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Year 2 - BRS > 5.7 - Lung cancer > Flashcards

5.7 - Lung cancer Flashcards

1
Q

What is the epidemiology of lung cancer?

A
  • 3rd most common cancer in UK
  • leading cause of cancer death
  • 10-15% of patients with lung cancer never smoked
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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 factors (other than smoking) contribute to lung cancer? (7)

A
  • passive smoking (15% of never smokers)
  • asbestos - exposure (plumbers, ship-builders, carriage workers, carpenters) increases risk up to x2
  • radon (e.g. silver miners in Germany 1800s, uranium miners)
  • indoor cooking fumes - wood smoke, frying fats
  • chronic lung diseases (COPD, fibrosis)
  • air pollution
  • familial/genetic - several loci identified
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4
Q

What is the pathogenesis of lung cancer?

A
  • lung cancer may arise from all differentiated and undifferentiated cells
  • interaction between inhaled carcinogens and the epithelium of upper and lower airways –> 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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5
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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6
Q

Where do squamous cell carcinomas originate from?

A

Originating from bronchial epithelium, centrally located

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7
Q

Where do adenocarcinomas originate from?

A

Mucus-producing glandular tissue; more peripherally located
(Most common from 1980s onwards)

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8
Q

What is large cell lung cancer?

A

Heterogenous group, undifferentiated (peripheral)

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9
Q

Where do small cell lung cancers originate from?

A

Pulmonary neuroendocrine cells, highly malignant (central)

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10
Q

What are squamous cell carcinomas, adenocarcinomas and large cell lung cancers often grouped together as?

A

Non-small cell lung cancer (NSCLC)

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11
Q

What important oncogenes have been found to have mutations in lung cancer? (4)

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-cycle signalling mediator)
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12
Q

What are epidermal growth factor receptor (EGFR) tyrosine kinase mutations common in?

A
  • 15-30% of adenocarcinoma
  • more so in women, Asian ethnicity, never-smokers (if patient is never-smoker, most likely adenocarcinoma)
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13
Q

What are anaplastic lymphoma kinase (ALK) tyrosine kinase mutations common in?

A
  • 2-7% of non-small cell lung cancer
  • especially in younger patients and never-smokers
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14
Q

What are c-ROS oncogene 1 (ROS1) receptor tyrosine kinase mutations common in?

A
  • 1-2% of non-small cell lung cancer
  • especially in younger patients and never-smokers
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15
Q

What are BRAF (downstream cell-cycle signalling mediator) mutations common in?

A
  • 1-3% of non-small cell lung cancer
  • especially in smokers
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16
Q

What are the key symptoms of lung cancer? (6 + 1)

A
  • cough
  • weight loss
  • breathlessness
  • fatigue
  • chest pain
  • haemoptysis
  • OR FREQUENTLY ASYMPTOMATIC
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17
Q

Why does lung cancer kill so many based on symptoms?

A

Symptoms present quite late / frequently asymptomatic since lungs are a large organ and tumours have room to grow before you see signs

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18
Q

What are the features of advanced/metastatic lung cancer? (3)

A
  • neurological features - focal weakness, seizures, spinal cord compression
  • bone pain
  • paraneoplastic syndromes - clubbing, hypercalcaemia, hyponatraemia, Cushing’s
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19
Q

What are the common sites of lung cancer metastases? (5)

A
  • bones
  • liver
  • brain
  • lymph nodes
  • adrenal glands
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20
Q

What are some clinical signs of lung cancer? (4)

A
  • clubbing
  • Horner’s syndrome (constricted pupil, ptosis/droopy eyelid, sweating on one side of face)
  • superior vena cava obstruction –> Pemberton’s sign (lift arms up increases venous return which causes redness and swelling of face, as blood cannot drain out)
  • cachexia (extreme muscle wasting)
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21
Q

Describe the diagnostic strategy for lung cancer.

A
  • establish most likely diagnosis
  • establish fitness for investigation and treatment
  • confirm diagnosis and histological type (genomic testing key if considering systemic treatment in NSCLC)
  • confirm staging
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22
Q

Who is involved in the lung cancer MDT? (7)

A
  • respiratory
  • radiology
  • pathology
  • thoracic surgery
  • oncology
  • palliative care
  • patient is central
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23
Q

What forms of imaging can be used in investigating lung cancer? (3)

A
  • chest X-ray
  • staging CT (chest and abdomen)
  • PET scan
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24
Q

What does big white cloudy area on left side of X-ray image show?

A

Pleural effusion - high chance of metastatic lung cancer as pleura is a different tissue to the lung

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25
Q

What are black dots on a lung as seen on a staging CT (chest and abdomen)?

A

Emphysema

26
Q

What are blobs on the liver as seen on a staging CT (chest and abdomen)?

A

Metastases

27
Q

Why are PET scans useful in lung cancer?

A

Most useful to exclude occult metastases (metastases that are initially undetected) - bright areas = high metabolic activity

28
Q

What are the different methods of doing a lung biopsy? (3)

A
  • bronchoscopy - for tumours of central and segmental airways where tissue staging not important
  • endobronchial ultrasound and transbronchial-needle aspiration of mediastinal lymph nodes (EBUS [TBNA]) - to stage mediastinum with/without achieving tissue diagnosis
  • CT-guided lung biopsy (needle through chest wall to take sample) - to access peripheral lung tumours
29
Q

What do you choose lung biopsy method based on? (3)

A

Accessibility, availability, impact on staging

30
Q

What is the TNM system of lung cancer staging?

A
  • T1-4: tumour size and location
  • N0-3: lymph node involvement (mediastinal + beyond)
  • M0-1c: metastases + number
31
Q

What are some general rules about the TNM staging system and stages I-IV lung cancer?

A
  • all stage I-III tumours are M0
  • stage I tumours are T1/2,N0
  • stage II tumours are T1/2/3,N0/1
  • stage III tumours are T3/4,N0/1/2/3
  • stage IV tumours are all M1
32
Q

What are the size ranges for T1-T4 lung tumours?

A
  • T1: </=3cm
  • T2: 3-5cm
  • T3: 5-7cm
  • T4: >7cm
33
Q

How else can we stage lung cancer?

A

Early vs locally-advanced vs metastatic

34
Q

What are the determinants of treatment of lung cancer? (5)

A
  • patient fitness
  • cancer histology
  • cancer stage
  • patient preference
  • health service factors
35
Q

How is patient fitness classified by the WHO performance status?

A
  • 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 able to carry out any light/sedentary work activities)
  • 2 - symptomatic, up and about >50% of waking hours (ambulatory and capable of all self-care but unable to carry out any work activities)
  • 3 - symptomatic, confined to bed or chair >50% of waking hours (capable of only limited self-care)
  • 4 - completely disabled (cannot carry on any self-care, fully confined)
  • 5 - death
36
Q

Which levels of WHO performance status are usually required for treatment?

A

0/1(/ 2) as 3/4 will not benefit much from treatment (supportive care instead)

37
Q

What else is important to consider when deciding patient fitness along with WHO performance status?

A

Comorbidity and lung function

38
Q

What is surgery of the lung?

A
  • surgical resection is standard of care for early stage disease
  • lobectomy + lymphadenectomy is the usual approach
  • sublobar resection if stage 1 (<3cm)
39
Q

What are the types of surgical resection of the lung? (4)

A
  • wedge resection - removes small section of lung that contains the tumour along with margin of healthy tissue (rare)
  • segmental resection - removes larger portion of lung, but not entire lobe
  • lobectomy - removes entire lobe
  • pneumonectomy - removes entire lung (rare)
40
Q

What is an alternative treatment for early stage lung cancer other than surgery?

A
  • stereotactic ablative body radiotherapy (SABR) - technique of choice, high-precision targeting, multiple convergent beams
  • particularly useful if you have a comorbidity
41
Q

When is systemic oncogene-directed treatment used?

A

First line for metastatic NSCLC with mutation (blocks mutated protein)

42
Q

What are the NICE approved treatments for specific oncogenes?

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

‘Tinibs’

43
Q

How good is the efficacy of systemic oncogene-directed treatments?

A
  • improvements in progression-free survival, modest overall survival vs standard chemotherapy
  • e.g. erlotinib PFS 14 vs 5 months, OS 23 vs 29 months
  • e.g. crizotinib PFS 8 vs 3 months, OS 20 vs 23 months
44
Q

What are some side effects of systemic oncogene-directed treatment?

A
  • generally well-tolerated (tablets)
  • rash, diarrhoea and uncommonly pneumonitis
45
Q

How does systemic immunotherapy work against lung cancer?

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

What is systemic immunotherapy first line for in lung cancer?

A

First line for metastatic NSCLC with no mutation (and PD-L1 >50%)

47
Q

What NICE-approved systemic immunotherapy treatments are there for lung cancer? (3)

A
  • pembrolizumab
  • atezolizumab
  • nivolumab
48
Q

What is the efficacy like for systemic immunotherapy targeting lung cancer?

A
  • improvements in progression-free survival and overall survival vs standard chemotherapy
  • e.g. pembrolizumab PFS 10 vs 6 months, OS >30 vs 14 months
  • 32% alive at five years
49
Q

What are some side effects of systemic immunotherapy?

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

When is systemic cytotoxic chemotherapy first line for lung cancer treatment?

A

Metastatic NSCLC with no mutation and PD-L1<50% (in combination with immunotherapy)

51
Q

How does systemic cytotoxic chemotherapy work?

A
  • target rapidly dividing cells and kills
  • platinum-based regiments e.g. carboplatin, cisplatin, paclitaxel, pemetrexed
52
Q

What is the efficacy like of systemic cytotoxic chemotherapy?

A
  • when used alone, modest improvements in overall survival vs best supportive care
  • usually given with immunotherapy now = boosts outcomes
53
Q

What are some side effects of systemic cytotoxic chemotherapy?

A
  • frequent - fatigue, nausea, bone marrow suppression, nephrotoxicity
  • QOL poorly evaluated in trials - no evidence for improvement
54
Q

Summary - what are the three systemic therapies for lung cancer?

A
  • oncogene-directed tyrosine kinase inhibitors
  • immunotherapy
  • cytotoxic chemotherapy
55
Q

When is palliative and supportive care offered?

A

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

56
Q

What is focused on in palliative care? (5)

A
  • symptom control
  • psychological support
  • education
  • practical and financial support
  • planning for end of life
57
Q

How well does palliative care work?

A
  • evidence for survival and symptomatic benefit
  • study done on 151 patients with new diagnosis of NSCLC and standard oncology care with/without palliative care given
  • at 12 weeks improved QOL and lower depression scores
  • median survival 11.6 vs 8.9 months
58
Q

Treatment summary - how do you treat early stage lung cancer?

A

Surgery or radiotherapy (SABR) with curative intent

59
Q

Treatment summary - how do you treat locally advanced disease (involving thoracic lymph nodes)?

A
  • surgery + adjuvant chemotherapy
  • radiotherapy + chemotherapy +/- immunotherapy
60
Q

Treatment summary - how do you treat metastatic lung cancer?

A
  • with targetable mutation (e.g. EGFR, ALK, ROS-1) - tyrosine kinase inhibitor
  • no mutation, PDL1 positive - immunotherapy alone
  • no mutation, PDL1 negative - cytotoxic ‘standard’ chemotherapy + immunotherapy
  • palliative care alone or with the above
61
Q

How many patients with lung cancer live beyond ten years?

A
  • only 10%
  • higher-staged disease = live less long

Year 2 - BRS (84 decks)

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