery of the lung, there are a variety of incisions allowing access to the chest cavity. The common feature to all is to place the incision in a way which allows better surgical treatment for the lesion. The commonest approach is postero-lateral thoracotomy through the fifth inter space, with the patient placed on the operating table in an appropriate lateral position. This allows exploration of the lungs as well as the mediastinum. A prone position/face down also allows good exploration of the lungs and the postero mediastinum. All the anterior and anterolateral incisions allow limited exploration of the lungs and arterial mediastinum. In this chapter, the variety of incisions for the approach to the lung at different angles have been briefly described and illustrated. Important advantages of standard thoracotomy incisions and approaches to the thoracic cavity for lung cancer operations are: Firstly, ample visual inspection with/without optical technology assistance. Secondly, to enable the surgeon to use the palpation method, which is an important attribute not endowed by the minimal access VATS methods.

In this chapter, the principles of standard techniques of pulmonary resection are described. The chapter comprises of a number of sections:

In the first section, the focus of attention has been the issues related to the pulmonary arteries and veins and their safe and secure handling.

1. In the second, reference is made to some aspects of bronchoplastic operation.

2. Surgery for lung cancer affecting the lower tracheal bifurcation (carina and main stem bronchi) is dealt with in a separate section.

3. A separate section is devoted to lung cancer involving the lung, carina and also portion of the lateral wall of the trachea, which needs carinal resection or tracheal Sleeve Pneumonectomy (TSP).

4. Pancoast tumour/Superior Sulcus tumour is also a separate section.

5. Finally, lung cancer invading the chest wall is dealt with separately

6. The reason for targeting the above topics in lung cancer surgery in separate sections is that each of these requires separate expertise and their surgical treatment needs special consideration and expertise.

(Section 1) Video-Assisted Thoracoscopic Surgery has evolved significantly over the last twenty years and is increasingly becoming the preferred method for lung resection. It has and continues to be refined and improved with an increasing body of evidence to support it over open surgery.

(Section 2) In this chapter, the author defines and briefly describes Mini-Uniportal VATS (Uni-VATS).

The introduction of Video-assisted thoracic surgery (VATS) via a short (Mini) Single skin incision and a port (trocar) provides an alternative to already established access to the thoracic cavity and a novel surgical approach to pulmonary operations.

There has been a debate about the definition of “Uni- VATS” and how short in extent characterizes the adjective “mini”? Many surgeons define “uniportal” as a VATS operation performed through an incision of 4-8 cm, others believe that when the skin exceeds 2 cm the name should be mini-thoracotomy. We define Uni-VATS an operation in which the operation in the chest is performed when a port (trocar) is introduced via a minimal skin incision of 2-3 cm, whereas when a larger incision is made, the operation should be called single–incision-video assisted-mini thoracotomy.

Uni- VATS for lung cancer has been successfully used to perform a range of pulmonary operations from wedge excision to pneumonectomy and more sophisticated procedures. Double lumen tube and controlled ventilation is the preferred method to carry out Uni-VATS, but more recently, the feasibility of non-intubated normal breathing method has also been explored in selected patients undergoing major lung resection. Although the first uniportal lobectomy was performed almost 10 years ago, there have only been a few retrospective comparative studies and only one prospective randomized trial between single-port and multi-port lobectomy.

With the advance in technology and imaging devices matched by experience and surgical expertise, one may speculate that within a decade uniportal computer-assisted, instrument-controlled surgery will open up a new horizon, allowing Uni- VATS to become a routine practice for surgical treatment of lung cancer.

The aim of this chapter is to describe the role of radiotherapy in the management of lung carcinoma. The introduction covers general information about radiotherapy followed by a more detailed description of the basic principles of nuclear physics and radiotherapy treatment planning and delivery showing the influence of recent rapid progress in technology on the efficacy of this treatment modality. Following the introduction of technical aspects of radiation oncology, the role of radiotherapy, emphasising novel techniques of stereotactic ablative body radiotherapy, is described as the definitive treatment in early non-small cell lung carcinoma. The next part of the chapter presents the current role of radiotherapy with curative intent in locally advanced inoperable non-small cell lung cancer in combination with chemotherapy and immunotherapy. The use of radiotherapy in operable locally advanced lung carcinoma is also analysed to complete all clinical indications for this clinical entity. The role of radiotherapy in the management of small cell lung carcinoma is subsequently presented where consolidation chest radiotherapy and prophylactic cranial irradiation in combination with standard chemotherapy and its input to overall outcome are analysed for both limited and extensive disease. The basic principles of standard palliative radiotherapy are then presented with its input in the management of incurable stage of lung carcinoma in addition to palliative systemic treatment and the best supportive care. A brief description of new stereotactic techniques in the palliative setting is also presented. The chapter concludes with the management of radiotherapy related toxicity presenting most frequently observed side effects and their treatment.

The aim of this chapter is to describe the role of systemic anti-cancer therapy in the management of lung cancer. The introduction describes the different sub-types of lung cancer as this is highly pertinent to the treatment options available. We move on to discuss the main sub-types of systemic anti-cancer therapy used for lung cancer and their mechanisms of action; specifically regarding cytotoxic chemotherapy, targeted therapy including tyrosine kinase inhibitors, monoclonal antibodies and immunotherapy, namely checkpoint inhibitors. From here we move on to discuss adjuvant systemic anti-cancer therapy following surgical resection for both small cell lung cancer and non-small cell lung cancer. Following this, we move on to describe systemic anti-cancer therapy for incurable lung cancer starting with the recent historical perspective and the remarkable changes and developments that have occurred in this field over the last ten years. We discuss systemic therapy for small cell lung cancer and non-small cell lung cancer, focussing on non-mutated adenocarcinoma, EGFR and ALK mutant adenocarcinoma and squamous cell lung cancer. In conclusion, we describe future perspectives and the importance of a joined-up approach to diagnosis, investigation and management to improve outcomes for patients with lung cancer.

Patients with lung cancer are often diagnosed late and the disease in such cases is often advanced. Common symptoms include breathlessness, haemoptysis and pain and these can have an impact on their quality of life. Patients might have challenging palliative and supportive care needs and in order to address these, palliative care should be offered earlier in the disease trajectory. An interdisciplinary approach, working jointly with the oncologists, respiratory teams and palliative care teams provide a holistic, comprehensive assessment in response to their changing needs. Advance care planning is best to be started early on especially in patients with a prognosis of about a year, in a sensitive manner, in order to involve the patient in discussion about their future wishes and priorities for care. It is important to recognise dying to be able to communicate with the patient and their family, recognise any symptoms and manage them proactively and achieve preferred place of care and death; a patient-centred approach is needed.

Laser application for lung cancer was introduced early in the 1980s to remove malignant obstructive lesion of the lower trachea and main bronchi. The main indication was in patients with inoperable central lung cancer. Intraoperative use of Thermal laser began later. In the early and mid-1980s, Photodynamic Therapy (PDT) became available.

In this chapter, the laser and laser light physics are briefly described prior to their applications and indications in lung cancer. The Nd;YAG laser, which is the most commonly employed thermal laser and its effects on lung tissue, is described, followed by its brief indication in the clinical practice of lung cancer.

The principle and mechanisms of PDT in destroying cancer tissues have also been discussed in this chapter. PDT indications in a variety of lung cancer are also discussed to some extent.

An important issue in the treatment of malignant tumours is concerned with the completeness of the resection/or destruction destruction of cancer and precancerous lesions, without which no curative intent can be contemplated. In lung cancer, be it central or peripheral, the pre-cancerous lesions, usually at the margin of cancer itself, will have to be treated.

Image-guided lung cancer surgery and/or therapy is a method in which intraoperative real-time and updated images are provided to the operator, to allow him to access not only the tumour but also provide him with the outline of pre-cancerous lesions. As such, image-guided surgery and therapy provide navigational tools and real insight to perform complete treatment of cancer.

In this chapter, the various methods to identify small lesions within the wide field of the lung tissue are referred to and some of the methods which are currently under translational studies are explored.

In this chapter, we highlight the evolution of pathways for patients with suspected undiagnosed lung cancer from presentation to treatment in the 20th Century. We focus on the pathway which is currently in progress in the UK as well as some of the developed countries. We discuss the pros and cons of the system and we then propose a concept of a Lung Cancer Unit within Primary Care, City/Region and a Supra Regional Centre for lung cancer diagnosis and treatment.