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Cancer of the breast — Primary irradiation
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Radiation Oncology, Biology, Physics Volume 21, Supplement 1
103 CANCER OF THE BREAST - PRIMARY IRRADIATION Barbara L. Fowble, M.D. Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 In the last 10 years both prospective randomized clinical trials and retrospective series have established the role of conservative surgery and radiotherapy as an alternative to mastectomy in the treatment of early breast cancer. This discussion will focus on some of the unresolved issues in the conservative management of breast cancer including patient selection, the extent of surgery in the breast, the importance of microscopic margins of resection, radiotherapy technique including the region to be treated as well as the role of the boost, and the integration of adjuvant systemic chemotherapy with primary radiotherapy. Each of these issues will be addressed and current treatment policies and recommendations will be outlined. The important aspects of the follow-up of the conservatively treated breast will also be presented. An emphasis will be placed on the long term results of conservative surgery and radiation both in terms of overall and disease-free survival as well as breast recurrence rate. Factors which predict for breast recurrence will be analyzed. The diagnosis and treatment of breast and regional node recurrences will be reviewed. Data regarding the omission of radiation in breast conservation treatment will be presented as well as the clinical trials that address this issue. The role of neoadjuvant chemotherapy and radiation with or without conservative surgery will be presented. Finally, the role of conservative surgery and radiotherapy in the treatment of noninvasive intraductal caminoma will be discussed.
104 MONOCLGNAL ANTIBODIES Donald J. Buchsbaum, Ph.D. Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL 35233 The use of radionuclide-labeled monoclonal antibodies (MoAbs) against human tumor-associated antigens for the detection and treatment of cancer has been the focus of much recent investigation. Radiolabeled MoAbs offer potential advantages over conventional diagnostic and therapeutic procedures by providing greater sensitivity and specificity as a result of preferential binding to tumor cells. The uuruose of this refresher course is: 1) to summarize the techniaues for the uroduction and radiolabeline of MoAbs. 2) to summarize the work &aihas been done with radiolabeled MoAbs for the localiz.ation*and tmatment of cancer, primarily in ex~&rimental an&J models, 3) to review methods to increase MoAb tumor targeting and radioimmunotherapy, and 4) to discuss new trends in the use of radiolabeled MoAbs for the treatment of cancer. The advent of the hybridoma technology in 1975 made possible the production of large quantities of a single antibody, a monoclonal antibody. Protein iodination and chelation techniques provide MoAbs conjugated to a variety of radionuclides. The choice of mdionuclide for diagnosis or therapy is influenced by the physical and chemical properties of the nuclide, and the biodistribution and biological half-life of the radiolabeled MoAb. The radionuclides that are most widely used for radiolabeling MoAbs can be grouped as emitters of either gamma rays, high energy electrons, alpha particles, or Auger electrons. Although gamma rays am useful for imaging, their role in therapy is controversial. They increase the total body dose which may have some utility in sensitive disseminated diseases like lymphomas, but will also increase hematologic toxicity. Beta emitters deposit energy more locally but still over many cell diameters. The average track length is a function of the energy of the emission. This is in contrast to alpha emitters and Auger electrons, whose average path lengths are substantially less than 1 cell diameter. Auger emitters may require transport to the nucleus in otder for the radiolabeled antibody to be cytotoxic. A number of approaches that may increase the degree of tumor localization and therapeutic efficacy of radiolabeled MoAbs will be discussed, including quantity of administered antibody, frequency of administration, selection of radionuclide, regional administration of antibody, irradiation of the tumor site, use of second generation MoAbs, fragments of antibodies, chimeric antibodies, bifunctional antibodies, human MoAbs, cocktails of antibodies, use of a second antibody, use of interferon and radiosensitizers. A particular concern in therapy is to improve radiolabeling techniques, or to develop other approaches to decrease radiation to normal tissues. In the future, one can expect the development of new MoAbs with greater specificity for particular tumor types. With this additional information, it is hoped that radiolabeled MoAbs wlll become effective agents for the treatment of cancer.
105 ROLE OF RADIATION THERAPY IN MANAGEMENT OF PATIENTS WITH SARCOMA OF SOFT TISSUE Herman D. Suit, M.D. Dept. of Radiation Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Sarcomas of soft tissue comprise the malignant tumors arising from the mesenchymal soft tissue of all histologic types and the peripheral nerves at all sites within the body. There is a broad spectrum of histologic types; they are usually designated according to the apparent soft tissue of origin. In the U.S. there are approximately 5600 newly diagnosed patients with STS per year. The course will consider etiologic factors, the role of several oncogenes (Rb, ~53, etc.) and the cytogenetic characteristics of several of the samomas~ This is to be followed by a review of the epidemiology and role of environmental carcinogens and radiation. The naturaJ history will be described with reference to local invasion and spread to regional and distal sites. The evaluation of the patients suspected of a sarcoma
Radiation Oncology, Biology, Physics Volume 21, Supplement 1
103 CANCER OF THE BREAST - PRIMARY IRRADIATION Barbara L. Fowble, M.D. Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 In the last 10 years both prospective randomized clinical trials and retrospective series have established the role of conservative surgery and radiotherapy as an alternative to mastectomy in the treatment of early breast cancer. This discussion will focus on some of the unresolved issues in the conservative management of breast cancer including patient selection, the extent of surgery in the breast, the importance of microscopic margins of resection, radiotherapy technique including the region to be treated as well as the role of the boost, and the integration of adjuvant systemic chemotherapy with primary radiotherapy. Each of these issues will be addressed and current treatment policies and recommendations will be outlined. The important aspects of the follow-up of the conservatively treated breast will also be presented. An emphasis will be placed on the long term results of conservative surgery and radiation both in terms of overall and disease-free survival as well as breast recurrence rate. Factors which predict for breast recurrence will be analyzed. The diagnosis and treatment of breast and regional node recurrences will be reviewed. Data regarding the omission of radiation in breast conservation treatment will be presented as well as the clinical trials that address this issue. The role of neoadjuvant chemotherapy and radiation with or without conservative surgery will be presented. Finally, the role of conservative surgery and radiotherapy in the treatment of noninvasive intraductal caminoma will be discussed.
104 MONOCLGNAL ANTIBODIES Donald J. Buchsbaum, Ph.D. Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL 35233 The use of radionuclide-labeled monoclonal antibodies (MoAbs) against human tumor-associated antigens for the detection and treatment of cancer has been the focus of much recent investigation. Radiolabeled MoAbs offer potential advantages over conventional diagnostic and therapeutic procedures by providing greater sensitivity and specificity as a result of preferential binding to tumor cells. The uuruose of this refresher course is: 1) to summarize the techniaues for the uroduction and radiolabeline of MoAbs. 2) to summarize the work &aihas been done with radiolabeled MoAbs for the localiz.ation*and tmatment of cancer, primarily in ex~&rimental an&J models, 3) to review methods to increase MoAb tumor targeting and radioimmunotherapy, and 4) to discuss new trends in the use of radiolabeled MoAbs for the treatment of cancer. The advent of the hybridoma technology in 1975 made possible the production of large quantities of a single antibody, a monoclonal antibody. Protein iodination and chelation techniques provide MoAbs conjugated to a variety of radionuclides. The choice of mdionuclide for diagnosis or therapy is influenced by the physical and chemical properties of the nuclide, and the biodistribution and biological half-life of the radiolabeled MoAb. The radionuclides that are most widely used for radiolabeling MoAbs can be grouped as emitters of either gamma rays, high energy electrons, alpha particles, or Auger electrons. Although gamma rays am useful for imaging, their role in therapy is controversial. They increase the total body dose which may have some utility in sensitive disseminated diseases like lymphomas, but will also increase hematologic toxicity. Beta emitters deposit energy more locally but still over many cell diameters. The average track length is a function of the energy of the emission. This is in contrast to alpha emitters and Auger electrons, whose average path lengths are substantially less than 1 cell diameter. Auger emitters may require transport to the nucleus in otder for the radiolabeled antibody to be cytotoxic. A number of approaches that may increase the degree of tumor localization and therapeutic efficacy of radiolabeled MoAbs will be discussed, including quantity of administered antibody, frequency of administration, selection of radionuclide, regional administration of antibody, irradiation of the tumor site, use of second generation MoAbs, fragments of antibodies, chimeric antibodies, bifunctional antibodies, human MoAbs, cocktails of antibodies, use of a second antibody, use of interferon and radiosensitizers. A particular concern in therapy is to improve radiolabeling techniques, or to develop other approaches to decrease radiation to normal tissues. In the future, one can expect the development of new MoAbs with greater specificity for particular tumor types. With this additional information, it is hoped that radiolabeled MoAbs wlll become effective agents for the treatment of cancer.
105 ROLE OF RADIATION THERAPY IN MANAGEMENT OF PATIENTS WITH SARCOMA OF SOFT TISSUE Herman D. Suit, M.D. Dept. of Radiation Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Sarcomas of soft tissue comprise the malignant tumors arising from the mesenchymal soft tissue of all histologic types and the peripheral nerves at all sites within the body. There is a broad spectrum of histologic types; they are usually designated according to the apparent soft tissue of origin. In the U.S. there are approximately 5600 newly diagnosed patients with STS per year. The course will consider etiologic factors, the role of several oncogenes (Rb, ~53, etc.) and the cytogenetic characteristics of several of the samomas~ This is to be followed by a review of the epidemiology and role of environmental carcinogens and radiation. The naturaJ history will be described with reference to local invasion and spread to regional and distal sites. The evaluation of the patients suspected of a sarcoma