Biological basis of radiation sensitivity. Part 1: Factors governing radiation tolerance

Local tumor recurrence after radiation therapy is due primarily to the failure to eradicate all of the tumor cells within the treatment fields. Theoretically, all cancers could be controlled locally if a sufficiently high radiation dose could be delivered to a treatment volume that encompassed all of the tumor cells. In practice, however, the administration of a radiation dose high enough to sterilize all of the tumor cells would pose an unacceptably high risk of severe damage to normal tissues. Technologic improvements in the delivery of therapeutic radiation have led to some improvements in the therapeutic ratio (i.e., the ratio of the dose required to eradicate every tumor cell to the dose that produces unacceptable normal tissue toxicity). Further significant improvements in the therapeutic ratio will drive from an understanding of the mechanisms governing the sensitivity of malignant and normal cells to radiation. Part 1 of this two-part article reviews the clinical and tissue kinetic factors that govern the sensitivity of normal tissues and organs to ionizing radiation. Part 2, which will appear in next month's issue, describes recent insights into the cellular and molecular pathways that determine the sensitivity of normal cells and tumor cells to radiation.