The use of tertiary collimation for spinal irradiation with extended SSD electron fields.

PURPOSE: The spine can be treated with an electron beam when its maximum posterior depth is within the therapeutic range of electrons. Electron fields treated at extended source-to-surface distances (SSDs), however, have larger penumbras and narrower therapeutic isodose widths relative to those at the standard SSD of 100 cm. We investigated the use of tertiary collimation close to the patient surface for these fields to sharpen the penumbra, minimizing dose to normal tissue and maximizing target coverage. METHODS AND MATERIALS: Using film dosimetry in a polystyrene phantom, we measured the dose distribution for electron fields at extended SSD under varying collimation conditions. Beam penumbra and therapeutic width as a function of depth, SSD, applicator insert size, and tertiary collimator opening were determined. We also measured the dose distributions in the junction region for various gaps between x-ray fields and an electron field as used for craniospinal irradiation. RESULTS: Measurements show that tertiary collimation close to the skin surface reduces penumbra width (lateral distance between the 90 and 20% isodose lines) by 56% and increases therapeutic isodose width (lateral width of the 90% isodose curve) by 25% at a depth of dmax relative to standard collimation. These numbers change to 23 and 13%, respectively, at an average depth of the spine. When lateral brain and posterior spine fields are used to irradiate the entire craniospinal axis, tertiary collimation aids in reducing the volume of the hot spot in the junction region by as much as 10% without compromising target coverage. CONCLUSIONS: Tertiary collimation for extended SSD electron fields is preferable to standard collimation in order to minimize dose to normal tissue and increase target coverage. This technique can be applied to both spinal and craniospinal irradiation. Support structures for the tertiary blocking are needed because the weight of the lead is usually too great for placement on the skin.

Clinical pharmacokinetic study of tiazofurin administered as a 1-hour infusion.

Tiazofurin, 2-beta-D-ribofuranosylthiazole-4-carboxamide, is cytotoxic to murine and human tumor cells. In earlier Phase-I/-II trials performed in other centers in patients with solid tumors, the drug was given mainly as a 10-min bolus or as a continuous i.v. infusion for 5 days. These protocols were associated with serious side effects, including neurotoxicity, pleuropericarditis, and occasional myelosuppression. In our study, 26 patients with end-stage leukemia were treated with tiazofurin with 1-hr daily i.v. infusions, resulting in lower incidence and less severity of side effects. In this group, 7 attained complete remission and 7 showed hematologic responses. Out of 12 evaluable patients with myeloid blast crisis of chronic granulocytic leukemia, 10 (83%) responded to therapy, with 6 attaining complete response. We present pharmacokinetic parameters of our clinical study and examine some of the reasons for the lower toxicity found in our trials. In leukemic patients during and after infusion at doses of 1,100, 2,200 and 3,300 mg/m2 tiazofurin peak plasma concentrations were 245, 441 and 736 microM, respectively, values one-half of those calculated from other reports with a 10-min bolus administration. In our 1-hr infusion method, biphasic pharmacokinetics were noted with alpha t1/2 and beta t1/2 of 0.5 and 6.2 hr, and tiazofurin was eliminated at a faster rate than in previous trials with continuous infusion. The area under the curve with our 1-hr infusion was 52% of that reported for the same dose given by continuous infusion. Our 1-hr infusion method and prompt and effective treatment of side effects enabled us to administer higher doses and larger total amounts of tiazofurin in longer treatment cycles than in any previous trials elsewhere. Tiazofurin therapy using 1-hr infusion may be feasible for other carefully selected types of malignancies.