Radiation Therapy

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What is the Goal of Radiation Therapy
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Is to sterilize a targeted tumor completely while preserving the integrity of surrounding normal structures.
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Principles of Radiation Therapy
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High-energy ionizing radiation destroys the cancer cell’s ability to grow and multiply. Some cells are directly damaged by the ionizing rays or particles. More cells are indirectly affected when the ionizing rays or particles penetrate the cell’s nucleus and interact with the water content of the nucleus to form oxygen radicals.
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Radiosensitivity of Cancer Cells
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Radiosensitivity of cells depend on several factors: Type of Cell Phase of the Cell Cycle Division rate of the cell Degree of differentiation Oxygenation
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Radiation Therapy Limitations
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Body tissues have limits to the amount of radiation that can be tolerated. Exceeding those limits can result in serious complications. Emami Article Qualtrex
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Principles of Radiation Therapy
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Radiation dose is determined by: Radiosensitivity of the tumor. Normal tissue tolerance. Volume of tissue to be irradiated.
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Radiation Therapy
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Factors which decide the choice of modality to be used: General condition of patient Extent of Disease Histologic nature of tumor
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What are the treatment types
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Types of Treatment Radical – Curative – Definitive Combined modality Prophylaxis Palliative
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Radical -Curative -Definitive
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An attempt to remove all of the malignancy present. Early stages (I and II) Some stage III
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Seven Factors in the Decision To Treat for Cure
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Type of tumor Condition of patient Age of patient Stage of tumor Extent of disease Availability of treatment facilities Patient’s consent
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Palliative Radiation Therapy
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Shorter courses Lower doses Symptom relief bone pain bleeding obstruction brain mets liver mets
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Tumor sensitivity
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Radiosensitive Responds to a dose of ~2000-4000 cGy in 2 – 4 weeks Moderately Sensitive Responds to a dose of ~ 5000 – 6000 cGy in 4 – 6 weeks Radioresistant May show no response at all to a dose of 8000 – 10,000 cGy in 6-8 weeks
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Parameters of Therapy Tolerance Doses and Tolerance Volumes
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Dose Fractionation Volume Time Chemotherapy Innovations
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Doses
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There is no absolute or fixed dose that ablates normal tissues because of the TD 5/5 and TD 50/5.
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TD 5/5
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Minimal Tolerance Dose The dose which will produce a given complication in no more than 5% of patients in 5 years.
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TD 50/5
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Maximal Tolerance Dose The dose which will produce a 50% complication rate in 5 years
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Standard Set of Conditions-Supervoltage radiation
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Supervoltage radiation Dose delivery of 200 +/- 10% cGy per day, 5 fractions per week (1000 cGy), 2-day rest interval Completion of treatment in 6-8 weeks Doses conditioned by partial volume organ irradiation
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Dose Selection
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Depends on weighing the probability of cure versus the probability of complications. Cost-benefit analysis. When cure rates are similar for different modalities – surgery Vs radiation Vs chemotherapy- negative outcomes, their frequencies, and severity often are the basis of the final choice of dose. State of host Volume to be treated
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Classification of Organs
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Class I Organs Radiation damage results in severe morbidity or mortality Class II Organs Radiation damage results in either no morbidity or mild transient reversible effects Class III Organs Radiation damage results in mild to moderate morbidity (rarely mortality) and generally late effects are compatible with survival.
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Fractionation
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When a given dose of radiation is divided into increments and delivered over a period of several hours or days.
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Hyperfractionation
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Increase in the number of fractions and reduction in dose per fraction in the same overall time Delivers smaller than standard fractional doses (100-120 cGy). 2-3 times per day. 4-6 hour intervals. Overall treatment time remains the same 6-8 weeks. Total dose increase by 10-20%.
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Accelerated Fractionation
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A reduction in overall time without a change in dose per fraction or total dose Delivers fractional doses of 150-200 cGy Multiple treatments per day Total dose remains the same Overall treatment time is halved
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Hypofractionation
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Use of large daily fractions, however, the patient is not treated 5 days per week Dose per fraction is increased Total dose is decreased Late side effects are greater
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Split Course Treatment
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Larger fractions are used daily causing an increased reaction which requires the course to be split with a few weeks rest between courses.
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Irradiated Volume
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A major factor in determining a tolerance dose is whether whole organ versus partial organ is exposed to radiation
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Time
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The interval between fractions and overall duration of treatment affect tolerance dose.
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Controlling Factors
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Three major factors that must be controlled and monitored when administering radiation therapy Treatment volume Dose distribution Dose fractionation
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Chemotherapy
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Adding chemotherapy and the timing of its delivery relative to treatment has a major impact on sensitivity
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Innovations
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Hyperthermia Radiosensitizers Radioprotectors Immunological and biological response modifiers
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Tolerance
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Organ tolerance is determined by the radiosensitivity of the relevant stem cell subpopulations, which may not always be proliferating or dividing The tolerance of the normal tissue is the limiting factor in the dose given
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Tumor Lethal Dose
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A dose of radiation that creates complete and permanent regression (removal – killing) of the tumor. Is defined as the dose which achieves 95% tumor control
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Nominal Standard Dose
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Used to compare and contrast treatment regimens and the biologic effects that differ in dose, fractionation and overall treatment time
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Tumor Control
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Tumor control is directly related to the radiation dose and inversely proportional to the number of tumor cells
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Radiation Therapy
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Usually fails at the center of the tumor where the concentration of the tumor clonogens is the largest and conditions may be hypoxic.
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Surgery
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Surgical resection fails because the tumor extends further than the margins of excision.
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Radiation alone is inadequate for achieving a cure in some situations because:
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Number of stem cells is too large Some or all of the tumor cells are radioresistant Tolerance of contiguous normal tissue is too low
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Radiation Therapy advantages over surgery:
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Functionality Cosmetic outcomes
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Major Limiting Factor of Radiation
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Normal tissue tolerance within the irradiated volume.

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