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.

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.

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."

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."

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 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.

Scope and ideas of the workshop The workshop which took place at the University of Giessen from Oct. 3 to Oct. 7, 2002 and whose proceedings are collected in this volume started from the idea to convene a number of scientists with the aim to outline their "visions" for the future of radiation research on the basis of their expertise. As radiation research is a very wide field restrictions were unavoidable. It was decided to concentrate this time mainly on molecular and cellular biology because it was felt that here action is par-ticularly needed. This did not exclude contributions from neighbouring fields as may be seen from the table of contents. It was clearly not planned to have a c- prehensive account of the present scientif fic achievements but the results presented should only serve as a starting point for the discussion of future lines of research, with the emphasis on the "outreach" to other parts of life sciences. If you are interested in the future ask the young - we attempted, therefore, to invite mainly younger colleagues (with a few exceptions) who had, however, already left their marks in the field. They were asked to describe what they felt is important in radiation research and may have significant influences on other branches of life sciences. They were given the task to demonstrate what is lost for science "if we do no longer exist."

Neurosurgery o/the Future: Computers and Robots in Clinical Neurosurgical Practice and in Training - a Philosophical Journey into the Future Many present day neurosurgeons believe that they already obtain good results in operative surgery with the benefit of the operating microscope and other aids which have become available in the last three decades and that the introduction of computers and robots to the operating theatre is superfluous. However, it is clear from analogy with the function of the airline pilot, another profession where there are great demands on manual skill and on spatial awareness, that these devices do have much to offer neurosurgery. Classical neurosurgery, in the time of Cushing, Dandy and Scarff, was based on a three dimensional picture of the patient's brain formed in the surgeon's mind and often illustrated in elegant drawings. Such pictures were based on neuroradiological studies by pneumoencephalography, ventriculography or by angiography. Generally these stud ies showed the presence and position of a lesion by displacement of normal brain structures and the picture was built up by interference. This was then converted by the experienced neurosurgeon into a plan for the craniotomy site and the trajectory of the surgical approach. Once the brain was exposed further pre-operative information was obtained by visual inspection and by palpation with the brain needle. These classical forms ofneuroradiology have largely been superseded by computerised tomography and by magnetic resonance imaging."

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.

The European School of Oncology came into existence to respond to a need for information, education and training in the field of the diagnosis and treatment of cancer. There are two main reasons why such an initiative was considered necessary. Firstly, the teaching of oncology requires a rigorously multidiscipli nary approach which is difficult for the Universities to put into practice since their system is mainly disciplinary orientated. Secondly, the rate of technological development that impinges on the diagnosis and treatment of cancer has been so rapid that it is not an easy task for medical faculties to adapt their curricula flexibly. With its residential courses for organ pathologies and the seminars on new techniques (laser, monoclonal antibodies, imaging techniques etc.) or on the principal therapeutic controversies (conservative or mutilating surgery, primary or adjuvant chemotherapy, radiotherapy alone or integrated), it is the ambition of the European School of Oncology to fill a cultural and scientific gap and, thereby, create a bridge between the University and Industry and between these two and daily medical practice. One of the more recent initiatives of ESO has been the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on future developments in specific fields of on cology."

Cancers of the head and neck are among the most morbid of cancers. Convention al surgery and/or radiation therapy have a high cure rate for patients with early stage disease. However, despite optimal treatment with surgery and radiotherapy, patients with nodal spread or extensive local disease have a low cure rate. Even if a cancer is cured, a patient is often left with long-term debilities from the treatment and/or cancer. The major causes for decreased survival in patients with advanced head and neck cancer include local recurrence, distant metastases, and second primaries. All of these need to be addressed if one is to improve upon the curability of advanced disease. There are several new techniques, surgical and radiotherapeutic, designed to improve local control. Brachytherapy, or interstitial implantation, delivers a high dose of localized radiation with minimal normal tissue injury. This technique as discussed by Goffinet, may be even more efficacious when combined with hyperthermia. New, creative methods of radiation therapy delivery, such as the use of multiple fractions per day, as discussed by Parsons and Million, are also contributing to long-term local control. Laser therapy, discussed by Ossoff and Nemeroff, provides another tool for treatment of local disease."

It was not too many years ago that the role of chemotherapy for head and neck cancer consisted of single-agent methotrexate for selected patients with recurrent disease. In the past decade, multiple new agents, high-dose chemotherapy, combinations, and intra-arterial approaches have been used for the patient with recurrent disease. Wheeler critically assesses the current status of these approaches. When oncologists began testing chemotherapy in the combined modality approach, trials consisted of induction chemotherapy and use of single agents as radiosensitizers. Although a great deal has been learned from these trials, benefit in terms of survival has been marginal. Even more promising may be the concomitant use of combination chemo therapy and radiation. Taylor describes the encouraging results as well as the potential. Induction chemotherapy may have a second important goal in addition to improving curability-it could be used for organ preservation. Dimery et al., present the background for this approach in the patient with laryngeal cancer as well as a description of their randomized trial for voice preservation. Head and neck squamous cancers are a heterogeneous group of diseases, and surgeons have long sought parameters that will help predict outcome."

This book attempts to combine many different threads into a comprehensible whole. Since the subject is the Gamma Knife and the author is a neurosurgeon, the field of clinical interest is restricted to intracranial pathology. The discipline of radiosurgery now applies to patients who may reasonably be referred by internists, neurologists, otolaryngologists, endocrinologists and several others. Some of the topics, touched upon, such as stereotaxy and the construction of a radio surgical instrument are unfamiliar to the majority of medical men. Other topics, such as those pertaining to the reactions between radiation and living tissue, are not exactly unfamiliar and yet, for most of us, they are not comfortable areas of expertise: in that we have some basic knowledge but not enough to draw conclusions and interpret. In particular, it is not easy to answer the very sensible questions that patients ask, when being considered for this particular form of treatment. The author has attempted to describe the basic relevant phenomenology in terms that should be readily understandable to a non-specialist physician. To do this, he has been heavily dependent on the expertise of a number of mathematically sophisticated collaborators, who have checked his manuscript. They are named in the acknowledgments section. The relevance of the different sections of this book will naturally be assessed differently, according to the experience and interest of the reader. To simplifY access to the information that is required, the book is divided into three main sections.

This monograph represents an attempt to collect the methods developed within the past decade in which echocardiography was being used to guide or to assess the results of some cardiovascular interventions or to overcome the imaging limitations of transthoracic approaches. I have entitled this book Echocardio graphy in Cardiac Interventions, although I am aware that this title is not entirely applicable to all the included methods. In these interventive procedures echocar diography preserves its noninvasive nature, and by combining it with invasive procedures, they become more accurate, safer and less invasive. The book is divided into 8 sections and 42 chapters written by many authorities in the field. When such comprehensive contributions from many authors are used, some overlapping cannot be avoided. I would like to express my appreciation to the individual contributors for their A. 1. Tajik dedication and cooperation in preparing this book. I am indebted to Dr. from the Mayo Clinic, who created a pleasant milieu for preparing the book during my sabbatical year at the Mayo Clinic. It is hoped that the reader will derive from this book a sense of where and how the ultrasound can be used in cardiovascular interventions today and what new approaches might be forthcoming. Iva Cikes List of contributors M. L. Antunes, MD., Department of Surgery, Columbia University College of Physicians and Surgeons, New York, New York, USA. J. Areeda, Cedars-Sinai Medical Center, Los Angeles, California, USA."

An in-depth introduction to radiotherapy physics emphasizing the clinical aspects of the field. This second edition gradually and sequentially develops each of its topics in clear and concise language. It includes important mathematical analyses, yet is written so that these sections can be skipped, if desired, without compromising understanding. The book consists of seven parts covering basic physics (Parts I-II), equipment for radiotherapy (Part III), radiation dosimetry (Parts IV-V), radiation treatment planning (Part VI), and radiation safety and shielding (Part VII). An invaluable text for radiation oncologists, radiation therapists, and clinical physicists.

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.

When in the future improved and more flexible heating equipment becomes available, and when hyperthermia is applied more routinely, computerized simulations of treatments will become commonplace, as they are in radia tion therapy. For hyperthermia, however, such simulations will be used not only for the traditional role of planning patient treatment, but also for three other applications not needed in radiation therapy - the comparative evalu ation of equipment, feedback control during treatment, and the post-treat ment evaluation of therapy. The present simulations of hyperthermia are crude and simple when compared with what is required for these future ap plications, a fact which indicates the nedd for considerable research and de velopment in this area. Indeed, this research is proceeding rapidly within the hyperthermia community, whre three-dimensional power deposition and temperature calculations have just become available for realistic patief\t anatomies. Of equal significance are the even more rapid development in diagnostic imaging for the determination and display of patient anatomy and blood flow rates - information required for the planning of realistic hyperthermia treatment. These simulations will be very valuable tools which can be used to great ad vantage when combined with data obtained from treatments of patients."

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.

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."

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.

Defining the Lung Cancer Problem 1 Lung cancer is the leading cause of cancer death in the world. It kills almost as many Americans as cancers of the breast, prostate, colon, rectum, pancreas, and 2 kidney combined, and accounts for 28.6% of all US cancer deaths. With an increase in the 5-year relative survival rate from 13% to only 16% in the more than 2 30 years from 1974 to the present, it will take us another 840 years to eradicate lung cancer deaths if we do not improve the current rate of progress. As discussed in this text, lung cancer prevention has received substantial att- tion. The decrease in smoking in recent decades has helped, but smoking is not the only problem. Lung cancer in people who have never smoked is currently the 5th 3 leading cause of cancer death in the United States. Several factors contribute to the lethality of lung cancer, including the rapidity of tumor growth, advanced stage at diagnosis (due to nonspecificity of early sy- toms and the uncertain efficacy of screening), early development of metastases, and resistance to therapy. Several chapters in this book discuss new molecular targets that may be potentially exploitable in the future, as well as discussing our track record to date in exploiting them.

Radiosurgery is a rapidly developing form of minimally invasive neurosurgery. Selected papers from the first meeting of the International Stereotactic Radiosurgery Society in Stockholm, June 1993, reflect current multidisciplinary approaches to difficult intracranial neurosurgical problems. Neurosurgeons, radiotherapists, oncologists, radiobiologists, physicists and representatives of several other clinical disciplines inform about the state-of-the-art of radiosurgical treatment of a multitude of intracranial problems such as arteriovenous malformations, pituitary and pineal tumors, vestibular schwannomas as well as metastatic brain tumors and gliomas.

While it is true that certain types of neoplasms, such as those of the pancreas and brain, are still lesions with a grave prognosis, there are many other common cancers for which appropriate treatment can be curative in substantial numbers of patients .. This hopeful aspect of cancer is insufficiently appreciated, even by the medical profession itself; too many pessimistic patients find themselves consulting equally pessimistic physicians. WHO Expert Committee on Cancer Treatment *. The aim of this monograph is to present the latest information on the treatment of cancer, and the words quoted above from the report of a WHO Expert Committee on Cancer Treatment form an appropriate introduction to the subject. The pessimism to which they refer is still all too often characteristic of the attitude towards cancer and its treatment. The various chapters have been specially written for this monograph by specialists of international repute, and it will be noted that some of them were participants in the meeting of the WHO Expert Committee on Cancer Treatment mentioned above."

A number of vital therapeutic modalities are not covered adequately in current dermatology textbooks. This book is intended to fill that gap. It originated in a series of special lectures on modem applications of physical modalities given at recent annual meetings of the American Academy of Dermatology; the main topics were radiotherapy, electrosurgery, phototherapy, cryosurgery, and related therapeutic modalities. The authors, recognized authorities in their field, have included much addi tional information which could not be covered in the original lectures because of time limitations. The indications for modem dermatological x-ray therapy reflect the basic views of the recently published guide lines of the National Academy of Sciences-National Research Council. Both text and illustrations are oriented toward the practical aspects of therapy with physical modalities. A special effort was made to bring the contributions up to date; pertinent references have been added for those who wish to pursue particular topics still further. Where there is an apparent overlap between chapters, it was felt to be advantageous because different authors approached their subject from different perspectives. I am most grateful to the various authors who generously contributed despite their many other commitments. I wish, also, to thank the staff of Springer-Verlag for their advice and assistance in the preparation of the manuscript."

Rapid advances in nanotechnology have enabled the fabrication of nanoparticles from various materials with different shapes, sizes, and properties, and efforts are ongoing to exploit these materials for practical clinical applications. Nanotechnology is particularly relevant in the field of oncology, as the leaky and chaotic vasculature of tumors-a hallmark of unrestrained growth-results in the passive accumulation of nanoparticles within tumors. Cancer Nanotechnology: Principles and Applications in Radiation Oncology is a compilation of research in the arena of nanoparticles and radiation oncology, which lies at the intersection of disciplines as diverse as clinical radiation oncology, radiation physics and biology, nanotechnology, materials science, and biomedical engineering. The book provides a comprehensive, cross-disciplinary survey of basic principles, research techniques, and outcomes with the goals of eventual clinical translation. Coverage includes A general introduction to fabrication, preferential tumor targeting, and imaging of nanoparticles The specific applications of nanomaterials in the realms of radiation therapy, hyperthermia, thermal therapy, and normal tissue protection from radiation exposure Outlooks for future research and clinical translation including regulatory issues for ultimate use of nanomaterials in humans Reflecting profound advances in the application of nanotechnology to radiation oncology, this comprehensive volume demonstrates how the unique physicochemical properties of nanoparticles lead to novel strategies for cancer treatment and detection. Along with various computational and experimental techniques, each chapter highlights the most promising approaches to the use of nanoparticles for radiation response modulation.