Oncology & Respiratory >
Lung Cancer

“Uncontrolled growth of abnormal cells in one or both lungs

  • Very common, more common in men but women catching up
  • Survival rates are poor – USA 15%, Europe 10%, Developing 8.9%
Risk Factors
  • Combination of asbestos & smoking is multiplicative, not addictive
  • Smoking (80%):
    • 16% of heavy smokers develop lung cancer
    • 20% increase in risk for passive smoking spouses
    • Decrease smoking 50% reduces risk carcinoma 27% – Never too late to give up
  • Other:
    • ASBESTOS exposure – a lot in SOTON
    • HIV increased risk
    • Cooking oil vapour
    • TB, Papilloma virus, microsporum canis
    • Nickel
    • Coke ovens
  • Arsenic
  • Chernobyl repair workers
  • Insecticides
  • Decreased physical activity
  • Air pollution 1-2% increased risk
Types
TypeDifferences in presentationDifferences in metastatic spread & response to therapy
Non-small-cell carcinomaEpithelially derived tumours (~75%)
o   Adenocarcinoma – most common
o   Squamous cell
o Large cell
– Less often metastatic
– Less responsive to chemo
– More responsive to surgery
Small-cell carcinomaDerived from neuroendocrine cells
o Less common
o 13%
– Most often metastatic
– High initial response to chemo
– NO Surgery
Others8%
Pathophysiology
  • Chemicals in tobacco smoke can damage DNA & if mutations affect genes that are involved in cell proliferation or cell death → neoplasm produced
    • KRAS (signal transduction)
    • TP53 (cell cycle & apoptosis regulation)
    • BCL-2 (apoptosis inhibition
  1. Metaplasia:
    • Adaptive response to irritation
    • Bronchial squamous epithelia → stratified squamous epithelia (more resistant to smoke)
    • Not neoplastic but increased risk
  1. Dysplasia – intraepithelial neoplasia:
    • An intermediate stage of abnormal growth
    • Neoplasia confined to where tissue should be attached to BM
    • Now no longer responding to normal limiters on cell growth
    • It is a benign stage but will develop into the malignant stage
    • Can be reversible, less likely to happen in later stages
  1. Carcinoma:
    • Able to move into underlying tissues
    • Type of lung carcinoma usually reflects the tissue in which it arises
Clinical Presentation

Very varied in how it presents not always respiratory symptoms

  • Local in Chest:
    • Cough – chronic (>6wks) / change in nature in a smoker
    • Haemoptysis – Not that common and can be other things but get CXR in a smoker
    • Breathlessness / dyspnoea
    • Chest wall pain – tumour invades something with somatic nerve supply (pleura, bones, muscles)
    • Hoarse voice – Left recurrent laryngeal nerve palsy
    • SVC obstruction – facial swelling especially in the morning
    • Arm weakness, pain, numbness – Superior sulcus tumours (Pancoast tumour) invades the brachial plexus
    • Horner’s syndrome – a combination of symptoms that arise when the sympathetic trunk is damaged
      • Miosis, Partial ptosis, Apparent anhidrosis, With or without enophthalmos
  • Constitutional:
    • Anorexia
    • Weight loss
    • Fevers / sweats
  • Metastases:
    • Majority of patients present with metastases which is the reason for high mortality rate:
      • Lymph nodes
      • Brain
      • Bone
      • Liver
      • Adrenal Glands
      • Skin
  • Paraneoplastic syndromes:
    • Syndromes where there are non-metastatic systemic effects that accompany the malignant disease
    • Occur as a result of substances produced by tumour and occurring remotely from the tumour itself
    • Not very common & patients present in bizarre ways
    • Neurological paraneoplastic syndromes → caused by auto-antibodies attacking
      • Cerebellar → clumsiness, abnormal gait, failure to articulate speech
      • Myasthenic like syndrome (Eaton Lambert)
      • Peripheral neuropathy
      • Limbic encephalitis
  • Ectopic hormone production:
    • Parathormone related peptide:
      • Controls Calcium
      • Presentation → Hypercalcaemia (MEDICAL EMERGENCY)
      • Symptoms can be treated – dehydration/constipation
    • Syndrome of inappropriate ADH (SIADH):
      • Produced in posterior pituitary and controls plasma osmolality
      • Presentation → dilute plasma & hyponatraemia (low sodium)
      • Lung cancer is not the only cause of inappropriate
    • ACTH:
      • Controls adrenal gland producing cortisol
      • Presentation → biochemical abnormality with hypokalaemic alkalosis
Investigations
  • Staging:
    • To establish suitability for radical (intent to cure) or palliative treatment → CT / PET
    • Patients usually present with stage III or IV
    • Grade – how closely cancer resembles normal tissue
      • Well-differentiated = closely resemble normal tissue → better prognosis
      • Poorly differentiated = do not resemble normal tissue → grow quickly & aggressively
    • Stage – the anatomical spread of malignant neoplasms & important in prognosis & treatment
  • Imaging:
    • Chest x-ray – diagnosis
    • Computed Axial Tomography (CT) – for the precision of location/spread & staging
    • Bronchoscopy – view & biopsy central lesions
    • Mediastinoscopy – rarely used
    • Thoracoscopy – Good for peripheral cancer rather than central
    • Endobronchial ultrasound technology – the technique of choice for sampling nodes
    • PET scan – Positron Emission Tomography
      • Tells you about the metabolic activity so can see whether benign or malignant
      • Done in conjunction with a CT
  • Special:
    • Histology – Establish whether non-small cell or small cell
Management
  • Just in the lung (stage 1):
    • Surgery (if fit) → wedge resection, segmentectomy, lobectomy, pneumonectomy
    • Ablation
    • Stereotactic radiotherapy
  • Localised to lung & 1/2 Lymph Nodes (stage 2/3):
    • Depends if lymph nodes are in hilum (surgery) or mediastinum (radiotherapy)
    • Surgery +/- chemotherapy
    • Radiotherapy +/- chemotherapy
  • Metastatic (stage 4):
    • Chemotherapy – improve QOL, prolongs life by a short amount (few months avr)
    • Tyrosine kinase inhibitors (Gefitinib) – Blocks the downstream effect of mutated EGFR
    • Immunotherapy (Nivolumab) – Drugs wake up the immune system to the cancer
    • Palliative radiotherapy – an advanced disease in pts with poor performance status
    • Clinical trials

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