In spite of great advance made by ENT and maxillofacial surgeons as well as radiotherapists to improve therapy of cancer of the oral cavity and oropharynx, it has not been possible in the past 4 decades to raise the chances of patient survival above 40%-45%. However, recent studies with different combination therapies indicate that better results can be expected in the future. In this volume, the current status and results of therapeutic studies are presented by distinguished clinicians in the three disciplines. The book provides up-to-date information and encourages interdisciplinary cooperation.

Blood stem cell transplantation has become an established therapeutic option in the treatment of malignant diseases. At the same time molecular therapeutic approaches (i.e. gene therapy) are promising alternatives to the classical treatment of cancer. The proceedings give an overview of the biology of hematopoietic progenitor cells, peripheral stem cell transplantation in patients with hematological malignancies, recent developments in molecular diagnosis and gene therapeutic concepts, and show that successful future developments require cooperative research connecting basic science with clinical application.

Transplantation of syngeneic (donor is a monozygous twin) or allogeneic (donor is an HLA-identical sibling) marrow provides the opportunity for aggressive antileukemic therapy without regard to marrow toxicity. Until 1975, marrow transplantation was carried out only after failure of all other therapy. Consequently, most patients were in advanced relapse. Six of 16 recipients of syngeneic marrow and 13 of 100 recipients of allogeneic marrow are still in remission after 5. 5-10 years [3, 7]. An actuarial survival curve of the first 100 patients grafted in Seattle after conditioning with cyclophos phamide (60 mg/kg on each of 2 successive days) and total body irradiation (1,000 rad) showed three periods of interest: (1) The first 4 months showed a rapid loss of patients associated with advanced illness, graft-versus-host disease, infections (in particular interstitial pneumonias), and recurrent leukemia; (2) from 4 months to 2 years, the curve showed a much slower rate of decline attributable primarily to recurrent leukemia; and (3) from 2-10 years, the curve was almost flat with a negligible loss of patients and no recurrent leukemia. This flat portion of the curve corresponded to 13% of the patients and indicates a strong probability that the majority of these survivors are cured of their disease [8]. Attempts at reducing the incidence of leukemic relapse after transplantation were made by a number of marrow transplant groups by added chemotherapy.

When compiling the present atlas our aim has been to provide the practis ing radiotherapist with a handbook which would help him to plan the radiation therapy of tumours of individual organs. Apart from a few ex ceptions, all isodose charts in this atlas show dose distributions resulting from external irradiation. Combination of external irradiation with intra cavitary radium therapy is presented in the treatment of carcinoma of the uterine cervix, in which case the two techniques are complementary. Thd immense material of the pertinent literature could, naturally, not have been included in the atlas. As a result of scrupulous selection, the isod-.: se charts shown may not invariably be the optimum ones, and some of them may not be the most modern. However, the usefulness of the information they provide has made us to keep them all the same. We did not intend to change the original charts in any way and stan dardization of the isodoses was not undertaken. Radiation parameters are given in the figure captions and, if available, information has also been provided on the phantoms used by the authors. Naturally, the isodoses presented will not automatically apply to all situ ations and all apparatuses without due attention to the individual patient:: Jnd technical details such as penumbra and source diameter. They merely serve as a starting point and will help to save time and work during treat ment planning also with the computer."

Material for this book was gathered in the early 1980's in Manchester, where a higher incidence than usual of complications in the gastro-intestinal and urinary tract was observed. Part I describes the principles and methods of radiotherapy for pelvic tumours, pathological features and radiological analysis of bowel and urinary tract changes. Parts II and III are devoted to clinical assessment and management, where the need for a multi-diciplinary approach is emphasized.

2. Virological Findings. 90 3. Immunity. . . . . 90 C. Secondary Dengue: Dengue Hemorrhagic Fever and the Shock Syndrome 92 1. General Remarks. . . . . . . . . . . . . . 92 2. Clinical Course and Clinical Laboratory Findings 93 3. Virological and Serological Findings. . . 95 4. Immunopathology of Secondary Dengue. 98 XI. Immunization. . . . . . . . . . . . . . . 104 A. Anamnestic Immune Responses in Sequential Infections With Dengue and Other Group B Togaviruses . . . . . . . . 104 1. Results With Members of the Dengue Subgroup 104 2. Results With Dengue and Other Flaviviruses. 107 B. Dengue Vaccines for Use in Man 108 XII. Opportunities for the Future 113 Acknowledgments. 114 References. . . . . . . . . . . 114 I. Introduction Dengue fever is a mosquito-transmitted disease of man which has afflicted untold millions of people over the past two centuries. It is caused by viruses classified as a subgroup of the group B togaviruses. Along with other members of that group as well as group A, the dengue viruses have been investigated intensively during recent years. Certain unique aspects of their structure, composition, antigenicity, replication, and antigenic relationships have established the togavirus family as quite distinct from other families of enveloped RNA viruses (see recent review of PFEFFERKORN and SHAPIRO, 1974). The basic studies leading to this conclusion have coincided with epidemiological field investigations which have resulted in a continuing increase in the number of viruses now designated as group A or B togaviruses. This, in turn, has led to a growing appreciation of their immense importance as actual or potential pathogens of man and beast.

The tumors of the brain similar to other pathological changes of that particular organ claim for a separate position in scientific medicine regarding biology, morphology, features of clinical manifestation, diagnostics and therapy. During the past years due to rapid progress in basic neurosciences and medical biotechnics the situation of the neuroclinician in front of brain tumors has been dramatically changed. The prerequisites for early and accurate diagnosis as well as for successful treatment also of malignant neoplasms have increased and remarkably improved. At the same time the information necessary for an appropriate pragmatic use of the available cognitive methods and therapeutic means increased along the same scale and is permanently being critically modified or changed due to fundamental new insights which come up in always shorter intervals. These facts necessitate the preparation of publications in which the state of the art is presented in possible completeness, systematic order and proper disposability for rational management and therapeutic strategies.

A great deal of new information has been obtained during the past four years, and this monograph provides a clear and well reviewed update on biochemical mechanisms and the results of important new clinical studies using the interferons. Reviews include what is presently known about the biosynthesis, physiological role and mechanisms of action of the interferons (alpha, beta, gamma). New biochemical information on interferon-receptor interactions and signalling pathways is provided. The pharmacokinetic considerations in treating leukemia, lymphoma, myeloma, neuroendocrine tumors and other solid tumors are reviewed with special emphasis on studies of adjuvant chemotherapy in malignancies of the immune system.

How to treat advanced prostatic cancer remains controversial, despite intense basic and clinical research investigating the pathogenesis and natural history of this unique cancer highly prevalent in elderly males. Nine experts were asked to meet and discuss the facts. This resulting monograph gives an overview of the available knowledge on all aspects of the subject. The objective evaluation and consensus opinion of the authors presented here set this book apart from other publications with conflicting viewpoints. For readers eager to obtain a comprehensive and balanced view of the thousands of clinical contributions and clear advice on the choices, this book is a must.

Recent advances in technology have opened up new possibilities in the diagnosis and treatment of cerebrospinal vascular diseases. It is now possible to use magnetic resonance imaging to map brain function and metabolism as an aid to diagnosis. Novel applications of magnetic resonance angiography allow three-dimensional imaging, and the magnetization transfer contrast technique gives us a new window on cerebral vascular function. This volume presents work in all these fields as well as previewing the techniques of endovascular surgery for cerebrospinal vascular diseases. These include modern stereotactic radiosurgery for arteriovenous malformations and for angiographically occult vascular malformations of the brain. This book presents an overview of the latest applications of technology to this rapidly developing and challenging field.

One out of every two men over eigthy suffers from carcinoma of the prostate.It is discovered incidentally in many patients with an alleged benign prostatic hyperplasia. In treating patients, the authors make clear that primary radical prostatectomy is preferred over transurethral resection due to the lower complication rate.

Attempts to influence survival of patients with colorectal cancer (CRC) by adjuvant chemotherapy are limited by the variability of survival in different prognostic groups [4] and the paucity of drugs that have shown activity in the advanced disease [10]. Of the few drugs which are active in the advanced disease, only 5-fluorouracil (5-FU) and razoxane "+/-1,2-bis(3,4-dioxopiperazin-1-yl)propane) are suitable for long-term adjuvant treatment [2, 9]. 5-FU has been widely and intensively studied as adjuvant chemotherapy in CRC [7], but there is no unanimity that it has even the marginal influence on survival that has been claimed [3, 10]. Razoxane has not previously been tested for adjuvant or maintenance treatment in CRC. It has however a number of biological activities which might be thought useful in the treatment of residual or minimal tumours [1] and which might therefore make it useful as an adjuvant. Thus it specifically prevents tumour dissemination and metastases in some tumours and normalizes the neovasculature which the tumours induce [6, 8, 11]. The drug is not cytotoxic in the usual sense, does not affect non-dividing cells, and only blocks cell division during a brief period of the cell cycle in late G and/or early mitosis [12]. It does so non-selectively and most cells capable of 2 division examined so far have been affected by the drug. Even affected cells however are not destroyed immediately, but may increase in size and become multinucleate [5].

Malignant melanoma is the focus of investigations which range from basic re search to clinical trials with conventional therapy and with biological response modifiers. The involvement of investigators with different backgrounds in combi nation with recent progress in biotechnology has facilitated the characterization of the antigenic profile of melanoma cells, the analysis of the structural and function al properties of melanoma-associated antigens, and the application of immuno diagnostic and immunotherapeutic approaches to melanoma. As a result, a large body of information about various aspects of melanoma has been rapidly accumu lated during the past few years. In organizing this book I aimed at providing a readily available source of infor mation on the current research in melanoma. To this end I invited investigators with active research programs to contribute chapters describing and discussing the significance of their most recent results. To facilitate the preparation of the manu scripts and to avoid duplicating other recently published books on melanoma, I discouraged the contributors from providing extensive reviews of the literature on the various topics. Although I made every effort to be as complete as possible in the selection of the contributors, while writing this preface I realized that I had overlooked at least three investigators whose work should have been included.

Radiation therapy of cutaneous cancers and other dermatologic disorders is not covered adequately in many current textbooks of dermatology and radiation oncology. This book is intended to fill that gap. Both text and illustrations are oriented toward the practical aspects of radiation therapy. The beginner will find a concise introduction to physical and biological principles, selec tion of radiation factors, dose definitions, indications for treatment, and radiation seque lae. The experienced dermatologist and radiation oncologist will find a detailed discussion of specific indications for various radiation techniques in different body regions. A special effort was made to add pertinent references to the world literature for those who wish to pursue particular topics still further. We have tried to include all major American and European publications of the last 20 years in our bibliography of more than 500 refer ences, and we also have attempted to review the most important scientific papers on prin ciples and practice of ionizing radiation therapy in a constructive way. We are grateful to Professor Gorson, Dr. Breneman, and Professor Lindel6f, who generously contributed chapters in their areas of expertise despite their many other com mitments."

Almost a century ago Paul Ehrlich introduced the "magic bullet" concept of targeting therapeutic agents to specific tissues in order to reduce systemic toxicity. Due to the advances in hybridoma technology in the 1980s, monoclonal antibodies (MAbs) with their exquisite affinity to tumor antigens have become powerful tools in the treatment of cancer, especially when linked to therapeutic agents such as radionuclides, drugs, toxins, or enzymes. It can now be expected that such agents will lead to new cancer treatments with high therapeutic success rates. However, there are major problems in developing this therapeutic concept to a routine treatment modality. This is partly due to factors such as heterogenous distribution of tumor antigens, insufficient blood supply of tumors, high interstitial pressure, and the large interstitial space that antibodies have to traverse. This book is focused on the development in radio immunotherapy (RIT) using radio labeled monoclonal antibodies as tumoritoxic agents. This area of research has attracted the interest of clinicians and scientists from many different disciplines. It is now clear that the full potential of RIT can only be realized through the concerted efforts of laboratory scientists (molecular biologists, cell physiologists, chemists, radiation physicists, and biologists) and cancer clinicians in nuclear medicine, radiooncology, and internal oncology."

The ultimate "consumer" of the data presented at conferences on the primary treatment of operable breast cancer is the patient, and when, as in this disease, the benefits of therapy are relatively mod est, the availability and interpretation of the data from trials be comes an issue of primary importance. The effects of present treat ment are in fact such that more patients relapse despite therapy than are estimated to benefit from it. It is, therefore, extremely dif ficult for the physician to recommend unequivocally one particular adjuvant treatment modality for the vast population of women with breast cancer. The interpretation of results from clinical research-oriented pro grams is constantly applied, however, in the treatment of breast cancer patients outside of clinical trials. From presented or publish ed data, many physicians extrapolate indications for the use of a given treatment regimen for their patients, perceiving it as the "best available therapy. " It is essential that the "best available therapy" be selected individually for each patient. However, considering the modest effect of treatment upon outcome, it is imperative that those who provide the data - those who are involved in both pa tient care and clinical research - make it known that the best cur rent treatment for the population of breast cancer patients is avail able within the framework of clinical trials. In this way not only present-day patients but also future ones will derive the greatest benefit.

Tumour therapy depends essentially on being able to destroy the clonogenic activity of tumour cells while keeping the damage to the normal tissue low. Clinical experience shows that tumour response varies greatly even if tumours with the same localisation, clinical, and histopathological staging are compared. Some tumours appear to be resistant to conventional radiotherapy (X-rays, y-rays or fast electrons) or chemotherapy. In these cases new therapy modalities are necessary. Combined therapy modalities seem to have advan- tages for some resistant tumours; one possibility of such a treatment is to combine radiotherapy or chemotherapy with hyperthermia. This means that the local tumour, the tumour region or even the whole body of the patient has to be heated to temperatures between 40 to 45 C (in case of whole body hyperthermia to 42 C maximal) for a certain time (usually 30-60 min are adequate). Hyperthermia has a long tradition in medicine as a treatment modality for various diseases. Inscriptions of the old Egyptians and texts of the Greeks have pointed out its importance. Usually whole body hyperthermia has been used by the induction of fever. Local hyperthermia began around 1900 when Westermark treated unre- sectable cervix carcinomas with hot water in a metallic coil. By the beginning of this century an increase of radiation effects was hy- pothesised with hypothermia and later observed. However, only in the 1960s and 1970s were systematic investigations started which showed radiosensitisation and chemosensitisation by hyperthermia in cells and tissues including tumours.

The ninth annual multidisciplinary symposium on clinical oncology organized by the Royal College of Radiologists was jointly arranged with the International Society for Radiation Oncology. It was held in London in February 1987 and discussed the biological and clinical basis of the effects of radiotherapy. Wherever possible lectures by an experimental scientist were paired with those of a clinical scientist in order to emphasize clinical relevance. It is hoped that this has resulted in a widely balanced view of the subject. The volume presents an updated version of these subjects based on those talks. After surgery, radiotherapy is the main treatment used in the management of patients with cancer. Its empirical success when first introduced is now backed up by a wealth of laboratory, clinical and experimental experience. New techniques for adminis tering the conventional X-ray therapy have been supplemented by methods which can be used to modify the radiation response. These include changes in dose rate or fractionation, and combined modality treatments including sensitization by drugs or heat. Other types of radiation, such as neutrons and other particles, are also now available which have enhanced physical and biological advantages.

Conformal radiation therapy represents a new challenge for radiation oncologists. It offers the prospect of either increasing the radiation dose to target tissues while delivering a similar dose to organs at risk, or reducing the dose to organs at risk while maintaining the dose to target tissues. First, lymph node areas at risk are established using the available data from pathological examination of surgical specimens and/or pattern of locoregional relapse. Then, based on a three-dimensional description of the anatomical regions where the areas at risk are located, guidelines for the delineation of the clinical target volumes are proposed. The data presented should enable the reader to make appropriate decisions regarding the selection and delineation of the target volumes when confronted with the most frequent tumor types and sites.The book will contribute to paving the way for more effective radiation oncology in the twenty-first century.

After historical introduction, the aspiration technique and imaging modalities are described. Thereafter, the use of aspiration cytology in the diagnosis and mainly in the sta- ging of urologic cancers is on still not well known appli- cations of the procedure in the staging of some organs (bladder, adrenals, penis, testis and secondary ureteral strictures) are reported.

Carcinoma of the prostate increasingly dominates the attention of urologists for both scientific and clinical reasons. The search for an explanation and the prediction of the variable behaviour of the malignant prostatic cell continues unabated. The search for more precise tumour staging and more effective treatment is equally vigorous. Editors Andrew Bruce and John Trachtenberg have assembled acknowledged leaders in prostate cancer to present those areas of direct interest to the clinician. There are a number of other topics that might have been considered but most of these, such as experimental tumour models or biochemical factors affecting cell growth, still lack immediate application for the clinician. Carcinoma of the prostate continues to have its highest incidence in the western world, and the difference in comparison with the incidence in the Far East appears to be real and not masked by diagnostic or other factors. A number of other epidemiological aspects need careful analysis: Is the incidence increasing? Is the survival improving? Is the prognosis worse in the younger patient? Epidemiological data are easily misused and misinterpreted so that a precise analysis of the known facts makes an important opening chapter to this book.

The present challenge in the treatment of tumors is to reduce the number of patients that still die as a result of primary tumors. Today, the percentage of such deaths remains high at 30%, even when all the common therapeutic methods, namely surgery, radiotherapy, and chemotherapy, are applied. In order to reduce this percentage, new types of radiation sources with a higher linear energy transfer have been intro duced, such as neutrons and pions. Fractionation patterns have been modified and radiosensitizers have been applied to in crease biological efficiency. Studies of the combined application of chemotherapy and radiotherapy have been made to find the best therapeutic effect. In the early 1970s biological findings confirmed the effect of hyperthermia on tumor cells. The first clinical studies on hyper thermia treatment demonstrated that it resulted in better local tumor control. Further application of this treatment modality showed that hyperthermia should be used in addition to radio therapy and chemotherapy. Despite these encouraging results, hyperthermia has not been introduced into common clinical use, due primarily to technical problems. There are a number of methods of transferring heat into tumors; however, with regard to physical conditions, an op timum method has not yet been found. One of the reasons is that up to now we have had no reliable method of obtaining thermal mapping of all parts of the human body. Such measurements are required not only for dosimetric purposes but also for the regula tion of a hyperthermic system."

During the last decade the therapeutic approach to musculoskeletal tumors has changed dramatically, from ablative surgery with ampu tation ofthe limb to reconstructive surgery with transplantation of bone and vessels combined with radio-and chemotherapy. This has changed the demands on radiologists and pathologists to a considerable degree. At the same time there has been a manifold increase in the diagnostic possibilities offered by modern radiology, with several new modalities affording a potential for morphologic depiction and tissue character ization that was unattainable a decade ago. Today, the definitive diagnostic work-up and treatment of patients with musculoskeletal tumors is most often done in tumor centers, by groups that ideally should be composed of an orthopedic surgeon, radiotherapist, oncologist, radiologist, pathologist and cytologist. It is necessary for all the members of this team to be well versed in the surgi cal and other treatment principles, in the pathologic concepts, and in the radiologic interpretation of musculoskeletal tumors. Moreover, it is important that the modern diagnostic approach to musculoskeletal tumors is well known also at the referring center, be it a private practi tioner's office or a large hospital. This will avoid unnecessary biopsies, and repetition of radiologic and other diagnostic procedures that have already been performed at the referring center."

Neuroblastoma is the third most common malignancy of childhood. accounting for 8% of all cancers in patients under 15 years of age. In the majority of cases. by the time neuroblastoma is diagnosed. it has already spread from its site of origin to involve distant sites. Approximately 90% of cases of neuroblastoma can be diagnosed by a combination of techniques including detection of specific tumour markers in the urine. histopathological and immunocytological assessment of involved bone marrow and the 'characteristic' appearances of tumours dem- onstrated by computerised tomography and ultrasonography. However. despite this plethora of techniques. up to. 10% of cases of neuroblastoma are still difficult to diagnose and rely on excisional biopsy of a site of disease. It was against this background that the scintigraphic localisation of neuroblastoma with the radiolabelled guanethidine analogue. mIBG. became available. With mIBG scintigraphy it is now possible to demonstrate the presence of neuro- blastoma (and related tumours) at the primary site. soft tissue sites. in the bone marrow and in cortical bone. in a single investigation. The success of mIBG scintigraphy depends on many factors including the choice of isotope for labelling the mIBG. the equipment used to carry out the procedure. and the manipulation and interpretation of the information obtained. At the Royal Marsden Hospital we have performed over 100 mIBG studies in children. and our advice has frequently been sought by other centres who are. or intend to become.

Biologists and radiotherapists present their experimental work and clinical data in the field of radiation injuries of normal tissues and organs. Particular regard is payed to the relevance of biological mechanisms in clinical situations. Principles of radiation damage and combined treatment toxicity in radio-chemotherapy are being explained. The main topics discussed are the importance of microvasculature, time, doseand fractionation and factors modifying clinical radioresponse for early andlate radiation effects. Tissues and organs considered in this volume are mucosa and skin, lung and heart, bladder and muscle, CNS and eye. Special problems of pediatric radiotherapy, TBI, IORT and second malignacies are also mentioned.