Cardio - Lung Cancer

Question 1

What is the epidemiology of lung cancer?

Answer 1

→ 3rd most common in the world

→ leading cause of cancer death

Question 2

What are the demographics of lung cancer?

Answer 2

→ Age = 75 to 90
→ More males than females
→ Lower socioeconomic status (reduced access to health care, etc)
→ Smoking history (duration, intensity, when stopped)

Question 3

What causes lung cancer?

Answer 3

→ Smoking 
→ Passive smoking
→ Asbestos (exposure increases risk up to 2 times)
→ Radon (silver mines, uranium mining)
→ Indoor cooking fumes (wood smoke, frying fats)
→ Chronic lung diseases (COPD, CF)
→ Immunodeficiency 
→ Familial or Genetic factors

Question 4

What are the 4 types of lung cancer?

Answer 4

→ Squamous cell carcinoma (30%)
→ Adenocarcinoma (40%)
→ Large cell lung cancer (15%)
→ Small cell lung cancer (15%)

Question 5

What types of lung cancer are grouped together? Why not all?

Answer 5

→ squamous, adenocarcinoma and large cell = non-small cell lung cancer

Question 6

What is a squamous cell carcinoma?

Answer 6

→ previously the most common

→ originating from bronchial epithelium; centrally located

Question 7

What is an adenocarcinoma?

Answer 7

→ most common from 1980s onwards – low tar cigarettes, inhaled more deeply / retained longer
→ originating from mucus-producing glandular tissue; more peripherally-locate

Question 8

What is large cell carcinoma?

Answer 8

→ heterogenous group, undifferentiated

Question 9

What is small-cell lung cancer?

Answer 9

→ originates from pulmonary neuroendocrine cells

→ highly malignant

Question 10

What are the changes in tissue in early lung cancer

Answer 10

→ normal epithelium
→ hyperplasia
→ squamous metaplasia

Question 11

What is the intermediate stage of lung cancer development?

Answer 11

→ 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 12

What are the late stages of lung cancer development?

Answer 12

→ carcinoma in situ

→ invasive carcinoma

Question 13

What are some important oncogenes?

Answer 13

• epidermal growth factor receptor (EGFR) tyrosine kinase
• anaplastic lymphoma kinase (ALK) tyrosine kinase
• c-ROS oncogene 1 (ROS1) receptor tyrosine kinase
• BRAF (downstream cell-cycle signalling mediator)

Question 14

Why is EGFR tyrosine kinase important?

Answer 14

• 15-30% of adenocarcinoma

* more so in women, Asian ethnicity, never-smokers

Question 15

Why is ALK tyrosine kinase important?

Answer 15

• 2-7% of non-small cell lung cancer

* especially in younger patients and never smokers

Question 16

Why is ROS1 receptor tyrosine kinase important?

Answer 16

• 2-7% of non-small cell lung cancer

* especially in younger patients and never smokers

Question 17

Why is BRAF important?

Answer 17

• 1-3% of non-small cell lung cancer

* especially in smokers

Question 18

What are the key symptoms of lung cancer?

Answer 18

→ Cough
→ Weight loss
→ Breathlessness
→ Fatigue 
→ Chest pain
→ Haemoptysis (coughing up blood)
→ Frequently patients are asymptomatic

Question 19

What are some neurological symptoms of advanced lung cancer (metastatic)?

Answer 19

→ Focal weakness
→ Seizures
→ Spinal chord compression

Question 20

What are some other significant symptoms of metastatic disease?

Answer 20

→ Bone pain

→ Paraneoplastic symptoms : e.g. Cushing’s syndrome, clubbing, hypercalaemia, hyponatraemia, Cushing’s

Question 21

What are some clinical signs of lung cancer?

Answer 21

→ Cachexia
→ Horner’s syndrome
→ Superior vena cava obstruction
→ Clubbing

Question 22

What is the diagnostic strategy?

Answer 22

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

Question 23

What imaging is used to diagnose lung cancer?

Answer 23

→ Staging CT (abdomen + chest)
→ Chest X-ray
→ PET

Question 24

Why are PET’s useful?

Answer 24

Most useful to exclude occult metastases

Question 25

What is the best way to make a diagnosis? What are the different types?

Answer 25

Biopsy: → Bronchoscopy → Endobronchial ultrasound and transbronchial-needle aspiration of mediastinal lymph nodes (EBUS [TBNA]) → CT- guided lung biopsy

Question 26

What is the purpose of biopsy via bronchoscopy?

Answer 26

* for tumours of central airway | * where tissue staging not important

Question 27

What is EBUS [TBNS] used for?

Answer 27

To stage mediastinum +/- achieve tissue diagnosis

Question 28

What is a CT guided lung biopsy used for?

Answer 28

to access peripheral lung tumours

Question 29

How are lung cancers assessed and given a stage?

Answer 29

→ T1-4 : tumour size + location → N0-3 : lymph node involvement - mediastinum + beyond → M0-1c : metastases + number → Early vs locally-advanced vs metastatic

Question 30

What are the determinants of treatment?

Answer 30

``` → Patient fitness → Cancer histology → Cancer stage → Patient preference → Health service factors ```

Question 31

How are patient categorised by patient fitness?

Answer 31

WHO performance status: → 0 = asymptomatic + fully active → 1 = symptomatic but completely ambulatory → 2 = symptomatic, less than 50% of time in bed during the day → 3 = symptomatic, but more than 50% in bed, not bed bound → 4 = bed bound → 5 = death

Question 32

How is lung cancer surgically treated?

Answer 32

Surgical resection = standard of care of early stage disease → Lobectomy = removal of lobe → Lymphadenectomy = removal of lymph nodes in tumour → Sublobar resection if stage 1 (less than 3cm) = small section of lung removed → Pneumonectomy = removal of whole lung

Question 33

What is the alternative to surgery for tackling early stage disease?

Answer 33

Radical radiotherapy

Question 34

Why choose radical radiotherapy over surgery?

Answer 34

* Alternative to surgery for early stage disease | * Particularly if comorbidity

Question 35

How does radical radiotherapy work?

Answer 35

* Stereotactic ablative body radiotherapy (SABR) aimed at tumour * Technique of choice * High-precision targeting, multiple convergent beams

Question 36

What are the systemic treatments for lung cancer?

Answer 36

→ Oncogene directed → Immunotherapy → Cytotoxic Chemotherapy

Question 37

What are some of the oncogene directed drugs?

Answer 37

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

Question 38

What is the efficacy of oncogene directed therapy?

Answer 38

• 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 39

What are the side effects of oncogene-directed drugs?

Answer 39

* Generally well tolerated * Rash * Diarrhoea * Uncommon but pneumonia

Question 40

How does the immunotherapy work?

Answer 40

* PD-L1/PD-1 binding inhibits T cell killing of tumour cell | * Immunotherapy blocks PD-L1 or PD-1

Question 41

When are oncogene-directed drugs used?

Answer 41

First line for metastatic NSCLC with mutation

Question 42

When is immunotherapy used?

Answer 42

First line for metastatic NSCLC with no mutation (and PDL1 ≥50%

Question 43

What are the NICE approved drugs for immunotherapy?

Answer 43

* Pembrolizumab * atezolizumab * nivolumab

Question 44

What is the efficacy of immunotherapy?

Answer 44

* improvements in progression-free survival and overall survival vs standard chemotherapy: * e.g. pembrolizumab PFS 10 vs 6 months, OS >30 vs 14 months (KEYNOTE-024 trial) • [32% alive at 5 years]

Question 45

What are the side effects of immunotherapy?

Answer 45

* generally well-tolerated | * Immune-related side-effects in 10-15% (thyroid, skin, bowel, lung, liver)

Question 46

When is cytotoxic chemotherapy used?

Answer 46

First line for metastatic NSCLC with no mutation and PDL1 ≤50% (in combination with immunotherapy)

Question 47

What is cytotoxic chemotherapy?

Answer 47

* Target any rapidly dividing cells | * Platiunum-based regimens, e.g. carboplatin, cisplatin, paclitaxel, pemetrexed

Question 48

What is the efficacy of cytotoxic chemotherapy?

Answer 48

* when used alone (old data, pre-2000) modest improvements in overall survival vs best supportive care * e.g. 29 vs 20% one year survival in clinical trials * with pembrolizumab (Keynote 189), a lot better (23% 2y survival vs 5% for standard chemo alone)

Question 49

What are the side effects of cytotoxic chemotherapy?

Answer 49

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

Question 50

What is the palliative and supportive care offered to patients with lung cancer?

Answer 50

``` • Should be offered as standard to all patients with advanced stage disease • Symptom control, psychological support, education, practical and financial support, planning for end of life • Lung cancer specialist nurses key • At 12 weeks: • Improved quality of life • Lower depression scores • Median survival 11.6 v 8.9 months ```

Question 51

In summary, what are the main treatments for early stage lung cancer?

Answer 51

Surgery or radiotherapy with curative intent

Question 52

In summary, what are the main treatments for Locally advanced disease (involving thoracic lymph nodes)?

Answer 52

* Surgery + adjuvant chemotherapy | * Radiotherapy + chemotherapy +/- immunotherapy

Question 53

In summary, what are the main treatments for Metastatic disease?

Answer 53

* With targetable mutation (e.g. EFGR, ALK, ROS-1): tyrosine kinase inhibitor * No mutation, PDL-1 positive: immunotherapy alone * No mutation, PDL-1 negative: ‘standard’ chemotherapy + immunotherapy * Palliative care, alone or with the above

Question 54

What is the usual prognosis of lung cancer?

Answer 54

Only 10% live >10 years | Little change in survival in last 40 years