Radiation Therapy RT 265 HISTORY zX-rays discovered in 1895 zBecquerel’s accidental experiment showed the first radiobiological effects of x-rays zExperimentation of ram testicles revealed radiosensitivity of different tissues zHigher energy units available in 1950s and advent of linear accelerators

Basis of radiation for therapy zElectromagnetic radiations release energy indirectly to cause cellular damage zX-rays and Gamma rays are similar in action; their production is different zX-rays are produced extranuclearly zGamma rays produced intranuclearly

Production of radiation to cause effect zDepth of irradiation depends on radiation beam zLower energy beams affect skin zHigher energy beams spares skin zDifference between Cobalt-60 and lower energy linear accelerators involves beam shape

Radiation Dose Quantification zRad has generally been replaced by Gray zMeasurement of dose is difficult directly zAbsorbed dose is calculated based on indirect measurements of ionization of air zPattern of energy deposition varies with types of particles causing cellular disruption

Effects on Tumors zBoth malignant cells and normal cells respond similarly to radiation zBoth undergo repair of sublethal damage zBoth cell types are more sensitive during the mitotic phase zOnly malignant cells have areas of hypoxia - reason for fractionation

Systemic Effects zA value often used is LD50 which is the lethal dose for 50% of the population sample zDeaths due to total body exposure zWhen TBI used before bone marrow transplant interstitial pneumonitis is the limiting factor zEffects on immune reactions vary zDepressions generally occur only when large tumors are irradiated or large surface areas zNausea and vomiting secondary to irradiation or disease processes zNausea that presents later during treatment may be secondary to underlying disease process

Radiobiology zFractionation zReassortment of cells zRepair of sublethal damage zAccelerated repopulation

Fractionation zSingle prolonged dose has profound effects on normal tissues zStudies on spermatogenesis of rams zReason for fractionation - allows tumor cells to reassort into the mitotic phase zReduces hypoxia while sparing normal tissues

Reassortment zCells more radiosensitive in mitosis or late in G2 zSurvival curve is steep in these stages zFractionation permits cells to reassort themselves into more sensitive phases of the cell cycle to allow better killing

Sublethal Damage Repair zMolecular basis not understood zDefined as increase in survival when a dose of radiation is split zThis feature is ubiquitous among cells zBecause of ability to repair damage quickly, melanomas have been thought of as “relatively radioresistant”

Rationale for fractionation zReassortment allows for better cell killing zRepair of sublethal damage should be minimized zReoxygenation allows for better cell killing zHyperfractionation used to minimize the late effects of irradiation while increasing dose and tumor control

Tumor volume and control by dose of irradiation zDifficult to extrapolate data zAssumptions must be made: - number of cells proportional to volume - hypoxia does not vary with tumor size z60 Gy leads to depopulation of 10,000,000,000 or regression of a 2 cm mass in 90% of patients

Sequelae of Treatment zAcute and late effects zMucositis zDysphagia zOsteoradionecrosis increases with irradiated volume and increased dose and proximity of dose to mandible zLhermitte’s syndrome and transverse myelitis

Brachytherapy zRadioactive sources placed close to the target zTemporary and permanent implants zAdvantages zEntire tumor must be accessible zLymph node metastases preclude sole use of brachytherapy

Radiotherapy Treatment Planning zPlanning zSimulation zTreatment Every treatment using radiotherapy has to be rigorously planned. The planning process consists of three phases:

Radiotherapy Treatment Planning Planning The 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 zIrradiation using high energy gamma rays. zIrradiation using high energy x-rays. Cancerous tumours can be treated using radiotherapy as follows:

Irradiation Using High Energy Gamma Rays zGamma rays are emitted from a cobalt- 60 source – a radioactive form of cobalt. zThe cobalt source is kept within a thick, heavy metal container. zThis container has a slit in it to allow a narrow beam of gamma rays to emerge.

Radiotherapy Treatment Irradiation Using High Energy X-rays zThe x-rays are generated by a linear accelerator (linac). zThe linac fires high energy electrons at a metal target and when the electrons strike the target, x-rays are produced. zThe x-rays produced are shaped into a narrow beam by movable metal shutters.

Treatment of Cancer Radiotherapy zThe apparatus is arranged so that it can rotate around the couch on which the patient lies. zThis allows the patient to receive radiation from different directions. zThe diseased tissue receives radiation all of the time but the healthy tissue receives the minimum amount of radiation possible. zTreatments 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 zThis involves placing implants in the form of seeds, wires or pellets directly into the tumour. zSuch implants may be temporary or permenant depending on the implant and the tumour itself. zThe benefit of such a method is that the tumour receives nearly all of the dose whilst healthy tissue hardly receives any.

Radiation Therapy Brachytherapy zUterus zCervix zProstate zIntraocular zSkin zThyroid zBone Brachytherapy is used to treat the following cancers: