RT24 Endterm - Radiation Biology in Radiation Therapy PDF

RT24: Radiation Therapy 1st Sem, A.Y. 2024-2025 Radiobiologic Principles Law of Bergonie and Tribondeau Stem cells are radiosensitive; mature cells are radioresistant. Younger tissues and organs are radiosensitive. Tissues with high metabolic activity are radiosensitive. A high...

RT24: Radiation Therapy 1st Sem, A.Y. 2024-2025 Radiobiologic Principles Law of Bergonie and Tribondeau Stem cells are radiosensitive; mature cells are radioresistant. Younger tissues and organs are radiosensitive. Tissues with high metabolic activity are radiosensitive. A high proliferation rate for cells and a high growth rate for tissues result in increased radiosensitivity. Principle of Justification Principle of Optimization Principle of Individual Dose and Risk Limits On DNA Could be due to ‘direct’ or ‘indirect’ hit Change in or loss of one or more of the four nitrogenous bases Breakage of hydrogen bonds between the A-T and C-G base pairs  Breakage of bonds between the components of the backbone of each DNA strand, leading to intra-strand or inter-strand cross- linking of DNA On Chromosomes Could be due to ‘direct’ or ‘indirect’ hit Gross structural changes are called ‘aberrations’, ‘lesions’, or ‘anomalies’ Structural changes include ‘single breaks’, ‘multiple breaks’, and a phenomenon known as ‘chromosome stickiness’ or ‘clumping’  Chromosome aberration - radiation administered during the G1 phase or before the cell replicates its DNA in the S phase - may involve both daughter cells after mitosis  Chromatid aberration - radiation administered during the G2 phase, or after they have completed DNA synthesis - only one of the two daughter cells is affected As Cellular Response Division delay Interphase death Reproductive failure Apoptosis Factors Influencing Fractionated Treatment Repair Redistribution Repopulation Reoxygenation Tissue-organ Level EARLY EFFECTS LATE EFFECTS Deterministic effects Stochastic effects Acute exposure Chronic exposure Example: acute radiation Example: radiation- lethality induced malignancy and genetic effects Deterministic Effects of Radiation Exposure EFFECT ANATOMIC SITE THRESHOLD DOSE Death Whole Body 2 Gy (200 rad) Hematologic Depression Whole Body 250 mGy (25 rad) Skin Erythema Small Field 3 Gy (300 rad) Epilation Small Field 3 Gy (300 rad) Gonadal Dysfunction Local Tissue 100 mGy (10 rad)  ARS PERIOD APPROXIMATE MEAN SURVIVAL CLINICAL SIGNS AND SYMPTOMS DOSE (Gy) TIME (Days) PRODROMAL >1 - Nausea, vomiting, diarrhea LATENT 1-100 - None HEMATOLOGIC 2-10 10-60 Nausea, vomiting, diarrhea, anemia, leukopenia, hemorrhage, fever, infection GASTROINTESTINAL 10-50 4-10 Same as hematologic plus electrolyte imbalance, lethargy, fatigue, shock CENTRAL NERVOUS >50 0-3 Same as gastrointestinal system plus SYSTEM ataxia, edema, vasculitis, meningitis Radiosensitivity and Radiocurability Radiosensitivity Radiocurability Inversely related to cell Refers to the eradication of tumor at differentiation, response of tumor the primary or regional site and and may vary in relation to the its reflects the direct effect of location, leading to difference in radiation. timing of reactions. Modification of Response Oxygen Radiosensitizer and Radioprotectors Cytotoxic Chemotherapy Hyperthermia High Let Radiation Dose Fractionation Oxygen Radiosensitivity of tissue increases with presence of oxygen OER – ratio of dose needed under anoxic conditions to produce an effect to the dose needed under aerobic conditions to produce the same effect Radiosensitizers and Radioprotectors Radiosensitizers- agents that enhance the effect of radiation. Ex. Halogenated pyrimidines, methotrexate, actinomycin D, hydroxyurea, vitamin K Radioprotectors- agents that reduces the effects of radiation. Ex. Cysteine, cysteamine Cytotoxic Chemotherapy Concomitant chemotherapy Decrease micrometastasis Kills hypoxic cells Kills radioresistant cells in S phase of cell cycle Hyperthermia As an adjuvant treatment considers heating of the tumor (area) above a physiological temperature up to 40–43 °C for approximately an hour Results to increased blood flow, increasing reoxygenation, and deeper penetration of chemotherapeutic agent used High LET Linear energy transfer (LET) is a parameter that quantifies amount of transferred energy / unit length High LET radiation leads to high RBE, means more effective in inducing biological damage Radiation Dose Fractionation Hyperfractionation improve therapeutic ratio Accelerated fractionation reduce the opportunity for accelerated repopulation of cells Hypofractionation allow tumor cells to recover between fraction intervals