Lung cancer Flashcards by Mohamed Yusuf

Poor survival rates

Patients present late with advanced stage

Early symptoms similar to common smokers symptoms

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Causes

90% are caused by smoking

Deaths in men have reduced by more than a quarter

Lung cancer deaths in women are increasing

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Symptoms

Usually in a smoker of more than 20 years:
Respiratory
Metastatic- from spread to distant sites
Paraneoplastic/systemic

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Common symptom presentation - respiratory

Cough
haemoptysis
dyspnoea
wheeze
chest pain
hoarseness
recurrent pneumonia

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Common systemic and metastatic presenting symptoms in lung cancer

Weight loss
Anorexia, nausea
Malaise
Fatigue
From secondary sites eg CNS, bone, skin
Metastases - brain/bone

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Paraneoplastic syndromes in lung cancer

Hyponatraemia (due to SIADH)- small cell carcinoma

Hypercalcaemia (due to PTH like activity)- squamous cell carcinoma

Less commonly- gynaecomastia, pruritis, cerebellar degeneration, peripheral neuropathy

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Lung cancer presentation

Presenting symptoms = highly variable and may involve sites distant from the chest, or be very non-specific

The approach is to have a high index of suspicion in any (ex) smoker

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Hyponatraemia

due to SIADH - small cell carcinoma

Paraneoplastic syndrome

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Hypercalcaemia

due to PTH like activity - squamous cell carcinoma

Paraneoplastic syndrome

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Subtypes

Non-small cell (NSCLC) 
squamous 
adenocarcinoma 
large cell 
undifferentiated

Small cell - central, early lymphatic spread - paraneoplastic syndrome

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Squamous lung cancer

Non small cell

central; invade locally; frequent cavitation; hypercalcaemia common (20%)

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Adenocarcinoma

peripheral lung; more common in non-smokers Most common (40%)

non small cell

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Common signs on examination

clubbing
cachexia
supraclavicular, cervical lymphadenopathy
Stridor due to large airway disease or vocal cord palsy (hoarse voice)
focal chest signs of lung collapse, fixed wheeze
pleural effusion

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Investigations reasons

Confirm diagnosis
Determine tumour cell type
Stage extent

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Types of investigation

CT
Bronchoscopy
Endobronchial Ultrasound Needle aspiration
Other biopsy procedure eg percutaneous CT thorax, peripheral lymph node/liver
PET scanning- a nuclear medicine scan, utilising the high uptake of a glucose analogue (2,3 FDG) in tumour cells

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TNM staging in lung cancer

Important factor in determining treatment and prognosis in lung cancer (general fitness and patient wishes being the others)

It takes into account tumour size, involvement of local structures, lymph and blood metastases

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Management of newly diagnosed lung cancer

Small cell or non-small cell lung cancer
If NSCLC is resectable

Otherwise, other radical treatment appropriate
- high dose radiotherapy, stereotactic radio/microwave ablation

Role of surgery in NSCLC

Consider surgery for all patients with stage 1 and 2 disease
Usually involves lobectomy (pneumonectomy sometimes performed)
In practice around 10% in UK undergo potentially curative resection for lung cancer

Other radical treatment

Radical (high dose) radiotherapy
+/- chemotherapy
Usually reserved for those with stage 1 or 2 disease who are unfit (or unwilling) for surgery

Palliative radiotherapy/chemotherapy in NSCLC

Offers good symptom relief for haemoptysis, intractable cough or dyspnoea from bronchial or tracheal obstruction, chest and skeletal pain
Not expected to cure

Chemotherapy regimens can improve quality of life
Also offer a modest improvement in survival (measured in weeks)
May be used in conjunction with radiotherapy

Differential diagnosis of lung mass

Neoplastic vs non-neoplastic 
Benign vs malignant 
Primary vs secondary 
Site of origin 
Histological type 
Prognostic and predictive features 
Carcinoma, sarcoma and lymphoma

Pathological diagnosis of lung cancer

Clinical history & examination
Distribution, gross appearance (number, shape and size)
Growth pattern at margin of tumour
Histological type, prognostic and predictive features
All requires a MDT approach

Main histological types of lung cancer

Small Cell (AKA Oat Cell) Carcinoma (10-15%)

Non Small Cell Carcinoma (85-90%)
Squamous Cell Carcinoma 20-30%
Adenocarcinoma 40%
Undifferentiated / Large Cell Carcinoma 10- 5%
Mixed and others

Small cell carcinoma

Widespread bulky disease

Small, dark, delicate cells with little cytoplasm

‘Salt and pepper’ chromatin in the nuclei

Squamous cell carcinoma

Central origin often Cigarette smoke provoking squamous metaplasia, then dysplasia of bronchial epithelium Thought to arise from squamous metaplasia & dysplasia of bronchial epithelium

Adenocarcinoma

May first begin with malignant cells lining alveolar spaces Typically peripheral, contains fibrous tissue and shows variable differentiation which correlates with prognosis

Difficult to distinguish between SCC and AC

Looking for specific proteins can help | eg TTF1 expression is typical of adenocarcinoma

Molecular pathology of adenocarcinoma

Adenocarcinomas are subdivided according to key driver mutations EGFR mutations may be targeted with tyrosine kinase inhibiting agents (eg erlotinib, gefitinib) ALK fusion proteins may be targeted with crizotinib Tissue is prioritized for testing to permit rational therapy

Pattern of spread of lung cancer

local and direct spread lymphatic system spread

Pattern of spread of lung cancer - local and direct spread

Adjacent lung, Intrapulmonary metastasis | Pleura and Pleural Cavity

Pattern of spread of lung cancer - lymphatic

Lymphatics within Lung | Lymph Nodes – Hilar, Mediastinal

Pattern of spread of lung cancer - system spread

Liver, Bone, Brain, Adrenal

Making a diagnosis

Multidisciplinary Effort Clinical Features, Imaging ``` Histological type Small cell carcinoma Non small cell carcinoma Squamous cell carcinoma Adenocarcinoma ``` Confirm by looking for proteins Prognostic and predictive molecular pathology Increasingly diagnosis is made on tiny specimens obtained by minimally invasive procedures (e.g. EBUS)

Lung cancer associations

Smoking Fibrosis alveolitis Ionising radiation, air pollution and diesel engine exhaust Chromium Iron oxide, nickel Mesothelioma - asbestos exposure

Surgical considerations

``` Operative mortality Cardiovascular mordidity Lung function Post-operative quality-of-life/dyspnoea Surgical approach Chemotherapy – pre or post-op Post-operative radiotherapy ```

Outcome for surgery

5 year survival approx 50% | (only approx 15% of pts are suitable for resection)

Radiation damage

``` Base damage Protein-protein cross-links DNA-protein cross-links Intra-strand cross-links Inter-strand cross-links intercalation ```

Cell death | - chromosomal breaks and abberations

Chromosomal breaks -> early apoptosis | Chromosomal -> mitotic death, reproductive death and late apop

Locally advanced lung cancer treatments

Radiotherapy + chemotherapy Chemo and/or radiotherapy with surgery Chemo followed by consolidation RT for small cell

Outcomes from radical treatment

Locally advanced disease - median survival = 18-24 months | Outcome worse if: performance status poor or weight

Chemotherapy

Cochrane review (52 trials, 9387 pts) Surgery + chemo vs surgery alone Tumours >4cm +/- nodes involved absolute benefit 5% at 5 yrs RT + chemo vs RT alone absolute benefit 4% at 5 yrs (Cisplatin based)