5.7 - Lung cancer Flashcards
What is the epidemiology of lung cancer?
- 3rd most common cancer in UK
- leading cause of cancer death
- 10-15% of patients with lung cancer never smoked
Who gets lung cancer more often?
- age - peak is 75-90
- sex - M>F
- lower socioeconomic status
- smoking history - duration, intensity, when stopped
What factors (other than smoking) contribute to lung cancer? (7)
- 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
What is the pathogenesis of lung cancer?
- 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
What are the four main types of lung cancer?
- squamous cell carcinoma (30%)
- adenocarcinoma (40%)
- large cell lung cancer (15%)
- small cell lung cancer (15%)
Where do squamous cell carcinomas originate from?
Originating from bronchial epithelium, centrally located
Where do adenocarcinomas originate from?
Mucus-producing glandular tissue; more peripherally located
(Most common from 1980s onwards)
What is large cell lung cancer?
Heterogenous group, undifferentiated (peripheral)
Where do small cell lung cancers originate from?
Pulmonary neuroendocrine cells, highly malignant (central)
What are squamous cell carcinomas, adenocarcinomas and large cell lung cancers often grouped together as?
Non-small cell lung cancer (NSCLC)
What important oncogenes have been found to have mutations in lung cancer? (4)
- 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)
What are epidermal growth factor receptor (EGFR) tyrosine kinase mutations common in?
- 15-30% of adenocarcinoma
- more so in women, Asian ethnicity, never-smokers (if patient is never-smoker, most likely adenocarcinoma)
What are anaplastic lymphoma kinase (ALK) tyrosine kinase mutations common in?
- 2-7% of non-small cell lung cancer
- especially in younger patients and never-smokers
What are c-ROS oncogene 1 (ROS1) receptor tyrosine kinase mutations common in?
- 1-2% of non-small cell lung cancer
- especially in younger patients and never-smokers
What are BRAF (downstream cell-cycle signalling mediator) mutations common in?
- 1-3% of non-small cell lung cancer
- especially in smokers
What are the key symptoms of lung cancer? (6 + 1)
- cough
- weight loss
- breathlessness
- fatigue
- chest pain
- haemoptysis
- OR FREQUENTLY ASYMPTOMATIC
Why does lung cancer kill so many based on symptoms?
Symptoms present quite late / frequently asymptomatic since lungs are a large organ and tumours have room to grow before you see signs
What are the features of advanced/metastatic lung cancer? (3)
- neurological features - focal weakness, seizures, spinal cord compression
- bone pain
- paraneoplastic syndromes - clubbing, hypercalcaemia, hyponatraemia, Cushing’s
What are the common sites of lung cancer metastases? (5)
- bones
- liver
- brain
- lymph nodes
- adrenal glands
What are some clinical signs of lung cancer? (4)
- 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)
Describe the diagnostic strategy for lung cancer.
- 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
Who is involved in the lung cancer MDT? (7)
- respiratory
- radiology
- pathology
- thoracic surgery
- oncology
- palliative care
- patient is central
What forms of imaging can be used in investigating lung cancer? (3)
- chest X-ray
- staging CT (chest and abdomen)
- PET scan
What does big white cloudy area on left side of X-ray image show?
Pleural effusion - high chance of metastatic lung cancer as pleura is a different tissue to the lung
What are black dots on a lung as seen on a staging CT (chest and abdomen)?
Emphysema
What are blobs on the liver as seen on a staging CT (chest and abdomen)?
Metastases
Why are PET scans useful in lung cancer?
Most useful to exclude occult metastases (metastases that are initially undetected) - bright areas = high metabolic activity
What are the different methods of doing a lung biopsy? (3)
- 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
What do you choose lung biopsy method based on? (3)
Accessibility, availability, impact on staging
What is the TNM system of lung cancer staging?
- T1-4: tumour size and location
- N0-3: lymph node involvement (mediastinal + beyond)
- M0-1c: metastases + number
What are some general rules about the TNM staging system and stages I-IV lung cancer?
- 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
What are the size ranges for T1-T4 lung tumours?
- T1: </=3cm
- T2: 3-5cm
- T3: 5-7cm
- T4: >7cm
How else can we stage lung cancer?
Early vs locally-advanced vs metastatic
What are the determinants of treatment of lung cancer? (5)
- patient fitness
- cancer histology
- cancer stage
- patient preference
- health service factors
How is patient fitness classified by the 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 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
Which levels of WHO performance status are usually required for treatment?
0/1(/ 2) as 3/4 will not benefit much from treatment (supportive care instead)
What else is important to consider when deciding patient fitness along with WHO performance status?
Comorbidity and lung function
What is surgery of the lung?
- surgical resection is standard of care for early stage disease
- lobectomy + lymphadenectomy is the usual approach
- sublobar resection if stage 1 (<3cm)
What are the types of surgical resection of the lung? (4)
- 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)
What is an alternative treatment for early stage lung cancer other than surgery?
- stereotactic ablative body radiotherapy (SABR) - technique of choice, high-precision targeting, multiple convergent beams
- particularly useful if you have a comorbidity
When is systemic oncogene-directed treatment used?
First line for metastatic NSCLC with mutation (blocks mutated protein)
What are the NICE approved treatments for specific oncogenes?
- EGFR - erlotinib, gefitinib, afatinib, dacomitinib, osimertinib
- ALK - crizotinib, ceritinib, alectinib, brigatinib, lorlatinib
- ROS-1 - crizotinib, entrectinib
‘Tinibs’
How good is the efficacy of systemic oncogene-directed treatments?
- 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
What are some side effects of systemic oncogene-directed treatment?
- generally well-tolerated (tablets)
- rash, diarrhoea and uncommonly pneumonitis
How does systemic immunotherapy work against lung cancer?
- 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
What is systemic immunotherapy first line for in lung cancer?
First line for metastatic NSCLC with no mutation (and PD-L1 >50%)
What NICE-approved systemic immunotherapy treatments are there for lung cancer? (3)
- pembrolizumab
- atezolizumab
- nivolumab
What is the efficacy like for systemic immunotherapy targeting lung cancer?
- 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
What are some side effects of systemic immunotherapy?
- generally well-tolerated
- immune-related side effects in 10-15% (thyroid, skin, bowel, lung, liver)
When is systemic cytotoxic chemotherapy first line for lung cancer treatment?
Metastatic NSCLC with no mutation and PD-L1<50% (in combination with immunotherapy)
How does systemic cytotoxic chemotherapy work?
- target rapidly dividing cells and kills
- platinum-based regiments e.g. carboplatin, cisplatin, paclitaxel, pemetrexed
What is the efficacy like of systemic cytotoxic chemotherapy?
- when used alone, modest improvements in overall survival vs best supportive care
- usually given with immunotherapy now = boosts outcomes
What are some side effects of systemic cytotoxic chemotherapy?
- frequent - fatigue, nausea, bone marrow suppression, nephrotoxicity
- QOL poorly evaluated in trials - no evidence for improvement
Summary - what are the three systemic therapies for lung cancer?
- oncogene-directed tyrosine kinase inhibitors
- immunotherapy
- cytotoxic chemotherapy
When is palliative and supportive care offered?
Should be offered as a standard to all patients with advanced stage disease
What is focused on in palliative care? (5)
- symptom control
- psychological support
- education
- practical and financial support
- planning for end of life
How well does palliative care work?
- 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
Treatment summary - how do you treat early stage lung cancer?
Surgery or radiotherapy (SABR) with curative intent
Treatment summary - how do you treat locally advanced disease (involving thoracic lymph nodes)?
- surgery + adjuvant chemotherapy
- radiotherapy + chemotherapy +/- immunotherapy
Treatment summary - how do you treat metastatic lung cancer?
- 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
How many patients with lung cancer live beyond ten years?
- only 10%
- higher-staged disease = live less long
