Key Points

• Normal cells and tumor cells show a radiation response at a rate proportional to their rate of proliferative turnover.
• A series of fractionated doses amplifies the therapeutic difference between normal tissues and tumor.
• The four R’s—repair of cellular injury, redistribution within the division cycle, repopulation by surviving cells, and reoxygenation of the tumor—are the major players in determining the response to radiation.
• For locally advanced esophageal cancer, a trimodality treatment (concurrent chemoradiation therapy followed by surgery) is standard of care.
• The target volume in radiotherapy should encompass the macroscopic and microscopic tumor. The question remains if clinically uninvolved drainage area lymph node stations have to be included in the irradiated volume and whether such policy eventually improves the long-term survival as compared with a more limited target volume.

Radiation produces breaks in the DNA. Single-strand breaks are of little consequence because the cell has efficient mechanisms to repair them. These mechanisms have evolved to protect us against injury from environmental radiation and other toxins. However, if the radiation dose is high enough, two single-strand breaks will be close enough to one another to cause a double-strand break. Without intact templates for their mutual repair, double-strand breaks may be misrepaired and disrupt the integrity of the chromosome. Chromosomal aberrations do not normally affect survival or function of the cells between the time they are irradiated and the time they attempt to replicate. Thus, normal tissues and tumors show a radiation response at a rate proportional to their rate of proliferative turnover. The mucosa of the esophagus, which is actively proliferative, develops a detectable reaction within 2 or 3 weeks of first exposure in a course of radiation treatment. Slowly proliferating tissues such as lung, bones, and spinal cord respond slowly to x-irradiation with signs of damage only months or years after exposure.

Radiation also induces a variety of stress responses leading quickly to apoptosis. With notable exceptions (e.g., lymphocytes, serous cells in the parotid), apoptosis occurs more frequently in proliferating than in nonproliferating cell populations and therefore contributes to the early development of a response.