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Surgery Surgery is used for diagnosis, staging of cancer, tumor removal, and palliation (i.e., relief of symptoms) when a cure cannot be achieved. 52 The type of surgery to be used is determined by the extent of the disease, the loca- tion and structures involved, the tumor growth rate and invasiveness, the surgical risk to the patient, and the quality of life the patient will experience after the sur- gery. If the tumor is small and has well-defined margins, the entire tumor often can be removed. If, however, the tumor is large or involves vital tissues, surgical removal may be difficult if not impossible. RadiationTherapy Radiation can be used as the primary method of treat- ment, as preoperative or postoperative treatment, with chemotherapy, or along with chemotherapy and sur- gery. 53–57 It can also be used as a palliative treatment to reduce symptoms in persons with advanced can- cers. It is effective in reducing the pain associated with bone metastasis and, in some cases, improves mobility. Radiation also is used to treat several oncologic emer- gencies, such as spinal cord compression, bronchial obstruction, and hemorrhage. Radiation therapy exerts its effects through ioniz- ing radiation, which affects cells by direct ionization of molecules or, more commonly, by indirect ionization. Indirect ionization produced by x-rays or gamma rays causes cellular damage when these rays are absorbed into tissue and give up their energy by producing fast- moving electrons. These electrons interact with free or loosely bonded electrons of the absorber cells and sub- sequently produce free radicals that interact with criti- cal cell components (see Chapter 2). It can immediately kill cells, delay or halt cell cycle progression, or, at dose levels commonly used in radiation therapy, cause dam- age to the cell nucleus, resulting in cell death after rep- lication. Cell damage can be sublethal, in which case a single break in the strand can repair itself before the next radiation insult. Double-stranded breaks in DNA are generally believed to be the primary damage that leads to cell death. Cells with unrepaired DNA damage may continue to function until they undergo cell mito- sis, at which time the genetic damage causes cell death. The therapeutic effects of radiation therapy derive from the fact that the rapidly proliferating and poorly differentiated cells of a cancerous tumor are more likely to be injured by radiation therapy than are the more slowly proliferating cells of normal tissue. To some extent, however, radiation is injurious to all rapidly proliferating cells, including those of the bone marrow and the mucosal lining of the gastrointestinal tract. This results in many of the common adverse effects of radia- tion therapy, including infection, bleeding, and anemia due to loss of blood cells, and nausea and vomiting due to loss of gastrointestinal tract cells. In addition to its lethal effects, radiation also produces sublethal injury. Recovery from sublethal doses of radiation occurs in the interval between the first dose of radiation and subse- quent doses. This is why large total doses of radiation

miniature assays to detect and quantify the expression of large numbers of genes at the same time. 2 DNA arrays are now commercially available to assist in making clini- cal decisions regarding breast cancer treatment. In addi- tion to identifying tumor types, microarrays have been used for predicting prognosis and response to therapy, examining tumor changes after therapy, and classifying hereditary tumors. 2 Staging and Grading of Tumors The two basic methods for classifying cancers are grad- ing according to the histologic or cellular characteristics of the tumor and staging according to the clinical spread of the disease. Both methods are used to determine the course of the disease and aid in selecting an appropriate treatment or management plan. Grading of tumors involves the microscopic exami- nation of cancer cells to determine their level of dif- ferentiation and the number of mitoses. The closer the tumor cells resemble comparable normal tissue cells, both morphologically and functionally, the lower the grade. Accordingly, on a scale ranging from grade I to IV, grade I neoplasms are well differentiated and grade IV are poorly differentiated and display marked anaplasia. 2,3 The clinical staging of cancers uses methods to deter- mine the extent and spread of the disease. It is useful in determining the choice of treatment for individual patients, estimating prognosis, and comparing the results of different treatment regimens. The significant criteria used for staging that vary with different organs include the size of the primary tumor, its extent of local growth (whether within or outside the organ), lymph node involvement, and presence of distant metastasis. 2,3 This assessment is based on clinical and radiographic exami- nation (CT and MRI) and, in some cases, surgical explo- ration. Two methods of staging are currently in use: the TNM system (T for primary tumor, N for regional lymph node involvement, and M for metastasis), which was developed by the Union for International Cancer Control, and the American Joint Committee (AJC) system. 2 In the TNM system, T1, T2, T3, and T4 describe tumor size, N0, N1, N2, and N3, lymph node involvement; and M0 or M1, the absence or presence of metastasis . In the AJC system, cancers are divided into stages 0 to IV incorpo- rating the size of the primary lesions and the presence of nodal spread and distant metastasis. CancerTreatment The goals of cancer treatment methods fall into three categories: curative, control, and palliative. The most common modalities are surgery, radiation, chemother- apy, hormonal therapy, and biotherapy. The treatment of cancer involves the use of a carefully planned pro- gram that combines the benefits of multiple treatment modalities and the expertise of an interdisciplinary team of specialists including medical, surgical, and radiation oncologists; clinical nurse specialists; nurse practitio- ners; pharmacists; and a variety of ancillary personnel.