Lung Cancers Flashcards
What is angiosarcoma?
Malignancy of vascular endothelial cells
Of skin, heart, liver, etc
UK annual incidence 1.5 cases per million
What is the prevalence of cardiovascular cancer?
Incredibly rare
What are the features of cardiac tumours?
E.g. myxoma, tumour of connective tissue
Annual incidence <1 case per million
Why are cardiac cancers so rare?
Low exposure of cells to carcinogens
Turnover rate: cardiac myocytes divide very rarely
Strong selective advantage against anything which could compromise function
Why might other organs be exposed more too carcinogens?
Lung- inhaled particles, smoking etc
Kidney/Liver - exposed to toxins
Why is the shape of cardiac cells relevant to low incidence of cancer?
Shape in cells is highly specialised
Any change will prevent the cardiovascular system from working
What is the scale of lung cancer?
3rd most common cancer in UK
~48,000 diagnoses/ year
~35,000 deaths/ year
Leading cause of cancer death
What are risk factors for lung cancer?
Age, peak 75-90
Sex, M>F
Lower socioeconomic status
Smoking history
What is relevant in a smoking history?
Duration
Intensity
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
Familial/ genetic – several loci identified
What are the different types of lung cancer?
Squamous cell carcinoma
Adenocarcinoma
Large cell lung cancer
Small cell lung cancer
What are the features of squamous cell carcinomas?
Squamous cell carcinoma (~30% of cases).
– previously the most common
– originating from bronchial epithelium; centrally located
What are the features of adenocarcinomas?
Adenocarcinoma (~40%)
– most common from 1980s onwards – low tar cigarettes, inhaled more deeply / retained longer
– originating from mucus-producing glandular tissue; more peripherally-locate
What are the features of large cell lung cancer?
Large cell lung cancer (~15%)
heterogenous group, undifferentiated
What are the features of small cell lung cancer?
Small cell lung cancer (~15%)
originate from pulmonary neuroendocrine cells
highly malignant
What is NSCLC?
Non small cell lung cancer
Describe the model of lung cancer development?
Normal Epithelium Hyperplasia Squamous metaplasia Dysplasia Carcinoma in situ Invasive carcinoma
What is metaplasia?
reversible change in which one adult cell type 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
What are some oncogenes?
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 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 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 symtoms
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 is Pemberton’s sign indicative of?
Superior vena cava obstruction
Engourgement of the face due to decreased blood flow
Redness
Facial swelling
Distention of veins of neck and chest
What is Horner’s syndrome caused be?
Apical lung tumour
Loss of sweating on side of face
Ptosis
Pupillary reconstruction
What is cachexia?
Muscle wastage
Weight loss
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?
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 to pleura from lung
What is PET useful for?
To exclude occult metastases
What are tests use to confirm diagnosis?
Biopsy
via bronchoscopy
via endobronchial ultrasound and trans bronchial needle
via CT guided lung biopsy
How do you stage lung cancer?
T1-4: tumour size and location
N0-3: lymph node involvement – mediastinum + beyond
M0-1c: metastases + number
How is biopsy conducted via bronchoscopy?
Tube passed down
for tumours of central airway
where tissue staging not important
How is biopsy conducted via endobronchial ultrasound?
Endobronchial ultrasound and transbronchial-needle aspiration of mediastinal lymph nodes (EBUS [TBNA])
To stage mediastinum +/- achieve tissue diagnosis
How is biopsy conducted via CT guided biopsy?
CT-guided lung biopsy
To access peripheral lung tumours
What determines treatment selection?
Patient fitness Cancer histology Cancer stage Patient preference Health service factors
What are the treatment options?
Surgical
Radiological
Pharmacological
Supportive
How do assess patient fitness?
WHO performance status
0-5 scale
What does 0 on the fitness scale mean?
Asymptomatic (Fully active, able to carry on all predisease activities without restriction)
What does 1 on the fitness scale mean?
– 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)
What does 0 on the fitness scale mean?
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)
What does 0 on the fitness scale mean?
Symptomatic, >50% in bed, but not bedbound (Capable of only limited self-care, confined to bed or chair 50% or more of waking hours)
What does 0 on the fitness scale mean?
Bedbound (Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair)
What does 0 on the fitness scale mean?
Death
Which numbers on the scale are radical treatments restricted to?
0-2
How is surgery used to treat lung cancer?
Surgical resection is standard of care for early stage disease
Lobectomy + lymphadenectomy usual approach
Sublobar resection if stage 1 (≤3 𝑐𝑚)
How is radical radiotherapy used to treat lung cancer?
Alternative to surgery for early stage disease
Particularly if comorbidity
Stereotactic ablative body radiotherapy (SABR)
- Technique of choice
- High-precision targeting, multiple convergent beams
How is surgery conducted?
Open thoracotomy
now VATS
When is radiotherapy used instead of surgery?
Not fit enough for surgery
Refuse surgery
When are oncogene systemic pharmacological treatments used?
First line for metastatic NSCLC with mutation
What are some NICE approve drug treatments?
EGFR: erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib
ALK: crizotinib, ceritinib, alectinib, brigatinib, lorlatinib
ROS-1: crizotinib, entrectinib
What is the efficacy of drug treatments?
improvements in progression-free survival, but not necessarily overall survival vs standard
chemotherapy:
e.g. erlotinib PFS 13 vs 5 months, OS 23 vs 27 months compared to chemo (OPTIMAL trial)
What are the side effects of the drug treatments?
generally well-tolerated (tablets)
rash, diarrhoea, and (uncommonly) pneumonitis
What is the desired effect for drug treatments?
Not always to cure
But to improve QoL
Alleviate some symptoms
Palliative
What is PFS?
Progression free survival
What is immunotherapy?
New, progressive field, radical approach
Harnesses own immune system to attack cancer cells
What are NICE approved immunotherapy drugs?
Pembrolizumab, atezolizumab, nivolumab
When is immunotherapy used?
First line for metastatic NSCLC with no mutation (and PDL1 ≥50%)
What is the efficacy 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)
What are side effects of immunotherapy?
generally well-tolerated
Immune-related side-effects in 10-15% (thyroid, skin, bowel, lung, liver)
When is cytoxic chemotherapy used?
First line for metastatic NSCLC with no mutation and PDL1 ≤50% (in combination with immunotherapy)
What are the features of chemo?
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?
Should be offered as standard to all patients with advanced stage disease
Symptom control, psychological support, education, practical and financial support, planning for end of life
Who is key in palliative care?
Lung cancer specialist nurses key
What does palliative care 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
Via what two methods can you perform a lung biopsy?
Bronchoscopy - more deep
Transthoracic needle - more superficila
What blood results might be seen in lung cancer?
High Calcium (bone mets) High ALP (bone mets) Derranged LFTs (liver mets)
What is seen on a CXR in secondary lung cancer?
Coin-shaped lesions
Cannonball mets
What cancer is caused by asbestos exposure?
Mesothelioma
Hear a pleural friction rub on ausculatation
What is mesothelioma?
Malignant neoplasm of mesothelial cells of the pleura
What is thoracentesis?
Pleural tap
Aspiration of pleural fluid
What might be see on a CXR in mesothelioma?
Pleural thickening
Pleural plaques - due to asbestos
