Treatment volume and tissue tolerance

Abstract

Hypotheses regarding tissue organization and radiation response were described and, on the basis of simple modeling, tentative conclusions were drawn regarding the influence on “tolerance” doses of tissue organization and the volume of an organ irradiated. (1) A functional subunit (FSU) may be defined structurally (e.g. as in a nephron), or only functionally, as the largest unit of cells capable of being regenerated from a surviving clonogenic cell without loss of the specified function. (2) Functional subunits may be arranged in parallel or in series: in parallel they give rise to graded dose responses, whereas in series, they give rise to threshold binary, or quantum responses. (3) Tolerance doses are a function of the number and radiosensitivity of target cells in an FSU, tissue organization and the functional reserve (i.e. the proportion of functional subunits necessary for adequate organ function). (4) An influence of treatment volume on “tolerance” doses is more likely to depend upon tissue organization than upon differences in cellular radiosensitivity. (5) The volume of tissue irradiated would be expected to be irrelevant to the “tolerance” of tissues showing a graded dose response (e.g. skin desquamation), except when the injury becomes severe, when tolerance for a large severe wound is likely to be less than for a small volume of injury, for non-radiobiological reasons. (6) Tissues with FSU's arranged in series, for example, spinal cord or peritoneal sheath along small bowel, should show a threshold-binary response. Sigmoid dose response curves should have a lower threshold and be steeper the larger the treatment volume. The effect of increase in volume is greatest with changes in small volumes: once a large number of FSU's are being irradiated, a further increase in volume has little effect on the position or slope of the probability curve for such complications. (7) Because their sigmoid dose-response curves are steep, threshold-binary tissues are sensitive to small increases in “biologically effective” dose. For example, when the spinal cord is treated with large dose fractions the biological effectiveness per unit of dose increases sharply. Thus, using a large volume together with large dose fractions, as could happen in palliative prescriptions, could augment the danger of myelitis. (8) Because of the low density of cells potentially the “targets” for peritoneal adhesion formation and small bowel obstruction, and because a measurable incidence of obstruction is usually already “tolerated,” the most marked effect of changes of treatment volume on complications in clinical practice may be found with postoperative abdominal and pelvic irradiation.