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With continued advances in strategies to detect cancer early and treat it effectively along with the aging of the population, the number of individuals living years beyond a cancer diagnosis can be expected to continue to increase. Most therapeutic modalities for cancer, while beneficial and often lifesaving against the diagnosed malignancy, are associated with a spectrum of late complications ranging from minor and treatable to serious or, occasionally, potentially lethal. Investigators conducting research among cancer survivors are reporting that long-term or late adverse outcomes of cancer and its treatment are more prevalent, serious, and persistent than expected in survivors of both pediatric and adult cancer. However, these adverse sequelae remain poorly documented and understood, especially among those diagnosed as adults. These findings underscore the need for continued cancer survivorship research. [ABSTRACT FROM AUTHOR]

Philosophically, the TNM Cancer Classification is based on the premise that all malignant tumors have a similar life cycle. Cancers originate in a normal tissue, then spread regionally into lymph nodes and then to systematic distant sites hematogenously. In a parallel fashion, the conceptual design of a normal tissue TNM classification is based on a similarity of normal tissue injury following multimodal cancer treatment which is often greatest in the structure/organ of cancer origin and decreases in neighboring normal tissues. There may be a generalized or systemic toxicity. NT = The normal Tissue, anatomic structure, organ in which the cancer arose and spreads initially. NN = Neighboring or surrounding normal tissues or organs, viscera that are not involved by the tumor but in the regional nodal drainage zone. NM = SysteMic effects that are generalized and include hematologic, hepatic toxicity, weight loss. [ABSTRACT FROM AUTHOR]

Cancer-related fatigue (CRF) is widely recognized as the most distressing adverse effect experienced by cancer patients. We report on a large prospective survey conducted in part to characterize CRF severity in relation to depression and shortness of breath and to compare symptom severity in radiation and chemotherapy patients and over time. Careful characterization of CRF will aid in the development of effective methods to manage this disabling symptom. [ABSTRACT FROM AUTHOR]

Sophisticated planning systems now readily provide the treatment planner with an increasing number of competing treatment plans. There is, however, no generally accepted method to compare and rank these competing treatment plans. A "realistic" approach utilizing decision analysis tools to rank treatment plans based on quality adjusted life years (QALY) expectancy was developed. The decision analysis methods were applied to the concept of uncomplicated tumor control probability (UTCP). The expected outcome for an anticipated course of radiation was described as a series of probabilities: alive, free of disease without complication; alive with disease; alive with complication, etc. For each of these states of health, a utility can be assigned based on published work or empirical estimates. The total QALYs for a particular treatment plan represent the product of duration-weighted states of health. The formalism for UTCP was generalized to incorporate the total QALY (UTCPQALY) for a particular treatment. [ABSTRACT FROM AUTHOR]

Radiation has an established place in the diagnosis and therapy of cancer. About 10% of patients presenting with cancer at major centers have a second malignancy. Most are a result of genetic predisposition or continued lifestyle, but some are treatment-related. For example, in patients treated for prostate cancer, about 1 in 70 develop a radiation-induced cancer by 10 years post therapy. Most second cancers are carcinomas arising in organs close to or remote from the treatment site. There is also an incidence of sarcomas within or close to the treatment volume, in the high dose region. The absolute risk is small, but the relative risk is high for these tumors. Animal studies show that the risk of a radiation-induced sarcoma approaches 100% following high doses in animals followed for a lifetime. This suggests that the reason for the low sarcoma risk in patients receiving radiotherapy for prostate cancer is their short life expectancy. [ABSTRACT FROM AUTHOR]

The renin-angiotensin system, local or systemic, plays a key role in normal tissue radiation injury. Angiotensin converting enzyme (ACE) inhibitors, which act to attenuate the conversion of angiotensin I to angiotensin II, are beneficial in mitigating experimental renal, lung, or brain normal tissue radiation injury. The benefit of ACE inhibitors and angiotensin II blockers has been particularly well documented in experimental radiation nephropathy, for either mitigation or treatment. The mechanism for this benefit remains incompletely understood. In particular, control of hypertension, proteinuria, or radiation-induced cell proliferation alone does not appear to determine the benefit of ACE inhibitors or angiotensin II blockers. Nonetheless, the significant experimental benefit of those agents fully justifies their use in human radiation nephropathy. Clinical trials using ACE inhibitors are underway in subjects undergoing radiation-based bone marrow transplantation and also in subjects undergoing curative radiotherapy for lung cancer. [ABSTRACT FROM AUTHOR]

The tolerance of normal tissues to irradiation remains the major limitation to the use of ionizing radiation in the treatment of many malignancies. Recent progress in understanding the mechanisms underlying the development of late injury following cancer treatment points toward chronic hypoxia and oxidative stress as an important contributor to this problem. In this chapter, the authors review the evidence to support this new paradigm of late normal tissue injury and discuss potential approaches to the prevention and treatment of this condition. [ABSTRACT FROM AUTHOR]

The recognition and assessment of normal tissue injury is an important aspect of radiation oncology practice and a critical endpoint in clinical studies. One of the major challenges in the study of radiation (RT)-induced normal tissue injury is determining the appropriate endpoint. Patients' symptoms have obvious clinical relevance; however, the scoring of symptoms is relatively subjective. Conversely, radiologic endpoints are potentially quantifiable and are available for objective study. Furthermore, radiologic evidence of sub-clinical normal tissue injury is far more common than are clinical symptoms, providing a larger number of patients with identifiable injury for study. We review herein radiologically-detected normal tissue injury as it relates to the lung, heart, brain, and salivary glands. The concepts described are likely to be similar for other organs. We conclude that: (1)radiologically-defined normal tissue injury in human patients may be related to longterm, clinically meaningful injury, but further study is needed to better quantify this association; [ABSTRACT FROM AUTHOR]

Radiation therapy is an effective means of killing tumor cells, although this effectiveness is tempered by limitations of the normal tissue to the adverse effects of radiation. An excellent example of this is radiation treatment for thoracic tumors, in particular, lung cancers. Despite advances in the technical delivery of radiation by three-dimensional (3D) planning via computed tomography (CT), radiation-induced injury to normal lung tissue still occurs in a large proportion of treated patients. The primary endpoints for radiation-induced pulmonary toxicity include early onset pneumonitis and late onset fibrosis. A significant amount of research has produced some insight into the mechanism(s) behind this injury. This knowledge has provided potential targets for drug development that could improve the therapeutic ratio for radiation by reducing both early and late toxicity. In this article, we review and update the pathologic mechanisms underlying radiation-induced lung injury as well as potential treatments, with particular interest in cell adhesion molecules and inflammation. [ABSTRACT FROM AUTHOR]

Endothelial cells (EC) are the most radiosensitive among the fixed elements of the mesenchyme. Depending on dose, ionizing radiation can produce lethal or sublethal injury to EC. The latter may alter considerably the complex physiology of the endothelium. Some functions are inhibited or abolished: fibrinolysis, synthesis of various enzymes and cytokines, attachment of EC to the basal lamina, angiogenesis, etc. [ABSTRACT FROM AUTHOR]

Radiation oncologists, biologists, epidemiologists, and health physicists have a long-standing interest in understanding the risk, etiology, prevention, and treatment of radiation damage to normal tissue as a consequence of exposure of healthy populations, as well as from cancer treatment. The recent threat of radiological and nuclear terrorism as a consequence of a radiological dispersion device (RDD) or improvised nuclear device (IND) has raised public awareness of the consequences of radiation exposure. Normal tissue injury results from local cellular and tissue processes directly damaged by the radiation, as well as from the response of the entire organism. The development of effective medical countermeasures to protect, mitigate, and/or treat normal tissue injury requires investigation from basic molecular mechanisms to multicellular systems to relevant animal models to clinical trials. With renewed interest and support, the radiation biology/oncology research community has a critical opportunity for scientific investigation and service to society by advancing knowledge, helping oncology patients, and enhancing the well-being of entire populations living under the threat of accidental or intentional radiation exposure. [ABSTRACT FROM AUTHOR]

Surveillance and management for therapy-related normal tissue damage in survivors of both childlhood and adult-onset cancer is necessary to maximize health-related quality of life. Progress by the (Children's Oncology Group (COG) can be modeled or adapted for a adult malignancy, and is described in this report. Investigators from COG developed risk-based, exposure-related guidelines to provide recommendations for screening and management of late effects that may arise as a result of therapeutic exposures used during treatment for childhood, adolescent and young adult cancer. The guidelines are both evidences-based and grounded in the collective clinical experience of experts providing clinical care to thesw patient populations. A therapy-based design was choses to permit modular formatting of the guidelines by therapeutic exposure and based on the patient's age presenting features, and treatment era. Multidisciplinary system-based (e.g., cardiovascular, neurocognitive, reproductive, etc.) task forces organized within the COG Late Effects Committee are responsible for monitoring the literature, evaluating guideline content, and providing recommendations for guideline revision as new information becomes available. [ABSTRACT FROM AUTHOR]