Oncology - Treatment of cancer Flashcards
What is radiotherapy?
Radiotherapy uses ionising radiation to kill malignant cells. Unlike chemotherapy it is a local treatment, rather than systemic.
But like chemotherapy, radiotherapy cannot differentiate between malignancy and normal rapidly dividing cells and this causes side effects (mostly local in radiotherapy).
E.g. radiotherapy for prostate cancer produces radiation cystitis (frequency and dysuria) and radiation proctitis (diarrhoea and rectal bleeding)
What acute and late effects can occur in radiotherapy for breast cancer?
Acute effects - radiation inflammation, normally resolves when treatment is finished
Late effects - lymphadenopathy, due to fibrosis of the lymphatic ducts
What are the types of radiotherapy?
1) Teletherapy - external beam radiotherapy
- most common
2) Brachytherapy - source in or near to the tumour
3) Radioisotope therapy - ingestion/ injection of radioactive elements
- uncommon, e.g. radioactive iodine in treating thyroid cancer, radioactive strontium for boney secondaries, radioactive phosphorous for primary polycythaemia
What are the most common indications for brachytherapy?
In the UK, the most common indications are treating gynaecological and prostate cancers. There are various radionucleotides used, but radioactive Caesium is probably the most common.
How does radiotherapy damage DNA?
Radiation displaces orbiting electrons leading to ionisation of water molecules. This forms a hydroxyl free radical which damages DNA.
How does prostate brachytherapy work?
Steele pellets containing radioactive iodine are inserted under anaesthesia, via the anterior rectal wall or perineal approach, and remain permanently in place. With time, the decaying radioactive iodine gives off radiation that locally kills the prostate cancer. This accounts for less than 10% of all cancer radiotherapy.
What skin cancers respond best to external beam radiotherapy?
SCC and BCC are very sensitive to radiotherapy.
Malignant melanoma is best managed surgically and not with radiotherapy.
What is radiation measured in?
The rad was the old unit of radiation which has been replaced with Grays (Gy)
1 rad = 1 centiGray (cGy)
How is radiotherapy administered?
Radiotherapy is administered as a total dose given in specific fractions over a certain time frame. Usually, radiotherapy is given during week days.
Thus, a dose of 40Gy in 15 fractions over 3 weeks would be 2.6 fractions per day. Different dosing regimes have the same biologically equivalent doses of radiation by increasing the total fraction and giving it over longer periods of time.
What is the difference between curative and palliative radiotherapy?
The main difference between the two is the dose of radiation.
Curative treatments usually involve multiple high dose treatments (e.g. 60Gy/30 fractions/ 6 weeks). A single dose of 8Gy/ 1 fraction is a useful dose for palliation.
What is the concept of repair in radiobiology?
There is no cancer that cannot be cured with a large enough dose of radiation, but whilst this would kill the cancer cells it would also kill the patient. The way around this is to give smaller doses of radiation, often. Normal cells are damaged alongside cancerous ones when radiation is given. But because non cancerous cells have a greater capacity for repair (which can start after 4 hours or so) compared to cancerous cells, successive treatments (e.g. over 24 hours) deplete cancer cell numbers but give time for normal cells to repair.
What is the oxygen effect?
There needs to be sufficient levels of oxygen for radiotherapy to work. Radiosensitivity is highest when oxygen tension is at the level of arterial blood. Clinically, if you are treating a patient who is anaemic with a Hb of less than 10, you should give them a blood transfusion before radiotherapy.
What is the mechanism of action of alkylating agents?
Alkylating agents transfer an alkyl group to purine (adenine and guanine) DNA bases. Alkylating agents can either be bifunctional or monofunctional. Bifunctional alkylating agents form covalent bonds form between two different bases which introduces interstrand cross links. Monofunctional alkylating agents cannot cause cross links but form adducts. Both of these alterations inhibit DNA synthesis, so alkylating agents work best during the S phase of the cell cycle (phase specific agents). Examples of alkylating agents include mitomycin C, chlorambucil, and cyclophosphamide.
What side effects are associated with cyclophosphamide?
Haemorrhagic cystitis
Myelosuppression
Transitional cell carcinoma
What is the mechanism of action of antimetabolites?
Antimetabolites are structurally similar to natural compounds and interfere with cellular enzymes. These agents inhibit the metabolism (usually synthesis) of compounds necessary for DNA, RNA or protein synthesis. This includes: (1) purine analogues, (2) pyrimidine analogues, (3) folic acid analogues, and (4) others, e.g. hydroxyurea. Most antimetabolites have their greatest effect during S phase.
Examples include:
- methotrexate: inhibits dihydrofolate reductase
- 5-FU: pyrimidine analogue inducing cell cycle arrest and apoptosis by blocking thymidylate synthase
- 6 mercaptopurine: decreasing purine synthesis
- cytarabine: pyrimidine antagonist
What are the side effects of methotrexate?
Myelosuppression
Mucositis
Liver fibrosis
Lung fibrosis
What is the mechanism of action of intercalating agents?
Intercalating agents interrupt the integrity of the DNA double helix. There exact mechanism of action is unknown, although anthracycline antibiotics intercalate into the major DNA groove between base pairs of the double helix and this action is non covalent with no base sequence specificity. Platinum agents also intercalate and form intrastrand links similar to alkylating agents.
Examples include:
1) Platins - e.g. cisplatin, carboplatin, oxaliplatin
2) Antibiotics - e.g. doxorubicin, bleomycin
What are the side effects of cisplatin?
Ototoxicity
Peripheral neuropathy
Hypomagnesaemia
What is the mechanism of action of the spindle poisons?
Antimicrotubule drugs can be divided into two groups, those that stabilise microtubules by inhibiting depolymerisation (e.g. taxanes) and those that are depolymerising agents that inhibit polymerisation of tubulin (e.g. vinca alkaloids). Spindle poisons inhibit the mitotic spindle function and therefore act during M phase of the cell cycle.
What are the side effects of the vinca alkaloids?
This includes vincristine and vinblastine.
Vincristine: peripheral neuropathy (reversible), paralytic ileus
Vinblastine: myelosuppresion
What are the side effects of the taxanes?
The most clinically useful taxane is docetaxel which causes neutropaenia.
What is the mechanism of action of the topoisomerase inhibitors?
Topoisomerase prevents DNA strands from becoming tangled by cutting DNA and allowing it to wind and unwind. There are two classes of topoisomerase: topoisomerase type I breaks single strands of DNA, whilst topoisomerase type II breaks two strands of DNA. Topoisomerase type I inhibitors include topotecan and irinotecan. Type II inhibitors include etoposide and teniposide.
What cancers have a low sensitivity to chemotherapy?
Some tumours have an intrinsic resistance to chemotherapy which in part accounts for for the variable sensitivity of different cancer types to chemotherapy.
Kidney cancer, melanoma, adult brain tumours and prostate cancer generally have low sensitivity so chemotherapy is of limited use.
What causes resistance to chemotherapy?
Resistance to chemotherapy can be to one drug or a combination of drugs. The latter is normally caused by expression of efflux pumps on tumour cell membranes. The most commonly found pump in multi-resistant tumour cells is P-glycoprotein or the multidrug resistance protein (MDR).
Cytotoxic specific resistance occurs through a number of mechanisms - e.g. efficient DNA repair, reduced drug uptake, increased drug efflux, intracellular inactivation.
Name some examples of cancers were chemotherapy is used neoadjuvantly and adjuvantly
Neoadjuvant:
- Soft tissue sarcoma
- Osteosarcoma
- Locally advanced breast cancer
Adjuvant:
- Wilm’s tumour
- Osteosarcoma
- Breast cancer
- Colorectal cancer