Physical aspects of total-body irradiation at the Middlesex Hospital (UCL group of hospitals), London 1988-1993: I. Phantom measurements and planning methods.

This paper, which is divided into parts I and II, describes the physical aspects of work on total-body irradiation (TBI) at the Middlesex Hospital, London, from 1988 to 1993. Irradiation is fractionated and bi-lateral with horizontal accelerator photon beams of 8 MV (1988-1992) at a source-surface distance (SSD) of 3.36 m and 10 MV (1992-1993) at an SSD of 4.62 m. The main aims were maximum patient comfort, a simple, accurate set-up with overall times per fraction of 30 min or less, dose homogeneity throughout the body within +/- 10 to +/- 15%, pre-irradiation treatment planning on nine CT slices using our commercial IGE RTplan (1988-1992) and Target 2 (1992-1993) treatment planning systems and, most important, verification of the plans by in vivo dosimetry to within +/- 5%. Verification of the planned lung doses, which are distributed over five CT slices, was given special attention. In part I of this paper we describe the preliminary work, most of which was done prior to patient treatment. This consisted of standard dosimetric measurements (central axis depth doses, beam profiles at several depths, build-up and build-down curves, beam output calibrations, effect of body compensators, etc), in evaluating silicon diode dosimeters for in vivo dosimetry and of adapting and verifying the methods of treatment planning for TBI conditions. The results obtained with phantoms, including a Rando body phantom, showed that, in principle, our aims could be achieved. The final proof depended, however, on an analysis of the results of the in vivo work and this forms the subject of part II of this paper.

Physical aspects of total-body irradiation at the Middlesex Hospital (UCL group of hospitals), London 1988-1993: II. In vivo planning and dosimetry.

Part II of this paper gives the results of applying the TBI methods described in part I, to in vivo patient planning and dosimetry. Patients are planned on nine CT based body slices, five of which pass through the lungs. Planned doses are verified with ten silicon diodes applied bi-laterally to five body sites, at each treatment. LiF TLDs are applied to seven other body sites at the first treatment only. For 84 patients and at least 1016 measurements per body site with the diodes, the mean measured total doses agreed with planned doses within at most 2% except at lung levels, where the mean measured dose was 3% too low. Standard deviations of the measurements about the mean were between 2.4 and 3.1%. For the LiF TLDs, the mean measured doses for all seven body sites were with in +/- 5% of planned doses. A separate assessment of measured entrance and transmitted doses showed that the former agreed well with planned doses, but that the latter tended to be low, especially over the lungs, and that they had a wider dispersion. Possible reasons for this are discussed. These results show measurement uncertainties similar to those for non-TBI treatments of Nilsson et al, Leunens et al and Essers et al. An analysis of the treatment plans showed a mean dose inhomogeneity in the body (75 patients, nine slices) of 19 +/- 6.0% (1 s.d.) and in the lungs (40 patients, five slices) of 9.2 +/- 2.85% (1 s.d.). The conclusions are that, overall, the methods are reasonably satisfactory but that, with an extra effort, even closer agreement between measured and planned doses and a further limited reduction in the body dose inhomogeneity could be obtained. However, if it were thought desirable to make a substantial reduction in the dose inhomogeneity in the body and lungs, this could only be achieved with the available equipment by changing from lateral to anterior-posterior irradiation and any potential advantages of this change would have to be balanced against a likely deterioration in patient comfort and an increase in treatment set-up times.

DNA alkylation by 1,2-dimethylhydrazine in the rat large intestine and liver: influence of diet and enzyme induction.

Male Wistar rats were fed a semi-purified diet (MID - minimal inducing diet) with or without addition of 50 ppm of beta-naphthoflavone (BNF) for 1 week. After 1 week the rats were dosed with 20 mg/kg of 1,2-dimethylhydrazine (DMH) subcutaneously and killed at various time intervals from the injection. Enzyme levels were determined in microsomal and cytosolic fractions prepared from the liver and the intestinal mucosa. Feeding of BNF for 1 week caused a 6.5-fold increase of 7-ethoxyresorufin (7-ERR) deethylase in the colon as compared to the controls, but did not alter glutathione (GSH) content nor glutathione-S-transferase (GSHST) activity. Hepatic cytochrome P-450 and 7-ERR deethylation were not significantly altered by feeding of BNF at this concentration, whereas GSH and GSHST were increased by a factor of 1.6 and 2, respectively. In the DMH-dosed rats, O6-methylguanine was formed to a greater extent in the BNF-treated colon than in the controls at 1, 12 and 24 h, whilst N7-methylguanine levels were essentially the same in the induced and uninduced rats. No significant difference was found in the degree of hepatic DNA alkylation at any time points. As shown by our results, the nature of the diet would appear to be able to modulate the rate of metabolic activation of DMH and its binding to DNA in the target organ.