CA Lung

 

• Background

  Epidemiology

  • Lung cancer is the biggest cancer killer of men and women.
  • Mean age of onset: 68.

  Pathology

  95% arise in the bronchi.

  Non-small cell lung cancer (NSCLC):

  • 85% of lung cancer cases, most of which are squamous or adenocarcinomas.
  • Squamous: usually in the central bronchi. Relatively late metastasis.
  • Adenocarcinoma: arising from mucous producing cells, usually in the more peripheral bronchi. Adenocarcinoma in situ and minimally invasive adenocarcinoma are localised sub-types formerly known as broncho-alveolar cancer.
  • Large cell (LCC): poorly-differentiated tumours which cannot be classified as squamous or adenocarcinoma.

  Small cell lung cancer (SCLC):

  • 15% of cases.
  • Aka oat cell carcinoma.
  • Grows and spreads rapidly, with distant mets in ⅔ of patients at presentation.
  • Derive from neuroendocrine amine precursor uptake and decarboxylation (APUD) cells, which may secrete hormones such as ADH or ACTH.

  Secondary lung cancer:

  • Commonly from breast, renal, or thyroid primary cancers.

• Signs and symptoms

  Symptoms

  • Respiratory symptoms: persistent cough, SOB, haemoptysis, chest pain, recurrent infection
  • In lung disease patients (e.g. COPD), this may just manifest as an increase in pre-existing symptoms.
  • Weight loss.
  • Compression: dysphagia (oesophagus), hoarse voice (recurrent laryngeal nerve).
  • Mets: neuro symptoms, bone pain.

  Signs

  • Clubbing
  • Lymphadenopathy
  • Hepatomegaly
  • SVC obstruction leading to distended neck veins.
  • Lung complications: pneumonia, lobar collapse, pleural effusion.
  • Tender chest wall.
  • Pancoast syndrome.

  Paraneoplastic syndromes

  Non-specific:

  • Common: anorexia and cachexia.
  • Rare: acanthosis nigricans, ↓Ca2+, ↓glucose, ↓LH or FSH.

  NSCLC:

  • Hypertrophic pulmonary osteoarthropathy: clubbing, long bone periostitis.
  • Squamous: ↑PTH-like peptide → ↑Ca2+

  SCLC:

  • ↑ADH (10%) → ↓Na+
  • ↑ACTH (7%) → Cushing's
  • Lambert-Eaton myasthenic syndrome (2%).
  • Other encephalomyelopathies: seizures, hallucinations, personality changes.
  • Cerebellar degeneration.

• Risk factors

  • Smoking: 90% of cases are due to smoking. 15% of smokers get it, versus 1.5% of non-smokers. Smokers can develop any histological sub-type, while non-smokers tend to get adenocarcinomas.
  • Passive smoking.
  • Asbestos
  • Radon gas exposure.

• Investigations

  Diagnosis

  Initial imaging:

  • CXR. Indicated in patients with haemoptysis or >3 weeks cough. May show nodule(s), effusion, lobar collapse, or mediastinal or hilar lymphadenopathy.
  • Contrast-enhanced CT chest if there are any suspicious findings on CXR or in smokers with concerning symptoms despite a negative CXR. Contrast helps distinguish blood vessels from lymph nodes, and highlight vascularised tumours. Lower neck and upper abdomen often scanned at same time for mets.
  • CXR and chest CT are also used for long-term follow up and to monitor response to treatment

  Pathological confirmation:

  • Sputum cytology: easy, but only around 50% sensitive. Better for central lesions.
  • Bronchoscopy with biopsy or lavage if CT shows an accessible lesion or node. Biopsy can be endobronchial or transbronchial (TBNA), and endobronchial ultrasound (EBUS) can help guide TBNA.
  • Transthoracic CT- or US-guided needle biopsy if CT suggests that lesions are inaccessible by bronchoscopy.
  • Surgical biopsy might be the only way to confirm diagnosis in some.
  • Thoracocentesis if there is pleural effusion. Consider thoracoscopy if pleural cytology negative.

  Staging investigations

  Staging is often done in parallel with diagnosis as it may be possible to confirm the diagnosis with a nodal or distant lesion. The staging classification is complex, with stage 1-4 groupings based on the TNM system.

  Nodal disease:

  • PET-CT or chest CT.
  • EBUS-guided TBNA, endoscopic ultrasound (EUS)-guided FNA, or mediastinoscopy allow pathological confirmation.
  • Ultrasound-guided biopsy of neck or supraclavicular nodes is sometimes used.

  Metastases:

  • PET-CT can show extent of thoracic and distant disease.
  • Contrast-enhanced CT neck and abdomen, usually done with initial chest CT.
  • Contrast-enhanced CT or MRI brain.

  Further investigations

  Bloods:

  • Basics: FBC, U&E, LFT.
  • LDH may be raised, especially in SCLC, due to tissue necrosis
  • Ca2+ may be ↑ (squamous) or ↓.

  Lung function tests:

  • Use before surgery or radiotherapy to ensure there is sufficient reserve.

• Management

  NSCLC

  Surgery:

  • A curative option for localized disease with no mediastinal spread (i.e. stage 1-2 and some stage 3a), usually lobectomy.
  • Accompanied by adjuvant chemotherapy for most, and in some patients, neoadjuvant chemo and/or adjuvant radiotherapy.

  Radiotherapy:

  • Used in combination with chemotherapy for stage 1-3 (including some 3b) not suitable for surgery due to disease or patient characteristics.
  • May be curative, especially stage 1-2, but rarely for stage 3.

  Systemic therapy:

  • 1st line in advanced disease (stage 4 and some 3b). Not curative but survival times are increasing with novel therapies.
  • Tyrosine kinase inhibitor monotherapy is 1st line for tumours with a 'driver mutation' in EGFR-TK (afatinib, gefitinib, erlotinib, osimertinib), ALK (crizotinib, ceritinib, alectinib), or ROS1 (crizotinib).
  • Immunotherapy with pembrolizumab (anti-PD-1) is 1st line for those without a driver mutation, as monotherapy (if tumour PD-L1 expression ≥50%) or combined with chemotherapy (if tumour PD-L1 expression <50%). Nivolumab (anti-PD-1) and atezolizumab (anti-PD-L1) are 2nd line options.
  • Traditional chemotherapy is typically used as an adjunct to surgery, radiotherapy, or another systemic therapy. Usually a platinum-based doublet regimen: {cisplatin or carboplatin} plus {pemetrexed or etoposide or gemcitabine or vinorelbine or paclitaxel or docetaxel}.

  SCLC

  • Chemotherapy: {cisplatin or carboplatin} plus {etoposide}.
  • Radiotherapy: combined with chemo in limited disease. Can also be considered in extensive disease if there is a good response to chemo.
  • Rarely diagnosed early enough for surgery.

• Complications and prognosis

  Complications of disease:

  • Metastases to lung, liver, brain, bone, adrenals, skin.
  • 10% 5 year survival.
  • Treatment extends median life expectancy from 3 to 12 months.

  Common, severe complications of treatment:

  • Chemotherapy → neutropenic sepsis.
  • Radiotherapy → radiation pneumonitis.

• Pancoast tumour

  Pathophysiology

  An apical lung cancer, usually squamous.

  Signs and symptoms

  • Pain C8-T2: shoulder, arms, hand.
  • Small muscle wasting in the hand (T1 compression).
  • Horner's syndrome (occurs in 20%): ptosis, miosis, anhidrosis, enophthalmos.
  • SVC obstruction.

• Lambert-Eaton myasthenic syndrome (LEMS)

  Pathophysiology

  • Autoimmune destruction of presynaptic voltage-gated Ca2+ channels (VGCC) in the neuromuscular junction, leading to reduced ACh release.
  • 50% of cases are linked to small cell lung cancer, due to cross reaction with tumour antigen.
  • Can also occur in the context of lymphoproliferative disease, or other autoimmune diseases such as thyroid disease.

  Signs and symptoms

  • Weakness, usually starting in proximal legs.
  • Areflexia
  • ANS dysfunction, especially dry mouth and postural hypotension.
  • Dysphagia and dysarthria.
  • Diplopia and ptosis.
  • Differs from myasthenia gravis in that strength and reflexes increase with repetition.
  • Continues even after the removal of the tumour, due to the continued presence of autoantibodies.

  Investigations

  • Serum antibodies: VGCC Ab present in 90%. AChR Ab suggests myasthenia gravis, but can be found in around 10% of LEMS.
  • Electrophysiology: EMG, nerve conduction studies, and low-frequency repetitive nerve stimulation.
  • Chest CT to look for lung cancer.

  Management

  • Find and treat underlying cause.
  • Amifampridine, a K+ channel blocker which leads to presynaptic membrane depolarisation and VGCC opening, improves symptoms.
  • In severe disease, consider immunosuppression (e.g. steroids), IVIG, or plasma exchange.
  • Supportive care if needed e.g. mechanical ventilation.

• Superior vena cava obstruction

  Causes

  • 50% due to lung cancer.
  • Remainder due to lymphoma, germ cell tumours (GCT), or intravascular devices.

  Signs and symptoms

  • Engorged veins in chest and arms. ↑JVP.
  • Swollen face, neck, or arm.
  • Tracheal compression leading to SOB, wheeze, stridor.
  • Orthopnea
  • Headache
  • Facial plethora or cyanosis. Pemberton's sign is eliciting these signs by lifting both arms up so that elbows touch ears, and holding for 1 minute.

  Investigations

  • CXR and CT chest.
  • Venography

  Management

  1. Dexamethasone IV stat then PO. Consider diuretics.
  2. Radiotherapy is usually effective within 2 weeks. Chemotherapy in lymphoma or GCT.
  3. SVC stenting if radiotherapy ineffective.