Brain Tumors in Adults, An Issue of Neurologic Clinics - Patrick Wen, David Schiff.pdf - Neurochirurgia - podręczniki - MMikulicz

Neurol Clin 25 (2007) xiii–xv

Preface

Patrick Y. Wen, MD David Schiﬀ, MD

Guest Editors

Each year in the United States there are approximately 40,000 new cases

of primary brain tumors and 150,000 to 200,000 new cases of brain metas-

tases in adults. These tumors tend to occur between the 4th and 7th decades

of life, and they produce a disproportionately signiﬁcant impact in terms of

morbidity and mortality compared to other neoplasms. Since the last issue

of Neurologic Clinics that was devoted to brain tumors in adults was

published more than 10 years ago, there has been substantial progress in

understanding the molecular pathogenesis of these tumors, especially in

the critical role of tumor stem cells. In addition, there have been important

technologic advances in surgery and radiation therapy that have signiﬁ-

cantly improved the safety of these therapies, and these advances have

allowed the widespread application of techniques, such as stereotactic

radiosurgery, to treat brain metastases and some primary brain tumors that

cannot be removed surgically. Most excitingly, improved understanding of

the biology of brain tumors ﬁnally is being translated into novel therapies

using targeted molecular agents, inhibitors of angiogenesis, and immuno-

therapies. The preliminary results with these therapies are encouraging,

but there remains signiﬁcant work ahead before the promise of these treat-

ments are fulﬁlled.

This issue of Neurologic Clinics attempts to summarize the recent

progress made in the diagnosis and treatment of brain tumors in adults.

The focus of the majority of articles in this volume is on patient manage-

ment. However, the scientiﬁc and technologic underpinnings of current

doi:10.1016/j.ncl.2007.08.001

neurologic.theclinics.com

xiv

PREFACE

practice also are reviewed and referenced to allow readers to investigate par-

ticular areas in more detail as their interest or clinical needs demand.

This issue is divided into three parts. The ﬁrst part reviews, in dedicated

articles, the epidemiology of brain tumors, the molecular pathogenesis of

brain tumors and the role of stem cells, and the genetic syndromes that give

rise to brain tumors and the important insights they have contributed to our

understanding of the pathogenesis of these tumors.

The second set of articles summarizes the advances in technologies that di-

agnose and treat brain tumors. The ﬁrst article in this set discusses the impor-

tant advances inmagnetic resonance imaging that have signiﬁcantly improved

brain tumor diagnosis and potentially may allow better monitoring of thera-

pies and prediction of responses in the future. Other articles discuss the ad-

vances in neurosurgery and radiation therapy that have been responsible for

much of the progress in the treatment of brain tumors over the past decade.

The third set of articles focuses upon the management of the most com-

mon forms of brain tumors in adults. The ﬁrst article in this third set reviews

the optimal medical management of brain tumors. This important topic in-

cludes the optimal use of antiepileptic drugs and the treatment of peritu-

moral edema, venous thromboembolism, fatigue, and cognitive deﬁcits.

Succeeding articles cover the diagnosis and treatment of speciﬁc types of

brain tumors, including low grade gliomas, anaplastic oligodendrogliomas

and oligoastrocytomas, anaplastic astrocytomas and glioblastomas, primary

central nervous system lymphomas, brain metastases, and benign brain tu-

mors, such as meningiomas, schwannomas, and pituitary tumors. Novel

therapies for malignant gliomas also are discussed.

As this issue demonstrates, there has been much progress in understand-

ing the pathogenesis of brain tumors and in the development of more eﬀec-

tive therapies over the past decade. Nonetheless, for many patients who

have brain tumors, the prognosis remains poor. There remains an urgent

need to develop more eﬀective therapies for these patients.

We thank all of the authors for their outstanding contributions and the

editor, Donald Mumford, and his colleagues at WB Saunders/Elsevier for

their help with this issue. We especially thank our patients and their families.

Their courage and strength in the face of terrible adversity provide the inspi-

ration for all of us to work toward the day when we will have cures for these

devastating tumors.

Patrick Y. Wen, MD

Center for Neuro-Oncology

Dana Farber/Brigham and Women’s Cancer Center

SW430

44 Binney Street

Boston, MA 02115, USA

E-mail address: pwen@partners.org

PREFACE

David Schiﬀ, MD

Departments of Neurology, Neurological Surgery, and

Medicine (Hematology/Oncology)

University of Virginia

Box 800342

Charlottesville, VA 22908, USA

E-mail address: ds4jd@virginia.edu

Neurol Clin 25 (2007) 1089–1109

Anaplastic Oligodendroglioma

and Oligoastrocytoma

Martin J. van den Bent, MD

Neuro-Oncology Unit, Daniel den Hoed Cancer Clinic/Erasmus University Medical Center,

PO Box 5201, 3008AE Rotterdam, the Netherlands

Until approximately 15 years ago, the diagnosis of an oligodendroglioma

(OD) was merely as a pathologic entity. The only clinical relevant meaning

of this histologic diagnosis was the observation that the prognosis of OD

was in general better than that of astrocytic tumors of similar grade. This

changed with the recognition of the marked sensitivity to procarbazine,

CCNU, and vincristine (PCV) chemotherapy of these tumors, although

the best timing of chemotherapy still is unclear [1,2] . A major leap forward

was the identiﬁcation of the combined loss of the short arm of chromosome

1 (1p) and the long arm of chromosome 19 (19q) as the typical genetic le-

sions of OD, followed by the recognition these 1p/19q codeleted tumors

that, in particular, have an excellent response to chemotherapy [3–5] . This

1p/19q codeletion is an early event in the tumorigenesis of OD, mediated

by an unbalanced translocation of 19p to 1q:der(1;19)(p10;q10) [6,7] . ODs

with this combined loss of 1p/19q not only have a better response to chemo-

therapy but also have a more indolent clinical behavior and a longer-lasting

response to radiotherapy (RT). These observations have led to the current

tendency to consider 1p/19q loss low-grade and anaplastic OD (AOD) a sep-

arate biologic entity, at least within clinical trials [5,8] .

For many years, it has been standard practice to distinguish between low-

grade tumors and high-grade tumors. Because low-grade and high-grade

tumors carry a diﬀerent prognosis, this separation is a clinically relevant dis-

tinction, but also it is an artiﬁcial distinction based on subjective histologic

criteria. As a consequence, signiﬁcant interobserver variation in the grading

of OD is the rule. Combined 1p/19q loss low-grade oligodendroglial tumors

may have more in common with their anaplastic counterparts than with

low-grade astrocytoma. From this perspective, it is questionable if in

E-mail address: m.vandenbent@erasmusmc.nl

doi:10.1016/j.ncl.2007.07.013

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VAN DEN BENT

textbooks low-grade OD should be lumped together with low-grade astrocy-

toma or with their anaplastic counterparts.

The histologic distinction between pure ODs, mixed oligoastrocytoma,

and astrocytoma is subjective, which raises fundamental discussions on

the classiﬁcation of anaplastic oligoastrocytoma (AOA) with necrosis and

glioblastoma with oligodendroglial morphology. At present, it is unclear

what clinical signiﬁcance, if any, should be given to the presence of some

oligodendroglial elements in these otherwise high-grade astrocytic tumors.

Despite ongoing attempts to classify oligodendroglial tumors and grade

III glial tumors according to their genetics, the new WHO classiﬁcation con-

tinues to classify these tumors according to their histologic appearance.

Incidence, clinical presentation, localization

Oligodendroglioma and mixed oligoastrocytoma constitute 5% to 20% of

all glial tumors. They predominantly are a tumor of adulthood, with a peak

incidence between the fourth and sixth decades of life. Low-grade OD tends

to arise in slightly younger patients. Although low-grade OD, in particular,

may have a median survival time of more than 10 years, the outcome almost

invariably is fatal. Thus, these tumors never should be considered benign.

Most ODs arise in the whitematter of cerebral hemispheres, predominantly

in the frontal lobes. They can arise, however, throughout the CNS, including

infratentorial sites and the spinal cord. Similarly to other astrocytoma, OD

tend to remain localized to the CNS. Extra-CNS metastases (especially

bone metastases) are described but this is rare and occurs occasionally in pa-

tients at later stages of the disease. Leptomeningeal spread is far from rare, but

this usually does not develop until the time of recurrence.

The presenting signs and symptoms of OD are unspeciﬁc, and depend on

the localization and progression of the tumor. They may present with sei-

zures, cognitive deﬁcits, or focal deﬁcits. Low-grade ODs tend to present

with seizures, whereas patients who have high-grade tumors often present

with focal deﬁcits, increased intracranial pressure or cognitive deﬁcits early

in the course of their disease.

Pathology and genetics

Findings that the majority of ODs are characterized by combined loss of

1p/19q and that this deletion deﬁnes a speciﬁc subgroup of OD has altered

the approach toward these tumors signiﬁcantly. Table 1 summarizes the dif-

ferences between tumors with and without combined 1p1/19q loss.

Histology

Like all diﬀuse glioma, OD and AOD inﬁltrate brain tissue diﬀusely but,

in contrast to astrocytoma, areas of remarkable sharp borders with sur-

rounding brain tissue often can be found. The current WHO deﬁnition of

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