Lung Cancer Flashcards
What is the leading cause of cancer death?
Lung cancer
Lung cancer is the ____ most common cancer in the UK
3rd
What is the main risk factor for lung cancer?
Smoking
What is the peak age for lung cancer and which sex is it more common in?
75-90
Males
Is lower socioeconomic status a risk factor for lung cancer?
Duration, intensity, when they stopped
What are other aetiological factors than smoking?
Asbestos exposure (plumbers, ship-builders, carriage workers, carpenters) - risk up to 2x
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
(Passive smoking is also a risk factor)
Describe the pathogenesis of lung cancer
May arise from any differentiated or undifferentiated cell
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
Persistence/misrepair of DNA adducts may result in a mutation and can cause genomic alterations
Key if they occur in critical oncogenes and tumour suppressor genes
Name the 3 types of non-small cell lung cancer (NSCLC)
Squamous cell carcinoma
Adenocarcinoma
Large cell lung cancer
What do squamous cell carcinomas originate from?
Bronchial epithelium
Centrally located
What do adenocarcinomas originate from?
Mucus-producing glandular tissue
Peripherally located
Are large cell lung cancers differentiated?
No
Heterogeneous group
What does small cell lung cancer originate from?
Pulmonary neuroendocrine cells
How malignant is small cell lung cancer?
Highly
What is the most common type of lung cancer?
Adenocarcinoma (~40%)
(previously squamous cell carcinoma)
What is the definition of metaplasia?
Reversible change in which one adult cell type is replaced by another adult cell type; adaptive
What is 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
Mutations in what 4 genes are important for directed treatments of lung cancer?
Epidermal growth factor receptor (EGFR) tyrosine kinase (adenocarcinomas)
Anaplastic lymphoma kinase (ALK) tyrosine kinase
c-ROS oncogene 1 (ROS1) receptor tyrosine kinase
BRAF (downstream cell-cycle signalling mediator) - especially in smokers
What are the key symptoms of lung cancer?
Cough
Breathlessness
Fatigue
Chest pain
Weight loss
Haemoptysis
Can lung cancer frequently be asymptomatic?
Yes
Why is making an initial diagnosis of lung cancer through the symptoms difficult?
The key symptoms overlap with many other respiratory diseases
Why is it important to screen for lung cancer?
The tumour can get quite large before it starts to cause issues
What are the neurological features of metastatic lung cancer?
Focal weakness - due to cardiac vegetations that embolize to main cerebral arteries
Seizures - due to chemo given via spine or when cancer reaches brain
Spinal cord compression
Why is there bone disease in lung cancer?
When lung cancer spreads to the bones, it’s calledbone metastasis
Bone metastasis can result in complications such as weakened bones and fractures, nerve damage in your spinal cord, and severe pain
What are the paraneoplastic syndromes characteristic of metastatic lung cancer?
Clubbing - result of hypoxaemia - increased blood flow to the finger area, leading to the accumulation of fluid in the soft tissues at the terminal portion of the finger and subsequent bulging of the area
Cushing’s - Small cell lung cancer canoccasionally be a source of ectopic ACTH secretion
Hypercalcaemia - dueto increased bone resorption and release of calcium from bone
Hyponatraemia - result of SIADH
What are the 4 signs of lung cancer?
Clubbing
Cachexia (body weakness and wasting) - increased breakdown and depletion of skeletal muscle proteins
Horner’s syndrome - compression of sympathetic ganglion/disrupted supply - leading to partial ptosis, miosis and facial anhidrosis
Superior vena cava obstruction (Pemberton’s sign) - cancer may be compressing SVC/spread to the lymph nodes nearby, which become swollen
What 4 general things must be confirmed in the diagnostic strategy plan for lung cancer?
Establish most likely diagnosis
Establish fitness for investigation and treatment
Confirm diagnosis - specific type of cancer if considering systemic treatment
Confirm staging
After a chest X-Ray, what is the next imaging technique that must be used?
Staging CT
Look for swelling of mediastinal lymph nodes and can also look for sign of metastases to abdomen
What is PET-CT (fluorodeoxyglucose) most useful for in a diagnosis of lung cancer?
Definitive imaging for staging
Most useful to exclude occult (initially undetected) metastases
Detects mediastinal lymph nodes involvement
The method of biopsy for suspected lung cancer is determined by what?
Accessibility
Availability
Impact on staging
When would a bronchoscopy be performed?
For tumours of central airway
Where tissue staging is not important
How do you stage mediastinum and/or achieve tissue diagnosis?
Endobronchial ultrasound and transbronchial-needle aspiration of mediastinal lymph nodes (EBUS [TBNA])
TBNA - used to obtain tissue from lung or hilar/mediastinal lesions that are in close proximity to the endobronchial tree
How do you access peripheral lung tumours?
CT-guided lung biopsy
How do you access peripheral lung tumours?
CT-guided biopsy
What do the stages T1-4 tell you?
Location and size of the tumour
What does N0-3 show?
Lymph node involvement - mediastinum + beyond
What does M0-1c tell you?
Distant metastasis:
Non-regional lymph node metastases
Extrathoracic metastases
What are the 5 determinants of treatment?
Patient fitness (0-asymptomatic → 5-death)
Cancer histology
Cancer stage
Patient preference
Health service factors
Outline patient fitness scores 0-5 according to the WHO performance status.
0 – Asymptomatic (Fully active, able to carry on all pre-disease activities without restriction)
1 – Symptomatic but completely ambulatory (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)
2 – Symptomatic, <50% in bed during the day (Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50% of waking hours)
3 – Symptomatic, >50% in bed, but not bed-bound (Capable of only limited self-care, confined to bed or chair 50% or more of waking hours)
4 – Bed-bound (Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair)
5 – Death
Surgery and chemotherapy is usually restricted to a WHO performance status of what?
0-2
What types of patients is surgical resection usually reserved for?
Early stage lung cancer
What types of surgery is the usual approach to treat lung cancer?
Lobectomy + lymphadenectomy
What types of surgery is the usual approach to treat lung cancer?
Lobectomy + lymphadenectomy
What surgery is done if stage 1 (≤3cm)?
Sub-lobar resection
Can radiotherapy be curative?
Yes
If there is comorbidity, is radiotherapy preferred or is surgery preferred?
Radiotherapy
What is the technique of choice for radiotherapy and why is this the preferred technique?
Stereotactic ablative body radiotherapy (SABR)
High-precision targeting, multiple convergent beams
What is the NICE-approved first-line treatment for metastatic NSCLC with mutation?
Oncogene directed drugs targeting mutations in the following oncogenes:
EGFR: erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib
ALK: crizotinib, ceritinib, alectinib, brigatinib, lorlatinib
ROS-1: crizotinib, entrectinib
How would you describe the efficacy of oncogene directed drugs?
Improvements in progression-free survival, but not necessarily overall survival vs standard chemotherapy
What are the side effects of oncogene directed drugs?
Tablets generally well-tolerated
Rash, diarrhoea, and (uncommonly) pneumonitis
What is the 2nd class of drug treatments?
Immunotherapy
What type of binding do cancer cells have that inhibits T cell killing of tumour cells?
PD-L1/PD-1 binding
What does blocking of PD-L1/PD-1 binding allow?
Blocking PD-L1 or PD-1 allows T cell killing of tumour cell
What is the first line treatment for metastatic NSCLC with no mutation (and PDL1≥50%)?
Immunotherapy
What are the 3 NICE approved immunotherapies for lung cancer?
Pembrolizumab, atezolizumab, nivolumab
How would you describe the efficacy of these immunotherapies against NSCLC?
Improvements in progression-free survival and overall survival vs standard chemotherapy
What are the side effects for immunotherapies against lung cancer?
Generally well-tolerated
Immune-related side effects in 10-15% (thyroid, skin, bowel, lung, liver)
What is the first line for metastatic NSCLC with no mutation and PDL1≤50% (in combo with immunotherapy)?
Cytotoxic chemotherapy
What do cytotoxic chemotherapies target?
Any rapidly dividing cells
List examples of the platinum-based regimens that are a part of cytotoxic chemotherapy
Carboplatin, cisplatin, paclitaxel, pemetrexed
How would you describe the efficacies of cytotoxic chemotherapies?
Efficacy when used alone (old data, pre-2000) → modest improvements in overall survival vs best supportive care
Efficacy when used with pembrolizumab a lot better
Therefore should use cytotoxic chemotherapy with immunotherapy
What are the side effects of cytotoxic chemotherapy?
Frequent: fatigue, nausea, bone marrow suppression, nephrotoxicity
Quality of life poorly evaluated in trials; no evidence for improvement
Who should palliative care and supportive care be offered to?
Should be offered as standard to all patients with advanced stage disease
What does palliative and supportive care involve?
Symptom control
Psychological support
Education
Financial support
Practical support
Planning for end of life
If there is early stage disease, what treatment should be given
Surgery or radiotherapy with curative intent
If there is locally advanced disease (involving thoracic lymph nodes) what treatment should be given?
Surgery + adjuvant chemotherapy
Radiotherapy + chemotherapy +/- immunotherapy
If the patient has metastatic disease, what are the treatment options?
With targetable mutation (e.g. EFGR, ALK, ROS-1)
tyrosine kinase inhibitor
No mutation, PDL-1 positive: immunotherapy along
No mutation, PDL-1 negative: ‘standard’ chemotherapy + immunotherapy
Palliative care, alone or with the above
What percent of lung cancer patients live beyond 10 years?
~10%
