🫀🫁Cardio & Resp🫀🫁 - Lung Cancer Flashcards
What are the key epidemiological facts about lung cancer?
3rd most common cancer in the UK
48000 diagnoses/year
35000 deaths/year
Leading cause of cancer death
What groups of people are statistically more likely to get lung cancer?
Peak age 75-90
Males>females
Lower socioeconomic status
Smoking history strong indicator - duration, intensity, when stopped
Despite this, 10-15% patients with lung cancer never smoked
What other causes are there for lung cancer, other than smoking?
Asbestos - exposure associated with up to 2x risk
Radon - historically mining
Indoor cooking fumes
Chronic lung diseases
Air pollution
Fx/genetic factors
What is the basic pathogenesis of lung cancer?
Lung cancer may arise from all differentiated and undifferentiated cells
Interaction between inhaled carcinogens and epithelium of upper and lower airways - leads to the formation of DNA adducts - pieces of DNA covalently bound to a cancer-causing chemical
Persisting/misrepaired adducts result in mutations - cause genomic alterations
What are the various pathophysiologies of lung cancer?
- Squamous cell carcinoma (~30% of cases)
- Adenocarcinoma (~40%)
- Large cell lung cancer (~15%)
- Small cell lung cancer (~15%)
1-3 often grouped together as non-small cell lung cancer (NSCLC)
Outline squamous cell carcinoma lung cancer
30% of cases
Previously the most common
Originating from the bronchial epithelium - centrally located
(Coughing, haemoptysis, recurrent infections due to airway obstruction)
(Moderately fast - slower than small cell but can invade nearby structures early - better prognosis than small cell but worse than adenocarcinoma)
Outline adenocarcinoma lung cancer
40% of cases
Most common from 1980s onwards
Originates from mucus-producing glandular tissue- more peripheral
Accounts for most non-smoking lung cancer cases
(Later presentation with vague symptoms like shortness of breath/chest pain)
(Slower growing, can metastasize early, especially to bones and brain - generally better prognosis, especially if detected early)
Outline large cell lung cancer
15% of cases
Heterogenous group, undifferentiated
Often peripheral, but can be anywhere
(Non-specific symptoms; can cause chest pain, cough, or symptoms based on where it spreads)
(Aggressive, rapid growth, high likelihood of metastasis.
Poor prognosis due to rapid progression and late detection)
Outline small cell lung cancer
15% of cases
Originate from pulmonary neuroendocrine cells
Highly malignant
(Rapid onset of cough, weight loss, and paraneoplastic syndromes (e.g., SIADH, Cushing syndrome))
(Very fast growing, early and widespread metastasis.
Poorest prognosis, high recurrence rate even with treatment)
Name the 4 most important oncogenes in the pathogenesis of lung cancer, specifically mutations in them
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 is the significance of an Epidermal growth factor receptor (EGFR) tyrosine kinase mutation?
15-30% of adenocarcinoma
More so in women, Asian ethnicity, never-smokers
What is the significance of an Anaplastic lymphoma kinase (ALK) tyrosine kinase mutation?
2-7% of non-small cell lung cancer
Especially in younger patients and never-smokers
What is the significance in a c-ROS oncogene 1 (ROS1) receptor tyrosine kinase mutation?
1-2% of non-small cell lung cancer
Especially in younger patients and never-smoker
What is the significance of a BRAF (downstream cell-cycle signalling mediator) mutation?
1-3% of non-small cell lung cancer
Especially in smokers
What are the key symptoms of lung cancer?
Cough
Weight loss
Breathlessness
Fatigue
Chest pain
Haemoptysis
Can be frequently asymptomatic
What are the key features of advanced/metastatic lung cancer?
Neurological features:
Focal weakness, seizures, spinal cord compression
Bone pain
Paraneoplastic syndromes:
Clubbing, hypercalcaemia, hyponatraemia, Cushing’s
What is clubbing?
What is cachexia
Severe, rapid weight loss
Also features prominent muscle wasting
What is Pemberton’s sign?
What is Horner’s syndrome?
Decreased pupil size, a drooping eyelid and decreased sweating on the affected side of the face
What is the diagnostic strategy for suspected 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 in the lung cancer MDT?
Respiratory doctor
Radiologist
Pathology doctor
Thoracic surgeon
Oncologist
Palliative care
(Patient)
Who is currently eligible for lung cancer screening?
Current or ex-smokers aged between 55 and 74 are invited via their GP to attend a lung health check
Offered an appointment for a low dose CT scan
RMP pilot: Lung cancer detected in 29/1145 (2.5 %) participants scanned (stage 1, 58.6 %)
How is PET-CT useful?
Helps exclude occult metastases
What are occult metastases?
Metastatic cancer cells that have spread from the primary tumour site but are too small to be detected with conventional imaging techniques or during physical examination
How do you choose a method of biopsy for lung cancers?
Choose method based on accessibility, availability and impact on staging
What would you use a bronchoscopy for?
Tumours of central and segmental airways
How would you stage the mediastinum +/- achieve tissue diagnosis?
Endobronchial ultrasound and transbronchial-needle aspiration of mediastinal lymph nodes (EBUS [TBNA])
When would you use navigational bronchoscopy + robotic Bronchoscopy?
For peripheral lesions/nodules that are not amenable to conventional bronchoscopy or CT guided biopsy
How are biopsies taken from peripheral lung tumours?
CT-guided lung biopsy
How are lung cancers staged?
T1-4: tumour size and location
N0-3: lymph node involvement – mediastinum + beyond
M0-1c: metastases + number
Describe what you would see in early vs locally-advanced vs metastatic
What 5 factors act as determinants of treatment for lung cancer?
Patient fitness
Cancer histology
Cancer stage
Patient preference
Health service factors
What is the WHO performance status?
Scale that measures patient fitness
0 - Asymptomatic
1- Symptomatic but completely ambulatory
2 - Symptomatic, up and about >50% of waking hours
3 - Symptomatic, confined to bed or chair >50% of waking hours
4 - Completely disabled
5 - Death
Radical treatment usually restricted to PS 0-2
What is meant by “asymptomatic” on the WHO performance status?
Fully active, able to carry on all predisease activities without restriction
What is meant by “symptomatic but completely ambulatory” on the WHO performance status?
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature. For example, light housework, office work
What is meant by “symptomatic, up and about >50% of waking hours” on the WHO performance status?
Ambulatory and capable of all self care but unable to carry out any work activities
What is meant by “symptomatic, confined to bed or chair >50% of waking hours” on the WHO performance status?
Capable of only limited self-care
What is meant by “completely disabled” on the WHO performance status?
Completely disabled. Cannot carry on any self-care
Totally confined to bed or chair
What is meant by “death” on the WHO performance status?
Take a wild guess
What must also be considered when assessing a patient’s WHO performance status?
Comorbidity + lung function also very important
What is the standard care for early stage disease?
Surgical resection is standard of care for early stage disease
Lobectomy + lymphadenectomy usual approach
Sublobar resection if stage 1 (≤3 𝑐𝑚)
What is an alternative to surgery in early stage disease?
Radical radiotherapy
Particularly relevant if there is a comorbidity
Stereotactic ablative body radiotherapy (SABR)
Technique of choice
High-precision targeting, multiple convergent beams
What are the systemic treatments available for lung cancer treatment
Oncogene-directed drugs
Immunotherapy
Cytotoxic chemotherapy
When are systemic treatments used to treat lung cancers?
First line for metastatic NSCLC with mutation
What are the NICE approved drugs for use in oncogene-directed therapy?
EGFR: erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib
ALK: crizotinib, ceritinib, alectinib, brigatinib, lorlatinib
ROS-1: crizotinib, entrectinib
What is the reported efficacy of oncogene-directed therapy?
Improvements in progression-free survival, modest overall survival vs standard chemotherapy
What side effects can be experienced in oncogene-directed systemic treatment?
Generally well-tolerated (tablets)
Rash, diarrhoea, and (uncommonly) pneumonitis
When is immunotherapy used to treat lung cancer?
First line for metastatic NSCLC with no mutation (and PDL1 ≥50%)
What are the NICE approved immunotherapy drugs?
Pembrolizumab, atezolizumab, nivolumab
How does immunotherapy help treat lung cancer?
What is the reported efficacy of immunotherapy in treating lung cancer?
Improvements in progression-free survival AND overall survival vs standard chemotherapy
What are the potential side effects of immunotherapy?
Generally well-tolerated
Immune-related side-effects in 10-15% (thyroid, skin, bowel, lung, liver)
When is cytotoxic chemotherapy used to treat lung cancer?
First line for metastatic NSCLC with no mutation and PDL1 ≤50% (in combination with immunotherapy)
Outline the function of cytotoxic chemotherapy
Long established
Target any rapidly dividing cells
Platinum-based regimens, e.g. carboplatin, cisplatin, paclitaxel, pemetrexed
What is the reported efficacy of cytotoxic chemotherapy?
When used alone (old data, pre-2000) - modest improvements in overall survival vs best supportive care:
e.g. 29 vs 20% one year survival in clinical trials
With pembrolizumab, a lot better (23% 2y survival vs 5% for standard chemo alone)
What are the potential side effects of cytotoxic chemotherapy?
Frequent: fatigue, nausea, bone marrow suppression, nephrotoxicity
Quality of life poorly evaluated in trials; no evidence for improvement
When does palliative and supportive care become relevant?
Should be offered as standard to all patients with advanced stage disease
What is the aim of palliative and supportive care?
Symptom control, psychological support, education, practical/financial support, planning for end of life
Lung cancer specialist nurses key
What is the evidence that supports palliative care?
Evidence for survival as well as symptomatic benefit:
151 patients, new diagnosis NSCLC in USA
Standard oncology care +/- early palliative care
At 12 weeks:
-Improved quality of life
-Lower depression scores
-Median survival 11.6 v 8.9 months
Give a summary of lung cancer treatment
What is the general prognosis for lung cancer?
Only 10% live >10 years
Little change in survival in last 40 years (BUT this may be now out of date)
