Radiation Oncology Advances (eBook)

Contents 6
Contributors 13
Radiation Oncology Advances: An Introduction 17
Advances in Imaging and Theragnostic Radiation Oncology 17
Advances in Molecular Biology and Targeted Therapies 18
Advances in Treatment Delivery and Planning 19
Clinical Advances 20
References 20
Section I Advances in Imaging and Biologically-Based Treatment Planning 21
Advanced Image-Guided External Beam Radiotherapy 22
Introduction 22
Image Guidance for Defining Target Volumes 24
Image Guidance at the Time of Delivery 28
Optical Guidance 29
Optical Tracking Systems 30
Optical Tracking in Fractionated Stereotactic Radiotherapy, Intracranial, and Head and Neck IMRT 31
Optically Guided Ultrasound 33
In-Room CT Guidance 35
Image Guidance and Organ Motion 42
Image Guidance for Follow-Up Imaging and Retreatments 44
Summary 46
References 47
Dose Painting and Theragnostic Imaging: Towards the Prescription, Planning and Delivery of Biologically Targeted Dose Distributions in External Beam Radiation Oncology 55
Radiation Theragnostics 55
From Anatomical to Biological Targeting in Radiation Therapy 56
From Target Selection and Delineation to 4D Dose Prescription 57
The Case for Nonuniform Theragnostic Dose Distributions 58
Precision Requirements 61
Targeting Hypoxia Using EBRT: Are We Ready for Dose Painting by Numbers? 62
Hypoxia as a Cause of Clinical Failure of Radiation Therapy 62
Hypoxia Imaging 64
Spatiotemporal Stability of the PET Hypoxia Map 67
Dose Painting by Numbers 70
Dose Delivery and Expected Change in Outcome 71
Conclusion 71
References 72
Molecular and Functional Imaging in Radiation Oncology 77
Introduction 77
Molecular and Functional Imaging Modalities 78
Positron Emission Tomography 78
Single Photon Emission Tomography 79
Dynamic Contrast Enhanced Computer Tomography (DCE-CT) 79
Dynamic Contrast Enhanced Magnetic Resonance Imaging ( DCE- MRI) 79
Magnetic Resonance Spectroscopy 80
Optical Imaging 80
Comparison Between Different Imaging Modalities 80
Molecular and Functional Imaging Targets 81
Cellular Metabolism 82
Cellular Proliferation 86
Cellular Death 87
Cellular Regulation 88
Tumor Microenvironment 91
Future 94
References 96
Prognostic and Predictive Markers in Radiation Therapy: Focus on Prostate Cancer 110
Introduction 110
The Need for Biomarkers of Radiation Response in Prostate Cancer 110
Optimal Biomarkers and Patient Cohort Characteristics 111
Evaluation of Candidate Markers Biological Rationale 112
Biomarker Frequency 115
Biomarker Assessment Methods 115
Immunohistochemistry 116
Markers of Cell Cycle Control, DNA Repair and Apoptosis 118
Proliferation 118
Hypoxia 119
Clinical Correlative Data in Prostate Cancer 117
Limitations of Existing Studies 119
Future Studies and Directions 120
Large Prospective Clinical Trials 120
Biomarker-Based Adaptive Therapy 121
Conclusion 122
References 122
Section II Advances in Molecular Biology and Targeted Therapies 128
Overview of Cancer Molecular Radiobiology 129
Introduction 129
Interaction of Radiation with Living Cells 129
Cellular Response to Ionizing Radiation 130
Cell Cycle Arrest 130
DNA Repair 132
Apoptosis 133
Cell Survival Signaling 134
Ras Signaling 134
Receptor Tyrosine Kinases 135
mTOR Signaling 135
Targeting Housekeeping Proteins 136
HSP90 Inhibitors 137
HDAC Inhibitors 138
Proteosome Inhibitors 140
Conclusion 141
References 142
Clinical Application of EGFR Inhibitors in Head and Neck Squamous Cell Cancer 146
Introduction 146
EGFR Biology 147
Anti-EGFR Monoclonal Antibodies 149
Radiation Plus Cetuximab For Locoregionally Advanced HNSCC 149
Cetuximab, Cisplatin, and Radiation in Locoregionally Advanced HNSCC 151
Cetuximab ± Chemotherapy in Recurrent and/ or Metastatic HNSCC 152
Cetuximab with Chemotherapy in the First-Line Treatment of Patients with Recurrent and/ or Metastatic HNSCC 153
EGFR Tyrosine Kinase Inhibitors (TKIs) 154
TKI Monotherapy in HNSCC 155
TKIs in Combination with Radiation Therapy 155
TKIs with Dual Specificity 156
Patient Selection 156
Conclusions 157
References 158
Advancement of Antiangiogenic and Vascular Disrupting Agents Combined with Radiation 164
Introduction 164
Tumor Vasculature 164
Targeting the Tumor Vasculature 166
Antiangiogenic Agents 166
Vascular Disrupting Agents 169
Combining Antiangiogenic and Vascular Disrupting Agents with Radiation 171
Antiangiogenic Agents and Radiation in the Laboratory 171
Angiogenesis Inhibitors and Radiation in the Clinic 173
Vascular Disrupting Agents and Radiation in the Laboratory 174
Vascular Disrupting Agents with Radiation in the Clinic 175
Future Directions 176
Conclusion 177
References 178
Overcoming Therapeutic Resistance in Malignant Gliomas: Current Practices and Future Directions 183
Introduction 183
Signal Transduction Pathways Involved in Treatment Resistance 183
Angiogenesis Pathways 185
Conventional Chemotherapeutic Agents in Malignant Gliomas 187
Biotherapeutic Strategies 192
Antiepidermal Growth Factor Receptor (EGFR) Strategies 192
mTor Pathway Inhibition: CCI-779 194
Antiangiogenic Strategies 195
Summary 196
References 196
Section III Advances in Treatment Delivery and Planning 200
Advances in Intensity-Modulated Radiotherapy Delivery 201
Introduction 201
Background 201
Fixed-Field IMRT 202
Direct Aperture Optimisation and Jaws-Only Linear Accelerator IMRT 207
Tomotherapy 207
Axial Tomotherapy 208
Helical Tomotherapy 209
Future Developments 214
CyberKnife 216
Summary 217
References 218
Image-Based Modeling of Normal Tissue Complication Probability for Radiation Therapy 223
Introduction 223
NTCP Models: Tools or Toys? 224
Why Image-Based NTCP Analysis? 226
Tissue Dose–Response Classification 227
The Concepts of “Serial” and “Parallel” Tissue Dose–Response 227
Local vs. Global Organ Injuries 229
NTCP Models 230
The Generalized Equivalent Uniform Dose Equation 231
Basic Mathematical Features of Common NTCP Functions 233
Cluster Models 235
A Data-Mining/Data-Driven Approach to NTCP Modeling 235
Selection of Relevant Input Variables 239
Selection of Model Functional Form 240
Selection of Model Order 241
Model Order Based on Information Theory 241
Model Order Based on Cross-validation Methods 243
Model Variable Stability 243
Model Parameter Fitting 243
Image-Based Factors and Radiosensitivity Predictors 244
Some Critical NTCP Endpoints 245
Late Rectal Toxicity Due to External Beam Prostate Cancer Treatment 245
Radiation Pneumonitis Due to Thoracic Irradiation for Lung Cancer 246
Xerostomia Due to Head and Neck Cancer Treatment 248
Drawbacks to Treatment Planning Based on Dose–Volume Limits 251
Uncertainties in NTCP Models 252
Incorporating Fractionation Sensitivity 253
Summary 256
References 256
Optimization of Radiotherapy Using Biological Parameters 265
Introduction 265
The Need for Optimization Based on Biological Parameters 267
Radiobiological Models 268
Biological Optimization 272
Subvolume-Based Radiobiological Models 272
Impact of Diagnostic Accuracy on Biological Optimization 278
Functional Imaging in Oncology 278
Theragnostic Imaging in Risk-Adaptive Radiotherapy 278
The Impact of Imaging Sensitivity on Risk-Adaptive Radiotherapy 279
Clinical Parameters Necessary for Biological Optimization 280
Summary 282
References 283
Section IV Clinical Advances 287
Combined Chemoradiotherapy Advances 288
Introduction 288
Head and Neck Cancers 289
Nonsmall Cell Lung Carcinoma 295
Cervical Carcinoma 299
Esophageal Carcinoma 301
Rectal Adenocarcinoma 303
Anal Squamous Cell Carcinoma 305
Muscle Invasive Bladder Cancer 306
Conclusion 307
References 307
Cytoprotection for Radiation-Associated Normal Tissue Injury 313
Biologic Rationale of Cytoprotectors 313
Assessment of Amifostine in Patients with Head and Neck Cancer 315
Assessment of Amifostine in Patients with Thoracic Tumors 315
Lung Injury 315
Esophageal Injury 318
Assessment of Amifostine in Patients with Pelvic Tumors 318
Assessment of Amifostine in Patients with Tumors at Other Sites 318
Impact of Amifostine on Tumor Control and Survival 320
Amifostine-Related Toxicity 320
Administration of Amifostine 320
Other Cytoprotectors 327
Conclusion 329
References 329
Index 334