Name: Radiation Oncology Advances
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ISBN: 9780387367439

Radiation Oncology Advances: An Introduction	p. 1
Advances in Imaging and Theragnostic Radiation Oncology	p. 1
Advances in Molecular Biology and Targeted Therapies	p. 2
Advances in Treatment Delivery and Planning	p. 3
Clinical Advances	p. 4
References	p. 4
Advances in Imaging and Biologically-Based Treatment Planning
Advanced Image-Guided External Beam Radiotherapy	p. 7
Introduction	p. 7
Image Guidance for Defining Target Volumes	p. 9
Image Guidance at the Time of Delivery	p. 13
Optical Guidance	p. 14
Optical Tracking Systems	p. 15
Optical Tracking in Fractionated Stereotactic Radiotherapy, Intracranial, and Head and Neck IMRT	p. 16
Optically Guided Ultrasound	p. 18
In-Room CT Guidance	p. 20
Image Guidance and Organ Motion	p. 27
Image Guidance for Follow-Up Imaging and Retreatments	p. 29
Summary	p. 31
References	p. 32
Does Painting and Theragnostic Imaging: Towards the Prescription, Planning and Delivery of Biologically Targeted Dose Distributions in External Beam Radiation Oncology	p. 41
Radiation Theragnostics	p. 41
From Anatomical to Biological Targeting in Radiation Therapy	p. 42
From Target Selection and Delineation to 4D Dose Prescription	p. 43
The Case for Nonuniform Theragnostic Dose Distributions	p. 44
Precision Requirements	p. 47
Targeting Hypoxia Using EBRT: Are We Ready for Dose Painting by Numbers?	p. 48
Painting by Numbers?	p. 48
Hypoxia as a Cause of Clinical Failure of Radiation Therapy	p. 48
Hypoxia Imaging	p. 50
Spatiotemporal Stability of the PET Hypoxia Map	p. 53
Dose Painting by Numbers	p. 56
Dose Delivery and Expected Change in Outcome	p. 57
Conclusion	p. 57
References	p. 58
Molecular and Functional Imaging in Radiation Oncology	p. 63
Introduction	p. 63
Molecular and Functional Imaging Modalities	p. 64
Positron Emission Tomography	p. 64
Single Photon Emission Tomography	p. 65
Dynamic Contrast Enhanced Computer Tomography (DCE-CT)	p. 65
Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI)	p. 65
Imaging (DCE-MRI)	p. 65
Magnetic Resonance Spectroscopy	p. 66
Optical Imaging	p. 66
Comparison Between Different Imaging Modalities	p. 66
Molecular and Functional Imaging Targets	p. 67
Cellular Metabolism	p. 68
Cellular Proliferation	p. 72
Cellular Death	p. 73
Cellular Regulation	p. 74
Tumor Microenvironment	p. 77
Future	p. 80
References	p. 82
Prognostic and Predictive Markers in Radiation Therapy: Focus on Prostate Cancer	p. 97
Introduction	p. 97
The Need for Biomarkers of Radiation Response in Prostate Cancer	p. 97
Optimal Biomarkers and Patient Cohort Characteristics	p. 98
Evaluation of Candidate Markers	p. 99
Biological Rationale	p. 99
Biomarker Frequency	p. 102
Biomarker Assessment Methods	p. 102
Immunohistochemistry	p. 103
Clinical Correlative Data in Prostate Cancer	p. 104
Markers of Cell Cycle Control, DNA Repair and Apoptosis	p. 105
Proliferation	p. 105
Hypoxia	p. 106
Limitations of Existing Studies	p. 106
Future Studies and Directions	p. 107
Large Prospective Clinical Trials	p. 107
Biomarker-Based Adaptive Therapy	p. 108
Conclusion	p. 109
References	p. 109
Advances in Molecular Biology and Targeted Therapies
Overview of Cancer Molecular Radiobiology	p. 117
Introduction	p. 117
Interaction of Radiation with Living Cells	p. 117
Cellular Response to Ionizing Radiation	p. 118
Cell Cycle Arrest	p. 118
DNA Repair	p. 120
Apoptosis	p. 121
Cell Survival Signaling	p. 122
Ras Signaling	p. 122
Receptor Tyrosine Kinases	p. 123
mTOR Signaling	p. 123
Targeting Housekeeping Proteins	p. 124
HSP90 Inhibitors	p. 125
HDAC Inhibitors	p. 126
Proteosome Inhibitors	p. 128
Conclusion	p. 129
References	p. 130
Clinical Application of EGFR Inhibitors in Head and Neck Squamous Cell Cencer	p. 135
Introduction	p. 135
EGFR Biology	p. 136
Anti-EGFR Monoclonal Antibodies	p. 138
Radiation Plus Cetuximab For Locoregionally Advanced HNSCC	p. 138
Cetuximab, Cisplatin, and Radiation in Locoregionally Advanced HNSCC	p. 140
Cetuximab ± Chemotherapy in Recurrent and/or Metastatic HNSCC	p. 141
Cetuximab with Chemotherapy in the First-Line Treatment of Patients with Recurrent and/or Metastatic HNSCC	p. 142
EGFR Tyrosine Kinase Inhibitors (TKIs)	p. 143
TKI Monotherapy in HNSCC	p. 144
TKIs in Combination with Radiation Therapy	p. 144
TKIs with Dual Specificity	p. 145
Patient Selection	p. 145
Conclusions	p. 146
References	p. 147
Advancement of Antiangiogenic and Vascular Disrupting Agents Combined with Radiation	p. 153
Introduction	p. 153
Tumor Vasculature	p. 153
Targeting the Tumor Vasculature	p. 155
Antiangiogenic Agents	p. 155
Vascular Disrupting Agents	p. 158
Combining Antiangiogenic and Vascular Disrupting Agents with Radiation	p. 160
Antiangiogenic Agents and Radiation in the Laboratory	p. 160
Angiogenesis Inhibitors and Radiation in the Clinic	p. 162
Vascular Disrupting Agents and Radiation in the Laboratory	p. 163
Vascular Disrupting Agents with Radiation in the Clinic	p. 164
Future Directions	p. 165
Conclusion	p. 166
References	p. 167
Overcoming Therapeutic Resistance in Malignant Gliomas: Current Practices and Future Directions	p. 173
Introduction	p. 173
Signal Transduction Pathways Involved in Treatment Resistance	p. 173
Angiogenesis Pathways	p. 175
Conventional Chemotherapeutic Agents in Malignant Gliomas	p. 177
Biotherapeutic Strategies	p. 182
Antiepidermal Growth Factor Receptor (EGFR) Strategies	p. 182
mTor Pathway Inhibition: CCI-779	p. 184
Antiangiogenic Strategies	p. 185
Summary	p. 186
References	p. 186
Advances in Treatment Delivery and Planning
Advances in Intensity-Modulated Radiotherapy Delivery	p. 193
Introduction	p. 193
Background	p. 193
Fixed-Field IMRT	p. 194
Direct Aperture Optimisation and Jaws-Only Linear Accelerator IMRT	p. 199
Tomotherapy	p. 199
Axial Tomotherapy	p. 200
Helical Tomotherapy	p. 201
Future Developments	p. 206
CyberKnife	p. 208
Summary	p. 209
References	p. 210
Image-Based Modeling of Normal Tissue Complication Probability for Radiation Therapy	p. 215
Introduction	p. 215
NTCP Models: Tools or Toys?	p. 216
Why Image-Based NTCP Analysis?	p. 218
Tissue Dose-Response Classification	p. 219
The Concepts of "Serial" and "Parallel" Tissue Dose-Response	p. 219
Local vs. Global Organ Injuries	p. 221
NTCP Models	p. 222
The Generalized Equivalent Uniform Dose Equation	p. 223
Basic Mathematical Features of Common NTCP Functions	p. 225
Cluster Models	p. 227
A Data-Mining/Data-Driven Approach to NTCP Modeling	p. 227
Selection of Relevant Input Variables	p. 231
Selection of Model Functional Form	p. 232
Selection of Model Order	p. 233
Model Order Based on Information Theory	p. 233
Model Order Based on Cross-validation Methods	p. 235
Model Variable Stability	p. 235
Model Parameter Fitting	p. 235
Image-Based Factors and Radiosensitivity Predictors	p. 236
Some Critical NTCP Endpoints	p. 237
Late Rectal Toxicity Due to External Beam Prostate Cancer Treatment	p. 237
Radiation Pneumonitis Due to Thoracic Irradiation for Lung Cancer	p. 238
Xerostomia Due to Head and Neck Cancer Treatment	p. 240
Drawbacks to Treatment Planning Based on Dose-Volume Limits	p. 243
Uncertainties in NTCP Models	p. 244
Incorporating Fractionation Sensitivity	p. 245
Summary	p. 248
References	p. 248
Optimization of Radiotherapy Using Biological Parameters	p. 257
Introduction	p. 257
The Need for Optimization Based on Biological Parameters	p. 259
Radiobiological Models	p. 260
Biological Optimization	p. 264
Subvolume-Based Radiobiological Models	p. 264
Impact of Diagnostic Accuracy on Biological Optimization	p. 270
Functional Imaging in Oncology	p. 270
Theragnostic Imaging in Risk-Adaptive Radiotherapy	p. 270
The Impact of Imaging Sensitivity on Risk-Adaptive Radiotherapy	p. 271
Clinical Parameters Necessary for Biological Optimization	p. 272
Summary	p. 274
References	p. 275
Clinical Advances
Combined Chemoradiotherapy Advances	p. 281
Introduction	p. 281
Head and Neck Cancers	p. 282
Nonsmall Cell Lung Carcinoma	p. 288
Cervical Carcinoma	p. 292
Esophageal Carcinoma	p. 294
Rectal Adenocarcinoma	p. 296
Anal Squamous Cell Carcinoma	p. 298
Muscle Invasive Bladder Cancer	p. 299
Conclusion	p. 300
References	p. 300
Cytoprotection for Radiation-Associated Normal Tissue Injury	p. 307
Biologic Rationale of Cytoprotectors	p. 307
Assessment of Amifostine in Patients with Head and Neck Cancer	p. 309
Assessment of Amifostine in Patients with Thoracic Tumors	p. 309
Lung Injury	p. 309
Esophageal Injury	p. 312
Assessment of Amifostine in Patients with Pelvic Tumors	p. 312
Assessment of Amifostine in Patients with Tumors at Other Sites	p. 312
Impact of Amifostine on Tumor Control and Survival	p. 314
Amifostine-Related Toxicity	p. 314
Administration of Amifostine	p. 314
Other Cytoprotectors	p. 321
Conclusion	p. 323
References	p. 323
Index	p. 329
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Radiation Oncology Advances

9780387367439

0387367438

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