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Preview Radiation Oncology Advances

Radiation Oncology Advances MMeehhttaa__FFMM..iinndddd ii 88//2288//22000077 66::2244::2277 PPMM 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) MMeehhttaa__FFMM..iinndddd iiii 88//2288//22000077 66::2244::2277 PPMM 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 permission of the publisher (Springer Science + Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. Printed on acid-free paper. 9 8 7 6 5 4 3 2 1 springer.com MMeehhttaa__FFMM..iinndddd iivv 88//2288//22000077 66::2244::2288 PPMM 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 MMeehhttaa__FFMM..iinndddd vv 88//2288//22000077 66::2244::2288 PPMM 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 MMeehhttaa__FFMM..iinndddd vvii 88//2288//22000077 66::2244::2288 PPMM 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 MMeehhttaa__FFMM..iinndddd vviiii 88//2288//22000077 66::2244::2288 PPMM 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 MMeehhttaa__FFMM..iinndddd vviiiiii 88//2288//22000077 66::2244::2288 PPMM 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 MMeehhttaa__FFMM..iinndddd iixx 88//2288//22000077 66::2244::2288 PPMM

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