cancers of lung, heart and vasculature

Question 1

how prevalent is primary cancer of blood vessels and heart?

Answer 1

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

Question 2

what are the types of primary cancer of blood vessels and heart?

Answer 2

1. angiosarcoma
   
   1. malignancy of vascular endothelial cells
   2. of skin, heart, liver etc
2. cardiac tumors
   
   1. E.g Myxoma, tumour of connective tissue

Question 3

how common is lung cancer in UK?

Answer 3

3rd most common

leading cause cancer mortality in men and women

prior to smoking popularity lung cancer rare

Question 4

what are the lung cancer prevalence trends?

Answer 4

• Age peak 75-90
• Mex: M>F
• Low socioeconomic status
• Smoking history
  
  • Duration, intensity, when stopped

Question 5

what are causes of lung cancer?

Answer 5

• 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

Question 6

what are the different types of cancer cells?

Answer 6

squamous cell carcinoma

adenocarcinoma

large cell carcinoma

small cell carcinoma

Question 7

what is squamous cell carcinoma?

Answer 7

2nd most common

originating from bronchial epithelium

centrally located

Question 8

what is adenocarcinoma?

Answer 8

40% lung cancer

most common from 1980’s onwards- low tar cigarettes, retained longer

originating from mucus-producing glandular tissue more peripherally located

Question 9

what is large lung cell cancer?

Answer 9

1. Heterogenous group, undifferentiated

Question 10

what are the features of small cell lung cancer?

Answer 10

1. Originate from pulmonary neuroendocrine cells
2. Highly malignant and very aggressive, presenting at late stage

Question 11

what is metaplasia?

Answer 11

reversible change in which one adult cell type replaced by another cell type; adaptive

Question 12

what is dysplasia?

Answer 12

abnormal pattern of growth in which some of the cellular and architectural feature of malignancy are present; pre invasive stage with intact basement membrane

Question 13

what are the stages of lung cancer development?

Answer 13

Question 14

what are the key features of cancer cells?

Answer 14

Question 15

what are DNA adducts?

Answer 15

• DNA adducts= segment of DNA bound to a cancer causing chemical
• Normally corrected by anti-tumour genes such as p53 or Rb

Question 16

what are the important oncogenes in lung cancer treatments?

Answer 16

1. EGFR tyrosine kinase
2. anaplastic lymphoma kinase (ALK) tyrosine kinase
3. c-ROS oncogene 1 (ROS1) receptor tyrosine kinase
4. BRAF

Question 17

in what ethnicity is EGFR tyrosine kinase mutation prevalent?

Answer 17

high in women, Asian ethnicities, never-smoked

15-30% adenocarcinomas

Question 18

in what population is ALK mutation more likely?

Answer 18

2-7% non-small cell lung cancer

especially in younger patients and never smokers

Question 19

in what population is ROS1 oncogene more likely?

Answer 19

1-2% non-small cell lung cancer

especially in younger people and never smoked

Question 20

in what population is BRAF oncogene more likely?

Answer 20

1-3% non-small cell lung cancers

especially in smokers

Question 21

what are the key symptoms of lung cancer?

Answer 21

• cough
• weight loss (cachexia)
• breathlessness
• fatigue
• chest pain
• haemoptysis

frequently asymptomatic

Question 22

what are the features of advanced lung cancer/metastatic disease?

Answer 22

• 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)

Question 23

what is horner’s syndrome?

Answer 23

ptosis (drooping eyelid)

miosis (constriction pupil)

anhydrosis (absence sweating face)

Question 24

what is pemberton’s sign?

Answer 24

positive sign= bilateral arm elevation causes facial plethora

Question 25

what are the common sites of lung cancer metastases?

Answer 25

liver brain bones lymph nodes adrenal glands

Question 26

what is a pet scan most useful for?

Answer 26

most useful to exclude occult metastases ingestion of radioactively labeled glucose (taken up by all parts metastasising)

Question 27

what are the different methods used to biopsy lung tumour? what are each method used for?

Answer 27

* 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

Question 28

how is cancer staged?

Answer 28

stages 0-4 * Stage 1= early single nodule with no evidence of spread * Stage 4= metastatic disease in multiple sites

Question 29

What are the staging of TNM system?

Answer 29

* T1-4: tumour size and location * N0-3: lymph node involvement- mediastinum + beyond * M0-1c: metastases + number

Question 30

what are the treatment options for lung cancer?

Answer 30

surgical radiological pharmacological supportive

Question 31

when is surgical treatment used?

Answer 31

* 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)

Question 32

what are the types of surgical treatment?

Answer 32

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

Question 33

when is radiological treatment done for lung cancer?

Answer 33

* Alternative to surgery for early stage disease * Particularly if comorbidity * Stereotactic ablative body radiotherapy (SABR) * Technique of choice * High precision targeting, multiple convergent beams

Question 34

what are the types of systemic treatments?

Answer 34

1. oncogene directs 2. immunotherapy 3. cytotoxic chemotherapy

Question 35

when is oncogene-directed treatment used?

Answer 35

first line for metastatic NSCLC with mutation

Question 36

how does oncogene-directed treatment work?

Answer 36

1. Tyrosine kinase inhibitors 1. ETFR, ALK, ROS-1 inhibitors 2. Efficacy- improvements in progression free-survival, but not necessarily overall survival vs standard chemotherapy 3. Still palliative therapy 4. Side effects 1. Generally well tolerated (tablets) 2. Rash, diarrhoea and pneumonitis

Question 37

how does immunotherapy work?

Answer 37

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 1. Imporvements in progression- free survival and overall survival vs standard chemotherapy * Side effects 1. Generally well tolerated 2. Immune related side effects in 10-15% (thyroid, skin, bowel, lung, liver)

Question 38

when is cytotoxic chemotherapy used?

Answer 38

1. First line for metastotic non-small cell lung cancer with no mutation and PDL1 \<50% (in combination with immunotherapy) 2. Long established 1. Target any rapidly dividing cells 2. Platinum-based regimens

Question 39

what is an example of cytotoxic chemotherapy?

Answer 39

Carboplatin, cisplatin 1. Efficacy- modest improvements in overall survival vs best supportive care 2. Side effects 1. Frequent: fatigue, nausea, bone marrow suppression, nephrotoxicity 2. Quality of life poorly evaluated in trials; no evidence for improvement QOL

Question 40

when should palliative and supportive care be offered?

Answer 40

* Should be offered as standard to all patients with advanced stage disease

Question 41

what are the benefits of palliative and supportive care?

Answer 41

* 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

Question 42

what is lung cancer treatment determined by?

Answer 42

patient fitness ( ECOG/WHO) cancer histology cancer stage patient preference health service factors

Question 43

what is the classification of patient fitness?

Answer 43

* 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

Question 44

what is the prognosis for lung cancer?

Answer 44

* Only 10% live \>10yrs * Depends performance status and stage at diagnosis

Question 45

what is the simplified treatment for different stages of lung cancer?

Answer 45