Principles of Treatment

Question 1

Smallest clinically detected mass of a tumour

Answer 1

1g (10^9 cells)

Question 2

Tumour is usually detected at ____?

Answer 2

10g (10^10 cells)

Question 3

Lethal size of a tumour?

Answer 3

1kg (10^12 cells)

Question 4

Factors affecting the slope of the Gomperzian Growth curve

Answer 4

Ratio of cell division to cell loss
Growth fraction
Doubling time (TD)
Host factors

Question 5

What are the host factors that affect the slope of the Gomperzian Growth Curve?

Answer 5

Vasculature
Space restrictions
Necrosis
Presence of other cell populations

Question 6

Mechanism of Metastasis?

Answer 6

Dissolution of basement membrane by lytic enzymes, facilitating invasion and movement

Invasion and movement through defects due to increased cell motility, decreased cell to cell adhesiveness

Binding of tumour to basement membrane through the mediation of altered receptors on the cell surface

Question 7

What are the goals of cancer treatment??

Answer 7

Curative
Maintenance of quality and duration of life
Symptom relief
Clinical trials for experimental therapies

Question 8

What are the characteristics of an ideal treatment?

Answer 8

Safe, effective and discriminating
Targets only the cancer cells
Few side-effects
Return patient to former state of health

Question 9

Uses for surgical debulking?

Answer 9

Decrease the size of the tumour to allow chemo/radiotherapy to be more effective

Pain/symptom relief

Remove source of ectopically expressed hormones

Prevention - removal of polyps, moles

Question 10

MOA of radiation therapy?

Answer 10

Destruction of cancer cells by ionizing radiation

Question 11

Target of radiation therapy?

Answer 11

Cellular DNA

Question 12

Two methods of radiation therapy?

Answer 12

1) External Beam

2) Brachytherapy/ Interstitial brachytherapy - Insertion of implant near or inside tumour

Question 13

Curability of radiation therapy depends on?

Answer 13

Size, location of tumour, type of tumour, tumour radiosensitivity

Question 14

Dose-limiting factor of radiotherapy?

Answer 14

Normal tissue damage

Question 15

Preventive measure to minimise normal tissue damage?

Answer 15

RT with curative intent fractionated and given in small doses

Question 16

What are the basic principles of cancer chemo?

Answer 16

1) Drug kills a constant proportion of tumour cells
2) Chemo has the greatest effect on actively proliferating cells
3) Chemo drugs has a narrow therapeutic index, treatment is a balance between toxic effects an efficacy
4) Combi therapy can be used to improve treatment outcomes

Question 17

Advantages of Combi therapy

Answer 17

1) Maximum cell kill
2) Broad coverage against multiple cell lines
3) Slower emergence of resistant strains

Question 18

Disadvantages of combi therapy

Answer 18

1) Complicated and expensive to administer
2) Impact of dose effect
3) Multiple toxicities with greater patient discomfort

Question 19

What is the unit for chemo doses?

Answer 19

1) Unit weight

2) Body surface area

Question 20

What is the benefit of BSA

Answer 20

Provides a more accurate cross-species comparison of activity and toxicity

Question 21

Formula of BSA?

Answer 21

Square root (Weight [kg]) * Height [cm] / 3600)

Question 22

Function of the schedule of administration?

Answer 22

1) Followed to achieve optimal therapeutic benefit with minimal toxicity
2) Allow for “drug rest”

Question 23

How do you intensify the chemo treatment?

Answer 23

1) Reduce dosing interval

2) Increase dose

Question 24

Factors affecting the selection of chemotherapy regimen?

Answer 24

1) Histological documentation of tumour type
2) Stage of disease
3) Prognostic variable
4) Patient-related variables
5) Toxicities
6) Risk vs benefits

Question 25

What are the patient-related variables affecting selection of chemo?

Answer 25

1) Organ function
2) Concomitant disease
3) Nutritional status
4) Social
5) Economic
6) Cultural
7) Lifestyle

Question 26

What are the factors affecting response to chemotherapy?

Answer 26

1) Drug
2) Tumour
3) Patient

Question 27

What are the drug factors affecting response to chemo?

Answer 27

1) Drug intensity
2) Drug scheduling
3) Cell-cycle specificity

Question 28

What are the tumour factors affecting response to chemo?

Answer 28

1) Size
2) Location (Anatomic site)
3) Resistance
4) Blood supply

Question 29

What are the patient factor affection response to chemo?

Answer 29

1) Drug tolerance

2) Renal/ Hepatic function

Question 30

Combination therapy is used to overcome what challenges?

Answer 30

1) Sensitivity - Tumour may be non responsive to clinically achievable dose
2) Toxicity - Avoid the use of high doses
3) Resistance - Inherent genetic instability can result in non-random mutation that confers resistance

Question 31

What are the mechanism of chemo resistance?

Answer 31

1) Decrease accumulation of drug - Via increased efflux, decrease uptake and altered intracellular trafficking
2) Decrease in drug activation
3) Increase in drug metabolism
4) Increase ability to repair drug-induced damage
5) Use alternative biochemical pathway
6) Altering drug target

Question 32

Desirable characteristics of combi therapy?

Answer 32

1) Must not antagonise one another
2) Effective
3) Different dose-limiting toxicities
4) Different pharmacological action
5) Increase overall intensity of treatment
6) Given in a dose equivalent to that used when the drug is given alone

Question 33

The larger the tumour, the _______?

Answer 33

1) Greater chance of metastasis
2) Greater probability of drug-resistance cells
3) Greater chance of poor drug distribution - Central necrosis

Question 34

Where are the sanctuary sites? Why do they affect chemo outcome?

Answer 34

CNS , Testis

1) Poor drug penetration
2) Poor blood supply