Big 4 - Lung Cancer Flashcards
What is the prevalence of lung cancer?
What are the outcomes usually like?
It is reasonably common - accounts for 13% of all cancers but 21% of all cancer deaths
It has poor outcomes with a 5% 10-year survival - this is mainly because it presents at more advanced stages
What gender / age range tends to be affected by lung cancer?
- it is more commonly seen in men, but trends are increasing for both genders
- it is a cancer of the elderly population - takes off around 60 but peak is at 80-85
Are the number of lung cancer cases increasing or decreasing?
- lung cancer cases in men are decreasing (blue line)
- lung cancer cases in females are becoming more common (pink line)
When does lung cancer tend to present?
How does this affect survival?
lung cancer tends to present at an advanced stage - stage IV, followed by III
survival is highest for the earlier stages and lower for stage IV
How is lung cancer associated with socioeconomic deprivation?
it is linked with deprivation
What type of cancer are the majority of lung cancers?
How does smoking affect this?
- most lung cancers are non-small cell carcinomas (NSCC)
these may be adenocarcinomas, large cell carcinomas or squamous cell carcinomas
- smoking is the largest risk factor for ALL lung cancers
- adenocarcinoma has the largest proportion of non-smokers affected
- it is very rare to see small cell cancer (SCC) in a non-smoker
How has the histology of the most common lung cancer changed with smoking habits?
- squamous cell carcinoma was originally the most common sub-type
- adenocarcinoma has become more common after introduction of fine filter cigarettes
- this allows for smaller particles to be deposited within the alveoli
How does lung cancer typically present?
- cough
- breathlessness
- haemoptysis
- chest pain
- weight loss
- bone pain
- RUQ pain
- headaches / nausea / neurological signs
Why is it concerning when someone presents with symptoms of lung cancer?
symptoms only tend to appear in advanced disease which is difficult to treat
Why is haemoptysis a particularly concerning sign in lung cancer?
- it shows that the cancer is sitting very centrally
- the cancer may not be advanced, but is likely to be a T3/T4 lesion that may not be suitable for surgery
What localised therapies may be used in lung cancer?
surgery or radiotherapy
radiotherapy can be curative or palliative
What systemic therapies can be used in lung cancer?
- chemotherapy
- immunotherapy
- targeted therapy
these are NOT curative when used on their own
used palliatively or as an adjunct to localised therapies
What are the typical symptoms of a Pancoast (apical) tumour?
- ptosis (drooping of the eyelid)
- meiosis (constriction of the pupil)
- anhidrosis
- pain / numbness / tingling in the ipsilateral arm
- weakness of the small muscles in the ipsilateral hand
Why is it important to determine comorbidities and performance status of a patient?
- performance status (how well a patient can perform ADLs without assistance) tells you how aggressive you can be with treatment
- some treatments can be contraindicated with other medical conditions
Can you stage lung cancer from a CXR?
- CXR allows you to estimate the stage, but you cannot know this for sure without an image of the abdomen
Before deciding on how to treat a patient, what do you need to know?
- the intent of the treatment - curative or palliative?
- the stage of the disease - is there nodal or metastatic disease?
If a fit patient has locally advanced cancer (no spread), what is the usual treatment approach?
trimodality treatment
- this involves neoadjuvant chemoradiation followed by surgery
- this allows for downsizing of the tumour prior to surgery
- if surgery is not possible (e.g. brachial plexus involvement) then definitive concurrent chemoradiation would be preferred
What is the most aggressive chemotherapy for lung cancer?
What are the drawbacks of using this?
cisplatin
chemotherapy is NOT curative for lung cancer
the chances of response are only around 30%
When might cisplatin not be used?
it cannot be used with some comorbidities
- lung cancer patients are often smokers with diabetes + ischaemic disaeses where cisplatin might not be recommended
When might chemotherapy be chosen over chemoradiation?
- in more severe disease where nodes of the supraclavicular fossa are involved (T3), there is concern about whether cervical nodes may be affected
- in this case, radiation is not suitable
What symptoms may a patient present with if the cancer has occluded the trachea?
What management must be performed here?
- they may present with stridor due to narrowing of the airway
- airway compression is managed with high flow O2 and steroids
What does small-cell lung cancer appear like under a microscope?
it is typical of small, oval, purple cells with:
- grainy / scanty cytoplasm
- frequent mitoses (divisions)
- open nuclei
- absent nucleoli
- dense neurosecretory granules
How do small cell lung cancers tend to present differently to NSCLCs?
- SCLCs tend to be present more centrally and cause irritation / obstruction of major airways
- haemoptysis is also more common
- they are also associated with paraneoplastic syndromes
What are the 3 most common paraneoplastic syndromes?
- ectopic ACTH production (Cushing’s syndrome)
- SIADH
- Eaton Lambert syndrome
cancer does not present with chest symptoms, but those of the syndrome
Why can Cushing’s syndrome occur in SCLC?
- the cancer starts in the neuroendocrine cells of the lungs
- these cells produce glucocorticoids, including cortisol
- constant exposure to high levels of cortisol results in symptoms of Cushing’s syndrome
What are some of the symptoms of Cushing’s syndrome?
- increased hair growth
- decreased libido
- weight gain with thin arms + legs
- easy brusing
- round “moon” face
- wide purple stretch marks, mainly on the abdomen and breasts
What is SIADH?
syndrome of inappropriate ADH secretion
- lung cancer cells release ADH
- unlike ADH release by the pituitary gland, ADH from cancer cells is NOT suppressed by low sodium levels / normal blood volume
this results in hyponatraemia
What are the symptoms of SIADH in lung cancer?
- N&V
- tiredness
- muscle cramps
- shaking
- headaches / confusion
- decreased urine volume + increased concentration
the symptoms are caused by hyponatraemia and tend to be vague
What is meant by Lambert-Eaton syndrome and why does it occur?
- there is generation of antibodies against voltage-gated calcium channels on presynaptic nerve terminals
- this results in a decrease in acetylcholine (ACh)
- the primary presentation is muscle weakness
over 50% cases are associated with SCLC, the rest are autoimmune
What symptoms are associated with Lambert-Eaton syndrome?
- muscle weakness, fatigue + pain
- difficulty walking
- reduced reflexes
- weakness in muscles of eyes, face + throat
- speech + swallowing problems
What is the main treatment approach for SCLC?
CHEMOTHERAPY
- surgery is rarely used
- the cancer has a fast doubling time so need to start systemic treatment fast
- depending on how well the patient is and where the tumour is, radiotherapy may be used as well
Where does radiotherapy tend to be used in a SCLC patient?
- SCLC has a predominance of going to the brain as a first site of relapse
- radiotherapy to the brain is given even if there are no mets
- relapse / brain mets often mean it is the end of life
How is chemotherapy given in SCLC?
- it is the only cancer where chemotherapy is given as an in-patient
- there are often 4 cycles, but the patient is discharged after the first one
How is the response rate to chemotherapy different for SCLC and NSCLC?
- NSCLC has a 30% response rate to chemotherapy
- SCLC has a 70-80% response rate
- due to the fast doubling time, the responses are not long-lived
- radiotherapy is also given to try and consolidate this
What chemotherapy agent is commonly used for SCLC?
carboplatin etoposide
What is a significant side effect of radiotherapy to the brain in SCLC?
there is often significant memory impairment (particularly short term)
What is the mainstay treatment for lung cancers in general?
radiotherapy
- many patients with lung cancer have other comorbidities and are not suitable for surgery
radiotherapy aims to hit the cancer and spare organs at risk
Why is radiotherapy becoming increasingly favoured over surgery?
- early-stage cancers can have similar local control rates to surgery
- high doses can be supplied to the tumour and spare organs at risk
- treatment can be delivered over a short period of time (3-8 tx)
- can treat patients who are unwell
What is meant by oncogene addiction?
some cancers with genetic, epigenetic or chromosomal irregularites become dependent on one or several genes for survival
cancer cells rely on continuous signalling from these oncogenes for survival
What does oncogene addiction mean for treatment?
- drugs can be developed to specifically target certain mutations that are driving division of that cancer
e.g. ALK & EGFR in adenocarcinoma
Oncogene driven tumours are NOT common and < 10% of all lung cancer cases
How does immunotherapy in NSCLC work?
- tumour cells switch off the immune system in order to grow
- they bind to T-cell receptors PD-1 and PD-L1
- immunotherapies block the attachment of tumour cells to T cells
- the immune system can recognise the tumour cells and mount a response to kill the cancer cells
What are the benefits of immunotherapy over chemotherapy?
- immunotherapy is discriminatory, whereas chemotherapy attacks any cells that are actively dividing
- this results in death of the bone marrow, gut lining, hair loss + skin rashes
- immunotherapy does not have the toxic side effects of chemotherapy
death of bone marrow results in neutropenic spesis, thrombocytopenia + anaemia
What are the common side effects of immunotherapy?
- thyroid imbalance is the most common, but any organ can be affected
caused by the immune system attacking other organs + cancer cells
When can immunotherapy be used to treat lung cancer?
1st line treatment:
- it can be used alone to treat stage IV disease
- or combined with chemotherapy
2nd line treatment:
- it can be used after radical treatment for maintenance in stage III disease
