Oncology Flashcards
What is the defining characteristic of a malignant tumour?
It’s ability to invade and metastasise to other tissues
Give a definition of cancer cells
Cells which undergo uncontrolled and unregulated cell proliferation with the ability to metastasise to other places in the body.
Name 4 of the 10 hallmark characteristics of cancer cells according to Hanahan and Weinberg.
Sustaining proliferative signalling Evading growth suppressors Avoiding immune destruction Enabling replicative immortality Tumour-promoting inflammation Activating invasion and metastasis Inducing angiogenesis Genome instability and mutation Resisting cell death Deregulating cellular energetics
Name the 5 stages of the cell cycle and what happens at each
G0= resting phase G1= pre-DNA synthesis S1= DNA synthesis G2= post-DNA synthesis M= Mitosis
What are the 3 different sub-populations of cells present in a tissue at one time?
1) Cells in resting phase that can be recruited into cell cycle
2) Cells that are terminally differentiated and can’t be recruited
3) Cells that are actively proliferating
What is the tumour marker in ovarian cancer?
Ca-125
What is the UK National Screening Committee definition of screening?
A process of identifying apparently healthy people who may be at increased risk of a disease or condition
List 4 of Wilson’s criteria for screening.
1- Important health problem
2- Accepted treatment
3- Facilities for diagnosis and treatment
4- Recognisable latent or early symptomatic stage
5- Suitable test or examination
6- Test acceptable to the population
7- Natural history of condition adequately understood
8- Agreed policy on whom to treat
9- Cost-effectiveness
10- Case-finding should be a continuous process
What is the grade of a tumour?
The extent to which the neoplasm resembles its cells or tissue of origin
Which type of tumours more resemble their parent tissue: well differentiated or poorly differentiated?
Well differentiated
Poorly differentiated tumours do not resemble their parent tissue, tend to grow more rapidly and behave more aggressively compared to well differentiated.
What does the stage of a cancer describe?
Its size and how far it has spread
What are the components of the TNM staging classification?
Tumour, Nodes, Metastasis
Metastasis to distant organs generally correlates with what stage of cancer?
Stage 4
Symptoms with a risk of cancer warrant what type of referral?
What does this mean?
Suspected Cancer Pathway Referral. Means a patient will have the appropriate investigations and specialist review within 2 weeks
What is it imperative to identify before deciding on cancer treatment?
The aims of the treatment e.g. curative or palliative.
What is the primary treatment for most early/non-metastatic solid tumours?
Surgical resection of primary areas and areas at risk of microscopic spread (e.g. sentinel LNs in breast cancer)
What might cause recurrence of disease following resection of a primary tumour?
The presence of microscopic disease/micrometastases
What is the difference between neo-adjuvant and adjuvant chemotherapy?
Neo-adjuvant= prior to surgery/radiotherapy Adjuvant= post-surgery
Briefly outline the mechanism of action of radiotherapy.
- Makes free radicals and ROS are formed
- They react with covalent bonds in DNA
- Causes apoptosis
What are the three main ways of delivery radiotherapy?
External beam therapy, brachytherapy (internal to the body) and systemically
What produces the external beam radiation therapy?
A linear accelerator (LINAC)
What does the radiation dose entail and what is it measured in?
The amount of irradiation absorbed by each kilogram of tissue, measured in Grays (Gy)
When treating a patient with curative intent with radiation, what treatment regime (total dose, dose pe fraction) would be used and why?
High total dose but spread over many fractions to reduce the risk of long term adverse effects
When treating a patient with palliative intent with radiation, what treatment regime (total dose, dose per fraction) would be used and why?
High dose per fraction but low overall dose to reduce short-term adverse effects.
Some chemotherapy drugs are radio-sensitising, what does this mean?
The chemotherapy makes the cancer cells more sensitive to radiotherapy.
What is the most common acute side effect of radiotherapy. Is this dependent or independent of the area of the body being treated?
Fatigue. Independent.
List 4 other possible side effects of radiation.
Nausea, vomiting, anorexia, mucositis, oesophagitis, diarrhoea
Side effects are typically worst how long following completion of treatment?
After how long have they typically resolved?
2 weeks.
6 weeks.
True or false: early side effects of radiation generally involve local inflammation and late side effects involve local fibrosis.
True
Give 2 examples of types of molecular targeted therapies used for cancer treatment.
Small molecule inhibitors e.g. Tyrosine kinase inhibitors
Monoclonal antibodies
Immunotherapy
What part of the cell cycle do these anti-cancer drugs affect:
1- corticosteroids
2- vinca alkaloids
3- antimetabolites
1- G1
2- Mitosis
3- S1
What are the 4 broad categories of cytotoxic chemotherapies?
Alkylating agents, antimetabolites, DNA linking agents, and ‘natural products’ (cytotoxic antibiotics, taxanes)
How do alkylating agents work?
They add an alkyl group to the guanine base of DNA, so crosslinks form between these. This disrupts DNA synthesis by preventing DNA replication and RNA transcription.
True or false, alkylating agents only work in phase G1 of the cell cycle?
False, they work at all stages of the cell cycle, they aren’t phase specific.
Antimetabolites are cell specific. What phase do they particularly effect, and what phase do they have very little effect?
Primarily effect the synthetic/S phase. Very little effect on G0
Are antimetabolites most effective against slow or rapidly growing cancers?
Rapidly growing
Generally how do antimetabolites work?
Inhibition of enzymes or metabolites involved in DNA or RNA synthesis.
How do DNA linking agents work?
They contain platinum complexes which produce inter-strand and intra-strand DNA cross links which prevents replication.
Are DNA linking agents cell cycle specific or non-specific?
Non-specific
What is a big reason why many chemotherapy treatment regimens fail?
Drug resistance- either natural or developed
Give 5 side effects of chemotherapy
Nausea, alopecia, heart failure, immune suppression, renal impairment, hepatic impairment, skin rashes, bowel upset, peripheral neuropathy, taste changes
What are the three main groups of drugs which make up the molecular targeted therapies?
Monoclonal antibodies, small molecule kinase inhibitors, and immunotherapy
What two routes are monoclonal antibodies administered?
IV or S/C
What part of the cell do monoclonal antibodies work on?
Recognise specific protein markers on the outside of cells
Small molecule inhibitors act intracellularly, typically on what type of pathways?
Tyrosine kinase
What do small molecule inhibitors names end in? How are they administered?
-nib. Usually given orally
How does immunotherapy work?
Makes cancer cells that have previously managed to hide from the body’s immune system visible again, stimulating the body’s own immune response to kill off the abnormal cancer cells
When should patients be treated for neutropenic sepsis?
When they have a temperature of >= 38 and an absolute neutrophil count <=1 x 10^9/L
You should suspect neutropenic sepsis in any patients presenting with a new clinical deterioration within how many weeks of cytotoxic chemotherapy.
Within 6 weeks.
Name two associated risk factors with neutropenic sepsis
Poor nutrition, mucosal barrier defect, central venous line, abnormal host colonisation
What investigations would you perform in suspected neutropenic sepsis?
FBC, U&E, LFT, CRP/ESR, coag screen, septic screen (blood cultures, urine output, lactate), clinically relevant swabs/cultures, CXR
What is the initial management of neutropenic sepsis?
Initial empirical antibiotics (Tazocin) within an hour of arriving at hospital. Do not wait for results from blood tests.
After how long, if patient is improving, would you swap to oral antibiotics from IV in neutropenic sepsis? What to do if not improving?
24-48 hours.
Start second line antibiotics, then if that doesn’t work consider opportunistic infections
Give an example of opportunistic infections that may infect patients on chemotherapy.
PCP, fungal infections
Patients with high risk of developing significant neutropenia should be offered prophylaxis with what three possible agents?
Fluoroquinolone antibiotics, anti-fungals, Granulocyte colony-stimulating factor
Approximately 40% of circulating calcium is bound to what?
Albumin
Why should corrected calcium be used for diagnosing hypercalcaemia?
Because it’s only unbound, ionised calcium that is physiologically important
Give 2 causes of hypercalcaemia
Osteolysis (lytic bone mets), humoral (PTHrP in SCLC), dehydration, other tumour specific mechanisms
What is the presentation of hypercalcaemia?
Bones, stones, groans, and psychic moans
Give further investigations for hypercalcaemia.
Repeat sample, PTH, ECG, imaging for bone mets
What ECG change may be caused by hypercalcaemia?
Shortened QT interval
What are the two main steps in the management of hypercalcaemia?
1= correct dehydration. (0.9% NaCl 4-6L) 2= IV bisphosphonates (zolendronate or pamidronate commonly used)
Give 2 side effects of bisphosphonates
Flu-like symptoms, bone pain, myalgia, reduced phosphate levels, nausea and vomiting, headache, osteonecrosis of the jaw
What drug is used in persistent or relapsed hypercalcaemia of malignancy and how does it work?
Denosumab: monoclonal antibody that inhibits RANK ligand, so inhibiting the maturation of osteoclasts
What are the two mechanisms of malignant spinal cord compression?
Crush fracture, or soft tissue tumour extension
Give 3 possible presenting features of spinal cord compression.
Worsening back pain, weakness in limbs below compression, sensory level, bowel or bladder dysfunction (LATE SIGN), radicular pain, UMN signs below that lesion
What is the gold standard investigation for malignant spinal cord compression?
MRI whole spine
What are the 4 components of management of malignant spinal cord compression?
1= high dose corticosteroids 2= definitive treatment depending on tumour and patient (surgery, radiotherapy, chemotherapy, hormone deprivation) 3= Analgesia 4= VTE prophylaxis and pressure sore prevention
Recovery from spinal cord compression is uncommon if what two features are present?
Paraplegia and sphincter involvement
What structure provides the venous drainage of the head, neck, upper limb and upper thorax?
Superior vena cava
Give 4 causes of superior vena cava obstruction
Thrombus, intravascular device, direct tumour invasion, tumour pressing onto the vessel, lung cancer, lymphoma, germ cell tumours, fibrosing mediastinitis
Give 3 symptoms of SVC obstruction
Chest pain, dyspnoea, cough, neck and face swelling, arm swelling, dizziness, headache, visual disturbance, syncope
Give 2 signs of SVC obstruction.
Dilated veins (arms, neck, anterior chest), oedema (of upper torso, arms, neck and face), severe respiratory distress, cyanosis, engorged conjunctiva, convulsions and coma
SVC obstruction may be a clinical diagnosis but what are two possible investigations you may do?
CXR, CT scan
What two actions may provide symptomatic relief of SVC obstruction?
Elevation of head and oxygen therapy
What is the management of SVC obstruction?
High dose steroids (acutely), endovascular stenting. May consider chemotherapy, radiotherapy, anticoagulation (if central vein thrombosis present)
