Howard R. Elson

Effect of in vivo exposure to iodine‐131 on the frequency and persistence of micronuclei in human lymphocytes

The validity of the micronucleus test as a biomarker of chromosome damage in dividing mammalian cells is well established. This assay was used to study the response of peripheral lymphocytes of a 34-yr-old male patient following treatment with 131I ablative radiation therapy following a total thyroidectomy. Coincidentally, 8 mo before diagnosis, the patient had provided a blood sample for an in vitro study of micronucleus induction following exposure to graded doses of x-rays. The background frequency in the unexposed culture showed a mean count of 6.0 micronuclei per 1000 binucleated (first division) lymphocytes, while mean values of 18.5, 29.0, 41.0, 61.0 and 75.5 micronuclei/1000 cells were observed following x-ray doses of 5, 10, 15, 20, and 25 cGy, respectively. These data fit a nonthreshold, linear dose-response function (y = 2.78x + 3.71; r = .99). Eight months after the in vitro x-ray study, the subject was diagnosed with thyroid cancer. Surgery was performed, and 5 wk later the patient received 1.78 GBq (48 mCi) of 131I as adjuvant radiation therapy. Blood was drawn 11 d after the radiation treatment and at monthly intervals thereafter to analyze the frequency and persistence of micronuclei. The first posttreatment sample showed 35.5 micronuclei per 1000 binucleate cells. Based on the linear dose-response equation from the earlier study, the sixfold increase in micronucleus frequency suggests a dose to the peripheral blood of approximately 11 cGy. The cytogenetic dose estimate compares to approximately 30 cGy using a new model based on external whole-body counting data. Nine consecutive monthly samples have been analyzed to date. Although the micronucleus count has fluctuated (four- to sixfold above background), the frequency after 8 mo is equivalent to the first posttreatment sample. Data show that radiation-induced cellular lesions persist for months following relatively brief radiation exposure to a medical isotope. Results of this study support the conclusion that the lymphocyte micronucleus test is a rapid, sensitive, and perhaps quantitative biomarker of low-dose (< 25 cGy) radiation exposure.

Transient radiation myelopathy (Lhermitte's sign) in patients with Hodgkin's disease treated by mantle irradiation.

Abstract Transient radiation myelopathy diagnosed by Lhermittes sign was noted in four of 44 patients with Hodgkins disease who were treated with 4000 rad/four wks. mantle irradiation from 1969 to 1977. Symptoms appeared four, six, six and twenty weeks after treatment and lasted for four, eight and twenty-four weeks respectively; one patient developed late minor neurological disability two years later. There was no correlation within this group of patients between incidence and time dose fractionation (TDF) or equivalent single dose (ED ret) but a dose response-incidence relationship was noted when this study was compared to others in the literature.

The distribution of power and heat produced by interstitial microwave antenna arrays: II. The role of antenna spacing and insertion depth☆

The distribution of power and temperature generated by 915 MHz interstitial microwave antenna arrays was studied in static muscle-equivalent phantoms and both perfused and non-perfused canine thigh muscle. These arrays, which would form the geometric basis of larger volume implants, consisted of four parallel antennas oriented such that transverse to their long axes they formed the corners of a square. Arrays with 2 and 3 cm sides were compared at various depths of insertion where the nodes for all four antennas were coincident at the same depth. The position relative to the antenna nodes of the maximum power and highest temperature within the array volume varied with the depth of insertion of the antennas. Though power dropped rapidly distal to the nodes at all depths, a shift in the location of the maximum power proximal to the nodes resulted in an increase in the effective heating volume at certain insertion depths. For 2 cm array spacing the highest power and temperature were measured along the central axis of the array at all insertion depths. However, arrays using 3 cm spacing generated their maximum power adjacent to the antennas with only 50% of this level occurring along the central axis. When the temperature produced by 3 cm arrays was measured in phantoms midway through simulated 30-minute hyperthermia treatments, the effect of thermal conduction on the temperature distribution was evident. Though power was only 50% centrally, the highest temperatures occurred there. This same pattern of central heating occurred in perfused canine muscle demonstrating the importance of conductive and convective heat redistribution in reducing thermal gradients within the array volume.

External beam radiation attenuates venous neointimal hyperplasia in a pig model of arteriovenous polytetrafluoroethylene (PTFE) graft stenosis

PURPOSE Hemodialysis vascular access dysfunction is an enormous clinical problem that causes great morbidity and costs well over one billion dollars per annum. The vast majority of hemodialysis vascular access dysfunction occurs as a result of venous stenosis and thrombosis at the graft-vein anastomosis. At a cellular level, this venous stenosis is the result of venous neointimal hyperplasia (VNH). There are, unfortunately, no effective therapies for VNH. The purpose of this study was to assess the role of external radiation therapy in preventing VNH and venous stenosis. METHODS AND MATERIALS Seven-centimeter polytetrafluoroethylene loop grafts were placed bilaterally between the femoral artery and vein of 12 Yorkshire Cross pigs. One side was treated with a single 16-Gy dose of external beam radiation with a linear accelerator, while the contralateral side served as an internal control. Swine were killed after 28 days, and the grafts were carefully dissected out and removed. Neointimal hyperplasia and luminal stenosis were then assessed morphometrically at the graft-vessel anastomoses. RESULTS External beam radiation therapy significantly reduced the amount of luminal stenosis at the graft-vein anastomosis, with minimal local and systemic toxicity. CONCLUSIONS External beam radiation therapy could be a useful and clinically relevant local treatment for venous stenosis in polytetrafluoroethylene dialysis grafts.

A comparison of the effectiveness of thermoluminescent crystals LiF:Mg,Ti, and LiF:Mg,Cu,P for clinical dosimetry

This study compared the relative effectiveness of TLD crystals LiF:Mg,Ti (TLD-100) and LiF:Mg,Cu,P (TLD-700H) for clinical dosimetry, focusing on reproducibility, linearity, and energy response. Experimental results indicated that TLD-700H was superior to TLD-100 with regard to reproducibility, lack of supralinearity, and the absence of variation in TL signal with radiation quality. TLD-700H also had the additional advantages of higher sensitivity and immediate readability. The investigators conclude that this relatively new TLD crystal shows promising potential for clinical dosimetry.

The distribution of power and heat produced by interstitial microwave antenna arrays: I. Comparative phantom and canine studies

To adequately plan and administer localized hyperthermia with interstitial microwave antennas, the thermal distribution patterns generated by such antennas must be characterized. This study evaluated the performance of single node 915 MHz antennas operating either alone or as a 2 cm square array of four parallel antennas using both muscle-equivalent phantoms and canine thigh muscle. Two types of measurements were compared. Specific absorption rate (SAR), where temperature increases resulting from short duration microwave pulses were used to define power distribution, and temperature gradients during simulated hyperthermia treatments. SAR measurements in phantoms were comparable to those obtained in non-perfused canine muscle demonstrating the usefulness of the phantom for these measurements. For a single antenna there was a rapid decrease in power radially which resulted in a steep thermal gradient at distances within 0.5 cm. However, the power generated by a four-antenna array was highest along its central axis and declined to approximately 50% near the antennas at the array periphery. Along the central axis of the array power decreased most rapidly distal to the antenna nodes. The distribution of temperature measured during simulated hyperthermia treatments in phantoms paralleled the SAR distribution and was comparable to the temperature gradient observed in perfused canine muscle, suggesting that phantoms could be used to predict temperature distributions in resting muscle tissue.

Magnetic resonance imaging of microbubbles in a superheated emulsion chamber for brachytherapy dosimetry

This paper describes development of magnetic resonance imaging (MRI) techniques for three-dimensional (3D) imaging of a position-sensitive detector for brachytherapy dosimetry. The detector is a 0.5 l chamber containing an emulsion of halocarbon-115 droplets in a tissue-equivalent glycerin-based gel. The halocarbon droplets are highly superheated and expand into vapor microbubbles upon irradiation. Brachytherapy sources can be inserted into the superheated emulsion chamber to create distributions of bubbles. Three-dimensional MRI of the chamber is then performed. A 3D gradient-echo technique was optimized for spatial resolution and contrast between bubbles and gel. Susceptibility gradients at the interfaces between bubbles and gel are exploited to enhance contrast so microscopic bubbles can be imaged using relatively large voxel sizes. Three-dimensional gradient-echo images are obtained with an isotropic resolution of 300 microns over a 77 mm x 77 mm x 9.6 mm field-of-view in an imaging time of 14 min. A post-processing technique was developed to semi-automatically segment the bubbles from the images and to assess dose distributions based on the measured bubble densities. Relative dose distributions are computed from MR images for a 125I brachytherapy source and the results compare favorably to relative radial dose distributions calculated as recommended by Task Group 43 of the American Association of Physicists in Medicine.

Respiratory motion effects on whole breast helical tomotherapy

The effects of intrafraction respiratory motion on nonhelical intensity-modulated radiotherapy have been well addressed in the literature, both theoretically and experimentally. However, the consequences of respiratory motion on helical tomotherapy, for patient-specific treatment plans, are less well known. Parameters specific to this treatment modality such as pitch, gantry speed, and degree of modulation may play prominent roles in radiation delivery with respect to intrafraction respiratory motion. This phantom-based study specifically addressed the effects of intrafraction respiratory motion on whole breast helical tomotherapy. A device capable of driving an acrylic phantom with reproducible, one-dimensional, anterior-posterior motion resembling a sinusoid of 4.6 mm crest-trough amplitude was developed. A plan to irradiate the corner of an acrylic phantom using parameters typical of a whole breast helical tomotherapy technique was developed using the TomoTherapy Hi-Art-II System. The treatment was delivered to the phantom, with Kodak EDR2 film in the axial plane, for each of the following conditions: (i) phantom at 270 degrees initial sinusoidal phase and 12 cycles/min motion, (ii) phantom at 270 degrees initial sinusoidal phase and 18 cycles/min motion, and (iii)-(v) phantom at 18 cycles/min motion with 0 degrees, 90 degrees, and 180 degrees initial sinusoidal phases. A measure of technique reproducibility was also performed for several irradiations with the phantom static at 270 degrees initial sinusoidal phase. Films were processed using a Kodak MIN-R mammography film processor, scanned with a Vidar NXR-16 Dosimetry Pro scanner and analyzed with RIT113 v.4.2 software. Films were compared to a reference film irradiated under the conditions of no motion and 270 degrees sinusoidal phase. For all comparisons, 5% dose difference threshold, 3% dose difference and 2 mm distance-to-agreement gamma analysis, and isodose plots were generated. The results of this study show a small area of greater than 5% decrease in dose at the phantoms anterior surface and a 1.5-3 mm posterior-medial shift of isodose lines in the penumbral and apex regions of the PTV. Frequency and phase effects are apparent within the PTV where dose varies with high spatial frequency. As the reference film was produced by delivering the treatment plan to the phantom static and in the position corresponding to maximum expiration, results are representative of extreme deviations between planned and delivered dose with respect to sinusoidal motion of clinically relevant magnitudes and frequencies.

Therapeutic responses of spontaneous canine malignancies to combinations of radiotherapy and hyperthermia

Abstract The goals of this ongoing Phase III study of adjuvant local hyperthermia with radiotherapy were to evaluate how tumor control and normal tissue complications were related to patient and treatment variables. Canine veterinary patients with localized malignancies were stratified by histology and anatomic site and randomized into three groups. All patients received radiotherapy ( 60 CO) in 3.5 Gy fractions given Mon-Wed-Fri to 14 treatments (49 Gy). One group received radiotherapy alone while the others also received microwave-induced hyperthermia (44°C) for 30 minutes once each week. Hyperthermia followed radiotherapy and was given to one group immediately and delayed 4–5 hours in the other. Adjuvant hyperthermia resulted in a significant ( p p

Incorporation of Patient Immobilization, Tissue Compensation and Matchline Junction Technique for Three-Field Breast Treatment

A protocol for the treatment of the intact breast was developed to maximize dose homogeneity and reproducibility. This protocol uses patient and breast immobilization, three-dimensional tissue compensators, and a technique for geometric matching of fields when the supraclavicular area is treated. A series of phantom measurements and analysis of patient port films was performed to evaluate dose homogeneity and reproducibility using this technique, and the potential adverse effect of loss of skin sparing from the immobilization device was investigated. Dose homogeneity throughout the phantom breast was within +/- 6% of the prescribed central axis dose, and homogeneity at the supraclavicular match line was +/- 10%. This represented a significant improvement over techniques not using tissue compensation or geometrically matched fields. Reproducibility of patient treatments was not significantly improved from previous non-immobilized treatment techniques, but there was no loss of skin sparing from the device, and other advantages of immobilization were observed. Details of the protocol are discussed together with changes that are currently being made to improve the results obtained thus far.