Cured II - LENT Cancer Survivorship Research And Education (eBook)

Dedications 5
Foreword 7
Introduction 8
Table of Contents 10
1 CONCURED: Defining the Leading Edge in Research of Adverse Eff ects of Treatment for Adult-Onset Cancers 12
1.1 Introduction 12
1.2 Research Infrastructure for Studies of Cancer Survivorship 12
1.3 A Platform for Studies of Gene–Environment Interactions 14
1.4 Development of Epidemiologic Methods and Predictive Models 14
1.5 Evidence-Based Clinical Practice Guidelines 14
1.6 A Trans-disciplinary Approach 15
Comment 15
Acknowledgement 16
References 16
2 Bioimaging In Vivo to Discern the Evolution of Late Eff ects Temporally and Spatially 18
2.1 Introduction 18
2.2 Lung Injury 19
2.3 Heart Injury 21
2.3.1 SPECT 22
2.3.2 MRI 22
2.3.3 Cardiac PET 22
2.4 Liver Injury 24
2.4.1 CT Perfusion Studies 24
2.4.2 MRI 24
2.5 Brain Injury 25
2.5.1 SPECT 25
2.5.2 PET 25
2.5.3 MRI 27
2.5.4 Magnetic Resonance Spectroscopy 27
2.5.5 Functional Magnetic Resonance Imaging 28
2.6 Parotid Gland Injury 28
2.6.1 SPECT and PET 28
2.6.2 MRI 28
2.7 Conclusions 28
Acknowledgements 28
References 30
3 Association Between Single Nucleotide Polymorphisms and Susceptibility for the Development of Adverse Eff ects Resulting from Radiation Therapy 35
3.1 Summary 35
3.2 Introduction 35
3.3 Predictive Assays 36
3.4 Candidate Gene Studies 37
3.5 Genome Wide SNP Association Studies 37
3.6 Conclusion 40
Acknowledgements 40
References 40
4 Prospective Second-Cancer Risk Estimation for Contemporary Radiotherapeutic Protocols 43
4.1 Introduction: Radiotherapy-Related Second-Cancer Risks 43
4.2 The Potential Signifificance of Altered Normal-Tissue Dose Distributions: Intensity-Modulated Radiation Therapy and Second-Cancer Risks 44
4.3 Mechanisms of Radiation-Induced Cancer at Radiotherapeutic Doses 44
4.3.1 The Standard Model 44
4.3.2 A More Realistic Model 45
4.4 An Application: Prospective Estimation of Radiotherapy-Induced Second-Cancer Risks 46
4.5 Future Directions 46
Acknowledgments 48
References 48
5 Bioengineering in the Repair of Irradiated Normal Tissue by Bone Marrow Derived Stem Cell Populations 51
5.1 Introduction 51
5.1.1 The New Paradigm for Understanding IonizingIrradiation Tissue Damage 51
5.1.2 General Concepts of Bioengineering for Tissue Repair 52
5.2 Bone Marrow Origin of Stem Cells for Epithelial Tissues 53
5.2.1 Repopulation of Recipient Target Organs with Bone Marrow Derived Stem Cell Progenitors: A Double Edged Sword 55
5.2.2 Bone Marrow Derived Stem Cells in Bioengineering Repair of Irradiated Oral Cavity and Oropharyngeal Mucosa 55
5.2.3 Bioengineering for Repair of Irradiation Damage in the Esophagus Using Bone Marrow Derived Stem Cell Progenitors 56
5.2.4 Bioengineering of Irradiation Damaged Lung Through Use of Bone Marrow Derived Stem Cell Progenitors 58
5.3 Summary 60
References 60
6 Development of a Queriable Database for Oncology Outcome Analysis 65
6.1 Introduction 65
6.2 Efforts to Date 66
6.2.1 Quality Assurance Review Center 66
6.2.2 Database Function 67
6.2.3 Advanced Technology Consortium 70
6.2.4 American College of Radiology Imaging Network (ACRIN) 70
6.2.5 Virtual Imaging Evaluation Workspace (VIEW) 71
6.2.6 CaBIG 71
6.3 Future Strategies for Cancer Clinical Trials 73
References 75
7 Post-Radiation Dysphagia 77
7.1 Evaluation of the Swallowing Mechanism 78
7.1.1 Objective Evaluation: Instrumental Assessment 78
7.1.2 Objective Evaluation: Observer-Assessed 78
7.1.3 Subjective Evaluation: Patient-Reported Quality of Life 78
7.2 Baseline Swallowing Function in Patients with Head and Neck Cancer 78
7.3 Swallowing Disorders Induced by Radiation Alone 79
7.4 Surgery and Radiation-Induced Swallowing Dysfunctions 80
7.5 Chemoradiation-Induced Swallowing Dysfunctions 80
7.6 Organ at Risk and the Dose–Volume–Effect Relationship 81
7.7 Preventive Intervention to Reduce Swallowing Disorders 83
7.8 Radiation Modulation 83
7.9 Oral Feeding vs Feeding Tube 84
7.10 Cytoprotectors 84
7.11 Oropharyngeal Exercises 84
7.12 Therapeutic Intervention to Improve Swallowing Disorders 84
7.13 Therapy Procedures 85
7.14 Summary 85
References 86
8 Lithium as a Diff erential Neuroprotector During Brain Irradiation 90
8.1 Introduction 90
8.2 Neurotoxicity from Brain Radiotherapy 91
8.2.1 Acute Complications 91
8.2.2 Early-Delayed Complications 91
8.2.3 Delayed Complications 91
8.2.3.1 Neurocognitive Effects 92
8.2.3.1.1 Cognitive Dysfunction/Leukoencephalopathy 92
8.2.3.1.2 Radiation-Induced Dementia 92
8.2.3.1.3 Mild or Moderate Neuropsychological Impairment 93
8.2.3.2 Radiation Necrosis 93
8.2.3.3 Other Adverse Consequences 93
8.3 Mechanisms of Brain Injury 93
8.4 Potential Neuroprotectors 94
8.5 Mechanisms of Lithium-Mediated NeuroprotectionAgainst Radiation-Induced Apoptosis 94
8.6 Future Directions 97
8.6.1 Clinical Phase I Trial of Lithium 97
8.6.2 Potential Disadvantages of Lithium 97
8.6.3 GSK-3ß Inhibitors 97
8.6.4 Summary 98
References 98
9 Risks and Surveillance of Second Malignant Tumors in Prostate and Bladder Cancer Survivors 102
9.1 Introduction 102
9.2 Risk of Second Malignant Tumors after Prostate Cancer 102
9.3 Rectal Cancer 103
9.4 Bladder Cancer 104
9.5 Sarcoma 104
9.6 Lung Cancer 106
9.7 Male Breast Cancer 106
9.8 Pancreas Cancer 106
9.9 Leukemia 106
9.10 Surveillance Strategies for Prostate Cancer Patients Treated with Radiotherapy 107
9.11 Second Malignant Tumors after Treatment for Bladder Cancer 107
9.12 The Effect of Technology on Second Malignant Tumor Development after Prostate Radiotherapy 108
9.13 Cost-Effectiveness of Screening for Second Malignant Tumors 108
References 109
10 Cardiotoxic Eff ects of Radiation Therapy in Hodgkin’s Lymphoma and Breast Cancer Survivors and the Potential Mitigating Eff ects of Exercise 111
10.1 Introduction 111
10.2 Cardiopulmonary Sequelae 112
10.3 Fatigue and Its Relationship to Cardiopulmonary Sequelae 115
10.3.1 Cancer Related Fatigue 115
10.3.2 Fatigue in HL Patients and Possible Associations with Cardiopulmonary Status 115
10.4 Exercise Interventions for Fatigue and Cardiopulmonary Function Among Cancer Survivors 116
10.4.1 Rationale for Exercise Interventions in Cancer Survivors Treated with Mediastinal Radiotherapy 116
10.4.2 Exercise Interventions: Safety and Effi cacy in Cancer Survivors 117
10.5 Conclusion 120
References 120
11 Biodetection and Biointervention: Cytokine Pathways as a Rationale for Anticytokine Interventions Post-Radiation 124
11.1 Introduction 124
11.2 Molecular Mechanisms of Radiation Injury 124
11.3 The Importance of Transforming Growth Factor ß in Radiation-Induced Injury 126
11.4 Using Plasma TGFß Levels to Predict Injury Risk 127
11.5 The Role of Other Cytokines in Radiation-Induced Injury 127
11.6 Using Other Markers to Predict Radiation-Induced Injury 127
11.7 Chronic Inflammation as a Mediator of Radiation Induced-Malignancy 128
11.8 Candidate Proteins for Predicting Radiation Injury 128
11.9 Strategies and Potential Targets for Intervention 129
References 131
12 Late Toxicity from Hypofractionated Stereotactic Body Radiation 136
12.1 Introduction 136
12.2 Technical Aspects of SBRT 137
12.3 Radiobiology of Hypofractionated Radiation 137
12.4 University of Rochester Experience with Hypofractionated SBRT 139
12.5 Review of Select Clinical Trials Using Hypofractionated SBRT: Late Toxicity 139
12.5.1 Lung 140
12.5.2 Liver 142
12.5.3 Pancreas 143
12.5.4 Prostate 143
12.5.5 Spine 144
12.6 Conclusions 144
References 145
13 The Radiation Spectrum of Normal Tissue Toxicity and Tolerance – Multiorgan Domino Effect 148
13.1 Introduction 148
13.2 Phase I: Release and Regeneration 148
13.3 Phase II: Recruitment and Repopulation 151
13.4 Phase III: Replacement and Reoxygenation 152
13.5 Phase IV: Reassortment and Remodeling 154
13.6 Phase V: Cell Repair and Resurgence 154
13.7 Discussion 155
References 159
14 Risk Factors for Second Malignancies Following Stem Cell Transplant 161
14.1 Introduction 161
14.2 Risk Factors for SMN Following Autologous Versus Allogeneic Transplant 161
14.2.1 SMN Following Autologous HSCT 161
14.2.2 SMN Following Allogeneic HSCT 163
14.3 Genetic Risk Factors for SMNs Following Transplant 165
14.3.1 Radiation Exposure and Sensitivity 165
14.3.2 Genetic Biomarkers for Second Malignancies Following HCT and Radiation Therapy 165
14.3.3 Genetic Susceptibility to Toxicity from Combined Cancer Therapy and Environmental Carcinogens: Common Pathways of Metabolism, DNA Damage and Repair 165
14.4 Conclusions 166
References 166
List of Contributors 176
Subject Index 169