Lung cancer is a malignant neoplasm arising from the epithelial cells of the bronchial tree or lung parenchyma, most commonly classified as non-small cell or small cell carcinoma.

CA Lung (Bronchial Carcinoma)

2. Epidemiology

	Males	Females
Smoking status	~80% smokers	< 40% smokers ^[2]
Predominant histology	SCC / SCLC (smokers)	> 75% adenocarcinoma ^[2]
Molecular drivers	Variable	EGFR mutation much more common

Why do non-smoking Asian women get lung cancer?

This is a classic exam question. Postulated causes include: (1) passive smoking ^[2], (2) cooking fume exposure (especially wok cooking with high-temperature oils — generates polycyclic aromatic hydrocarbons) ^[2], (3) higher prevalence of EGFR driver mutations in Asian adenocarcinomas (~55% in HK vs ~15% in Caucasians) ^[2], and (4) possible genetic susceptibility. The exact answer is multifactorial and not fully understood.

3. Risk Factors

Risk Factor	Mechanism	Details
Cigarette smoking	Carcinogens (benzopyrene, nitrosamines) cause DNA damage → accumulation of oncogenic mutations (p53, KRAS)	Responsible for ~90% of CA lung; 40× death rate in smokers ^[2]. Risk falls after cessation but never returns to baseline ^[2]. Dose-response: pack-years matter.
Passive (secondhand) smoking	Same carcinogens at lower dose	~1.3× relative risk. Particularly relevant in HK female non-smokers ^[1]^[2].
Asbestos exposure	Chronic inflammation → fibrosis → malignant transformation	Synergistic with smoking (multiplicative, not additive risk). Ask occupation: renovation/demolition workers ^[2]. Can cause mesothelioma (pleural) or bronchial carcinoma.
Cooking fumes	PAHs, aldehydes from high-temperature stir-frying	Particularly relevant in HK and Chinese populations ^[2].
Radiation exposure	Direct DNA damage	Thoracic RT for prior malignancy; radon gas exposure (natural radioactive gas in some buildings/mines) ^[2].
Air pollution	PM2.5 particulates cause chronic airway inflammation and oxidative DNA damage	Growing recognition as independent risk factor.

Risk Factor	Details
Family history	1.5× risk if positive family history ^[2]
Previous lung disease	Idiopathic pulmonary fibrosis (IPF), COPD — chronic inflammation and scarring provide a nidus for malignant transformation ^[2]
Previous TB	"Scar tumours" — classically described in textbooks ^[2]. Chronic granulomatous inflammation → fibrosis → malignant change (typically adenocarcinoma in scar tissue).
Genetic drivers	EGFR mutation (55% in local adenocarcinoma) — much more common in Asians ^[2]; ALK translocation (5%) ^[2]; KRAS mutation (5–10%) ^[2]. These are both risk factors and therapeutic targets.

Smoking and Lung Cancer — Key Numbers for Exams

90% of lung cancers are attributable to smoking.
40× increased death rate in heavy smokers vs non-smokers.
Risk falls after quitting but still rises with age faster than never-smokers ^[2] — i.e., the damage is partially irreversible.
Pack-years = (packs/day) × (years smoked). > 20 pack-years = significant risk.

4. Anatomy and Function (Relevant to CA Lung)

Understanding the anatomy is critical because lung cancer symptoms are determined by where the tumour is and what structures it invades.

The mediastinum is a tight space packed with critical structures. A growing central tumour or enlarged lymph nodes can compress any of these:

Structure	Consequence of Compression/Invasion
Recurrent laryngeal nerve (RLN)	Hoarseness of voice (left RLN loops under aortic arch — left-sided tumours more commonly cause this)
Phrenic nerve	Diaphragmatic paralysis → elevated hemidiaphragm on CXR
Oesophagus	Dysphagia
Superior vena cava (SVC)	SVC obstruction syndrome
Pericardium	Pericardial effusion ± tamponade
Sympathetic chain / stellate ganglion	Horner's syndrome (miosis, ptosis, anhidrosis, enophthalmos)
Brachial plexus (C8–T1)	Arm pain, weakness, small muscle wasting
Thoracic duct	Chylothorax (rare)
Vertebral body	Cord compression, back pain

5. Aetiology and Pathogenesis

Mutation/Alteration	Prevalence in HK Adenocarcinoma	Significance
EGFR mutation	~55% ^[2]	Most common actionable driver in Asian adenocarcinoma. Much higher than Caucasians (~15%). Targeted by TKIs (gefitinib, erlotinib, osimertinib).
ALK translocation	~5% ^[2]	EML4-ALK fusion. Targeted by crizotinib, alectinib. Typically younger, non-smokers.
KRAS mutation	5–10% ^[2]	More common in Western populations. Historically "undruggable" but sotorasib now targets KRAS G12C.
ROS1 rearrangement	~1–2%	Similar to ALK; responds to crizotinib.
PD-L1 expression	Variable	Not a mutation but a biomarker for immunotherapy response.
p53 mutation	Very common (~50% all subtypes)	Tumour suppressor loss. Not directly targetable but important in pathogenesis.
BRAF V600E	~1–2%	Targetable with dabrafenib + trametinib.

EGFR in Asian Lung Cancer — Why It Matters So Much

In HK/East Asia, EGFR mutation is present in ~55% of adenocarcinomas ^[2]. This means more than half of adenocarcinoma patients in HK have a targetable mutation. EGFR TKIs (tyrosine kinase inhibitors) dramatically improved survival in these patients. This is why molecular testing is mandatory for all non-squamous NSCLC in current practice. Never start treatment without knowing the EGFR status.

6. Classification

The fundamental division is into Non-Small Cell Lung Cancer (NSCLC) (~85%) and Small Cell Lung Cancer (SCLC) (~15%). This distinction is the single most important one because it determines the entire management approach.

Feature	Adenocarcinoma (ADC)	Squamous Cell Carcinoma (SCC)	Large Cell Carcinoma (LCLC)	Small Cell Carcinoma (SCLC)
% of all lung cancers	~40–55% ^[1]^[2]	~20–30% ^[1]^[2]	~5–10% ^[1]^[2]	~5–15% ^[1]^[2]
Smoking association	Weakest (but still significant) ^[1]	Strongest ^[1]	Moderate	Strong ^[1]
Typical location	Peripheral ^[1]	Central ^[1]	Peripheral ^[1]	Central ^[1]
Cell of origin	Type II pneumocytes / Clara cells	Bronchial squamous epithelium (via metaplasia)	Undifferentiated large cells	Neuroendocrine cells (Kulchitsky cells)
IHC markers	TTF-1 ^[1]	p40, p63 ^[1]	Often negative	Synaptophysin, Chromogranin ^[1]
Key demographics	Young females, non-smokers (especially in Asia)	Older male smokers	Non-specific	Male smokers
Growth rate	Moderate	Moderate	Moderate–fast	Very fast, tend to metastasize early ^[1]
Molecular targets	EGFR, ALK, ROS1, KRAS, BRAF	Rare actionable mutations	Rare	Rarely tested (chemo is mainstay)
Key feature	Most common subtype; glandular differentiation; mucin production	Keratin pearls, intercellular bridges; can cavitate (central necrosis)	Diagnosis of exclusion (no glandular/squamous/neuroendocrine features)	"Oat cell" carcinoma ^[1]; very high mitotic rate; crush artefact on biopsy; strong paraneoplastic associations

	NSCLC	SCLC
Surgery	Potentially curative if early stage	Almost never surgical (usually disseminated at diagnosis)
Chemosensitivity	Moderate	Very chemosensitive (but almost always relapses)
Radiosensitivity	Moderate	Very radiosensitive
Staging system	TNM staging (I–IV)	Limited vs Extensive disease
Prognosis	Better overall (especially with targeted therapy)	Very poor (median survival ~10–12 months even with treatment)

7. Clinical Features

7.2 Symptoms

I'll organise symptoms by mechanism — this is how you should think about them on a ward round.

Symptom	Pathophysiological Basis
Malaise, fatigue	Tumour-derived cytokines (TNF-α, IL-6) cause systemic inflammation and catabolism
Weight loss, cachexia	Cancer cachexia syndrome: tumour releases proteolysis-inducing factor (PIF) and lipid-mobilising factor (LMF) → skeletal muscle wasting and fat loss. Also mediated by TNF-α ("cachectin").
Loss of appetite (anorexia)	Central appetite suppression by tumour-derived cytokines acting on the hypothalamus
Fever	Tumour necrosis releasing pyrogens; also post-obstructive pneumonia

These occur when the tumour grows within or compresses the airway lumen.

Symptom	Pathophysiological Basis
Cough ^[1]	Irritation of cough receptors in the bronchial mucosa by tumour mass. May be dry or productive. A change in the character of a chronic cough in a smoker is a red flag.
Haemoptysis ^[1]	Tumour is vascular and friable → erosion of mucosal blood vessels → blood-streaked sputum. Massive haemoptysis (rare but lethal) occurs if tumour erodes into a pulmonary artery or bronchial artery.
Shortness of breath (SOB) ^[1]	Partial or complete bronchial obstruction → distal atelectasis (collapse) → reduced functional lung volume. Also from large pleural effusions.
Wheeze / Stridor ^[1]	Fixed, monophonic wheeze from partial airway obstruction (unlike the polyphonic wheeze of asthma/COPD). Stridor occurs with tracheal/main bronchus obstruction — an emergency.
Post-obstructive pneumonia	Tumour blocks bronchus → mucus stagnation distal to obstruction → bacterial superinfection. Suspect lung cancer in any patient with recurrent or non-resolving pneumonia in the same lobe.

Exam Tip

A common exam scenario: "A 65-year-old smoker presents with recurrent right lower lobe pneumonia." The key differential is post-obstructive pneumonia due to endobronchial tumour. Always think CA lung in recurrent/non-resolving pneumonia in a smoker.

C. Symptoms from Regional Spread / Local Invasion

These depend on which mediastinal or thoracic structure is invaded.

Symptom	Pathophysiological Basis
Pleural effusion ^[1]	Tumour cells seed the pleura → irritation and increased vascular permeability → exudative effusion. Also lymphatic obstruction impairs pleural fluid reabsorption.
Pleuritic chest pain ^[1]	Parietal pleura (innervated by intercostal nerves) is invaded or inflamed by tumour. Visceral pleura has no somatic innervation, so pain only occurs when the parietal pleura is involved.

Symptom	Pathophysiological Basis
Pericardial effusion ± cardiac tamponade ^[1]	Direct tumour invasion or metastatic seeding of the pericardium → fluid accumulation → if rapid/large, compresses the heart → reduced cardiac filling → tamponade (Beck's triad: hypotension, distended neck veins, muffled heart sounds).

Symptom	Pathophysiological Basis
Hoarseness of voice ^[1]	Left RLN loops under the aortic arch and then ascends to the larynx in the tracheo-oesophageal groove. Tumours of the left hilum or aortopulmonary window lymph nodes can compress/invade it → unilateral vocal cord paralysis → hoarse, breathy voice. Right RLN loops under the right subclavian artery (higher up), so right-sided tumours less commonly cause this.
Dysphagia ^[1]	Direct compression/invasion of the oesophagus by tumour or enlarged subcarinal lymph nodes. The oesophagus lies posterior to the trachea in the mediastinum.

A Pancoast tumour is a tumour at the lung apex invading the structures of the thoracic inlet. The resulting clinical syndrome is called Pancoast syndrome ^[1]:

Component	Structure Involved	Clinical Feature
Horner's syndrome ^[1]	Stellate ganglion (T1 sympathetic ganglion)	Miosis (pupil constriction — loss of sympathetic pupil dilator), ptosis (drooping eyelid — loss of sympathetic innervation to Müller's muscle), anhidrosis (loss of facial sweating on ipsilateral side), enophthalmos (apparent sinking of the eye). Mnemonic: MAP — Miosis, Anhidrosis, Ptosis.
Brachial plexopathy ^[1]	Lower trunk of brachial plexus (C8, T1)	Pain radiating down the medial arm/forearm (T1 dermatome), numbness in medial 1.5 fingers (ulnar nerve territory).
Small hand muscle wasting ^[1]	T1 nerve root → intrinsic hand muscles	Claw hand appearance, weakness of finger abduction/adduction (interossei), thumb opposition (thenar eminence — but T1 involvement mainly affects hypothenar/interossei).
Shoulder pain ^[1]	Invasion of chest wall, ribs, and adjacent soft tissues	Deep, boring, constant pain in the shoulder/scapular region.

Why is Horner's Syndrome Always on the Same Side as the Tumour?

The sympathetic chain runs ipsilaterally from the hypothalamus → brainstem → C8–T2 (ciliospinal centre of Budge) → exits the spinal cord → synapses in the stellate ganglion (at the lung apex) → postganglionic fibres travel along the internal carotid artery to reach the eye. A Pancoast tumour destroys the stellate ganglion on the same side → ipsilateral Horner's syndrome.

Symptom	Pathophysiological Basis
Puffy face / facial oedema ^[1]	Compression/invasion of the SVC by tumour or enlarged right paratracheal lymph nodes → obstruction of venous return from the head and upper limbs → raised venous pressure → oedema of the face, neck, and upper limbs.
Dilated chest veins / collateral veins ^[1]	Blood finds alternative venous drainage pathways → dilated superficial veins over the anterior chest wall (collateral circulation).
Pemberton's sign ^[1]	Raising both arms above the head for > 1 minute → further compresses the thoracic inlet → worsening facial congestion, cyanosis, and JVP elevation. This is a clinical bedside test for SVC obstruction or thoracic inlet narrowing.
Headache, visual disturbance	Raised intracranial venous pressure (the internal jugular veins drain into the SVC).
Arm swelling	Venous congestion of the upper extremities.

SVCO is most commonly caused by lung cancer (especially SCLC, which is central and aggressive) or lymphoma. It is an oncological emergency — can progress to cerebral oedema if untreated.

Symptom/Sign	Structure	Pathophysiological Basis
Phrenic nerve palsy → elevated hemidiaphragm ^[1]	Phrenic nerve (C3, C4, C5 — "C3, 4, 5 keeps the diaphragm alive")	Tumour or lymph nodes compress/invade the phrenic nerve as it descends along the mediastinum → diaphragmatic paralysis → hemidiaphragm rises on the affected side (seen on CXR). Patient may report orthopnoea.
Lymphangitis carcinomatosis ^[1]	Pulmonary lymphatic channels	Tumour cells spread through pulmonary lymphatics → diffuse lymphatic obstruction → interstitial oedema, septal thickening → progressive dyspnoea, dry cough. CXR/CT shows reticular/reticulonodular pattern with septal (Kerley B) lines.

Site	Symptoms	Pathophysiological Basis
Supraclavicular / cervical lymph nodes ^[1]	Painless, hard, fixed lump in the neck	Lymphatic spread via mediastinal → supraclavicular lymph nodes. Left supraclavicular (Virchow's node) suggests thoracic/abdominal malignancy.
Liver ^[1]	Right upper quadrant discomfort, hepatomegaly, deranged LFTs ^[1]	Haematogenous spread → hepatic metastases → liver capsule (Glisson's capsule) stretching → pain. Hepatocyte destruction → elevated transaminases and ALP.
Adrenal glands ^[1]	Usually asymptomatic; rarely glucocorticoid insufficiency ^[1] (Addisonian crisis)	Bilateral adrenal metastases → destruction of > 90% of adrenal cortical tissue → adrenal insufficiency (hypotension, hyponatraemia, hyperkalaemia). Often found incidentally on staging CT.
Bone ^[1]	Bone pain, back pain, pathological fractures, hypercalcaemia, cord compression ^[1]	Lytic bone metastases (osteoclast activation by tumour-derived PTHrP, RANKL, IL-6) → weakened bone → fractures. Vertebral body involvement → collapse → spinal cord compression (oncological emergency).
Brain ^[1]	Unilateral limb weakness, seizures ^[1], headache, personality change, nausea/vomiting	Haematogenous spread across the blood-brain barrier → space-occupying lesion → raised ICP, focal neurological deficits depending on location. Lung is the most common primary to metastasise to the brain.

Spinal Cord Compression — Don't Miss This

Any lung cancer patient presenting with back pain + lower limb weakness/sensory level/urinary retention → suspect spinal cord compression. This is an oncological emergency. Needs urgent MRI whole spine and dexamethasone. Delay → irreversible paraplegia.

Paraneoplastic syndromes are clinical manifestations caused by substances produced by the tumour (hormones, antibodies, cytokines) rather than by direct tumour invasion. They can be the presenting feature and may precede the diagnosis of cancer by months.

Syndrome	Tumour Type	Mechanism	Clinical Features
SIADH (Syndrome of Inappropriate ADH secretion)	SCLC	Ectopic ADH (vasopressin) secretion → water retention → dilutional hyponatraemia	Confusion, seizures, nausea, concentrated urine, low serum Na+, low serum osmolality with inappropriately concentrated urine
Ectopic Cushing's syndrome	SCLC	Ectopic ACTH secretion → bilateral adrenal hyperplasia → cortisol excess	Hypertension, hypokalaemic metabolic alkalosis, hyperglycaemia, proximal myopathy, moon face. Note: rapid onset so classic Cushingoid features may not have time to develop.
Hypercalcaemia of malignancy	SCC (most commonly)	Ectopic PTHrP (parathyroid hormone-related peptide) → acts on PTH receptors → osteoclast activation, renal calcium reabsorption	"Bones, stones, abdominal moans, psychic groans" — bone pain, renal stones, constipation, confusion. Also from osteolytic bone metastases (any subtype).
Lambert-Eaton Myasthenic Syndrome (LEMS)	SCLC	Antibodies against presynaptic voltage-gated calcium channels (VGCC) at the neuromuscular junction → reduced ACh release	Proximal muscle weakness (improves with repeated use — opposite to myasthenia gravis), hyporeflexia, autonomic dysfunction (dry mouth).
Cerebellar degeneration	SCLC	Anti-Hu, anti-Yo antibodies → autoimmune destruction of Purkinje cells	Progressive cerebellar ataxia, dysarthria, nystagmus
Peripheral neuropathy	SCLC	Anti-Hu (ANNA-1) antibodies → sensory > motor neuropathy	Numbness, paraesthesia, sensory ataxia
Dermatomyositis / Polymyositis	Any	Autoimmune — tumour antigens cross-react with muscle antigens	Proximal muscle weakness, heliotrope rash, Gottron's papules, elevated CK
Hypertrophic pulmonary osteoarthropathy (HPOA)	NSCLC (especially adenocarcinoma)	Unknown mechanism — possibly VEGF, PDGF. Results in periosteal new bone formation.	Clubbing (earliest sign), painful wrist/ankle swelling, bone pain. X-ray: periosteal reaction in long bones (distal tibia, radius, ulna). May resolve after tumour resection.
Clubbing	NSCLC (especially SCC and ADC)	Likely due to VEGF and PDGF release → endothelial proliferation in nail bed	Loss of the normal angle between nail and nail bed (Lovibond angle > 180°). Check by Schamroth's test (loss of diamond-shaped window).
Thrombophilia / migratory thrombophlebitis (Trousseau syndrome)	Any	Tumour secretes procoagulants (tissue factor, mucin) → hypercoagulable state	DVT, PE, migratory superficial thrombophlebitis. Cancer patients have 4–7× increased VTE risk.
Gynaecomastia	Large cell carcinoma	Ectopic β-hCG secretion → aromatase stimulation → oestrogen excess	Bilateral breast enlargement in males

Paraneoplastic Syndromes — Key Associations for Exams

SCLC = SIADH, ectopic Cushing's, LEMS, anti-Hu neuropathy
SCC = Hypercalcaemia (PTHrP), clubbing
Adenocarcinoma = HPOA, clubbing
Large cell = Gynaecomastia (β-hCG)

Think of SCLC as the "endocrine" cancer — it comes from neuroendocrine cells and loves to secrete hormones.

7.3 Signs

On examination, you are looking for signs that confirm the symptoms above and help stage the disease.

Sign	What It Indicates
Dull percussion + reduced breath sounds + reduced vocal resonance on one side	Pleural effusion (fluid between the visceral and parietal pleura)
Dull percussion + reduced breath sounds + bronchial breathing above the level	Lobar collapse (atelectasis) due to endobronchial obstruction
Fixed monophonic wheeze	Partial airway obstruction by tumour (localised to one area — unlike diffuse polyphonic wheeze of COPD/asthma)
Stridor	Tracheal or main bronchus obstruction — ominous sign
Tracheal deviation	Towards the lesion if collapse; away if large effusion
Reduced chest expansion on one side	Effusion, collapse, or chest wall invasion
Dilated superficial chest veins	SVCO — blood finding alternative drainage routes

Sign	What It Indicates
Hepatomegaly (hard, irregular, non-tender)	Liver metastases
Tender bony points (vertebrae, ribs, long bones)	Bone metastases
Focal neurological deficits	Brain metastases
Wasting of small muscles of the hand	T1 root involvement (Pancoast)
Pemberton's sign	SVCO
Pericardial rub or muffled heart sounds	Pericardial involvement

8. Special Topics from Lecture Slides

To tie it all together — here is a concept map of how pathology drives clinical features:

High Yield Summary

Key Points for CA Lung (Definition → Clinical Features):

Definition: Bronchial carcinoma = malignant neoplasm from bronchial epithelium. 95% of lung cancers.
Epidemiology (HK): 2nd in incidence, 1st in mortality. M:F = 2:1. Female non-smokers with adenocarcinoma/EGFR mutation is a distinctive HK pattern. Peak 60–70y. 85% NSCLC.
Risk factors: Smoking (90%), passive smoking, asbestos, cooking fumes, radiation, radon, family history, IPF, previous TB. EGFR mutation in 55% of local adenocarcinoma.
Classification: NSCLC (adenocarcinoma [peripheral, TTF-1+], SCC [central, p40+], large cell) vs SCLC (central, neuroendocrine markers, fast, early metastasis).
Clinical features by mechanism:
- Constitutional: cachexia, weight loss (cytokine-mediated)
- Endobronchial: cough, haemoptysis, SOB, wheeze/stridor
- Regional: pleural effusion, RLN palsy (hoarseness), phrenic palsy, SVCO, Pancoast syndrome, pericardial effusion, dysphagia, lymphangitis carcinomatosis
- Metastatic: BLAB (Brain, Liver, Adrenals, Bone)
- Paraneoplastic: SCLC → SIADH, Cushing's, LEMS; SCC → hypercalcaemia; NSCLC → HPOA, clubbing
Surgical principles: VATS lobectomy is standard for early-stage NSCLC. R0 resection is the goal. MDT approach is essential.

Active Recall - CA Lung (Definition to Clinical Features)

Differential Diagnosis of CA Lung

When you encounter a patient with a suspected lung mass, the clinical challenge is not simply "is this lung cancer?" — it is "what else could this be, and how do I systematically narrow down the list?" The differential diagnosis depends heavily on the clinical presentation (i.e., what brought the patient in) and the radiological appearance (solitary nodule vs mass vs multiple nodules vs diffuse infiltrate). Let me walk you through this the way you'd think on a ward round.

2. Differential Diagnosis by Radiological Pattern

A nodule is defined as a rounded opacity ≤ 3 cm; a mass is > 3 cm ^[7]. This distinction matters because masses are much more likely to be malignant.

Category	Specific Diagnoses	Key Distinguishing Features
Primary lung malignancy	Adenocarcinoma, SCC, SCLC, large cell, carcinoid tumour	Spiculated margins, eccentric calcification, enhancement on contrast CT (HU > 15), pleural retraction, growth on serial imaging ^[8]^[9]
Metastatic deposit	From breast, colorectal, renal, melanoma, sarcoma, head & neck	Usually well-circumscribed and multiple (but can be solitary); known primary elsewhere; round "cannonball" appearance ^[7]
Granuloma	TB, histoplasmosis, sarcoidosis	Well-circumscribed, central/uniform/"popcorn" calcification, stable over time. TB very common in HK — always consider ^[8]^[9]
Benign tumour	Hamartoma	Most common benign lung tumour. Fat-containing on CT (pathognomonic), "popcorn" calcification, well-circumscribed ^[8]^[9]
Lung abscess	Bacterial (Klebsiella, Staph aureus, anaerobes), fungal (Aspergillus)	Cavitating lesion with air-fluid level, thick irregular wall, fever, productive cough with foul-smelling sputum
AVM	Pulmonary arteriovenous malformation	Well-circumscribed, feeding vessel visible on CT, associated with HHT (hereditary haemorrhagic telangiectasia — Osler-Weber-Rendu) ^[8]^[9]
Pulmonary sequestration	Congenital abnormal lung tissue	Connected to blood supply but not the bronchial tree (therefore not ventilated) ^[8]. Recurrent infections in same location.
Inflammatory pseudotumour	Organising pneumonia, IgG4-related disease	Can mimic malignancy on imaging; may need biopsy to distinguish
Extrapulmonary density	Nipple shadow, pleural mass, bone lesion, skin lesion, electrodes ^[7]	On CXR only — eliminated by CT or repeat CXR with nipple markers

Characteristics distinguishing benign from malignant nodules ^[7]^[8]^[9]:

Feature	Malignant (30% of SPNs)	Benign (70% of SPNs)
Size	> 2 cm	< 2 cm
Location	Upper lobe more likely malignant	Lower lobe slightly more likely benign
Margin	Spiculated (corona radiata sign — irregular, sunburst-like projections into surrounding parenchyma; reflects desmoplastic reaction to invading tumour)	Well-defined, smooth
Calcification	Eccentric (or absent)	Central, "popcorn" (hamartoma), laminated, diffuse ^[8]^[9]
Contrast enhancement	HU > 15 (vascular tumour takes up contrast)	HU < 15 (avascular/fibrotic) ^[7]
Growth	Doubling time 20–400 days	Stable > 2 years (very reassuring)
Patient factors	Age > 50, smoking, family history, prior cancer	Age < 40, non-smoker

Consider other predictors for malignancy: age, smoking, family history ^[7]. Compare with previous film ^[7] — if a nodule has been stable for > 2 years, it is almost certainly benign.

A lesion > 3 cm is a mass, and the probability of malignancy increases dramatically. The differential narrows:

Diagnosis	Key Features
Primary bronchial carcinoma	Most likely diagnosis. Spiculated, enhancing, may have chest wall/mediastinal invasion.
Metastatic tumour	Usually round, well-circumscribed. May be solitary. Requires search for primary.
Lymphoma	Usually mediastinal/hilar lymphadenopathy dominant; anterior mediastinal mass. Young patient. B symptoms (fever, night sweats, weight loss).
Lung abscess	Cavitating with air-fluid level. Acute/subacute illness with fever, productive cough.
Organising pneumonia / round pneumonia	May mimic mass; usually responds to antibiotics. More common in children.
Large granuloma / tuberculoma	Especially in HK where TB is endemic. Calcification, upper lobe.

Category	Diagnoses
Metastatic disease	Most common cause of multiple pulmonary nodules in adults. "Cannonball" metastases (renal, colorectal, sarcoma, melanoma, testicular).
Infection	Abscess (bacterial — multiple, with cavitation), granulomatous lung disease (TB, fungal, GPA) ^[7]
Granulomatous / autoimmune	Granulomatosis with polyangiitis (GPA/Wegener's) — cavitating nodules + upper respiratory involvement + glomerulonephritis. Rheumatoid nodules (Caplan syndrome in coal miners). Sarcoidosis ^[7].
Septic emboli	IV drug use, infective endocarditis. Multiple peripheral nodules with feeding vessel sign, may cavitate.
Benign	Multiple hamartomas (rare), lymphangioleiomyomatosis (young women)

Diagnosis	Key Features
Central bronchial carcinoma (SCC, SCLC)	Most common cause of unilateral hilar mass in an adult smoker
Lymphoma	Bilateral hilar lymphadenopathy (especially Hodgkin's — "bulky mediastinal disease"). Anterior mediastinum.
Sarcoidosis	Bilateral symmetrical hilar lymphadenopathy (BHL) — classically stage I/II sarcoidosis. Young, Black patients. Non-caseating granulomas.
TB	Unilateral hilar lymphadenopathy (especially primary TB in children/young adults). Paratracheal nodes.
Thymoma	Anterior mediastinum. Associated with myasthenia gravis.
Retrosternal goitre	Superior mediastinum, continuous with thyroid on CT.

3. Differential Diagnosis by Presenting Symptom

Because many patients with suspected CA lung present not with a visible mass, but with a symptom, here are the key DDx organised by the symptom that brings them in:

Category	Differentials
Respiratory (productive)	COPD, TB, bronchiectasis, malignancy ^[7]
Respiratory (dry)	Postnasal drip, post-viral cough, asthma, lung fibrosis ^[7]
GI	GORD, recurrent aspiration ^[7] — acid reflux stimulates vagal cough receptors in the lower oesophagus and larynx
Cardiac	Heart failure ^[7] — pulmonary congestion stimulates J-receptors in the alveolar walls
Drug-induced	ACEI (↑bradykinin accumulation in the lungs → cough), beta-blockers (bronchospasm) ^[7]

The classic exam scenario: A 60-year-old smoker with a change in the character of chronic cough, especially if accompanied by haemoptysis or weight loss → CA lung until proven otherwise.

Category	Differentials
Airway disease	CA lung, nasopharyngeal carcinoma (NPC — important in HK!), bronchiectasis ^[7]
Parenchymal disease	TB, pneumonia, lung abscess ^[7]
Vascular disease	PE, LV failure (CHF, mitral stenosis — pink frothy sputum), vasculitis (Goodpasture's syndrome, GPA, MPA), HHT ^[7]
Others	Bleeding tendency, anticoagulants, pulmonary endometriosis (rare, catamenial haemoptysis) ^[7]

NPC in HK

Nasopharyngeal carcinoma is an important DDx for haemoptysis in Hong Kong due to its high endemic prevalence (strongly associated with EBV and Southern Chinese ethnicity). Always examine the nasopharynx in a haemoptysis work-up, especially if associated with unilateral conductive hearing loss, nasal obstruction, or cranial nerve palsies.

Acuity	Key Differentials
Acute	Pneumothorax, PE, acute pulmonary oedema (APO), asthma exacerbation, AECOPD ^[7]
Subacute	Pneumonia, TB, pleural effusion ^[7]
Chronic	COPD, malignancy, interstitial lung disease (ILD) ^[7]
Cardiac	CHF, ACS, arrhythmia ^[7]
Metabolic	Anaemia, metabolic acidosis, hyperthyroidism ^[7]
Neuromuscular	Myasthenia gravis, GBS, stroke ^[7]
Psychological	Anxiety, hyperventilation syndrome ^[7]

If a patient presents with back pain and is subsequently found to have a lung mass:

DDx Category	Diagnoses
Malignant	Primary lung cancer with bone metastasis; other primary with bone mets (breast, prostate, thyroid, kidney — "paired organ" primaries) ^[10]
Infective	TB spine (Pott's disease), epidural abscess ^[10]
Degenerative	Spondylosis, disc prolapse ^[10]
Fracture	Osteoporotic compression fracture, pathological fracture ^[10]
Inflammatory	Ankylosing spondylitis ^[10]

This is a critical distinction because it completely changes management. A solitary lung mass in a patient with a known extracranial malignancy is not metastasis in 10–15% of cases ^[11] — it could be a new primary lung cancer, and this has curative implications.

Feature	Primary Lung Cancer	Lung Metastasis
Number	Usually solitary	Often multiple (but can be solitary)
Margins	Spiculated, irregular	Round, well-circumscribed ("cannonball")
Location	Upper lobe predominance	Random distribution (haematogenous seeding) — often peripheral, basal
Associated findings	Hilar/mediastinal lymphadenopathy, endobronchial component	Known extrathoracic primary, other organ metastases
Histology	Matches bronchial subtypes (ADC, SCC, etc.)	Matches the primary tumour histology
IHC	TTF-1+ (adenocarcinoma), p40+ (SCC)	Organ-specific markers (e.g., ER/PR for breast, CDX2 for colorectal, PAX8 for renal)

Exam Pearl — Solitary Brain Lesion in Known Cancer

10–15% of solitary cerebral mass lesions in patients with pre-existing cancer are NOT metastasis ^[11] — they may be primary brain tumours or brain abscesses. Do not assume all lesions in cancer patients are metastatic without tissue confirmation when it would change management.

When you find a hard, irregular, non-tender hepatomegaly in a patient with a lung mass, the differential for the liver lesion includes:

Diagnosis	Key Features
Hepatic metastases from lung cancer	Most likely if known/suspected lung primary. CT shows hypovascular lesions (lung cancer typically produces hypovascular mets) ^[13].
HCC	Background chronic liver disease (HBV/HCV, cirrhosis). Arterial enhancement with portal venous washout on triphasic CT. AFP > 400 ng/mL almost diagnostic ^[13].
Other metastases	If the lung mass itself is a metastasis, the liver lesion may also be from the same primary (e.g., colorectal cancer metastatic to both lung and liver).
Benign lesions	Haemangioma (peripheral nodular enhancement, centripetal fill-in), FNH, adenoma — important not to assume malignancy without imaging characterisation.

Presentation	Top Differentials to Exclude	Key Discriminators
Solitary lung nodule/mass	TB granuloma, hamartoma, metastasis, abscess, organising pneumonia	Imaging features, stability on serial imaging, biopsy
Multiple lung nodules	Metastases, TB, GPA, septic emboli, sarcoidosis	Clinical context, distribution pattern, cavitation
Cavitating lesion	SCC, TB, abscess, GPA, infarct	Wall thickness, clinical features, microbiology
Haemoptysis	Bronchiectasis, TB, PE, NPC	Volume, imaging, bronchoscopy
Chronic cough in smoker	COPD, TB, bronchiectasis, GORD, ACEI cough	Sputum studies, PFTs, imaging, medication review
SVC obstruction	Lymphoma, thymoma, fibrosing mediastinitis	Imaging, biopsy
Pancoast syndrome	Neurogenic tumour (schwannoma), TB of lung apex, metastasis to apex	MRI of thoracic inlet, biopsy
Brain metastasis with unknown primary	Primary brain tumour, brain abscess	Imaging features, search for primary, stereotactic biopsy

High Yield Summary — DDx of CA Lung

Not all lung nodules are cancer — 70% of incidentally found pulmonary nodules are benign ^[7]^[8].
Key benign mimics: TB granuloma (very common in HK), hamartoma (fat + popcorn calcification), lung abscess, organising pneumonia, AVM.
Malignant DDx: primary lung cancer, metastatic deposit (search for primary!), lymphoma, carcinoid.
Cavitating lesions: SCC is the most common malignant cause; TB and abscess are the most common infectious causes ^[8]^[9].
Always distinguish primary lung cancer from lung metastasis — different management entirely. Use IHC (TTF-1 for lung adenocarcinoma, p40 for lung SCC).
Haemoptysis DDx in HK: always consider NPC (nasopharyngeal carcinoma) alongside CA lung and TB.
10–15% of solitary brain lesions in known cancer patients are NOT metastasis ^[11] — don't assume.
Compare with previous films ^[7] — stability over > 2 years is very reassuring for benign aetiology.

Active Recall - DDx of CA Lung

References

^[7] Senior notes: Maksim Medicine Notes.pdf (p.278–281, Respiratory Medicine — DDx of cough, haemoptysis, dyspnoea, and incidental lung nodules) ^[8] Senior notes: Ryan Ho Respiratory.pdf (p.43, Approach to solitary pulmonary nodule and cavitating lesions) ^[9] Senior notes: Ryan Ho Fundamentals.pdf (p.236, Approach to lung nodules and cavitating lesions) ^[10] Senior notes: Maksim Surgery Notes.pdf (p.222–223, Approach to spine diseases — DDx of back pain and cauda equina syndrome) ^[11] Senior notes: Ryan Ho Neurology.pdf (p.164,

Diagnostic Criteria, Algorithm, and Investigations for CA Lung

2. Initial Investigations — The Baseline Work-Up

When you suspect lung cancer (e.g., a smoker with chronic cough, haemoptysis, weight loss, or an incidental finding on CXR), the initial work-up proceeds in layers.

Test	Rationale / What to Look For
CBC	Anaemia of chronic disease (↓Hb), thrombocytosis (reactive — common in malignancy), polycythaemia (paraneoplastic — rare, via ectopic EPO). Leukocytosis may suggest post-obstructive infection.
LFTs (liver function tests)	Deranged LFTs (especially ↑ALP, ↑GGT) suggest liver metastases. Also serves as baseline before chemotherapy (hepatotoxic drugs).
RFTs (renal function tests)	Baseline for chemotherapy (cisplatin is nephrotoxic). Hypercalcaemia from bone mets or PTHrP can cause renal impairment.
LDH	Non-specific tumour marker; elevated in extensive disease, especially SCLC. Prognostic value.
Calcium, phosphate	Hypercalcaemia from PTHrP (SCC) or bone metastases.
CRP / ESR	Non-specific inflammatory markers; elevated in malignancy and infection.
Coagulation profile	Baseline for biopsy procedures. Also relevant if considering anticoagulation for VTE (cancer-associated thrombosis).
ABG	Assess oxygenation — particularly if dyspnoeic. Type 1 respiratory failure (↓PaO₂, normal/↓PaCO₂) in large effusion, lymphangitis carcinomatosis, or extensive parenchymal disease.

Test	Rationale
Sputum cytology	Can occasionally identify malignant cells (especially central tumours shedding into the airway). Low sensitivity (~40-60% for central, much lower for peripheral tumours). Useful for patients unfit for invasive biopsy ^[2]. Collect early morning sputum × 3 samples to maximise yield.
Sputum AFB smear + TB culture	Always exclude TB in HK — TB is endemic and can mimic CA lung radiologically (upper lobe mass, cavitation, constitutional symptoms).
Sputum Gram stain + C/ST	If post-obstructive pneumonia is suspected.

3. Radiological Assessment — The Imaging Ladder

Imaging is done in a stepwise fashion: CXR → CT → PET-CT (± MRI). Each modality adds information.

Role: Raises suspicion of malignancy (non-diagnostic) ^[2]. It is the first-line imaging for any patient presenting with respiratory symptoms.
Sensitivity: Limited — can miss lesions < 1–2 cm, retrocardiac/apical tumours, and early-stage disease. A normal CXR does not exclude lung cancer.

CXR features of CA lung ^[2]:

CXR Finding	Interpretation
1 — Unilateral hilar mass	Central tumour or hilar lymph node enlargement ^[2]
2 — Peripheral pulmonary opacity	Irregular but well-circumscribed ± cavitation (mimics abscess) ^[2]
3 — Collapsed lung	Tumour obstruction of bronchus or nodal compression on main bronchus ^[2] — look for volume loss signs (raised hemidiaphragm, mediastinal shift toward the lesion, reduced rib spaces)
4 — Pleural effusion	Tumour invasion of pleural space; less commonly parapneumonic effusion secondary to obstruction ^[2]
5 — Broadening of mediastinum	Paratracheal lymphadenopathy ^[2]
6 — Enlarged cardiac shadow	Malignant pericardial effusion ^[2]
7 — Elevated hemidiaphragm	Phrenic nerve palsy ^[2]
8 — Rib destruction	Direct invasion or blood-borne metastasis; osteolytic in nature ^[2]

Other CXR patterns to recognise:

Golden S sign: RUL collapse with a concave lateral border of the collapsed lobe — the "S" is formed by the mass compressing the horizontal fissure ^[7].
Reticulonodular shadowing: if diffuse, consider lymphangitis carcinomatosis.

CXR Collapse Patterns — High Yield for Exams

RUL collapse: Golden S sign (mass compression on horizontal fissure) ^[7]
LUL collapse: Luftsichel sign (compensatory enlarged LLL wraps around medial LUL, creating a crescent of hyperaerated lung around the aortic knuckle) ^[7]
LLL collapse: Sail sign (triangular opacity behind the heart) ^[7]
RLL collapse: Triangular opacity in the right lower zone, loss of right hemidiaphragm silhouette ^[7]

This is the workhorse investigation for lung cancer — it simultaneously serves diagnostic, staging, and biopsy-planning functions.

CT is favoured because of low cost, speed of examination, and simultaneous evaluation of intrathoracic and abdominal organs ^[2].

Function	Details
Diagnostic	Radiological features of the mass: size, margins (spiculated vs smooth), density, cavitation, enhancement. Assess extent of local disease. ^[2]
Guide biopsy	Assess location → plan biopsy method ^[2] — a peripheral lesion may be sampled by CT-guided transthoracic needle biopsy; a central lesion by bronchoscopy.
Staging (modality of choice) ^[2]	Assess T (tumour size, invasion of chest wall/mediastinum/other structures), N (lymph node status), M (liver, adrenal metastases).
Treatment planning	RT planning: assessment of anatomic relationship, disease extent and surrounding tissue thickness ^[2]. Also assess treatment response on follow-up CT ^[2].

Coverage: Must cover liver and adrenals ^[2] — because these are common sites of lung cancer metastasis. This is why it's "CT thorax + upper abdomen," not just "CT thorax."

Key caveats for CT staging ^[2]:

Nodal metastasis depends on size criteria: > 10 mm on short axis (or SUV > mediastinal blood pool on PET-CT) considered malignant nodes ^[2].
- Caveat 1: Cannot tell between reactive vs metastatic ^[2] — a 12 mm node could be reactive inflammation, not cancer. This is why pathological confirmation is often needed.
- Caveat 2: Cannot detect microscopic metastasis ^[2] — a 6 mm node could harbour tumour cells.
- → Usually require further confirmation by biopsy ^[2].
Poor soft tissue visualisation → indeterminate chest wall and mediastinal invasion ^[2]. Presence of these precludes surgical resection because a good resection margin cannot be achieved ^[2]. MRI is better for soft tissue assessment.

CT characteristics of the primary lesion ^[14]^[9]:

Feature	Malignant	Benign
Shape/outline	Irregular or infiltrative ^[14] → spiculated, lobulated	Well-circumscribed, round/oval
Calcification	Eccentric or absent	Central, uniform, "popcorn" (hamartoma), laminated
Enhancement	HU > 15	HU < 15 (minimal or none)
Other	Pleural retraction, heterogeneous attenuation	Fat-containing (hamartoma — pathognomonic)

PET-CT has become a near-standard part of lung cancer staging, though its routine use remains debated.

Principle ^[2]:

Injection of 18FDG tracer → tissues with ↑metabolic rate show ↑glucose uptake → tracer retained because FDG cannot be incorporated into glycolysis (it gets phosphorylated by hexokinase to FDG-6-phosphate, which cannot proceed further in glycolysis and becomes trapped) → tissues with ↑metabolic rate will "light up" ^[2].

SUVmax > 2.5 considered suspicious for malignancy ^[2].
PET alone has low resolution → combination with CT provides anatomical detail ^[2].

Advantage	Limitation
High sensitivity for occult metastasis ^[2] — detects bone, adrenal, contralateral lung, and distant nodal metastases that CT alone might miss	No evidence for improvement in overall survival ^[2]
Useful in marginally resectable or high surgical risk cases to ↓risk of futile surgery ^[2]	False positives: infection, inflammation (TB, sarcoidosis, pneumonia)
Helpful in evaluating mediastinal nodes (functional rather than purely size-based)	False negatives: low-grade tumours (carcinoid, lepidic-predominant adenocarcinoma, mucinous adenocarcinoma), small lesions < 8 mm
Can detect unsuspected second primaries	PET-CT is NOT good for brain — background activity is too hypermetabolic ^[2] (the brain uses ~20% of total body glucose)

PET-CT and the Brain

PET-CT is not good for detecting brain metastases because the normal brain has very high background FDG uptake ^[2]. If you need to assess for brain metastases, use contrast MRI brain (or CT brain if MRI is contraindicated). Always order brain imaging separately if there is clinical suspicion (headache, focal neurology, seizures) or if the patient has a high-risk tumour type (adenocarcinoma, SCLC).

Clinical Scenario	Imaging Approach
Initial work-up	CXR → CT thorax + upper abdomen with contrast
Staging	PET/CT (whole body) ± MRI brain
Pancoast tumour	MRI thoracic inlet
Suspected brain mets	Contrast MRI brain
Suspected cord compression	MRI whole spine (urgent)
Suspected liver mets	Triphasic CT or MRI liver

4. Tissue Diagnosis — How to Get Pathology

A tissue diagnosis is always required ^[2]. The choice of biopsy method depends on the location of the tumour and accessibility. The general principle is: sample the highest-stage site — because this gives you both diagnosis and staging in one step. For example, if there is a lung mass with a suspicious supraclavicular node, biopsy the node (if positive, it confirms N3 → stage IIIB/C and avoids unnecessary mediastinal staging).

Method	Indication	How It Works	Key Points
Sputum cytology	Patient unfit for invasive biopsy ^[2]	Patient coughs up sputum → cytologist examines for malignant cells	Low sensitivity (30–65%), especially for peripheral tumours. Requires 3 early morning samples.
Conventional bronchoscopy ^[2]	Usually only for directly visualised lesions ^[2]	Flexible bronchoscope inserted via nose/mouth into airways → directly visualise endobronchial tumour	Modalities: (1) Saline washing, (2) Brushing, (3) Endobronchial forceps biopsy for directly visualised lesions ^[2]. Transbronchial biopsy or needle aspiration for lesions close to airways ^[2]. Bronchoalveolar lavage (BAL) for peripheral lesions ^[2]. Yield is ~80% for central tumours, much lower for peripheral.
EBUS-TBNA (Endobronchial Ultrasound – Transbronchial Needle Aspiration)	Diagnosis and staging by sampling central tumours and paratracheal/subcarinal/hilar lymph nodes ^[2]	Ultrasound probe on the tip of the bronchoscope → real-time visualisation → needle aspiration through the bronchial wall into the target node/mass	Also used to R/O alternative dx for mediastinal lymphadenopathy (e.g., TB, sarcoidosis, lymphoma) ^[2]. Limitation: Cannot access some lymph node stations (levels 3a, 5, 6, 8, 9) and peripheral tumours ^[2].
EUS-FNA (Endoscopic Ultrasound – Fine Needle Aspiration)	Subcarinal and para-oesophageal nodes ^[2]	Ultrasound on oesophageal endoscope → needle through oesophageal wall into mediastinal nodes	Complements EBUS — accesses nodes that EBUS cannot reach (stations 8, 9, and some station 7).
CT-guided transthoracic needle aspiration/biopsy (TTNA/TTNB)	Sample peripheral nodules when other modalities are not available ^[2]	CT-guided ^[2] — radiologist advances a needle percutaneously through the chest wall into the peripheral lesion	Fine needle biopsy is quite accurate (80–95% accuracy) and safe (< 2% complication rate) ^[14]. Risk: pneumothorax ^[2] (~15–25%, but only ~5% require chest drain). Also risk of haemorrhage. Contraindications: uncorrected bleeding diathesis (platelet < 50,000, INR > 1.5), inaccessible lesion, uncooperative patient ^[14].
Electromagnetic navigation bronchoscopy	Peripheral lesions ^[2]	New technique using electromagnetic field to guide bronchoscope to peripheral lesions (like GPS for the bronchial tree)	Image-guided ^[2]; increasing availability. Particularly useful when CT-guided biopsy carries high pneumothorax risk (e.g., emphysematous lungs).
Mediastinoscopy	Mediastinal nodes when less invasive strategies fail ^[2]	Scope through pretracheal plane ^[2] under GA → directly visualise and biopsy paratracheal and subcarinal nodes	Risk of injury of great vessels ^[2]. Being replaced by EBUS-TBNA in many centres.
VATS ^[2]	Suspicious lesions amenable to wedge resection; otherwise inaccessible nodes; pleural biopsy ^[2]	Minimally invasive surgery under GA with thoracoscope	Can be both diagnostic (wedge resection for frozen section) and therapeutic (proceed to lobectomy if malignant).
Diagnostic thoracocentesis ^[2]	Pleural effusion	Needle aspiration of pleural fluid → send for cytology	Diagnosis only, no histopathological information ^[2] (cytology, not histology). Positive cytology for malignant cells = confirmed malignant pleural effusion (M1a).
Medical thoracoscopy (pleuroscopy) ^[2]	Pleural disease — especially when thoracocentesis cytology is negative	Semi-rigid instrument with one port of entry through flexible trocar → allows direct visualisation of pleural cavity → ↑yield ^[2]	Can simultaneously perform drain + biopsy + pleurodesis ^[7]. Requires IV sedation (cf. GA in VATS).
Sampling of metastatic disease ^[2]	M1a–c or N3 scalene/supraclavicular nodes ^[2]	By appropriate route: thoracocentesis, liver FNAC, adrenal FNAC, supraclavicular node biopsy ^[2]	Always sample the highest stage site — gives diagnosis + staging simultaneously.

Tissue Diagnosis Strategy — Sample the Highest Stage

If a patient has a lung mass + enlarged supraclavicular lymph node + suspicious liver lesion, biopsy the liver (M1b) or the supraclavicular node (N3) first. If positive, it simultaneously gives you the tissue diagnosis AND confirms advanced stage, avoiding unnecessary mediastinal staging procedures. This principle saves time, reduces risk, and avoids futile surgery.

5. Staging

AJCC8 TNM staging for CA lung ^[2]:

T — Primary Tumour:

T Stage	Criteria
Tis	Carcinoma in situ ^[2]
T1	Tumour ≤ 3 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus ^[2]
T1a(mi)	Minimally invasive adenocarcinoma ^[2]
T1a	Tumour ≤ 1 cm ^[2]
T1b	Tumour > 1 cm but ≤ 2 cm ^[2]
T1c	Tumour > 2 cm but ≤ 3 cm ^[2]
T2	Tumour > 3 cm but ≤ 5 cm; or involves main bronchus regardless of distance from carina but without involvement of carina; or invades visceral pleura; or associated with atelectasis/obstructive pneumonitis extending to hilar region involving part or all of the lung ^[2]
T2a	> 3 cm but ≤ 4 cm
T2b	> 4 cm but ≤ 5 cm
T3	> 5 cm but ≤ 7 cm; or direct invasion of chest wall (including superior sulcus tumours), phrenic nerve, parietal pericardium; or separate tumour nodule(s) in the same lobe
T4	> 7 cm; or invasion of diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, oesophagus, vertebral body, carina; or separate tumour nodule(s) in a different ipsilateral lobe

N — Regional Lymph Nodes:

N Stage	Criteria
N0	No regional lymph node metastasis
N1	Ipsilateral peribronchial and/or hilar nodes and intrapulmonary nodes
N2	Ipsilateral mediastinal and/or subcarinal nodes
N3	Contralateral mediastinal/hilar; ipsilateral or contralateral scalene/supraclavicular nodes

M — Distant Metastasis:

M Stage	Criteria
M0	No distant metastasis
M1a	Separate tumour nodule in contralateral lobe; pleural/pericardial nodules; malignant pleural/pericardial effusion
M1b	Single extrathoracic metastasis (including single distant lymph node)
M1c	Multiple extrathoracic metastases in one or more organs

Stage Grouping (Simplified):

Stage	TNM	5-Year Survival (approx.)
IA1	T1a N0 M0	~90%
IA2	T1b N0 M0	~85%
IA3	T1c N0 M0	~80%
IB	T2a N0 M0	~73%
IIA	T2b N0 M0	~65%
IIB	T1-2 N1 M0 or T3 N0 M0	~56%
IIIA	T1-2 N2 M0 or T3 N1 M0 or T4 N0-1 M0	~36%
IIIB	T1-2 N3 M0 or T3-4 N2 M0	~26%
IIIC	T3-4 N3 M0	~13%
IVA	Any T, Any N, M1a-b	~10%
IVB	Any T, Any N, M1c	~< 5%

Stage	Definition	Proportion
Limited disease	Confined to one hemithorax + ipsilateral supraclavicular nodes (can be encompassed in a single radiation field)	~30%
Extensive disease	Anything beyond limited disease (contralateral lung, distant mets, malignant pleural effusion)	~70%

Why this simpler system? Because SCLC almost always presents with disseminated disease, and the key treatment decision is simply: "Can I give concurrent chemoradiation (limited) or chemo ± immunotherapy only (extensive)?"

This is from the senior notes and represents the systematic approach to confirming N stage ^[2]:

Risk Category	Criteria	Approach
Low risk	Peripheral tumours with stage IA1–3	Upfront lobectomy + mediastinal lymph node dissection (risk of occult N2 disease is low) ^[2]
Moderate risk	Central stage IA, any stage IB–II, adenocarcinoma, young age	Biopsy of primary tumour by appropriate route. Pre-op mediastinal staging by EBUS-TBNA ± EUS-FNA (risk of occult N2 disease 10–15%) ^[2]
High risk	T3–4 disease without obvious mediastinal involvement	Biopsy of primary tumour by appropriate route. Pre-treatment mediastinal staging by EBUS-TBNA ± EUS-FNA ^[2]
Suspected mediastinal mets	FDG-avid or enlarged N2/3 mediastinal nodes or mediastinal involvement	Targeted mediastinal biopsy at highest suspected stage by EBUS-TBNA ± EUS-FNA for staging and diagnosis → invasive biopsy if initial test negative/non-diagnostic ^[2]
Metastatic disease	M1a–c or N3 scalene or supraclavicular nodes	Sampling of metastatic disease by appropriate route (e.g., thoracocentesis, liver and adrenal FNAC) ^[2]

6. Fitness Assessment — Can the Patient Tolerate Treatment?

Even if a tumour is technically resectable by staging, you must assess whether the patient can survive the surgery.

Mandatory in potentially operable cases to assess lung reserve ^[2].

Test	How It's Used	Key Thresholds
Spirometry: FEV₁ and DLCO ^[2]	Calculate predicted postoperative values (ppoFEV₁, ppoDLCO) ^[2]	↑risk for major respiratory complications (pneumonia, stump failure, mortality) if either ppoFEV₁ or ppoDLCO < 40% predicted ^[2]. Post-op mechanical ventilation likely if ppo ≤ 30% predicted ^[2].
	Method: ppo = pre-op value × (19 − number of resected segments) / 19 ^[2] (the lung has 19 segments total)

Example: If pre-op FEV₁ = 2.0 L (80% predicted) and you plan right lower lobectomy (5 segments):

ppoFEV₁ = 2.0 × (19 − 5) / 19 = 2.0 × 14/19 = 1.47 L (~59% predicted) → acceptable.

Test	Threshold
6-minute walk test / shuttle walk test	Able to walk > 400 m ^[2]
Stair climbing test	5 flights of stairs (FOS) for pneumonectomy, 3 FOS for lobectomy, 1 FOS for GA operation ^[2]
Cardiopulmonary exercise test (CPET)	VO₂ max (maximal oxygen consumption per unit body weight, mL/kg/min) ^[2]: > 20 (not increased risk), < 15 (↑risk of perioperative complications), < 10 (very high risk for perioperative complications or death) ^[2]

If clinical features suggest a paraneoplastic syndrome, directed investigations include:

Suspected Syndrome	Key Investigations
SIADH	Paired serum and urine osmolality, serum Na+, urine Na+ (serum osm < 275, urine osm > 100, urine Na+ > 40, euvolaemic hyponatraemia)
Ectopic Cushing's	ACTH level (high), LDDST (no suppression), HDDST (no suppression — unlike pituitary Cushing's which suppresses) ^[16]^[17], 24h urinary free cortisol, CXR for any obvious CA lung ^[16]
Hypercalcaemia	Serum Ca²+ (corrected), PTH (suppressed if PTHrP-mediated), PTHrP level
LEMS	Anti-VGCC antibodies, nerve conduction studies (incremental response with repetitive nerve stimulation — opposite of myasthenia gravis)

If a pleural effusion is present, thoracocentesis is performed ^[7]:

Pleural fluid analysis ^[7]:

Test	Interpretation
Appearance	Straw-coloured (transudate), turbid (empyema), milky (chylothorax), bloody (malignancy, PE, trauma) ^[7]
Light's criteria (Protein, LDH)	Exudative if any one: (1) pleural protein/serum protein > 0.5, (2) pleural LDH/serum LDH > 0.6, (3) pleural LDH > 2/3 upper limit of normal serum LDH. Malignant effusions are exudative.
pH	< 7.2 suggests empyema or advanced malignant effusion (poor prognosis for pleurodesis)
Glucose	Low (< 3.3 mmol/L) in empyema, RA, malignancy, TB
ADA	> 30 suggests TB ^[7]
Cell count and differential	Lymphocyte-predominant: TB, malignancy, lymphoma. Neutrophil-predominant: parapneumonic.
Microbiology	Gram stain, AFB smear, bacterial culture, TB culture, MTB-PCR ^[7]
Cytology	20 mL × 3 if suspect malignant effusion ^[7] — sensitivity ~60% for malignant pleural effusion (one sample ~50%, three samples ~70%)

If cytology is negative but clinical suspicion remains high → proceed to medical thoracoscopy (pleuroscopy) or VATS pleural biopsy for definitive tissue diagnosis ^[2]^[7].

Modality	Utility
CXR screening	Not useful ^[7] — multiple trials (including the PLCO trial) showed no mortality reduction with CXR screening.
Annual low-dose CT (LDCT) thorax ^[7]	Recommended for high-risk individuals ^[7]: age 55–74 years (some guidelines extend to 50–80y), current or former smokers (≥ 20 pack-years, quit < 15 years ago), fit for curative surgery ^[7]. Based on NLST and NELSON trials showing ~20% reduction in lung cancer mortality.

Note: There is currently no population-wide lung cancer screening programme in Hong Kong (as of 2025–2026), though some private centres offer it. The HK government has been evaluating the feasibility of a targeted LDCT screening programme.

For nodules found incidentally (not in a known cancer patient), the Fleischner Society provides follow-up recommendations based on size, morphology (solid vs subsolid), and patient risk factors ^[7]:

Solid nodules in patients ≥ 35 years:

Size	Low Risk	High Risk
< 6 mm	No routine follow-up	Optional CT at 12 months
6–8 mm	CT at 6–12 months, then consider CT at 18–24 months	CT at 6–12 months, then CT at 18–24 months
> 8 mm	Consider CT at 3 months, PET-CT, or tissue sampling	Consider CT at 3 months, PET-CT, or tissue sampling

Subsolid (ground-glass / part-solid) nodules:

GGO < 6 mm: no routine follow-up
GGO ≥ 6 mm: CT at 6–12 months → if persistent, CT every 2 years for minimum 5 years
Part-solid ≥ 6 mm: CT at 3–6 months → if persistent and solid component ≥ 6 mm, consider PET-CT or biopsy

High Yield Summary — Diagnosis of CA Lung

No formal "diagnostic criteria" — diagnosis requires clinical suspicion + imaging + tissue confirmation.
CXR raises suspicion; CT thorax + upper abdomen with contrast is the key staging modality. Must cover liver and adrenals.
CXR features: hilar mass, peripheral opacity, collapse, effusion, mediastinal widening, elevated hemidiaphragm, rib destruction, pericardial effusion.
PET-CT: high sensitivity for occult metastasis; SUVmax > 2.5 suspicious. NOT useful for brain (too hypermetabolic).
MRI: for Pancoast tumours (soft tissue/brachial plexus invasion) and brain metastases.
Tissue diagnosis is mandatory: choose method based on location — bronchoscopy (central), EBUS-TBNA (mediastinal nodes), CT-guided TTNA (peripheral), thoracocentesis/pleuroscopy (effusion). Always sample highest-stage site first.
Pathological assessment: subtype by IHC (TTF-1, p40, synaptophysin); molecular profiling (EGFR, ALK, ROS1, PD-L1, NGS) mandatory for all non-squamous NSCLC.
TNM 8th edition for NSCLC; limited vs extensive for SCLC.
Mediastinal staging: risk-stratified approach — peripheral IA can go straight to surgery; higher risk needs EBUS-TBNA ± EUS-FNA pre-operatively.
Fitness: ppoFEV₁ and ppoDLCO ≥ 40% predicted; VO₂ max > 15; stair climbing ≥ 3 FOS for lobectomy.
Screening: annual LDCT for high-risk (age 55–74, ≥ 20 pack-years, current/recent smoker). CXR screening is NOT useful.

Active Recall - Diagnosis and Staging of CA Lung

References

^[1] Senior notes: Maksim Medicine Notes.pdf (p.51, Lung Cancer — Pathology, IHC markers) ^[2] Senior notes: Ryan Ho Respiratory.pdf (p.141–147, Lung Cancer — Epidemiology, Radiological Assessment, Tissue Diagnosis, Staging, Fitness Assessment, Mediastinal Staging) ^[7] Senior notes: Maksim Medicine Notes.pdf (p.278–281, Respiratory Medicine — Pleural effusion, clinical approach, investigations, Fleischner guidelines, screening) ^[9] Senior notes: Ryan Ho Fundamentals.pdf (p.236, Approach to lung nodules — benign vs malignant features) ^[14] Senior notes: Ryan Ho Diagnostic Radiology.pdf (p.39, 43, 62, 79 — CT interpretation, interventional radiology, fine needle biopsy) ^[15] Senior notes: Maksim Surgery Notes.pdf (p.124–125, IHC for liver metastasis of unknown origin) ^[16] Senior notes: Ryan Ho Endocrine.pdf (p.63, Cushing's syndrome — HDDST, ectopic ACTH, CXR for CA lung) ^[17] Senior notes: Ryan Ho Fundamentals.pdf (p.437, Cushing's syndrome work-up)

Management of CA Lung

2. NSCLC Management — Stage-by-Stage

For NSCLC, treatment and prognosis depends heavily on staging and molecular markers ^[2]:

Surgery for early stages (i.e., stage I–II + selected stage III) ^[2]
Concurrent chemoirradiation for unresectable stage III (e.g., N2+ disease) ^[2]
Systemic treatment for stage IV ^[2]

2.1 Resectable NSCLC (Stage I, II, Selected IIIA)

Three conditions must ALL be met:

Criterion	Details
Appropriate stage	Stage I, stage II, T3N1, selected T4N0–1 ^[2]
NO mediastinal involvement	N2 precludes resection ^[2] — confirmed by EBUS-TBNA/mediastinoscopy. Why? Because N2 disease means tumour has spread beyond what can be reliably cleared by surgery alone; outcomes are better with chemoradiation ± surgery.
Adequate cardiac and lung reserve	Patient must survive the operation and the postoperative period with remaining lung function ^[2]

Surgical approach: now nearly all can be done under VATS ^[2].

VATS lobectomy is the standard of care for early-stage NSCLC ^[3]. Why VATS over open thoracotomy? Smaller incisions → less postoperative pain, faster recovery, shorter hospital stay, reduced postoperative complications, with equivalent oncological outcomes ^[3].

Operation	Description	Indication
Lobectomy	Gold standard for CA lung ^[2]. Removal of the entire lobe containing the tumour.	Standard operation for stage I–II NSCLC with adequate lung reserve
Sublobar resection (segmentectomy / wedge resection)	Removal of less than a full lobe	For those who cannot tolerate full lobectomy + primary tumour ≤ 3 cm ^[2]. Recent evidence (JCOG0802, CALGB 140503) supports segmentectomy for tumours ≤ 2 cm with equivalent survival. Wedge resection has slightly higher local recurrence.
Sleeve lobectomy	Lobectomy + resection of a segment of bronchus involved → rejoin the rest of the lung to the main bronchus ^[2]	Alternative to pneumonectomy for tumour close to main bronchus ^[2]. Preserves more lung tissue. Like cutting out a segment of a sleeve (shirt sleeve analogy) and sewing the remaining parts together.
Pneumonectomy	Removal of the entire lung	May be required for proximal tumours ^[2] that cannot be managed by sleeve lobectomy. Carries higher morbidity/mortality. Requires sufficient contralateral lung reserve.
± en bloc resection of chest wall	Lobectomy with resection of involved chest wall (ribs, intercostal muscles)	In tumours invading chest wall (T3) ^[2]. Achieves R0 resection margins.

All curative resections include + mediastinal lymph node dissection (usually routine in resectable NSCLC) ^[2]. This is both therapeutic (removes potentially involved nodes) and prognostic (pathological staging determines need for adjuvant therapy).

The Goal of Surgery — R0 Resection

The goal of curative surgery is complete (R0) resection — removal of all macroscopic and microscopic tumour with negative margins ^[5]. R0 = no residual tumour. R1 = microscopic residual. R2 = macroscopic residual. Only R0 gives the best chance of cure. This is why adequate margins and mediastinal lymph node dissection are critical.

Adjuvant Treatment	Indication	Rationale
Adjuvant chemotherapy	Pathologic stage II–III or high-risk stage IB ^[2]	Micrometastatic disease may already be present even after complete resection. Adjuvant cisplatin-based doublet chemotherapy (e.g., cisplatin + vinorelbine) improves 5-year survival by ~5% in stage II–III.
Adjuvant RT	Positive surgical margin, or mediastinal LN involvement detected intraoperatively ^[2]	To sterilise residual microscopic disease at the resection margin or in the mediastinum.
Adjuvant targeted therapy	EGFR-mutant stage IB–IIIA (after complete resection + adjuvant chemo)	Osimertinib (3rd-gen EGFR TKI) for 3 years — ADAURA trial showed dramatic improvement in DFS. Now standard of care (2024–2026 guidelines).
Adjuvant immunotherapy	PD-L1 ≥ 1%, stage II–IIIA, after complete resection + adjuvant chemo	Atezolizumab (IMpower010 trial) for 1 year.

Neoadjuvant therapy is increasingly used, particularly for stage II–IIIA NSCLC ^[5]:

Approach	Details
Neoadjuvant chemoimmunotherapy	Nivolumab + platinum-doublet chemotherapy × 3 cycles before surgery (CheckMate 816 trial). Dramatically improved pathological complete response (pCR) rates. Now standard for resectable stage IB ( ≥ 4 cm)–IIIA.
Neoadjuvant chemoRT (if N2) ^[1]	For potentially resectable N2 disease — downstage the mediastinal nodes before surgery.

Why neoadjuvant? (1) Tumour may shrink → easier/safer surgery. (2) Treats micrometastatic disease early. (3) In-vivo chemosensitivity test — if the tumour doesn't respond, you know the chemo isn't working. (4) Better drug delivery before surgical disruption of blood supply.

Concurrent chemoirradiation as treatment of choice ^[2]:

Component	Details
Chemotherapy regimen	Usually cisplatin + etoposide or weekly carboplatin + paclitaxel ^[2]. Cisplatin is a platinum compound that cross-links DNA → prevents replication. Etoposide is a topoisomerase II inhibitor → prevents DNA unwinding.
Radiotherapy	Usually full-dose IMRT (60 Gy in 30 daily fractions) ^[2]. IMRT = intensity-modulated radiation therapy — shapes the radiation beam to conform to the tumour, sparing surrounding normal tissue.
Consolidation immunotherapy	± Durvalumab (anti-PD-L1) if no progression after concurrent chemoirradiation ^[2] — PACIFIC trial showed significant OS improvement (~47% vs 34% at 5 years). Now standard for unresectable stage III with PD-L1 ≥ 1%. Given for up to 12 months.

Why "concurrent" (not sequential)? Because giving chemo and RT simultaneously is synergistic — chemo sensitises cancer cells to radiation (radiosensitisation), improving local control and survival. The trade-off is more toxicity (especially oesophagitis and pneumonitis).

Cisplatin + etoposide + full-dose IMRT (2 Gy × 30 days) ^[1] — this is the classic regimen. Note from the lecture slides that the dose is 2 Gy per fraction × 30 fractions = 60 Gy total.

2.3 Advanced / Metastatic NSCLC (Stage IV)

This is where the revolution has happened. Treatment has moved from "one-size-fits-all chemotherapy" to precision medicine based on molecular profiling.

Molecular Subtype	Prevalence (HK)	First-Line Treatment	Mechanism	Key Points
EGFR mutation	~55% of adenocarcinoma ^[2]	Osimertinib (3rd-gen EGFR TKI)	"Osimertinib" — targets EGFR (epidermal growth factor receptor) tyrosine kinase. Blocks the signal that tells cancer cells to grow and divide. 3rd generation = also active against T790M resistance mutation.	FLAURA trial: osimertinib superior to 1st-gen TKIs (gefitinib/erlotinib). Median OS ~38 months. Also penetrates BBB (treats/prevents brain mets).
ALK rearrangement	~5% of adenocarcinoma ^[2]	Alectinib (2nd-gen ALK TKI)	ALK = anaplastic lymphoma kinase. EML4-ALK fusion creates a constitutively active kinase → drives proliferation. Alectinib blocks this.	ALEX trial: alectinib superior to crizotinib. Good CNS penetration. Lorlatinib (3rd-gen) for resistance.
ROS1 rearrangement	~1–2%	Crizotinib or entrectinib	ROS1 is structurally similar to ALK. Crizotinib inhibits both ALK and ROS1.	Respond well to ALK inhibitors due to structural homology.
KRAS G12C	~5–10% ^[2]	Sotorasib or adagrasib	KRAS = Kirsten rat sarcoma viral oncogene. G12C = specific glycine-to-cysteine mutation. Sotorasib covalently binds the cysteine, locking KRAS in its inactive state.	Historically "undruggable" — sotorasib was a breakthrough (2021).
BRAF V600E	~1–2%	Dabrafenib + trametinib	BRAF = serine/threonine kinase in the MAPK pathway. V600E = constitutively active. Dabrafenib inhibits BRAF; trametinib inhibits MEK (downstream).	Dual blockade of the same pathway — more effective than either alone.
MET exon 14 skipping	~3%	Capmatinib or tepotinib	MET = mesenchymal-epithelial transition factor. Exon 14 skipping → impaired MET degradation → constitutive signalling.
RET rearrangement	~1–2%	Selpercatinib or pralsetinib	RET = rearranged during transfection. Fusion → constitutively active kinase.
NTRK fusion	< 1%	Larotrectinib or entrectinib	NTRK = neurotrophic tyrosine receptor kinase. Tumour-agnostic indication.
No actionable mutation, PD-L1 ≥ 50%	Variable	Pembrolizumab monotherapy	Anti-PD-1 monoclonal antibody. Blocks PD-1 on T cells → prevents tumour from "hiding" from the immune system via PD-L1/PD-1 interaction.	KEYNOTE-024 trial.
No actionable mutation, PD-L1 1–49%	Variable	Pembrolizumab + platinum-doublet chemotherapy	Immunotherapy + chemo synergy — chemo causes immunogenic cell death, releasing tumour antigens, enhancing the immune response.	KEYNOTE-189 trial.
No actionable mutation, PD-L1 < 1%	Variable	Platinum-doublet chemotherapy ± ipilimumab/nivolumab	Chemotherapy backbone: cisplatin/carboplatin + pemetrexed (non-squamous) or gemcitabine (squamous).	CheckMate 9LA or KEYNOTE-189 (chemo + pembro still used regardless of PD-L1 in some guidelines).

Why EGFR-Mutant Patients Should NOT Receive Immunotherapy

Counterintuitively, EGFR-mutant and ALK-rearranged NSCLC responds poorly to checkpoint inhibitors. The tumour microenvironment in these driver-mutated cancers tends to be immunologically "cold" (low tumour mutational burden, few neoantigens). Furthermore, combining EGFR TKIs with immunotherapy increases toxicity (especially pneumonitis) without improving efficacy. Always test for driver mutations FIRST — if present, use targeted therapy, not immunotherapy.

2.4 Special Situations in NSCLC

Solitary brain metastasis: surgery + RT ^[1].

Approach	Details
Surgery + adjuvant RT	If solitary, operable, symptomatic, good performance status, controlled systemic disease ^[18]
Stereotactic radiosurgery (SRS)	Now more preferred ^[18] over WBRT as adjuvant. For small/inoperable lesions or small oligometastases ( < 3 cm) ^[18].
Whole-brain RT (WBRT)	If not eligible for SRS/surgery, e.g., multiple bulky tumours ^[18]. Treats micrometastases but has significant neurocognitive side effects.
Systemic therapy	EGFR TKIs (especially osimertinib) and ALK TKIs (alectinib, lorlatinib) have good CNS penetration — may be sufficient for brain mets in driver-mutated NSCLC.
Dexamethasone + AED	For symptomatic relief ^[18] — dexamethasone reduces peritumoral vasogenic oedema; AEDs for seizure prophylaxis if seizures present.

Occurs in 50% of all metastatic malignancy, especially NSCLC ^[7]:

Treatment	Details
Repeated chest drain	Every few weeks ^[7] — temporary relief but recurrence is almost inevitable
Chemical pleurodesis (1st line for recurrent MPE) ^[7]	Agents: talc (5 g in 100 mL NS), minocycline (300 mg in 100 mL NS), autologous blood ^[7]. Mechanism: sclerosing agent causes intense pleural inflammation → fibrosis → obliteration of the pleural space → prevents re-accumulation. Procedure: connect chest drain → apply sclerosant when lung re-expanded → clamp for 1–2 h → release → continue drainage until output < 150 mL/day × 2 days + CXR shows lung re-expanded ^[7].
Surgical pleurodesis	Consider if good performance status ^[7]. VATS pleurodesis with mechanical abrasion or pleurectomy. Recurrence ~3% ^[7].
Long-term ambulatory indwelling pleural catheter (IPC)	Consider if short life expectancy or trapped lung ^[7]. Patient drains at home.
Pleuroperitoneal shunt (e.g., Denver shunt)	Consider if short life expectancy or trapped lung ^[7]. Diverts fluid from pleural space to peritoneum.

What is a "trapped lung"? When the visceral pleura is encased by tumour (malignant cortex), the lung cannot re-expand even after fluid drainage. Pleurodesis will fail because the two pleural surfaces cannot come into contact. In this situation, IPC or shunt is preferred.

Chemical Pleurodesis — Important Procedural Detail

If co-existing pneumothorax or bubbling chest drain: do NOT clamp the drain (risk of tension pneumothorax). Instead, hang up the drain to ~50 cm above patient to drain air but not the sclerosant ^[7]. This allows air to escape while keeping the sclerosant in the pleural space. Also: avoid NSAIDs post-pleurodesis — inflammatory action is essential ^[7] for the pleurodesis to work. If you suppress the inflammation, the pleurodesis fails.

These are oncological emergencies managed alongside the main treatment:

Emergency	Management
SVCO	Palliative RT ^[1] (SVC stenting if severe/urgent, chemotherapy if SCLC — highly chemo-responsive). Dexamethasone, head elevation, loop diuretics.
Cord compression	Urgent MRI whole spine → dexamethasone 16 mg/day → surgical decompression (if single level, good prognosis) or emergency RT (if multiple levels or poor prognosis).
Airway obstruction	Bronchoscopic laser therapy or stenting to relieve airway obstruction ^[2]. Emergency if stridor present.
Bone pain	Palliative RT for bone metastases ^[1] (single fraction 8 Gy or 20 Gy in 5 fractions). Bisphosphonates or denosumab for skeletal-related events.

3. SCLC Management

SCLC is fundamentally different from NSCLC:

Metastases tend to occur early ^[2] — most patients present with extensive disease.
Very chemosensitive and radiosensitive — high initial response rates (~60–80%).
Almost invariably relapses — median survival even with treatment is ~10–12 months for extensive disease.
Surgery is rarely indicated — because occult metastases are almost always present.

For unresectable limited stage disease (i.e., included in single RT field = TNM I–IIIB) ^[2]:

Component	Details
Chemoirradiation (mainstay)	Usually 4 cycles of etoposide + cisplatin (EP) + thoracic EBRT ^[2]. RT should begin early (within 1st or 2nd cycle of chemo).
Prophylactic cranial irradiation (PCI)	If respond well to initial chemo/RT without brain mets ^[2]. Rationale: occult brain mets occur frequently in SCLC without neurological symptoms → brain mets often as sole site of relapse ^[2]. Effect: PCI → ↑overall survival + ↓incidence of brain metastasis ^[2].

Why PCI? The blood-brain barrier prevents most chemotherapy drugs from reaching the brain. So even if the body tumour is controlled, microscopic brain deposits survive and grow. Irradiating the whole brain prophylactically eliminates these before they become clinically apparent. Trade-off: neurocognitive decline.

For extensive stage disease ^[2]:

Component	Details
Induction chemotherapy (mainstay)	Usually given for 4–6 cycles ^[2]. Standard: platinum (cisplatin or carboplatin) + etoposide.
+ Immunotherapy	± Atezolizumab (PD-L1 monoclonal antibody) ^[2] — IMpower133 trial: adding atezolizumab to chemo improved OS (12.3 vs 10.3 months). Now standard first-line. Alternative: durvalumab (CASPIAN trial).
Further thoracic EBRT ± PCI	If good response to initial chemotherapy ^[2]. Consolidation thoracic RT can improve local control. PCI remains controversial in ES-SCLC (EORTC showed benefit; Japanese trial did not).

Supportive treatment ^[2]:

Intervention	Details
Analgesics for pain relief ^[2]	WHO pain ladder: Step 1 (paracetamol ± NSAID) → Step 2 (weak opioid, e.g., codeine, tramadol) → Step 3 (strong opioid, e.g., morphine, oxycodone, fentanyl). ± Adjuvants (gabapentin/pregabalin for neuropathic pain, dexamethasone for raised ICP).
Cough suppression ^[2]	Codeine, dextromethorphan. Low-dose morphine for intractable cough.
Pleurodesis for malignant pleural effusion ^[2]	As described above.
Bronchoscopic laser therapy or stenting	To relieve airway obstruction ^[2]. Laser (Nd:YAG) debulks endobronchial tumour. Self-expanding metal stents maintain airway patency.
Management of complications	Electrolyte imbalance ^[2] (hyponatraemia from SIADH, hypercalcaemia from PTHrP), bone pain (palliative RT + bisphosphonates), cord compression, brain mets.
Other support	End-of-life care, psychosocial support ^[2]. Smoking cessation counselling. Nutritional support. Advance care planning.

5. Treatment Summary Tables

Stage	Definition	Treatment	5-Year OS
I	Isolated lesions	Surgery + adjuvant chemo (if high-risk IB)	~80% ^[1]
II	Hilar node spread	Surgery + adjuvant chemo	~60% ^[1]
IIIA	Potentially resectable	Neoadjuvant chemoRT (if N2) → Surgery ^[1]; or concurrent chemoRT	~40% ^[1]
IIIB	Unresectable	ChemoRT: cisplatin + etoposide + full-dose IMRT (2 Gy × 30 days) ± durvalumab ^[1]. ± Targeted therapy ^[1]. Solitary brain metastasis: surgery + RT ^[1]. Palliative RT for complications (e.g., SVCO, cord compression) ^[1]. Supportive Tx: pleurodesis (MPE), bronchoscopic stenting, analgesic ^[1].	~20% ^[1]
IV	Metastatic	Molecular-guided systemic therapy (TKIs, immunotherapy, chemotherapy)	~4% ^[1]

Stage	Treatment	Median OS
cT1–2 N0 M0	Surgery + adjuvant chemo (± RT if LN+)	~2–3 years
Limited (unresectable)	Concurrent chemo/RT (EP × 4 + thoracic EBRT) + PCI	~15–20 months
Extensive	Chemo (EP × 4–6) + atezolizumab/durvalumab ± consolidation thoracic RT ± PCI	~12–13 months

Understanding drug names and their mechanisms helps you remember them:

Drug	Word Roots / Name Logic	Mechanism
Cis-platin	"Cis" = same side (geometry of the platinum molecule)	Platinum compound that cross-links DNA strands → prevents DNA replication and transcription → cell death. Dose-limiting toxicity: nephrotoxicity (always hydrate).
Carbo-platin	"Carbo" = contains a carboxylate group instead of chloride	Less nephrotoxic than cisplatin but more myelosuppressive.
Etoposide	Named after the podophyllotoxin it derives from	Topoisomerase II inhibitor → prevents DNA from unwinding during replication → DNA strand breaks → apoptosis.
Pem-etrex-ed	"Etrex" relates to its antifolate action	Multi-targeted antifolate → inhibits thymidylate synthase, DHFR, GARFT → blocks DNA and RNA synthesis. Used in non-squamous NSCLC (squamous has high thymidylate synthase → resistant). Must give with folic acid + B12 supplementation.
Osimer-tinib	"-tinib" = tyrosine kinase inhibitor	3rd-generation EGFR TKI. Covalently binds EGFR (including T790M resistance mutation). Also penetrates blood-brain barrier.
Alec-tinib	"-tinib" = TKI	2nd-generation ALK inhibitor. Better CNS penetration than crizotinib.
Pembrolizu-mab	"-mab" = monoclonal antibody; "lizu" = humanised	Anti-PD-1 monoclonal antibody. PD-1 = "programmed death-1" — a checkpoint receptor on T cells. Tumours express PD-L1 to engage PD-1, telling T cells to "stand down." Pembrolizumab blocks this → T cells remain active against the tumour.
Durvalumab	"-mab" = monoclonal antibody	Anti-PD-L1 monoclonal antibody. Same pathway as pembrolizumab but blocks the ligand (PD-L1) on the tumour rather than the receptor (PD-1) on the T cell.
Atezolizumab	"-zumab" = humanised monoclonal antibody	Anti-PD-L1. Used in ES-SCLC and NSCLC.
Sotora-sib	"-sib" reflects its KRAS-targeting mechanism	Covalently and irreversibly binds KRAS G12C in its inactive (GDP-bound) state → locks it inactive → blocks downstream MAPK signalling.

Treatment	Key Contraindications
Surgery	Medically unfit (ppoFEV₁ or ppoDLCO < 30% predicted, VO₂ max < 10), N2+ disease (relative), M1 disease (absolute, except oligometastatic scenarios), patient refusal
Cisplatin	Severe renal impairment (GFR < 30), hearing loss, peripheral neuropathy, unable to tolerate aggressive hydration
EGFR TKIs	No EGFR mutation (will be ineffective). Significant hepatic impairment. ILD/pneumonitis (TKI-induced pneumonitis can be fatal).
Immunotherapy (anti-PD-1/PD-L1)	Active autoimmune disease (risk of severe immune-related adverse events — pneumonitis, colitis, hepatitis, endocrinopathy). Organ transplant recipients (risk of graft rejection). Active untreated brain mets (relative). EGFR/ALK positive (poor response + ↑toxicity).
Radiotherapy	Poor lung function (risk of radiation pneumonitis), previous RT to same field (cumulative dose limits), very large radiation field (too much normal tissue damage)
Pleurodesis	Trapped lung (visceral pleura encasement — lung cannot re-expand → pleurodesis will fail). Parapneumonic effusion/empyema (difficult drainage and decortication) ^[7].

High Yield Summary — Management of CA Lung

NSCLC:

Stage I–II: Surgery (VATS lobectomy) + mediastinal LN dissection ^[2]^[3]. ± Adjuvant chemo (stage II–III), ± adjuvant osimertinib (EGFR+), ± adjuvant RT (R1/pN2).
Stage IIIA (resectable): Neoadjuvant chemo(immuno)therapy → surgery. Or neoadjuvant chemoRT if N2 ^[1].
Stage III (unresectable): Concurrent chemoRT (cisplatin + etoposide + IMRT 60 Gy) → durvalumab consolidation ^[1]^[2].
Stage IV: Molecular-guided — EGFR → osimertinib; ALK → alectinib; no driver → immunotherapy ± chemo (based on PD-L1). Never give immunotherapy to EGFR/ALK+ patients.
Resectability criteria: Appropriate stage + no N2+ + adequate cardiopulmonary reserve ^[2].
Fitness thresholds: ppoFEV₁/DLCO ≥ 40%; VO₂ max > 15; 3 FOS for lobectomy, 5 FOS for pneumonectomy ^[2].

SCLC:

Limited (cT1–2 N0): Surgery + adjuvant chemo ^[2].
Limited (unresectable): Concurrent chemoRT (EP × 4 + EBRT) + PCI ^[2].
Extensive: Chemo (EP × 4–6) + atezolizumab/durvalumab ± consolidation RT ± PCI ^[2].

Supportive/Emergencies:

MPE → pleurodesis (1st line: chemical) or IPC ^[7].
SVCO → palliative RT/stenting.
Cord compression → dexamethasone + urgent RT/surgery.
Airway obstruction → bronchoscopic laser/stenting ^[2].

Active Recall - Management of CA Lung

References

^[1] Senior notes: Maksim Medicine Notes.pdf (p.52, Lung Cancer — NSCLC treatment table, staging, surgical management) ^[2] Senior notes: Ryan Ho Respiratory.pdf (p.146–150, Lung Cancer — Resectable NSCLC, locally advanced, advanced, SCLC management, supportive treatment, molecular testing, fitness assessment) ^[3] Lecture slides: GC 196. Minimally Invasive Thoracic Surgery.pdf (VATS lobectomy, advantages over open thoracotomy) ^[5] Lecture slides: GC 202. Surgery may cure your cancer Surgical oncology.pdf (R0 resection, neoadjuvant therapy, MDT approach) ^[7] Senior notes: Maksim Medicine Notes.pdf (p.292–294, Malignant pleural effusion, pleurodesis — chemical and surgical, IPC, shunt) ^[18] Senior notes: Ryan Ho Neurology.pdf (p.165, Brain metastasis management — surgery, SRS, WBRT, dexamethasone)

Complications of CA Lung

Complications of lung cancer arise from four major sources: (1) the disease itself (local, regional, and distant), (2) paraneoplastic syndromes, (3) treatment side effects, and (4) procedural complications from diagnostic and staging investigations. On a ward round, you need to anticipate and recognise each of these — they are what actually kills patients and drives emergency presentations.

1. Complications of the Disease Itself

These complications are essentially the advanced clinical features of the tumour, but framed from a management perspective — i.e., the things that go wrong that require urgent action.

1.1 Oncological Emergencies

These are the "don't miss" complications. If you recognise them, the patient lives. If you don't, they die or suffer irreversible harm.

Complication	Mechanism	Key Points
Hyponatraemia (SIADH)	SCLC → ectopic ADH → water retention → dilutional hyponatraemia	Management of complications, e.g., electrolyte imbalance ^[2]. Fluid restriction (1st line). If severe/symptomatic: hypertonic saline (3% NaCl, very cautiously — risk of osmotic demyelination if corrected too fast).
Hypercalcaemia	SCC → ectopic PTHrP; any subtype → osteolytic bone metastases	Rehydration (aggressive IV NS), loop diuretics (only after rehydration), bisphosphonates (zoledronic acid — inhibits osteoclast activity), denosumab (anti-RANKL). Definitive: treat the cancer.
Ectopic Cushing's	SCLC → ectopic ACTH → adrenal cortisol overproduction	Hypokalaemic metabolic alkalosis, severe proximal myopathy, immunosuppression. May require ketoconazole/metyrapone to control cortisol before definitive cancer treatment.
Hypercoagulability (Trousseau syndrome)	Tumour secretes tissue factor, mucin → activation of coagulation cascade	DVT, PE, migratory thrombophlebitis. Cancer-associated VTE: treat with LMWH or DOAC (rivaroxaban, apixaban, edoxaban).

2. Complications of Treatment

VATS lobectomy has improved outcomes compared to open thoracotomy, but complications still occur.

From the HK VATS experience ^[3]:

Complications reported include persistent air leak over 10 days, wound infection, supraventricular tachycardia, and recurrence of tumour over the utility thoracotomy scar ^[3].

Significantly more postoperative complications occurred in the thoracotomy group compared to VATS ^[3], the majority of which were prolonged air leaks ^[3].

Complication	Mechanism	Management
Persistent air leak (> 7 days) ^[3]	Failure of the staple line or visceral pleural defect → air leaks from lung parenchyma into the pleural space via chest drain	Conservative: maintain chest drain with suction → most seal spontaneously. If > 10–14 days: pleurodesis (chemical or surgical), endobronchial valve (EBV) placement ^[7]. NEVER clamp a bubbling drain (risk of tension pneumothorax) ^[7].
Pneumonia / respiratory failure	↑risk if ppoFEV₁ or ppoDLCO < 40% predicted ^[2]. Post-operative atelectasis (hypoventilation, mucus retention) → secondary infection.	Chest physiotherapy (incentive spirometry/Triflow — 10× per 30 minutes ^[3]), early mobilisation (sit out day 1, self-mobilising by day 3 ^[3]), antibiotics.
Bronchopleural fistula (BPF)	Dehiscence (breakdown) of the bronchial stump → communication between bronchial tree and pleural space → pneumothorax, empyema	Continue chest drain with low wall suction → CT thorax to localise → pleurodesis or surgery ^[7]. This is the most feared surgical complication — mortality is high.
Supraventricular tachycardia ^[3]	Post-operative autonomic irritation, sympathetic surge, pericardial inflammation, electrolyte disturbance → atrial fibrillation or SVT	Rate control (metoprolol, diltiazem), correct electrolytes (Mg²⁺, K⁺), amiodarone if refractory.
Wound infection ^[3]	Surgical site contamination	Antibiotics, wound care. Less common with VATS (smaller incisions).
Tumour recurrence at thoracotomy scar ^[3]	Tumour cell implantation during surgery	Rare but reported. Reason to minimise tissue handling and use specimen retrieval bags.
Post-pneumonectomy pulmonary oedema	The remaining lung receives the entire cardiac output → increased hydrostatic pressure → oedema. Also, lymphatic disruption.	Restrict IV fluids post-pneumonectomy (aim for fluid negative balance). This complication has ~50% mortality.
Right-sided heart failure	Pneumonectomy reduces the pulmonary vascular bed → ↑pulmonary vascular resistance → ↑RV afterload → RV failure	More common after right pneumonectomy (larger vascular bed removed). Avoid excessive fluid loading.
Empyema	Infection of the pleural space, especially if BPF	Chest drain, antibiotics, consider decortication if chronic.

Post-operative care pathway (from the VATS clinical pathway) ^[3]:

Day 0: Intensive monitoring, chest drain to suction, IV fluids, IV antibiotics, PCA analgesia, sit up in bed as tolerated, begin Triflow use
Day 1: Off O₂, off suction, off PCA, off IV fluids, resume Aspirin/Plavix, post-op chest physiotherapy, sit out all day, mobilise
Day 2: Off chest drain if: no air leak, output acceptable, lung expanded on CXR
Day 3–5: Discharge if patient safe, mobile, independent
CXR is performed: after off suction, after drain removal, and before discharge ^[3]

Complication	Timing	Mechanism	Management
Acute radiation pneumonitis	4–12 weeks after RT ^[2]	RT damages alveolar epithelial cells and capillary endothelium → inflammatory exudate in alveoli → impaired gas exchange	S/S: dry cough, SOB, low-grade fever, pleuritic chest pain ^[2]. HRCT: GGO (acute) → consolidation (organising phase) conforming to RT field (diagnostic) ^[2]. Mx: observe if minimal; otherwise steroids ^[2]. Expect clinical + radiological response in 3–4 days. Continue steroid for 3–4 weeks before tapering ^[2].
Fibrotic radiation pneumonitis	6–12 months after RT ^[2]	Chronic fibrotic change in the irradiated lung parenchyma → permanent volume loss	Irreversible. Use of steroid does not reduce long-term risk of fibrosis ^[2]. Manage with bronchodilators, supplemental O₂ if needed.
Radiation oesophagitis	During/shortly after concurrent chemoRT	RT damages oesophageal mucosa → inflammation, ulceration	Dysphagia, odynophagia. Manage with PPI, viscous lidocaine, soft diet. Usually self-limiting. Can progress to stricture.
Radiation myelopathy	Months to years	Direct damage to spinal cord (if cord is within the radiation field)	Progressive weakness, sensory loss. Irreversible. Dose limit: 45–50 Gy to the spinal cord.
Radiation-induced cardiac disease	Years	Pericarditis, coronary artery disease, cardiomyopathy	More relevant with mediastinal RT. Monitor long-term cardiac risk.

Radiation Pneumonitis vs Lymphangitis Carcinomatosis

Both can cause progressive dyspnoea after treatment. The key differentiator is that radiation pneumonitis conforms to the RT field ^[2] (sharp geometric borders on HRCT), while lymphangitis carcinomatosis is diffuse with septal thickening (Kerley B lines). Getting this distinction wrong can lead to inappropriate steroid treatment or missed disease progression.

Drug	Key Toxicities	Mechanism
Cisplatin	Nephrotoxicity (dose-limiting), ototoxicity, peripheral neuropathy, severe nausea/vomiting	Direct tubular damage (requires aggressive IV hydration + monitoring of Cr, Mg²⁺). Damage to hair cells of cochlea. Axonal degeneration of sensory nerves. Stimulates CTZ → severe emesis (always give 5-HT3 antagonist + dexamethasone + NK1 antagonist).
Carboplatin	Myelosuppression (dose-limiting — especially thrombocytopenia), nausea (less than cisplatin)	Less nephrotoxic than cisplatin (no need for aggressive hydration). Dose calculated by AUC using Calvert formula (considers GFR).
Etoposide	Myelosuppression (neutropenia), alopecia, secondary leukaemia (AML — years later)	Topoisomerase II inhibition → can cause balanced translocations at MLL gene → secondary AML (~1–2% risk).
Pemetrexed	Myelosuppression, mucositis, rash, diarrhoea	Antifolate → must supplement with folic acid + vitamin B12 to reduce toxicity (folic acid daily for ≥ 5 doses before first pemetrexed, B12 IM every 9 weeks).
General	Neutropenic sepsis	Chemotherapy destroys rapidly dividing cells including bone marrow → neutropenia → susceptibility to infection → life-threatening sepsis. Febrile neutropenia (fever + ANC < 0.5 × 10⁹/L) is a medical emergency — IV broad-spectrum antibiotics (e.g., piperacillin-tazobactam) within 1 hour.

Drug Class	Key Toxicities	Mechanism
EGFR TKIs (osimertinib, gefitinib, erlotinib)	Skin rash (acneiform — face, trunk), diarrhoea, paronychia, interstitial lung disease/pneumonitis (rare but potentially fatal)	EGFR is expressed in skin and GI epithelium → blocking it causes dermatological and GI side effects. ILD: immune-mediated pneumonitis — must stop TKI immediately + steroids.
ALK TKIs (alectinib, crizotinib, lorlatinib)	Visual disturbance (crizotinib), peripheral oedema, hepatotoxicity, bradycardia, hyperlipidaemia (lorlatinib), CNS effects (lorlatinib — mood changes, cognitive slowing)	Variable off-target kinase effects. Monitor LFTs regularly.

Checkpoint inhibitors (pembrolizumab, durvalumab, atezolizumab, nivolumab) work by "releasing the brakes" on the immune system. The trade-off is that the unleashed immune system can attack normal tissues → autoimmune-like toxicities affecting virtually any organ:

Organ	irAE	Incidence	Management
Skin	Rash, pruritus, vitiligo	~30–40% (most common)	Topical steroids, antihistamines. Rarely requires treatment interruption.
GI	Colitis (diarrhoea, bloody stool, abdominal pain)	~10–20%	Grade 1–2: loperamide + budesonide. Grade 3–4: hold immunotherapy + high-dose IV methylprednisolone. If steroid-refractory: infliximab (anti-TNF).
Liver	Hepatitis (↑AST/ALT)	~5–10%	Monitor LFTs every cycle. Grade 3–4: hold immunotherapy + steroids. If refractory: mycophenolate mofetil.
Endocrine	Thyroiditis (hypo > hyper), hypophysitis (pituitary inflammation), adrenalitis, Type 1 DM	~10–15%	TFTs every cycle. Thyroid: thyroxine replacement if hypothyroid. Hypophysitis: hydrocortisone replacement (often permanent). Type 1 DM: insulin.
Lung	Pneumonitis	~3–5% (but potentially fatal)	Most feared pulmonary complication. Cough, dyspnoea, GGO/organising pneumonia on CT. Grade 1: monitor. Grade 2: hold immunotherapy + oral prednisolone. Grade ≥ 3: permanently discontinue + IV methylprednisolone.
Neurological	Myasthenia gravis, Guillain-Barré, encephalitis	~1%	Rare but serious. High-dose steroids, IVIG, plasmapheresis. Permanently discontinue immunotherapy.
Cardiac	Myocarditis	< 1%	Rare but ~50% mortality. Troponin monitoring. High-dose steroids. Permanently discontinue.

Immunotherapy Pneumonitis — Critical Distinction

You must distinguish immunotherapy-induced pneumonitis (which requires stopping the drug and giving steroids) from disease progression (which requires escalating treatment) and infection (which requires antibiotics, not steroids). All three can present with new dyspnoea + new infiltrates on CT during treatment. Get a BAL (bronchoscopy with lavage) if in doubt.

3. Complications of Diagnostic and Staging Procedures

Complication	Details
Bleeding	From biopsy site. Usually minor and self-limiting. Rarely significant enough to require intervention.
Pneumothorax	Especially after transbronchial biopsy. ~1–4%.
Bronchospasm	Particularly in asthmatic/COPD patients.
Respiratory depression	From sedation.
Laryngospasm	Reflex vagal response to airway instrumentation.

4. Long-Term Complications and Prognosis

Type	Timing	Mechanism	Surveillance
Local recurrence	Months to years	Residual microscopic disease at resection margins or in regional lymph nodes	CT thorax Q6 months for 2 years, then annually for 5 years (at minimum).
Distant recurrence	Months to years	Micrometastases present at diagnosis but undetectable by imaging → grow over time	Same surveillance. Symptoms: new bone pain, headache, weight loss.
Second primary lung cancer	Years	Field cancerisation — the entire bronchial epithelium was exposed to carcinogens → multiple areas can undergo malignant transformation independently	Annual LDCT in continued smokers. Risk of second primary is ~1–2% per year.

Complication	Cause	Timeline
Chronic radiation fibrosis	Thoracic RT	6–12 months post-RT; permanent
Secondary malignancy	Alkylating agents (cisplatin), etoposide	Etoposide → secondary AML (~1–2%, years later). RT → secondary cancers in radiation field (years–decades).
Permanent endocrinopathy	Immunotherapy-induced hypophysitis or thyroiditis	During or after immunotherapy; often requires lifelong hormone replacement.
Neurocognitive decline	Whole-brain RT (PCI in SCLC)	Progressive. Reason why SRS is now preferred over WBRT where possible.
Peripheral neuropathy	Cisplatin, taxanes	Often irreversible. "Stocking-glove" distribution. Affects fine motor function and proprioception.

References

^[1] Senior notes: Maksim Medicine Notes.pdf (p.52, Lung Cancer — NSCLC treatment, complications of CT-guided FNAC, palliative RT indications) ^[2] Senior notes: Ryan Ho Respiratory.pdf (p.126–128, 141–150, Lung Cancer — prognosis, radiation pneumonitis, supportive treatment, airway management, reasons for poor prognosis; asbestos-related lung disease and CA lung risk) ^[3] Lecture slides: GC 196. Minimally Invasive Thoracic Surgery.pdf (p.22–49, 123 — VATS complications, HK experience, post-op care pathway, persistent air leak, SVT, wound infection, tumour recurrence at scar) ^[7] Senior notes: Maksim Medicine Notes.pdf (p.292–296, Malignant pleural effusion, pleurodesis complications, chest drain complications, trapped lung, re-expansion pulmonary oedema) ^[14] Senior notes: Ryan Ho Diagnostic Radiology.pdf (p.80, Complications of image-guided biopsy — pneumothorax rates, haemoptysis, tumour seeding) ^[18] Senior notes: Ryan Ho Neurology.pdf (p.165, Brain metastasis — prognosis, management with dexamethasone, SRS, WBRT)

Ca Lung

1. Definition

2. Epidemiology

2.1 Global Perspective

2.2 Hong Kong Perspective

2.3 Sex-Specific Patterns in HK

3. Risk Factors

3.1 Environmental / Modifiable

3.2 Host / Non-Modifiable

4. Anatomy and Function (Relevant to CA Lung)

4.1 Bronchial Tree

4.2 Mediastinal Structures (Why Regional Spread Matters)

4.3 Lung Apex (Pancoast Tumour Territory)

4.4 Lymphatic Drainage

4.5 Common Sites of Distant Metastasis

5. Aetiology and Pathogenesis

5.1 Molecular Pathogenesis — From First Principles

5.2 Key Driver Mutations and Molecular Targets

5.3 Carcinogenesis by Smoking

6. Classification

6.1 Histological Classification (WHO)

6.2 Why the NSCLC vs SCLC Distinction Matters

6.3 Adenocarcinoma Subtypes (2021 WHO Classification)

6.4 Staging Overview (Brief — Will Expand in Diagnosis Section)

7. Clinical Features

7.1 Overview — Why Many Present Late

7.2 Symptoms

A. Constitutional Symptoms (Non-Specific)

B. Symptoms from Endobronchial Growth (Central Tumours)

C. Symptoms from Regional Spread / Local Invasion

i. Pleura

ii. Pericardium

iii. Recurrent Laryngeal Nerve (RLN) and Oesophagus

iv. Pancoast Syndrome (Superior Sulcus Tumour)

v. Superior Vena Cava Obstruction (SVCO)

vi. Other Local Structures

D. Symptoms from Distant Metastases

E. Paraneoplastic Syndromes

7.3 Signs

A. General Inspection

B. Chest Examination

C. Extrathoracic Signs

8. Special Topics from Lecture Slides

8.1 Minimally Invasive Thoracic Surgery (MITS) in CA Lung

8.2 Surgical Oncology Principles Applied to CA Lung

8.3 Gastric Cancer Lecture — Relevance to CA Lung

8.4 Large Liver (Hepatomegaly) — Relevance to CA Lung

9. Summary of Key Pathophysiological Connections

Active Recall - CA Lung (Definition to Clinical Features)

References

1. Conceptual Framework — How to Think About the DDx

2. Differential Diagnosis by Radiological Pattern

A. Solitary Pulmonary Nodule (SPN) — ≤ 3 cm

B. Lung Mass ( > 3 cm)

C. Multiple Pulmonary Nodules [7]

D. Cavitating Lesion [8][9]

E. Hilar / Mediastinal Mass

3. Differential Diagnosis by Presenting Symptom

A. Chronic Cough ( > 8 weeks) [7]

B. Haemoptysis [7]

C. Dyspnoea [7]

D. Constitutional Symptoms (Weight Loss + Cachexia)

E. Back Pain / Bony Pain [10]

4. Distinguishing Primary Lung Cancer from Lung Metastases

5. Approach to Hepatomegaly in Context of Suspected Lung Cancer [12]

6. DDx Decision-Making Algorithm

7. Summary Table — Key DDx for CA Lung by Presentation

Active Recall - DDx of CA Lung

1. Overview — What Does "Diagnosing Lung Cancer" Actually Mean?

2. Initial Investigations — The Baseline Work-Up

A. Blood Tests

B. Sputum Studies

3. Radiological Assessment — The Imaging Ladder

A. Chest X-Ray (CXR)

B. Contrast CT Thorax + Upper Abdomen

C. Whole-Body PET/CT (18F-FDG PET/CT)

D. MRI Thorax

E. Brain Imaging

F. Bone Imaging

G. Summary of Imaging Algorithm