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Technical note: reconstructing dose distributions from manually planned electron boosts in breast radiotherapy.

PURPOSE: In breast radiotherapy, delivery of manually-calculated electron boosts limits retrospective dose-response analyses as dose distribution is unavailable. This work evaluates the feasibility of reconstructing dose distributions from manually planned electron boosts in breast-conserving radiotherapy. METHODS: Only 72 out of 198 breast cancer patients had complete stored dose distributions from sequential electron boosts in the REQUITE study. Arbitrary data from 70/72 patients were used to develop and validate dose reconstruction method. Twenty patients were used to determine optimal parameters for Monte-Carlo-based (MC) electron dose reconstruction on RayStation (v.11B-R), considering CT-calibration curve, MC-history number, andcalculation grid resolution. Remaining 50 patients were used to quantify dose reconstruction accuracy. The similarity between reconstructed and stored dose was evaluated using 3D-gamma index and dosimetric parameters extracted from breast and tumour bed contours. Dose difference location was evaluated using dose-location histogram. RESULTS: Calculation grid resolution significantly impacted electron dose distribution (p&#xa0;<&#xa0;0.01), where the finest grid (0.15&#xa0;cm) showed highest similarity to stored doses. CT-calibration curve and MC-history number had a negligible influence on dose reconstruction. Dosimetric difference between reconstructed and stored doses was&#xa0;<&#xa0;1&#xa0;Gy for breast and tumour bed. Reconstructed dose was achieved&#xa0;>&#xa0;90% gamma passing rate in the validation set. However, around 2.5&#xa0;Gy dose differences were observed at the skin and tissue interface regions. CONCLUSIONS: Retrospective electron boost dose reconstruction is feasible with acceptable accuracy, and could increase data completeness in large cohort studies. Caution is advised when assessing dose near tissue interface and further validation is needed outside the REQUITE dataset.

Electrons

Dose reconstruction of x-ray irradiation of the larynx.

The authors have determined the dose distribution in the neck for parallel opposed and three field orthovoltage X-ray irradiation techniques of the larynx. LiF:Mg, Ti rods and pellets combined with film densitometry were used. Absorbed dose measured in the region of vocal chords is about 20% lower than that assessed by assuming full backscatter (perpendicular incidence) and by using standard isodose tables.

Film Dosimetry

Epidemiologic studies of cancer in populations near nuclear facilities.

We reviewed over 40 epidemiologic studies around nuclear power stations, fuel reprocessing plants, and weapons production facilities and testing sites in the United Kingdom, the United States, France, and Canada. We examined these studies for their potential to support a cause and effect relationship between cancer risk and radiation exposure. The extent to which an epidemiologic study supports a causal relation between radiation exposure and increased cancer risk can be evaluated using a set of criteria that have become known as Hill's postulates. In our review, epidemiologic studies yielded results that were biologically plausible and were supported by experimental data, but in almost all of the studies the methodologies were not adequate for evaluating causality. In the majority of cases, the methodologies did not permit examination of dose-response associations, making it impossible to support or refute causal relations. We suggest that investigators consider these issues when designing studies and employ dose reconstruction methodology to estimate radiation doses for specific individuals and population groups.

Adolescent

Low-dose electron image reconstruction of negatively stained contractile phage sheath from Bacillus subtilis (PBS-Z).

The structure of the contractile sheath of the defective phage from B. subtilis (PBS-Z) has been investigated by low-dose electron microscopy and image reconstruction. The extended and contracted sheath particles were imaged by means of two negative stains which consisted of uranyl- and phosphotungstate-containing solutions of a pH of 4.2 and 7.0 respectively. Images of identical parts of the same type of specimen were recorded at a total electron dose of 80 C/m2 (5 electrons/A2) and 4 x 10(3) C/m2 (250 electrons/A2). The low-dose reconstructions of the extended and contracted sheath structure in the two stains show good correspondence and made it possible to draw the following structural conclusions. The sheath protein in both types of structure has an elongated shape, and in both structures the long molecular axis lies in a plane perpendicular to the helical sheath axis. The orientation of the protein in the extended and contracted sheath is different; the long axes differ by about 35 degrees in orientation. The reconstructions did not permit conclusions about different conformational states of the protein in both structures. These data, together with the packing parameters of the protein subunits in the contractile sheath [1], form the complete structural analysis of this biological structure by electron microscopy. The radiation damage effects which have been monitored in analyzing image pairs to the full extent may be summarized as follows. (1) Diameters of the sheath structure increase, which indicate flattening. (2) There is no loss in resolution, and layerline altitudes of the Fourier-transformed images do not change. (3) Uranyl stain behaves differently compared to phosphotungstate. In both negative stains the structural noise level increases upon irradiation as follows from the increase in phase residuals of the digital layerline data. In uranyl-stained images also more aperiodic noise appears. (4) The Fourier amplitudes of the principal layerline maxima shift towards lower spatial frequencies; phases of corresponding maxima generally remain constant. This pattern is more pronounced in the extended sheath data; there is no rationale describing these positional shifts. Moreover, in the case of contracted sheath the amplitudes of Fourier components also change more in absolute value. Therefore the damage effects also seem to depend on the type of structure embedded in the stain. (5) In the reconstructed images these radiation effects create artificial stain-excluded volumes of a type and at a radius which depend on the stain and structure.

Bacillus subtilis

Radiation necrosis of the brain: correlation between computed tomography, pathology, and dose distribution.

Delayed necrosis of the brain following exposure to high doses of radiation is a recognized hazard. It is important to predict the nature of these postradiation changes, since surgical removal of radiation necrosis may reverse neurological deterioration of patients so affected. The present report stresses the importance of correlating the findings on computed tomography (CT) scans and zones of high radiation dose on dose reconstruction plans in order to differentiate between delayed radiation necrosis and tumors of the brain. This differentiation is not possible using the criteria of CT alone.

Adult

The reconstruction and dose-rate calculation of radium needle implants.

A comprehensive computer program has been developed for carrying out the various tasks associated with radium needle implants. Data input for the program are obtained by digitizing an orthogonal pair of radiographs with an analogue tracing system. Corresponding needles in the two radiographs are automatically located, and the implant may be rotated to any desired position in three dimensional space, at the same time presenting a view of the rotation on a storage oscilloscope. Automatic determination of the mean plane of a planar implant is possible, and the dose-rate distribution may be calculated in any specified plane. A Paterson--Parker exposure rate calculation may be performed with a biological dose and treatment time correction incorporated. The program is written in Fortran and runs on a small interactive computer system.

Computers

Low dose dextran 40 in reconstructive hip surgery patients.

Preoperative and postoperative bilateral lower extremity venography was used to evaluate the efficacy of low dose dextran 40 in prophylaxis of deep venous thrombosis in reconstructive hip surgery patients. Patients were given dextran 40 at 50 cc/hr, with 250 cc given perioperatively and 500 cc given on postoperative days two and four. Five of 227 patients had positive venograms preoperatively. Of these 227 patients, 179 met protocol requirements and had venography postoperatively. Venous thrombosis occurred in 33 (18%) of those studied postoperatively. Of these, 11 were calf clots without extension to the popliteal region. Therefore, there were 22 patients (12%) with femoral or popliteal involvement overall. There were two deaths, neither of which was secondary to pulmonary embolus or a complication of dextran. There were two wound complications. These results suggest that low dose dextran 40 administered as indicated is a safe and efficacious means of deep venous thrombosis prophylaxis in reconstructive hip surgery patients.

Arthroplasty

Evaluation of high energy photon external beam treatment planning: project summary. Photon Treatment Planning Collaborative Working Group.

A three-year project for the "Evaluation of High Energy Photon External Beam Treatment Planning," sponsored by the National Cancer Institute, is summarized. The participants in this project were determined on a competitive basis and included staff from four institutions: Massachusetts General Hospital; Memorial Sloan-Kettering Cancer Center; the University of Pennsylvania; and Mallinckrodt Institute of Radiation. This project built on the developments in three-dimensional anatomical and dose distribution reconstruction at these institutions and on the clinical guidance at these centers for quantitative evaluation of treatment plans. Protocols for acceptance of patients with lesions at eight different sites were developed and utilized. The technical methodology for interchange of treatment planning tapes, specifications for computerized tomography sections and their reconstruction, and the employment of dose-volume histograms of target regions and specified normal tissues and organs were all developed. Data were accumulated for tumor control probabilities (TCP) and for normal tissue complication probabilities (NTCP) for use in treatment plan design and evaluation. Several treatment parameters were studied as influenced by the availability of three-dimensional treatment planning and specific conclusions were reached.

Humans

The next decade in external dosimetry.

In recent years, a number of external dosimetry problems have been solved. However, changes in standards and legal concepts relating to the application of dosimetry results will require further enhancements in measurement techniques and philosophy in the next 10 y. The introduction of effective dose equivalent and the legal use of probability of causation will require that much greater attention be given to determination of weighted organ dose from external exposure. An imminent change--an increase in the fast neutron quality factor--will require a new round of technology development in a field that has just received a decade of close scrutiny. For the future, we must take advantage of developments in microelectronics. The use of random access memory (RAM) and metal-on-silicon (MOS) devices as detector elements, particularly for neutron dosimetry, has exciting possibilities that are just beginning to be explored. Advances in microcircuitry are leading, and will continue to lead, in the development of a new generation of small, rugged and "smart" radiation survey instruments that will make the most of detector data. It has become possible with very compact instruments to obtain energy spectra, linear-energy-transfer (LET) spectra, and quality factors in addition to the usual integrated dosimetric quantities: exposure, absorbed dose, and dose equivalent. These instruments will be reliable and easy to use. The user will be able to select the level of sophistication that is required for any specific application. Moreover, since the processing algorithms can be changed, changes in conversion factors can be accommodated with relative ease. During the next decade, the use of computers will continue to grow in value to the health physicist. Personal computers and codes designed for dosimetry applications will become prominent, providing the health physicist with the ability to perform sophisticated data reduction, spectra unfolding and even radiation modeling and transport calculations on the desk top. In the far term, the use of computers could extend to the development of sophisticated tracking systems that would follow and record the workers' movements throughout a radiation area. These data, together with information from area monitors, air samplers and personnel dosimeters, could be used to develop truly integrated dose estimates, including reconstruction of organ doses.

Beta Particles

ORERP (Off-Site Radiation Exposure Review Project) internal dose estimates for individuals.

A method was developed to reconstruct the internal radiation dose to off-site individuals who were exposed to fallout from nuclear weapons tests at the Nevada Test Site (NTS). By this method, committed absorbed doses can be estimated for 22 target organs of persons in four age groups and for selected organs of the fetus. Ingestion doses are calculated by combining age-group dose factors and intakes specific for age group, test event, and location as calculated by the PATHWAY food-chain model. Inhalation doses are calculated by combining age-group dose factors and breathing rates, and time-integrated air concentrations that are derived from the ORERP Air-Quality Data Base. Dose estimates are calculated for the radionuclides that contribute significantly to the total dose; these number 20 via the ingestion pathway and 46 via the inhalation pathway. Internal doses to nonspecified individuals and nonspecified fetuses are being reconstructed for each location in the ORERP Town Data Base for which exposure rates and cloud-arrival times are listed. Examples of reconstructing internal dose are presented. This method will also be adapted to reconstruct internal doses from NTS fallout to specific individuals in accordance with the person's age, past residence, life-style, and living pattern.

Aerosols

Leukemia risk following radiotherapy for breast cancer.

To evaluate further the relationship between high-dose radiotherapy and leukemia incidence, a nested case-control study was conducted in a cohort of 22,753 women who were 18-month survivors of invasive breast cancer diagnosed from 1935 to 1972. Women treated for breast cancer after 1973 were excluded to minimize the possible confounding influence of treatment with chemotherapeutic agents. The cases had histologically confirmed leukemia reported to the Connecticut Tumor Registry (CTR) between 1935 and 1984. A total of 48 cases of leukemia following breast cancer were included in the study. Two controls were individually matched to each leukemia case on the basis of age, calendar year when diagnosed with breast cancer, and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. Local radiation doses to each of the 16 bone marrow components for each patient were reconstructed; the dose averaged over the entire body was 530 rad (5.3 Gy). Based on this dosage and assuming a linear relationship between dose and affect, a relative risk (RR) in excess of 10 would have been expected. However, there was little evidence that radiotherapy increased the overall risk of leukemia (RR = 1.16; 90% confidence interval [CI], 0.6 to 2.1). The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not significantly increased (RR = 1.8; n = 10); nor was the risk for all other forms of leukemia (RR = 1.0; n = 38). There was no indication that risk varied over categories of radiation dose. These data exclude an association between leukemia and radiotherapy for breast cancer of 2.2-fold with 90% confidence, and provide further evidence that cell death predominates over cell transformation when high radiation doses are delivered to limited volumes of tissue.

Aged

Limited-angle 3D reconstruction of PET images for dose localization in light ion tumour therapy.

In vivo dose localization in light ion tumour therapy can be performed by measuring the range distributions of beta+ active ions in tissue employing positron emission tomographic techniques. For this purpose a multiplicative iteration scheme for reconstructing three-dimensional images from shift-variant, limited-angle data is presented. In the iterative correction steps the algorithm uses the geometric means of quotients calculated from the three-dimensional Radon transforms of the backprojected measured and approximated source distributions. When sources measured with poor statistics are reconstructed, an effective noise suppression is achieved.

Algorithms

Cardiovascular and neuromuscular responses to high-dose pancuronium-metocurine in pediatric burned and reconstructive patients.

The efficacy of the combined use of pancuronium and metocurine (Pm-MTC) in high doses to produce rapid-onset muscle paralysis was evaluated in 15 patients with acute burns and 18 recovered burned patients scheduled for reconstructive surgery. Two and three times the previously determined ED95 of the combination for each group was used. (ED95 for Pm-MTC combination is 0.032/0.129 mg/kg for acute burns and 0.013/0.051 mg/kg for reconstructive patients.) Doubling ED95 produced 95% paralysis in 3.1 +/- 0.9 min in acutely burned children and in 4.3 +/- 0.7 min in reconstructive children (mean +/- SEM). These onset times were not significantly different from each other. Tripling the ED95 of the combination in burned children reduced the onset time to 1.3 +/- 0.14 min, but this was not significantly different from 2 X ED95 onset time in burned patients. The administration of 3 X ED95 to the reconstructive group, however, resulted in a significantly more rapid onset time of 1.8 +/- 0.4 min compared with 2 X ED95 in the same population. With 3 X ED95 the onset times between burn and reconstructive patients were not significantly different. Time for recovery of twitch to 25% of control twitch height (75% twitch depression) was significantly prolonged in burned patients compared with reconstructive patients for equipotent doses administered. Although the occasional patient showed prominent changes in heart rate and blood pressure, overall cardiovascular stability was impressive.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure

A comparison of dose calculations at points around an intracavitary cervix applicator.

An intercomparison was made between dose-rate calculations performed in 10 institute in The Netherlands for intracavitary applications with the Selectron-LDR remote afterloading machine. The results of 11 computer planning systems of five different manufacturers were compared with reference dose-rate calculations. The difference in clinically relevant dose-points like rectum and bladder, were less than 2% if the values of the coordinates of source and dose-points were given, except for one type of planning system, that showed differences up to 10%. The errors observed for the latter system were probably due to a coarse calculation grid, which becomes important in regions with a high dose gradient. If the reconstruction process of source and dose-point positions from radiographs was included as it usually is in practice, then the accuracy became worse and the planning system that showed large errors before, gave unacceptable errors of 30% to 40% in the rectal area. This is due to additional errors introduced in the reconstruction. The intercomparison showed that it is very important that computer treatment planning systems for brachytherapy calculations are tested before clinical use. The reconstruction technique for source and dose-point positions should be part of this test. Radiographs should be made of a phantom that simulates the cervix application, and the radiography technique should be similar to the one that is clinically employed.

Brachytherapy

Three-dimensional display in planning radiation therapy: a clinical perspective. Photon Treatment Planning Collaborative Working Group.

We describe the experience with 3-D display capabilities of four institutions engaged in a comparative three-dimensional treatment planning study. A high degree of interactivity was found to be desirable, which puts great demands on the hardware. Displays which were found particularly helpful included: display of multiple 2-D sections (transverse, sagittal, coronal and/or oblique) of one or more imaging studies; superimposition of outlines of structures of interest; superimposition of dose distributions displayed as isodose lines or as a color-wash overlay; beam's eye view displays of: structures displayed as contour-stacks or as shaded surfaces, dose distributions on the surface of structures, interactively viewed isodose surface displays, and digitally reconstructed radiographs. Dose-volume histograms provided valuable summarizations of dose data.

Humans