Lung Cancer Flashcards
Describe the scale of lung cancer in the UK
3rd most common cancer, 48,000 diagnoses every year with 35,000 deaths, leading cause of cancer death
Who is most likely to get lung cancer?
Peaks between 75-90. More males than females affected. Impacts those of lower socioeconomic status and duration, intensity + when stopped smoking all impact.
What other causes of lung cancer apart from smoking?
Asbestos – exposure (plumbers, ship-builders, carriage workers, carpenters, etc) – risk up to x2
Radon – e.g. silver miners in Germany late 19th century; 1950s uranium mining in Colorado
Indoor cooking fumes – wood smoke, frying fats
Chronic lung diseases (COPD, fibrosis)
Immunodeficiency
Familial/ genetic – several loci identified
What pathophysiologies count as lung cancer?
- Small cell lung cancer - originates from pulmonary neuroendocrine cells, highly malignant
- Non-small cell lung cancer includes:
- Squamous cell carcinoma: originates from bronchial epithelium, centrally located and was previously most common (30%)
- Adenocarcinoma: originating from mucus-producing glandular tissue; more peripherally-locate (40%)
- Large cell lung cancer: heterogenous morphologies, undifferentiated (15%)
Describe progression of lung cancer development
Normal epithelium becomes hyperplastic and then squamous metaplasia occurs - these are the early stages. Dysplasia occurs in intermediate stage. Late stages involve carcinoma in situ and then invasive carcinoma.
Define metaplasia and dysplasia
Metaplasia = reversible change in which one adult cell type replaced by another adult cell type; adaptive Dysplasia = abnormal pattern of growth in which some of the cellular and architectural features of malignancy are present; pre-invasive stage with intact basement membrane
What are 4 important oncogenes which can mutate to cause cancer?
- EGFR: epidermal growth factor receptor tyrosine kinase
- ALK: anaplastic lymphoma kinase tyrosine kinase
- ROS1: c-ROS oncogene 1 tyrosine kinase receptor
- BRAF: downstream cell-cycle signalling mediator
BEAR
What are the implications of an EGFR mutation?
Cause 15-30% of adenocarcinoma
more so in women, Asian ethnicity, never-smokers
What are the implications of an ALK mutation?
2-7% of non-small cell lung cancer
especially in younger patients and never smokers
What are the implications of a ROS1 mutation?
1-2% of non-small cell lung cancer
especially in younger patients and never smokers
What are the implications of a BRAF mutation?
1-3% of non-small cell lung cancer
especially in smokers
What are key symptoms of lung cancer?
Can frequently be asymptomatic but includes cough, weight loss, breathlessness, fatigue, chest pain and haemoptysis.
What are features of advanced/metastatic disease?
Neurological features: focal weakness, seizures, spinal cord compression
Bone pain
Paraneoplastic syndromes: Clubbing, hypercalaemia, hyponatraemia, Cushing’s
What are signs of lung cancer?
Clubbing, cachexia, Horner’s syndrome and superior vena cava obstruction (Pemberton’s sign)
Describe the diagnostic strategy
Establish most likely diagnosis
Establish fitness for investigation and treatment
Confirm diagnosis - specific type of cancer if considering systemic treatment
Confirm staging
Why are different imaging techniques?
CT of chest and abdomen used to determine stage
PET - Most useful to exclude occult metastases
What are 3 methods of obtaining a biopsy?
- Bronchoscopy - for tumours of central airway where tissue staging not important
- Endobronchial ultrasound and transbronchial-needle aspiration of mediastinal lymph nodes (EBUS [TBNA]). To stage mediastinum +/- achieve tissue diagnosis
- CT-guided lung biopsy - To access peripheral lung tumours
What are the 3 components of staging?
T1-4: tumour size and location
N0-3: lymph node involvement – mediastinum + beyond
M0-1c: metastases + number
What 5 things are the determinants of treatment?
Patient fitness Cancer histology Cancer stage Patient preference Health service factors
How is patient fitness determined?
WHO performance status used.
0- asymptomatic (fully active, no restriction)
1 - Symptomatic but completely ambulatory
2 - Symptomatic, <50% in bed during the day
3 - Symptomatic, >50% in bed, but not bedbound
4 - Bedbound
5 - Death
What is standard of 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 for early stage disease?
Radical radiotherapy used - especially if patient has comorbidities. Stereotactic ablative body radiotherapy (SABR) - is the technique of choice and high-precision targetting, multiple convergent beams.
What treatment is first line for metastatic NSCLC with mutation?
EGFR: erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib
ALK: crizotinib, ceritinib, alectinib, brigatinib, lorlatinib
ROS-1: crizotinib, entrectinib
What is efficacy of oncogene-directed treatment like?
improvements in progression-free survival, but not necessarily overall survival vs standard chemotherapy:
e. g. erlotinib PFS 14 vs 5 months, OS 23 vs 29 months compared to chemo (OPTIMAL trial)
e. g. crizitonib PFS 8 vs 3 months, OS 20 vs 23 months
How is immunotherapy used to kill tumour cells?
PD-L1 on tumour cell binds PD-1 on T-cell preventing T-cell killing the tumour cell. Blocking PD-L1 and PD-1 with drugs allows the T-cell to then bind the tumour cell and kill it.
What immunotherapy is used as first line for metastatic NSCLC with no mutation?
Pembrolizumab, atezolizumab, nivolumab
What is cytotoxic chemotherapy?
Targets any rapidly dividing cells. Uses platiunum-based regimens, e.g. carboplatin, cisplatin, paclitaxel, pemetrexed. When used alone, modest improvements in overall survival vs best supportive care.
What are side effects of cytotoxic chemotherapy?
Frequent: fatigue, nausea, bone marrow suppression, nephrotoxicity. Quality of life poorly evaluated in trials; no evidence for improvement.
What does palliative and supportive care involve?
Symptom control, psychological support, education, practical and financial support, planning for end of life. There is evidence for survival and symptomatic benefit.
Simplify the treatment schedule for lung cancer
Slide 35
