Radiobiology for the Radiologist

Name: Radiobiology for the Radiologist
Brand: Wolters Kluwer Health
Price: 181.99 EUR
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Eric J. Hall Amato J. Giaccia(Autor*in)

Wolters Kluwer Health (Verlag)

1. Auflage

Erschienen am 16. April 2018

624 Seiten

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Intro
Preface to the First Edition
Preface
Acknowledgments
SECTION I For Students of Diagnostic Radiology, Nuclear Medicine, and Radiation Oncology
1 Physics and Chemistry of Radiation Absorption
TYPES OF IONIZING RADIATIONS
Electromagnetic Radiations
Particulate Radiations
ABSORPTION OF X-RAYS
DIRECT AND INDIRECT ACTION OF RADIATION
ABSORPTION OF NEUTRONS
ABSORPTION OF PROTONS AND HEAVIER IONS SUCH AS CARBON
SUMMARY OF PERTINENT CONCLUSIONS
BIBLIOGRAPHY
2 Molecular Mechanisms of DNA and Chromosome Damage and Repair
GENERAL OVERVIEW OF DNA STRAND BREAKS
MEASURING DNA STRAND BREAKS
DNA REPAIR PATHWAYS
Base Excision Repair
Nucleotide Excision Repair
DNA Double-Strand Break Repair
Nonhomologous End-Joining
Homologous Recombination Repair
Crosslink Repair
Mismatch Repair
RELATIONSHIP BETWEEN DNA DAMAGE AND CHROMOSOME ABERRATIONS
CHROMOSOMES AND CELL DIVISION
THE ROLE OF TELOMERES
RADIATION-INDUCED CHROMOSOME ABERRATIONS
EXAMPLES OF RADIATION-INDUCED ABERRATIONS
CHROMOSOME ABERRATIONS IN HUMAN LYMPHOCYTES
SUMMARY OF PERTINENT CONCLUSIONS
BIBLIOGRAPHY
3 Cell Survival Curves
REPRODUCTIVE INTEGRITY
THE IN VITRO SURVIVAL CURVE
THE SHAPE OF THE SURVIVAL CURVE
MECHANISMS OF CELL KILLING
DNA as the Target
The Bystander Effect
Apoptotic and Mitotic Death
Autophagic Cell Death
Senescence
SURVIVAL CURVES FOR VARIOUS MAMMALIAN CELLS IN CULTURE
SURVIVAL CURVE SHAPE AND MECHANISMS OF CELL DEATH
ONCOGENES AND RADIORESISTANCE
GENETIC CONTROL OF RADIOSENSITIVITY
INTRINSIC RADIOSENSITIVITY AND CANCER STEM CELLS
EFFECTIVE SURVIVAL CURVE FOR A MULTIFRACTION REGIMEN
CALCULATIONS OF TUMOR CELL KILL
Problem 1
Answer
Problem 2
Answer
Problem 3
Answer
Problem 4
Answer
THE RADIOSENSITIVITY OF MAMMALIAN CELLS COMPARED WITH MICROORGANISMS
SUMMARY OF PERTINENT CONCLUSIONS
BIBLIOGRAPHY
4 Radiosensitivity and Cell Age in the Mitotic Cycle
THE CELL CYCLE
SYNCHRONOUSLY DIVIDING CELL CULTURES
THE EFFECT OF X-RAYS ON SYNCHRONOUSLY DIVIDING CELL CULTURES
MOLECULAR CHECKPOINT GENES
THE EFFECT OF OXYGEN AT VARIOUS PHASES OF THE CELL CYCLE
THE AGE-RESPONSE FUNCTION FOR A TISSUE IN VIVO
VARIATION OF SENSITIVITY WITH CELL AGE FOR HIGH-LINEAR ENERGY TRANSFER RADIATIONS
MECHANISMS FOR THE AGE-RESPONSE FUNCTION
THE POSSIBLE IMPLICATIONS OF THE AGE-RESPONSE FUNCTION IN RADIOTHERAPY
SUMMARY OF PERTINENT CONCLUSIONS
BIBLIOGRAPHY
5 Fractionated Radiation and the Dose-Rate Effect
OPERATIONAL CLASSIFICATIONS OF RADIATION DAMAGE
Potentially Lethal Damage Repair
Sublethal Damage Repair
MECHANISM OF SUBLETHAL DAMAGE REPAIR
REPAIR AND RADIATION QUALITY
THE DOSE-RATE EFFECT
EXAMPLES OF THE DOSE-RATE EFFECT IN VITRO AND IN VIVO
THE INVERSE DOSE-RATE EFFECT
THE DOSE-RATE EFFECT SUMMARIZED
BRACHYTHERAPY OR ENDOCURIETHERAPY
Intracavitary Brachytherapy
Permanent Interstitial Implants
SUMMARY OF PERTINENT CONCLUSIONS
Potentially Lethal Damage Repair
Sublethal Damage Repair
Dose-Rate Effect
Brachytherapy
BIBLIOGRAPHY
6 Oxygen Effect and Reoxygenation
THE NATURE OF THE OXYGEN EFFECT
THE TIME AT WHICH OXYGEN ACTS AND THE MECHANISM OF THE OXYGEN EFFECT
THE CONCENTRATION OF OXYGEN REQUIRED
CHRONIC AND ACUTE HYPOXIA
Chronic Hypoxia
Acute Hypoxia
THE FIRST EXPERIMENTAL DEMONSTRATION OF HYPOXIC CELLS IN A TUMOR
PROPORTION OF HYPOXIC CELLS IN VARIOUS ANIMAL TUMORS
EVIDENCE FOR HYPOXIA IN HUMAN TUMORS
TECHNIQUES TO MEASURE TUMOR OXYGENATION
Oxygen Probe Measurements
Markers of Hypoxia
REOXYGENATION
TIME SEQUENCE OF REOXYGENATION
MECHANISM OF REOXYGENATION
THE IMPORTANCE OF REOXYGENATION IN RADIOTHERAPY
HYPOXIA AND CHEMORESISTANCE
HYPOXIA AND TUMOR PROGRESSION
SUMMARY OF PERTINENT CONCLUSIONS
BIBLIOGRAPHY
7 Linear Energy Transfer and Relative Biologic Effectiveness
THE DEPOSITION OF RADIANT ENERGY
LINEAR ENERGY TRANSFER
RELATIVE BIOLOGIC EFFECTIVENESS
RELATIVE BIOLOGIC EFFECTIVENESS AND FRACTIONATED DOSES
RELATIVE BIOLOGIC EFFECTIVENESS FOR DIFFERENT CELLS AND TISSUES
RELATIVE BIOLOGIC EFFECTIVENESS AS A FUNCTION OF LINEAR ENERGY TRANSFER
THE OPTIMAL LINEAR ENERGY TRANSFER
FACTORS THAT DETERMINE RELATIVE BIOLOGIC EFFECTIVENESS
THE OXYGEN EFFECT AND LINEAR ENERGY TRANSFER
RADIATION WEIGHTING FACTOR
SUMMARY OF PERTINENT CONCLUSIONS
BIBLIOGRAPHY
8 Acute Radiation Syndrome
ACUTE RADIATION SYNDROME
EARLY LETHAL EFFECTS
THE PRODROMAL RADIATION SYNDROME
THE CEREBROVASCULAR SYNDROME
THE GASTROINTESTINAL SYNDROME
THE HEMATOPOIETIC SYNDROME
THE FIRST AND MOST RECENT DEATHS FROM THE HEMATOPOIETIC SYNDROME
PULMONARY SYNDROME
CUTANEOUS RADIATION INJURY
SYMPTOMS ASSOCIATED WITH THE ACUTE RADIATION SYNDROME
TREATMENT OF RADIATION ACCIDENT VICTIMS EXPOSED TO DOSES CLOSE TO THE LD
TRIAGE
SURVIVORS OF SERIOUS RADIATION ACCIDENTS IN THE UNITED STATES
RADIATION EMERGENCY ASSISTANCE CENTER
SUMMARY OF PERTINENT CONCLUSIONS
BIBLIOGRAPHY
9 Medical Countermeasures to Radiation Exposure
INTRODUCTION AND DEFINITIONS
THE DISCOVERY OF RADIOPROTECTORS
MECHANISM OF ACTION
DEVELOPMENT OF MORE EFFECTIVE COMPOUNDS
AMIFOSTINE (WR-2721) AS A RADIOPROTECTOR IN RADIOTHERAPY
AMIFOSTINE AS A PROTECTOR AGAINST RADIATION-INDUCED CANCER
A NEW FAMILY OF AMINOTHIOL RADIOPROTECTORS
RADIATION MITIGATORS
RADIONUCLIDE ELIMINATORS
DIETARY SUPPLEMENTS AS COUNTERMEASURES TO RADIATION
SUMMARY OF PERTINENT CONCLUSIONS
BIBLIOGRAPHY
10 Radiation Carcinogenesis
TISSUE REACTIONS (DETERMINISTIC EFFECTS) AND STOCHASTIC EFFECTS
CARCINOGENESIS: THE HUMAN EXPERIENCE
THE LATENT PERIOD
ASSESSING THE RISK
COMMITTEES CONCERNED WITH RISK ESTIMATES AND RADIATION PROTECTION
RADIATION-INDUCED CANCER IN HUMAN POPULATIONS
Leukemia
Thyroid Cancer
Breast Cancer
Lung Cancer
Bone Cancer
Skin Cancer
QUANTITATIVE RISK ESTIMATES FOR RADIATION-INDUCED CANCER
DOSE AND DOSE-RATE EFFECTIVENESS FACTOR
SUMMARY OF RISK ESTIMATES
SECOND MALIGNANCIES IN RADIOTHERAPY PATIENTS
Second Cancers after Radiotherapy for Prostate Cancer
Radiation Therapy for Carcinoma of the Cervix
Second Cancers among Long-Term Survivors from Hodgkin Disease
DOSE-RESPONSE RELATIONSHIP FOR RADIATION CARCINOGENESIS AT HIGH DOSES
CANCER RISKS IN NUCLEAR INDUSTRY WORKERS
EXTRAPOLATING CANCER RISKS FROM HIGH TO LOW DOSES
MORTALITY PATTERNS IN RADIOLOGISTS
CHILDHOOD CANCER AFTER RADIATION EXPOSURE IN UTERO
NONNEOPLASTIC DISEASE AND RADIATION
SUMMARY OF PERTINENT CONCLUSIONS
BIBLIOGRAPHY
11 Heritable Effects of Radiation
GERM CELL PRODUCTION AND RADIATION EFFECTS ON FERTILITY
REVIEW OF BASIC GENETICS
MUTATIONS
Mendelian
Chromosomal Changes
Multifactorial
RADIATION-INDUCED HERITABLE EFFECTS IN FRUIT FLIES
RADIATION-INDUCED HERITABLE EFFECTS IN MICE
RADIATION-INDUCED HERITABLE EFFECTS IN HUMANS
INTERNATIONAL COMMISSION ON RADIOLOGICAL PROTECTION ESTIMATES OF HEREDITARY RISKS
MUTATIONS IN THE CHILDREN OF THE A-BOMB SURVIVORS
CHANGING CONCERNS FOR RISKS
EPIGENETICS
Imprinted Genes
SUMMARY OF PERTINENT CONCLUSIONS
BIBLIOGRAPHY
12 Effects of Radiation on the Embryo and Fetus
HISTORICAL PERSPECTIVE
OVERVIEW OF RADIATION EFFECTS ON THE EMBRYO AND FETUS
DATA FROM MICE AND RATS
Preimplantation
Organogenesis
The Fetal Period
EXPERIENCE IN HUMANS
Survivors of the A-Bomb Attacks on Hiroshima and Nagasaki Irradiated In Utero
Exposure to Medical Radiation
COMPARISON OF HUMAN AND ANIMAL DATA
CANCER IN CHILDHOOD AFTER IRRADIATION IN UTERO
OCCUPATIONAL EXPOSURE OF WOMEN
THE PREGNANT OR POTENTIALLY PREGNANT PATIENT
SUMMARY OF PERTINENT CONCLUSIONS
BIBLIOGRAPHY
13 Radiation Cataractogenesis
CATARACTS OF THE OCULAR LENS
LENS OPACIFICATION IN EXPERIMENTAL ANIMALS
RADIATION CATARACTS IN HUMANS
THE LATENT PERIOD
DOSE-RESPONSE RELATIONSHIP FOR CATARACTS IN HUMANS
SUMMARY OF PERTINENT CONCLUSIONS
BIBLIOGRAPHY
14 Radiologic Terrorism
POSSIBLE SCENARIOS FOR RADIOLOGIC TERRORISM
AVAILABILITY OF RADIOACTIVE MATERIAL
HEALTH EFFECTS OF RADIATION
EXTERNAL EXPOSURE TO RADIATION AND CONTAMINATION WITH RADIOACTIVE MATERIALS
EXTERNAL CONTAMINATION
INTERNAL CONTAMINATION
MEDICAL MANAGEMENT ISSUES IN THE EVENT OF RADIOLOGIC TERRORISM
FURTHER INFORMATION
SUMMARY OF PERTINENT CONCLUSIONS
BIBLIOGRAPHY
15 Doses and Risks in Diagnostic Radiology, Interventional Radiology and Cardiology, and Nuclear Medicine
DOSES FROM NATURAL BACKGROUND RADIATION
Cosmic Radiation
Natural Radioactivity in the Earth's Crust
Internal Exposure
Areas of High Natural Background
COMPARISON OF RADIATION DOSES FROM NATURAL SOURCES AND HUMAN ACTIVITIES
DIAGNOSTIC RADIOLOGY
Dose
Effective Dose
Collective Effective Dose
INTERVENTIONAL RADIOLOGY AND CARDIOLOGY
Patient Doses and Effective Doses
Dose to Personnel
NUCLEAR MEDICINE
Historical Perspective
Effective Dose and Collective Effective Dose
Principles in Nuclear Medicine
Positron Emission Tomography
The Therapeutic Use of Radionuclides
MEDICAL IRRADIATION OF CHILDREN AND PREGNANT WOMEN
Irradiation of Children
Irradiation of Pregnant Women
DOSES TO THE EMBRYO AND FETUS
RECOMMENDATIONS ON BREASTFEEDING INTERRUPTIONS
SUMMARY
SUMMARY OF PERTINENT CONCLUSIONS
Computed Tomography
Effective Dose and Cancer
Interventional Procedures
Nuclear Medicine
Medical Radiation of Children and Pregnant Women
Summary
BIBLIOGRAPHY
16 Radiation Protection
DE MINIMIS DOSE AND NEGLIGIBLE INDIVIDUAL DOSE
RADIATION DETRIMENT
NATIONAL COUNCIL ON RADIATION PROTECTION AND MEASUREMENTS AND THE INTERNATIONAL COMMISSION ON RADIOLOGICAL PROTECTION COMPARED
THE HISTORY OF THE CURRENT DOSE LIMITS
DOSE RANGES
SUMMARY OF PERTINENT CONCLUSIONS
GLOSSARY OF TERMS
BIBLIOGRAPHY
THE ORIGINS OF RADIATION PROTECTION
ORGANIZATIONS
QUANTITIES AND UNITS
Dose
Radiation Weighting Factor
Equivalent Dose
Effective Dose
Committed Equivalent Dose
Committed Effective Dose
Collective Equivalent Dose
Collective Effective Dose
Collective Committed Effective Dose
Summary of Quantities and Units
TISSUE REACTIONS AND STOCHASTIC EFFECTS
PRINCIPLES OF RADIATION PROTECTION
BASIS FOR EXPOSURE LIMITS
LIMITS FOR OCCUPATIONAL EXPOSURE
Stochastic Effects
Tissue Reactions (Formerly Known as Deterministic Effects)
AS LOW AS REASONABLY ACHIEVABLE
PROTECTION OF THE EMBRYO/FETUS
EMERGENCY OCCUPATIONAL EXPOSURE
EXPOSURE OF PERSONS YOUNGER THAN 18 YEARS OF AGE
EXPOSURE OF MEMBERS OF THE PUBLIC (NONOCCUPATIONAL LIMITS)
EXPOSURE TO INDOOR RADON
SECTION II For Students of Radiation Oncology
17 Molecular Techniques in Radiobiology
HISTORICAL PERSPECTIVES
THE STRUCTURE OF DNA
RNA AND DNA
TRANSCRIPTION AND TRANSLATION
THE GENETIC CODE
AMINO ACIDS AND PROTEINS
RESTRICTION ENDONUCLEASES
VECTORS
Plasmids
Bacteriophage ?
Bacterial Artificial Chromosomes
Viruses
LIBRARIES
Genomic Library
cDNA Library
HOSTS
Escherichia Coli
Yeast
Mammalian Cells
DNA-MEDIATED GENE TRANSFER
AGAROSE GEL ELECTROPHORESIS
POLYMERASE CHAIN REACTION
Polymerase Chain Reaction-mediated Site-directed Mutagenesis
GENE-CLONING STRATEGIES
GENOMIC ANALYSES
Mapping
Contiguous Mapping
DNA Sequence Analyses
Polymorphisms or Mutations
Restriction Fragment Length Polymorphisms
Comparative Genome Hybridization
GENE KNOCKOUT STRATEGIES
Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR Associated Protein
Homologous Recombination to Knockout Genes
Knockout Mice
GENE EXPRESSION ANALYSIS
Northern Blotting
RNA Interference
Reverse Transcription Polymerase Chain Reaction
Quantitative Real-Time Polymerase Chain Reaction
Genetic Reporters
Promoter Bashing
Chromatin Immunoprecipitation
Protein-DNA Interaction Arrays (Chromatin Immunoprecipitation-Chips)
Microarrays to Assay Gene Expression
RNA-Seq to Assay Gene Expression
Chromatin Immunoprecipitation-Seq
PROTEIN ANALYSIS
Western Blotting
Antibody Production
Immunoprecipitation
Far Western Blotting
Fluorescent Proteins
Two-Hybrid Screening
Split Luciferase Complementation Assay
Proteomics
Two-Dimensional Electrophoresis
DATABASES AND SEQUENCE ANALYSIS
SUMMARY OF PERTINENT CONCLUSIONS
GLOSSARY OF TERMS
BIBLIOGRAPHY
18 Cancer Biology
MECHANISMS OF CARCINOGENESIS
ONCOGENES
MECHANISMS OF ONCOGENE ACTIVATION
Retroviral Integration through Recombination
DNA Mutation of Regulatory Sites
Gene Amplification
Chromosome Translocation
MUTATION AND INACTIVATION OF TUMOR SUPPRESSOR GENES
The Retinoblastoma Paradigm
The Li-Fraumeni Paradigm
Familial Breast Cancer, BRCA1 and BRCA2
SOMATIC HOMOZYGOSITY
THE MULTISTEP NATURE OF CANCER
FUNCTION OF ONCOGENES AND TUMOR SUPPRESSOR GENES
Dysregulated Proliferation
Failure to Respond to Growth-Restrictive Signals
Failure to Commit Suicide (Apoptosis)
Escaping Senescence
Angiogenesis
Invasion and Metastasis
THE CONCEPT OF GATEKEEPERS AND CARETAKERS
MISMATCH REPAIR
HERITABLE SYNDROMES THAT AFFECT RADIOSENSITIVITY, GENOMIC INSTABILITY, AND CANCER
Ataxia-Telangiectasia
Seckel Syndrome
Mouse versus Human Severe Combined Immunodeficiency
Ataxia-Telangiectasia-Like Disorder
Nijmegen Breakage Syndrome
Fanconi Anemia
Homologues of RecQ-Bloom Syndrome, Werner Syndrome, and Rothmund-Thompson Syndrome
RADIATION-INDUCED SIGNAL TRANSDUCTION
Early Response Genes
The Ceramide Pathway
T CELL CHECKPOINT THERAPY
SUMMARY OF PERTINENT CONCLUSIONS
BIBLIOGRAPHY
Signal Transduction
Heritable Syndromes that Affect Radiosensitivity, Genomic Instability, and Cancer
Oncogenes and Tumor Suppressor Genes
Cancer Genetics
Multistep Nature of Cancer and Mismatch Repair
Genes and Ionizing Radiation
19 Dose-Response Relationships for Model Normal Tissues
DOSE-RESPONSE RELATIONSHIPS
Therapeutic Ratio (Therapeutic Index)
TYPES OF CELL DEATH: HOW AND WHY CELLS DIE
ASSAYS FOR DOSE-RESPONSE RELATIONSHIPS
CLONOGENIC END POINTS
Clones Regrowing In Situ
Skin Colonies
Crypt Cells of the Mouse Jejunum
Testes Stem Cells
Kidney Tubules
Cells Transplanted to Another Site
Bone Marrow Stem Cells
Mammary and Thyroid Cells
SUMMARY OF DOSE-RESPONSE CURVES FOR CLONOGENIC ASSAYS IN NORMAL TISSUES
DOSE-RESPONSE RELATIONSHIPS FOR FUNCTIONAL END POINTS
Pig Skin
Rodent Skin
Early and Late Response of the Lung Based on Breathing Rate
Spinal Cord Myelopathy
Latency
Fractionation and Protraction
Volume Effects
Retreatment after Long Time Intervals
INFERRING THE RATIO a/ß FROM MULTIFRACTION EXPERIMENTS IN NONCLONOGENIC SYSTEMS
SUMMARY OF PERTINENT CONCLUSIONS
BIBLIOGRAPHY
20 Clinical Response of Normal Tissues
CELLS AND TISSUES
EARLY (ACUTE) AND LATE EFFECTS
FUNCTIONAL SUBUNITS IN NORMAL TISSUES
THE VOLUME EFFECT IN RADIOTHERAPY: TISSUE ARCHITECTURE
RADIATION PATHOLOGY OF TISSUES
CASARETT'S CLASSIFICATION OF TISSUE RADIOSENSITIVITY
MICHALOWSKI'S H- AND F-TYPE POPULATIONS
GROWTH FACTORS
SPECIFIC TISSUES AND ORGANS
Skin
Skin Appendages: A Special Case
Hematopoietic System
Blood Cell Counts after Total Body Irradiation
Partial Body Irradiation
Radiation and Chemotherapy Agents
Lymphoid Tissue and the Immune System
Digestive Tract
Oral Mucosa
Esophagus
Stomach
Small and Large Intestines
Lungs
Kidneys
Liver
Bladder Epithelium
Central and Peripheral Nervous Systems
Brain
Spinal Cord
Peripheral Nerves
Testes
Ovaries
Female Genitalia
Blood Vessels and the Vascular System
Heart
Bone and Cartilage
QUANTITATIVE ANALYSIS OF NORMAL TISSUE EFFECTS IN THE CLINIC
LATE EFFECTS OF NORMAL TISSUE AND SOMA
The SOMA Scoring System
APPLICATION OF STEM CELLS TO REGENERATE RADIATION-SENSITIVE ORGANS-SALIVARY GLAND REGENERATION
SUMMARY OF PERTINENT CONCLUSIONS
BIBLIOGRAPHY
21 Model Tumor Systems
TRANSPLANTABLE SOLID TUMOR SYSTEMS IN EXPERIMENTAL ANIMALS
APOPTOSIS IN TUMORS
TUMOR GROWTH MEASUREMENTS
TUMOR CURE (TCD
DILUTION ASSAY TECHNIQUE
LUNG COLONY ASSAY
IN VIVO/IN VITRO ASSAY
XENOGRAFTS OF HUMAN TUMORS
PATIENT-DERIVED XENOGRAFTS MODELS
AUTOCHTHONOUS AND TRANSGENIC TUMOR MODELS
SPHEROIDS: AN IN VITRO MODEL TUMOR SYSTEM
SPHEROIDS OF HUMAN TUMOR CELLS
ORGANOID MODELS OF HUMAN TUMORS
COMPARISON OF THE VARIOUS MODEL TUMOR SYSTEMS
SUMMARY OF PERTINENT CONCLUSIONS
BIBLIOGRAPHY
22 Cell, Tissue, and Tumor Kinetics
THE CELL CYCLE
CYCLINS AND KINASES
CHECKPOINT PATHWAYS
QUANTITATIVE ASSESSMENT OF THE CONSTITUENT PARTS OF THE CELL CYCLE
THE PERCENT-LABELED MITOSES TECHNIQUE
EXPERIMENTAL MEASUREMENTS OF CELL CYCLE TIMES IN VIVO AND IN VITRO
PULSED FLOW CYTOMETRY
THE GROWTH FRACTION
POTENTIAL DOUBLING TIME
CELL LOSS
DETERMINATIONS OF CELL LOSS IN EXPERIMENTAL ANIMAL TUMORS
GROWTH KINETICS OF HUMAN TUMORS
SUMMARY OF PERTINENT CONCLUSIONS
BIBLIOGRAPHY
23 Time, Dose, and Fractionation in Radiotherapy
THE INTRODUCTION OF FRACTIONATION
THE FOUR Rs OF RADIOBIOLOGY
THE STRANDQUIST PLOT AND THE ELLIS NOMINAL STANDARD DOSE SYSTEM
PROLIFERATION AS A FACTOR IN NORMAL TISSUES
THE SHAPE OF THE DOSE-RESPONSE RELATIONSHIP FOR EARLY- AND LATE-RESPONDING TISSUES
A POSSIBLE EXPLANATION FOR THE DIFFERENCE IN SHAPE OF DOSE-RESPONSE RELATIONSHIPS FOR EARLY- AND LATE-RESPONDING TISSUES
FRACTION SIZE AND OVERALL TREATMENT TIME: INFLUENCE ON EARLY- AND LATE-RESPONDING TISSUES
ACCELERATED REPOPULATION
THE IMPORTANCE OF OVERALL TREATMENT TIME
MULTIPLE FRACTIONS PER DAY
HYPOFRACTIONATION: RENEWED INTEREST
USING THE LINEAR-QUADRATIC CONCEPT TO CALCULATE EFFECTIVE DOSES IN RADIOTHERAPY
Choice of a/ß
Model Calculations
Allowance for Tumor Proliferation
Calculations Suggested by Fowler
Pragmatic Approach of Peters and Colleagues
SUMMARY OF PERTINENT CONCLUSIONS
BIBLIOGRAPHY
24 Retreatment after Radiotherapy: The Possibilities and the Perils
THE NATURE OF THE PROBLEM
EARLY- AND LATE-RESPONDING TISSUES
PRECLINICAL DATA
CLINICAL STUDIES
Spinal Cord
Brain
Head and Neck
Rectum
Bone Metastases
Breast
Lung
Recurrent Vaginal Metastases
SUMMARY OF PERTINENT CONCLUSIONS
Animal Studies
Clinical Studies
BIBLIOGRAPHY
Reviews
Preclinical (Animal Studies)
Clinical
25 Alternative Radiation Modalities
FAST NEUTRONS
Rationale
The Hammersmith Neutron Experience
The United States Neutron Experience
BORON NEUTRON CAPTURE THERAPY
Boron Compounds
Neutron Sources
Clinical Trials
PROTONS
Depth-Dose Patterns and the Bragg Peak
Advantages of Protons
CARBON ION RADIOTHERAPY
Depth-Dose Profiles
Radiobiologic Properties
Design of a Carbon Ion Beam for Clinical Use
Scattering and Fragmentation
Positron Emission Tomography Verification of Treatment Plans
Reasons for the Choice of Carbon Ions
SUMMARY OF PERTINENT CONCLUSIONS
Hadron Therapy
Neutrons
Boron Neutron Capture Therapy
Protons
Carbon Ion Radiotherapy
BIBLIOGRAPHY
26 The Biology and Exploitation of Tumor Hypoxia
HYPOXIA-INDUCIBLE FACTOR
Oxygen-Dependent Regulation of Hypoxia-Inducible Factor
Cancer Mutations that Activate Hypoxia-Inducible Factor
Important Roles of Hypoxia-Inducible Factor in Tumors
Tumor Angiogenesis
Tumor Metabolism
Tumor Metastasis
Hypoxia-Inducible Factor and Radiotherapy
UNFOLDED PROTEIN RESPONSE
RADIOSENSITIZING HYPOXIC CELLS
Hyperbaric Oxygen
Improving the Oxygen Supply to Tumors
Hypoxic Cell Radiosensitizers
Misonidazole
Etanidazole and Nimorazole
Overgaard's Meta-analysis of Clinical Trials Addressing the Problem of Hypoxia
Nicotinamide and Carbogen Breathing
HYPOXIC CYTOTOXINS
Tirapazamine
Clinical Trials with Tirapazamine and New Bioreductive Drugs
TARGETING TUMOR METABOLISM TO KILL HYPOXIC CELLS
Targeting Tumor Metabolism to Enhance the Efficacy of Radiotherapy
SUMMARY OF PERTINENT CONCLUSIONS
Hypoxia-Inducible Factor
The Unfolded Protein Response
Radiosensitizing Hypoxic Cells
Hypoxic Cytotoxins
BIBLIOGRAPHY
27 Chemotherapeutic Agents from the Perspective of the Radiation Biologist
BIOLOGIC BASIS OF CHEMOTHERAPY
CLASSES OF AGENTS AND THEIR MODE OF ACTION
Alkylating Agents
Procarbazine
Cis-Platinum
Antibiotics
Antimetabolites
5-Fluorouracil
Hydroxyurea
Nucleoside Analogues
Vinca Alkaloids
Taxanes
Hormone Targeted Therapies
Topoisomerase Inhibitors
Targeted Therapy
Cetuximab (Erbitux)
Bevacizumab (Avastin)
Poly Adenosine Diphosphate-Ribose Polymerase Inhibitors
Immune Checkpoint Therapies
DOSE-RESPONSE RELATIONSHIPS
SUBLETHAL AND POTENTIALLY LETHAL DAMAGE REPAIR
THE OXYGEN EFFECT AND CHEMOTHERAPEUTIC AGENTS
RESISTANCE TO CHEMOTHERAPY AND HYPOXIC CYTOTOXINS
DRUG RESISTANCE AND CANCER STEM CELLS
COMPARISON OF CHEMOTHERAPEUTIC AGENTS WITH RADIATION
ADJUNCT USE OF CHEMOTHERAPEUTIC AGENTS WITH RADIATION
ASSAYS FOR SENSITIVITY OF INDIVIDUAL TUMORS
SECOND MALIGNANCIES
SUMMARY OF PERTINENT CONCLUSIONS
BIBLIOGRAPHY
28 Hyperthermia
HISTORICAL
RESPONSE TO HEAT AT CYTOTOXIC TEMPERATURES
Dose Response
Sensitivity to Heat as a Function of Cell Age in the Mitotic Cycle
Hypoxia and Hyperthermia
Effect of pH and Nutrient Deficiency on Sensitivity to Heat
Response of Normal Tissues to Heat
Thermotolerance
Heat and Tumor Vasculature
METHODS OF HEATING AND THE IMPACT ON CLINICAL HYPERTHERMIA
Methods of Heating in Experimental Systems
Methods of Heating in Patients
Thermal Ablation
RESPONSE TO HEAT AT NONCYTOTOXIC TEMPERATURES
Reoxygenation
Immunologic Effects of Hyperthermia
THERMAL ENHANCEMENT RATIO
HEAT AND THE THERAPEUTIC GAIN FACTOR
MEASURING THERMAL DOSE IN PATIENTS
PHASE III CLINICAL TRIALS TESTING BENEFITS OF HYPERTHERMIA FOR ENHANCING RADIATION THERAPY
CLINICAL TRIALS ASSESSING THE BENEFIT OF HYPERTHERMIA IN COMBINATION WITH CHEMOTHERAPEUTIC AGENTS
Development and Evaluation of "Thermosensitive" Liposomes for Improved Tumor Targeting of Chemotherapy
METHODS OF TUMOR HEATING
Magnetic Hyperthermia
CLINICAL THERMOMETRY
Invasive Thermometry Methods
Progress toward Clinically Achievable Noninvasive Thermometry
SUMMARY OF PERTINENT CONCLUSIONS
Hyperthermia at Cytotoxic Temperatures (42° to 45° C)
Hyperthermia at Modest Temperatures that Can Be Achieved in Human Tumors
BIBLIOGRAPHY
Glossary
Index

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