An automated phantom-film QA procedure for intensity-modulated radiation therapy.

To verify that the calculated dose distribution is delivered accurately during intensity-modulated radiation therapy (IMRT), we have implemented an automated plan/film validation protocol. The cubic polystyrene film phantom provided with the Peacock IMRT system and the Radiation Imaging Technology (RIT) film dosimetry system were used to compare planned and delivered dose distributions. The calculated dose matrix from CORVUS was transferred to RIT and analyzed. The analysis included dose-difference histograms, dose comparison in low-gradient areas, distance to agreement in high-gradient areas, dose profiles, and isodose comparisons. Dose differences of up to 5% were commonly observed in the high-dose and low-gradient areas between verification films and treatment plans for prostate patients. The most prominent discrepancies were detected in the high-gradient areas of dose distributions. The automated protocol is an efficient technique that provides information about spatial differences between calculated and delivered doses.

The relationship between dose heterogeneity ("hot" spots) and complications following high-dose rate brachytherapy.

PURPOSE: It is generally believed that "hot" spots should be avoided in radiotherapy because they lead to complications. Dose homogeneity within the target volume is much more difficult to achieve during brachytherapy than during external beam irradiation, and implants are rarely geometrically perfect. To not underdose some parts of the target volume, therefore, it may be necessary to accept hot spots in other parts of the target volumes, but it is not at all clear from the literature how much dose heterogeneity should be considered excessive. We undertook this study in an effort to determine just how high a dose to a hot spot is associated with clinically significant complications. METHODS AND MATERIALS: We studied 40 patients treated by high-dose rate brachytherapy with or without external irradiation. For each patient, we calculated the minimum dose to the "hottest" 1 cubic centimeter (cc) volume (Dmax1) and, for 18 patients, the minimum dose to the hottest 10 cc volume (Dmax10) as well. RESULTS: Considerable dose heterogeneity existed within the target volume. The Dmax1 ranged from 150-2000% (median 320%) of the minimum target dose (MTD). The median MTD/fraction was 2.50 Gy (range 1.50-25.00), and the median Dmax1/fraction was 10.00 Gy (range 3.75-150.00). The median Dmax1 from the entire course of brachytherapy was 75.00 Gy (range 25.00-550.00). Adding the doses from planned external irradiation, plus any prior irradiation to the same area, the median total Dmax1 was 112.50 Gy (range 30.00-580.00), yet the incidence of complications, even among those in the highest quartile of this dose range, was not greater than the lowest quartile. The total median Dmax10 was 85.00 Gy (range 32.00-130.00), but the incidence of complications was, again, similar whether the dose was in the lower or the upper half of this range (32.00-85.00 Gy, or 86.00-130.00 Gy, respectively). CONCLUSIONS: We had expected to find that the patients with the highest Dmax1 and/or Dmax10 would be the ones most likely to suffer complications, but the results did not support this hypothesis. Thus, dose heterogeneity, within the scope of our study, turned out to be rather unimportant with regard to complications. This finding contradicts the conventional wisdom and suggests that concerns about hot spots need not preclude optimization to ensure adequate dosage to all parts of the target volume.

Close or positive margins after surgical resection for the head and neck cancer patient: the addition of brachytherapy improves local control.

PURPOSE: Microscopically positive or close margins after surgical resection results in an approximately 21-26% local failure rate despite excellent postoperative external radiation therapy. We sought to demonstrate improved local control in head and neck cancer patients who had a resection with curative intent, and had unexpected, microscopically positive or close surgical margins. METHODS AND MATERIALS: Twenty-nine patients with microscopically close or positive margins after curative surgery were given definitive, adjuvant external radiation therapy and 125I brachytherapy. All 29 patients had squamous cell cancer and tonsil was the most common subsite within the head and neck region. After external radiation therapy and thorough discussions with the attending surgeon and pathologists, the slides, gross specimens, and appropriate radiographs were reviewed and a target volume was determined. The target volume was the region of the margin in question and varied in size based on the surgery and pathologic results. Once the target volume was identified the patient was taken back to the operating room for insertion of 125I seeds. Activity implanted (range 2.9-21.5 millicuries) was designed to administer a cumulative lifetime dose of 120-160 Gy. RESULTS: Twenty-nine patients were followed for a median of 26 months (range 5-86 months). Two-year actuarial local control was 92%. CONCLUSION: 125I, after external radiation therapy, is an excellent method to improve local control in the subset of patients with unexpectedly unsatisfactory margins.

Total body irradiation with an arc and a gravity-oriented compensator.

PURPOSE: To deliver uniform dose distributions for total-body irradiation (TBI) with an arc field and a gravity-oriented compensator. This technique allows the patient to be treated lying on the floor in a small treatment room. METHODS AND MATERIALS: Through the sweeping motion of the gantry, a continuous arc field can deliver a large field to a patient lying on the floor. The dose profile, however, would not be uniform if no compensator were used, due to the effects of inverse square variation of beam intensity with distance as well as the slanted depth in patient. To solve this problem, a gravity-oriented compensator made of cerrobend alloy was designed. This compensator has a cross-section of an inverted isosceles triangle, with the apex always pointing downward, due to gravity. By properly selecting the thickness of the compensator, the width of the base, and the distance between the pivots to the base, the difference in the path length through the compensator can be made just right to compensate the effects of inverse-square and slanted depth, thus producing a uniform dose profile. RESULTS: Arc fields with a gravity-oriented compensator were used for 6, 10, 15, and 18 MV photon beams. The arc field can cover a patient with a height up to 180 cm. The field width was chosen from 32 to 40 cm at the machine isocenter. The optimal thickness of the compensator was found to be 2.5 cm, and its base was 25 cm wide. The distance from the pivot points to the flat surface of the compensator proximal to the beam ranges from 13 to 14 cm for different beam energies. The dose uniformity at a depth of 10 cm is within +/-5% for all beam energies used in this study. CONCLUSIONS: Highly uniform dose profiles for TBI treatments can be delivered with an arc and a gravity-oriented compensator. The proposed technique is simple and versatile. A single compensator can be used for all energies, because the amount of compensation can be adjusted by changing the distance to the pivot and/or the field size.

DNA damage by the glycation products of glyceraldehyde 3-phosphate and lysine.

In order to evaluate whether base modifications, apurinic/apyrimidinic site formation, strand breaks, or a combination of these lesions results from the interaction of glycation products with DNA, plasmid DNA was first reacted with these products, and then subjected to digestion with endonuclease III and endonuclease IV of Escherichia coli. Analysis of the differential effects of digestions with these enzymes by electrophoresis on agarose gels demonstrated that reactive glycation products produce both base modification and apurinic/apyrimidinic sites in DNA, in addition to the strand breaks observed after incubation with glycation products alone. These types of DNA damage may occur in specific diabetic cells where elevated levels of glycating sugars are associated with pathologic dysfunction.

[Interaction of ribulose-1,5-diphosphate carboxylase with ribulose-1,5-diphosphate and with the magnesium ion by the spin label method]. / Issledovanie vzaimodeistviia ribulozo-1,5-difosfatkarboksilazy s ribulozo-1,5-difosfatom i ionom magniia metodom spinovoi metki.

A selective modification of external SH-groups of riboluse 1,5-diphosphate carboxylase (EC 4.1.1.39) from spinach by a spin label on the basis of maleimide was performed. From the EPR spectra of spin labels of three types of SH-groups were classified. It is shown that part of spin labels pre-reduced with dithiothreitol are reoxidized by the enzyme after the removal of dithiothreitol from the reaction mixture. The reoxidation is connected with the fact that one of the spin labels is bound to the SH-group at the enzyme active site and can act as its substrate, which results in alteration of the electron structure of the greater than N--O fragment in the spin label upon interaction of the spin-labeled enzyme with the substrate and Mg2+.