1
Q

Survival rate of lung cancer

A

Very low, 1 and 5 year survival.

Due to patients presenting late with advanced stages.

Symptoms are also very similar to those who already smoke.

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2
Q

Causes of lung cancer

A

90% caused by smoking.

Lung cancer deaths in women increasing despite those in men decreasing.

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3
Q

General Symptoms

A

Usually in smoker >20 years

Respiratory:
Cough
Haemoptysis (red flag)
Dyspnoea
Wheeze
Chest pain (more advanced stage)
Hoarseness
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4
Q

Common systemic and metastatic symptoms

A

Weight loss

Anorexia, nausea

Malaise

Fatigue

Secondary site: CNS, bone and skin (i.e pain and masses).

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5
Q

Paraneoplastic syndromes

A

Hyponatremia

Hypercalcaemia

Less commonly: itching, gynaecomastia.

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6
Q

Sub-types of lung cancer

A

Non-small cell:
Squamous- central, cavitation, hypercalcaemia.

Adenocarcinoma: peripheral lung, more common in non-smokers.

Small cell:
central
early lymphatic spread.

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7
Q

Common signs of lung cancer seen in examination

A

Clubbing

Cachexia- muscle wasting

Supraclavicular/ cervical lymphadenopathy

Stridor

Lung collapse/ pleural effusion.

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8
Q

Investigations to confirm diagnosis and determine tumour type/ extent

A

CT

Biopsy:

  • Bronchoscopy.
  • Endobronchial ultrasound- needle aspiration.
  • Percutaneous CT thorax
  • P eripheral lymph node/liver

Complete staging:
PET scanning- glucose analogue shows areas of high uptake, locates cancer.

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9
Q

Staging in lung cancer

A

Takes into account:

  • Tumour size
  • Involvement of any local structures and invasion
  • Lymph/ blood metastases.

TNM staging
T- size and invasion
N- nodal stage
M- metastasis

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10
Q

Surgery non small cell lung cancer

A

Considered in all patients with stage 1/2

Lobectomy or even pneumonectomy (whole lung removal)

Radical radiotherapy with or without chemotherapy- given to stage 1/2 who are not fit enough/ unwilling to do surgery.

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11
Q

Palliative radiotherapy- in NSCLC

A
Relieves symptoms like:
- haemoptysis
- Intractable cough
- Dyspnoea
 but not expected to cure.
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12
Q

Small cell lung cancer treatment

A

Chemotherapy is primary- more effective than in NSCLC

Controls symptoms and can induce remission

Prolongs survival by months

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13
Q

Small cell carcinoma

A

Accounts for 10-15% of lung cancers.

Present very darkly in microscope as they are mainly nucleus.

Little cytoplasm

Salt and pepper chromatin in nuclei.

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14
Q

Squamous cell carcinoma

A

Central origin

Cigarette smoke stimulates squamous metaplasia then dysplasia of bronchial epithelium.

Accounts for 20-30% of NSCC- second most common type

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15
Q

Adenocarcinoma

A

Most common type of non-small cell carcinoma- around glands

Typically happen at periphery of the lung.

Fibrotic: the cells make fibrotic protein

Tissues can be stained to look for specific proteins: TTF1 most typical.

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16
Q

Mutations targeted in adenocarcinoma

A

Key mutations in adenocarcinoma:
EGFR
ALK
PD1/ PD-L1

These mutations are targeted with specific agent.

New treatment that can be used to treat adenocarcinomas.

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17
Q

Spread of lung cancer

A

Local and direct:
Adjacent lung
Pleura and pleural cavity.

Lymphatic:
Pulmonary lymphatics
Lymph nodes- hilar and mediastinal.

Systemic:
Liver
Bone
Brain
Adrenal
18
Q

Erlotinib

A

Tyrosine kinase inhibiting agent that targets epidermal growth factor receptor mutations (EGFR)

19
Q

Gefitinib

A

Tyrosine kinase inhibiting agent that targets epidermal growth factor receptor mutations (EGFR)

20
Q

Why are survival rates for lung cancer so poor?

A

Patients present late with advanced stage lung cancer

Due to early symptoms being similar to those who smoke.

21
Q

Hyponatraemia

A

Increased retention of sodium in the blood.

This is a paraneoplastic syndrome in small cell carcinoma due to SIADH- increased secretion of ADH.

22
Q

Hypercalcaemia

A

Too much calcium in the blood.

A paraneoplastic symptom in in sqaumous cell carcinoma.

Caused by an increase in Parathyroid hormone activity.

23
Q

Associations linked to lung cancer

A

Smoking

Fibrosing alveolitis

Ionising radiation

Air pollution

Chromium

Iron oxide

Nickel

Mesothelioma

24
Q

Surgical considerations for lung cancer

A

The operative mortality

Cardiovascular morbidity

Effect on lung function

Post-op quality of life

Post-op radiotherapy?

Chemotherapy?

The actual surgical approach?

25
Q

The three types of resection in lung cancer

A

Wedge resection- remove small part of a lobe.

Lobectomy

Pneumonectomy

26
Q

Effects of ionising radiation (seen in radiotherapy)

A

Double/ single strand DNA break.

Base damage

Cross links between DNA, proteins and strands.

Cell death

27
Q

Chromosomal breaks

A

Can be caused by ionising radiation.

Causes early apoptosis

28
Q

Chromosomal aberrations

A

Abnormal structure of chromosomal that can be caused by radiotherapy.

This causes:
Mitotic death
Reproductive death
Late apoptosis.

29
Q

Radical treatment options for locally advanced lung cancer

A

Cancer treatments with aims to cure rather than palliate.

Options:

  • Radiotherapy +/- chemotherapy.
  • Chemo, radiotherapy + surgery.
  • Chemo + consolidation radiotherapy (small cell)
30
Q

Radiation pneumonitis

A

Lung disease that is induced by radiation- i.e radiotherapy

Fibrosis can occur in the late stage of the disease

31
Q

Palliative chemotherapy

A

Chemotherapy with aims of reducing symptoms, not curing.

Increases survival by around 8 months in NSCLC.

In limited stage SCLC, increases survival by 16-24 months.
In extensive stage- 6-12 months.

32
Q

Uses of palliative radiotherapy

A

Uses to relieve symptoms associated with lung cancer metastasis:

Bone pain
Spinal cord compression
SVC obstruction- stent placed
Brain metastasis
Haemoptysis.
33
Q

Personalised therapy for palliative care

A

Creating therapy based on tumour gene expression.

Mutations targeted- i.e EGFR, ALK

34
Q

EGFR inhibitor

A

Cancer therapy used to target EGFR mutations.

Can be:
Tyrosine-kinase inhibitors
Antibodies specific to EGFR

35
Q

Immunotherapy for lung cancer

A

Immune checkpoint inhibitors:
- PD-L1 antibodies. Prevent immune response from being suppressed. Used for NSCLC.

  • Nivolumab
  • Pembrolizumab

Therapeutic vaccines- stimulate the body to attack tumour specific antigens.

36
Q

Nivolumab

A

Immune checkpoint inhibitor that is used in squamous cell carcinoma

Used second line

37
Q

Pembrolizumab

A

Immune checkpoint inhibitor used for lung cancer.

38
Q

The normal immune surveillance of a tumour

A
  1. Tumours contain antigens which are presented by dendritic cells.
  2. This activates T-cells in the lymph node- produces CD4 and CD8
  3. CD4 help to further activate CD8 cells which release chemicals to kill tumour.
    Includes perforin, granzyme, IFN-gamma.
39
Q

PD-L1 on tumours

A

PD-L1 is a co-inhibitory molecule that decreases T-cell mediated responses

Allows tumour to evade immune system

40
Q

Co-stimulatory molecules

A

Found on antigen presenting cells- promote immune response in T cells.

Examples:
CD80/86
CD28

41
Q

Co-inhibitory molecules

A

Dampen T cell-mediated responses- avoids damaging the body during infections.

Examples:
CTLA-4 + PD-I (receptors)
PD-L1/2- on APCs

42
Q

Neo-adjuvant chemotherapy

A

Chemotherapy taken before surgical tumour resection.

Examples: gemcitabine and carboplatin.