1B lung cancer Flashcards
(78 cards)
1
Q
Describe the epidemiology of lung cancer
A
- 3rd most common cancer in UK
- Leading cause of cancer death
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
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
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%)
5
Q
Where does squamous cell carcinoma originate from?
A
Bronchial epithelium, centrally located
6
Q
Where do adenocarcinomas originate from?
A
Mucus-producing glandular tissue- more peripherally located
Most common lung cancer from 80s onwards
7
Q
What is large cell lung cancer?
A
Heterogenous group, undifferentiated
8
Q
Where does small cell lung cancer originate?
A
From pulmonary neuroendocrine cells.
Highly malignant.
9
Q
What are squamous cell carcinoma, adenocarcinoma and large cell lung cancer often grouped as?
A
Non-small cell lung cancer (NSCLC)
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.
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)
12
Q
What is EGFR tyrosine kinase common in?
A
- 15-30% of adenocarcinoma
- More common in women, Asian, never-smokers
13
Q
What is ALK tyrosine kinase common in?
A
- 2-7% of NSCLC
- Especially in younger patients and never smokers
14
Q
What is ROS1 receptor tyrosine kinase common in?
A
- 1-2% of NSCLC
- Especially in younger patients and never smokers
15
Q
What is BRAF common in?
A
- 1-3% of NSCLC
- Especially in smokers
16
Q
What are the key symptoms of lung cancer?
A
- Cough
- Breathlessness
- Chest pain
- Haemoptysis (coughing up blood)
- Weight loss
- Fatigue
Frequently asymptomatic
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
18
Q
What common sites of lung cancer metastases are there?
A
- Bones
- Liver
- Brain
- Lymph nodes
- Adrenal glands
19
Q
What are the clinical signs of lung cancer?
A
- Clubbing
- Horner’s syndrome
- Superior vena cava obstruction (Pemberton’s sign)
- Cachexia
20
Q
What clinical sign of lung cancer does this image show?
A
Clubbing
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
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
23
Q
What does this image show?
A
Cachexia
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
25
What does the bottom right show?
Pleural effusion- this counts as metastatic lung cancer since pleura is different tissue from lung
26
What are the black dots in the top left image patient's lung?
Emphysema
27
What are the blobs on the liver of the middle patient?
Metastases
28
Why are PET scans used for lung cancer?
Most useful to exclude occult metastases (metastases that are initially undetected)
29
Describe how lung biopsies are done?
1) Choose method based on accessibility, availability and impact on staging
2) Bronchoscopy for tumours of **central airway where tissue staging** not important
30
What is EBUS[TBNA]?
- Endobronchial ultrasound and transbronchial-needle aspiration of mediastinal lymph nodes (EBUS [TBNA])
- To stage mediastinum with or without achieving tissue diagnosis
31
What is CT-guided lung biopsy?
- Needle put through chest wall to take tissue sample
- Done to access peripheral lung tumours
- For bronchoscopy, tumour has to be central near airway
32
What is the TNM system of staging done for lung cancer?
- 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
How else can we stage lung cancer aside from TNM?
Early vs locally-advanced vs metastatic
34
What determinants of treatment are there for lung cancer?
- Patient fitness
- Cancer histology
- Cancer stage
- Patient preference
- Health service factors
35
How is patient fitness classified?
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
Which levels are usually required in the WHO performance status for treatment of lung cancer?
0 or 1 because 3 or 4 won't get much benefit from treatment
37
What is surgery standard of care in lung cancer?
- For **early stage disease**
- **Lobectomy** and **lymphadenectomy** is the usual approach
- Sublobar resection if stage 1 (≤3cm)
38
What is the alternative treatment for early stage disease than surgery?
- Radical radiotherapy
- Particularly if comorbidity
- **Stereotactic ablative body radiotherapy (SABR)**
- Technique of choice
- High-precision targeting, multiple convergent beams
39
When is oncogene-directed treatment used?
First line for metastatic NSCLC with mutation
Blocks the mutated protein
40
What are the NICE approved treatments for EGFR mutations?
- erlotinib
- gefitinib
- afatinib
- dacomitnib
- osimertinib
41
What are the NICE approved treatments for ALK mutations?
- crizotinib
- ceritinib
- alectinib
- brigatinib
- lorlatinib
42
What are the NICE approved treatments for ROS-1 mutations?
- crizotinib
- entrectinib
43
How efficacious is oncogene-directed treatment?
Improvements in progression-free survival, but not necessarily overall survival vs standard chemo
44
What side effects are there for oncogene-directed treatment?
- Generally well tolerated (tablets)
- Rash, diarrhoea and uncommonly pneumonitis
45
How does immunotherapy work against lung cancer?
- 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
What is immunotherapy first in line for in lung cancer?
Metastatic NSCLC with no mutation (and PDL1 ≥50%)
47
What NICE approved immunotherapy treatments for lung cancer are there?
- Pembrolizunab
- Atezolizumab
- Nivolumab
48
How efficacious is immunotherapy?
- Improvements in progression-free survival and overall survival vs standard chemotherapy
- 32% alive at 5 years
49
What side-effects are there of immunotherapy?
- Generally well-tolerated
- Immune-related side effects in 10-15% (thyroid, skin, bowel, lung, liver)
50
When is cytotoxic chemotherapy first line?
For metastatic NSCLC with no mutation and PDL1 ≤50% (in combo with immunotherapy)
51
What does cytotoxic chemotherapy do?
Targets rapidly dividing cells and kill them
Uses platinum-based regimens, e.g. carboplatin, cisplatin, paclitaxel, pemetrexed
52
How efficacious is cytotoxic chemotherapy?
- When used alone, there are modest improvements in overall survival vs best supportive care
- Usually given with immunotherapy now which boosts outcomes
53
What side effects are there of cytotoxic chemotherapy?
- Frequent- fatigue, nausea, bone marrow suppression, nephrotoxicity
- Quality of life poorly evaluated in trials- no evidence for improvement
54
When is palliative and supportive care offered for lung disease?
Should be offered as a standard to all patients with advanced stage disease
55
What is focussed on in palliative care?
- Symptom control
- Psychological support
- Practical and financial support
- Education
- Planning for end of life
56
How well does palliative care work?
- 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
What's given in early stage disease?
Surgery or radiotherapy with curative intent
58
What's given in locally advanced disease (involving thoracic lymph nodes)?
- Surgery + adjuvant chemotherapy
- Radiotherapy + chemotherapy +/- immunotherapy
59
What's given in metastatic disease?
- 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
How many patients with lung cancer live beyond 10 years?
Only 10%
Higher staged disease means you less live long
61
What does Tis mean in lung cancer?
Carcinoma in situ (squamous or adenocarcinoma)
62
What does T1 mean?
Tumour ≤ 3cm
63
What does T1a(mi)/T1a mean?
T1a(mi): Minimally invasive adenocarcinoma
T1a: superficial spreading tumour in central airways
Tumour ≤ 1cm
64
What does T1b mean in lung cancer?
Tumour 1-2cm
65
What does T1c mean in lung cancer?
Tumour 2-3cm
66
What does T2 mean in lung cancer?
Tumour 3-5cm; or tumour involving:
- visceral pleura
- main bronchus, atelectasis to hilum
67
What does T2a mean in lung cancer?
Tumour 3-4cm
68
What does T2b mean in lung cancer?
Tumour 4-5cm
69
What does T3 mean in lung cancer?
- Tumour 5-7cm or
- Invading chest wall, pericardium, phrenic nerve or
- Separate tumour nodules in the same lobe
70
What does T4 mean in lung cancer?
- 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
What does N0 mean in lung cancer?
No regional node metastasis
72
What does N1 mean in lung cancer?
Metastasis in ipsilateral pulmonary or hilar nodes
73
What does N2 mean in lung cancer?
Metastasis in ipsilateral mediastinal/subcarinal nodes
74
What does N3 mean in lung cancer?
Metastasis in contralateral mediastinal/hilar, or supraclavicular nodes
75
What does M0 mean in lung cancer?
No distant metastasis
76
What does M1a mean in lung cancer?
Malignant pleural/pericardial effusion or pleural/pericardial nodules or
Separate tumour nodule(s) in a contralateral lobe
77
What does M1b mean in lung cancer?
Single extrathoracic metastasis
78
What does M1c mean in lung cancer?
Multiple extrathoracic metastases (1 or >1 organ)
