Although radiation therapy is frequently given as a single treatment modality, it is also used in combination with other treatment modalities. When combined with surgery, radiation therapy can be given either as preoperative or postoperative radiation therapy. The potential advantages of preoperative radiation therapy include eradication of subclinical or microscopic disease beyond the margins of the surgical resection, diminished tumor implantation by decreasing the number of viable cells within the operative field, sterilization of metastases in lymph nodes inside and/or outside of the operative field, decrease in the potential for dissemination of viable clonogenic tumor cells, and an increase in the possibility of resectability. The main disadvantage of preoperative radiation therapy is possible interference with the process of normal healing of tissues affected by irradiation. The potential advantages of postoperative radiation therapy include elimination of subclinical disease remaining in the tumor bed, the possibility to administer higher doses of radiation therapy for overt disease found in surgical specimens, and the possibility to tailor the irradiation fields according to the pathological staging. The delay in initiation of postoperative radiation therapy until wound healing is completed is a potential disadvantage of postoperative radiation therapy. In addition, radiation effects may be impaired by vascular changes occurring post-surgery in the operative field.
Radiation therapy and chemotherapy are combined in order to improve effects on both local/regional and distant levels (Halperin et al., 2004; Smith and McKenna, 2004). There are four possibilities that this combination may explore: spatial cooperation (drugs affect tumor cells outside the radiation therapy field), independent cell kill (drugs can independently affect tumor cells within the radiation therapy field), enhancement (drugs can enhance effects in radiation therapy field), and protection of normal tissues (Steel, 2002; Hall and Giacca, 2006). Whereas the first two mechanisms do not require interaction, the latter two depend on the interaction of these two treatment modalities. One mechanism does not necessarily exclude employment of another mechanism; for example, an active agent can act on a local level as well as affect micro metastasis outside the radiation therapy field. There are several generations of agents used in combined radiation therapy and chemotherapy, and clinical research in this field is one of the most important research areas in human oncology. Recent years also brought improvements in molecular oncology that ultimately led to the introduction of targeted therapy. Agents such as those targeting epidermal growth factor receptor hold promise of improving loco regional tumor control at least in some tumor types, such as head and neck, and another class of agents is targeting tumor microvasculature.
Timing of combined radiation therapy and chemotherapy can include, first, chemotherapy followed by radiation therapy given with the main goal of addressing the issue of micro metastasis control and local or regional tumor decrease or down staging, as well as using reduced irradiation fields, thus decreasing the radiation morbidity (Halperin et al., 2004; Smith and McKenna, 2004; Price and Sikora, 2005). It can also include, second, adjuvant or consolidation timing when chemotherapy follows radiation therapy. A third possibility is concurrent radiation therapy and chemotherapy, aimed mostly at an improvement on a local or regional level. A fourth possibility involves alternating radiation therapy with chemotherapy in order to increase therapeutic benefit by decreasing toxicity, which can occur with any concurrent regimen, by giving both modalities separated by short periods of time. In addition to these, many hybrid combinations exist that explore different mechanisms of the combined treatment approach. Combination radiation therapy and chemotherapy is nowadays considered the standard of treatment in many tumor types, especially for locally advanced, inoperable cases.
A combined treatment modality approach may also include all treatment methods. Examples of such combination may include postoperative treatment of breast cancer or gastric cancer. Frequently, less radical surgery followed by radiation therapy with or without chemotherapy yields the same local tumor control at the primary tumor site and survival as do radical procedures such as is the case in soft tissue sarcomas or breast cancer. This approach offers organ preservation and is frequently coupled with an improvement in functioning and quality of life.
In addition to these, hormonotherapy is frequently used in hormone-sensitive tumors such as those of breast or prostate. Its use and timing largely depends on initial and/or postsurgical tumor volumes, hormone receptor status, and administration of other treatment modalities (surgery and/or chemotherapy).