H IGH -G RADE G LIOMAS

H^IGH-G^RADE G^LIOMAS

C^URRENT C^LINICAL O^NCOLOGY

Maurie Markman, ^MD, S^ERIES E^DITOR

Colorectal Cancer: Evidence-Based Chemotherapy Strategies, edited by L^EONARD B. S^ALTZ, 2007

High-Grade Gliomas: Diagnosis and Treatment, edited by G^ENE H. B^ARNETT, 2006 Cancer in the Spine: Comprehensive Care, edited by R^OBERT F. M^CL^AIN, K^AI-U^WE LEWANDROWSKI,

M^AURIE M^ARKMAN, R^ONALD M. B^UKOWSKI, R^OGER M^ACKLIS, ^AND E^DWARD C. B^ENZEL, 2006 Squamous Cell Head and Neck Cancer, edited by DAVID J. ADELSTEIN, 2005

Hepatocellular Cancer: Diagnosis and Treatment, edited by BRIAN I. CARR, 2005 Biology and Management of Multiple Myeloma, edited by JAMES R. BERENSON, 2004 Cancer Immunotherapy at the Crossroads: How Tumors Evade Immunity and What Can

Be Done, edited by JAMES H. FINKEAND RONALD M. BUKOWSKI, 2004

Treatment of Acute Leukemias: New Directions for Clinical Research, edited by CHING- HON PUI, 2003

Allogeneic Stem Cell Transplantation: Clinical Research and Practice, edited by MARY J.

LAUGHLINAND HILLARD M. LAZARUN, 2003

Chronic Leukemias and Lymphomas: Biology, Pathophysiology, and Clinical Manage- ment, edited by G^ARY J. S^CHILLER, 2003

Colorectal Cancer: Multimodality Management, edited by L^EONARD S^ALTZ, 2002

Breast Cancer: A Guide to Detection and Multidisciplinary Therapy, edited by M^ICHAEL H. T^OROSIAN, 2002

Melanoma: Biologically Targeted Therapeutics, edited by E^RNEST C. B^ORDEN, 2002 Cancer of the Lung: From Molecular Biology to Treatment Guidelines, edited by A^LAN B.

W^EITBERG, 2001

Renal Cell Carcinoma: Molecular Biology, Immunology, and Clinical Management, edited by R^ONALD M. B^UKOWSKIAND A^NDREW N^OVICK, 2000

Current Controversies in Bone Marrow Transplantation, edited by B^RIAN J. B^OLWELL, 2000

Regional Chemotherapy: Clinical Research and Practice, edited by MAURIE MARKMAN, 2000

Intraoperative Irradiation: Techniques and Results, edited by L. L. GUNDERSON, C. G.

WILLETT, L. B. HARRISON, AND F. A. CALVO, 1999

H

-G

G

Diagnosis and Treatment

Edited by

G^ENE H. B^ARNETT, ^MD

Brain Tumor Institute, Department of Neurological Surgery Cleveland Clinic Foundation, Cleveland, OH

© 2007 Humana Press Inc.

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Library of Congress Cataloging-in-Publication Data

High-grade gliomas : diagnosis and treatment / edited by Gene H. Barnett.

p. ; cm. — (Current clinical oncology) Includes bibliographical references and index.

ISBN 1-58829-511-7 (alk. paper)

1. Gliomas. I. Barnett, Gene H. II. Series: Current clinical oncology (Totowa, N.J.)

[DNLM: 1. Glioma—therapy. 2. Glioma—diagnosis. 3. Therapies, Investigational. QZ 380 H638 2007]

RC280.B7H54 2007

616.99’481—dc22 2006024846

Preface

This is truly an exciting time in the field of neuro-oncology, particularly in the area of high- grade gliomas. The management of patients with high-grade gliomas has historically been one of the most challenging and disheartening fields in medicine, where failure is the rule and longevity is the exception. The jaded often state that despite purported advances in surgical and radiotherapeutic techniques and a myriad of clinical trials of medical therapies, the sur- vival statistics for glioblastoma have not changed in the last three decades. The nihilism associated with these tumors is such that some practitioners still advise against treatment or even biopsy, recommending palliative care with the diagnosis based only on history and an MRI scan. If the current state-of-the-art in the diagnosis and management of high-grade gliomas was truly so bleak, there would be no reason to compile and publish a monograph on the subject. The fact is that we have recently entered an era where real progress is being made in our understanding and treatment of high-grade gliomas that is directly benefiting some patients.

We are slowly but surely chipping away at this problem. One approach has exploited correlations between particular molecular markers and therapeutic response. The first such

“breakthrough” in high-grade glioma was the observation that loss of chromosomes 1p and 19q uniformly predict chemosensitivity in anaplastic oligodendrogliomas (1). Subsequent work has refined this relationship using additional markers to forecast longevity in patients with these tumors (2). More recently we have seen similar observations in glioblastoma where methylation of the methyl-guanine-methyl transferase (MGMT) gene promoter is associated with better response to temozolomide (TMZ) (3). Similarly, co-expression of the vIII muta- tion of epidermal growth factor receptor (EGFR) and the PTEN tumor suppressor gene pre- dicts response to EGFR inhibitors (4).

Another approach has been large multi-center clinical trials using conventional and uncon- ventional agents. Stupp et al have shown that radiotherapy with concurrent low dose temozo- lomide and subsequent high dose TMZ leads to longer survival than radiotherapy alone for newly diagnosed glioblastoma (5). Presently a large multicenter trial is comparing the use of an immuotoxin (IL13-PE39QQR) delivered by convection enhanced delivery against carmustine-impregnated biodegradable wafers in patients with operable glioblastoma at first recurrence. Yet another avenue of investigation is to use preclinical animal testing to improve response by refining traditional therapeutic delivery schedules, combining agents and inves- tigating various modes of delivery and concentrations of agents achieved in tumor, brain and CSF.

So in this volume we present the spectrum of issues pertaining to high-grade gliomas from the basics of clinical characteristics and management to the state-of-the-art in diagnosis and therapeutics, as well as current areas of investigation that may lead to the treatments of tomorrow. We explore whether molecular diagnosis complements histology or is likely to supercede it, the most current information in imaging techniques to assist us in diagnosing and monitoring treatment, and the latest in “conventional” treatments such as surgery, radiation, and cytotoxic chemotherapy.

v

After decades of uniformly poor outcomes, we have entered an era where meaningful advances are being made in our understanding of the biology of high-grade gliomas that is leading to better, more rational, patient-specific treatments. I hope you find this book infor- mative and useful.

Gene Barnett, MD, FACS

REFERENCES

1. Cairncross JG, Ueki K, Zlatescu MC, et al. Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 1998;90(19):1473–1479.

2. Ino Y, Betensky RA, Zlatescu MC, et al. Molecular subtypes of anaplastic oligodendroglioma: implications for patient management at diagnosis. Clin Cancer Res 2001;7(4):839–845.

3. Hegi M E, Diserens A-C, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblas- toma. N Engl J Med 2005;352:997–1003.

4. Mellinghoff IK, Wang MY, Vivanco I, et al. Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N Engl J Med 2005;353:2012–2024.

5. Stupp R., Mason W P, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352:987–996.

vi Preface

Contents

Preface ...v Contributors ... ix Companion CD ROM ... xiii PART I: CLASSIFICATIONOF HIGH-GRADE GLIOMA

1. Histologic Classification of High-Grade Gliomas ...3 Richard A. Prayson

2. Molecular Classifications ... 37 Gregory N. Fuller

PART II: CLINICAL CHARACTERISTICS

3. Pediatric High-Grade Glioma ... 45 Bruce H. Cohen

4. Adult High-Grade Glioma ... 59 Nicholas Butowski and Susan Chang

PART III: DIAGNOSTIC TOOLSFOR HIGH-GRADE GLIOMA

5. Computerized Tomography ... 73 Manzoor Ahmed and Thomas J. Masaryk

6. Magnetic Resonance Imaging ... 105 Paul M. Ruggieri

7. Magnetic Resonance Spectroscopy ... 133 G. Evren Keles, Soonmee Cha, and Mitchell S. Berger

8. Imaging Tumor Biology: Physiological and Molecular Insights ... 141 Timothy P. L. Roberts and Andrea Kassner

9. Nuclear Imaging of Gliomas ... 161 Alexander M. Spence, David A. Mankoff, Mark Muzi, and Kristin Swanson

10. Magnetoencephalography ... 187 Michael P. Steinmetz, Jürgen Lüders, and Edward C. Benzel

PART IV: MANAGEMENT

11. General Considerations ... 199 Glen H. J. Stevens

12. Surgery for High-Grade Gliomas ... 213 Gene H. Barnett

13. Radiation Therapy ... 231 Hiral K. Shah and Minesh P. Mehta

14. Brachytherapy ... 245 Marcus L. Ware, P. K. Sneed, and Michael W. McDermott

vii

viii Contents 15. Radiosurgery ... 257

John H. Suh and Gene H. Barnett

16. Chemotherapy ... 267 Manmeet Singh Ahluwalia and David M. Peereboom

17. Nursing Considerations ... 283 Kathleen Lupica and Gail Ditz

PART V: CONTEMPORARY INVESTIGATIONAL TREATMENTS

18. Convection-Enhanced Delivery ... 303 Andrew A. Kanner

19. Immunotoxins for Glioma Therapy ... 315 Syed Rafat Husain and Raj K. Puri

20. Small Molecule Agents ... 337 Michael Vogelbaum and Tina Thomas

21. Cytokine Immuno-Gene Therapy for Malignant Brain Tumors ... 357 Roberta P. Glick, Terry Lichtor, Henry Lin, and Edward P. Cohen

22. Monoclonal Antibodies ... 373 Abraham Boskovitz, David A. Reardon, Carol J. Wikstrand,

Michael R. Zalutsky, and Darell D. Bigner

23. Clinical Trials of Oncolytic Viruses for Gliomas ... 391 E. Antonio Chiocca and M. L. Lamfers

24. Biological Modifiers ... 405 Alexander Mason, Steven Toms, and Aleck Hercbergs

25. Gene Therapy for High-Grade Glioma ... 419 Maciej S. Lesniak and Alessandro Olivi

26. Boron Neutron Capture Therapy of Brain Tumors:

Current Status and Future Prospects ... 431 Rolf F. Barth, Jeffrey A. Coderre, M. Graça H. Vicente,

Thomas E. Blue, and Shin-Ichi Miyatake

27. Photodynamic Therapy ... 461 Bhadrakant Kavar and Andrew H. Kaye

Index ... 485

Contributors

ix

MANMEET SINGH AHLUWALIA, MD • Fairview Hospital, Cleveland, OH

MANZOOR AHMED, MD • Department of Diagnostic Radiology, The Cleveland Clinic Foundation, Cleveland, OH

GENE H. BARNETT, MD • The Brain Tumor Institute, Department of Neurological Surgery, The Cleveland Clinic Foundation, Cleveland, OH

ROLF F. BARTH, MD • Department of Pathology, The Ohio State University, Columbus, OH EDWARD C. BENZEL, MD • Cleveland Clinic Spine Institute, Department of Neurological

Surgery, The Cleveland Clinic Foundation, Cleveland, OH

MITCHELL S. BERGER, MD • Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA

DARELL D. BIGNER, MD, PhD • Department of Pathology, Neuro-Oncology Program, Duke University Medical Center, Durham, NC

THOMAS E. BLUE, PhD • Department of Nuclear Engineering Program, The Ohio State University, Columbus, Ohio

ABRAHAM BOSKOVITZ, MD • Neuro-Oncology Program, Department of Pathology, Duke University Medical Center, Durham, NC

NICHOLAS BUTOWSKI, MD • Neuro-Oncology Service, Department of Neurological Surgery, UCSF School of Medicine, San Francisco, CA

SOONMEE CHA, MD • Department of Radiology, University of California, San Francisco, San Francisco, CA

SUSAN CHANG, MD • Neuro-Oncology Service, Department of Neurological Surgery, UCSF School of Medicine, San Francisco, CA

E. ANTONIO CHIOCCA, MD, PhD • Dardinger Center for Neuro-Oncology, Department of Neurosurgery, The Ohio State University Medical Center, James Cancer Hospital and Solove Research Center, Columbus, OH

JEFFREY A. CODERRE, PhD • Department of Nuclear Engineering, Massachusetts Institute of Technology, Cambridge, MA

BRUCE H. COHEN, MD • Department of Neurology, The Cleveland Clinic Foundation, Cleveland, OH

EDWARD P. COHEN, MD • Department of Neurological Surgery, Rush Medical College, Cook County Hospital and Hektoen Institute for Medical Research; and Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL

GAIL DITZ, RN • The Brain Tumor Institute, The Cleveland Clinic Foundation, Cleveland, OH GREGORY N. FULLER, MD, PhD • Department of Pathology, MD Anderson Cancer Center,

Houston, TX

ROBERTA P. GLICK, MD • Department of Neurological Surgery, Rush Medical College, Cook County Hospital and Hektoen Institute for Medical Research; and Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL ALECK HERCBERGS, MD • Department of Radiation Oncology, The Cleveland Clinic

Foundation, Cleveland, OH

x Contributors SYED RAFAT HUSAIN, PhD • Tumor Vaccines and Biotechnology Branch, Division

of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, FDA, Bethesda, MD

ANDREW A. KANNER, MD • Department of Neurosurgery, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

ANDREA KASSNER, PhD • Department of Medical Imaging, University of Toronto, University Health Network, Toronto, Ontario

BHADRAKANT KAVAR, MD, ChB, FCS, FRACS • Departments of Neurosurgery and Surgery, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia ANDREW H. KAYE, MB, BS, MD, FRACS • Departments of Neurosurgery and Surgery,

University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia G. EVREN KELES, MD • Department of Neurological Surgery, University of California,

San Francisco, San Francisco, CA

M. L. LAMFERS, PhD • Division of Gene Therapy, Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands

MACIEJ S. LESNIAK, MD • Division of Neurological Surgery, The University of Chicago Pritzker School of Medicine, Chicago, IL

TERRY LICHTOR, MD, PhD • Department of Neurological Surgery, Rush Medical College, Cook County Hospital and Hektoen Institute for Medical Research; and Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL HENRY LIN, MD • Department of Neurological Surgery, Rush Medical College, Cook County

Hospital and Hektoen Institute for Medical Research; and Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL

JÜRGEN LÜDERS, MD • Neurosurgeon, Grand Rapids, MI

KATHLEEN LUPICA, MSN, CNP • The Brain Tumor Institute, The Cleveland Clinic Foundation, Cleveland, OH

DAVID A. MANKOFF, MD, PhD • Department of Radiology, University of Washington School of Medicine, Seattle, WA

THOMAS J. MASARYK, MD • Department of Diagnostic Radiology, The Cleveland Clinic Foundation, Cleveland, OH

ALEXANDER MASON, MD • Department of Neurosurgery, The Cleveland Clinic Foundation, Cleveland, OH

MICHAEL W. MCDERMOTT, MD • Departments of Neurosurgery and Radiation Oncology, University of California, San Francisco, CA

MINESH P. MEHTA, MD • Department of Human Oncology, University of Wisconsin, Madison, WI

SHIN-ICHI MIYATAKE, MD, PhD • Department of Neurosurgery, Osaka Medical College, Takatsuki, Osaka Prefecture, Japan

MARK MUZI, MS • Department of Radiology, University of Washington School of Medicine, Seattle, WA

ALESSANDRO OLIVI, MD • Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD

DAVID M. PEEREBOOM, MD • The Brain Tumor Institute, Department of Medical Oncology, The Cleveland Clinic Foundation, Cleveland, OH

RICHARD A. PRAYSON, MD • Department of Anatomic Pathology, The Cleveland Clinic Foundation, Cleveland, OH

RAJ K. PURI, MD, PhD • Tumor Vaccines and Biotechnology Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, FDA, Bethesda, MD

DAVID A. REARDON, MD • Neuro-Oncology Program, Department of Surgery, Duke University Medical Center, Durham, NC

TIMOTHY P. L. ROBERTS, PhD • Department of Medical Imaging, University of Toronto, University Health Network; and Toronto Western Research Institute, Toronto, Ontario PAUL M. RUGGIERI, MD • Department of Diagnostic Radiology, The Cleveland Clinic

Foundation, Cleveland, OH

HIRAL K. SHAH, MD • Department of Human Oncology, University of Wisconsin, Madison, WI P. K. SNEED, MD • Department of Radiation Oncology, University of California,

San Francisco, CA

ALEXANDER M. SPENCE, MD • Department of Neurology, University of Washington School of Medicine, Seattle, WA

MICHAEL P. STEINMETZ, MD • Department of Neurological Surgery, The Cleveland Clinic Foundation, Cleveland, OH

GLEN H. J. STEVENS, DO, PhD • The Brain Tumor Institute, Department of Neurology, The Cleveland Clinic Foundation, Cleveland, OH

JOHN H. SUH, MD • The Brain Tumor Institute, Department of Radiation Oncology, The Cleveland Clinic Foundation, Cleveland, OH

KRISTIN SWANSON, PhD • Department of Neuropathology, University of Washington School of Medicine, Seattle, WA

TINA THOMAS, MD • The Brain Tumor Institute, The Cleveland Clinic Foundation, Cleveland, OH

STEVEN TOMS, MD, MPH • The Brain Tumor Institute, Department of Neurological Surgery, The Cleveland Clinic Foundation, Cleveland, OH

M. GRAÇA H. VICENTE, PhD • Department of Chemistry, Louisiana State University, Baton Rouge, LA

MICHAEL VOGELBAUM, MD, PhD • The Brain Tumor Institute, Department of Neurological Surgery, The Cleveland Clinic Foundation, Cleveland, OH

MARCUS L. WARE, MD, PhD • Departments of Neurosurgery and Radiation Oncology, University of California, San Francisco, CA

CAROL J. WIKSTRAND, PhD • Neuro-Oncology Program, Department of Pathology, Duke University Medical Center, Durham, NC

MICHAEL R. ZALUTSKY, PhD • Department of Radiology, Neuro-Oncology Program, Duke University Medical Center, Durham, NC

Contributors xi

Companion CD ROM

All illustrations, both black and white and color, are contained on the accomapnying CD ROM.

xiii