Makindo Medical Notes.com

Related Subjects: |Bronchogenic Lung Cancer |Hypercalcaemia |Oncological emergencies |Malignant Hyperparathyroidism due to PTHrP |Lambert-Eaton syndrome (LEMS) |Superior Vena Caval Obstruction syndrome |Syndrome of Inappropriate ADH (SIADH) secretion |Cushing's Syndrome due to Ectopic ACTH

They are divided into 20% which are small cell and the remainder of 80% non-small cell. 90% of patients being smokers or ex-smokers

About

• Commonest malignancy in developed countries.
• 40,000 cases in the UK per year and females more commonly affected
• Increasing where smoking is increasing

Aetiology

• 85-90% of lung cancers are smoking related
• Smoking is by far the main cause with squamous and small cell
• Occupational exposure - Asbestos, arsenic, nickel, silicosis, chromium, radon
• Commoner with Idiopathic pulmonary fibrosis and dermatomyositis

Histologically and Prognostically differentiated

• Small cell (SCLC) 20-30%
  • Prognosis very poor with usually central aggressive tumour s. The tumour secrete ACTH, ADH, PRL from oat cell and so may have unusual presentations.
  • In general, small-cell carcinomas have already spread at the time of presentation so that curative surgery cannot be performed, and they are managed primarily by chaemotherapy, usually cisplatin, with or without radiotherapy
• Non-small cell lung carcinomas (NSCLC) 80%
  • Adenocarcinoma (40% of all lung cancer): often peripheral, sometimes in scar tissue. Best prognosis.
  • Alveolar cell: Cancer of the glandular cells that secret mucin. There are several types: Acinar, Bronchoalveolar, Mucus-secreting, Papillary. They may not be accessible by bronchoscopy and need a needle lung biopsy under imaging (CT or USS) control.
  • Squamous (30% of all tumour s): usually central and may cavitate, histologically have keratin pearls and arise from trachea or bronchi. Can cause hypercalcaemia due to the release of PTH-related peptide. Squamous cell carcinoma shows a remarkable dose dependence with cigarette smoking. squamous cell carcinoma is usually found centrally. Therefore causes cough, haemoptysis and lobar pneumonia and can present earlier than other tumour s.
  • Large cell> (15% of all lung cancers) large peripheral mass on CXR. On Microscopy appear as sheets of abnormal cells with an area of dead cells in the middle. They often occur near the edge of the lung rather than near a bronchus (in the centre). Therefore, a needle biopsy may or may not be possible, depending on location. If a needle biopsy is not possible, a tissue sample may need to be gathered using a surgical approach. When this is needed, the entire tumour may be removed both for purposes of diagnosis and treatment.

Clinical

• Cough, sputum, haemoptysis, Cachexia, Finger clubbing
• Chest - Consolidation, collapse or pleural effusion
• Chest or shoulder pain
• Cervical or supraclavicular lymphadenopathy
• Hoarseness (Recurrent Superior laryngeal nerve)
• Upper thorax: Horner syndrome, SVC obstruction
• Focal Neurological symptoms with Cerebral metastases - weakness, focal seizures, altered personality, lateralising signs.
• Myasthenic/Eaton Lambert syndrome
• Cerebellar signs - paraneoplastic
• Hepatomegaly from metastases, also adrenal and bone.
• Cushing's syndrome
• Skin: Clubbing, Acanthosis nigricans, Dermatomyositis

WHO/Zubrod performance status for lung cancer staging

• Stage 0: Asymptomatic
• Stage 1: Symptomatic and ambulatory
• Stage 2: Symptomatic and in bed < 50% of day. Not working but managing at home with assistance
• Stage 3: Symptomatic and in bed > 50% of day. Unable to self-care
• Stage 4: Bedridden

Investigations

• FBC: anaemia from marrow involvement in small cell
• U&E - look for hyponatraemia due to SIADH or hypernatraemia due to hypercalcaemia
• ? Calcium is associated with the squamous cell. Can cause confusion. Always test.
• CXR - central or peripheral mass, hilar lymphadenopathy, pleural effusion
• Sputum cytology
• CT chest + liver + adrenals ( + brain if symptoms)
• CT/PET scanning - more sensitive and specific than CT for identifying metastatic disease and can be combined with CT
• CT shows central lesion - bronchoscopy and biopsy
• CT shows peripheral lesion - percutaneous needle biopsy
• Tissue to support diagnosis:
  • Fibreoptic bronchoscopy
  • Percutaneous needle aspiration of peripheral lesions
  • Mediastinoscopy
  • Lymph node biopsy with USS
  • Biopsy of metastasis
  • Open lung biopsy via thoracotomy

Paraneoplastic

• Cushing's Syndrome (Small cell)
• SIADH (Small cell)
• Hypercalcaemia (Squamous cell)
• Gynaecomastia (Large cell)
• Clubbing (Squamous cell/Adenocarcinoma/large cell)
• Peripheral neuropathy (small cell)
• Subacute cerebellar degeneration (small cell)
• Eaton Lambert (small cell)
• Dermatomyositis (all)
• Anaemia (all)
• DIC (all)
• Eosinophilia (all)
• Thrombocytosis (all)
• Thrombophlebitis (Adenocarcinoma)
• Nonbacterial thrombotic endocarditis (Adenocarcinoma)

Management

• Better decisions are made by using a multidisciplinary approach to management involving respiratory physicians, oncologists and surgeons. Each case is judged on its own merits. Operability if the tumour is > 2cm from the carina.
• In selected cases lesions may be simply observed over time where suspicion is low and curative procedure of dubious merit

Staging

Management based on staging

• T1N0M0 to T1-3N2M0/T3N1M0 - consider radiotherapy/surgery.
• Greater than T3N2M0/T3M1N0 - consider chaemotherapy/radiotherapy
• Once there are metastases or invasion close to or of the carina or a malignant effusion then surgical resection is not an option

Additional therapies for Unresectable NSCLC

• Platinum-based chaemotherapy e.g. cisplatin/vinblastine and radiation therapy. Docetaxel may further improve outcome.
• Biological therapies: EGFR tyrosine kinase inhibitors e.g. gefitinib show some promise
• Small cell: Tend to have disseminated before the presentation. Chemotherapy may be given but relapse is common. Cisplatin and etoposide and chest irradiation may improve outcome. May be used for localised or extensive disease. The prognosis is very poor.
• Advanced metastatic disease - palliation.

Management of complications

• Hypercalcaemia: IV Hydration 3-4 L/day, Furosemide once hydrated, IV Pamidronate
• SVC obstruction: Dexamethasone 4 mg 8h and refer radiotherapy and/or stenting
• Bone pain: Pamidronate, Radiotherapy
• Cord Compression: Dexamethasone 4 mg 8h and get MRI spine and refer for radiotherapy/surgery
• Liver capsule pain: steroids
• Stridor: ABC, Dexamethasone 4 mg 8h. Needs bronchoscopy for Stenting or Radiotherapy
• Pleural effusion: Pleural drainage and pleurodesis

Surgical Management

New Developments

• Low-Dose CT scan: low radiation scans for those at high risk
• Video-Assisted Thoracic Surgery (VATS): less invasive surgery. There is also "robotic-assisted surgery."
• Image-Guided Radiation Therapy: precision delivery of radiotherapy
• Immune-based Treatments
  • Checkpoint inhibitors: Atezolizumab (Tecentriq), durvalumab (Imfinzi), nivolumab (Opdivo) and pembrolizumab (Keytruda) target these checkpoints and basically take the brakes off your immune system so that it can mount a better attack.
  • Monoclonal antibodies: Made in a lab, these molecules target specific signs, called antigens, that are found on tumour s. Examples used to treat lung cancer are bevacizumab (Avastin) and ramucirumab (Cyramza).
  • Targeted Treatments: specific genetic combinations may benefit from targeted therapies like EGFR (epidermal growth factor receptor) blockers.
  • ALK gene and other genetics can be targeted
  • Chemotherapy: new chaemotherapy drugs or improvements on existing ones.