lung cancer Flashcards
what is the epidemiology of lung cancer?
3rd most common cancer in UK
~48,000 diagnoses/ year
~35,000 deaths/ year
Leading cause of cancer death
Prior to the 1930s lung cancer rare; smoking only popular from WW1 onwards
what is the role of smoking in lung cancer?
Smoking not recognised initially, other suggested causes:
air pollution; asphalted roads; road traffic; gas exposure
in World War I; influenza pandemic 1918; working with petroleum.
Doll + Hill – 1950s, classic prospective case-control study of >40,000 British doctors’ smoking habits and development of lung cancer
Strong influence of tobacco companies
who gets lung cancer?
Age, peak 75-90
Sex, M>F
Lower socioeconomic status
Smoking history - duration, intensity, when stopped
Cigarettes cause ~1.5 m deaths from lung cancer/ year (1 lung cancer death per 3 or 4 m. smoked)
what are some causes of lung cancer other than smoking?
10-15% patients with lung cancer never smoked Passive smoking (~15% of these)
Other aetiological factors:
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
wha tare the types of lung cancer?
- Squamous cell carcinoma (~30% of cases).
– previously the most common
– originating from bronchial epithelium; centrally located - Adenocarcinoma (~40%)
– most common from 1980s onwards – low tar cigarettes, inhaled more deeply / retained longer
– originating from mucus-producing glandular tissue; more peripherally-locate - Large cell lung cancer (~15%)
heterogenous group, undifferentiated - Small cell lung cancer (~15%)
originate from pulmonary neuroendocrine cells
highly malignant
1-3 often grouped together: non-small cell lung cancer (NSCLC)
how does lung cancer develop?
early:
normal epithelium ->
hyperplasia ->
squamous metaplasia (reversible change in which one adult cell type replaced by another adult cell type; adaptive) ->
intermediate:
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) ->
late:
carcinoma in situ ->
invasive carcinoma
what are some important oncogenes in lung cancer?
Mutations in the following genes are important for directed treatments
epidermal growth factor receptor (EGFR) tyrosine kinase:
15-30% of adenocarcinoma
more so in women, Asian ethnicity, never-smokers
anaplastic lymphoma kinase (ALK) tyrosine kinase:
2-7% of non-small cell lung cancer
especially in younger patients and never smokers
c-ROS oncogene 1 (ROS1) receptor tyrosine kinase
1-2% of non-small cell lung cancer
especially in younger patients and never smokers
BRAF (downstream cell-cycle signalling mediator)
1-3% of non-small cell lung cancer
especially in smokers
what are the key symptoms and signs of lung cancer?
symptoms: Cough Weight loss Breathlessness (dyspnoea) Fatigue Chest pain Haemoptysis (coughing up blood)
Or frequently asymptomatic
signs: cachexia (the only one really seen) horners syndrome clubbing superior vena cava obstruction (pembertons sign) (red fave due to less blood drainage)
what are the features of advanced/metastatic disease?
Neurological features:
focal weakness, seizures, spinal cord compression
Bone pain (due to PArathyroid related peptides, ectopic release from lung cancer and hypercalcaemia of malignancy)
Paraneoplastic syndromes
clubbing
hypercalaemia, hyponatraemia, Cushing’s (ectopic release of ACTH)
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 done for lung cancer?
chest X ray:
Posterior anterior
may see a tumour (more white)
or pleural effusion due to metastases
CT:
for staging
chest and abdomen
PET:
Most useful to exclude occult metastases
(ie in lymph nodes that arent yet bigger)
what is biopsy in terms of lung cancer?
Choose method based on accessibility, availability and impact on staging
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
(big needle)
how is lung cancer staged?
TNM staging
T1-4: tumour size and location
N0-3: lymph node involvement – mediastinum + beyond
M0-1c: metastases + number
Late stage at diagnosis is common
early vs locally advanced vs metastatic
what helps determine the method of treatment of lung cancer?
Patient fitness Cancer histology Cancer stage Patient preference Health service factors
what is the WHO performance status for patient fitness?
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
Radical treatment usually restricted to PS 0-2
Comorbidity + lung function also very important
how/when is lung cancer treated surgically?
Surgical resection is standard of care for early stage disease
Lobectomy + lymphadenectomy usual approach
Sublobar resection if stage 1 (≤3 𝑐𝑚)
how and when is radical radiology used to treat lung cancer surgically?
Alternative to surgery for early stage disease
Particularly if comorbidity
Stereotactic ablative body radiotherapy (SABR):
Technique of choice
High-precision targeting, multiple convergent beams
what are oncogene directed treatments for lung cancer?
First line for metastatic NSCLC with mutation
NICE-approved,
EGFR: erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib
ALK: crizotinib, ceritinib, alectinib, brigatinib, lorlatinib
ROS-1: crizotinib, entrectinib
Efficacy
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
Side effects
generally well-tolerated (tablets)
rash, diarrhoea, and (uncommonly) pneumonitis
what are PD-L1 immunotherapy treatments for lung cancer?
PD-L1/PD-1 binding inhibits T cell killing of tumour cell
blocking Pd-L1 or PD-1 allows T cell killing of tumour cell
(theres a nice diagram for this in the slides)
what are immunotherapy treatments of lung cancer?
First line for metastatic NSCLC with no mutation (and PDL1 ≥50%)
NICE-approved,
Pembrolizumab, atezolizumab, nivolumab
Efficacy
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)
[32% alive at 5 years]
Side effects
generally well-tolerated
Immune-related side-effects in 10-15% (thyroid, skin, bowel, lung, liver)
what is cytotoxic chemotherapy for lung cancer?
First line for metastatic NSCLC with no mutation and PDL1 ≤50% (in combination with immunotherapy)
Long established
Target any rapidly dividing cells
Platiunum-based regimens, e.g. carboplatin, cisplatin, paclitaxel, pemetrexed
Efficacy,
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 (Keynote 189), a lot better (23% 2y survival vs 5% for standard chemo alone)
Side effects
Frequent: fatigue, nausea, bone marrow suppression, nephrotoxicity
Quality of life poorly evaluated in trials; no evidence for improvement
what are palliative and supportive care for lung cancer?
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
Lung cancer specialist nurses key
UK world leaders
Evidence for survival as well as symptomatic benefit: Temer et al. N Engl J Med. 2010;363:733
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
how are different stages of lung cancer treated?
Early stage disease:
Surgery or radiotherapy with curative intent
Locally advanced disease (involving thoracic lymph nodes):
Surgery + adjuvant chemotherapy
Radiotherapy + chemotherapy +/- immunotherapy
Metastatic disease:
With targetable mutation (e.g. EFGR, ALK, ROS-1): tyrosine kinase inhibitor
No mutation, PDL-1 positive: immunotherapy alone
No mutation, PDL-1 negative: ‘standard’ chemotherapy + immunotherapy
Palliative care, alone or with the above
what is the prognosis of lung cancer?
Only 10% live >10 years
Little change in survival in last 40 years
higher the stage the worse the prognosis
