1.01 - Introduction to Oncology Flashcards
Modifiable risk factors for cancer.
- tobacco use
- infectious agents
- unhealthy diet
- obesity
- physical inactivity
- alcohol consumption
Which cancers is smoking associated with in particular?
- lung
- oesophagus
- oral cavity
- pancreas
Smoking is responsible for approximately 2.3 million cancer deaths globally. An additional 190,000 cancer deaths are associated with smokeless tobacco and secondhand smoke.
Infectious agents are responsible for what proportion of new cancer diagnoses worldwide?
15%
What are the main infectious agents that contribute to the following cancers?
a) stomach cancer
b) cervical cancer
c) liver cancer
a) H. pylori infection
b) HPV (also causes vulvar, vaginal, anal and penile cancer).
c) Hepatitis B virus (low SES) or Hepatitis C virus (high SES)*
*high SES have vaccination against hepatitis B
Alcohol is a risk factor for which cancers?
- pharynx
- lip and oral cavity
- larynx
- oesophagus
- colon / rectum
- liver
- breast
How can skin cancers caused by ultraviolet radiation be prevented?
Sun protection and banning sunbeds - Australia implemented UV protection campaigns in the 1980s, and rates of melanoma are now decreasing in younger generations.
Environmental risk factors for cancer.
- air pollution
- radon gas exposure
- arsenic in drinking water (ie. China, Bangladesh)
Occupational risk factors for cancer.
- UV radiation (skin and eye)
- asbestos (lung, mesothelioma, ovary)
- benzene (leukaemia, lymphoma)
- xray radiation
Non-modifiable risk factors for cancer.
- sex (M>F)
- age
- low SES*
- genetics (ie. germline mutations)
- race
- PMHx (e.g. UC, cirrhosis)
*higher rates of smoking, obesity, inactivity; poor vaccination programmes, low vaccine uptake
What are some ways of controlling tobacco use?
- tax tobacco products
- smoke-free air laws
- health warnings on tobacco packaging
- restrictions on the promotion and advertising of tobacco
Note we should focus on preventing people starting smoking, and also on helping people to stop smoking; the risk of dying from lung cancer can be substantially reduced by quitting at any age.
How can unhealthy diet and physical activity be controlled?
- tax sweetened beverages
- pedestrian and cycle lanes
- green prescriptions
What is the role of vaccination in cancer prevention?
HPV and HBV vaccination is safe and available in the UK.
What is the benefit of early cancer detection?
Less aggressive treatment required, leading to a better quality of life and reduced mortality.
What are the approaches to early detection of cancer?
- screening
- early diagnosis
What are the three cancer screening programmes in the UK?
- Bowel cancer screening
- Breast cancer screening
- Cervical screening
For screening to be useful, the tests must be:
- reliable
- sensitive and specific
- benefit > harm
- cost-effective
- something people are willing to do
Bowel cancer screening programme in England.
Bowel cancer screening kit sent in the post to men and women aged 60 to 74, once every 2 years.
The test looks for trace blood in the faeces, which may indicate cancer.
What are the benefits of the bowel cancer screening programme?
Bowel cancer screening saves lives - it aims to detect cancer at an early stage where treatment is more likely to work.
What are the risks of the bowel cancer screening programme?
False positive result - results in anxiety and further unnecessary tests.
False negative result - rarely, screening may miss cancer.
Overdiagnosis - chance that some people are diagnosed and treated for bowel growths that would not have caused harm.
How are people deemed to be at high risk of bowel cancer screened?
Colonoscopy
Which people are deemed to be at high risk of bowel cancer?
- FAP
- Lynch syndrome (HNPCC)
- SPS
- FHx bowel cancer
- UC / Crohn’s disease
- polyps
- previous history of bowel cancer
What is breast cancer screening?
Mammogram takes x-rays of the breast, aiming to detect breast cancer when it is too small to see or feel.
These cancers are usually easier to treat than large cancers.
Who has breast cancer screening?
Women aged 50 to 70 are invited for a mammogram every 3 years.
Is breast cancer screening offered to trans people?
Breast screening is offered to:
- trans men and non-binary people assigned female at birth, who have not had bilateral mastectomy
- trans women and non-binary people assigned male at birth, who have taken feminising hormones
What is cervical cancer screening?
Tests for HPV, which can cause infected cervical cells to become abnormal.
A sample of the cervical cells are taken using a smear. If HPV is found in the cells, then they are looked at under a microscope for cell changes.
Who can have cervical screening?
Women aged 25 to 64:
- invited every 3 years between 25 and 49
- invited every 5 years between 50 and 64
What happens if you test positive for HPV?
The laboratory will also test your sample for cell changes. These changes are also called dyskaryosis.
If there are cell changes, you will be invited for a colposcopy to look closely at your cervix.
You will be invited back for cervical screening earlier than normal if there are no cell changes. This is usually after 1 year.
How is cervical cancer prevented?
HPV vaccination programme rolled out in England - given to boys and girls aged 13 and 14.
It protects against cervical, mouth, throat, anal and penile cancers.
What are the most common cancers in the UK?
- breast
- prostate
- lung
- bowel
Phases of clinical trials.
Phase 1
1-2 dozen participants.
The safety and best dosage levels of a drug is determined.
Phases of clinical trials.
Phase 2
<100 participants.
The response to new treatment is recorded and analysed.
Phases of clinical trials.
Phase 3
> 100 participants.
The results are studied; submission to a regulatory agency for approval.
Phases of clinical trials.
Phase 4
> 1000 partipants.
The treatment is marketed, and allows opportunity to learn more about rare side effects and long term effects.
What proportion of cancer diagnoses are preventable in the UK?
38%
Incidence of cancer in the UK annually.
Around 1000 diagnoses per day.
375,400 per year.
What is hyperplasia?
Increase in a size of tissue by an increase in the number of cells in the tissue.
Example of physiological hyerplasia.
Endometrial hyperplasia upon stimulation of oestrogen in the menstrual cycle.
Example of pathological hyperplasia.
Unopposed oestrogen HRT after menopause for symptomatic relief can cause endometrial hyperplasia.
This pathological hyperplasia increases the risk of dysplasia, then neoplasia.
What is metaplasia?
Transformation of one cell type to another.
What is pathological metaplasia?
In response to chronic insult, cells transform from one cell type to another. These cells are precancerous:
- some progress to malignant cells
- some regress to normal cells
What is dysplasia?
Disordered growth of epithelium characterised by frequent mitotic figures and loss of cell size and shape.
Precancerous but reversible if the stimulus is removed.
What is neoplasia?
Cancerous growth of epithelium that is irreversible.
What is anaplasia?
The progression of dysplasia to the point where the cells have mutated extensively.
At this point, the cells are malignant.
Define benign neoplasm.
A non-invasive tumour that remains confined to its site of origin.
They tend to be encapsulated by a thin layer of epithelial tissue, well circumscribed and cells are well differentiated under microscopy.
Define malignant neoplasm.
A tumour with the ability to spread to different sites, compromising the basement membrane.
They are often fast growing and have irregular edges.
Histology of malignant neoplasms.
- poorly differentiated cells
- mitotic figures
- hyperchromasia
- chromatin clumping
- pleomorphism
How is cancer staged?
TNM staging.
Tumour size
Node involvement
Metastases
What is tumour grade?
Describes the behaviour of the malignancy from histological features of the tissue:
- degree of differentiation
- appearance of nuclei
- presence of mitoses
What is a tumour suppressor gene?
Genes that normally work to inhibit the growth of tumours.
Both alleles need to be inactivated to allow growth of tumours.
Give some examples of tumour suppressor genes.
- retinoblastoma gene
- p53 gene
Inactivation of retinoblastoma gene.
The Rb gene usually stops damaged cells from passing the restriction point in the cell cycle, preventing replication.
Inactivation of both Rb genes results in uncontrolled cell growth, resulting in familial retinoblastoma.
Children with the faulty gene can develop retinoblastoma at a very young age.
Inactivation of the p53 gene.
Normally encodes for a transcription factor involved in DNA repair.
Inherited mutations of the p53 gene results in Li-Fraumeni syndrome, increasing the risk of developing several cancers:
- osteosarcoma
- breast cancer
- lung cancer
- melanoma
What is the two hit hypothesis of tumour suppressor genes?
Both alleles of tumour suppressor genes must be inactivated.
If one tumour suppressor gene is inherited as mutated, the second gene can still protect the cell to protect tumour growth. However, if the second gene becomes mutated the chance of tumour growth is very high.
A person with no germline mutation is less likely to develop a neoplasm.
What is a proto-oncogene?
A gene which, when mutated (ie. oncogene), enhances growth of tumours.
Only one allele needs to be mutated to allow growth of tumours.
Examples of oncogenes.
- RAS
- HER-2
- BRCA1/BRCA2
RAS oncogene.
Codes for a G-protein that allows cells to get past restriction point in the cell cycle.
A mutation causes the protein to always be active, allowing any cell to move through the cell cycle and divide.
HER-2 oncogene.
Codes for growth factor receptors. Overexpression of the gene by mutation leads to many growth factors being expressed on the tumour cell surface, increasing the sensitivity of the cell to growth factors.
This accelerates growth of the neoplasm.
What are the six hallmarks of cancer.
- self-sufficiency in growth signals
- resistance to growth stop signals
- cell immortalisation through the action of telomerase
- angiogenesis
- resistance to apoptosis
- ability to invade and produce metastases
What is epithelial to mesenchymal transition (EMT)?
A process by which epithelial cells undergo multiple changes until they closely resemble a mesenchymal cell. This reduces cell adhesion and increases motility, facilitating invasion.
What are the cellular changes that achieve EMT.
- decreased expression of E-cadherin reducing cell-cell adhesion
- changes to integrin receptor alters adhesion between cells and ECM
- MMP enzyme enables breakdown of surrounding connective tissue
- increased cell motility
In order to metastasise, malignant cells need to:
- invade the basement membrane to blood or lymphatic vessels
- avoid host immune defences
- attach to endothelium at a distant location
- leave the blood or lymphatic vessels to enter surrounding tissue
What are the methods of metastatic spread?
- haematological metastases
- lymphatic metastases
- transcoelaemic spread
What are tumour markers?
Substances released into the circulation by tumour cells, measured to monitor tumour burden and response to treatment.
What are some local effects of tumours?
- compression
- obstruction
- ulceration
- bleeding
- fistula formation
What are some systemic effects of tumours.
- paraneoplastic syndrome
- cachexia
- malaise
- immunosuppression
- thrombosis
ECOG performance status.
What is radical / curative cancer treatment?
Aims to completely eliminate cancer from the body, typically involving aggressive therapy:
- surgery
- chemotherapy
- radiotherapy
What is palliative cancer treatment?
Focus on improving quality of life for patients with advanced cancer, or those who are not candidates of curative treatment.
The goal is to manage symptoms, alleviate pain, and provide emotional and spiritual support for patients and their families.
What is adjuvent cancer treatment?
Additional treatment given after the primary treatment to lower the risk of cancer recurrence.
It is commonly used in cases where there is a high risk of cancer returning even after the primary treatment has removed the visible tumour.
What is neo-adjuvent cancer treatment?
Additional treatment given before the primary treatment, aiming to shrink the tumour and thus make it easier to remove surgically / increase the effectiveness of subsequent treatments.
What is maintenance cancer treatment?
A long-term treatment administered after the completion of initial therapy, aiming to prevent cancer recurrence or progression by suppressing any remaining cancer cells that may not be detectable.
What are the principles of palliative care, best supportive care and end-of-life care?
- focus on improving quality of life for patients with serious illness
- emphasise symptom management, comfort and support for patients and their families
- involve interdisciplinary teams of healthcare professionals
What are the challenges of survivorship?
- many cancer patients describe loss of self-confidence
- increased utilisation of health service
Increased risk of comorbid conditions:
- coronary heart disease
- osteoporosis
- diabetes
- hypothyroidism
What is the rationale of surgery in cancer treatment?
Surgery can be used to:
- diagnose cancer
- find out the stage of cancer
- remove cancer
- control cancer / improve symptoms
- prevent cancer
What is chemotherapy?
Cytotoxic drugs are administered and carried in the blood, disrupting the way cancer cells grow and divide.
They also affect healthy cells in the body, however the healthy cells can usually recover from damage; cancer cells cannot recover, and will eventually die.
Because chemotherapy drugs affect some healthy cells in the body, this can cause side effects.
Side effects of chemotherapy.
- increased risk of infection
- anaemia
- increased bleeding or bruising
- thinning hair / hair loss
- vomiting and diarrhoea
- constipation
- taste changes
- fatigue
- peripheral neuropathy
- increased risk of blood clots
Considerations of chemotherapy and sex life.
- contraception must be used as teratogenic
- breastfeeding not advised
- early menopause
- can affect fertility; can store eggs or sperm
Late effects of chemotherapy.
- reduced fertility
- peripheral neuropathy
- effects on heart, lungs or kidneys
- increased risk of second cancer
What is radiotherapy?
Use of high-energy rays to destroy cancer cells in the area where the radiotherapy is given.
Some normal cells in the area being treated can also be damaged by radiotherapy, causing side-effects.
What is chemoradiation?
When you have chemotherapy at the same time as radiotherapy.
Chemotherapy makes cancer cells more sensitive to radiotherapy, helping make the radiotherapy work better.
It may mean side effects are worse.
What are the reasons for having radiotherapy?
- curative intent
- palliative intent
Side effects of radiotherapy.
- fatigue
- appetite changes
- nausea
- skin reactions
- hair loss
- immunocompromise
- easy bleeding or bruising
What are the effects of radiotherapy on fertility?
Radiotherapy usually does not affect fertility, unless you have treatment to:
- the pelvic area
- the pituitary gland
Radiotherapy to these areas can affect how the body produced hormones needed to control sex, and may make it more difficult to get an erection or ejaculate.
What is hormonal cancer therapy?
Altering the production or activity of hormones that a cancer is sensitive to, allowing you to treat the cancer.
What is immunotherapy?
Treatments that use the immune system to find and attack cancer cells.
Types of immunotherapy.
- checkpoint inhibitors
- immune system modulators
- virus therapy
- monoclonal antibodies
- cancer vaccines
- adaptive cell transfer
Immunotherapy
Checkpoint inhibitors.
Checkpoint inhibitors block the signals that switch off lymphocytes, meaning the lymphocyte stays active and can attack cancer cells.
Immunotherapy
Immune system modulators.
Help the immune system to attack and destroy cancer cells.
Immunotherapy
Virus therapy.
Uses a virus that has been made or changed in a laboratory, which finds and infects the cancer cells.
It also trains the immune system to find and attack cancer cells.
Immunotherapy
Monoclonal antibodies.
Monoclonal antibodies are made to connect to a type of receptor on the cancer cells, which helps the immune system to find and attack cancer cells.
The receptors may be found on some other healthy cells in the body, which can cause side effects.
Immunotherapy
Cancer vaccines.
Vaccines train the immune system to find and attack certain types of abnormal cells. They usually protect us from infection, but can be used to help train the immune system to find and attack cancer cells.
Immunotherapy
Adaptive cell transfer.
Some white blood cells are collected from the body, and scientists then:
- choose the cells that are best at recognising cancer cells
- change cells to make them better at recognising cancer cells
These cells are grown in the laboratory and given back into the bloodstream, to find and attack cancer cells.
Side effects of immunotherapy.
- skin: rash, itching or changes in skin colour
- sweating
- weight changes
- diarrhoea
- pain / swelling of joints
Immunotherapy causes the immune system to become more active, meaning it is better at finding and attacking cancer cells. However, it can also cause the immune system to target some healthy cells, which may cause side effects.
Types of targeted cancer therapy.
- angiogenesis inhibitors
- cancer growth inhibitors
- monoclonal antibodies
- PARP inhibitors
Targeted cancer therapy
Angiogenesis inhibitors
Block the chemical signals that cells use to make new blood vessels grow, making it difficult for the tumour to get a blood supply.
Without a good blood supply, the tumour doesn’t get the oxygen or nutrients it needs, slowing the tumours growth or causing it to shrink.
Targeted cancer therapy
Cancer growth inhibitors.
Block cancer cells from receiving signals that tells them when to develop and divide, stopping them from doing so.
This may slow the growth of a cancer.
Targeted cancer therapy
Monoclonal antibodies.
Given into the blood and connect to a receptor on the cancer cells:
- angiogenesis inhibitor
- cancer growth inhibitor
- checkpoint inhibitor
- immunotherapy
- carry a chemotherapy drug straight to the cancer cell
Targeted cancer therapy
PARP inhibitors.
PARPs are proteins that help damaged cells repair themselves.
PARP inhibitors block PARP proteins, meaning cancer cells may become more damaged and die.
Key resources for patient information on cancer.
- Macmillan
- Cancer Research UK
- Cancer Support UK
