| I. |
Interaction of Radiation with Biological Systems (++) |
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Definition of ionizing radiation
Types of ionizing and non-ionizing radiation
Definition of LET and quality of ionizing radiation
Generation of free radicals
Direct and indirect action of ionizing radiation |
| II. |
Molecular Mechanisms of DNA Damage (+) |
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Assays for DNA damage |
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neutral and alkaline elution, pulsed field electrophoresis, comet, plasmid-based assay |
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Types of DNA lesions and numbers per cell/Gy
Multiply damaged sites
Single lethal hits and accumulated damage (inter- and intra-track)
Role of oxygen in the generation of damage
Role of LET and radiation quality |
| III. |
Molecular Mechanisms of DNA Repair (+++) |
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Different types of DNA repair mechanisms
Mechanisms involved in repair of base damage and DNA single strand breaks
Mechanisms involved in repair of double strand breaks |
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Homologous recombination
Non-homologous end joining |
| IV. |
Chromosome and Chromatid Damage (++) |
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Assays |
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Conventional smears, banding, comparative genomic hybridization (CGH) and FISH |
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Dose response relationships
Use of peripheral blood lymphocytes in in vivo dosimetry
Stable and unstable chromatid and chromosome aberrations
Human genetic diseases that affect DNA repair, fragility, and radiosensitivity |
| V. |
Mechanisms of Cell Death (+++) |
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Apoptotic death |
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Developmental and stress induced
Morphological and biochemical features of apoptosis
Molecular pathways leading to apoptosis
Radiation-induced apoptosis in normal tissues and tumors |
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Necrotic death |
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Morphological, pathological, and biochemical features of necrosis |
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Mitotic death following irradiation |
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Types of mitotic death - mitotic catastrophe vs. apoptosis
Cell division post-radiation and time to clonogenic cell death |
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Radiation-induced senescence |
| VI. |
Cell and Tissue Survival Assays (+) |
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In vitro clonogenic assays |
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Calculation of plating efficiency and surviving fraction |
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In vivo clonogenic assays |
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Bone marrow stem cell assays, jejunal crypt stem cell assay, skin clones, kidney tubules |
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Functional endpoints |
| VII. |
Models of Cell Survival (+++) |
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Random nature of cell killing and Poisson statistics
Doses for inactivation of viruses, bacteria, and eukaryotic cells after irradiation
Single hit, multi-target models of cell survival
Two component models
Linear quadratic model
Calculations of cell survival with dose
Effects of dose, dose rate, cell type |
| VIII. |
Modifiers of Cell Survival: Linear Energy Transfer (+) |
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Definition of RBE
RBE as a function of LET
Effect of LET on cell survival
Endpoint dependence of RBE
Effects of dose, dose rate, cell type |
| IX. |
Modifiers of Cell Survival: Oxygen Effect (++) |
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Definition of OER
Effect of dose, dose rate, cell type
OER as a function of LET
Impact of O2 concentration
Time scale of oxygen effect
Mechanisms of oxygen effect |
| X. |
Modifiers of Cell Survival: Repair (++) |
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Sub-lethal damage repair
Potentially lethal damage repair
Half-time of repair
Effects of dose, dose rate, and cell type
Effect of dose fractionation
Effect of LET
Effects of oxygen/hypoxia |
| XI. |
Solid Tumor Assay Systems (+) |
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50 limiting dilution assay
Tumor regrowth assay
TCD50 tumor control assay
Lung colony assay
In vitro/in vivo assay
Monolayers vs. 3-D spheroid cultures |
| XII. |
Tumor Microenvironment (+++) |
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Tumor vasculature
Angiogenesis
Hypoxia in tumors |
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Measurement of hypoxia
Transient and chronic hypoxia |
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Reoxygenation following irradiation
Relevance of hypoxia in radiation therapy
Hypoxia as a factor in tumor progression
Hypoxia-induced signal transduction
Cellular composition of tumors |
| XIII. |
Cell and Tissue Kinetics (+++) |
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Cell cycle |
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Measurement of cell cycle parameters by 3H-thymidine
Measurement by flow cytometry, DNA staining and BrdU |
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Cell cycle synchronization techniques and uses
Effect of cell cycle phase on radiosensitivity
Cell cycle arrest and redistribution following irradiation
Cell cycle checkpoints, cyclins, cyclin dependent kinase inhibitors
Tissue kinetics |
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Stem, progenitor, differentiated cells
Growth fraction
Cell loss factor
Volume doubling times
Tpot |
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Growth kinetics of clinical and experimental tumors |
| XIV. |
Molecular Signaling (++) |
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Receptor/ligand interactions
Phosphorylation/dephosphorylation reactions
Transcriptional activation
Radiation-induced gene expression |
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Gene expression profiling
Proteomics |
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Radiation-induced signals |
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DNA damage response
Non-DNA damage responses |
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Cell survival and death pathways |
| XV. |
Cancer (+++) |
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Cancer as a Genetic Disease
Oncogenes
Tumor suppressor genes
Telomeric changes in cancer
Epigenetic changes in cancer |
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e.g hypermethylation |
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Multi-step nature of carcinogenesis
Repair genes in carcinogenesis
The metastatic process
Molecular profiling and staging of cancer |
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Gene expression profiling
Proteomics |
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Signaling abnormalities in cancer
Effects of signaling abnormalities on radiation responses
Prognostic significance of tumor characteristics
Therapeutic targets and strategies for intervention |
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Monoclonals, small molecule inhibitors, gene therapy |
| XVI. |
Total Body Irradiation (++) |
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Prodromal radiation syndrome
Cerebrovascular syndrome
Gastrointestinal syndrome
Hematopoietic syndrome
Mean lethal dose and dose/time responses
Immunological effects
Assessment and treatment of radiation accidents or terrorism
Bone marrow transplantation |
| XVII. |
Clinically Relevant Normal Tissue Responses to Radiation (+++) |
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Responses in skin, oral mucosa, oropharyngeal and esophageal mucous membranes, salivary glands, bone marrow, lymphoid tissues, bone and cartilage, lung, kidney, testis, ovary, eye, central and peripheral nervous tissues
Scoring systems for tissue injury |
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LENT and SOMA |
| XVIII. |
Mechanisms of Normal Tissue Radiation Responses (+++) |
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Differences between slowly and rapidly proliferating tissues
Molecular and cellular responses in slowly and rapidly proliferating tissues |
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Cytokines and growth factors
Regeneration
Remembered dose
Functional subunits |
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Mechanisms underlying clinical symptoms |
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Latency
Inflammatory changes
Cell killing
Radiation fibrosis
Vascular damage
Volume effects |
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Pharmacological modification of normal tissue responses |
| XIX. |
Therapeutic Ratio (+++) |
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Tumor control probability (TCP) curves |
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Calculation of TCP
Factors affecting shape and slope of TCP curves
Influence of tumor repopulation/regeneration on TCP |
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Normal tissue complication probability (NTCP) curves |
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Influence of normal tissue regeneration on responses |
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Response of subclinical disease
Causes of treatment failure
Factors determining tissue tolerance |
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Normal tissue volume effects
Dose-volume histogram analysis |
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Effect of adjuvant or combined treatments on therapeutic ratio |
| XX. |
Time, Dose, Fractionation (+++) |
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The 4 R's of fractionation
The radiobiological rationale behind dose fractionation
The effect of tissue type on the response to dose fractionation
Effect of tissue/tumor types on a/b ratios
Quantitation of multifraction survival curves
BED and isoeffect dose calculations |
| XXI. |
Brachytherapy (+) |
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Dose rate effects (HDR and LDR)
Choice of isotopes
Interstitial and intracavitary use
Radiolabeled antibodies
BED and Isoeffective dose calculations |
| XXII. |
Radiobiological aspects of alternative dose delivery systems (+) |
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Protons, high LET sources, BNCT
Stereotactic radiosurgery/radiotherapy, IMRT, IORtd class="spacing"ose distributions and dose heterogeneity |
| XXIII. |
Chemotherapeutic agents and radiation therapy (+++) |
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Classes of agents
Mechanisms of action
The oxygen effect in chemotherapy
Multiple drug resistance
Interactions of chemotherapeutic agents with radiation therapy (chemoradiation therapy) |
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Photodynamic therapy |
| XXIV. |
Radiosensitizers, Bioreductive drugs, Radioprotectors (++) |
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Tumor radiosensensitization |
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Halogenated pyrimidines, nitroimidazoles |
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Hypoxic cell cytotoxins |
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tirapazamine |
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Normal tissue radioprotection |
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Mechanisms of action, sulfhydryl compounds, WR series, dose reduction factor (DRF) |
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Biological response modifiers |
| XXV. |
Hyperthermia (+) |
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Delivery modalities
Cellular response to heat
Heat shock proteins
Thermotolerance
Response of tumors and normal tissues to heat
Combination with radiation therapy |
| XXVI. |
Radiation Carcinogenesis (++) |
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Initiation, promotion, progression
Dose response for radiation-induced cancers
Importance of age at exposure and time since exposure
Malignancies in prenatally exposed children
Second tumors in radiation therapy patients
Effects of chemotherapy on incidence
Risk estimates in humans
Calculations based on risk estimates |
| XXVII. |
Heritable Effects of Radiation (+) |
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Single gene mutation
Chromosome aberrations
Relative vs. absolute mutation risk
Doubling dose
Heritable effects in humans
Risk estimates for hereditable effects |
| XXVIII. |
Radiation Effects in the Developing Embryo (+) |
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Intrauterine death
Congenital abnormalities and neonatal death
Microcephaly, mental retardation
Growth retardation
Dose, dose rate, and stage in gestation
Human experience of pregnant women exposed to therapeutic dose |
| XXIX. |
Radiation Protection (++) |
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General philosophy
Stochastic and deterministic effects
Effective dose - relative weighting factors
Equivalent dose - tissue weighting factor
Committed dose
Collective exposure dose
Dose limits for occupational and public exposure
ICRP and NCRP |