Chapter 23 Time, Dose, and Fractionation in Radiotherapy Flashcards
Fig 23.1 explain
The multifraction regimens commonly used in conventional radiation therapy are a conse-quence largely of radiobiologic experiments per-formed in France in the 1920s and in the 1930s. It was found that a ram could not be sterilized by exposing its testes to a single dose of radia-tion without extensive skin damage to the scro-tum, whereas if the radiation was spread out over a period of weeks in a series of daily fractions, sterilization was possible without producing un-acceptable skin damage (Fig. 23.1). It was postu-lated that the testes were a model of a growing tumor, whereas the skin of the scrotum repre-sented a dose-limiting normal tissue. The rea-soning may be fl awed, but the conclusion proved to be valid: Fractionation of the radiation dose produces, in most cases, better tumor control for a given level of normal tissue toxicity than a single large dose
THE FOUR Rs OF RADIOBIOLOGY
Repair of sublethal damage
Reassortment of cells within the cell cycle Repopulation
Reoxygenation
Explain basis of fractionation in radiotherapy
Dividing a dose into several fractions spares normal tissues because of repair of sublethal damage between dose fractions and repopulation of cells if the overall time is suffi ciently long.
It increases damage to the tumor because of reoxygenation and reassortment of cells into radiosensitive phases of the cycle between dose fractions
Explain STRANDQUIST PLOT Fig 23.2
Isoeffect curves relating the total dose to the overall treatment time for skin necrosis (A), cure of skin carcinoma (B), moist desquamation of skin (C ), dry desquamation of skin (D), and skin erythema (E)
Early attempts to understand and account for fractionation gave rise to the well-known Strandquist plot, in which total dose was plot-ted as a function of the overall treatment time
Explain nominal standard dose (NSD) system introduced by Ellis and his colleagues
according to this hypothesis, total dose for the tolerance of connective tissue is related to the number of fractions (N) and the overall time (T) by the relation
Total dose=(NSD)T 0.11N0.24
system is based on skin reaction data, it does not, in any way, predict late effects.
Experimental evidence indicates that the total dose required to produce a given biologic effect is not a power function of time, as postulated by the Ellis NSD system, but turns out to be more complex
NSD system is seldom used nowadays
Explain Fig 23.5
Highly speculative illustration attempting to extrapolate the experimental data for early- and late-responding tissue in rats and mice to principles that can be applied in clinical radiotherapy. The extra dose required to counter proliferation in early-responding tissues begins to increase after a few weeks into a fractionated regimen, certainly during the time course of conventional therapy. By contrast, conventional protocols are never suffi ciently long to include the proliferation of late-responding tissues.
Early reactions, such as reactions of the skin or of the mucosa, can be dealt with easily by the simple expedient of prolonging the overall time. Although such a strategy overcomes the problem of the early reactions, it has no effect whatsoever on the late reactions.
Explain Fig 23.6
The dose–response relationship for late-responding tissues is more curved than for early-responding tissues. In the linear-quadratic formulation, this translates into a larger alpha/beta ratio for early effects than for late effects. The ratio �/� is the dose at which the linear (�) and the quadratic ( �) components of cell killing are equal; that is, �D � �D 2 or D � �/�. (Based on the concepts of Withers.)
For early effects, �/� is large; as a conse-quence, � dominates at low doses, so that the dose-response curve has a marked initial slope and does not bend until higher doses. The linear and quadratic components of cell killing are not equal until about 10 Gy. For late effects, �/� is small, so that the � term has an infl uence at low doses. The dose-response curve bends at lower doses to appear more curved; the linear and qua-dratic components of cell killing are equal by about 2 Gy.
Proliferation as a factor in normal tissue, what is the shape of the curve relating extra dose to proliferation?
Sigmoidal
Early-responding tissues(human Skin) are triggered to proliferate within how many weeks of the start of a fractionated regimen?
4 weeks
