Current Scientific Issues Related to Clinical Radiation Oncology

As an introduction to the Radiation Research Program Workshop,1 this paper will briefly review the current state of clinical radiation oncology and propose questions designed to stimulate translational research in molecular and cellular biology related to the practice of radiation oncology. The goals of cancer treatment are obvious: to provide cure or extend life, and, if this is not possible, to provide relief of symptoms to improve quality of life. For both curative and palliative treatment, the goal is to preserve the function of normal tissue. Acute toxicity of treatment is expected and may include some "acceptable" risk of morbidity and mortality. Late effects may not become manifest for years or decades and include organ dysfunction and secondary malignancies, the latter possibly due to a combination of genetic and treatment-related factors. Specialists in clinical oncology disciplines are classically divided into three general areas based on the current established therapeutic tools: surgery for removal of the tumorous tissue; radiation oncology for delivery of energy to the tumor and surrounding regional tissue; and medical (and pediatric) oncology for the delivery of systemic agents to treat both local and systemic disease sites. The lines of distinction between disciplines are less well defined in an effective multi-modality setting, and there should be no boundaries when considering the basic science of cancer and the development of improved therapies. Being an "expert" in clinical oncology today means that one is knowledgeable about the indications, risks and benefits of currently established therapies. Even though these therapies are empirically derived and generally nonspecific in their effects, they have resulted in a substantial increase in the cure of pediatric neoplasms, lymphomas and leukemias; important advances in the functional results for breast, head and neck, gastrointestinal and prostate cancers and sarcomas; and small improvements in outcome in a range of non-hematological solid tumors, such as breast and colon cancer. However, for most cancers there has been little improvement in overall survival except for that to be expected as a result of earlier detection using a variety of modern methods. Even those patients treated successfully are often exposed to potentially long-term toxicity. The revolution in molecular and cellular biology has great promise for the future of clinical oncology. This revolution has provided the opportunity for new more specific therapies. The "expert" of tomorrow will be well versed not only in the technical and biological aspects of treatment, but also in the fundamental concepts underlying oncogenesis, tumor progression and response/resistance to treatment (1). Tomorrow's investigators will require a good working knowledge of the details of modern biology and a collaborative research environment. In this presentation, the current state of the art of clinical radiation oncology is put in context with potential benefits from translational and basic research. To make this clinically relevant, the stages from oncogenesis through follow-up will be followed, with points emphasized that are particularly relevant to radiation oncology (2). It is acknowledged that it is not possible to be encyclopedic in this article, and only a few examples of a particular concept will be given. Within each section, a few "clinically relevant" research issues will be proposed that lend themselves to translational research.