Radiation Oncology/Radiobiology/ABR Curriculum

American Board of Radiology Curriculum

ABR Study Guide

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


 * 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


 * 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


 * 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


 * 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