Cardio - Lung Cancer Flashcards
What is the epidemiology of lung cancer?
→ 3rd most common in the world
→ leading cause of cancer death
What are the demographics of lung cancer?
→ Age = 75 to 90
→ More males than females
→ Lower socioeconomic status (reduced access to health care, etc)
→ Smoking history (duration, intensity, when stopped)
What causes lung cancer?
→ 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
What are the 4 types of lung cancer?
→ Squamous cell carcinoma (30%)
→ Adenocarcinoma (40%)
→ Large cell lung cancer (15%)
→ Small cell lung cancer (15%)
What types of lung cancer are grouped together? Why not all?
→ squamous, adenocarcinoma and large cell = non-small cell lung cancer
What is a squamous cell carcinoma?
→ previously the most common
→ originating from bronchial epithelium; centrally located
What is an adenocarcinoma?
→ most common from 1980s onwards – low tar cigarettes, inhaled more deeply / retained longer
→ originating from mucus-producing glandular tissue; more peripherally-locate
What is large cell carcinoma?
→ heterogenous group, undifferentiated
What is small-cell lung cancer?
→ originates from pulmonary neuroendocrine cells
→ highly malignant
What are the changes in tissue in early lung cancer
→ normal epithelium
→ hyperplasia
→ squamous metaplasia
What is the intermediate stage of lung cancer development?
→ 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
What are the late stages of lung cancer development?
→ carcinoma in situ
→ invasive carcinoma
What are some important oncogenes?
- 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)
Why is EGFR tyrosine kinase important?
- 15-30% of adenocarcinoma
* more so in women, Asian ethnicity, never-smokers
Why is ALK tyrosine kinase important?
- 2-7% of non-small cell lung cancer
* especially in younger patients and never smokers
Why is ROS1 receptor tyrosine kinase important?
- 2-7% of non-small cell lung cancer
* especially in younger patients and never smokers
Why is BRAF important?
- 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 (coughing up blood) → Frequently patients are asymptomatic
What are some neurological symptoms of advanced lung cancer (metastatic)?
→ Focal weakness
→ Seizures
→ Spinal chord compression
What are some other significant symptoms of metastatic disease?
→ Bone pain
→ Paraneoplastic symptoms : e.g. Cushing’s syndrome, clubbing, hypercalaemia, hyponatraemia, Cushing’s
What are some clinical signs of lung cancer?
→ Cachexia
→ Horner’s syndrome
→ Superior vena cava obstruction
→ Clubbing
What is the diagnostic strategy?
→ Establish most likely diagnosis
→ Establish fitness for investigation and treatment
→ Confirm diagnosis of specific type of cancer considering systemic treatment
→ Confirm staging
What imaging is used to diagnose lung cancer?
→ Staging CT (abdomen + chest)
→ Chest X-ray
→ PET
Why are PET’s useful?
Most useful to exclude occult metastases
What is the best way to make a diagnosis? What are the different types?
Biopsy:
→ Bronchoscopy
→ Endobronchial ultrasound and transbronchial-needle aspiration of mediastinal lymph nodes (EBUS [TBNA])
→ CT- guided lung biopsy
What is the purpose of biopsy via bronchoscopy?
- for tumours of central airway
* where tissue staging not important
What is EBUS [TBNS] used for?
To stage mediastinum +/- achieve tissue diagnosis
What is a CT guided lung biopsy used for?
to access peripheral lung tumours
How are lung cancers assessed and given a stage?
→ T1-4 : tumour size + location
→ N0-3 : lymph node involvement - mediastinum + beyond
→ M0-1c : metastases + number
→ Early vs locally-advanced vs metastatic
What are the determinants of treatment?
→ Patient fitness → Cancer histology → Cancer stage → Patient preference → Health service factors
How are patient categorised by patient fitness?
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
How is lung cancer surgically treated?
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
What is the alternative to surgery for tackling early stage disease?
Radical radiotherapy
Why choose radical radiotherapy over surgery?
- Alternative to surgery for early stage disease
* Particularly if comorbidity
How does radical radiotherapy work?
- Stereotactic ablative body radiotherapy (SABR) aimed at tumour
- Technique of choice
- High-precision targeting, multiple convergent beams
What are the systemic treatments for lung cancer?
→ Oncogene directed
→ Immunotherapy
→ Cytotoxic Chemotherapy
What are some of the oncogene directed drugs?
- EGFR: erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib
- ALK: crizotinib, ceritinib, alectinib, brigatinib, lorlatinib
- ROS-1: crizotinib, entrectinib
What is the efficacy of oncogene directed therapy?
• 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
What are the side effects of oncogene-directed drugs?
- Generally well tolerated
- Rash
- Diarrhoea
- Uncommon but pneumonia
How does the immunotherapy work?
- PD-L1/PD-1 binding inhibits T cell killing of tumour cell
* Immunotherapy blocks PD-L1 or PD-1
When are oncogene-directed drugs used?
First line for metastatic NSCLC with mutation
When is immunotherapy used?
First line for metastatic NSCLC with no mutation (and PDL1 ≥50%
What are the NICE approved drugs for immunotherapy?
- Pembrolizumab
- atezolizumab
- nivolumab
What is the efficacy of immunotherapy?
- 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]
What are the side effects of immunotherapy?
- generally well-tolerated
* Immune-related side-effects in 10-15% (thyroid, skin, bowel, lung, liver)
When is cytotoxic chemotherapy used?
First line for metastatic NSCLC with no mutation and PDL1 ≤50% (in combination with immunotherapy)
What is cytotoxic chemotherapy?
- Target any rapidly dividing cells
* Platiunum-based regimens, e.g. carboplatin, cisplatin, paclitaxel, pemetrexed
What is the efficacy of cytotoxic chemotherapy?
- 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)
What are the side effects of cytotoxic chemotherapy?
- Frequent: fatigue, nausea, bone marrow suppression, nephrotoxicity
- Quality of life poorly evaluated in trials; no evidence for improvement
What is the palliative and supportive care offered to patients with 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 • At 12 weeks: • Improved quality of life • Lower depression scores • Median survival 11.6 v 8.9 months
In summary, what are the main treatments for early stage lung cancer?
Surgery or radiotherapy with curative intent
In summary, what are the main treatments for Locally advanced disease (involving thoracic lymph nodes)?
- Surgery + adjuvant chemotherapy
* Radiotherapy + chemotherapy +/- immunotherapy
In summary, what are the main treatments 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
What is the usual prognosis of lung cancer?
Only 10% live >10 years
Little change in survival in last 40 years
