Lung Cancer Flashcards
How common is lung cancer?
- 3rd most common (UK)
- leading cause of cancer death
- 48000 diagnoses per year
- 35000 deaths per year
- 10-15% never smoked
Who is most likely to have lung cancer?
- 75-90yrs old
- males
- low socioeconomic status
- smoking
What are the causes of lung cancer?
- smoking
- passive smoking
- asbestos (x2)
- radon
- indoor cooking fumes
- chronic lung disease (COPD, Fibrosis)
- Immunodeficiency
- genetics/family history
What are the 4 different types of lung cancer?
- squamous cell carcinoma
- adenocarcinoma
- large cell lung cancer
- small cell lung cancer
What is squamous cell carcinoma?
- 30% of cases
- originates in bronchial epithelium
- centrally located
- used to be the most common
What is adenocarcinoma?
- 40% of cases
- possible link to low tar cigarettes which are inhaled more deeply
- originates from mucus producing glandular tissue
- located peripherally
What is large cell lung carcinoma?
- 15%
- heterogenous composition
- large pleomorphic cells
- peripherally located
- originated from epithelial cells
What is small cell lung cancer?
- 15%
- originates at pulmonary neuroendocrine cells
- highly malignant
- centrally located
What cancers make up Non-Small Cell Lung Cancer?
- squamous cell carcinoma
- adenocarcinoma
- large cell lung cancer
What histology can be seen in early lung cancer development?
hyperplasia, followed by squamous metaplasia
What histology can be seen in intermediate lung cell cancer development?
dysplasia
What histology can be seen in late lung cell cancer development?
carcinoma in situ followed by an invasive carcinoma
What is metaplasia?
reversible change in which one adult cell type replaced by another adult cell type; adaptive
What is dysplasia?
abnormal pattern of growth in which some of the cellular and architectural features of malignancy are present; pre-invasive stage with INTACT basement membrane
What is an oncogene?
genetic mutations that predisposes someone to a particular cancer, important to inform treatment/prevention
What is impact of Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase mutation?
- 15-30% adenocarcinoma seen in: - women - asian ethnicity - never-smokers
What is the impact of Anaplastic Lymphoma Kinase (ALK) Tyrosine Kinase mutation?
- 2-7% of non-small cell lung cancer
seen in: - youth
- never-smokers
What is the impact of a mutation in c-ROS Oncogene 1 (ROS-1) Receptor Tyrosine Kinase?
- 1-2% of non-small cell lung cancer
seen in: - youth
- never-smokers
What is the impact of a mutation in BRAF (downstream cell-cycle signalling mediator)?
- 1-3% of non-small cell lung cancer
seen in: - smokers
What are the key symptoms of lung cancer?
- cough
- weight loss
- breathlessness
- fatigue
- chest pain
- haemoptysis
OFTEN ASYMPTOMATIC
What are the features of advanced/metastatic disease?
neurological features - focal weakness - seizures - spinal cord compression bone pain paraneoplastic syndromes: - clubbing - hypercalcaemia - hyponatraemia - cushing's
What are the common signs seen with lung cancer?
- clubbing
- cachexia
- Horner’s syndrome
- Pemberton’s sign
What is the most useful form of imaging to see occult metastases?
PET scan
What types of imaging are used to diagnose lung cancer?
- Chest x-ray
- Staging CT (chest+abdomen)
- PET scan
When should a bronchoscopy be used in lung cancer?
- tumours of the central airway
- no need for tissue staging
How do you choose the method of primary biopsy?
Choose based on:
- accessibility
- availability
- impact on staging
What is the aim of an Endobronchial US and Transbronchial-needle aspiration of the mediastinal lymph nodes?
stage mediastinum +/- achieve tissue diagnosis
Why would you do a CT-guided lung biopsy?
to access peripheral lung tumours
What does T1-4 represent in staging?
tumour size and location
What does N0-3 represent in staging?
lymph node involvement - mediastinum and beyond
What does M0-1c represent in staging?
metastases and the number of them
What are the determinants of treatment?
- patient fitness
- cancer histology
- cancer stage
- patient preference
- health service factors
What are the different classifications in the WHO performance status?
0 - Asymptomatic
1 - Symptomatic, completely ambulatory
2 - symptomatic, < 50% in bed during the day
3 - symptomatic, >50% in bed, not bedbound
4 - bedbound
5 - death
Which WHO performance statuses is radical treatment restricted to?
PS 0-2
What should also be taken into account with the WHO performance status?
- comorbidity
- lung function
What is the standard of care for early stage lung cancer?
- surgical resection
- radiotherapy with curative intent
What is the most common surgical resection done in lung cancer?
lobectomy (+/-) lymphandectomy
What is the surgical resection done if the cancer is stage I (<3cm)?
sublobar resection
What is a wedge resection?
- removal of a small part of the lung
- removes tumour + a margin of healthy tissue
What is a segmental resection?
removing a large part of the lung, but NOT an entire lobe
What is a pneumonectomy?
removal of an entire lung.
What is an alternative to surgery for early stage lung cancer due to comorbidities?
radical radiotherapy
What is Radical Radiotherapy?
Stereotactic Ablative Body Radiotherapy (SABR)
- high precision targeting
- multiple, convergent beams
What is the first line treatment for metastatic non-small cell lung cancer with mutation?
Oncogene-directed treatments
What is treatment of Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase mutation?
- tyrosine kinase inhibitors
- erlotinib
- gefitinib
- afatinib
- dacomitinib
- osimertinib
What is the treatment of Anaplastic Lymphoma Kinase (ALK) Tyrosine Kinase mutation?
- crizotinib
- ceritinib
- alectinib
- brigatinib
- lorlatinib
What is the treatment of a mutation in c-ROS Oncogene 1 (ROS-1) Receptor Tyrosine Kinase?
- cirzotinib
- entrectinib
What is the efficacy of oncogene-directed treatment?
- increase progression-free survival
- modest overall survival when compared to chemotherapy
What are the side effects on oncogene-directed treatment?
- generally well tolerated (tablets)
- rash
- diarrhoea
UNCOMMON: - pneumonitis
How does immunotherapy to treat lung cancer work?
blocks PD-L1/PD-1 to allow T-cell killing of the cell
What is the first line treatment for NSCLC with NO mutation (PDL1>50%)?
immunotherapy
- prembrolizumab
- atezolizumab
- nivolumab
What is the efficacy of immunotherapy?
greater progression-free survival and overall survival in comparison to chemotherapy
What are the side effects of immunotherapy?
- generally well tolerated
- (10-15%) immune-related side effects (thyroid, skin, bowel, lung and liver)
What is the first line treatment for metastatic NSCLC with NO mutation and PDL1 <50%?
cytotoxic chemotherapy (+ immunotherapy)
What is cytotoxic chemotherapy?
- targets rapidly dividing cells by interfering with RNA and DNA synthesis
- long established
- paltinum-based regimens (carboplatin, cisplatin, paclitaxel, premetrexed)
What is the efficacy of cytotoxic chemotherapy?
- modest survival improvements when used alone
- significantly better when combined with immunotherapy
What are the side effects of cytotoxic chemotherapy?
- fatigue
- nausea
- bone marrow suppression
- nephrotoxicity
- poor quality of life
What is palliative and supportive care?
- symptom control
- psychological support
- education
- practical and financial support
- end-of-life planning
When is palliative care given?
all patients with advanced stage disease
What is key for successful palliative care?
lung cancer specialist nurses
What is the impact of palliative care (+standard oncology care)?
- improved quality of life
- lower depression scores
- increased survival (2.5 months)
What is the expected treatment of locally advanced treatment (involving thoracic lymph nodes)?
- surgery and adjuvant chemotherapy
- radiotherapy and chemotherapy (+/- immunotherapy)
What is the treatment for metastatic lung disease with a targetable mutation?
- tyrosine kinase inhibitor
- palliative care
What is the treatment for metastatic lung disease with NO mutation, PDL-1 positive (>50%)?
- immunotherapy, ALONE
- palliative care
What is the treatment for metastatic lung disease with NO mutation, PDL-1 negative (<50%)?
- immunotherapy + chemotherapy
- palliative care
What is the prognosis of lung cancer?
- only 10% live longer than 10 years
- little change in the last 40 years
What is the pathogenesis of lung cancer?
- can arise from differentiated or undifferentiated cells
- inhaled carcinogens lead to DNA adducts in the epithelium of the upper and lower airways
- persisting DNA adducts cause genomic alterations
What is a DNA adduct?
pieces of DNA covalently bound to a cancer-causing chemical
What is this sign?
Clubbing
What is this sign?
Cachexia (loss of muscle mass)
What is this sign?
Horner’s syndrome
What is this sign?
Pemberton’s sign (superior vena cava obstruction)
How does prognosis change with stage?
The later the stage at diagnosis the shorter the survival
How does prognosis change with performance status?
The better the performance status the longer the survival
Who is part of the lung cancer MDT?
- Patient
- respiratory
- radiology
- pathology
-thoracic surgery - oncology
- palliative care
What is the diagnostic strategy for 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
What sort of imaging is this?
Chest X-ray
What sort of imaging is this?
Staging CT (chest and abdomen)
What sort of imaging is this?
PET-CT
