Introduction to Systemic Therapies and Radiotherapy

Question 1

What are the 4 broad categories of systemic therapy?

Answer 1

Chemotherapy
Biologics
Hormonal therapy
Immunology

Question 2

What are the aims of adjuvant/neoadjuvant therapy?

Answer 2

Improve chances of cure above definitive surgery/radiotherapy

Question 3

What are the aims of palliative therapy?

Answer 3

Symptom control
Improved QoL
Increased survival

Question 4

What is chemotherapy?

Answer 4

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

Question 5

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

Answer 5

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

Question 6

How does chemo work?

Answer 6

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

Question 7

What are the main classifications of chemotherapy?

Answer 7

Alkylating agents
Anti-metabolites
Mitotic inhibitors
Topoisomerase inhibitors
Other antitumour antibiotics

Question 8

What are the akylating agents?

Answer 8

Cisplatin, cyclophosphamide

Question 9

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

Answer 9

5FU, methotrexate, gemcitabine

Question 10

What are e.g.s of mitotic inhibitors?

Answer 10

Taxanes

Question 11

What are examples of topoisomerase inhibitors?

Answer 11

Topotecan, doxorubicin, etoposide

Question 12

What are the antitumour antibiotics?

Answer 12

Bleomycin, actinomycin

Question 13

How do antimetabolites work?

Answer 13

Disrupt DNA synthesis

Question 14

How do alkylating agents and topoisomerase inhibitors work?

Answer 14

Disrupting DNA integrity

Question 15

How do mitotic inhibitors work?

Answer 15

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

Question 16

What is a chemotherapy regimen and why is it used?

Answer 16

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

Question 17

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

Answer 17

Bleomycin, etoposide, cisplatin (BEP)

Question 18

What are biological agents?

Answer 18

Agents designed to inhibit the oncogenic stimulus

Question 19

What are the two main categories of biologics?

Answer 19

Monoclonal antibodies (-imabs)
Tyrosine kinase inhibitors (-inibs)

Question 20

What is the standard pattern for cell signalling?

Answer 20

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.)

Question 21

What is the action of rituximab?

Answer 21

CD-20 monoclonal antibody

Question 22

What biologic is used in the treatment of CML?

Answer 22

Imatinib (tyrosine kinase inhibitor against ABL-BCR mutation)

Question 23

What is trastuzumab?

Answer 23

Monoclonal Ab that prevents HER2 function

AKA Herceptin

Question 24

What is cetuximab?

Answer 24

Monoclonal AB that prevents EGF receptor function

Question 25

What is sunitinib?

Answer 25

TKI that prevents VEGF receptor tyrosine kinase function

Question 26

What is bevacizumab?

Answer 26

Monoclonal Ab that sequesters VEGF

Question 27

How does hormonal therapy work?

Answer 27

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

Question 28

What hormone therapies may be useful in treating breast cancer?

Answer 28

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

Question 29

What hormone therapies may be useful in prostate cancer?

Answer 29

``` Androgen suppression (goserelin/orchidectomy) Anti-androgens (bicalutamide) ``` Prostate cancer often driven by testosterone

Question 30

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

Answer 30

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

Question 31

What is immunotherapy (in cancer management)?

Answer 31

Treatments that stimulate the immune system as a whole

Question 32

What are the two main drugs used in immunotherapy?

Answer 32

Interferon | Interleukin

Question 33

How do many cancer evade detection by the immune system?

Answer 33

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

Question 34

What is radiotherapy?

Answer 34

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

Question 35

How does radiotherapy work?

Answer 35

--> 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

Question 36

How is the dose of radiotherapy measured?

Answer 36

In grays | 1Gy = 1 joule of energy deposited in 1kg of tissue

Question 37

What is radiation tolerance?

Answer 37

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

Question 38

What is tolerance dose?

Answer 38

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

Question 39

What is the aim of radiotherapy?

Answer 39

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

Question 40

Give examples of tissues that are extremely radiosensitive

Answer 40

Bone marrow | Lens of eye

Question 41

Give examples of tissues that are very radioresistant

Answer 41

Ureters, mature breasts, muscle

Question 42

How might palliative radiotherapy differ from radical radiotherapy?

Answer 42

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

Question 43

How can radiotherapy be delivered?

Answer 43

``` External beam (teletherapy) Brachytherapy - sealed source/unsealed source ```

Question 44

What is involved in teletherapy?

Answer 44

Using a linear accelerator to delivery X-Rays X-ray photons are produced by electrons being accelerated along the linear accelerator

Question 45

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

Answer 45

True

Question 46

What is the difference between teletherapy and brachytherapy?

Answer 46

Tele - radiation delivered from a distance | Brachy - radiation delivered in close proximity to the tumour

Question 47

What is involved in unsealed source treatments?

Answer 47

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

Question 48

Give examples of unsealed treatments?

Answer 48

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

Question 49

What is involved in sealed source radiotherapy?

Answer 49

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