Lung cancer (RESP) Flashcards
What is lung cancer the leading cause of?
Leading cause of cancer death worldwide
Describe the epidemiology of lung cancer. (2)
- M>F
- peak incidence 65-75y
What are some causes of lung cancer? (3)
- tobacco smoking
- exposure to carcinogens e.g. radon, asbestos
- family history
Describe the typical steps involved in cancer development.
Metaplasia –> dysplasia –> carcinoma in situ –> invasive carcinoma
How can lung cancer be divided into categories? (2)
- small cell lung cancer (SCLC)
- non-small cell lung cancer (NSCLC) - >80%
- adenocarcinoma
- squamous cell carcinoma
- large cell carcinoma
Describe small cell lung cancer (SCLC). (5)
- central
- originate from pulmonary neuroendocrine cells and highly malignant
- strong association with smoking
- associated with several paraneoplastic syndromes (SIADH, Cushing’s, Lambert-Eaton Syndrome AKA LEMS)
- also causes superior vena cava obstruction (SVCO)
How does superior vena cava obstruction present in small cell lung cancer? (6)
- dyspnoea
- swelling of face, neck and arms
- headache worse in mornings
- visual disturbance
- raised JVP
- positive Pemberton’s test - raising arms causes facial redness
What is the immediate management for superior vena cava obstruction in small cell lung cancer?
Oral dexamethasone
What are the three types of NSCLC?
- adenocarcinoma
- squamous cell carcinoma
- large cell carcinoma
Describe adenocarcinomas - NSCLC. (3)
- most common lung cancer
- peripheral (mucus-producing glandular tissue)
- non-smokers
Describe squamous cell carcinomas - NSCLC. (5)
- central (bronchial epithelium)
- associated with smoking
- PTHrP causes hypercalcaemia
- finger clubbing, wheeze, obstruction
- associated with cavitating lesions - upper lobe
Describe large cell carcinomas (NSCLC).
Heterogenous group of undifferentiated cells that are frequently aggressive
What is the SSS rule of lung cancer?
Squamous cell and Small cell lung cancers are both Sentrally located
What is epidermal growth factor receptor (EGFR) tyrosine kinase (lung cancer)?
- 15-20% adenocarcinoma
- more in women, Asians, never-smokers
What is anaplastic lymphoma kinase (ALK) tyrosine kinase (lung cancer)?
- 2-7% NSCLC
- younger patients and never-smokers
What is c-ROS oncogene 1 (ROS1) receptor tyrosine kinase?
- 1-2% of NSCLC
- younger patients and never-smokers
What is BRAF (downstream cell signalling mediator)?
- 1-3% NSCLC
- especially in smokers
What is a Pancoast tumour (lung cancer)?
Apical lung carcinoma, may cause Horner’s syndrome
What can a Pancoast tumour lead to? (1+5)
Horner’s syndrome:
- ipsilateral miosis
- ptosis
- anhidrosis (no sweat)
- laryngeal nerve damage (in some cases) –> hoarseness
- SVC obstruction
What is another cause of Horner’s syndrome, apart from a Pancoast tumour?
Carotid artery dissection
How does lung cancer often present?
Asymptomatic until late stages
What are the clinical features of lung cancer? (11)
- persistent cough
- haemoptysis
- progressive dyspnoea
- weight loss, fever, weakness
- chest pain
- hoarseness - Pancoast tumours pressing on recurrent laryngeal nerve
- neurological features - focal weakness, seizures, SC compression, dysphagia, arrhythmias
- bone pain
- recurrent pneumonia / pleural effusions
- SVC syndrome - head and neck oedema, arm swelling, distorted vision, headache, nasal stiffness, nausea, light-headedness
- hyperpigmentation (in SCLC - due to ectopic ACTH –> increased MSH)
What might you see on examination in lung cancer? (8)
- clubbing
- cachexia
- palpable mass
- supraclavicular or persistent cervical lymphadenopathy
- Horner’s syndrome (ptosis, miosis, anhidrosis, hoarseness, SVCO)
- SVC obstruction - dyspnoea, headache, swelling, raised JVP, vision, Pemberton’s
- Pemberton’s sign - SVC obstruction –> facial flushing when arms raised
- paraneoplastic syndrome
What sign is seen in superior vena cava obstruction (lung cancer)?
Positive Pemberton’s sign - raising arms causes facial redness
(Immediate management is oral dexamethasone)
What metastatic features of lung cancer may we see?
Brain, bone, liver, adrenals:
- headaches
- seizures
- bone pain
- jaundice
- hepatomegaly
What paraneoplastic syndrome features would you see in adenocarcinoma (lung cancer)?
Gynaecomastia
What paraneoplastic syndrome features would you see in SCLC (lung cancer)? (3)
- SIADH - hyponatraemia, high urine osmolality, high urine sodium
- Cushing’s (ACTH)
- Lambert-Eaton Syndrome (LEMS):
- difficulty walking (waddling gait)
- muscle tenderness
- hyporeflexia
- muscle weakness that improves with exercise (as opposed to myasthenia gravis)
What are the features of Lambert-Eaton Syndrome (paraneoplastic syndrome, SCLC)? (4)
- difficulty walking (waddling gait)
- muscle tenderness
- hyporeflexia
- muscle weakness that improves with exercise (as opposed to myasthenia gravis)
What antibodies do you find in Lambert-Eaton Syndrome (SCLC)?
Antibodies against pre-synaptic voltage-gated calcium channels at NMJ
What paraneoplastic syndrome features would you see in squamous cell carcinoma (lung cancer)? (2)
-
PTH-releasing peptide -
- hypercalcaemia (constipation, myopathy, polydipsia, polyuria, low mood, bone pain)
- clubbing
- cavitating lesions
- hyperthyroidism
- hypertrophic pulmonary osteoarthropathy - clubbing, periostitis of small hand joints
What are the features of PTH-releasing peptide (paraneoplastic syndrome in SCC of the lung)? (4)
- hypercalcaemia (constipation, myopathy, polydipsia, polyuria, low mood, bone pain)
- clubbing
- cavitating lesions
- hyperthyroidism
What are some risk factors for lung cancer? (8)
- cigarette smoking
- environmental tobacco exposure
- COPD
- family history
- radon gas exposure
- asbestos exposure
- older age
- male
What are the first-line investigations for lung cancer? (2)
- 1st: CXR
- then: contrast-enhanced CT (chest, liver, adrenals) should be performed before a fibreoptic bronchoscopy/endobronchial ultrasound needle aspiration as allows you to identify and localise the lesion
What other imaging can we do in lung cancer? (4)
- PET-CT to look for metastases and lymph node involvement
- bronchoscopy - central lesion (e.g. SCC/SCLC); biopsy and TNM staging
- CT-guided lung biopsy - peripheral lesion (e.g. adenocarcinoma)
- endobronchial ultrasound and transbronchial-needle aspiration (EBUS-TBNA) of mediastinal lymph nodes
What bloods do we look for in lung cancer? (5)
- raised platelets - thrombocytosis
- hyponatraemia - SCLC
- hypercalcaemia - bone metastases or PTHrP in SCC
- ALP - bone metastases
- LFTs - liver metastases
What are some differential diagnoses for lung cancer? (8)
- abscess
- granuloma
- carcinoid tumour
- pulmonary hamartoma
- A/V malformation
- cyst
- foreign body
- skin tumour
What are some determinants for treatment of lung cancer? (5)
- patient fitness - WHO scale 0-5, radical treatment limited to PS 0-2, comorbidity and lung function also considered
- cancer histology
- cancer stage
- patient preference
- health service factors
How is patient fitness in lung cancer classified by WHO performance status?
- 0 - asymptomatic (fully active, able to carry out 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 of lung cancer?
0-2 as 3/4 will not benefit much (supportive care instead)
What are the surgical options for lung cancer? (4)
- lobectomy and lymphadenectomy
- sublobar resection if stage 1 lung cancer <3cm
- video-assisted thoracoscopic surgery (VATS) more modern
- pneumonectomy in more severe cases
What is radical radiotherapy in lung cancer?
- stereotactic ablative body radiotherapy (SABR)
- 10 sessions once a day over 2 weeks
- early stage disease where patient has comorbidity
What are some contraindications to surgery in lung cancer? (4)
- SVC obstruction
- malignant pleural effusion
- vocal cord paralysis
- FEV<1/5
How do we manage SVC syndrome in lung cancer? (4)
- supplemental oxygen
- tilt head upwards
- oral dexamethasone 8mg BD
- emergency Rx: steroids, SVC balloon dilatation, stent insertion - indicated when brain oedema, decreased CO, upper airway compression
How do we manage Horner’s syndrome in lung cancer? (2)
- apraclonidine
- cocaine eye drops
What is the management plan for NSCLC (adenocarcinoma, SCC, large cell carcinoma)? (4)
- 1st line: lobectomy
- stages I, II, III: curative radiotherapy also offered
- stages III, IV: chemotherapy should be offered to control disease and improve QoL
- advanced NSCLC: targeted therapy - EGFR inhibitors, ALK tyrosine kinase inhibitors
What is an alternative treatment (rather than surgery) for early stage lung cancer?
- 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 in lung cancer?
First-line for metastatic NSCLC with mutation (blocks mutated protein)
What are the NICE approved systemic-oncogene directed treatments for metastatic NSCLC?
- EGFR - erlotinib, gefitinib, afatinib, dacomitinib, osimertinib
- ALK - crizotinib, ceritinib, alectinib, brigatinib, lorlatinib
- ROS-1 - crizotinib, entrectinib
How good is the efficacy of systemic oncogene-directed treatments in metastatic NSCLC?
Improvements in progression-free survival, modest overall survival vs standard chemotherapy
What are some side effects of systemic oncogene-directed treatment for metastatic NSCLC? (3)
Generally well-tolerated (tablets), but:
- rash
- diarrhoea
- uncommonly pneumonitis
How does systemic immunotherapy work against metastatic NSCLC?
- 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
Describe systemic immunotherapy as a treatment for metastatic NSCLC.
- first-line for metastatic NSCLC with no mutation and PD-L1>50%
- pembrolizumab, atezolizumab, nivolumab
- improves progression-free survival and overall survival vs standard chemotherapy
- generally well-tolerated
- immune-related side effects in 10-15% (thyroid, skin, bowel, lung, liver)
Describe systemic cytotoxic chemotherapy as a treatment for metastatic NSCLC. (4)
- first-line for metastatic NSCLC with no mutation and PD-L1<50% (in combination with immunotherapy to boost outcomes)
- targets rapidly dividing cells and kills
- platinum-based regimens e.g. carboplatin, cisplatin, paclitaxel, pemetrexed
- side effects: fatigue, nausea, BM suppression, nephrotoxicity
Summarise the three systemic therapies used for metastatic NSCLC. (4)
- targetable mutation (e.g. EGFR, ALK, ROS-1) - tyrosine kinase inhibitor (systemic oncogene-directed treatment)
- no mutation, PDL1 positive - immunotherapy alone
- no mutation, PDL1 negative - cytotoxic ‘standard’ chemotherapy + immunotherapy
- palliative care alone or with the above
What is the management for SCLC (lung cancer)? (2)
- palliative chemotherapy
- correct SIADH slowly - fluid restriction, demeclocycline (reduces responsiveness of collecting tubule cells to ADH), ADH receptor antagonists
What do you need to check in a lung cancer patient before putting in a chest drain for pleural effusion?
INR for bleeding risk
Summarise the treatments for different types of lung cancer. (3)
- NSCLC: lobectomy, SABR/curative radiotherapy
- metastatic NSCLC: systemic oncogene-directed therapy (mutation), immunotherapy (PD-L1>50%), cytotoxic chemotherapy
- SCLC: palliative chemotherapy
What is a complication of lung cancer?
Lobar collapse
What is the prognosis of NSCLC compared to SCLC?
NSCLC has better prognosis than SCLC
Only 10% of lung cancer patients survive beyond 10y
