8.1/8.2 radiotherapy I & II Flashcards
what is radiation therapy?
using ionizing radiation to kill tumors
what are radiation doses delivered to, and how are these doses decided?
- delivered to malignant tumors
- since we know the threshold dose for different types of tumors, we can set this amount of radiation to them to kill them
what are “deterministic effects” of radiation? how do we use this to our advantage regarding tumors?
- deterministic effects are short-term, adverse tissue reactions resulting from a dose that is significantly high enough to damage living tissues
- the severity of a deterministic effect increases with radiation dose above a threshold, below which the detectable tissue reactions are not observed
- because doses are in the deterministic regime, a predictable fraction of the tumor cells die
what is a major disadvantage to the use of radiotherapy to kill tumors? explain
- healthy tissues are also exposed to high doses, along with tumors
- this is because with ionizing radiation, we cannot focus the radiation as we can do with light photons
what is a consequence of healthy tissues being exposed to high radiation doses?
- these treatments deliver a stochastic dose to the rest of the body
- which may crease an increased risk of cancer at some later time (this small risk is weighed against an existing life-threatening disease)
what occurs before a patient undertakes radiotherapy?
- we use the ‘justification principle’
- we weigh the future risk of using the radiotherapy with the benefit
what does it mean for cancerous tumors to be radiosensitive?
responding well to radiotherapy
why are tumors radiosensitive?
because most malignant tumors fall into the class of rapidly reproducing cells, they are easily affected by radiation
what are two reasons destroying enough of a tumor to prevent its regrowth is a difficult task?
- because if one cell is left behind, the tumor will reseed
- because we are exposing healthy tissues to radiation
if cancer cells aren’t necessarily confined in separate, compact masses, what does that mean?
it means they can be spread throughout the body and infiltrate vital organs
if cancer is easily spread and can infiltrate many organs, treating cancer often involves?
treating an entire region surrounded by healthy tissue
in radiotherapy, what do we try to choose when treating cancer?
the optimum dose of radiation
what is the optimum dose?
a dose that will kill the cancer, but take into consideration the surrounding healthy tissues
what does choosing an optimum dose infer?
that a compromise is made between the effectiveness in tumor killing and in sparing nearby healthy tissue
what plot or graph is used to find the optimum dose?
the dose-response curve
what does the dose-response curve show?
- that even small variations in treatment dose leads to undesirable consequences
- too high a dose kills too many healthy cells
- too low a dose spares some tumor cells
what are the significant features of the dose-response curve?
- there is a threshold dose for cell killing
- the fraction of cells killed increases with dose via a characteristic S-shaped curve
- there is a dose at which 100% of cells are killed thus no effect is seen if dose is increased
if the threshold for the healthy tissue exceeds that for the tumor, treatments can use a dose that:
- kills most of the tumor cells
- affects relatively few of the healthy cells
there are situations where there is an appreciable overlap between the two curves in the plot, what does this mean?
that killing appreciable numbers of tumor cells will inflict great damage on healthy tissue
what does the form of the dose-response curve depend on generally?
- the tissue from which the cells originate
- the type of ionizing radiation used (ex: gamma photons, electrons)
- the energy (of those particles)
- the rate at which the radiation dose is delivered
how does the dose-response curve depend on the rate at which the radiation dose is delivered?
- more rapidly delivered doses cause more damage (to tumors) with a lower threshold
- this can protect more healthy tissue (fractionation)
what process is very important for the protection of healthy tissues in radiotherapy?
fractionation
what aspect of healthy cells makes the use of fractionation beneficial?
the tendency to have better DNA repair mechanisms than cancer cells do
what is fractionation?
dividing the high doses required to kill tumor cells into small fractions, giving healthy tissues time to repair
what is then made with these “smaller doses” during fractionation?
the smaller doses are delivered with a pause of a day or do between fractions
what are the consequences of using fractionation?
- giving time to healthy cells to recover and repopulate
- which means also exposing cancer cells to radiation for longer periods
how else does using fractions damage tumor cells?
by changing the point in the cell cycle at which the tumor cells are irradiated
what does the cure rate and effectiveness of radiation greatly depend on?
- cancer type
- specifics of individual cases
how does cancer type differ when it comes to responsiveness of treatment?
- for regions of the body such as superficial skin cancers, radiation is especially effective
- other areas, the responsiveness of tumor cells differ little from that of neighboring healthy cells (less responsive)
if a cure is unlikely, how can radiation therapy be used?
as a palliative measure
what are the 4 R’s of fractionation?
- repair
- redistribution
- re-oxygenation
- repopulation
describe repair
- lasts for: few hours
- healthy cells are allowed to repair sub-lethal damage
describe redistribution
- lasts for: few hours - days
- tumor cells are given time to redistribute themselves into more radiosensitive phases of the cell cycle between radiation fractions
describe re-oxygenation
- lasts for: few hours - days
- tumor cells are poly-oxygenated
- when exposed to oxygen, the oxygen makes the cancer cells more radiosensitive
- tumor hypoxia and greater radio-sensitivity is seen
what does the use of the 4 R’s determine?
the success or failure of standard clinical radiation treatments
describe repopulation
- lasts for: few weeks
- the tendency of healthy and cancer cells to repopulate after irradiation
what are the types of fractionation schemes?
- conventional
- hyper-fractionation
- accelerated fractionation
- hypo-fractionation
what do we usually choose the type of fractionation scheme based on?
based on the type of cancer
describe conventional fractionation
- dose/fraction: 1.8 - 2.2 Gy
- total dose: 45.0 - 50.4 Gy
- fractions/week: 5 (treatment given once a day)
- issues: can be too slow for fast growing tumors, dose too low for resistant cancers
describe hyper-fractionation
- dose/fraction: 1.1 - 1.3 Gy (v low)
- total dose: 70 - 80 Gy (v high)
- fractions/week: 10 (patient is sometimes irradiated twice a day)
- issues: burden on patients, staff & equipment, no clear benefit has been demonstrated
describe accelerated fractionation
- dose/fraction: 1.4 - 2.5 Gy
- total dose: 40 - 50 Gy
- fractions/week: 10 (treatment 2x a day)
- issues: burden on patients, staff & equipment, acute reactions
describe hypo-fractionation
- dose/fraction: above 2.5 Gy (relatively high)
- total dose: 20 - 55 Gy (low)
- fractions/week: 1 - 5 (treatment given once a day or less)
- issues: acute reactions (due to high dose/fraction)
why do some fractionation types with high dose/fraction cause acute reactions?
with high dose/fraction, in most cases this is a threshold for deterministic effects, which cause acute reactions
which type of fractionation is used for fast growing tumors?
accelerated fractionation
which type of fractionation is used to avoid late normal tissue complication?
hyper-fractionation
usually delivered to the chest wall & regional lymph nodes
conventional fractionation scheme
what is an advantage regarding hyper-fractionation?
- because dose/fraction is lower in this type, this results in avoiding deterministic effects
- lower doses = below deterministic threshold doses
- avoid normal tissue complications in the future
compare accelerated fractionation with conventional fractionation
- conventional: 4.6 weeks for dose to be delivered to tumor
- accelerated: 2 weeks for dose to be delivered
- the same amount of dose is delivered in twice the amount of time in conventional
- this is due to the 10 fractions/week for accelerated fractionation