Introduction to Systemic Therapies and Radiotherapy Flashcards

1
Q

What are the 4 broad categories of systemic therapy?

A

Chemotherapy
Biologics
Hormonal therapy
Immunology

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the aims of adjuvant/neoadjuvant therapy?

A

Improve chances of cure above definitive surgery/radiotherapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the aims of palliative therapy?

A

Symptom control
Improved QoL
Increased survival

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is chemotherapy?

A

Non-specific therapy that is broadly aimed at attacking rapidly dividing cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How does chemotherapy’s mode of action cause most of its side effects?

A

Chemo acts on rapidly dividing cells, hence it affects hair follicles –> alopecia, GI tract mucosa –> mouth ulcers, diarrhoea, and bone marrow stem cells –> neutropenia, thrombocytopenia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How does chemo work?

A

Interrupts process of mitosis (e.g. disrupts DNA synthesis, integrity or disrupts microtubule function etc.)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the main classifications of chemotherapy?

A
Alkylating agents
Anti-metabolites
Mitotic inhibitors
Topoisomerase inhibitors
Other antitumour antibiotics
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the akylating agents?

A

Cisplatin, cyclophosphamide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are e.g.s of anti-metabolites?

A

5FU, methotrexate, gemcitabine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are e.g.s of mitotic inhibitors?

A

Taxanes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are examples of topoisomerase inhibitors?

A

Topotecan, doxorubicin, etoposide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the antitumour antibiotics?

A

Bleomycin, actinomycin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How do antimetabolites work?

A

Disrupt DNA synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How do alkylating agents and topoisomerase inhibitors work?

A

Disrupting DNA integrity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How do mitotic inhibitors work?

A

Disrupting microtubule function that is essential for equal disruption of genetic material

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is a chemotherapy regimen and why is it used?

A

Combination of chemo drugs to achieve better tumour kill and reduce change of resistance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the standard chemo regimen used for metastatic testicular cancer?

A

Bleomycin, etoposide, cisplatin (BEP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are biological agents?

A

Agents designed to inhibit the oncogenic stimulus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the two main categories of biologics?

A
Monoclonal antibodies (-imabs)
Tyrosine kinase inhibitors (-inibs)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the standard pattern for cell signalling?

A
  1. Ligand binds to cell surface receptor
  2. Leading to dimerization of transmembrane receptor with
  3. Activation of intracellular tyrosine kinase domain and
  4. Downstream signalling events leading to
  5. nuclear events (up/down regulation of gene expression etc.)
21
Q

What is the action of rituximab?

A

CD-20 monoclonal antibody

22
Q

What biologic is used in the treatment of CML?

A

Imatinib (tyrosine kinase inhibitor against ABL-BCR mutation)

23
Q

What is trastuzumab?

A

Monoclonal Ab that prevents HER2 function

AKA Herceptin

24
Q

What is cetuximab?

A

Monoclonal AB that prevents EGF receptor function

25
Q

What is sunitinib?

A

TKI that prevents VEGF receptor tyrosine kinase function

26
Q

What is bevacizumab?

A

Monoclonal Ab that sequesters VEGF

27
Q

How does hormonal therapy work?

A

A number of cancer express hormone receptors and hence are amendable to treatment via hormone manipulation

28
Q

What hormone therapies may be useful in treating breast cancer?

A

Tamoxifen (anti-oestrogen)
Aromatase inhibitors (anastrazole)
GnRH agonists

29
Q

What hormone therapies may be useful in prostate cancer?

A
Androgen suppression (goserelin/orchidectomy) 
Anti-androgens (bicalutamide) 

Prostate cancer often driven by testosterone

30
Q

What hormone therapies may be useful in endometrial cancer and why?

A

Progestogens may benefit as endometrial cancer often driven by oestrogen and inhibited by progesterone

31
Q

What is immunotherapy (in cancer management)?

A

Treatments that stimulate the immune system as a whole

32
Q

What are the two main drugs used in immunotherapy?

A

Interferon

Interleukin

33
Q

How do many cancer evade detection by the immune system?

A

By supressing T cell function through interaction of PD-1 receptor (programmed cell death protein-1) on the T cell and PDL-1 protein on tumour cells

When PD-1 is activated by PDL-1, T cell response is inhibited, rendering the cancer invisible to the immune system

34
Q

What is radiotherapy?

A

Ionising radiation

Through ionisations and production of free radicals it can result in damage to DNA

35
Q

How does radiotherapy work?

A

–> DNA damage which can result in single strand DNA breaks (which are easier to repair) or double strand breaks (which are harder to repair) and so cell undertakes error prone repair
Error prone repair –> translocations (these become visible as chromosomal abberations

Translocations usually = no loss of critical DNA so cell = viable

However, radiotherapy –> loss of reproductive capacity since at mitosis, the absence of centromeres, or presence of more than one centromere on a chromosome etc. means microtubules fail to deliver equal amounts of DNA to daughter cells –> death of both daughter cells

36
Q

How is the dose of radiotherapy measured?

A

In grays

1Gy = 1 joule of energy deposited in 1kg of tissue

37
Q

What is radiation tolerance?

A

The amount of radiation a cell can receive and still remain functional

38
Q

What is tolerance dose?

A

Dose of radiation above which there is an unacceptably high probability of serious treatment complication

39
Q

What is the aim of radiotherapy?

A

To treat with a dose that achieves the intended outcome whilst keeping the critical nearby structures within their radiation tolerance

40
Q

Give examples of tissues that are extremely radiosensitive

A

Bone marrow

Lens of eye

41
Q

Give examples of tissues that are very radioresistant

A

Ureters, mature breasts, muscle

42
Q

How might palliative radiotherapy differ from radical radiotherapy?

A

Radical - high dose, low dose per fraction, longer treatment course

Palliative - low dose, high dose per fraction, delivered over short course

43
Q

How can radiotherapy be delivered?

A
External beam (teletherapy) 
Brachytherapy - sealed source/unsealed source
44
Q

What is involved in teletherapy?

A

Using a linear accelerator to delivery X-Rays

X-ray photons are produced by electrons being accelerated along the linear accelerator

45
Q

True or false:
During radiotherapy, using multiple field techniques the beam ‘overtreats’ the superficial tissue relative to the tumour, but the tumour receives a high dose while keeping the normal tissue within its tissue tolerance

A

True

46
Q

What is the difference between teletherapy and brachytherapy?

A

Tele - radiation delivered from a distance

Brachy - radiation delivered in close proximity to the tumour

47
Q

What is involved in unsealed source treatments?

A

Radioactive isotope delivered into patient (injection/ingestion) which concentrates in the region to be irradiated

48
Q

Give examples of unsealed treatments?

A

I131 taken up by thyroid tissue and ablates thyroid

Sr89 taken up by osteoblastic metastates + delivers high dose RT to multiple bony mets in prostate cancer

49
Q

What is involved in sealed source radiotherapy?

A

Radioactive needle/wire implanted or placed next to cancer in order to deliver extremely high dose to tumour but lower dose to adjacent critical structures