Table Of ContentC N C P
ANCER EUROLOGY IN LINICAL RACTICE
SECOND EDITION
C C O
URRENT LINICAL NCOLOGY
Maurie Markman, , S E
MD ERIES DITOR
Cancer Neurology in Clinical Practice: Neurologic Complications of Cancer and Its Treatment, edited by
DAVID SCHIFF, SANTOSH KESARI AND PATRICK Y. WEN, 2008
Integrative Oncology: Incorporating Complementary Medicine into Conventional Cancer Care, edited by
LORENZO COHENAND MAURIE MARKMAN, 2008
Prostate Cancer: Signaling Networks, Genetics, and New Treatment Strategies, edited by RICHARD G. PESTELL
AND MARJA T. NEVALAINEN, 2008
Intraperitoneal Cancer Therapy, edited by WILLIAM C. HELMAND ROBERT EDWARDS, 2007
Molecular Pathology of Gynecologic Cancer, edited by ANTONIO GIORDANO, ALESSANDRO BOVICELLI,AND ROBERT
KURMAN, 2007
Colorectal Cancer: Evidence-Based Chemotherapy Strategies, edited by LEONARD B. SALTZ, 2007
High-Grade Gliomas: Diagnosis and Treatment, edited by GENE H. BARNETT, 2006
Cancer in the Spine: Comprehensive Care, edited by ROBERT F. MCLAIN, KAI-UWE LEWANDROWSKI, MAURIE
MARKMAN, RONALD M. BUKOWSKI, ROGER MACKLIS,AND EDWARD C. BENZEL, 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. LAUGHLIN AND HILLARD
M. LAZARUS, 2003
Chronic Leukemias and Lymphomas: Biology, Pathophysiology, and Clinical Management, edited by GARY J.
SCHILLER, 2003
Colorectal Cancer: Multimodality Management, edited by LEONARD SALTZ, 2002
Breast Cancer: A Guide to Detection and Multidisciplinary Therapy, edited by MICHAEL H. TOROSIAN, 2002
Melanoma: Biologically Targeted Therapeutics, edited by ERNEST C. BORDEN, 2002
Cancer of the Lung: From Molecular Biology to Treatment Guidelines, edited by ALAN B. WEITBERG, 2001
Renal Cell Carcinoma: Molecular Biology, Immunology, and Clinical Management, edited by RONALD M.
BUKOWSKI AND ANDREW NOVICK, 2000
Current Controversies in Bone Marrow Transplantation, edited by BRIAN J. BOLWELL, 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
C N
ANCER EUROLOGY
C P
IN LINICAL RACTICE
Neurologic Complications of Cancer
and Its Treatment
Second Edition
Edited by
D S
AVID CHIFF, MD
School of Medicine, University of Virginia, Charlottesville, VA
S K
ANTOSH ESARI, MD, PhD
Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA
P Y. W
ATRICK EN, MD
Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA
Foreword
In the Foreword of the first edition of this book, Jerome Posner, one of the founding fathers of the field of
neuro-oncology, observed that in the years prior to the publication of the book interest in neuro-oncology had
increased. Since then, interest has only further increased. Both the North American and the European Society for
Neuro-Oncology are flourishing, and the number of manuscripts devoted to neuro-oncologic topics is increasing.
This development is a good thing. Many cancer patients suffer from neurological signs and symptoms, and all
too often these signs and symptoms have a tremendous impact on the quality of life for these patients. Adequate
treatmentandpalliationbeginswiththepromptrecognitionanddiagnosisofthesecomplications,andexpeditious
treatment if indicated. Because the nervous system has a limited potential for recovery, the sooner treatment is
initiated the better. Dedicated neurologists with ample knowledge of both cancer and neurology are required for
that task. This book will help them in their work.
JeromePosneraskedhimself:Whythisbook,whentherearealreadymanyneuro-oncologictextbooksavailable?
To that question we may add: Why a second edition? First of all, this one is special. Most textbooks on neuro-
oncology focus on primary brain tumors. There is a paucity of textbooks covering neurological complications
of systemic cancer and its treatment, which is exactly the scope of this book. One should realize that most
neurologists spend more time caring for patients with systemic cancer and neurological complications than for
primary brain tumor patients. At present there is no other book that provides such complete coverage of the
neurological complications of systemic cancer. And although progress may be slow, we are making progress;
thus, an update of this book is appropriate. New drugs are being utilized in the management of cancer patients;
the role of surgery in the management of spinal metastases is better defined; novel radiotherapy techniques
are being used; and novel imaging modalities are becoming more widely available. Therefore, I welcome this
secondedition,inwhichsomechaptershavebeencompletelyrewrittenandotherswereaddedtocoveradditional
topics.
The structure of this book meets the requirements of the daily practice of neuro-oncology. The differential
diagnosis of signs and symptoms in a cancer patient depends not only on those signs and symptoms, but also
on which cancer the patient is suffering from and what treatment has been given. The distinction between more
general chapters on metastases and on complications of treatment on the one hand, and tumor-specific chapters
on the other, allows the reader to approach a clinical problem from these different points of view. The separate
chaptersonseizuresandsteroidsreflectthegreatimportanceofthesetopicsinthemanagementofcancerpatients.
Seizures have a great impact on the quality of life of patients. Steroids are important in the management of many
neuro-oncologicconditions,buttheycomewithsignificantsideeffects.Thisbookwillhelpphysicianstomanage
these.
The decision to devote a separate section of the book to neurological complications of cancer treatment is
well considered: many cancer patients suffer from treatment-related neurological morbidity. And again, adequate
treatment starts with the recognition of possible treatment-related side effects. The chapter on pain focuses on an
area that is too often forgotten by neurologists. Many neurological complications of cancer are accompanied by
pain, and neurologists taking care of cancer patients need to know how to alleviate pain. Moreover, neurologists
have a special role in the management of pain in cancer patient because they are trained in localizing the
anatomical origin of signs and symptoms. Pain control is not just about anti-analgesic drugs: if a local cause of
the pain is discovered this may very well have treatment implications such as focal radiotherapy. Neurologists
should therefore participate in cancer pain management teams.
The second edition of Cancer Neurology in Clinical Practice will serve the needs of both residents and
experienced physicians. The editors deserve to be congratulated for the many experts they found willing to
contributetothisbook,comingfromvariousmedicaldisciplines.Thisalsoreflectsthemultidisciplinarycharacter
v
vi Foreword
of neuro-oncology. Because of this combination of outstanding collaborators and its structure, the first edition
of this book was already considered to be the new classic textbook on neurological complications of systemic
cancer. With this second edition, the editors have not only fulfilled the promise of the first edition, they now also
have the obligation to continue their work in future editions.
Martin J. van den Bent, MD
Neuro-Oncology Unit
Daniel den Hoed Cancer Center
Rotterdam, The Netherlands
Preface
Neuro-oncology has evolved substantially as a clinical and research discipline over the past few decades.
Initially the province of isolated devotees, it has become a well-recognized subspecialty of neurology, oncology,
and neurosurgery. The Society for Neuro-Oncology, founded in 1995, now has 900 members. Most tertiary
care hospitals have staff physicians who consider themselves neuro-oncologists. These physicians typically are
involved in evaluation and management of neurologic complications of systemic cancer and its treatment as well
as primary brain tumors. Neurologic complications occur in a substantial proportion of cancer patients, often
present complex diagnostic and management problems, and commonly have a major impact on quality of life.
As cancer patients live longer due to improvements in local and systemic therapies there will continue to be a
rise in late neurological complications such as brain metastases and neurotoxicity from these treatments.
Simultaneously, improvements in and the widespread availability of diagnostic studies such as magnetic
resonance scanning, as well as market forces, have resulted in most patients with neurologic complications of
cancer receiving treatment outside of the tertiary care setting. Many medical and radiation oncologists have
little formal training in the evaluation of neurologic symptoms. Conversely, most neurologists see relatively few
cancer patients and do not have time to keep abreast of technological and pharmacological advances in cancer
management. These circumstances contribute to the risk that some patients may not have access to a desirable
level of expertise.
The principal aim of this work is to provide clinicians from various backgrounds and levels of training with
a reference to help focus the differential diagnosis, diagnostic strategy, and treatment plan for the cancer patient
withneurologicsymptomsandfindings.Thevolumebeginswithanoverviewofthefieldofneuro-oncologyanda
reviewoftheroleofneuroimagingindiagnosisofneuro-oncologicdisease.Severalchaptersoninterpretationand
management of common neuro-oncologic symptoms follow. Subsequent sections contain chapters on the direct
and indirect neurologic complications of cancer as well as complications of therapy. The final section focuses on
the spectrum and management of neurologic disease in patients with cancer of specific organs. Although there is
necessarily some overlap between these chapters and the earlier, more general chapters, this approach allows the
readertheflexibilityofapproachingaclinicalproblemeitherfromthesymptomsorinthecontextofthepatient’s
known diagnosis of malignancy.
Ourgreathopeisthatinbroadeninganddeepeningthefamiliarityofclinicianswiththerangeandmanagement
of neuro-oncologic diagnoses we may improve the quality of care for cancer patients. The increased confidence
and competence of the treating physicians in securing a diagnosis, selecting a treatment plan, and communicating
prognosis should translate into increased peace of mind and quality of life for patients and their loved ones.
David Schiff, MD
Santosh Kesari, MD, PhD
Patrick Y. Wen, MD
vii
Acknowledgments
The warm reception that greeted the first edition of this book reflects the expertise and hard work of the
individual chapter authors; similarly, any success of the current edition owes credit to these same individuals.
The addition of Santosh Kesari as co-editor infused this project with fresh energy and helpful perspective in
addition to acumen; his leadership was critical to the book’s completion. Patrick Wen remains a valued friend
and role model of an academic physician; his wisdom, generosity, and good humor have provided me with
important sustenance over the years. Most importantly, I would like to thank my patients, Tanya Nezzer, M.D.,
and Harold Schiff for all they have taught me and for allowing me to do what I love.
David Schiff, MD
I would also like to thank all the individual chapter authors for their expert contribution. I have learned a
great deal from reviewing and editing these chapters, and will refer to them often. I am especially thankful for
my clinical and academic mentors, Patrick Wen and David Schiff, for involving me in this revised edition and
for all the support and advice over the years. I thank Ainsley Ross for providing secretarial assistance with good
cheer and competence. Finally, I dedicate this book to my parents Sriramloo Kesari, M.D. and Sarojini Kesari,
and to my family, Jyothsna, Sneha and Pranav for all their love and support.
Santosh Kesari, MD, PhD
I would like to thank the authors for their willingness to contribute to this book, despite their busy schedules;
the editors for their support and encouragement; and Ainsley Ross for administrative and secretarial assistance. I
am especially grateful for all the work that David Schiff did to make this book possible and for his friendship
over the years. I would like to dedicate this book to my parents Hsiang-Lai Wen, M.D., and Grace Wen, and to
my family, May, Katherine, and Jessica, and to Santosh Kesari for all his hard work on this book.
Patrick Y. Wen, MD
ix
Contents
Foreword......................................................................................... v
Preface........................................................................................... vii
Acknowledgments ................................................................................ ix
Contributors...................................................................................... xiii
List of Color Plates............................................................................... xv
Part I: Overview
1. The Prevalence and Impact of Neurologic Disease in Cancer..................................... 3
Evert C. A. Kaal and Charles J. Vecht
Part II: Diagnostic Studies
2. Imaging Neurologic Manifestations of Oncologic Disease........................................ 15
Arastoo Vossough, R. Gilberto Gonzalez and John W. Henson
Part III: Neurologic Symptoms
3. Seizures and Anti-Epileptic Drugs in Neuro-Oncology........................................... 33
Michael J. Glantz and Julia Batten
4. Corticosteroids in Neuro-Oncology............................................................. 47
Santosh Kesari, Nina A. Paleologos and Nicholas A. Vick
5. Headache .................................................................................... 57
Robert Cavaliere
6. Confusion and Delirium....................................................................... 65
Augusto Caraceni, Marco Bosisio, Jane M. Ingham
7. Cognitive Dysfunction, Mood Disorders, and Fatigue............................................ 91
Elana Farace and Zarui Melikyan
8. Cancer Pain.................................................................................. 113
Sebastiano Mercadante
Part IV: Direct Complications of Cancer
9. Brain Metastases.............................................................................. 131
Ahmir H. Khan and Lawrence Recht
10. Skull and Dural Metastases.................................................................... 145
Herbert B. Newton
11. Spinal Metastases............................................................................. 163
Jonathan H. Sherman, Dawit G. Aregawi, Mark E. Shaffrey, and David Schiff
12. Leptomeningeal Metastases.................................................................... 181
Ayman I. Omar and Warren P. Mason
13. Peripheral Nervous System Metastases.......................................................... 203
Nicholas Butowski
xi
xii Contents
Part V: Indirect Complications of Cancer
14. Cerebrovascular Complications of Cancer....................................................... 215
Lisa R. Rogers, Megan C. Leary, and Jeffrey L. Saver
15. Paraneoplastic Syndromes of the Nervous System ............................................... 237
Myrna R. Rosenfeld and Josep Dalmau
Part VI: Complications of Cancer Therapy
16. Neurologic Complications of Radiation Therapy................................................. 259
Daisy Chi, Anthony Béhin, and Jean-Yves Delattre
17. Neurologic Complications of Chemotherapy..................................................... 287
Jörg Dietrich and Patrick Y. Wen
18. Neurological Complications of Hematopoietic Stem Cell Transplantation.......................... 327
Eudocia Quant and Patrick Y. Wen
19. Central Nervous System Infections in Cancer Patients............................................ 353
Amy A. Pruitt
Part VII: Neurologic Complications of Specific Malignancies
20. Neurological Complications of Primary Brain Tumors ........................................... 381
Tracy T. Batchelor and Thomas N. Byrne
21. Neurologic Complications of Lung Cancer...................................................... 397
Suriya A. Jeyapalan and Anand Mahadevan
22. Neurologic Complications of Breast Cancer..................................................... 423
Willem Boogerd
23. Neurologic Complications of Female Reproductive Tract Cancer.................................. 449
Lauren E. Abrey
24. Neurologic Complications of Genitourinary Cancer.............................................. 459
David E Traul and David Schiff
25. Neurologic Complications of Gastrointestinal Cancer ............................................ 481
Jeffrey Raizer and Jeffrey Cilley
26. Neurologic Complications of Sarcoma.......................................................... 495
Santosh Kesari and Lara J. Kunschner
27. Neurologic Complications of Head and Neck Cancer ............................................ 507
Katherine B. Peters and David Schiff
28. Neurologic Complications of Melanoma........................................................ 523
Denise M. Damek
29. Neurologic Complications of Leukemia......................................................... 555
Marc C. Chamberlain
30. Neurological Complications of Lymphomas..................................................... 567
Brian P. O’Neill
31. Neurologic Complications of Plasma Cell Dyscrasias............................................ 591
John J. Kelly
32. Neurologic Complications of Pediatric Systemic Cancer.......................................... 607
Nicole J. Ullrich and Scott L. Pomeroy
Index............................................................................................ 621
