NSD Formula Research Articles

Proceedings: Dose-fractionation and skin tolerance to x rays in the pig; early response, late damage and combination with surgery.

We have seen the letter by Dr. J. S. Orr, and it seems to us that he has missed the point that the biological result produced by two different dose-fractionation patterns, for which the NSD formula predicts equivalent biological damage, was nonetheless quite different; there was more severe damage to the fields treated with small numbers of fractions in short overall time. No matter how one juggles with the figures or criticises our analytical methods, this much is clear—use of the NSD formula as it is recommended for clinical practice did not predict comparable levels of biological damage.

The NSD formula

Dr. Berry and colleagues deserve credit for their experimental work in the very important field of time/dose relationships (Berry et al., 1974) and the data given are interesting and instructive. The analysis and conclusions, however, lack credibility. The assumption on which their experiment is based appears to be that the ratio of the lengths of irradiated to unirradiated skin fields can be used as a scale of biological effect, presuming that the ratio decreases as the biological effect increases.

Excess late subcutaneous fibrosis after irradiation of pig skin, consequent upon the application of the NSD formula.

Abstract The development of subcutaneous fibrosis after X irradiation in courses of 1, 6 or 30 fractions has been studied quantitatively in the domestic pig. The NSD formula fails to predict the correct variation in dose for changes in the number of fractions so as to produce comparable levels of connective tissue damage even over the clinically used range from 6f./18d. to 3Of./39d.; the error in the prediction may amount to an excess dose of circa 30 per cent. The slope the iso-effect curve between 6 and 30 fractions is 0·46, compared with the combined fractionation and time factors of 0·33 in the NSD formula. The degree of late fibrosis did not correlate with the severity of the early skin reaction. The results suggest that the NSD formula is not suitable for use when planning new treatment schedules in which the number of dose fractions is reduced.

The NSD formula

Dr. Frank Ellis has let us see his comments on our paper “Excess late subcutaneous fibrosis after irradiation of pig skin, consequent upon application of the NSD formula”, and we feel that the attention of uncommitted readers should be drawn to certain points: Comment (2) of Dr. Ellis' letter quotes two references which have no bearing on the point he makes—namely that we have not applied the correct dose for our work.

Letter: The NSD Formula.

Dr. Roger Berry was kind enough to send to me a copy of the article on Excess Late Subcutaneous Fibrosis after Irradiation of Pig Skin Consequent Upon the Application of the NSD Formula. I feel that the following comments are justified. (1) The value of 0·33 as the regression coefficient for the isoeffect line when log dose is plotted against log time has considerable basis in many previous publications. This is used as a basis which, suitably partitioned according to the NSD concept for the first time, made possible for the first time separation of the effects of fractionation and of time (Ellis, 1966; 1968; 1971).

Skin tolerance to fractionated x-irradiation in the pig--how good a predictor is the NSD formula?

Abstract Fields on the flanks of domestic swine were irradiated with 250 kVp X rays in courses of one, six, or 30 fractions. The acute skin response was scored quantitatively using a numerical scheme. Late skin tolerance, up to one year after exposure, was determined by the presence or absence of skin necrosis in the irradiated fields. The Nominal Standard Dose was a poor predictor for early skin response; an approximately 30 per cent higher equivalent dose was required when administered in six fractions over 18 days to produce either dry or moist desquamation, than was required when given in 30 fractions over 39 days. The difference was even greater when compared with single radiation doses. Late skin tolerance was not closely correlated with the level of early response, but skin necrosis was well predicted by the NSD formula. These data in the pig correlate well with clinically determined late skin tolerance in three large radiotherapy centres. For a 64 cm2 skin field, however, skin tolerance in the pig...

Long-Term Recovery of Connective Tissue after Irradiation

C3H mice were given either no irradiation or a course of 4,000 or 5,000 rads in 10 fractions over a period of two weeks. Six months later, the right hind legs were given graded doses of 350–700 rads five times a week for two weeks. Analysis of the dose response curves for late necrosis scored eight months later showed that the data were described adequately by the Ellis NSD formula for retreatment of normal tissues.