🫀🫁Cardio & Resp🫀🫁 - Lung Cancer Flashcards by Oliver Durrant

What are the key epidemiological facts about lung cancer?

3rd most common cancer in the UK
48000 diagnoses/year
35000 deaths/year
Leading cause of cancer death

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What groups of people are statistically more likely to get lung cancer?

Peak age 75-90
Males>females
Lower socioeconomic status
Smoking history strong indicator - duration, intensity, when stopped
Despite this, 10-15% patients with lung cancer never smoked

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What other causes are there for lung cancer, other than smoking?

Asbestos - exposure associated with up to 2x risk
Radon - historically mining
Indoor cooking fumes
Chronic lung diseases
Air pollution
Fx/genetic factors

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What is the basic pathogenesis of lung cancer?

Lung cancer may arise from all differentiated and undifferentiated cells
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
Persisting/misrepaired adducts result in mutations - cause genomic alterations

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What are the various pathophysiologies of lung cancer?

Squamous cell carcinoma (~30% of cases)
Adenocarcinoma (~40%)
Large cell lung cancer (~15%)
Small cell lung cancer (~15%)
1-3 often grouped together as non-small cell lung cancer (NSCLC)

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Outline squamous cell carcinoma lung cancer

30% of cases
Previously the most common
Originating from the bronchial epithelium - centrally located
(Coughing, haemoptysis, recurrent infections due to airway obstruction)
(Moderately fast - slower than small cell but can invade nearby structures early - better prognosis than small cell but worse than adenocarcinoma)

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Outline adenocarcinoma lung cancer

40% of cases
Most common from 1980s onwards
Originates from mucus-producing glandular tissue- more peripheral
Accounts for most non-smoking lung cancer cases
(Later presentation with vague symptoms like shortness of breath/chest pain)
(Slower growing, can metastasize early, especially to bones and brain - generally better prognosis, especially if detected early)

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Outline large cell lung cancer

15% of cases
Heterogenous group, undifferentiated
Often peripheral, but can be anywhere
(Non-specific symptoms; can cause chest pain, cough, or symptoms based on where it spreads)
(Aggressive, rapid growth, high likelihood of metastasis.
Poor prognosis due to rapid progression and late detection)

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Outline small cell lung cancer

15% of cases
Originate from pulmonary neuroendocrine cells
Highly malignant
(Rapid onset of cough, weight loss, and paraneoplastic syndromes (e.g., SIADH, Cushing syndrome))
(Very fast growing, early and widespread metastasis.
Poorest prognosis, high recurrence rate even with treatment)

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Name the 4 most important oncogenes in the pathogenesis of lung cancer, specifically mutations in them

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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What is the significance of an Epidermal growth factor receptor (EGFR) tyrosine kinase mutation?

15-30% of adenocarcinoma
More so in women, Asian ethnicity, never-smokers

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What is the significance of an Anaplastic lymphoma kinase (ALK) tyrosine kinase mutation?

2-7% of non-small cell lung cancer
Especially in younger patients and never-smokers

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What is the significance in a c-ROS oncogene 1 (ROS1) receptor tyrosine kinase mutation?

1-2% of non-small cell lung cancer
Especially in younger patients and never-smoker

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What is the significance of a BRAF (downstream cell-cycle signalling mediator) mutation?

1-3% of non-small cell lung cancer
Especially in smokers

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What are the key symptoms of lung cancer?

Cough
Weight loss
Breathlessness
Fatigue
Chest pain
Haemoptysis
Can be frequently asymptomatic

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What are the key features of advanced/metastatic lung cancer?

Neurological features:
Focal weakness, seizures, spinal cord compression
Bone pain
Paraneoplastic syndromes:
Clubbing, hypercalcaemia, hyponatraemia, Cushing’s

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What is clubbing?

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What is cachexia

Severe, rapid weight loss
Also features prominent muscle wasting

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What is Pemberton’s sign?

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What is Horner’s syndrome?

Decreased pupil size, a drooping eyelid and decreased sweating on the affected side of the face

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What is the diagnostic strategy for suspected lung cancer?

Establish most likely diagnosis
Establish fitness for investigation and treatment
Confirm diagnosis and histological type
-genomic testing key if considering systemic treatment in NSCLC
Confirm staging

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Who is in the lung cancer MDT?

Respiratory doctor
Radiologist
Pathology doctor
Thoracic surgeon
Oncologist
Palliative care
(Patient)

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Who is currently eligible for lung cancer screening?

Current or ex-smokers aged between 55 and 74 are invited via their GP to attend a lung health check
Offered an appointment for a low dose CT scan
RMP pilot: Lung cancer detected in 29/1145 (2.5 %) participants scanned (stage 1, 58.6 %)

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How is PET-CT useful?

Helps exclude occult metastases

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What are occult metastases?

Metastatic cancer cells that have spread from the primary tumour site but are too small to be detected with conventional imaging techniques or during physical examination

How do you choose a method of biopsy for lung cancers?

Choose method based on accessibility, availability and impact on staging

What would you use a bronchoscopy for?

Tumours of central and segmental airways

How would you stage the mediastinum +/- achieve tissue diagnosis?

Endobronchial ultrasound and transbronchial-needle aspiration of mediastinal lymph nodes (EBUS [TBNA])

When would you use navigational bronchoscopy + robotic Bronchoscopy?

For peripheral lesions/nodules that are not amenable to conventional bronchoscopy or CT guided biopsy

How are biopsies taken from peripheral lung tumours?

CT-guided lung biopsy

How are lung cancers staged?

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

Describe what you would see in early vs locally-advanced vs metastatic

What 5 factors act as determinants of treatment for lung cancer?

Patient fitness Cancer histology Cancer stage Patient preference Health service factors

What is the WHO performance status?

Scale that measures patient fitness 0 - Asymptomatic 1- Symptomatic but completely ambulatory 2 - Symptomatic, up and about >50% of waking hours 3 - Symptomatic, confined to bed or chair >50% of waking hours 4 - Completely disabled 5 - Death Radical treatment usually restricted to PS 0-2

What is meant by "asymptomatic" on the WHO performance status?

Fully active, able to carry on all predisease activities without restriction

What is meant by "symptomatic but completely ambulatory" on the WHO performance status?

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

What is meant by "symptomatic, up and about >50% of waking hours" on the WHO performance status?

Ambulatory and capable of all self care but unable to carry out any work activities

What is meant by "symptomatic, confined to bed or chair >50% of waking hours" on the WHO performance status?

Capable of only limited self-care

What is meant by "completely disabled" on the WHO performance status?

Completely disabled. Cannot carry on any self-care Totally confined to bed or chair

What is meant by "death" on the WHO performance status?

Take a wild guess

What must also be considered when assessing a patient's WHO performance status?

Comorbidity + lung function also very important

What is the standard care for early stage disease?

Surgical resection is standard of care for early stage disease Lobectomy + lymphadenectomy usual approach Sublobar resection if stage 1 (≤3 𝑐𝑚)

What is an alternative to surgery in early stage disease?

Radical radiotherapy Particularly relevant if there is a comorbidity Stereotactic ablative body radiotherapy (SABR) Technique of choice High-precision targeting, multiple convergent beams

What are the systemic treatments available for lung cancer treatment

Oncogene-directed drugs Immunotherapy Cytotoxic chemotherapy

When are systemic treatments used to treat lung cancers?

First line for metastatic NSCLC with mutation

What are the NICE approved drugs for use in oncogene-directed therapy?

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

What is the reported efficacy of oncogene-directed therapy?

Improvements in progression-free survival, modest overall survival vs standard chemotherapy

What side effects can be experienced in oncogene-directed systemic treatment?

Generally well-tolerated (tablets) Rash, diarrhoea, and (uncommonly) pneumonitis

When is immunotherapy used to treat lung cancer?

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

What are the NICE approved immunotherapy drugs?

Pembrolizumab, atezolizumab, nivolumab

How does immunotherapy help treat lung cancer?

What is the reported efficacy of immunotherapy in treating lung cancer?

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

What are the potential side effects of immunotherapy?

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

When is cytotoxic chemotherapy used to treat lung cancer?

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

Outline the function of cytotoxic chemotherapy

Long established Target any rapidly dividing cells Platinum-based regimens, e.g. carboplatin, cisplatin, paclitaxel, pemetrexed

What is the reported 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, a lot better (23% 2y survival vs 5% for standard chemo alone)

What are the potential side effects of cytotoxic chemotherapy?

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

When does palliative and supportive care become relevant?

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

What is the aim of palliative and supportive care?

Symptom control, psychological support, education, practical/financial support, planning for end of life Lung cancer specialist nurses key

What is the evidence that supports palliative care?

Evidence for survival as well as symptomatic benefit: 151 patients, new diagnosis NSCLC in USA Standard oncology care +/- early palliative care At 12 weeks: -Improved quality of life -Lower depression scores -Median survival 11.6 v 8.9 months

Give a summary of lung cancer treatment

What is the general prognosis for lung cancer?

Only 10% live >10 years Little change in survival in last 40 years (BUT this may be now out of date)

🫀🫁Cardio & Resp🫀🫁 - Lung Cancer Flashcards

(62 cards)