Basics

Question 1

Modifiable and non-modifiable risk factors for cancer (lifestyle, environmental, genetics)

Answer 1

Modifiable:
Lifestyle: smoking (lung, stomach, pancreas, liver), alcohol (oral caivty, pharynx, larynx, liver, bowel), obesity/physical inactivity (kidney, oesophagus), diet (bowel, breast), chronic infections (cervix, liver)
Environmental: sunlight exposure, occupational exposure (bladder, mesothelioma), pollution (skin, lung), radiation

Non-modifiable:
Genetic: genetic susceptibility in family history, hormonal factors (breast), age

Question 2

Challenges of survivorship:

• Definition
• Challenges

Answer 2

Challenges of survivorship

• Definition: someone who has had a diagnosis of cancer and includes patients who no longer have signs, people receiving extended treatment to control/reduce risk recurrence, and people with advanced
• Challenges
  Mental health (self image, fear of recurrence, survivors guilt)
  Follow up medical care
  Long term physical SE (infertility, lymphoedema, secondary cancers, neuropathy, cognition/memory, heart/lung fibrosis)

Question 3

Health professionals involved in MDT (12)

Answer 3

• Medical oncologists: deals with medical diagnosis, treatment and organ transplantation during surgery. Doesn’t deal with radiotherapy
• Clinical oncologists: focuses on radiotherapy and chemotherapy treatment
• Histopathologists
• Radiologists
• Surgeons
• Palliative care physicians
• Clinical nurse specialists
• Dieticians
• Physios
• OT
• Psychologists

Question 4

Key resources for patient information

Answer 4

Cancer research UK
Macmillan UK
Specific organisations such as Bladder and bowel foundation

Question 5

Cancer screening:

• Definition
• Principles (5)
• Benefits and problems
• Aims of screening
• Controversial issues
• New screening problems being evaluated

Answer 5

Cancer screening:

• Definition: is a form of secondary prevention and is the process of identifying individuals with an elevated risk of cancer to allow earlier diagnosis and treatment which can decrease mortality from the disease
• Principles:
  1. Cancer is a serious and common problem
  2. Cancer more treatable if detected early
  3. Test should be acceptable to those eligible (simple, safe, ethically accepted)
  4. Inexpensive test
  5. Test has high sensitivity (those with cancer test pos) and specificity (those without cancer turn neg)
  6. Shown to reduce mortality in RCT
• Benefits and problems:
  Lead time bias (early diagnosis falsely appears to prolong life - but patient just knows for longer)
  Length time bias (picks up slow unthreatening causes so shows lengthens life but just curing those who didn’t need curing)
  Selection bias (those having regular screening likely to do other disease protection)
  False + and false - create unnecessary stress
• Aims of screening: gives a better outcome compared to finding it out in the usual way such as through symptoms
• Controversial issues: physical harm (e.g. serious bleeding after colonoscopy, radiation exposure), stress, inaccurate results, unnecessary follow ups, incidental findings
• New screening problems being evaluated: lung cancer 55-74yrs + smoking, new blood test for more than 50 cancers

Question 6

Pathophysiology and causes of cancer

• Definition of: neoplasm, malignant, tumour, dysplasia
• Causes
• Classes of regulatory genes where mutations occur
• How do cancers spread
• Local vs systemic effects of neoplasms
• Hallmarks of cancer

Answer 6

• Definition of cancer:

Neoplasm: abnormal growth of cells which persists after initial stimulus is removed
Malignant neoplasms: are cancerous cells which can spread and invade other tissues
Tumour: is abnormal mass of tissue resulting from excessive cell division and arrest of apoptosis which can be benign or malignant
Dysplasia: is pre neoplastic alteration where cell tissue is disorganised. Then step wise progression makes it into a high grade dysplasia (carcinoma in situ) which can become malignant

• Causes:

Damaging radiation, exposure to carcinogens (chemicals cig smoke/asbestos, radiation UV/radiation therapy, viruses introduce new material leading to recombination which may be malignant rather than damaging/altering DNA) causes mutations which means cell looses regulation and can grow and proliferate. These are called initiators
Hormones can influence cancer development in certain tissues such as breast, endometrium, ovary etc
Family history - in the two hit hypothesis 2 mutations are required to affect both alleles in tumour suppressor genes to cause cancer. However patients which have inherited a mutation also have one hit so only need another, hence are predisposed to cancer

• Classes:

Protooncogenes: drives proliferation. Mutations cause excessive activation (gain a function). Dominant. e.g. BRAF, RAS
TSG: stop cell prolif. Muts needed in both (loss of function)

• How do cancers spread:

lymphatic (breast), transcoelemic (fluid body cavities), haematogenous (sarcomas)

• Effects of neoplasm:

Local: direct invasion of normal tissue, ulceration, compression, blocking tubes, raised pressure
Systemic: tumour burden, cytokines released reduce appetite/immunosuppression/thrombosis, production of hormones

• Hallmarks of cancer:

1. Self sufficiency in growth signals
2. Resistance to stop signals
3. Cell immortalisation
4. Angiogenesis
5. Resistance to apoptosis
6. Ability to invade

Question 7

Epidemiological trends of cancer in UK

Answer 7

• More M than F
• > 50% over 70 years
• Breast, prostate, lung, colorectal most common in UK
• Cancer causes just over 1/4 deaths in UK a year
• Lung, bowel, prostate, breast most common causes of cancer death
• Worldwide most common are breast, lung, bowel, prostate with UK incidence one of highest

Question 8

Role of clinical trials in cancer management

Answer 8

Prevention, screening, treatment trials

Phase 1: small numbers, finding out best dose, what SE are, what happens to treatment in the body, healthy volunteers
Phase 2: 10s to hundreds, checking best dose, SE, looking how well treatment works (start looking at efficacy, patients
Phase 3: hundreds/thousands, comparing new treatment to old one or placebo, blinded, licensing and marketing authority
Phase 4: finding out long term benefits/SE, real world evidence, post licensing studies

Question 9

Health promotion and cancer prevention

Answer 9

• Primary prevention - before people are ill, posters, immunisation
• Secondary - when people at risk, drinking/smoking cessation, screening

Question 10

Describe:

• Grade
• Stage

Answer 10

• Grade: this refers to how abnormal the cancer appears under the microscope. Typically well, moderately or poorly differentiated (i.e. how much they look like the original cell type)
  Is a prognostic feature
  With worsening differentiation: inc nuclear size, inc nucleus: cytoplasm ration, hyperchomasia, mitotic figures, abnormal mitotic figures (mercedes benz), pleomorphism
• Stage: this refers to how far cancer has grown and spread. It is usually classified according to ‘TNM’ staging, which refers to T - tumour size, N - nodal spread, M - distant metastasis. Determines operability and choice of treatment

Classifications of tumours will also incorporate other factors such as:
• Location (e.g. cerebellum)
• Tumour type (e.g. glioma, oligodendroglioma)
• Genetic/molecular diagnosis (e.g. IDH-mutant)