Lung Cancer

Question 1

Describe the scale of lung cancer in the UK

Answer 1

3rd most common cancer, 48,000 diagnoses every year with 35,000 deaths, leading cause of cancer death

Question 2

Who is most likely to get lung cancer?

Answer 2

Peaks between 75-90. More males than females affected. Impacts those of lower socioeconomic status and duration, intensity + when stopped smoking all impact.

Question 3

What other causes of lung cancer apart from smoking?

Answer 3

Asbestos – exposure (plumbers, ship-builders, carriage workers, carpenters, etc) – risk up to x2
Radon – e.g. silver miners in Germany late 19th century; 1950s uranium mining in Colorado
Indoor cooking fumes – wood smoke, frying fats
Chronic lung diseases (COPD, fibrosis)
Immunodeficiency
Familial/ genetic – several loci identified

Question 4

What pathophysiologies count as lung cancer?

Answer 4

1. Small cell lung cancer - originates from pulmonary neuroendocrine cells, highly malignant
2. Non-small cell lung cancer includes:
   - Squamous cell carcinoma: originates from bronchial epithelium, centrally located and was previously most common (30%)
   - Adenocarcinoma: originating from mucus-producing glandular tissue; more peripherally-locate (40%)
   - Large cell lung cancer: heterogenous morphologies, undifferentiated (15%)

Question 5

Describe progression of lung cancer development

Answer 5

Normal epithelium becomes hyperplastic and then squamous metaplasia occurs - these are the early stages. Dysplasia occurs in intermediate stage. Late stages involve carcinoma in situ and then invasive carcinoma.

Question 6

Define metaplasia and dysplasia

Answer 6

Metaplasia = reversible change in which one adult cell type replaced by another adult cell type; adaptive         
Dysplasia = abnormal pattern of growth in which some of the cellular and architectural features of malignancy are present; pre-invasive stage with intact basement membrane

Question 7

What are 4 important oncogenes which can mutate to cause cancer?

Answer 7

1. EGFR: epidermal growth factor receptor tyrosine kinase
2. ALK: anaplastic lymphoma kinase tyrosine kinase
3. ROS1: c-ROS oncogene 1 tyrosine kinase receptor
4. BRAF: downstream cell-cycle signalling mediator

BEAR

Question 8

What are the implications of an EGFR mutation?

Answer 8

Cause 15-30% of adenocarcinoma

more so in women, Asian ethnicity, never-smokers

Question 9

What are the implications of an ALK mutation?

Answer 9

2-7% of non-small cell lung cancer

especially in younger patients and never smokers

Question 10

What are the implications of a ROS1 mutation?

Answer 10

1-2% of non-small cell lung cancer

especially in younger patients and never smokers

Question 11

What are the implications of a BRAF mutation?

Answer 11

1-3% of non-small cell lung cancer

especially in smokers

Question 12

What are key symptoms of lung cancer?

Answer 12

Can frequently be asymptomatic but includes cough, weight loss, breathlessness, fatigue, chest pain and haemoptysis.

Question 13

What are features of advanced/metastatic disease?

Answer 13

Neurological features: focal weakness, seizures, spinal cord compression
Bone pain
Paraneoplastic syndromes: Clubbing, hypercalaemia, hyponatraemia, Cushing’s

Question 14

What are signs of lung cancer?

Answer 14

Clubbing, cachexia, Horner’s syndrome and superior vena cava obstruction (Pemberton’s sign)

Question 15

Describe the diagnostic strategy

Answer 15

Establish most likely diagnosis
Establish fitness for investigation and treatment
Confirm diagnosis - specific type of cancer if considering systemic treatment
Confirm staging

Question 16

Why are different imaging techniques?

Answer 16

CT of chest and abdomen used to determine stage

PET - Most useful to exclude occult metastases

Question 17

What are 3 methods of obtaining a biopsy?

Answer 17

1. Bronchoscopy - for tumours of central airway where tissue staging not important
2. Endobronchial ultrasound and transbronchial-needle aspiration of mediastinal lymph nodes (EBUS [TBNA]). To stage mediastinum +/- achieve tissue diagnosis
3. CT-guided lung biopsy - To access peripheral lung tumours

Question 18

What are the 3 components of staging?

Answer 18

T1-4: tumour size and location
N0-3: lymph node involvement – mediastinum + beyond
M0-1c: metastases + number

Question 19

What 5 things are the determinants of treatment?

Answer 19

Patient fitness
Cancer histology
Cancer stage
Patient preference
Health service factors

Question 20

How is patient fitness determined?

Answer 20

WHO performance status used.
0- asymptomatic (fully active, no restriction)
1 - Symptomatic but completely ambulatory
2 - Symptomatic, <50% in bed during the day
3 - Symptomatic, >50% in bed, but not bedbound
4 - Bedbound
5 - Death

Question 21

What is standard of care for early stage disease?

Answer 21

Surgical resection is standard of care for early stage disease
Lobectomy + lymphadenectomy usual approach
Sublobar resection if stage 1 (≤3 𝑐𝑚)

Question 22

What is an alternative to surgery for early stage disease?

Answer 22

Radical radiotherapy used - especially if patient has comorbidities. Stereotactic ablative body radiotherapy (SABR) - is the technique of choice and high-precision targetting, multiple convergent beams.

Question 23

What treatment is first line for metastatic NSCLC with mutation?

Answer 23

EGFR: erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib
ALK: crizotinib, ceritinib, alectinib, brigatinib, lorlatinib
ROS-1: crizotinib, entrectinib

Question 24

What is efficacy of oncogene-directed treatment like?

Answer 24

improvements in progression-free survival, but not necessarily overall survival vs standard chemotherapy:

e. g. erlotinib PFS 14 vs 5 months, OS 23 vs 29 months compared to chemo (OPTIMAL trial)
e. g. crizitonib PFS 8 vs 3 months, OS 20 vs 23 months

Question 25

How is immunotherapy used to kill tumour cells?

Answer 25

PD-L1 on tumour cell binds PD-1 on T-cell preventing T-cell killing the tumour cell. Blocking PD-L1 and PD-1 with drugs allows the T-cell to then bind the tumour cell and kill it.

Question 26

What immunotherapy is used as first line for metastatic NSCLC with no mutation?

Answer 26

Pembrolizumab, atezolizumab, nivolumab

Question 27

What is cytotoxic chemotherapy?

Answer 27

Targets any rapidly dividing cells. Uses platiunum-based regimens, e.g. carboplatin, cisplatin, paclitaxel, pemetrexed. When used alone, modest improvements in overall survival vs best supportive care.

Question 28

What are side effects of cytotoxic chemotherapy?

Answer 28

Frequent: fatigue, nausea, bone marrow suppression, nephrotoxicity. Quality of life poorly evaluated in trials; no evidence for improvement.

Question 29

What does palliative and supportive care involve?

Answer 29

Symptom control, psychological support, education, practical and financial support, planning for end of life. There is evidence for survival and symptomatic benefit.

Question 30

Simplify the treatment schedule for lung cancer

Answer 30

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