Radiation Oncology/Radiobiology/ABR Curriculum
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American Board of Radiology Curriculum
Table of contents 2008
- Interaction of Radiation with Matter
- Definition of ionizing radiation and types
- Definition of LET and quality of radiation
- Generation of free radicals
- Direct and indirect action of radiation
- Role of oxygen
- Molecular Mechanisms of DNA Damage
- Assays for DNA damage
- Neutral and alkaline elution, pulsed field electrophoresis, comet, plasmid-based assays
- Types of DNA lesions and numbers per cell/Gy
- Multiply damaged sites
- Single lethal hits and accumulated damage (inter- and intratrack)
- Molecular Mechanisms of DNA Repair
- Types of repair
- Repair of base damage, single-strand and double-strand breaks
- Homologous recombination
- Nonhomologous end-joining
- Chromosome and Chromatid Damage
- Assays
- Conventional and FISH
- 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
- Mechanisms of Cell Death
- Apoptotic death
- Developmental and stress induced
- Morphological and biochemical features of apoptosis
- Molecular pathways leading to apoptosis
- Radiation-induced apoptosis in normal tissues and tumors
- Necrotic death
- Morphological, pathological, and biochemical features of necrosis
- Mitotic death following irradiation
- Catastrophic vs apoptotic death
- Cell division postradiation and time of clonogen death
- Radiation-induced senescence
- Apoptotic death
- Cell and Tissue Survival Assays
- In vitro clonogenic assays
- Effects of dose, dose rate, cell type
- In vivo clonogenic assays
- Bone marrow stem cell assays, jejunal crypt stem cell assay, skin clones, kidney tubules
- In vitro clonogenic assays
- Models of Cell Survival
- Random nature of cell killing and Poisson statistics
- Comparison of survival of viruses, bacteria, and eukaryotic cells after irradiation
- Single-hit, multitarget models of cell survival
- Two component models
- Linear quadratic model
- Calculations of cell survival with dose
- Linear Energy Transfer
- RBE defined
- RBE as a function of LET
- Tissue type
- Oxygen Effect
- Define OER
- Dose and dose per fraction effects
- OER vs LET
- Impact of O2 concentration
- Time scale of oxygen effect
- Mechanisms of oxygen effect
- Repair at the Cellular Level
- Sublethal damage repair
- Potentially lethal damage repair
- Half-time of repair
- Dose rate effects and repair
- Dose fractionation effects
- Solid Tumor Assay Systems
- Experimental models
- TD50 limiting dilution assay
- Tumor regrowth assay
- TCD50 tumor control assay
- Lung colony assay
- In vitro / in vivo assay
- Spheroid systems
- Tumor Microenvironment
- Tumor vasculature
- Angiogenesis
- Hypoxia in tumors
- Measurement of hypoxia
- Transient and chronic hypoxia
- Reoxygenation following irradiation
- Relevance of hypoxia in radiation therapy
- Hypoxia as a factor in tumor progression
- Hypoxia-induced signal transduction
- Cellular composition of tumors
- Cell and Tissue Kinetics
- Cell cycle
- Measurement of cell cycle parameters by 3H-thymidine
- Measurement by flow cytometry, DNA staining and BrdU
- 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
- Growth fraction
- Cell loss factor
- Volume doubling times
- Tpot
- Growth kinetics of clinical and experimental tumors
- Molecular Signaling
- Receptor/ligand interactions
- Phosphorylation/dephosphorylation reactions
- Transcriptional activation
- Gene expression profiling and radiation-induced gene expression
- Radiation-induced signals
- DNA damage response
- Non-DNA damage response
- Cell survival and death pathways
- Cancer
- Cancer as a genetic disease
- Oncogenes
- Tumor suppressor genes
- Telomeric changes in cancer
- Epigenetic changes in cancer (e.g., hypermethylation)
- Multistep nature of carcinogenesis
- Molecular profiling of cancer
- Signaling abnormalities in carcinogenesis
- Effects of signaling abnormalities on radiation responses
- Prognostic and therapeutic significance of tumor characteristics
- Total Body Irradiation
- Prodromal radiation syndrome
- Cerebrovascular syndrome
- Gastrointestinal syndrome
- Hematopoietic syndrome
- Mean lethal dose and dose/time responses
- Immunological effects
- Assessment and treatment of radiation accidents
- Bone marrow transplantation
- Clinically Relevant Normal Tissue Responses to Radiation
- Responses in skin, oral mucosa, oropharyngeal and esophageal mucous membranes, salivary glands, bone marrow, lymphoid tissue bone and cartilage, lung, kidney, testis, eye, central and peripheral nervous tissues
- Mechanisms of Normal Tissue Radiation Responses
- Molecular and cellular responses in slowly and rapidly proliferating tissues
- Cytokines and growth factors
- Regeneration
- Remembered dose
- Functional subunits
- Mechanisms underlying clinical symptoms
- Latency
- Inflammatory changes
- Cell killing
- Radiation fibrosis
- Volume effects
- Scoring systems for tissue injury
- LENT and SOMA
- Molecular and cellular responses in slowly and rapidly proliferating tissues
- Therapeutic Ratio
- Tumor control probability ( TCP) curves
- Calculation of TCP
- Factors affecting shape and slope of TCP curves
- Influence of tumor repopulation/regeneration on TCP
- Normal tissue complication probability (NTCP) curves
- Influence of normal tissue regeneration on responses
- Response of subclinical disease
- Causes of treatment failure
- Factors determining tissue tolerance
- Normal tissue volume effects
- Dose-volume histogram analysis
- Effect of adjuvant or combined treatments on therapeutic rationals
- Tumor control probability ( TCP) curves
- Time, Dose, Fractionation
- 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 cures
- BED and isoeffect dose calculations
- Brachytherapy
- Dose rate effects ( HDR and LDR)
- Choice of isotopes
- Interstitial and intracavitary use
- Radiolabeled antibodies
- Radiobiological aspects of alternative dose delivery systems
- Protons, high LET sources, BNCT
- Stereotactic radiosurgery/radiotherapy, IMRT, IORT
- Dose distributions and dose heterogeneity
- Chemotherapeutic agents and radiation therapy
- Classes of agents
- Mechanisms of action
- The oxygen effect for chemotherapy
- Multiple drug resistance
- Interactions of chemotherapeutic agents with radiation therapy
- Photodynamic therapy
- Gene therapy
- Radiosensitizers, Bioreductive Drugs, Radioprotectors
- Tumor radiosensensitization: Halogenated pyrimidines, nitroimidazoles
- Hypoxic cell cytotoxins: Tirapazamine
- Normal tissue radioprotection: Mechanisms of action, sulfhydryl compounds, WR series, dose reduction factor (DRF)
- Biological response modifiers
- Hyperthermia
- Cellular response to heat
- Heat shock proteins
- Thermotolerance
- Response of tumors and normal tissues to heat
- Combination with radiation therapy
- Radiation Carcinogenesis
- 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
- Heritable Effects of Radiation
- Single gene mutation
- Chromosome aberrations
- Relative vs absolute mutation risk
- Doubling dose
- Heritable effects in humans
- Risk estimates for hereditable effects
- Radiation Effects in the Developing Embryo
- 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
- Radiation Protection
- General philosophy
- Stochastic and deterministic effects
- Relative weighting factors
- Equivalent dose-tissue weighting factor
- Effective dose, committed dose
- Collective exposure dose
- Dose limits for occupational and public exposure
- ICRP and NCRP