Lung Cancer Flashcards by Elizabeth Akeju

What is the leading cause of cancer death?

Lung cancer

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Lung cancer is the ____ most common cancer in the UK

3rd

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What is the main risk factor for lung cancer?

Smoking

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What is the peak age for lung cancer and which sex is it more common in?

75-90
Males

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Is lower socioeconomic status a risk factor for lung cancer?

Duration, intensity, when they stopped

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What are other aetiological factors than smoking?

Asbestos exposure (plumbers, ship-builders, carriage workers, carpenters) - risk up to 2x
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

(Passive smoking is also a risk factor)

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Describe the pathogenesis of lung cancer

May arise from any differentiated or undifferentiated cell
Interaction between inhaled carcinogens and epithelium of upper and lower airways leads to the formation of DNA adducts: pieces of DNA covalently bound to a cancer-causing chemical
Persistence/misrepair of DNA adducts may result in a mutation and can cause genomic alterations
Key if they occur in critical oncogenes and tumour suppressor genes

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Name the 3 types of non-small cell lung cancer (NSCLC)

Squamous cell carcinoma
Adenocarcinoma
Large cell lung cancer

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What do squamous cell carcinomas originate from?

Bronchial epithelium
Centrally located

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What do adenocarcinomas originate from?

Mucus-producing glandular tissue
Peripherally located

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Are large cell lung cancers differentiated?

No
Heterogeneous group

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What does small cell lung cancer originate from?

Pulmonary neuroendocrine cells

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How malignant is small cell lung cancer?

Highly

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What is the most common type of lung cancer?

Adenocarcinoma (~40%)
(previously squamous cell carcinoma)

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What is the definition of metaplasia?

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

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What is 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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Mutations in what 4 genes are important for directed treatments of lung cancer?

Epidermal growth factor receptor (EGFR) tyrosine kinase (adenocarcinomas)
Anaplastic lymphoma kinase (ALK) tyrosine kinase
c-ROS oncogene 1 (ROS1) receptor tyrosine kinase
BRAF (downstream cell-cycle signalling mediator) - especially in smokers

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What are the key symptoms of lung cancer?

Cough
Breathlessness
Fatigue
Chest pain
Weight loss
Haemoptysis

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Can lung cancer frequently be asymptomatic?

Yes

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Why is making an initial diagnosis of lung cancer through the symptoms difficult?

The key symptoms overlap with many other respiratory diseases

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Why is it important to screen for lung cancer?

The tumour can get quite large before it starts to cause issues

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What are the neurological features of metastatic lung cancer?

Focal weakness - due to cardiac vegetations that embolize to main cerebral arteries
Seizures - due to chemo given via spine or when cancer reaches brain
Spinal cord compression

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Why is there bone disease in lung cancer?

When lung cancer spreads to the bones, it’s calledbone metastasis
Bone metastasis can result in complications such as weakened bones and fractures, nerve damage in your spinal cord, and severe pain

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What are the paraneoplastic syndromes characteristic of metastatic lung cancer?

Clubbing - result of hypoxaemia - increased blood flow to the finger area, leading to the accumulation of fluid in the soft tissues at the terminal portion of the finger and subsequent bulging of the area
Cushing’s - Small cell lung cancer canoccasionally be a source of ectopic ACTH secretion
Hypercalcaemia - dueto increased bone resorption and release of calcium from bone
Hyponatraemia - result of SIADH

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What are the 4 signs of lung cancer?

Clubbing Cachexia (body weakness and wasting) - increased breakdown and depletion of skeletal muscle proteins Horner's syndrome - compression of sympathetic ganglion/disrupted supply - leading to partial ptosis, miosis and facial anhidrosis Superior vena cava obstruction (Pemberton's sign) - cancer may be compressing SVC/spread to the lymph nodes nearby, which become swollen

What 4 general things must be confirmed in the diagnostic strategy plan 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

After a chest X-Ray, what is the next imaging technique that must be used?

Staging CT Look for swelling of mediastinal lymph nodes and can also look for sign of metastases to abdomen

What is PET-CT (fluorodeoxyglucose) most useful for in a diagnosis of lung cancer?

Definitive imaging for staging Most useful to exclude occult (initially undetected) metastases Detects mediastinal lymph nodes involvement

The method of biopsy for suspected lung cancer is determined by what?

Accessibility Availability Impact on staging

When would a bronchoscopy be performed?

For tumours of central airway Where tissue staging is not important

How do you stage mediastinum and/or achieve tissue diagnosis?

Endobronchial ultrasound and transbronchial-needle aspiration of mediastinal lymph nodes (EBUS [TBNA]) TBNA - used to obtain tissue from lung or hilar/mediastinal lesions that are in close proximity to the endobronchial tree

How do you access peripheral lung tumours?

CT-guided lung biopsy

How do you access peripheral lung tumours?

CT-guided biopsy

What do the stages T1-4 tell you?

Location and size of the tumour

What does N0-3 show?

Lymph node involvement - mediastinum + beyond

What does M0-1c tell you?

Distant metastasis: Non-regional lymph node metastases Extrathoracic metastases

What are the 5 determinants of treatment?

Patient fitness (0-asymptomatic → 5-death) Cancer histology Cancer stage Patient preference Health service factors

Outline patient fitness scores 0-5 according to the WHO performance status.

0 – Asymptomatic (Fully active, able to carry on all pre-disease 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 bed-bound (Capable of only limited self-care, confined to bed or chair 50% or more of waking hours) 4 – Bed-bound (Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair) 5 – Death

Surgery and chemotherapy is usually restricted to a WHO performance status of what?

0-2

What types of patients is surgical resection usually reserved for?

Early stage lung cancer

What types of surgery is the usual approach to treat lung cancer?

Lobectomy + lymphadenectomy

What types of surgery is the usual approach to treat lung cancer?

Lobectomy + lymphadenectomy

What surgery is done if stage 1 (≤3cm)?

Sub-lobar resection

Can radiotherapy be curative?

Yes

If there is comorbidity, is radiotherapy preferred or is surgery preferred?

Radiotherapy

What is the technique of choice for radiotherapy and why is this the preferred technique?

Stereotactic ablative body radiotherapy (SABR) High-precision targeting, multiple convergent beams

What is the NICE-approved first-line treatment for metastatic NSCLC with mutation?

Oncogene directed drugs targeting mutations in the following oncogenes: EGFR: erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib ALK: crizotinib, ceritinib, alectinib, brigatinib, lorlatinib ROS-1: crizotinib, entrectinib

How would you describe the efficacy of oncogene directed drugs?

Improvements in progression-free survival, but not necessarily overall survival vs standard chemotherapy

What are the side effects of oncogene directed drugs?

Tablets generally well-tolerated Rash, diarrhoea, and (uncommonly) pneumonitis

What is the 2nd class of drug treatments?

Immunotherapy

What type of binding do cancer cells have that inhibits T cell killing of tumour cells?

PD-L1/PD-1 binding

What does blocking of PD-L1/PD-1 binding allow?

Blocking PD-L1 or PD-1 allows T cell killing of tumour cell

What is the first line treatment for metastatic NSCLC with no mutation (and PDL1≥50%)?

Immunotherapy

What are the 3 NICE approved immunotherapies for lung cancer?

Pembrolizumab, atezolizumab, nivolumab

How would you describe the efficacy of these immunotherapies against NSCLC?

Improvements in progression-free survival and overall survival vs standard chemotherapy

What are the side effects for immunotherapies against lung cancer?

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

What is the first line for metastatic NSCLC with no mutation and PDL1≤50% (in combo with immunotherapy)?

Cytotoxic chemotherapy

What do cytotoxic chemotherapies target?

Any rapidly dividing cells

List examples of the platinum-based regimens that are a part of cytotoxic chemotherapy

Carboplatin, cisplatin, paclitaxel, pemetrexed

How would you describe the efficacies of cytotoxic chemotherapies?

Efficacy when used alone (old data, pre-2000) → modest improvements in overall survival vs best supportive care Efficacy when used with pembrolizumab a lot better Therefore should use cytotoxic chemotherapy with immunotherapy

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

Who should palliative care and supportive care be offered to?

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

What does palliative and supportive care involve?

Symptom control Psychological support Education Financial support Practical support Planning for end of life

If there is early stage disease, what treatment should be given

Surgery or radiotherapy with curative intent

If there is locally advanced disease (involving thoracic lymph nodes) what treatment should be given?

Surgery + adjuvant chemotherapy Radiotherapy + chemotherapy +/- immunotherapy

If the patient has metastatic disease, what are the treatment options?

With targetable mutation (e.g. EFGR, ALK, ROS-1) tyrosine kinase inhibitor No mutation, PDL-1 positive: immunotherapy along No mutation, PDL-1 negative: ‘standard’ chemotherapy + immunotherapy Palliative care, alone or with the above

What percent of lung cancer patients live beyond 10 years?

~10%