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