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Radiation Therapy RT 265HISTORY

X-rays discovered in 1895Becquerel’s accidental experiment

showed the first radiobiological effects of x-rays

Experimentation of ram testicles revealed radiosensitivity of different tissues

Higher energy units available in 1950s and advent of linear accelerators

Basis of radiation for therapy

Electromagnetic radiations release energy indirectly to cause cellular damage

X-rays and Gamma rays are similar in action; their production is different

X-rays are produced extranuclearlyGamma rays produced intranuclearly

Production of radiation to cause effect

Depth of irradiation depends on radiation beam

Lower energy beams affect skin Higher energy beams spares skin Difference between Cobalt-60 and

lower energy linear accelerators involves beam shape

Radiation Dose Quantification

Rad has generally been replaced by GrayMeasurement of dose is difficult directlyAbsorbed dose is calculated based on

indirect measurements of ionization of airPattern of energy deposition varies with

types of particles causing cellular disruption

Effects on Tumors

Both malignant cells and normal cells respond similarly to radiation

Both undergo repair of sublethal damage

Both cell types are more sensitive during the mitotic phase

Only malignant cells have areas of hypoxia - reason for fractionation

Systemic EffectsA value often used is LD50 which is the lethal dose for

50% of the population sampleDeaths due to total body exposureWhen TBI used before bone marrow transplant interstitial

pneumonitis is the limiting factorEffects on immune reactions varyDepressions generally occur only when large tumors are

irradiated or large surface areasNausea and vomiting secondary to irradiation or disease

processes Nausea that presents later during treatment may be

secondary to underlying disease process

Radiobiology

FractionationReassortment of cellsRepair of sublethal damageAccelerated repopulation

Fractionation

Single prolonged dose has profound effects on normal tissues

Studies on spermatogenesis of ramsReason for fractionation - allows

tumor cells to reassort into the mitotic phase

Reduces hypoxia while sparing normal tissues

Reassortment

Cells more radiosensitive in mitosis or late in G2

Survival curve is steep in these stages

Fractionation permits cells to reassort themselves into more sensitive phases of the cell cycle to allow better killing

Sublethal Damage Repair

Molecular basis not understoodDefined as increase in survival when a

dose of radiation is splitThis feature is ubiquitous among cellsBecause of ability to repair damage

quickly, melanomas have been thought of as “relatively radioresistant”

Rationale for fractionation

Reassortment allows for better cell killingRepair of sublethal damage should be

minimizedReoxygenation allows for better cell

killingHyperfractionation used to minimize the

late effects of irradiation while increasing dose and tumor control

Tumor volume and control by dose of irradiation

Difficult to extrapolate dataAssumptions must be made: - number of cells proportional to

volume - hypoxia does not vary with tumor size60 Gy leads to depopulation of

10,000,000,000 or regression of a 2 cm mass in 90% of patients

Sequelae of Treatment

Acute and late effectsMucositisDysphagiaOsteoradionecrosis increases with

irradiated volume and increased dose and proximity of dose to mandible

Lhermitte’s syndrome and transverse myelitis

Brachytherapy

Radioactive sources placed close to the target

Temporary and permanent implantsAdvantagesEntire tumor must be accessibleLymph node metastases preclude sole use

of brachytherapy

Radiotherapy Treatment Planning

PlanningSimulationTreatment

Every treatment using radiotherapy has to be rigorously planned. The planning process consists of three phases:

Radiotherapy Treatment Planning

PlanningThe cancerous tumour has to be located so that its size and position can be analysed. This information can be obtained from:

•X-rays•CT scans•MRI scans•Ultrasound images

Radiotherapy Treatment Planning

Simulation

Once the amount of radiation to be given has been accurately calculated, the patient then goes to the simulator to determine what settings are to be selected for the actual treatment using a linear accelerator.

The settings are determined by taking a series of x-rays to make sure that the tumour is in the correct position ready to receive the ionising radiation.

Radiotherapy Treatment Planning

Treatment

Irradiation using high energy gamma rays.

Irradiation using high energy x-rays.

Cancerous tumours can be treated using radiotherapy as follows:

Irradiation Using High Energy Gamma Rays Gamma rays are

emitted from a cobalt-60 source – a radioactive form of cobalt.

The cobalt source is kept within a thick, heavy metal container.

This container has a slit in it to allow a narrow beam of gamma rays to emerge.

Radiotherapy Treatment

Irradiation Using High Energy X-rays The x-rays are

generated by a linear accelerator (linac).

The linac fires high energy electrons at a metal target and when the electrons strike the target, x-rays are produced.

The x-rays produced are shaped into a narrow beam by movable metal shutters.

Treatment of Cancer

Radiotherapy

The apparatus is arranged so that it can rotate around the couch on which the patient lies.

This allows the patient to receive radiation from different directions.

The diseased tissue receives radiation all of the time but the healthy tissue receives the minimum amount of radiation possible.

Treatments are given as a series of small doses because cancerous cells are killed more easily when they are dividing, and not all cells divide at the same time – this reduces some of the side effects which come with radiotherapy.

Radiation Therapy

Brachytherapy This involves placing

implants in the form of seeds, wires or pellets directly into the tumour.

Such implants may be temporary or permenant depending on the implant and the tumour itself.

The benefit of such a method is that the tumour receives nearly all of the dose whilst healthy tissue hardly receives any.

Radiation Therapy

Brachytherapy

UterusCervixProstateIntraocularSkinThyroidBone

Brachytherapy is used to treat the following cancers: