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UNC-Duke Biology Course for Residents Fall 2018 15 Recommended Textbooks for Radiation and Cancer Biology Best two: New Edition! EJ Hall and AJ Giaccia. Radiobiology for the Radiologist, Eighth Edition. Wolters Kluer, Philadelphia, 2019. ISBN: 978-1496335418. New Edition! M Joiner and A van der Kogel, Editors. Basic Clinical Radiobiology, Fifth Edition. Taylor & Francis (CRC Press), London, 2019. ISBN: 978-1444179637. Useful vis-à-vis radiation effects in humans: FA Mettler and AC Upton. Medical Effects of Ionizing Radiation, 3rd Edition. Saunders- Elsevier, Philadelphia, 2008. ISBN: 978-0-7216-0200-4. DC Shrieve and JS Loeffler. Human Radiation Injury. Lippincott Williams & Wilkins, Philadelphia, 2011. ISBN: 798-1-60547-011-5. Best text for general cancer biology: RA Weinberg. The Biology of Cancer, 2 nd Edition. Garland Science, Taylor & Francis Group, LLC, New York, 2014. ISBN: 0-8153-4078-8.
UNC-Duke Biology Course for Residents Fall 2018 16 New content areas added within the last 3 years Radiation Oncology Initial Certification Qualifying (Computer-based) Examination: Study Guide for Radiation and Cancer Biology This exam tests your knowledge of the principles of cancer and radiation biology underlying the practice of radiation oncology. Included are questions on the following topics: Basic cancer biology and the molecular biology of cancer Response to radiation at the subcellular and cellular levels Radiation responses of normal and malignant tissues Radiation carcinogenesis Hereditary effects as they relate to radiation protection Categories for Radiation and Cancer Biology Interaction of radiation with matter o Definition of ionizing radiation and types o Generation of free radicals o Direct and indirect action of radiation Molecular and cellular damage and repair o Molecular mechanisms of DNA damage Assays for DNA damage Types of DNA lesions and numbers per cell per Gy Multiply damaged sites Single lethal hits and accumulated damage (inter- and intratrack) o Molecular mechanisms of DNA repair Types of repair Repair of base damage, single-strand and double-strand breaks Homologous recombination Nonhomologous end joining o Chromosome and chromatin damage Assays Dose-response relationships Use of peripheral blood lymphocytes in vivo dosimetry
UNC-Duke Biology Course for Residents Fall 2018 17 Stable and unstable chromatid and chromosome aberrations Human genetic diseases that affect DNA repair, fragility, and radiosensitivity Genomics o Repai r at the cellular level Sublethal damage repair Dose-rate effects and repair Dose-fractionation effects Cellular responses to radiation o Mechanisms of cell death Apoptotic death Necrotic death Mitotic-linked cell death Cell division postradiation and time to clonogen death Radiation-induced senescence Autophagy o Cell and tissue survival assays In vitro clonogenic assays - effects of dose, dose rate, and cell type In vivo clonogenic assays - bone marrow stem cell assays, jejunal crypt stem cell assay, skin clones, and kidney tubules o Models of cell survival Random nature of cell killing and poison statistics Single hit, multitarget models of cell survival Two-component models Linear-quadratic models Calculations of cell survival with dose Linear energy transfer (LET) and oxygen effect o Linear energy transfer Definition of LET and quality of radiation RBE defined RBE as a function of LET Tissue type o Oxygen Effect Definition of OER Dose or dose per fraction effects OER vs LET Impact of O2 concentration Mechanisms of oxygen effect Tumor biology and microenvironment o Solid tumor assay systems TCD50 tumor control assay o Tumor microenvironment Tumor vasculature Angiogenesis
UNC-Duke Biology Course for Residents Fall 2018 18 Hypoxia in tumors Reoxygenation after irradiation Relevance of hypoxia in radiation therapy Hypoxia as a factor in tumor progression Hypoxia-induced signal transduction Cellular composition of tumors o Immune microenvironment Cancer biology o Cell Cell cycle Effect of cell cycle phase on radiosensitivity Cell cycle arrest and redistribution after irradiation Cell cycle checkpoints, cyclins, cyclin-dependent kinase inhibitors o Molecular signaling Receptor/ligand interactions Phosphorylation/dephosphorylation reactions Transcriptional activation Radiation-induced signals Cell survival and death pathways o Mechanisms of cancer development Cancer as a genetic disease Oncogenes Tumor suppressor genes Telomeric changes in cancer Multistep nature of carcinogenesis Signaling abnormalities in carcinogenesis Effects of signaling abnormalities on radiation responses Prognostic and therapeutic significance of tumor characteristics o Cancer genetics/genomics Epigenetic changes in cancer Molecular profiling of cancer Radiobiology of normal tissues o Clinically relevant normal tissue responses to radiation Responses in skin, oral mucosa, oropharyngeal and esophageal mucous membranes, salivary glands, bone marrow, lymphoid tissues, bone and cartilage, lung, kidney, testis, eye, and central and peripheral nervous tissues Reirradiation o Mechanisms of normal tissue radiation responses Molecular and cellular responses in slowly and rapidly proliferating tissues Mechanisms underlying clinical symptoms Tissue kinetics o Total body irradiation
UNC-Duke Biology Course for Residents Fall 2018 19 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 Dose delivery o Therapeutic ratio Tumor control probability (TCP) curves Normal tissue complication probability (NTCP) curves Causes of treatment failure o Time, dose, and fractionation The four R's of fractionation Radiobiological rationale behind dose fractionation Effect of tissue type on the response to dose fractionation Effect of tissue/tumor types on A/B ratios Quantitation of multifraction survival curves BED and isoeffect dose calculations Hypofractionation o Brachytherapy Dose-rate effects (HDR and LDR) Choice of isotopes Radiolabeled antibodies o Radiobiological aspects of different radiation modalities Protons, high LET sources Stereotactic radiosurgery/radiotherapy, IMRT, IORT Dose distributions and dose heterogeneity Combined modality therapy o Chemotherapeutic agents and radiation therapy Classes of agents Mechanisms of action Oxygen effect for chemotherapy Multiple drug resistance Interactions of chemotherapeutic agents with radiation therapy Molecular-based therapy o Radiosensitizers, bioreductive drugs, and radioprotectors Tumor radiosensitization Normal tissue radioprotection Biological response modifiers DNA repair inhibitors Hyperthermia o Immune therapeutics
UNC-Duke Biology Course for Residents Fall 2018 20 Late effects and radiation protection o Radiation carcinogenesis 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 Risk estimates in humans Calculations based on risk estimates o Heritable effects of radiation Single gene mutation Relative vs absolute mutation risk Doubling dose Heritable effects in humans Risk estimates for hereditable effects o Radiation effects in the developing embryo Intrauterine death Congenital abnormalities and neonatal death Microcephaly, intellectual disabilities Dose, dose rate, and stage in gestation Human experience of pregnant women exposed to therapeutic doses o 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