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cardioresp > 1B lung cancer > Flashcards

1B lung cancer Flashcards

1
Q

Describe the epidemiology of lung cancer

A
  • 3rd most common cancer in UK
  • Leading cause of cancer death
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2
Q

Who gets lung cancer more often?

A
  • Age- peak is 75-90
  • Sex- M>F
  • Lower socioeconomic status
  • Smoking history- duration, intensity, when stopped
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3
Q

What other factors than smoking contribute to lung cancer?

A

10-15% patients with lung cancer never smoked

  • Passive smoking is 15% of these
  • Chronic lung diseases (COPD, fibrosis)
  • Asbestos- exposure increases risk up to x2
  • Radon e.g. silver miners in Germany in 1800s
  • Indoor cooking fumes- wood smoke, frying fats
  • Immunodeficiency
  • Familial/genetic- several loci identified
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4
Q

What are the four main types of lung cancer?

A
  • Squamous cell carcinoma (30%)
  • Adenocarcinoma (40%)
  • Large cell lung cancer (15%)
  • Small cell lung cancer (15%)
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5
Q

Where does squamous cell carcinoma originate from?

A

Bronchial epithelium, centrally located

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6
Q

Where do adenocarcinomas originate from?

A

Mucus-producing glandular tissue- more peripherally located

Most common lung cancer from 80s onwards

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7
Q

What is large cell lung cancer?

A

Heterogenous group, undifferentiated

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8
Q

Where does small cell lung cancer originate?

A

From pulmonary neuroendocrine cells.

Highly malignant.

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9
Q

What are squamous cell carcinoma, adenocarcinoma and large cell lung cancer often grouped as?

A

Non-small cell lung cancer (NSCLC)

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10
Q

Describe the pathogenesis of lung cancer

A
  • Lung cancer may arise from all differentiated and undifferentiated cells
  • The interaction between inhaled carcinogens and the epithelium of upper and lower airways leads to the formation of DNA adducts: pieces of DNA covalently bound to a cancer-causing chemical
  • Persisting DNA adducts/misrepaired adducts result in a mutation and can cause genomic alterations.
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11
Q

What important oncogenes are there that have mutations commonly in lung cancer?

A
  • Epidermal growth factor receptor (EGFR) tyrosine kinase
  • Anaplastic lymphoma kinase (ALK) tyrosine kinase
  • c-ROS oncogene 1 (ROS1) receptor tyrosine kinase
  • BRAF (downstream cell-cycling signalling mediator)
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12
Q

What is EGFR tyrosine kinase common in?

A
  • 15-30% of adenocarcinoma
  • More common in women, Asian, never-smokers
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13
Q

What is ALK tyrosine kinase common in?

A
  • 2-7% of NSCLC
  • Especially in younger patients and never smokers
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14
Q

What is ROS1 receptor tyrosine kinase common in?

A
  • 1-2% of NSCLC
  • Especially in younger patients and never smokers
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15
Q

What is BRAF common in?

A
  • 1-3% of NSCLC
  • Especially in smokers
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16
Q

What are the key symptoms of lung cancer?

A
  • Cough
  • Breathlessness
  • Chest pain
  • Haemoptysis (coughing up blood)
  • Weight loss
  • Fatigue

Frequently asymptomatic

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17
Q

What features are there of advanced/metastatic lung cancer?

A
  • Neurological features- focal weakness, seizures, spinal cord compression
  • Bone pain
  • Paraneoplastic syndromes- clubbing, hypercalcaemia, hyponatraemia, Cushing’s
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18
Q

What common sites of lung cancer metastases are there?

A
  • Bones
  • Liver
  • Brain
  • Lymph nodes
  • Adrenal glands
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19
Q

What are the clinical signs of lung cancer?

A
  • Clubbing
  • Horner’s syndrome
  • Superior vena cava obstruction (Pemberton’s sign)
  • Cachexia
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20
Q

What clinical sign of lung cancer does this image show?

A

Clubbing

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21
Q

What is this syndrome?

A

Horner’s syndrome

Apical lung tumour at top of lung and compresses thoracic outlet, reducing sympathetic supply to face.

Causes:

  • ptosis
  • miosis
  • anhidrosis
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22
Q

What does this image show?

A

Pemberton’s sign

Compression of superior vena cava in neck

If you raise arms, you increase venous return which causes swelling and redness in face

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23
Q

What does this image show?

A

Cachexia

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24
Q

Describe the diagnosis strategy for lung cancer

A
  • Establish most likely diagnosis
  • Establish fitness for investigation and treatment
  • Confirm diagnosis via tissue specimen- specific type of cancer if considering systemic treatment
  • Confirm staging
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25
Q

What does the bottom right show?

A

Pleural effusion- this counts as metastatic lung cancer since pleura is different tissue from lung

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26
Q

What are the black dots in the top left image patient’s lung?

A

Emphysema

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27
Q

What are the blobs on the liver of the middle patient?

A

Metastases

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28
Q

Why are PET scans used for lung cancer?

A

Most useful to exclude occult metastases (metastases that are initially undetected)

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29
Q

Describe how lung biopsies are done?

A

1) Choose method based on accessibility, availability and impact on staging

2) Bronchoscopy for tumours of central airway where tissue staging not important

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30
Q

What is EBUS[TBNA]?

A
  • Endobronchial ultrasound and transbronchial-needle aspiration of mediastinal lymph nodes (EBUS [TBNA])
  • To stage mediastinum with or without achieving tissue diagnosis
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31
Q

What is CT-guided lung biopsy?

A
  • Needle put through chest wall to take tissue sample
  • Done to access peripheral lung tumours
  • For bronchoscopy, tumour has to be central near airway
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32
Q

What is the TNM system of staging done for lung cancer?

A
  • T1-4 → tumour size and location
  • N0-3 → regional lymph node involvement- (within mediastinum)
  • M0-1c → number of extrathoracic metastases
  • Late stage diagnosis is common
33
Q

How else can we stage lung cancer aside from TNM?

A

Early vs locally-advanced vs metastatic

34
Q

What determinants of treatment are there for lung cancer?

A
  • Patient fitness
  • Cancer histology
  • Cancer stage
  • Patient preference
  • Health service factors
35
Q

How is patient fitness classified?

A

WHO performance status:

  • 0- asymptomatic- fully active, able to carry on all predisease activities without restriction
  • 1- symptomatic but completely ambulatory- restricted in physically strenuous activity but ambulatory and can carry out light work
  • 2- symptomatic, <50% in bed during day- ambulatory and capable of self care but can’t work
  • 3- symptomatic, >50% in bed not bedbound- capable of limited self-care, confined to bed or chair for more than half of waking hours
  • 4- bedbound- completely disabled, can’t self-care
  • 5- death
36
Q

Which levels are usually required in the WHO performance status for treatment of lung cancer?

A

0 or 1 because 3 or 4 won’t get much benefit from treatment

37
Q

What is surgery standard of care in lung cancer?

A
  • For early stage disease
  • Lobectomy and lymphadenectomy is the usual approach
  • Sublobar resection if stage 1 (≤3cm)
38
Q

What is the alternative treatment for early stage disease than surgery?

A
  • Radical radiotherapy
  • Particularly if comorbidity
  • Stereotactic ablative body radiotherapy (SABR)
    • Technique of choice
    • High-precision targeting, multiple convergent beams
39
Q

When is oncogene-directed treatment used?

A

First line for metastatic NSCLC with mutation

Blocks the mutated protein

40
Q

What are the NICE approved treatments for EGFR mutations?

A
  • erlotinib
  • gefitinib
  • afatinib
  • dacomitnib
  • osimertinib
41
Q

What are the NICE approved treatments for ALK mutations?

A
  • crizotinib
  • ceritinib
  • alectinib
  • brigatinib
  • lorlatinib
42
Q

What are the NICE approved treatments for ROS-1 mutations?

A
  • crizotinib
  • entrectinib
43
Q

How efficacious is oncogene-directed treatment?

A

Improvements in progression-free survival, but not necessarily overall survival vs standard chemo

44
Q

What side effects are there for oncogene-directed treatment?

A
  • Generally well tolerated (tablets)
  • Rash, diarrhoea and uncommonly pneumonitis
45
Q

How does immunotherapy work against lung cancer?

A
  • T cells can mop up and kill off early cancer cells
  • Many tumours bypass this system through PD-1 (a protein on T cells) which binds to PD-L1 receptor on tumour cell and blocks T cells from working
  • Immunotherapy blocks PD-L1 receptor or PD-1 allowing T cell to kill tumour cell
46
Q

What is immunotherapy first in line for in lung cancer?

A

Metastatic NSCLC with no mutation (and PDL1 ≥50%)

47
Q

What NICE approved immunotherapy treatments for lung cancer are there?

A
  • Pembrolizunab
  • Atezolizumab
  • Nivolumab
48
Q

How efficacious is immunotherapy?

A
  • Improvements in progression-free survival and overall survival vs standard chemotherapy
  • 32% alive at 5 years
49
Q

What side-effects are there of immunotherapy?

A
  • Generally well-tolerated
  • Immune-related side effects in 10-15% (thyroid, skin, bowel, lung, liver)
50
Q

When is cytotoxic chemotherapy first line?

A

For metastatic NSCLC with no mutation and PDL1 ≤50% (in combo with immunotherapy)

51
Q

What does cytotoxic chemotherapy do?

A

Targets rapidly dividing cells and kill them

Uses platinum-based regimens, e.g. carboplatin, cisplatin, paclitaxel, pemetrexed

52
Q

How efficacious is cytotoxic chemotherapy?

A
  • When used alone, there are modest improvements in overall survival vs best supportive care
  • Usually given with immunotherapy now which boosts outcomes
53
Q

What side effects are there of cytotoxic chemotherapy?

A
  • Frequent- fatigue, nausea, bone marrow suppression, nephrotoxicity
  • Quality of life poorly evaluated in trials- no evidence for improvement
54
Q

When is palliative and supportive care offered for lung disease?

A

Should be offered as a standard to all patients with advanced stage disease

55
Q

What is focussed on in palliative care?

A
  • Symptom control
  • Psychological support
  • Practical and financial support
  • Education
  • Planning for end of life
56
Q

How well does palliative care work?

A
  • Evidence that it boosts survival as well as symptomatic benefit
  • Study done on 151 patients with new diagnosis of NSCLC and standard oncology care with/without early palliative care given
    • At 12 weeks there was improved quality of life and lower depression scores
    • Median survival was 11.6 vs 8.9 months
57
Q

What’s given in early stage disease?

A

Surgery or radiotherapy with curative intent

58
Q

What’s given in locally advanced disease (involving thoracic lymph nodes)?

A
  • Surgery + adjuvant chemotherapy
  • Radiotherapy + chemotherapy +/- immunotherapy
59
Q

What’s given in metastatic disease?

A
  • With targetable mutation (e.g. EGFR, ALK, ROS-1) a tyrosine kinase inhibitor is given
  • No mutation, PDL-1 positive- immunotherapy alone
  • No mutation, PDL-1 negative- standard chemo + immunotherapy
  • Palliative care, alone or with the above
60
Q

How many patients with lung cancer live beyond 10 years?

A

Only 10%

Higher staged disease means you less live long

61
Q

What does Tis mean in lung cancer?

A

Carcinoma in situ (squamous or adenocarcinoma)

62
Q

What does T1 mean?

A

Tumour ≤ 3cm

63
Q

What does T1a(mi)/T1a mean?

A

T1a(mi): Minimally invasive adenocarcinoma
T1a: superficial spreading tumour in central airways

Tumour ≤ 1cm

64
Q

What does T1b mean in lung cancer?

A

Tumour 1-2cm

65
Q

What does T1c mean in lung cancer?

A

Tumour 2-3cm

66
Q

What does T2 mean in lung cancer?

A

Tumour 3-5cm; or tumour involving:
- visceral pleura
- main bronchus, atelectasis to hilum

67
Q

What does T2a mean in lung cancer?

A

Tumour 3-4cm

68
Q

What does T2b mean in lung cancer?

A

Tumour 4-5cm

69
Q

What does T3 mean in lung cancer?

A
  • Tumour 5-7cm or
  • Invading chest wall, pericardium, phrenic nerve or
  • Separate tumour nodules in the same lobe
70
Q

What does T4 mean in lung cancer?

A
  • Tumour >7cm or
  • Tumour invading: mediastinum, diaphragm, heart, great vessels, recurrent laryngeal nerve, carina, trachea, oesophagus, spine or
  • Tumour nodule(s) in a different ipsilateral lobe
71
Q

What does N0 mean in lung cancer?

A

No regional node metastasis

72
Q

What does N1 mean in lung cancer?

A

Metastasis in ipsilateral pulmonary or hilar nodes

73
Q

What does N2 mean in lung cancer?

A

Metastasis in ipsilateral mediastinal/subcarinal nodes

74
Q

What does N3 mean in lung cancer?

A

Metastasis in contralateral mediastinal/hilar, or supraclavicular nodes

75
Q

What does M0 mean in lung cancer?

A

No distant metastasis

76
Q

What does M1a mean in lung cancer?

A

Malignant pleural/pericardial effusion or pleural/pericardial nodules or

Separate tumour nodule(s) in a contralateral lobe

77
Q

What does M1b mean in lung cancer?

A

Single extrathoracic metastasis

78
Q

What does M1c mean in lung cancer?

A

Multiple extrathoracic metastases (1 or >1 organ)

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