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!!!!! BRS YR2 !!!!! > Cardio - Lung Cancer > Flashcards

Cardio - Lung Cancer Flashcards

1
Q

What is the epidemiology of lung cancer?

A

→ 3rd most common in the world

→ leading cause of cancer death

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2
Q

What are the demographics of lung cancer?

A

→ Age = 75 to 90
→ More males than females
→ Lower socioeconomic status (reduced access to health care, etc)
→ Smoking history (duration, intensity, when stopped)

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3
Q

What causes lung cancer?

A 
→ Smoking 
→ Passive smoking
→ Asbestos (exposure increases risk up to 2 times)
→ Radon (silver mines, uranium mining)
→ Indoor cooking fumes (wood smoke, frying fats)
→ Chronic lung diseases (COPD, CF)
→ Immunodeficiency 
→ Familial or Genetic factors
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4
Q

What are the 4 types of lung cancer?

A

→ Squamous cell carcinoma (30%)
→ Adenocarcinoma (40%)
→ Large cell lung cancer (15%)
→ Small cell lung cancer (15%)

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5
Q

What types of lung cancer are grouped together? Why not all?

A

→ squamous, adenocarcinoma and large cell = non-small cell lung cancer

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6
Q

What is a squamous cell carcinoma?

A

→ previously the most common

→ originating from bronchial epithelium; centrally located

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7
Q

What is an adenocarcinoma?

A

→ most common from 1980s onwards – low tar cigarettes, inhaled more deeply / retained longer
→ originating from mucus-producing glandular tissue; more peripherally-locate

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8
Q

What is large cell carcinoma?

A

→ heterogenous group, undifferentiated

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9
Q

What is small-cell lung cancer?

A

→ originates from pulmonary neuroendocrine cells

→ highly malignant

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10
Q

What are the changes in tissue in early lung cancer

A

→ normal epithelium
→ hyperplasia
→ squamous metaplasia

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11
Q

What is the intermediate stage of lung cancer development?

A

→ 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

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12
Q

What are the late stages of lung cancer development?

A

→ carcinoma in situ

→ invasive carcinoma

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13
Q

What are some important oncogenes?

A
  • 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)
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14
Q

Why is EGFR tyrosine kinase important?

A
  • 15-30% of adenocarcinoma

* more so in women, Asian ethnicity, never-smokers

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15
Q

Why is ALK tyrosine kinase important?

A
  • 2-7% of non-small cell lung cancer

* especially in younger patients and never smokers

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16
Q

Why is ROS1 receptor tyrosine kinase important?

A
  • 2-7% of non-small cell lung cancer

* especially in younger patients and never smokers

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17
Q

Why is BRAF important?

A
  • 1-3% of non-small cell lung cancer

* especially in smokers

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18
Q

What are the key symptoms of lung cancer?

A 
→ Cough
→ Weight loss
→ Breathlessness
→ Fatigue 
→ Chest pain
→ Haemoptysis (coughing up blood)
→ Frequently patients are asymptomatic
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19
Q

What are some neurological symptoms of advanced lung cancer (metastatic)?

A

→ Focal weakness
→ Seizures
→ Spinal chord compression

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20
Q

What are some other significant symptoms of metastatic disease?

A

→ Bone pain

→ Paraneoplastic symptoms : e.g. Cushing’s syndrome, clubbing, hypercalaemia, hyponatraemia, Cushing’s

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21
Q

What are some clinical signs of lung cancer?

A

→ Cachexia
→ Horner’s syndrome
→ Superior vena cava obstruction
→ Clubbing

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22
Q

What is the diagnostic strategy?

A

→ Establish most likely diagnosis
→ Establish fitness for investigation and treatment
→ Confirm diagnosis of specific type of cancer considering systemic treatment
→ Confirm staging

23
Q

What imaging is used to diagnose lung cancer?

A

→ Staging CT (abdomen + chest)
→ Chest X-ray
→ PET

24
Q

Why are PET’s useful?

A

Most useful to exclude occult metastases

25
Q

What is the best way to make a diagnosis? What are the different types?

A

Biopsy:
→ Bronchoscopy
→ Endobronchial ultrasound and transbronchial-needle aspiration of mediastinal lymph nodes (EBUS [TBNA])
→ CT- guided lung biopsy

26
Q

What is the purpose of biopsy via bronchoscopy?

A
  • for tumours of central airway

* where tissue staging not important

27
Q

What is EBUS [TBNS] used for?

A

To stage mediastinum +/- achieve tissue diagnosis

28
Q

What is a CT guided lung biopsy used for?

A

to access peripheral lung tumours

29
Q

How are lung cancers assessed and given a stage?

A

→ T1-4 : tumour size + location
→ N0-3 : lymph node involvement - mediastinum + beyond
→ M0-1c : metastases + number
→ Early vs locally-advanced vs metastatic

30
Q

What are the determinants of treatment?

A 
→ Patient fitness
→ Cancer histology
→ Cancer stage
→ Patient preference
→ Health service factors
31
Q

How are patient categorised by patient fitness?

A

WHO performance status:
→ 0 = asymptomatic + fully active
→ 1 = symptomatic but completely ambulatory
→ 2 = symptomatic, less than 50% of time in bed during the day
→ 3 = symptomatic, but more than 50% in bed, not bed bound
→ 4 = bed bound
→ 5 = death

32
Q

How is lung cancer surgically treated?

A

Surgical resection = standard of care of early stage disease
→ Lobectomy = removal of lobe
→ Lymphadenectomy = removal of lymph nodes in tumour
→ Sublobar resection if stage 1 (less than 3cm) = small section of lung removed
→ Pneumonectomy = removal of whole lung

33
Q

What is the alternative to surgery for tackling early stage disease?

A

Radical radiotherapy

34
Q

Why choose radical radiotherapy over surgery?

A
  • Alternative to surgery for early stage disease

* Particularly if comorbidity

35
Q

How does radical radiotherapy work?

A
  • Stereotactic ablative body radiotherapy (SABR) aimed at tumour
  • Technique of choice
  • High-precision targeting, multiple convergent beams
36
Q

What are the systemic treatments for lung cancer?

A

→ Oncogene directed
→ Immunotherapy
→ Cytotoxic Chemotherapy

37
Q

What are some of the oncogene directed drugs?

A
  • EGFR: erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib
  • ALK: crizotinib, ceritinib, alectinib, brigatinib, lorlatinib
  • ROS-1: crizotinib, entrectinib
38
Q

What is the efficacy of oncogene directed therapy?

A

• 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

39
Q

What are the side effects of oncogene-directed drugs?

A
  • Generally well tolerated
  • Rash
  • Diarrhoea
  • Uncommon but pneumonia
40
Q

How does the immunotherapy work?

A
  • PD-L1/PD-1 binding inhibits T cell killing of tumour cell

* Immunotherapy blocks PD-L1 or PD-1

41
Q

When are oncogene-directed drugs used?

A

First line for metastatic NSCLC with mutation

42
Q

When is immunotherapy used?

A

First line for metastatic NSCLC with no mutation (and PDL1 ≥50%

43
Q

What are the NICE approved drugs for immunotherapy?

A
  • Pembrolizumab
  • atezolizumab
  • nivolumab
44
Q

What is the efficacy of immunotherapy?

A
  • 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]
45
Q

What are the side effects of immunotherapy?

A
  • generally well-tolerated

* Immune-related side-effects in 10-15% (thyroid, skin, bowel, lung, liver)

46
Q

When is cytotoxic chemotherapy used?

A

First line for metastatic NSCLC with no mutation and PDL1 ≤50% (in combination with immunotherapy)

47
Q

What is cytotoxic chemotherapy?

A
  • Target any rapidly dividing cells

* Platiunum-based regimens, e.g. carboplatin, cisplatin, paclitaxel, pemetrexed

48
Q

What is the efficacy of cytotoxic chemotherapy?

A
  • 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)
49
Q

What are the side effects of cytotoxic chemotherapy?

A
  • Frequent: fatigue, nausea, bone marrow suppression, nephrotoxicity
  • Quality of life poorly evaluated in trials; no evidence for improvement
50
Q

What is the palliative and supportive care offered to patients with lung cancer?

A 
• 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
• At 12 weeks:
• Improved quality of life
• Lower depression scores
• Median survival 11.6 v 8.9 months
51
Q

In summary, what are the main treatments for early stage lung cancer?

A

Surgery or radiotherapy with curative intent

52
Q

In summary, what are the main treatments for Locally advanced disease (involving thoracic lymph nodes)?

A
  • Surgery + adjuvant chemotherapy

* Radiotherapy + chemotherapy +/- immunotherapy

53
Q

In summary, what are the main treatments for Metastatic disease?

A
  • 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
54
Q

What is the usual prognosis of lung cancer?

A

Only 10% live >10 years

Little change in survival in last 40 years

!!!!! BRS YR2 !!!!! (72 decks)

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