Cancers of the Lung, Heart and Vasculature Flashcards
What is cardiovascular cancer?
How common are cardiovascular cancers?
Primary cancer of blood vessels and heart
Very rare
What is angiosarcoma?
Malignancy of vascular endothelial cells
Of skin, heart, liver, etc
UK annual incidence 1.5 cases per million
What are primary cardiac tumours?
Most common = myxoma = tumour of connective tissue in the heart
Annual incidence <1 case per million
Why are cardiac cancers so rare?
Low exposure of cells to carcinogens (e.g. compared to lungs)
Turnover rate: cardiac myocytes divide very rarely
Strong selective advantage against anything, e.g. shape of cell which is highly specialised for CV function, as it could compromise function
Why might other organs be exposed more too carcinogens?
Lung- inhaled particles, smoking etc.
Kidney/Liver - exposed to toxins
How big of an issue is lung cancer?
3rd most common cancer in UK
~48,000 diagnoses/ year
~35,000 deaths/ year
Leading cause of cancer death
From when has lung cancer become more common?
Who linked smoking habits with lung cancer?
After the 1930s
Smoking was only really popular after WW1
Doll and Hill - in the 1950s, classic prospective case-control study >40,000 British doctors’ smoking habits and development of lung cancer
What are risk factors for lung cancer?
What is most relevant in smoking history?
Age, peak 75-90 Sex, M>F Lower socioeconomic status Smoking history - duration, intensity and if / when stopped
What are other causes of lung cancer other than smoking?
Passive 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 - HIV
Familial/ genetic – several loci identified
What are the different types of lung cancer?
Non-small cell lung cancer (NSCLC):
Squamous cell carcinoma
Adenocarcinoma
Large cell lung cancer
Small cell lung cancer (SCLC):
Small cell lung cancer
What are the features of the 4 different types of lung cancer?
Squamous cell carcinoma
Adenocarcinoma
Large cell lung cancer
Small cell lung cancer
Non-small cell lung cancer (NSCLC):
Squamous cell carcinoma - originating from bronchial epithelium; centrally located, 30% of cases
Adenocarcinoma - originating from mucus-producing glandular tissue; more peripherally-located, 40% of cases
Large cell lung cancer - heterogenous group, undifferentiated, 15% of cases
Small cell lung cancer (SCLS):
Small cell lung cancer - originate from pulmonary neuroendocrine cells, highly malignant, very aggressive, frequently presents at a later stage, 15% of cases
Describe the model of lung cancer development?
Normal Epithelium Hyperplasia Squamous metaplasia Dysplasia Carcinoma in situ Invasive carcinoma
What is meant by the terms 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 some important oncogenes and why are they relevant clinically?
Mutations in the genes below are important for directed treatment
Epidermal growth factor receptor (EGFR) tyrosine kinase - adenocarcinoma
Anaplastic lymphoma kinase (ALK) tyrosine kinase - NSCLC, young, non-smokers
c-ROS oncogene 1 (ROS1) receptor tyrosine kinase - NSCLC, young, non-smokers
BRAF (downstream cell-cycle signalling mediator) - NSCLC, smokers
What do genetic kinase defects cause?
Lung cancer most common in those who have never smoked
What are the key symptoms of lung cancer?
Cough Weight loss Breathlessness Fatigue Chest pain Haemoptysis - coughing up blood Or frequently asymptomatic
Why is lung cancer often diagnosed late?
Nature of lung
Lots of space in the thoracic cavity
Does not impede on other structures quickly
Non-specific symptoms = esp. in smokers, they experience coughs and breathlessness due to other co-morbidities
What are features of advanced/metastatic disease?
Neurological features:
e.g. focal weakness, seizures, spinal cord compression
Bone pain
Paraneoplastic syndromes:
e.g. clubbing, hypercalaemia, hyponatraemia, Cushing’s
What is finger clubbing?
What is cachexia?
Characteristic change in shape of the distal digits
Muscle wasting and weight loss = reduced nutritional intake due to loss of appetite / increased metabolism due to tumour
What is Pemberton’s sign?
What is Pemberton’s sign indicative of?
Characterised by: Engorgement of the face due to decreased blood flow Redness Facial swelling Distention of veins of neck and chest More evidence on elevation of the arms
Superior Vena Cava obstruction
What is Horner’s syndrome?
What is Horner’s syndrome caused by?
Characterised by decreased pupil size (pupillary reconstruction), a drooping eyelid (ptosis) and decreased sweating on the affected side of your face
Apical lung tumour
What is the diagnostic strategy 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
What imaging can be used to diagnose lung cancer?
What may be seen on this imaging?
Chest X-ray:
Tumours appear white
Might show unilateral pleural effusion
Staging ST (chest and abdomen)
PET
What is unilateral pleural effusion often indicative of?
Malignancy
Likely metastasised from lung to pleura
In what order are the imaging and other tests conducted and why?
First, chest x-ray, to see if anything is wrong - i.e. tumour, pleural effusion
Next, staging CT of chest and abdomen to confirm the findings seen on the chest x-ray and to look for spread of tumour i.e. into the mediastinum or abdomen
Then, PET scan as it is most useful to exclude occult metastases
Lastly, biopsy to confirm the diagnosis of lung cancer and to work out the histological subtype
How does a PET scan work?
Ingestion of radioactively labelled glucose
Taken up by all parts of the body metabolising
Tumours metabolise at a greater rate = radioactive glucose shows up brighter on the scan
What are the different types of biopsies and their methods?
How is a biopsy method chosen?
Bronchoscopy - fibro-optic tube passed down the bronchi, suitable for tumours in the central airway and where tissue staging is not important
Endobronchial ultrasound and trans bronchial needle - aspiration of mediastinal lumph nodes (ABUS [TBNA]), used to stage mediastinum and achive tissue diagnosis
CT guided lung biopsy - to access peripheral lung tumours
Choose method based on accessibility, availability, and impact on staging
How do you stage lung cancer?
The TNM system:
T1-4: tumour size and location
N0-3: lymph node involvement – mediastinum + beyond
M0-1c: metastases + number
TNM can be simplified to stages 1 to 4
What are the treatment options?
What determines treatment selection?
Surgical
Radiological
Pharmacological
Supportive
Patient fitness Cancer histology Cancer stage Patient preference Health service factors
For patient fitness, what are WHO’s 6 performance statuses?
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 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 bedbound (Capable of only limited self-care, confined to bed or chair 50% or more of waking hours)
4 = Bedbound (Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair)
5 = Death
At what WHO performance stages for patient fitness is radical treatment considered?
What other factors are considered for radical treatment?
0-2
Other co-morbidities and lung function
How is surgery used to treat lung cancer?
Surgical resection is standard of care for early stage disease
Wedge resection - tumour and small area of surrounding healthy tissue removed
Sublobar resection if stage 1 (≤3 𝑐𝑚) - larger portion of the lobe is removed containing the tumour
Lobectomy + lymphadenectomy usual approach - entire lobe containing the tumour and lymph nodes affected are removed
Pneumonectomy - entire lung removed
How is surgery conducted?
Open thoracotomy - cranking open the ribs at the side of the chest to remove part of the lung
Video-assisted thoracoscopic surgery (VATS) - more commonly used nowadays, keyhole surgery
Why is VATS preferred over open thoracotomy?
Less post-op pain
Lower risk of post-op infections
Fewer days spent post-op in hospital
Resection is still just as good performed via VATS vs open thoracotomy
How and when is radical radiotherapy used to treat lung cancer?
Alternative to surgery for early stage disease - used if not fit enough for surgery (particularly comorbidity) or refuse surgery
Stereotactic ablative body radiotherapy (SABR):
- Involves a lot of 3D planning due to high precision of target
- Technique of choice
- High-precision targeting, multiple convergent beams
When are oncogene-directed systemic pharmacological treatments used?
What are some NICE approved drugs for these treatments?
First line for metastatic NSCLC with specific mutation - the drugs are usually protein kinase inhibitors
EGFR: erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib
ALK: crizotinib, ceritinib, alectinib, brigatinib, lorlatinib
ROS-1: crizotinib, entrectinib
What is the efficacy of drug treatments?
Drugs are better than standard chemo therapy in terms of progression free survival and side effects (but not necessarily overall survival)
These are palliative treatments - to help control the disease and improve symptoms rather than cure the disease
e.g. erlotinib PFS 13 vs 5 months, OS 23 vs 27 months compared to chemo (OPTIMAL trial)
PFS = progression free survival, OS = overall survival
What are the side effects of the drug treatments?
Generally well-tolerated (tablets)
Rash, diarrhoea, and (uncommonly) pneumonitis
What is immunotherapy?
New, progressive field, radical approach
Harnesses own immune system to attack cancer cells
When are immunotherapy systemic pharmacological treatments used?
What are some examples of NICE approved drugs for these treatments?
First line for metastatic NSCLC with no mutation (and PDL1 >50%)
Pembrolizumab, atezolizumab, nivolumab
What is the efficacy of immunotherapy?
What are side effects of immunotherapy?
Improvements in progression-free survival and overall survival vs standard chemotherapy:
e.g. pembrolizumab PFS 10 vs 6 months, OS 30 vs 14 months (KEYNOTE-024 trial)
Generally well-tolerated
Immune-related side-effects in 10-15% (thyroid, skin, bowel, lung, liver)
When are cytotoxic chemotherapy systemic treatment used?
What are the features of chemo?
First line for metastatic NSCLC with no mutation and PDL1 ≤50% (in combination with immunotherapy)
Target any rapidly dividing cells
Platiunum-based regimens, e.g. carboplatin, cisplatin, paclitaxel, pemetrexed
What is the efficacy of chemo?
Modest improvements in overall survival vs best supportive care:
e.g. 29% vs 20% one year survival in clinical trials
What are the side effects of chemo?
Frequent: fatigue, nausea, bone marrow suppression, nephrotoxicity
Quality of life poorly evaluated in trials; no evidence for improvement
What is the fourth dimension in cancer care?
Palliative care
Supportive care
What are the features of palliative care?
What members of the MDT are key in delivering palliative care?
Should be offered as standard to all patients with advanced stage disease
Offers symptom control, psychological support, education, practical and financial support, planning for end of life
Lung cancer specialist nurse, other nurses
Why is palliative care important and what does it result in?
Improve QoL
Lower depression scores
Mean survival can increase
What treatment is used for early stage disease?
Surgery or radiotherapy with curative intent
What treatment is used for locally advances disease? (involving thoracic lymph nodes)
Surgery + adjuvant chemotherapy
Radiotherapy + chemotherapy +/- immunotherapy
What is the treatment for metastatic lung cancer?
With targetable mutation (e.g. EFGR, ALK, ROS-1): tyrosine kinase inhibitor
No mutation, PDL-1 positive: immunotherapy
No mutation, PDL-1 negative: ‘standard’ chemotherapy
Palliative care, alone or with the above
