Radiotherapy

Question 1

What is the primary treatment for breast cancer?

Answer 1

Surgery

Question 2

What is the primary treatment for oral pharynx cancer?

Answer 2

Radiotherapy

Question 3

What is the primary treatment for small cell lung cancer?

Answer 3

Chemotherapy

Question 4

How many patients in the UK at treated with radiotherapy at some point during their disease?

Answer 4

~50%

Question 5

How many patients in the UK are hugely impacted by radiotherapy?

Answer 5

~20%

Question 6

What are the 3 phases of a cell and tissues response to radiation?

Answer 6

The physical
The chemical
The biological

Question 7

Describe the physical phase

Answer 7

Deposition of energy: isolation and production of fast electrons
Direct action of radiation - electrons damage DNA

Question 8

Describe the chemical phase

Answer 8

Electrons interact with molecules to produce chemical changes: Free radical damage biological targets - indirect action

Question 9

Describe the biological phase

Answer 9

The chemical damage has biological effects

The whole system

Question 10

In terms of organic radicals, how does hypoxic conditions effect the cell?

Answer 10

The damage can be repaired and therefore the tissues are resistant to damage via radiation

Question 11

What is the effect if the cells are well-oxygenated?

Answer 11

Organic peroxide is formed and the tissues cannot repair the damage since the organic peroxide fixes the damage

Question 12

What is physical dose?

Answer 12

A measure of the energy deposited in the medium or the kinetic energy transferred

Question 13

What does the biological effect of a physical dose dependent on?

Answer 13

The type of radiation
Number of fractions into which dose has been divided
Interval between fractions
The time the radiation is received
Dose rate of each individual fraction
Biological tissue/ endpoint under consideration

Question 14

What are the two types of radiation?

Answer 14

Alpha particles

500NEB X-rays

Question 15

What is the difference between the types of radiation?

Answer 15

Alpha particles produce more ionisation per dose than x-rays, therefore, alpha particles have a greater biological effect

Question 16

How many Grey are fatal?

Answer 16

10 Grey

Question 17

How many joules is 10 Grey equivalent too?

Answer 17

700J

Question 18

Why does 700J kill you?

Answer 18

Due to the quantisation

Question 19

What is quantisation?

Answer 19

It is put into a small package rather than a large distribution

Question 20

Why is personalised medicine needed for radiotherapy?

Answer 20

We normally give the wrong dose of the drug

Question 21

What are acute effects?

Answer 21

Occur at or around the time of radiation

Effects on the tumour appear to be parallel with the effects on normal cells

Question 22

What are late effects?

Answer 22

Develop after 6 months of irradiation

Question 23

Name a late effect of radiotherapy in breast cancer patients

Answer 23

They can develop cardiovascular disease

Question 24

How long can the late effects of radiation occur for?

Answer 24

Can still occur 20 years later

Question 25

What is the main issue with radiotherapy?

Answer 25

It targets well oxygenated cells Normal cells are well oxygenated Cancer cells tend to be hypoxic

Question 26

What are the 5 R's of radiobiology?

Answer 26

``` Repair Repopulation Reoxygenation Redistribution Radiosensitivity ```

Question 27

What is reoxygenation?

Answer 27

during therapy, tumours reoxygenate - may be how some cells are responsive to therapy

Question 28

What is redistribution?

Answer 28

During the cell cycle, the tumours have high levels of oxygenation

Question 29

What is radiosensitivity?

Answer 29

Why some cells resist therapy and others don't

Question 30

What types of damage can radiotherapy and chemotherapy induce?

Answer 30

``` Missing base Single-strand break Bulky adduct Replication error (wrong base) Double-strand break ```

Question 31

What repair mechanisms counteract the damage induced by radiotherapy and chemotherapy?

Answer 31

Base excision repair Nucleotide excision repair Mismatch repair Homologous recombination end joining

Question 32

What are the clinical advantages of radiotherapy?

Answer 32

Elimination of adjacent pre-malignant cells Increased killing of tumour stem cells Differentiation of undifferentiated tumour cells Increased proliferation of normal cells Increased radioresistance in adapted normal cells Rapid relief of symptoms

Question 33

What are the clinical disadvantages of radiotherapy?

Answer 33

``` Second malignancies Increased acute toxicity Increased proliferation of tumour cells Increased radioresistance in adapted tumour cells Increased systemic effects Late organ damage ```

Question 34

What is radiogenomics?

Answer 34

The study of the link between germ line genotypic variations and the large clinical variability in response to radiotherapy

Question 35

How can radiation effect genes?

Answer 35

It can upregulate and downregulate them

Question 36

How can you use proteomics to see if a patient will respond to radiotherapy?

Answer 36

Look for hypoxic gene signatures in the tumour

Question 37

How much does nimorazole cost per patient?

Answer 37

25 dollars

Question 38

What is the function of nimorazole?

Answer 38

Sensitises hypoxic cells

Question 39

What cancer responds well to nimorazole?

Answer 39

Head and neck cancer

Question 40

How could you improve nimorazole distribution?

Answer 40

Use gene signatures to see if a patients tumour is hypoxic | It is more effective in more hypoxic cells

Question 41

Describe the concept of self-vaccinating

Answer 41

Radiation produces massive cell death -> releases a lot of antigens into the blood -> encounters the immune system -> immune system produces anti- tumour antibodies

Question 42

What is the issue with combining radiotherapy with immune modulation?

Answer 42

You could overwhelm the immune system and paralyse it

Question 43

What is cyberknife?

Answer 43

a multidimensional planning couch and treatment head moves | Patients lay on the coach, the machine goes around and it irradiates the bits you want to irradiate

Question 44

What is the novalis system?

Answer 44

A radiotherapy machine which rotates 360 degrees without moving a mm

Question 45

What is tomotherapy?

Answer 45

CT scanner in reverse the patients move through the tunnel and there is an array of x-rays targetting the tumour you know you are targetting the tumour since it takes pictures throughout

Question 46

What can go wrong with modernised machines?

Answer 46

They are all controlled by algorithms so if the algorithm is wrong it'll target the wrong thing