Brain, Vol. 122, No. 10, 2002-2005,
October 1999
© 1999 Oxford University Press
Book Reviews |
THE GLIOMAS.
.
Velindre NHS Trust, Cardiff, UK
In the Christmas issue of the BMJ (1998; p. 199), Christopher Martyn (Associate Editor of the BMJ), called the last 10 years of the 20th century `the decade of the brain'. Based on this background The Gliomas, edited by Mitchel S. Berger and Charles B. Wilson, is a welcome new textbook summarizing our current knowledge in the management of gliomas. The editors have been able to win contributors from both sides of the Atlantic to lead this field of oncology into the 21st century.
This new textbook focuses solely on the management of gliomas. In comparison with previous new textbooks within this area they have chosen to follow a different structure when approaching the subject. The book is divided into nine sections which are arranged in chronological order. Being used to a structure where each disease is reviewed separately after a broad general introduction, it took me some time to appreciate the benefits of this approach. As more space is dedicated to each treatment step it provides a more comprehensive review of the chosen topic, compared with a general introduction and more detailed information incorporated into each chapter of specific brain tumour management (e.g. details on surgical principles or experimental treatment approaches). I appreciated each chapter concluding with a very brief summary providing the clinical relevant information.
The book is structured in nine sections dealing with epidemiology, clinical genetics and basic science followed by experimental therapeutics, pathology, diagnostic imaging, preoperative assessment and management, resection strategies and treatment modalities, and concludes with sections on special topics and treatment induced complications.
The first section starts with `Epidemiology' followed by `Familial Gliomas'. The first two chapters themselves prove one point about oncology—the difficulty of obtaining exact epidemiological data. Both authors quote, independently, different papers regarding the incidence of gliomas in the USA, with nearly 20% difference in actual numbers of newly diagnosed patients with primary brain tumours. These chapters are followed by an excellent review of the genetic background of primary gliomas (`Neurofibromatosis and Other Phakomatoses'). This chapter is excellently written and concise in its presentation, it gives a well-referenced review, which could easily be recommended as basic reading for all clinicians involved in this area. The next two chapters are dedicated to the cytogenetic and molecular genetic background of this disease. They provide a good introduction as well as an explanation of the terminology and the techniques of obtaining adequate karyotypes of solid tumours. It might have been worthwhile to incorporate the fluorescence in situ hybridization technique (FISH) and its potential for obtaining genetic information on predefined genetic abnormalities in larger series. The chapter entitled `Cytogenetics' is an excellent summary of the cytogenetic findings in gliomas as well as the addition of a glossary defining cytogenetic terms. The chapter entitled `Tumour Invasiveness' includes a short but important paragraph on patterns of failure supplemented by a clinically very interesting table of the distance of recurrent disease from the resection margins. Unfortunately the figures provided for immunohistochemistry analysis are in black and white, and might have benefited from colour prints to expand the message of the author. The following chapter headed `Angiogenesis' is again highly recommended. Angiogenetic treatment has become a major focus of new experimental treatment approaches in a variety of diseases including primary brain tumours. A conceptual model of the angiogenesis cascade is provided supplemented by an excellent and easy to understand illustration. It finishes with a brief background of the use of angiostatic therapy mentioning the early works of Folkman and colleagues. Within this context thalidomide has been resurrected as a potential clinically active anti-angiogenic agent and is currently undergoing phase 2 trials, and should be mentioned within this context. The last two chapters are dedicated to peritumoral oedema and the blood–brain barrier. The first again benefits from a very stringent and logical approach starting from a definition, via the biochemical background basic mechanism, peritumoral oedema formation and resolution, blood flow and metabolic parameters, and concluding with clinical treatment guidelines. The last chapter of the first section is dedicated to the blood–brain barrier providing the physiological background. Noteworthy is the role of response of the blood–brain barrier to neoplasia outlining the difficulties in diagnostic imaging in differentiating between tumour infiltrated cerebral tissue and tumour associated oedema.
Section II starts with the chapters `Animal Models of Tumors of the Nervous System', and `Human Glioma Cultures and in vitro Analysis of Therapeutic Response'. Both chapters provide an excellent introduction for the later experimental treatment approaches of gene therapy and antisense oligonucleotide targets. The next chapter is entitled `DNA Repair Mediated Resistance to Alkylating Agents'. This is an extremely worthwhile chapter which benefits from clear summaries provided after each subdivision. It enables the reader to retain easily the most relevant clinical information. Despite the fact that `gene therapy' and `antisense oligonucleotide targets' are approaches still in their infancy, these two chapters provide an excellent review and explanation of the theoretical background, and provide some preliminary clinical results. The latter excellently bridges the gap between laboratory and clinic.
Section III (on pathology) starts with a review of the histopathological classification of gliomas. This chapter uses a structure as provided by the WHO classification of gliomas and relates it to alternative classification systems such as the St Anne–Mayo system. Furthermore, the authors clearly stress the difficulty of grading primary CNS gliomas. This pathological difficulty is further enhanced by the clinical uncertainty following a stereotactic biopsy as far as grading is concerned due to the risk of sampling errors. The authors explain the current use of Ki-67 (an immunochemical marker that defines a family of nuclear proteins necessary for the maintenance of the proliferative state) which appears to be related to the histopathological grade of astrocytomas. Nevertheless, these data are still conflicting and have therefore correctly not been incorporated into any classification system. The next chapter (`Immunologic Cell Markers') would have benefited from some colour photographs in order to enhance the author's message. The figures act as an excellent reference for typical immunohistological and pathological features of various variants of astrocytomas and ependymomas. The chapter entitled `Anatomy and Growth Patterns of Diffuse Gliomas' again has high clinical relevance. It outlines the differences of growth patterns of low grade and of high-grade gliomas. It provides an extremely valuable background for clinicians with advice on resection and clinical target volumes in this patient group. The last part is dedicated to tumour heterogeneity and clonal anatomy. It highlights the huge varieties of different clonal populations within a single tumour. This is further supported in the following chapter headed `Tumor Markers in Gliomas' which shows the high variability of genetic aberrations in primary gliomas. It provides an excellent statistical background to this area, which is not only comprehensive, but also short and easy to read.
The `Diagnostic Imaging' section starts with `computed tomography', followed by `magnetic resonance imaging'. CT scanning is the most available diagnostic tool at present but MRI is considered the gold standard in the examination for primary cerebral malignancies. Following a general introduction there follows a detailed description of the technique and individual diagnostic appearances of each histopathological entity. Both chapters cover the whole range of primary cerebral and spinal gliomas and provide an excellent library for CT and MRI appearances. Nevertheless, not every clinician would agree with the recommendation that patients with primary high-grade gliomas should routinely be scanned every 3–4 months following primary treatment. The following chapters on nuclear medicine summarize the current role of PET and single photon emission computed tomography (SPECT). PET using radiotracers other than [18F]fluorodeoxyglucose has a potential role in contributing to our understanding of the biological processes within this tumour group. Nevertheless, the author points out the limitations of these techniques due in part to the resolution achievable with PET.
Section V is one of the shortest sections of the book and includes preoperative assessment, as well as the role of functional imaging in the surgical management of brain neoplasms. The first chapter provides the clinical features of patients presenting with gliomas as well as an excellent summary of the evaluation of preoperative management. The summary of anticonvulsant therapy and corticosteroids is excellent. Furthermore, the myth that dexamethasone has to be given four times a day in the treatment of peritumoral oedema (still frequently used) is tackled. The complementary use of H2 blockers with steroids is commented on and the fact that the relationship between high dose steroids and gastrointestinal bleeding is much less firmly established than is often assumed.
Section VI is the largest section of the book dedicated to resection strategies. Although the overall book is aimed at postgraduate clinicians this section provides a description potentially justified in a neurosurgical textbook. There is an excellent concise review of the positioning during glioma planning, followed by surgical approaches to glioma-delineating surgical considerations of various approaches depending upon localization of the tumour. Hidden under the chapter headed `Localisation of Tumor and Margins' is the assessment of intraoperative smear preparations as well as some typical histopathological smear preparations. Particularly excellent is `Image Guided Surgical Technology for Glial Tumor Resection' which outlines the use of real time diagnostic images during the surgical procedure. The only minor limitation is that the recent introduction of open MRI's within theatre suites and their potential benefits or limitations are dealt with extremely briefly. `Techniques for Functional Brain Mapping during Glioma Surgery' provides an excellent review of medical treatment of seizures. Within this chapter current experimental treatment modalities are included (photodynamic therapy and hyperthermia) which are repeated in a later part of the book. The only weak chapter that I found within this section was the chapter on computer assisted stereotactic laser resection, which appears to reflect a precise description of the current practice of a single institution rather than a general review of this topic.
Section VII is dedicated to treatment modalities including radiotherapy, chemotherapy, immunotherapy and phototherapy. The first chapter deals with the basic principles of radiobiology and radiotherapy, and provides a good and easy to read introduction into the physical background. I was especially impressed by the way the authors explained the linear quadratic model. Unfortunately the only radiotherapy figure of a CT-based treatment planning appears to be slightly misleading. The CT outline of the gross tumour volume has been transferred on to the patient on a beams-eye-view simulator film and it appears that the composite volume does not include the outlined CT slices completely. It may be worthwhile reviewing this figure prior to the next edition. In the following chapter a substantial section is dedicated to the rationale and indication for radiosurgery (single fraction high dose radiotherapy). Due to the wide availability of 3D planning computer systems, conformally guided radiotherapy approaches become more and more part of the everyday practice. Nearly the whole chapter is dedicated to radiosurgery. Although it provides a good overview to this new treatment technique it appears that the use of conventional fractionated stereotactically guided conformal radiotherapy is under-referenced, especially with respect to the paediatric patient group. Compared with its clinical relevance the radiotherapy section appears relatively small compared with surgery or chemotherapy.
Six chapters on chemotherapy follow the radiotherapy section, starting with the pharmacology of currently used drugs which have shown activity in primary gliomas. Intra-arterial chemotherapy and high dose chemotherapy followed by autologous bone marrow rescue are treatment options currently perceived as experimental. The chapter on high dose chemotherapy is extremely well written and is surprisingly honest and modest with its conclusions. The chapters on chemotherapy cover techniques of intra-tumoral chemotherapy administration as well as the potential use of disruption of the blood–brain barrier. With the exception of one single cell culture experiment, a drug developed mainly by the Cancer Research Campaign is not referenced at all. Temozolomide (a dacarbazine derivative with high capability of CNS penetration) has shown some promising activity in Phase II and Phase III Trials. It has currently been licensed for recurrent glioblastoma multiforme. Another promising new drug could have been mentioned: irinotecan or CPT-11 (a topoisomerase I inhibitor). A phase II study has recently been completed in this patient group showing a response rate of 20%. Furthermore, data on the adjuvant use of chemotherapy are missing within this context.
The next part of the book is dedicated to immunotherapy, which has raised high hopes, especially in the treatment of primary brain tumours. Unfortunately it is currently not able to deliver the promised benefits and it remains experimental with major problems surrounding the technique itself. The chapters do provide an excellent review of the biological background and in vitro studies in this interesting area. Many of these studies are still in the preclinical stage but this part of the book provides a good basis for new treatment approaches which might become clinically more important in the next millennium.
Section VIII is dedicated to special topics. Six chapters are covered by 86 pages including tumour dissemination and management of recurrent gliomas and the extent of resection. It comes at the very end of the book, but from the clinicians' point of view it contains extremely relevant information, which is vital in everyday decision making. This is especially true of the chapter on extent of resection, which summarizes superbly the current evidence about resection strategies, and provides evidence based guidelines for the management of primary brain tumours. The next chapter is dedicated to the paediatric age group of CNS malignancies. There is an excellent summary of our knowledge of current management strategies. It provides a well-balanced view on the use and limitations of chemotherapy in this patient group and appreciates both the benefits and the limitations of radiotherapy. I personally would have appreciated within this context a review of stereotactically guided conformal treatment approaches with respect to improved tumour control as well as the possibility of reducing late toxicity. The book concludes with the difficult situation of gliomas arising in pregnant women. This is a very rare and extremely challenging situation for any medical professional and its incorporation as a separate chapter must be highly welcomed.
The last section of the book is dedicated to the long-term effects of patients treated for brain tumours (`Treatment-Induced Complications'). It includes radiation and chemotherapy related long-term side-effects. It comprises excellent chapters on treatment related cognitive and endocrine deficits which are the two most common clinical long-term toxicities seen in patients with primary brain tumours, especially in the paediatric group, and the chapters are again highly recommended to read.
Despite all these benefits the book has some weaknesses as well. Taking the book as a whole, the management of low-grade gliomas as well as ependymomas does not receive the same meticulous attention compared with high-grade gliomas. Given that in patients with high-grade gliomas the treatment approach is palliative, it is surprising that a chapter on quality of life is missing. Only the chapter `Clinical Presentation, Evaluation and Preoperative Preparation of the Patient' has dedicated a very small paragraph to this topic, giving some useful telephone numbers of patient oriented groups which provide emotional and psychological support, such as the American Brain Tumor Association. It would have been useful to have a chapter on the psychological problems (e.g. depression), as well as to have a review of the bereavement policies in this patient group. Given that we are currently living in a century where information is easily available for both clinicians and patients it is surprising that this book does not contain a chapter on the possible benefits or the litigator's use of the Internet. More and more patients arrive on their first appointment with information derived from the Internet. No reference is made to the general standard care guidelines as provided by the National Cancer Institute (PDQ® for patients, health professionals and basic researchers) accessible through the Internet (www.cancernet.nci.nih.gov/pdq.htm). Given the limited treatment options and the short remaining lifetime for the majority of patients with high-grade gliomas, many patients as well as their families would consider experimental treatment approaches such as alternative or complementary treatments. It would have been helpful to have a critical review of treatment modalities such as `shark's cartilage' or `anti-neoplaston treatment', which are currently promoted through the Internet. Despite these currently not being perceived as treatment options available through the standard medical system, there is quite considerable patient pressure to either comment on or to consider these treatment options.
In summary, The Gliomas provides a fundamental new approach towards the presentation of a textbook in an extremely challenging group of patients. It provides an excellent review of our current knowledge both in the standard treatment modalities as well as within experimental treatment approaches. Furthermore, it provides a review of our current clinical evidence and provides essential treatment guidelines. It benefits from an overall clear structure with each chapter finishing with a concise summary and a conclusion. It is very well referenced although the number of references following the beginning of the 90s is small. Despite minor shortcomings this new textbook is valuable to all clinicians with a special interest in neuro-oncology.
Notes
Edited by Mitchel S. Berger and Charles B. Wilson. 1999. Pp. 796. Philadelphia: WB Saunders Company. Price £156. ISBN 0-7216-48258.
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