Lung Cancer Flashcards
Who gets lung cancer?
Age, peak 75-90
Sex, M>F
Lower socioeconomic status
Smoking history
——–duration, intensity, when stopped
What are other aetiological factors for lung cancer apart from smoking and 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 is the pathogenesis of lung cancer?
Lung cancer may arise from all differentiated and undifferentiated cells
The interaction between inhaled carcinogens and the epithelium of upper and lower airways leads to the formation of DNA adducts: pieces of DNA covalently bound to a cancer-causing chemical
If DNA adducts persist or are misrepaired, they result in a mutation and can cause genomic alterations. These are key events in lung cancer pathogenesis, especially if they occur in critical oncogenes and tumour suppressor genes.
What are the different 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
Mutations in what 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 of lung cancer?
Cough
Weight loss
Breathlessness
Fatigue
Chest pain
Haemoptysis
Or frequently asymptomatic
What are the key symptoms of lung cancer?
Cough
Weight loss
Breathlessness
Fatigue
Chest pain
Haemoptysis
Or frequently asymptomatic
Coughing up blood
Repeated respiratory infection
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 common sites of lung cancer metastases?
Bones
Liver
Brain
Lymph nodes
Adrenal glands
What are signs of lung cancer?*
Clubbing
Cachexia
Horner’s syndrome
Superior vena cava obstruction (Pemberton’s sign)
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
Who is art of the lung cancer MDT?
Respiratory
Radiology
Pathology
Thoracic surgery
Oncology
Palliative care
Look at chest Xray and staging CT of chest and abdomen**
What is an example of definitive imaging for staging?**
PET-CT (fluorodeoxyglucose)
How is type of biopsy chosen?
Choose method based on accessibility, availability and impact on staging
What are the types of biopsy?*
CT-guided lung biopsy
To access peripheral lung tumours
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
How does staging work??
TNM based on characteristics
How else is staging assessed?
Early vs locally-advanced vs metastatic
What are the determinants of treatment?
Patient fitness
Cancer histology
Cancer stage
Patient preference
Health service factors
How is patient fitness assessed using the WHO performance status?
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
What is the 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 are the different types of surgical resection?
Wedge resection
Segmental resection
Lobectomy
Pneumonectomy
What is an alternative to surgery for early stage disease?
Radical radiotherapy
Particularly if comorbidity
Stereotactic ablative body radiotherapy (SABR)
—–Technique of choice
——High-precision targeting, multiple convergent beams
What is the treatment for early stage disease?
Surgery or radiotherapy with curative intent
What is the treatment for locally advanced disease (involving thoracic lymph nodes)?
Surgery + adjuvant chemotherapy
Radiotherapy + chemotherapy +/- immunotherapy
What is the treatment for 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
Describe the systemic treatment that is oncogene directed?
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. crizotinib PFS 8 vs 3 months, OS 20 vs 23 months
Side effects
generally well-tolerated (tablets)
rash, diarrhoea, and (uncommonly) pneumonitis
Describe the systemic treatment that is immunotherapy?***
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)
Describe the systemic treatment that is cytotoxic chemotherapy?
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
Describe how palliative and supportive care works?
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
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
