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Flashcards in Therapeutic Options Deck (31):
1

Prevention methods

- Diet
- Stop people smoking
- Screening
- Genetics
- Medication

2

Diet in prevention

- Inconsistent evidence, lots of confounding factors
- CRC is probably linked with red meat consumption
- Breast cancer: probably a link with saturated fat intake
- Physical activity decreases risk
- Current advice: 5 or more portions of fruits and vegetables a day, avoid obesity, take regular exercise 30 minutes a day

3

Screening in prevention

- Risks are involved with screening, so you may cause harm
- E.g. breast screening might perform a mammectomy on a patient who has a lump that may never turn into cancer
- High quality evidence for smear tests, CRC (faecal occult blood test), breast cancer
- Controversial: PSA blood test for prostate cancer, MR/CR or breath test for lung cancer

4

Genetics in prevention

- CRC and familial adenomatous polyposis coli (FAP)
- Autosomal dominant
- Screening families for APC mutations
- Regular colonoscopy
- Offer panprotocolectomy when adenomas found
- Breast cancer: BRCA1, BRCA2

5

Medication in prevention

- Also known as chemo-prevention
- More controversial

6

Primary medication in prevention

- Oesophageal cancer: high rate in parts of chine, they tried anti-oxidant supplements but there was no benefit
- Breast cancer: at risk women, prophylactic tamoxifen (higher risk of getting endometrial cancer with this)

7

Secondary medication in prevention

- Previous head and neck or lung cancers
- Give anti-oxidant supplements
- No benefit

8

Treatment

- Local or regional treatment: surgery or radiotherapy
- Systematic therapy: hormonal, chemo, immunotherapy

9

Surgery treatment of cancers

- Need anatomical clearance
- Get all the cancer out
- 50% of cancers cured this way

10

Radiotherapy treatment of cancers

- Needs anatomical coverage
- Can treat inoperable lesions
- Can treat things you can't remove and/or allow surgery to be possible
- Approx. 40% of cancers cured by this
- Can be combined with chemo: anal cancer, rectal cancer, oesophageal cancer
- Palliation
- Maintain function and/or appearance

11

Palliation

- Reduce pain
- Bleeding
- Swollen limbs
- Aims to improve symptoms

12

Maintaining function with radiotherapy

- Gullet cancer, you can't remove it so you need to maintain function
- Ear lesion, you can keep your ear with radiation therapy

13

5R's of radiobiology

- Radiosensitivity
- Repair
- Re-population
- Re-oxygenation
- Re-assortment

14

Radiosensitivity

- How sensitive the tumour is going to be to treatment
- Can anticipate outcome
- Certain drugs have been proven to increase radiosensitivity

15

Repair

- Radiation damages cells to a sublethal level, often the cell pathways repair themselves have been suppressed in malignant tumours
- The degree of suppression will affect the repair half-life and how effective the treatment is

16

Re-population

- Cells will all be in different parts of the cell cycle
- S phase: typically radioresistant
- Late in G2 or M phase are relatively sensitive
- Idea is you catch them at some point in the cycle when they're in a more sensitive phase

17

Re-oxygenation

- Tumours can be acutely or chronically hypoxic, this makes the resistant to radiation
- The aim of radiation is to make them oxic as oxic cells can be killed

18

Re-assortment

- Cells are in a cycle and you catch some cells at different stages, some are sensitive to radiotherapy and some aren't
- G2 and M are good, late S isn't so good

19

Systemic therapy

- Beneficial for widespread disease
- Can result in widespread toxicity
- Palliation in about 50% of cancers
- Potential to be very specific
- Therapeutic index: aim is to have the anti-tumour effect curve and normal tissue toxicity as far apart as possible. Separates side effects and anti-tumour effects

20

Hormonal therapy

- 'Specific' or 'targeted' therapy
- Benefits in breast cancer (oestrogen receptor positive and tamoxifen) and prostate cancer (luteinising hormone-releasing hormone antagonists)
- Trials in prevention for high risk groups e.g. tamoxifen

21

What are the 4 basic types of chemotherapy?

- Curative
- Palliative
- Adjuvant
- Neoadjuvant

22

Curative chemotherapy

- Only about 3% of cancers, testicular, lymphomas
- Can be used with radiotherapy
- Important to use biomarkers to see what genes the tumours have, assess treatment methods

23

Palliative therapy

- Accounts for around 50% of chemotherapy
- Aim is to relieve symptoms

24

Adjuvant

- When there is no longer evidence of pathology
- Can reduce risk of recurrence. Based on population statistics rather than the individual

25

Neoadjuvant

- Aim is to improve survival and reduce morbidity
- Precedes surgery or radiotherapy
- Before people have surgery to see how the cancer is going to behave and decide whether to do local or systematic therapy
- Can be used to assist the surgery by ensuring cancer cells are removed in the operation and not in the bloodstream

26

Immunotherapy

- Specific and non-specific types
- Antibodies can target cancer, you can have a combination of mouse and human antibodies... one half of the antibody could be targeting one part and the other half of the head could be targeting another

27

Types of immunotherapy

- Monoclonal antibodies
- Programmed cell death pathway (PD-1)
- Chimeric antigen receptor (CAR) T-cells

28

Programmed cell death pathway (PD-1)

- Uses immune system to attack 'foreign' cancer cells
- Cancer hides behind inhibitors, this drug allows the immune system to see the drug
- It can make things worse if you have co-morbidities
- being used in lung cancer and melanoma

29

Chimeric antigen receptor (CAR) T-cells

- Artificial T-cell receptors, using retroviral vectors to give a specific cell killing function directed against cancer cells
- Very new
- In lymphomas and leukaemias, not solid cancers
- Side effects: you're taking lymphocytes out of circulation
- You put them back via T cell adoptive transfer

30

CAR T-Cells monitoring

- Disease response: CT scans, bone marrow biopsies, peripheral blood flow cytometry
- CAR T-Cell persistence: Immunohistochemistry of bone marrow biopsy, RT-PCR and flow cytometry of blood and bone marrow aspirate

31

Designer therapies

- Specific, based on molecular science
- You look at intracellular growth points
- EGFR inhibitor - in lung cancer need to have a specific mutaiton