The dose distribution of medium energy electron boosts to the laryngectomy stoma.

An en face, medium energy electron boost of approximately 10 Gy is often given to stomal and peristomal tissues. Because the boost is considered a simple treatment, CT-based treatment planning is rarely used. Further, the results of such a plan might be inaccurate, as the complex dose distribution surrounding the stoma air cavity is poorly modeled by many treatment planning systems. We constructed three phantoms-two with a central vertical cavity to mimic the size and shape of the stoma and proximal trachea and one with a cavity inclined at 45 degrees to the horizontal to better simulate anatomy. These were used to investigate the dose distribution surrounding the stoma. In all cases, the entrance to the stoma opening was centered in a field defined by a 7-cm circular cutout and the phantom was irradiated at a source-surface distance (SSD) of 100 cm with either vertically incident 9- or 12-MeV electrons. Film measurements were made at a range of depths below and lateral to the cavity. For the vertical cavity phantoms, diode measurements were performed and isodose plans using CT scans of the phantoms were generated on a modern treatment planning system. For these two phantoms, the combined effects of lateral scatter from surrounding material and reduced equivalent thickness for electrons which pass directly through the cavity increases the dose within a centimeter of the bottom of cavity by as much as 50% for 9 MeV and 70% for 12 MeV. In material at the shallower ("superior") end of the inclined cavity, a 40-50% overdose was noted. The dose increase is geometry dependent and is not predicted by the available treatment planning system. The potential of such a dose increase to affect normal tissues such as the neopharynx should be considered.

Modeling the effects of inhomogeneous dose distributions in normal tissues.

Conformal radiation therapy frequently produces inhomogeneous dose distributions in normal tissues near the target. Most mathematical models of normal tissue complication probabilities (NTCP) are based on uniform whole or partial organ irradiation, and the model parameters are chosen to obtain agreement with clinical outcomes in these simple situations. Frequently used NTCP models and methods for including inhomogeneous dose distributions in model calculations are outlined in this report. It has been found that the model adopted may qualitatively affect prediction of complications. Limitations placed on current models by the scarcity of reliable complications data and other approaches to using the calculated dose distribution to predict NTCP are discussed.

Use of PET to monitor the response of lung cancer to radiation treatment.

Approximately 170,000 people are diagnosed with lung cancer in the United States each year. Many of these patients receive external beam radiation for treatment. Fluorine-18 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) is increasingly being used in evaluating non-small cell lung cancer and may be of clinical utility in assessing response to treatment. In this report, we present FDG PET images and data from two patients who were followed with a total of eight and seven serial FDG PET scans, respectively, through the entire course of their radiation therapy. Changes in several potential response parameters are shown versus time, including lesion volume (V(FDG)) by PET, SUVav, SUVmax, and total lesion glycolysis (TLG) during the course of radiotherapy. The response parameters for patient 1 demonstrated a progressive decrease; however, the response parameters for patient 2 showed an initial decrease followed by an increase. The data presented here may suggest that the outcome of radiation therapy can be predicted by PET imaging, but this observation requires a study of additional patients.

Can current models explain the lack of liver complications in Y-90 microsphere therapy?

Normal liver complications have not been observed in Y-90 microsphere therapy of hepatic tumors [selective internal radiation (SIR)], despite clinical studies reporting estimated absorbed doses to normal liver between 100 and 150 Gy. The purpose of the study was to see whether predictions of normal tissue complication probability (NTCP) models for liver based on clinical data from external beam therapy are consistent with clinical results of SIR. Liver NTCP was calculated using a parallel architecture model and normal liver dose-volume histograms that have been proposed for SIR. A parallel model including internal functional subunit structure is also proposed. Dose rate effects are incorporated. A criterion for comparing model calculations with clinical data is presented. For the parallel architecture model, the predicted NTCP is sensitive to the dose distribution in normal liver and to the model parameters, particularly the repair time. With reasonable assumptions about the microsphere distribution, the parallel model with parameters deduced from external beam therapy outcome analysis is consistent with the observed lack of liver complications. Inclusion of FSU structure widens the range of assumptions under which consistency is found. The parallel model can be consistent with the clinically observed lack of liver complications in SIR. More information about the activity distribution and the radiobiology of normal liver under conditions typical of microsphere therapy should be sought.

A dosimetric comparison of conventional vs conformal external beam irradiation of a stented coronary artery utilizing a new fluoroscopic imaging detector system.

UNLABELLED: Purpose. To determine whether conformal external photon beam irradiation may prevent or reduce the rate of restenosis of a stented coronary artery following percutaneous transluminal coronary angioplasty (PTCA). Optimal conformal external beam irradiation with limited cardiac dose requires adequate visualization of the stented vascular segment. With existing image intensifiers, identification of a coronary stent is poorly localized. We propose using an amorphous silicon panel detector to observe the movement of the stent during the cardiac cycle. BACKGROUND: Long-term radiation-induced coronary complications can be minimized by: (a) reducing the radiation field sizes, (b) fractionating the total dose over several days, and (c) applying multiple treatment beams. Localization of the movement of the stent during the cardiac cycle may allow for the design of radiation fields that conform to the stented vessel segment. This scheme may permit gating the radiation beam on or off relative to movement of the stent within or outside the radiation fields, respectively. METHODS: Using a new solid-state amorphous silicon planar detector, with a dynamic range of 12 bits, fluoroscopic images of a Palmaz-Schatz coronary stent were obtained. The stent was centered in a polystyrene phantom 20 cm thick and imaged using a 90-kVp, 3.5-ma, source-detector and source stent distances of 114 and 100 cm, respectively. With the solid-state silicon detector, the stent was identified in a single video frame (1/30 s). This fast image acquisition should allow for mapping the motion of the stent during the cardiac cycle. The stent movement during the cardiac cycle may then be correlated with the QRS complex in the electrocardiogram. CONCLUSIONS: The localization of a coronary stent during the cardiac cycle under fluoroscopy permits delivery of small conformal external radiation fields to treat stented coronary arteries, while minimizing radiation dose to surrounding normal cardiac tissue and vasculature. The best selection of treatment beam angles will be provided by high resolution fluoroscopic images of the stented region obtained from different beam directions. The three-dimensional movement of the stent, indexed in time with the QRS complex, will provide an important measure for gating radiation beams for conformal treatment delivery.

Dosimetric comparison of centered and off-centered posterior neck electron fields.

Approximately rectangular low or medium energy electron fields at extended SSD are often used to boost over the spinal cord in the treatment of head and neck cancer after cord tolerance is reached. A separate abutting photon field is used to continue treatment anterior to the spine. Typically, the electron and photon fields have different central axes and the electron cutout is symmetrically centered in the cone. However, a good match between the photon and electron fields is achieved more readily if the central axis of the electron field is located at the center of the area treated by the photon field. This displaces the electron cutout toward the edge of the cone. We measured and compared the percent depth dose (PDD), output factors and profiles for matched pairs of centered and off-centered rectangular and square cutouts for the 6, 9 and 12 MeV beams of three Varian linacs. The 10 x 10 and 15 x 15 cones were used at SSDs of 100 cm and 110 cm. Differences between centered and off-centered cutouts of the same dimensions were less than 1% for PDD and profiles and less than 5% for output factors. Therefore, the same central axis can be used for abutting photon and electron fields, without requiring extra dosimetric data to account for the off-center location of the electron cutout.

Use of the fast Hartley transform for three-dimensional dose calculation in radionuclide therapy.

Effective radioimmunotherapy may depend on a priori knowledge of the radiation absorbed dose distribution obtained by trace imaging activities administered to a patient before treatment. A new, fast, and effective treatment planning approach is developed to deal with a heterogeneous activity distribution. Calculation of the three-dimensional absorbed dose distribution requires convolution of a cumulated activity distribution matrix with a point-source kernel; both are represented by large matrices (64 x 64 x 64). To reduce the computation time required for these calculations, an implementation of convolution using three-dimensional (3-D) fast Hartley transform (FHT) is realized. Using the 3-D FHT convolution, absorbed dose calculation time was reduced over 1000 times. With this system, fast and accurate absorbed dose calculations are possible in radioimmunotherapy. This approach was validated in simple geometries and then was used to calculate the absorbed dose distribution for a patient's tumor and a bone marrow sample.

Treatment planning for radio-immunotherapy.

To foster the success of clinical trials in radio-immunotherapy (RIT), one needs to determine (i) the quantity and spatial distribution of the administered radionuclide carrier in the patient over time, (ii) the absorbed dose in the tumour sites and critical organs based on this distribution and (iii) the volume of tumour mass(es) and normal organs from computerized tomography or magnetic resonance imaging and appropriately correlated with nuclear medicine imaging techniques (such as planar, single-photon emission computerized tomography or positron-emission tomography). Treatment planning for RIT has become an important tool in predicting the relative benefit of therapy based on individualized dosimetry as derived from diagnostic, pre-therapy administration of the radiolabelled antibody. This allows the investigator to pre-select those patients who have 'favorable' dosimetry characteristics (high time-averaged target: non-target ratios) so that the chances for treatment success may be more accurately quantified before placing the patient at risk for treatment-related organ toxicities. The future prospects for RIT treatment planning may yield a more accurate correlation of response and critical organ toxicity with computed absorbed dose, and the compilation of dose-volume histogram information for tumour(s) and normal organ(s) such that computing tumour control probabilities and normal tissue complication probabilities becomes possible for heterogeneous distributions of the radiolabelled antibody. Additionally, radiobiological consequences of depositing absorbed doses from exponentially decaying sources must be factored into the interpretation when trying to compute the effects of standard external beam isodose display patterns combined with those associated with RIT.

A rapid phantom technique for checking blocked vertex fields.

A simple phantom technique for quality assurance in beam arrangements involving a vertex field is described. Clinical personnel can quickly check that blocks for the vertex field have been cut to the proper magnification and that the vertex field is in proper registration with accompanying isocentric transverse fields. Errors can be identified rapidly and corrections made with no inconvenience to the patient.

Tumor activity confirmation and isodose curve display for patients receiving iodine-131-labeled 16.88 human monoclonal antibody.

A study was performed to correlate activity quantitation derived from external imaging with surgical tumor specimens in patients who received radiolabeled monoclonal antibody. Patients were given I-131 labeled 16.88 human antibody and scanned 3-5 times by planar and/or single photon emission computed tomography imaging methods to acquire time-dependent activity data in tumor and normal tissues. A method also was developed to assess the heterogeneous activity distributions in tumor samples. Postsurgical tumor and normal tissue samples were subdivided into volume elements (voxels) of 0.5 cm x 0.5 cm x 0.05 cm thick, which were used to verify the activity quantitation computed by the conjugate view method and to appraise the heterogeneity of radiolabeled antibody uptake. Through the use of the measured voxel activities, along with the time-dependent activity curves available for the entire tumor specimen derived from imaging, the cumulated activity and absorbed dose for each voxel were uniquely determined. The calculated total absorbed dose values were color-coded as isodose curves and overlaid on a correlated computed tomographic image. In two patients, activity quantitation derived from external imaging correlated with surgical tumor resection specimens within +/- 11%. The tumor-absorbed dose heterogeneity ratio was found to be as high as 10:1, with an average tumor to whole body absorbed dose ratio of 4:1. The mapping of activity with a histologic overlay showed a good correlation among activity uptake, the presence of tumor, and antigen expression on a microscopic scale. The resultant isodose curves overlaid on correlative computed tomographic scans represent the first images obtained with actual radiolabeled antibody biodistribution data in patients.

Modeling the development of metastases from primary and locally recurrent tumors: comparison with a clinical data base for prostatic cancer.

For many types of cancer, patients who relapse locally following localized treatment such as surgery or radiation therapy are found to have a higher incidence of distant metastases than those who are locally controlled. In this study we developed a mathematical model to investigate whether the excess distant metastases arise mainly from the local recurrence or whether the primary tumors in this group of patients have an intrinsically higher metastatic potential than those of locally controlled patients of the same clinical stage. The parameters of the model were chosen to be representative of prostate cancer and the calculated results were compared with published clinical data for carcinoma of the prostate. The best agreement with the data was seen for parameters which imply somewhat more "aggressive" primary tumors for locally relapsing patients, yielding relatively high rates of micrometastatic dissemination prior to initial diagnosis. However, the model calculations indicate that more than half of the metastases in such patients originated in association with the development of a local recurrence. Therefore, achieving local control in this group of patients would be beneficial in improving long term survival.

Considerations on the calibration of small thermoluminescent dosimeters used for measurement of beta particle absorbed doses in liquid environments.

An investigation has been carried out on the factors which affect the absolute calibration of thermoluminescent dosimeters (TLDs) used in beta particle absorbed dose evaluations. Four effects on light output (LO) were considered: decay of detector sensitivity with time, finite TLD volume, dose linearity, and energy dependence. Most important of these was the decay of LO with time in culture medium, muscle tissue, and gels. This permanent loss of sensitivity was as large as an order of magnitude over a 21-day interval for the nominally 20-microns-thick disc-shaped CaSO4(Dy) TLDs in gel. Associated leaching of the dosimeter crystals out of the Teflon matrix was observed using scanning electron microscopy. Large channels leading from the outside environment into the TLDs were identified using SEM images. A possibility of batch dependence of fading was indicated. The second most important effect was the apparent reduction of light output due to finite size and increased specific gravity of the dosimeter (volume effect). We estimated this term by calculations as 10% in standard "mini" rods for beta particles from 90Y, but nearly a factor of 3 for 131I beta particles in the same geometry. No significant nonlinearity of the log (light output) with log (absorbed dose) over the range 0.05-20.00 Gy was discovered. Energy dependence of the LO was found to be not detectable, within measurement errors, over the range of 0.60-6.0 MeV mean energy electrons. With careful understanding of these effects, calibration via gel phantom would appear to be an acceptable strategy for mini TLDs used in beta absorbed dose evaluations in media.(ABSTRACT TRUNCATED AT 250 WORDS)

Probability of radiation-induced complications for normal tissues with parallel architecture subject to non-uniform irradiation.

A biologically based model is developed to predict radiation-induced normal tissue complication probability (NTCP) in inhomogeneously irradiated organs such as the lung or the kidney. The organ is assumed to be composed of independent functional subunits (FSUs) organized with a parallel architecture and it is assumed that the complication is produced only if a sufficiently large number of FSUs (the "functional reserve") are destroyed. A general expression for NTCP is derived, as well as simple expressions for the mean and standard deviation of the radiation damage to the FSUs. It is demonstrated that these results for inhomogeneous irradiation reproduce those of the serial and tumor control models when the functional reserve consists of one or all of the FSUs, respectively. When the number of FSUs is large, the dose response for organs with identical characteristics is very steep. Since clinical dose-response curves may arise from populations with varying functional reserves and radiosensitivities, we derive expressions for the NTCP for inhomogeneously irradiated organs that incorporate such variations.

Multicellular dosimetry for beta-emitting radionuclides: autoradiography, thermoluminescent dosimetry and three-dimensional dose calculations.

Inhomogeneities in activity distributions over distances from 10 to 10(4) microns are observed in many tumors treated with radiolabeled antibodies. Resulting nonuniformities in absorbed dose may have consequences for the efficacy of radioimmunotherapy. Activity variations may be directly studied with quantitative autoradiography (ARG). Converting these data to absorbed dose distributions requires additional information about pharmacokinetics, the use of a point source function and consideration of the complete three-dimensional activity distribution, as obtained from sequential autoradiographic slices. Thermoluminescent dosimetry with specially prepared CaSO4:Dy dosimeters implanted into tissue can directly measure absorbed dose in selected regions. The conditions under which thermoluminescent dosimeters (TLD) are used differ markedly from "normal" use conditions in external beam radiotherapy. Therefore special calibration and quality assurance precautions are needed to assure the precision of this technique. Procedures and pitfalls in the use of both techniques in radioimmunotherapy are described.

Probability of radiation-induced complications in normal tissues with parallel architecture under conditions of uniform whole or partial organ irradiation.

A biologically based model is developed for normal tissue complication probability as a function of dose and irradiated volume fraction for organs such as the kidney and the lung. The organ is assumed to be composed of functional subunits (FSUs) which are arranged in a parallel architecture. The complication is produced only if a sufficiently large fraction of the FSUs are inactivated by radiation and an FSU is inactivated only when all the clonogenic cells within it are killed. The linear-quadratic model is used for the dose-response of individual cells within an FSU. The predictions of this model are compared with those of an empirical power law function for uniform whole and partial organ irradiation.

Comparisons of sectioned micro-TLD dose measurements with predicted dose from 131I-labeled antibody.

The dose distribution from radioimmunotherapy is very heterogeneous because of variability in antigen expression, antibody penetration, and tumor architecture. Many models of dose distribution have been constructed but it has been very difficult to confirm these predictions with actual measured doses. The purpose of this study was to determine what degree of resolution could be obtained using mini-thermoluminescent dosimeter(s) (TLD) in a micrometastasis model. TLDs were inserted into 1-mm-diam multicell tumor spheroids that had been treated with 131I-labeled antibody. The spheroids were then sectioned at 30-microns intervals and the TLD sections (measuring 0.14 x 0.1 x 0.03 mm) were removed and read. Calibration of the TLDs was done with whole TLDs using external beam radiation and an 131I-containing gel, and with TLD sections using external beam radiation. Predicted doses were determined by measuring the activity in individual spheroids and the time the TLDs were in the spheroids and incorporating these numbers into a model that assumed either surface binding of 131I or some degree of penetration. There was a correlation between the measured TLD dose and the predicted absorbed dose when comparing the low- to high-dose regions. However, there was considerable variation within any particular dose range, probably due to heterogeneity in TLD grain size.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical implications of I-125 dosimetry of bone and bone-soft tissue interfaces.

The dose to bone from I-125 photon interactions is expected to be approximately five times greater than the dose to soft tissue for the same photon fluence because of the dominance of the photoelectric effect. However, adverse clinical effects are not observed for I-125 implants near bone. Both the strong absorption of I-125 photons in bone and the narrowness (about 10 mu) of the high dose transition zone at a bone-soft tissue interface act to limit the volume of radiation sensitive tissue in the high dose region. Examples of calculated implant dose distributions in bone and in soft tissue cavities in bone are presented. Radiobiological measurements are consistent with the theoretical interface calculations. Calculation of the macroscopic dose distribution uses a recently measured radial dose function, while at the bone-soft tissue interface an analytic theory of the transition zone that is applicable to regular shaped cavities is used. Radiobiological experiments comparing cell survival for cells irradiated with 70 kvP X rays at Al-water and polystyrene-water interfaces are consistent with the transition zone calculations.

Optimal antibody-radionuclide combinations for clinical radioimmunotherapy: a predictive model based on mouse pharmacokinetics.

A theoretical comparison was made of radioimmunotherapy (RIT) dosimetry estimates for eight radionuclides (90Y, 105Rh, 131I, 153Sm, 186Re, 188Re, 198Au, 211At) conjugated to IgG, F(ab')2, and Fab antibody forms. Antibody pharmacokinetics, derived from a nude mouse animal model were combined with appropriate physical data and S values to evaluate absorbed dose to a 0.5 kg centrally located tumor, total body and kidney. Radioimmunoconjugates of F(ab')2 with 90Y, 153Sm and 186Re were predicted to be the most promising for RIT.

Interface dosimetry for I-125 sources.

Use of I-125 in breast implants may be therapeutically beneficial due to the 40% higher dose to the tumor relative to the normal adipose tissue. The dose distribution in the interface between adipose and nonadipose tissues is studied with mathematical models and radiobiological measurements. The dose transition zone is narrow, about 10 mu, which is roughly the diameter of a cell. The dimension of the transition zone is weakly sensitive to the geometry of the interface. In most geometries, cells on either side of the interface receive doses that are significantly different (25%-35%). Radiobiological measurements are consistent with calculated results, providing a check on the theoretical model.