Radiation Oncology Advances

347 Pages·2008·22.919 MB·English

by  Professor Søren M. Bentzen Ph.D., D.Sc, Professor Paul M. Harari M.D (auth.), Professor Søren M. Bentzen Ph.D., D.Sc, Professor Paul M. Harari M.D, Associate Professor Wolfgang A. Tomé M.D., Ph.D, Professor Minesh P. Mehta M.D (eds.)

Radiation Oncology Advances
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Cancer Treatment and Research
Steven T. Rosen, M.D., Series Editor
Arnold, A.J. (ed.): Endocrine Neoplasms. 1997. ISBN 0-7923-4354-9.
Pollock, R.E. (ed.): Surgical Oncology. 1997. ISBN 0-7923-9900-5.
Verweij, J., Pinedo, H.M., Suit, H.D. (eds): Soft Tissue Sarcomas: Present Achievements
and Future Prospects. 1997. ISBN 0-7923-9913-7.
Walterhouse, D.O., Cohn, S. L. (eds): Diagnostic and Therapeutic Advances in Pediatric
Oncology. 1997. ISBN 0-7923-9978-1.
Mittal, B.B., Purdy, J.A., Ang, K.K. (eds): Radiation Therapy. 1998.
ISBN 0-7923-9981-1.
Foon, K.A., Muss, H.B. (eds): Biological and Hormonal Therapies of Cancer. 1998.
ISBN 0-7923-9997-8.
Ozols, R.F. (ed.): Gynecologic Oncology. 1998. ISBN 0-7923-8070-3.
Noskin, G.A. (ed.): Management of Infectious Complications in Cancer Patients. 1998.
ISBN 0-7923-8150-5.
Bennett, C.L. (ed.): Cancer Policy. 1998. ISBN 0-7923-8203-X.
Benson, A.B. (ed.): Gastrointestinal Oncology. 1998. ISBN 0-7923-8205-6.
Tallman, M.S., Gordon, L.I. (eds): Diagnostic and Therapeutic Advances in Hematologic
Malignancies. 1998. ISBN 0-7923-8206-4.
von Gunten, C.F. (ed.): Palliative Care and Rehabilitation of Cancer Patients. 1999.
ISBN 0-7923-8525-X.
Burt, R.K., Brush, M.M. (eds): Advances in Allogeneic Hematopoietic Stem Cell
Transplantation. 1999. ISBN 0-7923-7714-1.
Angelos, P. (ed.): Ethical Issues in Cancer Patient Care 2000. ISBN 0-7923-7726-5.
Gradishar, W.J., Wood, W.C. (eds): Advances in Breast Cancer Management. 2000.
ISBN 0-7923-7890-3.
Sparano, J.A. (ed.): HIV & HTLV-I Associated Malignancies. 2001.
ISBN 0-7923-7220-4.
Ettinger, D.S. (ed.): Thoracic Oncology. 2001. ISBN 0-7923-7248-4.
Bergan, R.C. (ed.): Cancer Chemoprevention. 2001. ISBN 0-7923-7259-X.
Raza, A., Mundle, S.D. (eds): Myelodysplastic Syndromes & Secondary Acute
Myelogenous Leukemia 2001. ISBN: 0-7923-7396.
Talamonti, M.S. (ed.): Liver Directed Therapy for Primary and Metastatic Liver Tumors.
2001. ISBN 0-7923-7523-8.
Stack, M.S., Fishman, D.A. (eds): Ovarian Cancer. 2001. ISBN 0-7923-7530-0.
Bashey, A., Ball, E.D. (eds): Non-Myeloablative Allogeneic Transplantation. 2002.
ISBN 0-7923-7646-3.
Leong, S.P.L. (ed.): Atlas of Selective Sentinel Lymphadenectomy for Melanoma, Breast
Cancer and Colon Cancer. 2002. ISBN 1-4020-7013-6.
Andersson, B., Murray, D. (eds): Clinically Relevant Resistance in Cancer
Chemotherapy. 2002. ISBN 1-4020-7200-7.
Beam, C. (ed.): Biostatistical Applications in Cancer Research. 2002.
ISBN 1-4020-7226-0.
Brockstein, B., Masters, G. (eds): Head and Neck Cancer. 2003. ISBN 1-4020-7336-4.
Frank, D.A. (ed.): Signal Transduction in Cancer. 2003. ISBN 1-4020-7340-2.
(continued after index)
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Radiation Oncology
Advances
Edited by
Søren M. Bentzen, Ph.D., D.Sc.
Professor
Department of Human Oncology
University of Wisconsin School of Medicine
Madison, Wisconsin, USA
Paul M. Harari, M.D.
Jack Fowler Professor and Chairman
Department of Human Oncology
University of Wisconsin School of Medicine
Madison, Wisconsin, USA
Wolfgang A. Tomé, M.D., Ph.D
Associate Professor
Department of Human Oncology
University of Wisconsin School of Medicine
Madison, Wisconsin, USA
Minesh P. Mehta, M.D.
Professor
Department of Human Oncology
University of Wisconsin School of Medicine
Madison, Wisconsin, USA
MMeehhttaa__FFMM..iinndddd iiiiii 88//2288//22000077 66::2244::2277 PPMM
Søren M. Bentzen, PhD
Paul M. Harari, MD
Wolfgang A. Tomé, PhD
Minesh P. Mehta, MD
University of Wisconsin
Department of Human Oncology
600 Highland Avenue, K4/310
Madison, WI 53792
USA
Series Editor:
Steven T. Rosen
Robert H. Lurie Comprehensive Cancer Center
Northwestern University
Chicago, IL
USA
ISBN-13: 978-0387-36743-9 e-ISBN-13: 978-0387-36744-6
Library of Congress Control Number: 2007925437
© 2008 Springer Science + Business Media, LLC
All rights reserved. This work may not be translated or copied in whole or in part without the written
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Printed on acid-free paper.
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Contents
1 Radiation Oncology Advances: An Introduction ..................................... 1
Søren M. Bentzen, Paul M. Harari, Wolfgang A. Tomé,
and Minesh P. Mehta
Advances in Imaging and Theragnostic Radiation Oncology ....................... 1
Advances in Molecular Biology and Targeted Therapies ............................. 2
Advances in Treatment Delivery and Planning ............................................. 3
Clinical Advances .......................................................................................... 4
References ...................................................................................................... 4
Section I. Advances in Imaging and Biologically-Based Treatment Planning
2 Advanced Image-Guided External Beam Radiotherapy ......................... 7
Thomas Rockwell Mackie and Wolfgang Tomé
Introduction .................................................................................................... 7
Image Guidance for Defining Target Volumes ......................................... 9
Image Guidance at the Time of Delivery ................................................... 13
Optical Guidance ....................................................................................... 14
Optical Tracking Systems .......................................................................... 15
Optical Tracking in Fractionated Stereotactic Radiotherapy,
Intracranial, and Head and Neck IMRT ..................................................... 16
Optically Guided Ultrasound ..................................................................... 18
In-Room CT Guidance ............................................................................... 20
Image Guidance and Organ Motion ........................................................... 27
Image Guidance for Follow-Up Imaging and Retreatments ...................... 29
Summary .................................................................................................... 31
References ...................................................................................................... 32
v
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vi Contents
3 Dose Painting and Theragnostic Imaging: Towards the Prescription,
Planning and Delivery of Biologically Targeted Dose Distributions in
External Beam Radiation Oncology ........................................................ 40
Søren M. Bentzen
Radiation Theragnostics .............................................................................. 40
From Anatomical to Biological Targeting in Radiation Therapy ............... 41
From Target Selection and Delineation to 4D Dose Prescription ............... 42
The Case for Nonuniform Theragnostic Dose Distributions....................... 43
Precision Requirements ............................................................................... 46
Targeting Hypoxia Using EBRT: Are We Ready for Dose
Painting by Numbers? .................................................................................. 47
Hypoxia as a Cause of Clinical Failure of Radiation Therapy ................ 47
Hypoxia Imaging ..................................................................................... 49
Spatiotemporal Stability of the PET Hypoxia Map ................................. 52
Dose Painting by Numbers ...................................................................... 55
Dose Delivery and Expected Change in Outcome ................................... 56
Conclusion ................................................................................................... 56
References .................................................................................................... 57
4 Molecular and Functional Imaging in Radiation Oncology .................. 62
Robert Jeraj and M. Elizabeth Meyerand
Introduction .................................................................................................. 62
Molecular and Functional Imaging Modalities ........................................... 63
Positron Emission Tomography ............................................................... 63
Single Photon Emission Tomography ..................................................... 64
Dynamic Contrast Enhanced Computer Tomography (DCE-CT) ........... 64
Dynamic Contrast Enhanced Magnetic Resonance
Imaging (DCE-MRI) ................................................................................ 64
Magnetic Resonance Spectroscopy .......................................................... 65
Optical Imaging ....................................................................................... 65
Comparison Between Different Imaging Modalities ............................... 65
Molecular and Functional Imaging Targets................................................. 66
Cellular Metabolism ................................................................................. 67
Cellular Proliferation ............................................................................... 71
Cellular Death .......................................................................................... 72
Cellular Regulation .................................................................................. 73
Tumor Microenvironment ........................................................................ 76
Future ........................................................................................................... 79
References .................................................................................................... 81
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Contents vii
5 Prognostic and Predictive Markers in Radiation Therapy: Focus
on Prostate Cancer .................................................................................... 95
Mark A. Ritter
Introduction .................................................................................................. 95
The Need for Biomarkers of Radiation Response
in Prostate Cancer ........................................................................................ 95
Optimal Biomarkers and Patient Cohort Characteristics............................. 96
Evaluation of Candidate Markers ................................................................ 97
Biological Rationale ................................................................................. 97
Biomarker Frequency ............................................................................... 100
Biomarker Assessment Methods ................................................................. 100
Immunohistochemistry ................................................................................ 101
Clinical Correlative Data in Prostate Cancer............................................... 102
Markers of Cell Cycle Control, DNA Repair and Apoptosis .................. 103
Proliferation ............................................................................................. 103
Hypoxia .................................................................................................... 104
Limitations of Existing Studies ................................................................... 104
Future Studies and Directions ...................................................................... 105
Large Prospective Clinical Trials ............................................................. 105
Biomarker-Based Adaptive Therapy ....................................................... 106
Conclusion ................................................................................................... 107
References .................................................................................................... 107
Section II. Advances in Molecular Biology and Targeted Therapies
6 Overview of Cancer Molecular Radiobiology ......................................... 115
Jann N. Sarkaria and Robert G. Bristow
Introduction .................................................................................................. 115
Interaction of Radiation with Living Cells .................................................. 115
Cellular Response to Ionizing Radiation ..................................................... 116
Cell Cycle Arrest ......................................................................................... 116
DNA Repair ................................................................................................. 118
Apoptosis ..................................................................................................... 119
Cell Survival Signaling ................................................................................ 120
Ras Signaling ........................................................................................... 120
Receptor Tyrosine Kinases ...................................................................... 121
mTOR Signaling ...................................................................................... 121
Targeting Housekeeping Proteins ................................................................ 122
HSP90 Inhibitors ...................................................................................... 123
HDAC Inhibitors ...................................................................................... 124
Proteosome Inhibitors .............................................................................. 126
Conclusion ................................................................................................... 127
References .................................................................................................... 128
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viii Contents
7 Clinical Application of EGFR Inhibitors in Head and Neck
Squamous Cell Cancer .............................................................................. 132
Igor Astsaturov, Roger B. Cohen, and Paul M. Harari
Introduction .................................................................................................. 132
EGFR Biology ............................................................................................. 133
Anti-EGFR Monoclonal Antibodies ............................................................ 135
Radiation Plus Cetuximab For Locoregionally Advanced HNSCC ........ 135
Cetuximab, Cisplatin, and Radiation in Locoregionally
Advanced HNSCC ................................................................................... 137
Cetuximab ± Chemotherapy in Recurrent
and/or Metastatic HNSCC ....................................................................... 138
Cetuximab with Chemotherapy in the First-Line Treatment
of Patients with Recurrent and/or Metastatic HNSCC ............................ 139
EGFR Tyrosine Kinase Inhibitors (TKIs) ................................................... 140
TKI Monotherapy in HNSCC .................................................................. 141
TKIs in Combination with Radiation Therapy ........................................ 141
TKIs with Dual Specificity ...................................................................... 142
Patient Selection .......................................................................................... 142
Conclusions .................................................................................................. 143
References .................................................................................................... 144
8 Advancement of Antiangiogenic and Vascular Disrupting Agents
Combined with Radiation ......................................................................... 150
Deborah Citrin and Kevin Camphausen
Introduction .................................................................................................. 150
Tumor Vasculature ...................................................................................... 150
Targeting the Tumor Vasculature ................................................................ 152
Antiangiogenic Agents ................................................................................ 152
Vascular Disrupting Agents ......................................................................... 155
Combining Antiangiogenic and Vascular Disrupting Agents
with Radiation .............................................................................................. 157
Antiangiogenic Agents and Radiation in the Laboratory ............................ 157
Angiogenesis Inhibitors and Radiation in the Clinic ............................... 159
Vascular Disrupting Agents and Radiation in the Laboratory ................. 160
Vascular Disrupting Agents with Radiation in the Clinic ....................... 161
Future Directions ......................................................................................... 162
Conclusion ................................................................................................... 163
References .................................................................................................... 164
9 Overcoming Therapeutic Resistance in Malignant Gliomas: Current
Practices and Future Directions ............................................................... 169
Arnab Chakravarti and Kamalakannan Palanichamy
Introduction .................................................................................................. 169
Signal Transduction Pathways Involved in Treatment Resistance ............. 169
Angiogenesis Pathways ............................................................................... 171
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Contents ix
Conventional Chemotherapeutic Agents in Malignant Gliomas ................. 173
Biotherapeutic Strategies ............................................................................. 178
Antiepidermal Growth Factor Receptor (EGFR) Strategies .................... 178
mTor Pathway Inhibition: CCI-779 ............................................................. 180
Antiangiogenic Strategies ............................................................................ 181
Summary ...................................................................................................... 182
References .................................................................................................... 182
Section III. Advances in Treatment Delivery and Planning
10 Advances in Intensity-Modulated Radiotherapy Delivery .................... 189
John D. Fenwick, Stephen W. Riley, and Alison J.D. Scott
Introduction .................................................................................................. 189
Background .................................................................................................. 189
Fixed-Field IMRT ........................................................................................ 190
Direct Aperture Optimisation and Jaws-Only
Linear Accelerator IMRT ........................................................................ 195
Tomotherapy ................................................................................................ 195
Axial Tomotherapy .................................................................................. 196
Helical Tomotherapy ............................................................................... 197
Future Developments ............................................................................... 202
CyberKnife ................................................................................................... 204
Summary ...................................................................................................... 205
References .................................................................................................... 206
11 Image-Based Modeling of Normal Tissue Complication Probability
for Radiation Therapy ............................................................................... 211
Joseph O. Deasy and Issam El Naqa
Introduction .................................................................................................. 211
NTCP Models: Tools or Toys? ................................................................ 212
Why Image-Based NTCP Analysis? ........................................................ 214
Tissue Dose–Response Classification ......................................................... 215
The Concepts of “Serial” and “Parallel” Tissue Dose–Response ............ 215
Local vs. Global Organ Injuries ............................................................... 217
NTCP Models .............................................................................................. 218
The Generalized Equivalent Uniform Dose Equation ............................. 219
Basic Mathematical Features of Common NTCP Functions ................... 221
Cluster Models ......................................................................................... 223
A Data-Mining/Data-Driven Approach to NTCP Modeling ................... 223
Selection of Relevant Input Variables ..................................................... 227
Selection of Model Functional Form ........................................................... 228
Selection of Model Order ............................................................................ 229
Model Order Based on Information Theory ............................................ 229
Model Order Based on Cross-validation Methods ................................... 231
Model Variable Stability .......................................................................... 231
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