Lung Cancer

Question 1

Brief background of lung cancer.

Answer 1

• Lung cancer is the biggest cancer killer of men and women.

* Mean age of onset: 68.

Question 2

Where do 95% of lung cancers occur?

Answer 2

In the bronchi

Question 3

What are the different types of lung cancer?

Answer 3

• 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.

Question 4

What are the signs and symptoms of lung cancer?

Answer 4

• 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.

Question 5

What are the risk factors for lung cancer?

Answer 5

• 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.

Question 6

Which initial investigations are performed in suspected lung cancer?

Answer 6

• 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.
• 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.

Question 7

How is staging of lung cancer carried out?

Answer 7

• 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.

Question 8

How is NSCLC managed?

Answer 8

• 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}.

Question 9

How is SCLC managed?

Answer 9

• 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.

Question 10

What is the prognosis of lung cancer and which complications may occur?

Answer 10

• 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.

Question 11

What is LEMS? How is it managed and how is it caused?

Answer 11

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