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 rationalc 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