Lung cancer

Question 1

What is the definition of lung cancer and what are the different cell types?

Answer 1

Cancer is when cells grow uncontrollably, if cancer starts in the lungs this primary cancer is called lung cancer. If its spreads from another part of the body and spreads to lungs this is called secondary lung cancer. The different cell types are Squamous (30%), Adenocarcinoma (30%), small cell (25%) and large cell ( 15%).

Question 2

Briefly describe the epidimeology of lung cancer?

Answer 2

Lung cancer is the commonest fatal malignancy for both men and women in the UK and the third commonest cause of death in the UK.

Worldwide, accounting for one million deaths each year. Has a poor prognosis as many types are rapidly growing, aggressive, and have usually metastasised at the time of presentation.

Often presents late because many of the symptoms, such as cough and breathlessness, are non‐specific and common in smokers.

There is no screening programme for lung cancer in the UK. Current studies are evaluating whether screening is feasible, cost‐effective, and likely to reduce mortality.

Question 3

What can lung cancer be divided into?

Answer 3

Small-cell lung cancer (SCLC) (15%) which originates neuroendocrine cells. and non-small cell Lung cancer (NSCLC) (85%).

Question 4

What are the further subdivisions of non-small-cell lung cancer NSCLC?

Answer 4

Lung adenocarcinoma LUAD which originates from alveolar type II epithelial cells.

Lung squamous-cell carcinoma LUSC which originates from basal epithelial cells.

Large-cell Carcinoma LCC which originates from various epithelial cells.

Question 5

What is the aetiology of lung cancer?

Answer 5

1. Active and passive smoking (85-90% of cases)
2. Occupational & Environmental Exposure:
   - Abestos exposure
   - Ionising radiation (radon gas): (background radiation from the ground and rocks)
   - Arsenic
   - Air pollution
   - Polycyclic aromatic hydrocarbons ( chemical in cigarettes)
3. Genetic & Familial Factors
   - Inherited mutations in tumor suppressor genes (e.g., TP53, RB1) and oncogenes (e.g., EGFR, ALK, KRAS) can contribute.
   - Family history of lung cancer
   - Genetics ( variation in ability to metabolise carcinogens)
   Non-smokers more likely to be caused by genetic mutations rather than environmental causes
4. Pre-existing Lung Diseases
   - Chronic obstructive pulmonary disease (COPD)
   - Idiopathic Pulmonary fibrosis
   - Tuberculosis (TB) scars
   Scar carcinoma: tumours can arise from areas of chronic fibrosis
5. Lifestyle & Diet
   - Poor diet (low in fruits and vegetables) → Reduces antioxidant protection against DNA damage.

-Heavy alcohol consumption → May increase lung cancer risk, especially in smokers.

Question 6

What is the pathophysiology of lung cancer?

Question 7

What are the physiological insults for the accumulation of genetic mutations?

Answer 7

Environmental: smoking, uranium, radon and asbestos

Inherited:
- Li fragment syndrome (p53 mutations)
- Polymorphisms in cytochrome P450

Question 8

What are some of the somatic mutations that play a role in one of the causes to lung cancer?

Answer 8

EGFR
ALK
PDL-1
KRAS
ROS-1

Question 9

What are examples of some disease states that lead to the accumulation of genetic mutations?

Answer 9

Fibrosis lung conditions such as pulmonary fibrosis and HPV.

Question 10

What is the initiation of the pathophysiology of lung cancer?

Answer 10

Carcinogens (e.g., cigarette smoke, asbestos, radon, pollution) damage lung epithelial cells.
Mutations occur in tumor suppressor genes (e.g., TP53, RB1) and oncogenes (e.g., KRAS, EGFR, ALK, MYC), disrupting normal cell cycle control.
Cells lose apoptosis (programmed cell death) mechanisms, leading to uncontrolled growth.

Question 11

What does the unregulated cell growth lead to?

Answer 11

• Mutated cells proliferate unchecked, forming dysplastic (abnormal) cells in the bronchial epithelium.
• Angiogenesis (new blood vessel formation) supplies nutrients, supporting tumor expansion.
• Chronic inflammation (e.g., in COPD) contributes to further DNA damage.

Question 12

What is the consequence of tumour formation?

Answer 12

As the tumor grows, it invades deeper lung tissues and spreads (metastasizes) via:

Local Invasion – Tumor extends into adjacent structures (bronchi, pleura, chest wall).

Lymphatic Spread – Cancer cells enter lymph nodes, especially in the mediastinum.

Hematogenous (Blood) Spread – Metastases commonly occur in:

Brain (causing headaches, seizures)

Liver (jaundice, weight loss)

Bones (pain, fractures)

Adrenal glands (asymptomatic in early stages)

Question 13

What does migration, adhesion and invasion of the tumour lead to?

Answer 13

Hyperplasia, metaplasia, dysplasia and carcinoma in situ. The carcinoma can either metastasise or compress/obstruct adjacent structures.

Question 14

Which type of lung cancer can secrete hormones?

Answer 14

Small Cell Lung Cancer (SCLC), can secrete hormones, causing systemic effects:

SIADH (Syndrome of Inappropriate ADH Secretion) → Leads to hyponatremia, confusion, seizures.

Cushing’s Syndrome (excess ACTH) → Causes weight gain, moon face, high blood pressure.

Lambert-Eaton Myasthenic Syndrome (LEMS) → Autoimmune attack on nerve-muscle connections, causing muscle weakness.

Question 15

Briefly describe the pathological classification of SCLC and NSCLC.

Answer 15

NSCLC: Slower-growing, invades locally before spreading. Has the common mutations of EGFR, KRAS, ALK and has a late stage metastatic pattern.

SCLC: Highly aggressive, early metastases. common mutations of TP53, RB1, MYC and has a metastatic pattern of a rapid spread to the brain, liver, bones

Question 16

What are the clinical signs of lung cancer?

Question 17

What are the common symptoms of lung cancer?

Answer 17

Shortness of breath
Chest Pain: excessive coughing
Blood clots: LC raises your risk of blood clots and PE
Drooping eyelids
Hoarsness
Coughing up blood: could mean tumours are present in your airways
Right side abdominal pain: Tumours in the liver or lung lining can cause this pain
Yellow eyes and Skin: Sign of jaundice; cancer can effect liver function
Hacking cough: producing blood tinged sputum
Headaches
Lumps and bumps
Generalised weakness

Question 18

What are the respiratory symptoms of Lung cancer?

Answer 18

Common Respiratory Symptoms

✅ Persistent cough (new or worsening). Longer than 8 weeks.
✅ Hemoptysis (coughing up blood) – Due to tumor invasion of blood vessels.
✅ Dyspnea (shortness of breath) – From airway obstruction, pleural effusion, or lung collapse.
✅ Chest pain – Due to tumor invasion of pleura or chest wall.
✅ Wheezing or stridor – From airway compression.
✅ Recurrent infections (pneumonia, bronchitis) – Due to tumor blocking the airways.

Advanced or Red Flag Symptoms

⚠️ Hoarseness – Due to recurrent laryngeal nerve compression.
⚠️ Superior vena cava (SVC) syndrome – Facial/neck swelling, dilated veins (tumor pressing on SVC).
⚠️ Pancoast tumor symptoms – Shoulder pain, Horner’s syndrome (ptosis, miosis, anhidrosis).

Cervical or supraclavicular lymphadenopathy

Question 19

What are the systemic symptoms of lung cancer?

Answer 19

✅ Unintentional weight loss – Due to cancer-related metabolism changes.
✅ Fatigue & weakness – Caused by cancer progression or anemia.
✅ Loss of appetite – Common in advanced disease.
✅ Fever & night sweats – Can indicate infection or malignancy.

Question 20

What are the clinical signs of lung cancer?

Answer 20

Cachexia
Clubbing
Hoarseness
Tachypnoa
Horner’s Syndrome
Cervical lymphadenopathy
Wheezing or stridor – From bronchial narrowing.
Reduced breath sounds, dullness on percussion – Suggests pleural effusion or lung collapse.

Question 21

What are pancoast tumours?

Answer 21

A Pancoast tumour isa rare form of lung cancer. This type of tumor is located at the very top (apex) of the right or left lung. As the tumor grows, it can invade surrounding nerves, muscles, lymph nodes, connective tissue, upper ribs, and upper vertebrae. This causes severe pain in the shoulder and arm.
This relates to invasion of the brachial plexus from which its other name arises - superior sulcus tumour. Most are non-small cell lung cancers (NSCLC), especially squamous cell carcinoma or adenocarcinoma.

Question 22

What are the key features of Pancoast tumours?

Answer 22

Severe shoulder pain – Most common early symptom, radiating to the arm.

Arm/hand weakness & numbness – Due to brachial plexus involvement.

Horner’s Syndrome (if sympathetic chain is affected):

• Ptosis (drooping eyelid).
• Miosis (constricted pupil).
• Anhidrosis (loss of sweating on one side of the face).

Rib destruction or chest wall pain – From bone invasion.

Question 23

What causes Hemoptysis?

Answer 23

Haemorrhage from tumour in airways

Question 24

Why does lung cancer have a poor prognosis?

Answer 24

Lung cancer has a poor prognosis because patients often present late with evidence of local or distant metastases.
This may be because neither the patient nor the doctor is alert to the common symptoms of lung cancer, which are often non‐specific.
Currently there is no screening programme to detect lung cancer early. Other factors resulting in low survival rates for lung cancer in the UK include poor surgical rates of only 15%.
Patients with lung cancer also have significant co‐morbidities which often preclude radical treatment.

Question 25

How is suspected lung cancer managed on Initial Assessment?

Answer 25

To improve early referral, diagnosis, and treatment, patients with symptoms or signs suggestive of lung cancer must be referred as a two‐week rule (TWR) to the respiratory team. The patient must be seen by a consultant respiratory physician within 14 days of referral. Have all investigations completed within 28days of referral. Be discussed at the lung cancer multidisciplinary team (MDT) meeting and have treatment within 62days of the original referral. These timeframes are likely to reduce in the next few years.

Question 26

When is an urgent X-ray (within 2 weeks) considered to assess for lung cancer?

Answer 26

In people 40+ with any one of the following: Persistent or recurrent chest infection Finger clubbing Supraclavicular lymphadenopathy or persistent cervical lymphadenopathy Chest signs consistent with lung cancer Thrombocytosis

Question 27

What are the CXR appearances of concern for suspected lung cancer?

Answer 27

Mass Lobar collapse Solitary pulmonary nodule (SPN) Lymphadenopathy Pleural effusion Unilateral raised hemidiaphragm Persistant consolidation (an area of lung opacity seen on a chest X-ray (CXR) that does not resolve after appropriate treatment (e.g., antibiotics for pneumonia) and remains visible beyond 6 weeks.) Repeat CXR after 6 weeks if consolidation persists. If the CXR or clinical judgment suggests lung cancer, patients should be urgently referred to a specialist, typically within two weeks, for further evaluation.

Question 28

What is the purpose of investigation?

Answer 28

Purpose of investigation are to diagnose/confirm diagnosis Establish histological cell type Define extent of the disease

Question 29

What are the investigations that are carried out?

Answer 29

1. Blood tests – tumour markers (CEA) 2. Radiological imaging: - X-ray, CT, USS, Radionucleotide bone scan - An urgent CT scan of the chest, extending to the upper abdomen, should be performed before any biopsy to assess the tumor's size, location, and potential spread. 3. Bronchoscopy: - Inspect intrabronchial portion of tumour and Biopsy if possible - Obtaining a tissue sample is crucial for confirming the diagnosis and determining the cancer subtype. - Bronchial washings – collect cells Cytology : – examination of sputum, bronchial washing/brushing

Question 30

When is a PET-CT required for suspected lung cancer investigation?

Answer 30

Recommended for patients being considered for curative treatment to evaluate both local and distant disease spread.

Question 31

What is non small lung cancer staging?

Answer 31

To find out extent of spread: Tumour Regional lymph Nodes Distant Metastasis TNM is the pneumonic Tumor, Node, Metastasis system

Question 32

What is the NSCLC TNM staging classification?

Answer 32

NSCLC TNM Staging: T (Tumor) – Size & Spread: T1 – ≤3 cm, confined to the lung. T2 – 3-5 cm or involves main bronchus/pleura. T3 – 5-7 cm or invades chest wall/diaphragm. T4 – >7 cm or invades mediastinum/trachea. N (Nodes) – Lymph Node Involvement: N0 – No lymph node spread. N1 – Nodes in same lung. N2 – Nodes in mediastinum. N3 – Nodes in opposite lung or supraclavicular. M (Metastasis) – Distant Spread: M0 – No metastasis. M1a – Spread to opposite lung or pleural effusion. M1b – Single distant metastasis. M1c – Multiple distant metastases.

Question 33

What happens when the lung tumour metastasises from the primary site of cancer?

Answer 33

The development of secondary malignant growths at a distance from a primary site of cancer. Through : Chest Wall leads to chest/rib pain Pleura leading to pleural effusion Lymphatic system -> most notable with supraclavicular lymphadenopathy Blood -> systemic Liver – hepatomegaly /jaundice Bone – fractures, bone pain, anaemia and hypercalcaemia Adrenals – Addisons - lack of steroid hormones Brain – personality change, new onset headaches, seizures With metastasis the presentations may be different

Question 34

How is small cell lung cancer staged?

Answer 34

The majority of SCLC present with evidence of metastases. If the disease is confined to the thorax, then it is staged as “limited” if there is evidence of spreading outside the thorax, then it is staged as “extensive”.

Question 35

What the current lung cancer treatment options?

Answer 35

Surgery: Recommended for patients with early-stage non-small-cell lung cancer (NSCLC) to remove tumors. Chemotherapy: Utilized for various stages of lung cancer, either alone or in combination with other treatments, to improve survival and quality of life. Radiotherapy: Applied to shrink tumors, alleviate symptoms, or as an adjuvant treatment post-surgery. Immunotherapy: Offered to patients with specific tumor characteristics, such as high PD-L1 expression, to enhance the body's immune response against cancer cells. Targeted Therapy: Prescribed for tumors with identifiable genetic mutations (e.g., EGFR mutations), using drugs like osimertinib to inhibit cancer cell growth.

Question 36

What is Neoadjuvant therapy?

Answer 36

Neoadjuvant therapy refers to treatment given before the main treatment (typically surgery) to shrink a tumor or improve surgical outcomes. In the context of lung cancer, it is commonly used to treat non-small cell lung cancer (NSCLC).

Question 37

What is the purpose of Neoadjuvant therapy?

Answer 37

Tumor Shrinking: Reduce the size of the tumor to make it easier to remove surgically. Improve Surgical Outcomes: Increase the chances of successful surgery by reducing the risk of cancer spread. Potential for Better Prognosis: In some cases, it may reduce the likelihood of cancer recurrence.

Question 38

What are the types of Neoadjuvant Therapy in Lung Cancer?

Answer 38

Chemotherapy: Given to shrink the tumor before surgery. Radiotherapy: May be used in certain cases to target localized tumors. Targeted Therapy: In specific cases, used for tumors with genetic mutations (e.g., EGFR). Immunotherapy: Sometimes used if the tumor is responsive to immune checkpoints.

Question 39

When is Neoadjuvant Therapy Used?

Answer 39

Stage II or III NSCLC where surgery alone may not be sufficient. Tumors that are locally advanced and not initially resectable.

Question 40

What's Adjuvant therapy?

Answer 40

refers to treatment given after the primary treatment (usually surgery) to help reduce the risk of cancer recurrence and improve overall survival outcomes. The goal is to eliminate any remaining cancer cells that may not have been removed during surgery.

Question 41

What is the Purpose of Adjuvant Therapy?

Answer 41

Prevent Recurrence: Help eliminate any remaining cancer cells after surgery. Improve Survival: Lower the risk of cancer returning by targeting microscopic disease. Target Undetected Metastasis: Treat small cancer deposits that are not visible but might spread in the future.

Question 42

When is Adjuvant Therapy Used?i

Answer 42

After surgical resection of tumors, especially in cases where there is a risk of cancer recurrence. For Stage II or III NSCLC or SCLC to prevent the cancer from coming back.

Question 43

What is the current treatment paradigm for NSCLC for early stage disease?

Answer 43

Surgical Intervention: Primary treatment involves surgical resection, such as lobectomy, to remove the tumor. Adjuvant Therapy: Post-surgery, chemotherapy may be administered to eliminate residual cancer cells and reduce recurrence risk.

Question 44

What is the current treatment paradigm for NSCLC for locally advanced disease?

Answer 44

Multimodal Approach: Combines chemotherapy, radiotherapy, and possibly surgery to manage the tumor effectively. Immunotherapy: Agents like durvalumab are used post-chemoradiotherapy to enhance the immune response against cancer cells.

Question 45

What is the current treatment paradigm for NSCLC for advanced or metastatic disease?

Answer 45

Targeted Therapy: For tumors with specific genetic mutations (e.g., EGFR, ALK), targeted drugs like osimertinib are employed to inhibit cancer growth. Immunotherapy: Drugs such as pembrolizumab or nivolumab boost the immune system's ability to attack cancer cells. Chemotherapy: Used when targeted or immunotherapies aren't suitable, aiming to control disease progression and alleviate symptoms.

Question 46

What is the current management of small cell lung cancer at the limited stage of disease?

Answer 46

Adjuvant chemotherapy Stereotactic body radiotherapy Combination radiation therapy and chemotherapy

Question 47

What is the current management of small cell lung cancer at the extensive stage of disease?

Answer 47

Combination of radiation therapy and chemotherapy Immunotherapy

Question 48

What is the current management of small cell lung cancer at the second line stage of disease?

Answer 48

Hycamtin (belongs to a class of drugs called topoisomerase I inhibitors, which work by preventing cancer cells from repairing their DNA, leading to cell death.) Repeating chemotherapy Immunotherapy drugs

Question 49

What are the side effects of chemotherapy?

Answer 49

Brain fog or chemo brain Anxiety and depression Hair loss Hot flashes and menopause Weak heart Nausea and Vomting Discoloured and cracked nails Loss of appetite Sexual dysfunction Digestive distress Lower blood cell count Mouth sores Red Urine Osteoporosis Tired and achy muscles Swollen hands and feet Decreased urination

Question 50

What are the drug treatments that are considered for patients with lung cancer?

Answer 50

Analgesia –codeine, morphine, (WHO step ladder for pain relief management) Corticosteroids Antiemetics Cough linctus (codeine) : Recommended as an anti-tussive for a non productive cough by oral administration. The usual dosage for adults is 5 to 10 ml, 3 to 4 times daily. Dosage should be reduced in elderly or debilitated patients. (cough suppressants) Bronchodilators Antidepressants – fluoxetine, prozax, sertraline Diet

Question 51

What is the end of life treatment considered for patients with lung cancer?

Answer 51

Palliative treatment, which focuses on the relief of symptoms, is the only option for most patients with SCLC and many with NSCLC. Symptoms that can be managed effectively include pain, breathlessness, nausea, constipation, anxiety, and insomnia. Also offer psychological and emotional support to the patient and their family. They can refer the patient to the occupational therapist, physiotherapist, and social services. They can offer support and discussion about where the patient wishes to spend the last days of their life and where they wish to die, whether in a hospital, hospice or at home with appropriate support