Lung Cancer

Question 1

Prevalence of lung cancers

Answer 1

3rd most common cancer
Leading cause of cancer death
Age around 75-90
Males more likely to get
10-15% of pt never smoked

Question 2

Causes of lung cancer other than smoking

Answer 2

Asbestos-exposure to plumbers carpenters for example which increases risk by 2-
Radon-eg silver miners
Indoor cooking fumes eg wood,smoke
Chronic lung disease eg COPD/fibrosis
Air pollution
Familial/genetic

Question 3

Pathogenesis

Answer 3

May arise from differentiated and undifferentiated cells

Interaction between inhaled carcinogens and epithelium of upper and lower airways causes DNA adducts to form (pieces of dna covalently bound to a cancer causing chemical)

Persisting dna adducts causes mutation and genomic alterations

Question 4

Types of lung cancer

Answer 4

Squamous cell carcinoma-oginiates from bronchial epithelium,centrally located

Adenocarcinoma-originates rom mucus producing glandular tissue so more peripherally located. From low tar cigarette which are more deeply inhaled and retained

Large cell lung cancer-heterogeneous group,undifferentiated

Small cell lung cancer-originate from pulmonary neuroendocrine cells and is highly malignant

1-3 are non small cell lung cancer (NSCLC)

Question 5

Oncogenes involved

Answer 5

EGFR tyrosine kinase-causes adenocarcinoma more so in women of Asian ethnicity and never smokers

Anaplastic lymphoma kinase (ALK) tyrosine kinase-non small cell lung cancer in younger patients and never smokers

c-ROS oncogene 1 (ROS1) receptor tyrosine kinase-non small lung cancer in younger patients and never smoked

BRAF (downstream xell cycle signal mediators)-non small cell lung cancer esp in smokers

Question 6

Symptoms

Answer 6

Cough
Weight loss
Breathlessness
Fatigue
Chest pain
Haemoptysis
Or asymptomatic

Question 7

Features of metastatic disease

Answer 7

Neurologist features:focal weakness,seizures,spinal chord compression

Bone pain
Paraneoplastic syndromes eg clubbing,hypercalcaemia,hyponaetraemia,cushings

Question 8

Signs

Answer 8

Clubbing
Horners syndrome
Superior vena cava obstruction (pembertons sign)
Cachexia

Question 9

Diagnostic strategy

Answer 9

Establish most likely diagnosis
Establish fitness for investigation and treatment
Confirm diagnosis and histology’s
Confirm stage

Question 10

Lung cancer screening

Answer 10

Current or ex smokers aged 55-74 invited

Question 11

What imaging is most useful to exclude occult metastasis

Answer 11

PET-CT

Question 12

Biopsy

Answer 12

Bronchoscopy-for tumours of central and segmental airways

Endobronchial ultrasound and transbronchial needle aspiration of mediastinal lymph nodes-to stage mediastinum

Navigational bronchoscopy and robotic sronchoscopy-for peripheral lesions/nodules that aren’t amenable to
conventional bronchoscopy or ct

Ct guided lung biopsy-to access peripheral lung tumours

Question 13

Staging

Answer 13

T1-4 tumour size and location

N0-3 lymph node involvement mediastinum and beyond

M0-1c metastasis and number

Question 14

Determinant of treatment

Answer 14

Patient fitness
Cancer histology
Cancer stage
Patient preference
Health servuce

Question 15

Patient fitness

Answer 15

0-asymptomatic (fully active to carry on all pre disease activity)
1-symptomatic but complete ambulatory (restricted in physical strenuous activity but able to do light or sedentary work
2-symptomatic and about >50% of waking hours (ambulatory and able to self care but can’t do work activities)
3-symptomatic confined to bed or chair >50% waking hour (limited self care)
4-completely disabled (can’t do self care,confined to bed)
5-death

Radical treatment restricted to PS0-2

Question 16

Surgery

Answer 16

Standard for early stage disease
Lobectomy and lymphadenoctom
Sublobar resection if stage 1 <3cm

Question 17

Radical radiotherapy and

Answer 17

Alternative to surgery for early disease
Stereotactic ablative body radiotherapy (SABR)
Technique of choice
High precision targeting multiple convergence beams

Question 18

Systemic treatments oncogene directed

Answer 18

EGFR-erlotinib,gefitinib,afatinib,dacomitiniv,osimertinib
ALK-critonizib,ceritinib,alectinib,brigatinib,lorlatinjb,
ROS-
Critozinjb,entrectinib

Cause little side effects but can get diarrhea,rash or pneuomoitis (rare)

Question 19

2b immunotherapy’s

Answer 19

First line for metastatic NSCLC with no mutation
Pemprolizumab,atezolizumab,nivolumab
Efficacy-improvement in progression free survival and overall survival
Side effects are well tolerated ,immune related usually (thyroid,skin,bowel,lung and liver)
Is an anti pdl-1 drug which reactivates the immune system

Question 20

3 cytotoxic chemo

Answer 20

First line for metastatic NSCLC
long established-targets rapidly dividing cells,platiunum based regiments eg carboplatin,cisplatin,paclitaxel,pemetrexed
Modest improvement in survival
Side effects-frequent causes fatigue,nausea,bone marrow suppression,nephrotoxicty
Quality of life poorly evaluated/no improvement

Question 21

Palliative and supportive care

Answer 21

Should be offered to all patients with advanced stage disease

Question 22

Summary of treatment

Answer 22

Early stage use surgery or radiotherapy with curative intent

Locally advanced stage involving thoracic lymph nodes do surgery and adjuvants chemo/radio

Metastatic disease use tyrosine kinase inhibitors. No mutation PDL-1 positive DI immunotherapy alone but if PDL-1 negative do standard chemo and immunotherapy

Question 23

PDL-1

Answer 23

Binds to PD-1 receptor on the t cell to turn it off so can’t destroy cancer cells