Lung Cancer

Lung cancer in Australia

• Lung cancer is the fourth most commonly diagnosed invasive cancer in Australia. Around 6000 men and 3800 women were diagnosed with lung cancer in Australia in 2007.
• Lung cancer is the leading cause of cancer death, for both non-Indigenous and Indigenous men and women.
• Only 14% of those diagnosed with lung cancer survive five years after diagnosis.
• The incidence of lung cancer is strongly related to age, with over 80% of new lung cancers diagnosed in people aged 60 years and older.
• While tobacco smoking is the largest single cause of lung cancer, people who have never smoked may also be diagnosed with lung cancer.
• About 90% of lung cancer in males and 65% in females is estimated to be a result of
• tobacco smoking.
• Indigenous people are about 1.7 times as likely to be diagnosed with lung cancer as non-Indigenous people. This difference may be partly explained by higher rates of smoking by Indigenous adults

Causes

• SMOKING
• Exposure to asbestos, synergistic effect with tobacco smoke
• Exposure to radon gas, arsenates, nickel, coal gas, chromates and silica
• Chronic airflow obstruction and pulmonary fibrosis
  • are associated with increased risk of lung cancer independent of tobacco smoke or environmental carcinogens.
• Familial tendency/susceptibility to tobacco-induced TP53 mutations and lung cancer also identified.
• Familial Lung Cancer
  • More important factor in the development of lung cancer in women.

Types

• Small Cell Ca:  (20-25%)-SCLC
  • Usually disseminated by the time of diagnosis 
  • strong relationship b/w small cell and cigarette smoking; 
  • only 1% occur in non smokers 
  • often hilar/central
  • Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is common in small cell lung cancer
  • Untreated extensive small cell lung cancer is rapidly progressive and has a median survival of 6 weeks.
  • distinctive epithelial cell type: small, little cytoplasm, round/oval lymphocyte-like cell (but twice the size of a lymphocyte)-Oat Cell
  • Spread:
    • haematogenous spread 
    • most aggressive type of lung cancer 🡪 metastasises widely.
    • to liver, bones, bone marrow, brain, adrenals, or elsewhere
  • Management:
    • Since they are so aggressive and metastasise so widely, they are virtually incurable by surgical removal ∴ NEED CHEMOTHERAPY.

• Non Small Cell :   (75-80%)-NSCLC
  • Adenocarcinoma:
    • Acinar,Papilary, Bronchioaleolar, mucus secreting
    • Females>males, and non-smokers(may be due to scarring)
    • usually more peripheral, smaller and well differentiated
    • Spread: grow slower than squamous cell
  • Squamous Cell:
    • high α with cigarette smoking
    • arise in larger, more central bronchi
    • Spread tends to be local
    • Spread:
      • Tends to be LOCAL. 
      • Metastasises LATER than small cell, but rate of growth at origin relatively fast.
    • Management:
      • amenable to surgical excision if there is no metastatic or pleural spread.  If inoperable, radical radiotherapy is an option.
  • Large Cell:
    • an “anaplastic carcinoma” (– Giant Cell & Clear Cell)
    • polygonal cells with vesicular nuclei
    • probably are an unrecognisable, very undifferentiated form of squamous cell and adenocarcinoma

• Other lung tumours
  • Bronchial adenoma: Rare, slow-growing tumour. 90% are carcinoid tumours; 10% are cylindromas. Treatment: surgery. 
  • Hamartoma: Rare, benign tumour. CT scan: lobulated mass with flecks of calcification. Often excised to exclude malignancy. 
  • Mesothelioma: a tumor of the mesothelium(pleural or parital), that can be benign (localized) or malignant (diffusely spread), and that is most commonly caused by the ingestion of asbestos particles.

• Coin lesions of the Lung
  • Malignancy (1° or 2°)
  • Abscesses
  • Granuloma(eg TB, sarcoidosis )
  • Carcinoid tumour
  • Pulmonary hamartoma
  • Arteriovenous malformation
  • Encysted effusion (fluid, blood, pus)
  • Cyst,   Foreign body
  • Skin tumour (eg seborrhoeic wart)

Methods of spread

• Grows locally 🡪 invades vascular/lymphatic channels
• Spread to local lymph nodes
  • N1: bronchopulmonary lymph
  • N2: Mediastinal – Ipslat N2 , CL :N3
• Wide spread to lymphatic thoracic duct & blood
• Distant Mets

• adrenals
• liver
• bone
• brain

Clinical:

1. Insidious, usually 7 month history of sx (in >60 year olds)
2. Many patients have no specific signs
   1. In some, they may be found to have lung cancer as an incidental finding on CXR performed for another reason.
3. History of unresolved pneumonia
   1.  >60 year olds repeat Chest Xray 6 weeks after resolution of a pneumonia
4. Major presenting compaints due to LOCAL spread include:
   1. Constitutional symptoms
      1. Fatigue
      2. Anorexia
      3. Weight loss 
   2. Cardiopulmonary symptoms
      1. Chest Pain (50%)
      2. Cough (75%)
      3. Dyspnea (60%)
      4. Hemoptysis (35%)
   3. ↑ sputum production

5. local tumour effects
   1. Persistent cough, or change in usual cough
   2. Haemoptysis (tumour necrosis/haemorage in large bronchi; invasion of large vx)
   3. Chest pain (suggests chest wall or pleural involvement)
   4. Unresolving pneumonia or lobar collapse(secondary to obstruction)
   5. Unexplained dyspnoea (due to bronchial narrowing or obstruction)
   6. Wheeze or stridor (bronchi/trachea secondary to metastatic lyphadenopathy in subcarinal and paratracheal glands)
   7. Shoulder pain (due to intercostal nerves or brachial plexus (pancoast sundrome) involvement)
   8. Pleural effusion (due to direct tumour extension or pleural metastases)
   9. Hoarse voice (tumour invasion left recurrent laryngeal nerve)
   10. Dysphagia (mediastinal spread to the oesophagus)
   11. Raised hemi-diaphragm (phrenic nerve paralysis)
   12. SVC Obstruction 
   13. Horner’s syndrome (meiosis, ptosis, enopthalmos, anhidrosis) due to apical or Pancoast’s tumour
       1. Pancoast’s tumours can directly invade sympathetic chain and brachial plexus and rib. Cause weakness of small muscles of the hand -C5/6, T1 motor loss and shoulder pain.

6. metastatic tumour effects
   1. Cervical/supraclavicular lymphadenopathy (common, present in 30%, and may be an easy site for diagnostic biopsy)
   2. Palpable liver edge
   3. Bone pain/pathological fracture due to bone metastases
   4. Neurological sequelae secondary to cerebral metastases (median survival of NSCLC with brain metastases is 2 months)
   5. Hypercalcaemic effects (due to bony metastases or direct tumour production of parathyroid hormone related peptide)
   6. Dysphagia (compression from large mediastinal nodes).

7. paraneoplastic manifestations
   1. Cachexia and wasting
   2. Clubbing (any cell type, more common in squamous and adenocarcinoma)
   3. Syndrome of inappropriate ADH (SIADH; mainly SCLC)
   4. Ectopic ACTH (Cushing’s syndrome, but due to rapid development; biochemical changes predominate, mainly SCLC)
   5. Hypertrophic pulmonary osteo-arthropathy (HPOA, often in association with clubbing, any cell type; more common in squamous and adenocarcinoma) 
   6. Eaton-Lambert myasthenic syndrome with SCLC. 
   7. Affects proximal limbs and trunk, with autonomic involvement and hyporeflexia and only a slight response to edrophonium. Repeated muscle contraction may lead to increasing strength and reflexes. Symptoms may predate lung cancer by up to 4 years

INVESTIGATIONS

1. urgent chest x-ray
   1. for unexplained, persistent symptoms and signs (lasting more than 3 weeks 
   2. if the chest X-ray is normal and symptoms persist repeat the chest x-ray at 6 weeks
      1. Peripheral nodule: Adeno Ca
      2. Central lesion with obstructive pneumonitis : Squamous
      3. Mediastinal/Hilar mass : Small Cell Ca

2. chest CT scan
   1. if there is a strong clinical suspicion of lung cancer
   2. persistent or unexplained haemoptysis
   3. signs of superior vena caval obstruction
   4. imaging findings suggest lung cancer within 2 weeks of the patient
      presenting with symptoms.
   5. The CT scan should be delivered with contrast unless contraindicated. 
   6. Concurrently, refer the patient to a specialist linked to a lung cancer multidisciplinary team (consider immediate telephone contact).

• Lung cancer may be diagnosed through:
  • additional imaging (may include a PET-CT scan)
  • bronchoscopy including endobronchial ultrasound-guided biopsy
  • CT or ultrasound-guided biopsy or aspiration
  • excisional biopsy or biopsy of a metastasis
  • sputum cytology in rare cases.

3. Non-invasive measures
   1. Sputum Cytology
      1. Test Sensitivity for central tumors: 71%
      2. Test Sensitivity for peripheral tumors: 50% 
      3. is more sensitive in tumours 3 – 6cm. 
      4. Sensitivity increases with increasing numbers of specimens.
      5. Haemoptysis is often associated with positive sputum.

4. Less invasive measures
   1. Pleural Effusion Thoracentesis
   2. Excisional Biopsy (if node accessible)
   3. Bronchoscopy with bronchial samples and biopsy
      1. Indicated for central tumors
      2. Test Sensitivity for central lesions: 88%
      3. Test Sensitivity for peripheral lesions: 70% 
   4. Transthoracic needle aspiration : FNA
      1. Indicated for peripheral lesions
      2. Test Sensitivity for peripheral lesions: 90% 
      3. Complications: pneumothorax, bleeding.
      4. Contra-indications: Pneumonectomy, mechanical ventilation, inability to cooperate, abnormal clotting, severe COPD?
5. Thoracotomy
   1. Indicated for non-small cell carcinoma
   2. Lesion amenable to surgery 

6. Staging for lung cancer involves:

• CT scans of the chest and upper abdomen (in all cases) and imaging (can be MRI) of the brain in some cases
• PET-CT scans where curative treatment is being considered
• assessment by a surgeon with thoracic/lung cancer expertise in cases where curative treatment is being considered.
• Imaging and/or pathological confirmation of the most advanced site of disease may
• be required.
• Molecular testing and biomarker testing can inform the most appropriate treatment for non-small cell lung cancer (NSCLC).
• Genetic testing
  • Familial causes are rare in lung cancer and testing is not usually needed.
• Treatment planning
  • The multidisciplinary team should discuss all newly diagnosed patients with lung cancer, usually before treatment begins.
• Research and clinical trials
  • Consider enrolment where available and appropriate

Treatment intent

• The intent of treatment can be defined as one of the following:
  • curative
  • anti-cancer therapy to improve quality of life and/or longevity without expectation of cure
  • symptom palliation