cancers of lung, heart and vasculature Flashcards
how prevalent is primary cancer of blood vessels and heart?
very rare
- Low exposure of cells to carcinogens
- Turnover rate: cardiac myocytes divide very rarely
- Growth via increasing size of individual cardiac myocytes rather than dividing
- Strongly selective advantage against anything which could compromise function
- Preventing any damage to cells
what are the types of primary cancer of blood vessels and heart?
- angiosarcoma
- malignancy of vascular endothelial cells
- of skin, heart, liver etc
- cardiac tumors
- E.g Myxoma, tumour of connective tissue
how common is lung cancer in UK?
3rd most common
leading cause cancer mortality in men and women
prior to smoking popularity lung cancer rare
what are the lung cancer prevalence trends?
- Age peak 75-90
- Mex: M>F
- Low socioeconomic status
- Smoking history
- Duration, intensity, when stopped
what are causes of lung cancer?
- smoking
- (10-15% patients have never smoked)
- passive smoking
- Asbestos- exposure (plumber)
- Radon gas (uranium mines)
- Indoor cooking fumes- wood smoke, frying fats
- Chronic lung diseases (COPD, fibrosis)
- Immunodeficiency (HIV)
- Familial/genetic
what are the different types of cancer cells?
squamous cell carcinoma
adenocarcinoma
large cell carcinoma
small cell carcinoma
what is squamous cell carcinoma?
2nd most common
originating from bronchial epithelium
centrally located
what is adenocarcinoma?
40% lung cancer
most common from 1980’s onwards- low tar cigarettes, retained longer
originating from mucus-producing glandular tissue more peripherally located
what is large lung cell cancer?
- Heterogenous group, undifferentiated
what are the features of small cell lung cancer?
- Originate from pulmonary neuroendocrine cells
- Highly malignant and very aggressive, presenting at late stage
what is metaplasia?
reversible change in which one adult cell type replaced by another cell type; adaptive
what is dysplasia?
abnormal pattern of growth in which some of the cellular and architectural feature of malignancy are present; pre invasive stage with intact basement membrane
what are the stages of lung cancer development?
what are the key features of cancer cells?
what are DNA adducts?
- DNA adducts= segment of DNA bound to a cancer causing chemical
- Normally corrected by anti-tumour genes such as p53 or Rb
what are the important oncogenes in lung cancer treatments?
- EGFR tyrosine kinase
- anaplastic lymphoma kinase (ALK) tyrosine kinase
- c-ROS oncogene 1 (ROS1) receptor tyrosine kinase
- BRAF
in what ethnicity is EGFR tyrosine kinase mutation prevalent?
high in women, Asian ethnicities, never-smoked
15-30% adenocarcinomas
in what population is ALK mutation more likely?
2-7% non-small cell lung cancer
especially in younger patients and never smokers
in what population is ROS1 oncogene more likely?
1-2% non-small cell lung cancer
especially in younger people and never smoked
in what population is BRAF oncogene more likely?
1-3% non-small cell lung cancers
especially in smokers
what are the key symptoms of lung cancer?
- cough
- weight loss (cachexia)
- breathlessness
- fatigue
- chest pain
- haemoptysis
frequently asymptomatic
what are the features of advanced lung cancer/metastatic disease?
- neurological features
- focal weakness, seizures, spinal cord compression, horner’s syndrome
- bone pain
- paraneoplastic syndromes
- clubbing, hypercalcaemia, hyponatraemia, Cushing’s
- superior vena cava obstruction (Pemberton’s sign)
what is horner’s syndrome?
ptosis (drooping eyelid)
miosis (constriction pupil)
anhydrosis (absence sweating face)
what is pemberton’s sign?
positive sign= bilateral arm elevation causes facial plethora
what are the common sites of lung cancer metastases?
liver
brain
bones
lymph nodes
adrenal glands
what is a pet scan most useful for?
most useful to exclude occult metastases
ingestion of radioactively labeled glucose (taken up by all parts metastasising)
what are the different methods used to biopsy lung tumour?
what are each method used for?
- Choosing 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)
- To stage mediastinum +/- achieve tissue diagnosis
- CT-guided lung biopsy
- Access peripheral lung tumours
how is cancer staged?
stages 0-4
- Stage 1= early single nodule with no evidence of spread
- Stage 4= metastatic disease in multiple sites
What are the staging of TNM system?
- T1-4: tumour size and location
- N0-3: lymph node involvement- mediastinum + beyond
- M0-1c: metastases + number
what are the treatment options for lung cancer?
surgical
radiological
pharmacological
supportive
when is surgical treatment used?
- Surgical resection is standard of care for early stage disease
- Lobectomy + lymphadenectomy usual approach
- Sublobar resection if stage 1 (<3cm)
Done via open thoracotomy or video-assisted thoracoscopic surgery (VATS)
what are the types of surgical treatment?
wedge resection
- removes small section of lung that contains tumour along with a margin of healthy tissue
Segmental resection
- removes a larger portion of lung, but not entire lobe
lobectomy
- removes entire lobe of one lung
pneunonectomy
- removes an entire lung
when is radiological treatment done for 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
what are the types of systemic treatments?
- oncogene directs
- immunotherapy
- cytotoxic chemotherapy
when is oncogene-directed treatment used?
first line for metastatic NSCLC with mutation
how does oncogene-directed treatment work?
- Tyrosine kinase inhibitors
- ETFR, ALK, ROS-1 inhibitors
- Efficacy- improvements in progression free-survival, but not necessarily overall survival vs standard chemotherapy
- Still palliative therapy
- Side effects
- Generally well tolerated (tablets)
- Rash, diarrhoea and pneumonitis
how does immunotherapy work?
use body’s own immune system to attack cancer cells
e.g block PDL-1 or PD-1 allows T cell killing of tumour cell
- First line for metastating non-small cell lung cancer with no mutation (PDL1>50%)
- Effecacy
- Imporvements in progression- free survival and overall survival vs standard chemotherapy
- Side effects
- Generally well tolerated
- Immune related side effects in 10-15% (thyroid, skin, bowel, lung, liver)
when is cytotoxic chemotherapy used?
- First line for metastotic non-small cell lung cancer with no mutation and PDL1 <50% (in combination with immunotherapy)
- Long established
- Target any rapidly dividing cells
- Platinum-based regimens
what is an example of cytotoxic chemotherapy?
Carboplatin, cisplatin
- Efficacy- modest improvements in overall survival vs best supportive care
- Side effects
- Frequent: fatigue, nausea, bone marrow suppression, nephrotoxicity
- Quality of life poorly evaluated in trials; no evidence for improvement QOL
when should palliative and supportive care be offered?
- Should be offered as standard to all patients with advanced stage disease
what are the benefits of palliative and supportive care?
- Symptom control, psychological support, education, practical and financial support, planning for end of life
- Evidence for survival as well as symptomatic benefit
- Improved QOL, lower depression scores
what is lung cancer treatment determined by?
patient fitness ( ECOG/WHO)
cancer histology
cancer stage
patient preference
health service factors
what is the classification of patient fitness?
- Radical treatment restricted to <50% in bed during day or better (0-2)
- 0- asymptomatic
- 1- symptomatic but completely ambulatory
- 2- symptomatic, <50% in bed during day
- 3- symptomatic >50% in bed, but not bedbound
- 4-bedbound
- 5-death
- Comorbidity + lung function also very important
what is the prognosis for lung cancer?
- Only 10% live >10yrs
- Depends performance status and stage at diagnosis
what is the simplified treatment for different stages of lung cancer?
