H.-P. Heilmann

This book provides an overview of recent advances in radiation oncology, many of which have originated from physics and engineering sciences. The new technologies in this field have a complex physical, mathematical and technical background that technical assistants, dosimetrists, and physicians frequently find difficult to comprehend. However, this book is specifically designed to be readily understandable by professionals and students with a medical background as well as by newcomers to radiation oncology from the field of physics. All relevant areas of the subject are covered in detail, including 3D imaging and image processing, 3D treatment planning, modern treatment techniques, patient positioning, and aspects of verification and quality assurance.

The aim of this book is to provide a uniquely comprehensive source of information on the entire field of radiation therapy physics. The very significant advances in imaging, computational, and accelerator technologies receive full consideration, as do such topics as the dosimetry of radiolabeled antibodies and dose calculation models. The scope of the book and the expertise of the authors make it essential reading for interested physicians and physicists and for radiation dosimetrists.

Age-related macular degeneration (ARMD) is a frequent disease of the elderly and the most common cause of blindness. Recently, various new treatment options have become available for ARMD. This book, written by recognized experts and including the results of international study groups, provides a comprehensive report on these treatments, documenting their rationale, uses, side-effects, and benefits. It will be of immense value to all with an interest in ARMD.

Hyperthermia has been found to be of great benefit in combination with radiation therapy or chemotherapy in the management of patients with difficult and com­ plicated tumor problems. It has been demonstrated to increase the efficacy, of ionising radiation when used locally but also has been of help in combination with systemic chemotherapy where hyperthermia is carried out to the total body. Problems remain with regard to maximizing the effects of hyperthermia as in­ fluenced by blood flow, heat loss, etc. The present volume defines the current knowledge relative to hyperthermia with radiation therapy and/or chemotherapy, giving a comprehensive overview of its use in cancer management. Philadelphia/Hamburg, June 1995 L. W. BRADY H.-P. HEILMANN Preface In an attempt to overcome tumor resistance, hypoxia, or unfavorable tumor condi­ tions, oncological research has come to focus on gene therapy, immunotherapy, new cytotoxic agents, and increasingly sophisticated radiotherapy. Radiation research has been directed towards heavy particle therapy and modification of the radiation response by either protecting or sensitizing agents. Improved dose localization using rotational or conformal strategies has also been implemented. Recently, changes in radiation fractionation schedules have shown promise of better results. Hyperthermia in cancer therapy can be viewed similarly as another means to increase the sensitivity of tumors to radio- and chemotherapy.

Increasing survival figures and the use of more intense combined treatment regimens in modern oncology have raised the problem of late therapeutic sequelae in long-term survivors after cancer. Recent scientific approaches to late sequelae concentrate on the evaluation of subclinical changes with sophisticated functional measurements and experimental investigation of the underlying pathophysiological mechanisms. The objective of the book is to bring together these recent clinical and experimental data from different medical disciplines to give an overview of the most relevant problems of late sequelae. In clinical practice the book may help regarding estimation of risks, selection of diagnostic methods, and estimation of the prognosis of late sequelae.

In the United States in 1993 the American Cancer Society estimated that there were about 1,300,000 new cases of invasive cancer diagnosed. At the time of presentation about 70% of those patients represented limited local regional disease without evidences of distant dissemination. About 30% of the patients had demonstrated metastatic disease at the time of initial diagnosis or about 390,000 patients. Of those patients with local regional disease about 56% would be cured by the best treatment programs including surgery, radiation therapy with or without chemotherapy when given for cure. Therefore, of the 1,300,000 new cases of invasive cancer, about 509,000 would be cured by the best treatments available. However, about 790,000 patients will have metastatic disease as a part of initial presentation or following the completion of definitive treatment. The majority of the patients with metastatic disease will have metastases to bone as the dominant site of metastatic disease primarily from cancers of the breast and lung but other metastatic sites will be common including lung, liver, mediastinal and retro-peritoneallymph node groups as well as brain and spinal cord. It has been suggested by SMITHERS, CARLING and WINDEYER that the management of the patient with metastatic disease or recurrent disease can be a more difficult problem in management than a patient who is treated for cure.

The development of the capacity to use electron beams at various energies stimulated the development of the new technology of intraoperative radiation therapy. The visual­ ization of the primary tumor, definition of the site to be irradiated, and knowledge of the size of tumor to be irradiated, including adequate margins for microscopic extent along with debulking of the tumor, have allowed intraoperative radiation therapy to be pur­ sued in a wide variety of disease processes. Not only is it possible to treat tumors that were highly resistant, but it is also possible to specifically localize the tumor with a mar­ gin adequate to encompass potential microscopic extensions and to choose the appro­ priate electron beam energy to treat the potential residual tumor and spare the adjacent normal structures. It is, furthermore, possible to treat patients with unresectable tumors. Central to this entire development is the fact that normal structures can be removed from the field of treatment. In the beginning, the emphasis was on single fractions of electron beam radiation without subsequent supplementation by external photon beam radiation therapy. How­ ever, more recently it has become necessary to use not only a single electron beam frac­ tion during the course of the operation, but to supplement it with external beam treat­ ment. The encouraging results obtained with intraoperative radiation therapy have led to clinical trials at a large number of institutions throughout the world.

In the last two decades, there has been a major increase in the actual numbers of women diagnosed with breast cancer (from 65000 new cases 20 years ago in the United States to 183000 in 1993). Concomitant with this has been a shift toward making the diagnosis earlier and toward diagnosing an earlier stage ofthe disease (more than 70% of diagnoses were of advanced-stage disease two decades ago, whereas more than 70% of diagnoses are now earlier-stage disease in 1992). These changes are clearly related to the woman's greater sensitivity to abnormalities in the breast and her seeking medical care, to the physician's greater awareness of the potential diagnosis of cancer, and to the major and important impact of mammographic screening. These changes have had a major impact on the questions of appropriate treatment, thereby contributing to the controversies in the disease. What is the role of surgery? What are the respective advantages of radical mastectomy, modified radical mastectomy, and conservation surgery with and without supplementary treatment? What is the role of radiation therapy? When should radiation therapy be performed after mastectomy, and what volumes should be irradiated post mastectomy? Where is radiation therapy indicated after conservation surgery, and when is radiation therapy an effective palliative treatment measure? When should chemotherapy and/or hormonal therapy be used as an adjuvant to primary treatment and when as an effective palliative treatment? This book by Levitt and Fletcher addresses these critical and important issues.

The use of hyperthermia in radiation oncology is well established. Many publications cover the whole field of possibilities and problems of this therapeutic modality. The new development of interstitial and intracavitary hyperthermia, however, is not well known: there are only a few relevant publications in different journals. Therefore, it was appropriate that SAUER and SEEGENSCHMIEDT organized an international meeting on this topic, where experiences with this new and promising technique were compiled and discussed by experts. The papers of this symposium together with additional review papers and clinical studies are published in this volume. The publication begins with the physical and biological background of interstitial and intracavitary hyperthermia continues with comprehensive review papers on clinical topics and then gives examples for a wide variety of clinical applications. This volume will contribute to better understanding and application of the treatment possibilities of radio oncology in combination with this new treatment modality.

The incidence, diagnosis, and treatment of gynecologic cancer have undergone major changes during the past 20 years. In addition to significant changes in the incidence of the diseases, there has been extensive application of new technologies in the field. - While the incidence of invasive cancers of the cervix has diminished sharply, there has been a marked increase in the number of patients presenting with in situ carcinomas of the cervix. This has resulted primarily from better education but also from the regular use of Papanicolaou screening for early diagnosis. This trend has been associated with a major shift from late stage disease to early stage disease, which has led to more effective utilization of surgical techniques in primary management, with less emphasis on radiation therapy techniques. Almost invariably, in situ cancers of the cervix can be cured by surgical management, and high cure rates can be achieved by surgical techniques in early invasive cancers of the cervix. Therefore, more patients are receiving definitive surgical management rather than definitive radiation therapy management. - Because of its tendency to present at an early stage, cancer of the endometrium is now more commonly managed by surgical techniques. Postoperative radiation therapy is used when there is persistent residual disease following surgery, a more advanced disease stage than indicated by preliminary study, transection or spillage of tumor during the operative procedure, or positive cytology at the time of the original surgery.

Die Strahlentherapie der otorhinolaryngologischen Tumoren sowie der Tumoren des Re- spirationstraktes stellt eine der wichtigsten Aufgaben des Radioonkologen dar. Er ist hier wesentlicher Partner im Rahmen der interdisziplinaren Onkologie und betreut gemeinsam mit dem Otorhinolaryngologen, dem Chirurgen oder Pulmologen die Patienten. In einzelnen Bereichen, so beim kleinzelligen Bronchus-Karzinom, ist eine enge Koopera- tion zwischen medizinischer Onkologie und Radioonkologie Voraussetzung einer sinnvollen Behandlung. Eine umfassende Darstellung der strahlentherapeutischen Moglichkeiten im Rahmen des Gesamtbildes der Erkrankungen der HNO-Tumoren-und der Tumoren des Respirationstrak- tes bildet damit ein wertvolles Hilfsmittel flir jeden Arzt, der mit der Behandlung dieser Tumoren befaBt ist. Die radiologischen Moglichkeiten in der Behandlung der malignen Schilddriisentumoren stellen ein Thema dar, bei dem besonders dringend eine fachkundige zusammenfassende Darstellung erforderlich wurde. Auch dieses Kapitel wird nicht nur dem Radioonkologen, sondern anderen, mit den Erkrankungen der Schilddriise befaBten Arzten eine wertvolle Hilfe sein. Hamburg H.-P. HElLMANN Preface Radiotherapy of otorhinolaryngolic tumors and tumors of the respiratory tract is one of the most important responsibilities of radio-oncologists. They are major partners in inter- disziplinary oncology and treat patients together with otorhinolaryngologists, surgeons, and pulmologists. In special problems, such as small-cell bronchial carcinoma, close cooperation between radio-oncologists and medical-oncologists is a precondition of meaningful treatment. The possible applications of radiology in treating malignant thyroid tumors also require a compre- hensive expert discussion.

The administration of chemotherapeutic agents by continuous infusion with concomitant radiation therapy heralds a new approach in the treatment of cancer. This comprehensive book on the subject includes, besides a discussion of its scientific basis, the most promising clinical data on the use of continuous infusion chemotherapy and radiation. Thus, it is an important update for clinical investigators involved in frontline research as well as for practicing physicians participating in the direct care of cancer patients. The contributions include the latest results of this new approach in a number of tumor sites. There is a detailed description of the principles of radiosensitization for malignant tumors and radioprotection for normal tissues; these are the principles which have led to concrete clinical applications. There is also a presentation of the most recent data on the beneficial effects resulting from the administration of commonly used drugs, such as 5-fluorouracil, cisplatinum and adriamycin, with concomitant radiation therapy. Much of the data has never before been published. The wealth of information in this volume makes it a valuable reference; at the same time it gives practicing physicians a detailed presentation of various therapeutic regimens which they could administer in their daily clinical practice. In the future, this innovative cancer treatment may lead to the decreased need for radical surgery and the increased ability to preserve organ function.

In the last decade brachytherapy experienced a dramatic up- swing. The introduction of new radioisotopes with favorable nuclear physical properties, computer-assisted dosimetry, and the advent of modified afterloading techniques set off this revolutionary development. The main topics discussed in this book are brain tumors and tumors of the head and neck, choroidal melanoma, breast cancer, carcinoma of the anal ca- nal, carcinoma of the prostate, and gynecological malignan- cies.

The diagnosis of cancer in a child is a devastating finding not only to the parents but often to the child. Even though the situation is relatively easy to accept among adults, it is difficult to accept among children because of their general helpless state. The advances that have been made in the management of a child with cancer in the last 20 years have been dramatic in character. These have occurred not only by virtue ofthe contributions from early diagnosis and more precise staging but also from the contribu­ tions made by surgery, radiation therapy, and the more widespread utilization of chemotherapy regimens. This volume by J. Robert Cassady sets forth the position of radiation oncology in the management of the child with cancer. Radiation therapy remains an important and significant part of the treatment of this group of diseases. The book presents the basic knowledge with regards to pediatric oncology and how it relates to radiation therapy. It gives a timely overview on the topic and is essential for all radiation oncologists involved in the management of children with cancer. Hamburg/Philadelphia, June 1994 H. -P. HEILMANN LUTHER W. BRADY Preface This book provides a thorough review of the role that radiation therapy currently plays in the management of most childhood tumors. Extensively augmented with figures and tables where appropriate, it also provides a concise review of current diagnostic and therapeutic approaches for major childhood malignancies. Extensive and up-to-date reference lists are an added benefit.

The biologic effects of radiation on normal tissues and tumors represent a complex area for investigation. These effects are of far-reaching consequence to the diagnostic radiologist and the radiation oncologist having a significant impact not only in concepts relative to radiation protection but also in concepts relative to tumor biology and its response to radiation injury. The volume edited by SCHERER, STREFFER, and TROTT represents an extension of basic radiation biology data into the effects of radiation in producing pathology in organs and tissues. The data presented by the multiple authors involved in this text cover essentially all tissues in the body with specific definition of radiopathology changes and their impact on clinical care of the patient. This volume represents an important and significant contribution toward a better understanding of these effects and the pathology produced by radiations. L. W. BRADY H.-P. HEILMANN F. HEUCK M. W. DONNER Philadelphia Hamburg Stuttgart Baltimore Preface This book represents an attempt to describe the clinical radiobiology of complications arising in different organs after radiotherapy of cancer patients. Since by their very nature malignant tumors infiltrate the organ in which they have arisen and the neighboring tissues, curative radiotherapy requires the planned irradiation of considerable amounts of healthy but potentially or microscopically involved normal tissues and organs with the full target dose. This may lead to early or late normal tissue radiation injury.

The impact of basic science radiobiological research is now being recognized of significant importance in clinical radiation oncology. Observations made in the laboratory using animals as'well as tissue culture have led to a better biologic understanding of techniques for altered fractionation, techniques for measuring tumor cell proliferation, the possi­ bilities and limitations of methods for evaluation of nonrandomized clinical studies in deriving time dose relationships for human tumors as well as a better understanding of repair kinetics in mammalian cells, fractionation sensitivity and the major impact oftechnologies to improve local/regional control with the subsequent impact on survival. These findings have led to changes in treatment schedules and have led to further close cooperation among the radiation oncologists and radiation biologists. Well support research efforts in radiation biology have a major and significant impact on the clinical care of the cancer patient. Studies that originated in the laboratory are now finding their way into clinical practice resulting in better local and regional control and improved number of patients surviving without disease.

Primary mediastinal tumors are relatively rare. The relative incidence of these tumors indicates that neurogenic tumors are the most common tumor seen constituting 21 % of all cases, thymomas 19%, lymphomas 12.5%, germ cell tumors 10%, primary carcinomas 4.6%, mesenchymal tumors 6%, endocrine tumors 6%, cysts 18%. In adults, the majority of thyroid tumors, thymomas, mediastinal germ cell tumors and teratomas are located in the superior and anterior mediastinum. Of the neurogenic tumors 18% are located in the posterior mediastinum, and 50% of mediastinal lymphomas are in the middle mediastinum. In adults, the incidence of anterosuperior, middle and posterior mediastinal tumors is about 54%, 20% and 26% respectively. However, in children the posterior mediastinum contains 63% of the lesions, the anterior mediastinum contains 26% and the middle mediastinum II %. The majority of the tumors are benign in character with a ratio of benign to malig­ nant of about 60 to 40. The relative incidence of malignant mediastinal tumors in children is about 50%. Even though mediastinal tumors are not common, they represent a unique problem with regards to treatment whether by surgery, radiation therapy and/or systemically administered chemotherapy. The volume by WOOD and THOMAS deals with each of these issues in detail and presents a logical and important approach to the management of mediastinal tumors.

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.

Bladder cancer represents a major challenge to the oncologist. In spite of new tech­ niques for early diagnosis and innovative imaging procedures for staging, the outcome in terms of cure has not improved during the past ten years. Fortunately, about 74% of the patients present with localized disease, with 18% presenting with localized and regional disease, and 3% with distant metastases at diagnosis. In accordance with the stage at presentation, 94% of patients with localized disease are controlled at 5 years, as are 50% of patients with local and regional disease but un­ fortunately only 7% of those with distant disease. The survival data for Afro-Americans are more grave, with only 79% of patients with localized disease surviving at 5 years, 38% with local and regional disease, and 4% with disseminated disease. Even after 5 years, however, patients continue to fail not only locally and regionally but also with disseminated disease, thereby creating enigmas as to the continued influence of basic molecular changes, basic etiologic agents, and unsuspected more advanced disease, as well as demonstrating the inadequacies of local surgical treatment programs. These factors have led to braoder programs of combined integrated multimodal treatment earlier in the course of the disease process. Clearly, these newer innovative programs have placed increasing emphasis on the combination of surgery with radiation therapy and chemotherapy.

The American Cancer Society anticipates that during 1995, 244000 new cases of cancer of the prostate will have been diagnosed in the United States, with 40400 deaths from the disease process. The rapid increase in the actual number of new cases in the United States is directly related to more regularized digital rectal examinations and the more frequent and widespread use of prostate-specific antigen (PSA) screening programs. As a conse­ quence, major controversies have emerged in how best to manage the patient with cancer of the prostate. These include the necessity of PSA screening programs, how to interpret PSA values, what imaging studies are most appropriate for definition of the true extent of the disease process, the value of pretreatment surgical staging of the disease process, and the value of different treatments. The latter encompass a wide range of options: observa­ tion, radical prostatectomy, the Walsh-type prostatectomy procedure, definitive external beam radiation therapy, local interstitial implantation using iodine-125, iridium-l92, or palladium-103, orchiectomy, cryosurgery, hyperthermia, and various antitestosterone agents such as estrogens or LH,RH agonists. The present volume deals with the major parameters of controversy with regard to cancer of the prostate and will enable the reader to acquire a better understanding of the disease and how best it might be managed to achieve an optimal outcome with a minimum of complications.