This exam tests your knowledge of the principles of cancer and radiation biology underlying the practice of radiation oncology. Included are questions on:

• basic cancer biology and the molecular biology of cancer
• the response to radiation at the subcellular and cellular levels
• the radiation responses of normal and malignant tissues
• radiation carcinogenesis
• hereditary effects as they relate to radiation protection

Categories for Cancer and Radiation Biology

 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

• RBE defined
• RBE as a function of LET
• Tissue type

• Define OER
• Dose and dose per fraction effects
• OER vs LET
• Impact of O2 concentration
• Time scale of oxygen effect
• Mechanisms of oxygen effect

• Sublethal damage repair
• Potentially lethal damage repair
• Half-time of repair
• Dose rate effects and repair
• Dose fractionation effects

• Experimental models
• TD50 limiting dilution assay
• Tumor regrowth assay
• TCD50 tumor control assay
• Lung colony assay
• In vitro / in vivo assay
• Spheroid systems

• 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 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

• 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 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

• 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

• 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

• 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

• 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

• Dose rate effects ( HDR and LDR)
• Choice of isotopes
• Interstitial and intracavitary use
• Radiolabeled antibodies

• Protons, high LET sources, BNCT
• Stereotactic radiosurgery/radiotherapy, IMRT, IORT
• Dose distributions and dose heterogeneity

• 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

• 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

• Cellular response to heat
• Heat shock proteins
• Thermotolerance
• Response of tumors and normal tissues to heat
• Combination with radiation therapy

• 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

• Single gene mutation
• Chromosome aberrations
• Relative vs absolute mutation risk
• Doubling dose
• Heritable effects in humans
• Risk estimates for hereditable effects

• 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

• 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

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