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Aim of the Study: Statistical analysis of pre-treatment dose verification of intensity-modulated radiotherapy (IMRT) fields to assess the quality of the IMRT practice at different radiotherapy centers., Materials and Methods: The dose verification data acquired by the institutional physicist of 10 different hospitals for various types of patients were collected and analyzed for mean, median, standard deviation (SD), range, minimum and maximum % deviation. The percentage of cases having positive and negative dose differences as well dose differences within ± 3% were also determined., Results: The mean values of percentage variation in difference between treatment planning systems calculated dose and difference between measured dose (D(TPS) and D(Meas)) are found to be from -1.79 to 1.48 and median from -1.79 to 1.51. The SDs are found to be from 0.76 to 3.70. The range of variation at these centers varies from 3.99 to 16.45 while minimum and maximum values of percentage variation in difference between D(TPS) and D(Meas) ranges from -10.33 to 13.38. The percentage of cases having positive dose difference ranges from 8 to 94 and cases having negative dose difference ranges from 6 to 92. The percentage of cases having dose difference within ± 3% varies from 57 to 100., Conclusion: IMRT centers are having random and biased (skewed towards over or under dose) distribution of the percentage variation in difference between measured and planned doses. The analysis of results of the IMRT pre-treatment dose verification reveals that there are systematic errors in the chain of IMRT treatment process at a few centers. The dosimetry quality audit prior to commissioning of IMRT may play an important role in avoiding such discrepancies.

Purpose: To review the type and frequency of patient events from external-beam radiotherapy over a time period sufficiently long to encompass significant technology changes., Methods and Materials: Ten years of quality assurance records from January 2001 through December 2010 were retrospectively reviewed to determine the frequency of events affecting patient treatment from four radiation oncology process steps: simulation, treatment planning, data entry/transfer, and treatment delivery. Patient events were obtained from manual records and, from May 2007 onward, from an institution-wide database and reporting system. Events were classified according to process step of origination and segregated according to the most frequently observed event types. Events from the institution-wide database were evaluated to determine time trends., Results: The overall event rate was 0.93% per course of treatment, with a downward trend over time led by a decrease in treatment delivery events. The frequency of certain event types, particularly in planning and treatment delivery, changed significantly over the course of the study, reflecting technologic and process changes. Treatments involving some form of manual intervention carried an event risk four times higher than those relying heavily on computer-aided design and delivery., Conclusions: Although the overall event rate was low, areas for improvement were identified, including manual calculations and data entry, late-day treatments, and staff overreliance on computer systems. Reducing the incidence of pretreatment events is of particular importance because these were more likely to occur several times before detection and were associated with larger dosimetric impact. Further improvements in quality assurance systems and reporting are imperative, given the advent of electronic charting, increasing reliance on computer systems, and the potentially severe consequences that can arise from mistakes involving complex intensity-modulated or image-guided treatments., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Our goal is to determine an optimized image-guided setup by comparing setup errors determined by two-dimensional (2D) and three-dimensional (3D) image guidance for head and neck cancer (HNC) patients immobilized by customized thermoplastic masks. Nine patients received weekly imaging sessions, for a total of 54, throughout treatment. Patients were first set up by matching lasers to surface marks (initial) and then translationally corrected using manual registration of orthogonal kilovoltage (kV) radiographs with DRRs (2D-2D) on bony anatomy. A kV cone beam CT (kVCBCT) was acquired and manually registered to the simulation CT using only translations (3D-3D) on the same bony anatomy to determine further translational corrections. After treatment, a second set of kVCBCT was acquired to assess intrafractional motion. Averaged over all sessions, 2D-2D registration led to translational corrections from initial setup of 3.5 ± 2.2 (range 0-8) mm. The addition of 3D-3D registration resulted in only small incremental adjustment (0.8 ± 1.5 mm). We retrospectively calculated patient setup rotation errors using an automatic rigid-body algorithm with 6 degrees of freedom (DoF) on regions of interest (ROI) of in-field bony anatomy (mainly the C2 vertebral body). Small rotations were determined for most of the imaging sessions; however, occasionally rotations > 3° were observed. The calculated intrafractional motion with automatic registration was < 3.5 mm for eight patients, and < 2° for all patients. We conclude that daily manual 2D-2D registration on radiographs reduces positioning errors for mask-immobilized HNC patients in most cases, and is easily implemented. 3D-3D registration adds little improvement over 2D-2D registration without correcting rotational errors. We also conclude that thermoplastic masks are effective for patient immobilization.

Respiration-induced tumor motion during intensity-modulated radiotherapy (IMRT) of non-small-cell lung cancer (NSCLC) could cause substantial differences between planned and delivered doses. While it has been shown that, for conventionally fractionated IMRT, motion effects average out over the course of many treatments, this might not be true for hypofractionated IMRT (IMHFRT). Numerical simulations were performed for nine NSCLC patients (11 tumors) to evaluate this problem. Dose distributions to the Clinical Target Volume (CTV) and Internal Target Volume (ITV) were retrospectively calculated using the previously-calculated leaf motion files but with the addition of typical periodic motion (i.e. amplitude 0.36-1.26cm, 3-8sec period). A typical IMHFRT prescription of 20Gy x 3 fractions was assumed. For the largest amplitude (1.26 cm), the average +/- standard deviation of the ratio of simulated to planned mean dose, minimum dose, D95 and V95 were 0.98+/-0.01, 0.88 +/- 0.09, 0.94 +/- 0.05 and 0.94 +/- 0.07 for the CTV, and 0.99 +/-0.01, 0.99 +/- 0.03, 0.98 +/- 0.02 and 1.00 +/- 0.01 for the ITV, respectively. There was minimal dependence on period or initial phase. For typical tumor geometries and respiratory amplitudes, changes in target coverage are minimal but can be significant for larger amplitudes, faster beam delivery, more highly-modulated fields, and smaller field margins.

Digital tomosynthesis (DTS) with a linear accelerator-mounted imaging system provides a means of reconstructing tomographic images from radiographic projections over a limited gantry arc, thus requiring only a few seconds to acquire. Its application in the thorax, however, often results in blurred images from respiration-induced motion. This work evaluates the feasibility of respiration-correlated (RC) DTS for soft-tissue visualization and patient positioning. Image data acquired with a gantry-mounted kilovoltage imaging system while recording respiration were retrospectively analyzed from patients receiving radiotherapy for non-small-cell lung carcinoma. Projection images spanning an approximately 30 degrees gantry arc were sorted into four respiration phase bins prior to DTS reconstruction, which uses a backprojection, followed by a procedure to suppress structures above and below the reconstruction plane of interest. The DTS images were reconstructed in planes at different depths through the patient and normal to a user-selected angle close to the center of the arc. The localization accuracy of RC-DTS was assessed via a comparison with CBCT. Evaluation of RC-DTS in eight tumors shows visible reduction in image blur caused by the respiratory motion. It also allows the visualization of tumor motion extent. The best image quality is achieved at the end-exhalation phase of the respiratory motion. Comparison of RC-DTS with respiration-correlated cone-beam CT in determining tumor position, motion extent and displacement between treatment sessions shows agreement in most cases within 2-3 mm, comparable in magnitude to the intraobserver repeatability of the measurement. These results suggest the method's applicability for soft-tissue image guidance in lung, but must be confirmed with further studies in larger numbers of patients.

A novel IMRT phantom was designed and fabricated using Acrylonitrile Butadiene Styrene (ABS) plastic. Physical properties of ABS plastic related to radiation interaction and dosimetry were compared with commonly available phantom materials for dose measurements in radiotherapy. The ABS IMRT phantom has provisions to hold various types of detectors such as ion chambers, radiographic/radiochromic films, TLDs, MOSFETs, and gel dosimeters. The measurements related to pre-treatment dose verification in IMRT of carcinoma prostate were carried out using ABS and Scanditronics-Wellhoffer RW3 IMRT phantoms for five different cases. Point dose data were acquired using ionization chamber and TLD discs while Gafchromic EBT and radiographic EDR2 films were used for generating 2-D dose distributions. Treatment planning system (TPS) calculated and measured doses in ABS plastic and RW3 IMRT phantom were in agreement within +/-2%. The dose values at a point in a given patient acquired using ABS and RW3 phantoms were found comparable within 1%. Fluence maps and dose distributions of these patients generated by TPS and measured in ABS IMRT phantom were also found comparable both numerically and spatially. This study indicates that ABS plastic IMRT phantom is a tissue equivalent phantom and dosimetrically it is similar to solid/plastic water IMRT phantoms. Though this material is demonstrated for IMRT dose verification but it can be used as a tissue equivalent phantom material for other dosimetry purposes in radiotherapy.

We present a unique case in which a patient with significant tissue loss was monitored for dosimetric changes using weekly cone beam computed tomography (CBCT) scans. A previously treated nasopharynx patient presented with a large, exophytic, recurrent left neck mass. The patient underwent re-irradiation to 70 Gy using intensity modulated radiation therapy (IMRT) with shielding blocks over the spinal cord and brain stem. Weekly CBCT scans were acquired during treatment. Target contours and treatment fields were then transferred from the original treatment planning computed tomography (CT) to the CBCT scans and dose calculations were performed on all CBCT scans and compared to the planning doses. In addition, a "research" treatment plan was created that assumed the patient had not been previously treated, and the above analysis was repeated. Finally, to remove the effects of setup error, the outer contours of 2 CBCT scans with significant tumor reductions were transferred to the planning scan and dose in the planning scan was recalculated. Planning treatment volume (PTV) decreased 45% during treatment. Spinal cord D05 differed from the planned value by 3.5 +/- 9.8% (average + standard deviation). Mean dose to the oral cavity and D05 of the mandible differed from the planned value by 0.9 +/- 2.1% and 0.6 +/- 1.5%, respectively. Results for the research plan were comparable. Target coverage did not change appreciably (-0.2 +/- 2.5%). When the planning scan was recalculated with the reduced outer contour from the CBCT, spinal cord D05 decreased slightly due to the reduction in scattered dose. Weekly imaging provided us the unique opportunity to use different methods to examine the dosimetric effects of an unusually large loss of tissue. We did not see that tissue loss alone resulted in a significant effect on the dose delivered to the spinal cord for this case, as most fluctuation was due to setup error. In the IGRT era, delivered dose distributions can be more readily determined during treatment, and this information can be useful in deciding whether replanning is necessary.

New technologies such as intensity modulated and image guided radiation therapy, computer controlled linear accelerators, record and verify systems, electronic charts, and digital imaging have revolutionized radiation therapy over the past 10-15 y. Quality assurance (QA) as historically practiced and as recommended in reports such as American Association of Physicists in Medicine Task Groups 40 and 53 needs to be updated to address the increasing complexity and computerization of radiotherapy equipment, and the increased quantity of data defining a treatment plan and treatment delivery. While new technology has reduced the probability of many types of medical events, seeing new types of errors caused by improper use of new technology, communication failures between computers, corrupted or erroneous computer data files, and "software bugs" are now being seen. The increased use of computed tomography, magnetic resonance, and positron emission tomography imaging has become routine for many types of radiotherapy treatment planning, and QA for imaging modalities is beyond the expertise of most radiotherapy physicists. Errors in radiotherapy rarely result solely from hardware failures. More commonly they are a combination of computer and human errors. The increased use of radiosurgery, hypofractionation, more complex intensity modulated treatment plans, image guided radiation therapy, and increasing financial pressures to treat more patients in less time will continue to fuel this reliance on high technology and complex computer software. Clinical practitioners and regulatory agencies are beginning to realize that QA for new technologies is a major challenge and poses dangers different in nature than what are historically familiar.

Purpose: Implanted gold markers and megavoltage (MV) portal imaging are commonly used for setup verification of paraspinal tumors treated with high-dose, single-fraction radiotherapy. We investigated whether the use of kilovoltage cone-beam computed tomography (CBCT) imaging eliminates the need for marker implantation., Methods and Materials: Patients with paraspinal disease who were eligible for single-fraction stereotactic body radiotherapy were accrued to an institutional review board-approved protocol. Each of 16 patients underwent implantation of fiducial markers near the target. The markers were visible on the MV images. Three MV image pairs were acquired for each patient (initial, verification, and final) and were registered to the reference images. Every MV pair was complemented by a CBCT scan. CBCT image registration was performed automatically by maximizing the mutual information using a region of interest that excluded the markers. The corrections, as determined from the MV images, were compared with these from CBCT and were used for actual patient setup., Results: The mean and standard deviation of the absolute values of the differences between the CBCT and MV corrections were 1.0 +/- 0.7, 1.0 +/- 0.6, and 1.0 +/- 0.8 mm for the left-right, anteroposterior, and superoinferior directions, respectively. The absolute differences between the corresponding pre- and post-treatment kilovoltage CBCT image registration were 0.6 +/- 0.5, 0.6 +/- 0.5, and 1.0 +/- 0.8 mm., Conclusion: The setup corrections found using CBCT without the use of implanted markers were consistent with the marker registration on MV projections. CBCT has additional advantages, including better positioning precision and robust automatic three-dimensional registration, as well as eliminating the need for invasive marker implantation. We have adopted CBCT for the setup of all single-fraction paraspinal patients. Our data have also demonstrated that target displacements during treatment are insignificant.

Purpose: To report the incidence and predictors of treatment-related toxicity at 10 years after three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) for localized prostate cancer., Methods and Materials: Between 1988 and 2000, 1571 patients with stages T1-T3 prostate cancer were treated with 3D-CRT/IMRT with doses ranging from 66 to 81 Gy. The median follow-up was 10 years. Posttreatment toxicities were all graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events., Results: The actuarial likelihood at 10 years for the development of Grade>or=2 GI toxicities was 9%. The use of IMRT significantly reduced the risk of gastrointestinal (GI) toxicities compared with patients treated with conventional 3D-CRT (13% to 5%; p<0.001). Among patients who experienced acute symptoms the 10-year incidence of late toxicity was 42%, compared with 9% for those who did not experience acute symptoms (p<0.0001). The 10-year incidence of late Grade>or=2 genitourinary (GU) toxicity was 15%. Patients treated with 81 Gy (IMRT) had a 20% incidence of GU symptoms at 10 years, compared with a 12% for patient treated to lower doses (p=0.01). Among patients who had developed acute symptoms during treatment, the incidence of late toxicity at 10 years was 35%, compared with 12% (p<0.001). The incidence of Grade 3 GI and GU toxicities was 1% and 3%, respectively., Conclusions: Serious late toxicity was unusual despite the delivery of high radiation dose levels in these patients. Higher doses were associated with increased GI and GU Grade 2 toxicities, but the risk of proctitis was significantly reduced with IMRT. Acute symptoms were a precursor of late toxicities in these patients.

Radiation treatment of large intact breasts with separations of more than 24 cm is typically performed using x-rays with energies of 10 MV and higher, to eliminate high-dose regions in tissue. The disadvantage of the higher energy beams is the reduced dose to superficial tissue in the buildup region. We evaluated 2 methods of avoiding this underdosage: (1) a beam spoiler: 1.7-cm-thick Lucite plate positioned in the blocking tray 35 cm from the isocenter, with 15-MV x-rays; and (2) combining 6- and 15-MV x-rays through the same portal. For the beam with the spoiler, we measured the dose distribution for normal and oblique incidence using a film and ion chamber in polystyrene, as well as a scanning diode in a water tank. In the mixed-energy approach, we calculated the dose distributions in the buildup region for different proportions of 6- and 15-MV beams. The dose enhancement due to the beam spoiler exhibited significant dependence upon the source-to-skin distance (SSD), field size, and the angle of incidence. In the center of a 20 x 20-cm(2) field at 90-cm SSD, the beam spoiler raises the dose at 5-mm depth from 77% to 87% of the prescription, while maintaining the skin dose below 57%. Comparison of calculated dose with measurements suggested a practical way of treatment planning with the spoiler--usage of 2-mm "beam" bolus--a special option offered by in-house treatment planning system. A second method of increasing buildup doses is to mix 6- and 15-MV beams. For example, in the case of a parallel-opposed irradiation of a 27-cm-thick phantom, dose to D(max) for each energy, with respect to midplane, is 114% for pure 6-, 107% for 15-MV beam with the spoiler, and 108% for a 3:1 mixture of 15- and 6-MV beams. Both methods are practical for radiation therapy of large intact breasts.

The purpose of the present study was to use a kilovoltage imaging device to measure interfractional and intrafractional setup deviations in patients with head-and-neck or brain cancers receiving intensity-modulated radiotherapy (IMRT) treatment. Before and after IMRT treatment, approximately 3 times weekly, 7 patients were imaged using the Varian On-Board Imager (OBI: Varian Medical Systems, Palo Alto, CA), a kilovoltage imaging device permanently mounted on the gantry of a Varian 21EX LINAC (Varian Medical Systems). Because of commissioning of the remote couch correction of the OBI during the study, online setup corrections were performed on 2 patients. For the other 5 patients, weekly corrections were made based on a sliding average of the measured data. From these data, we determined the interfractional setup deviation (defined as the shift from the original setup position suggested by the daily image), the residual error associated with the weekly correction protocol, and the intrafractional setup deviation, defined as the difference between the post-treatment and pretreatment images. We also used our own image registration software to determine interfractional and intrafractional rotational deviations from the images based on the template-matching method. In addition, we evaluated the influence of inter-observer variation on our results, and whether the use of various registration techniques introduced differences. Finally, translational data were compared with rotational data to search for correlations. Translational setup errors from all data were 0.0 +/- 0.2 cm, -0.1 +/- 0.3 cm, and -0.2 +/- 0.3 cm in the right-left (RL), anterior-posterior (AP), and superior-inferior (SI) directions respectively. Residual error for the 5 patients with a weekly correction protocol was -0.1 +/- 0.2 cm (RL), 0.0 +/- 0.3 cm (AP), and 0.0 +/- 0.2 cm (SI). Intrafractional translation errors were small, amounting to 0.0 +/- 0.1 cm, -0.1 +/- 0.2 cm, and 0.0 +/- 0.1 cm in the RL, AP, and SI directions respectively. In the sagittal and coronal views respectively, interfractional rotational errors were -1.1 +/- 1.7 degrees and -0.5 +/- 0.9 degrees, and intrafractional rotational errors were 0.3 +/- 0.6 degrees and 0.2 +/- 0.5 degrees. No significant correlation was seen between translational and rotational data. The OBI image data were used to study setup error in the head-and-neck patients. Nonzero systematic errors were seen in the interfractional translational and rotational data, but not in the intrafractional data, indicating that the mask is better at maintaining head position than at reproducing it.

The recently developed GATE (GEANT4 application for tomographic emission) Monte Carlo package, designed to simulate positron emission tomography (PET) and single photon emission computed tomography (SPECT) scanners, provides the ability to model and account for the effects of photon noncollinearity, off-axis detector penetration, detector size and response, positron range, photon scatter, and patient motion on the resolution and quality of PET images. The objective of this study is to validate a model within GATE of the General Electric (GE) Advance/Discovery Light Speed (LS) PET scanner. Our three-dimensional PET simulation model of the scanner consists of 12 096 detectors grouped into blocks, which are grouped into modules as per the vendor's specifications. The GATE results are compared to experimental data obtained in accordance with the National Electrical Manufactures Association/Society of Nuclear Medicine (NEMA/SNM), NEMA NU 2-1994, and NEMA NU 2-2001 protocols. The respective phantoms are also accurately modeled thus allowing us to simulate the sensitivity, scatter fraction, count rate performance, and spatial resolution. In-house software was developed to produce and analyze sinograms from the simulated data. With our model of the GE Advance/Discovery LS PET scanner, the ratio of the sensitivities with sources radially offset 0 and 10 cm from the scanner's main axis are reproduced to within 1% of measurements. Similarly, the simulated scatter fraction for the NEMA NU 2-2001 phantom agrees to within less than 3% of measured values (the measured scatter fractions are 44.8% and 40.9 +/- 1.4% and the simulated scatter fraction is 43.5 +/- 0.3%). The simulated count rate curves were made to match the experimental curves by using deadtimes as fit parameters. This resulted in deadtime values of 625 and 332 ns at the Block and Coincidence levels, respectively. The experimental peak true count rate of 139.0 kcps and the peak activity concentration of 21.5 kBq/cc were matched by the simulated results to within 0.5% and 0.1% respectively. The simulated count rate curves also resulted in a peak NECR of 35.2 kcps at 10.8 kBq/cc compared to 37.6 kcps at 10.0 kBq/cc from averaged experimental values. The spatial resolution of the simulated scanner matched the experimental results to within 0.2 mm.

The current study demonstrates that the large increase in normal tissue penalty often degrades target dose uniformity without a concomitant large improvement in normal tissue dose, especially in anatomically unfavorable patients. The excessively large normal tissue penalties do not improve treatment plans for patients having unfavorable geometry.

The relative inability of conventional radiotherapy to control localized prostate cancer results from resistance of subpopulations of tumor clonogens to dose levels of 65 to 70 Gy, the maximum feasible with traditional two-dimensional (2D) treatment planning and delivery techniques. Several technological advances have enhanced the precision and improved the outcome of external-beam radiotherapy. The three-dimensional conformal radiotherapy (3D-CRT) approach has permitted significant increases in the tumor dose to levels beyond those feasible with conventional techniques. Intensity-modulated radiotherapy (IMRT), an advanced form of conformal radiotherapy, has resulted in reduced rectal toxicity, permitting tumor dose escalation to previously unattainable levels with a concomitant improvement in local tumor control and disease-free survival. The combination of androgen deprivation and conventional-dose radiotherapy, tested mainly in patients with locally advanced disease, has also produced significant outcome improvements. Whether androgen deprivation will preclude the need for dose escalation or whether high-dose radiotherapy will obviate the need for androgen deprivation remains unknown. In some patients, both approaches may be necessary to maximize the probability of cure. In view of the favorable benefit-risk ratio of high-dose IMRT, the design of clinical trials to resolve these critical questions is essential.

Purpose: To design and implement a noninvasive stereotactic immobilization technique with daily CT image-guided positioning to treat patients with paraspinal lesions accurately and to quantify the systematic and random patient setup errors occurring with this method., Methods and Materials: A stereotactic body frame (SBF) was developed for "rigid" immobilization of paraspinal patients. The inherent accuracy of this system for stereotactic CT-guided treatment was evaluated with phantom studies. Seven patients with thoracic and lumbar spine lesions were immobilized with the SBF and positioned for 33 treatment fractions using daily CT scans. For all 7 patients, the daily setup errors, as assessed from the daily CT scans, were corrected at each treatment fraction. A retrospective analysis was also performed to assess what the impact on patient treatment would have been without the CT-based corrections (i.e., if patient setup had been performed only with the SBF)., Results: The average magnitude of systematic and random errors from uncorrected patient setups using the SBF was approximately 2 mm and 1.5 mm (1 SD), respectively. For fixed phantom targets, the system accuracy for the SBF localization and treatment was shown to be within 1 mm (1 SD) in any direction. Dose-volume histograms incorporating these uncertainties for an intensity-modulated radiotherapy plan for lumbar spine lesions were generated, and the effects on the dose-volume histograms were studied., Conclusion: We demonstrated a very accurate and precise method of patient immobilization and treatment delivery based on a noninvasive SBF and daily image guidance for paraspinal lesions. The SBF provides excellent immobilization for paraspinal targets, with setup accuracy better than 2 mm (1 SD). However, for highly conformal paraspinal treatments, uncorrected systematic and random errors of 2 mm in magnitude can result in a significantly greater (>100%) dose to the spinal cord than planned, even though the planned target coverage may not change substantially. With daily CT guidance using the SBF, we showed that the maximal spinal cord dose is ensured to be within 10-15% of the planned value.

Purpose: To evaluate and develop optimum inverse treatment planning strategies for the treatment of concave targets adjacent to normal tissue structures., Methods and Materials: Optimized dose distributions were designed using an idealized geometry consisting of a cylindrical phantom with a concave kidney-shaped target (PTV) and cylindrical normal tissues (NT) placed 5-13 mm from the target. Targets with radii of curvature from 1 to 2.75 cm were paired with normal tissues with radii between 0.5 and 2.25 cm. The target was constrained to a prescription dose of 100% and minimum and maximum doses of 95% and 105% with relative penalties of 25. Maximum dose constraint parameters for the NT varied from 10% to 70% with penalties from 10 to 1000. Plans were evaluated using the PTV uniformity index (PTV D(max)/PTV D(95)) and maximum normal tissue doses (NT D(max)/PTV D(95))., Results: In nearly all situations, the achievable PTV uniformity index and the maximum NT dose exceeded the corresponding constraints. This was particularly true for small PTV-NT separations (5-8 mm) or strict NT dose constraints (10%-30%), where the achievable doses differed from the requested by 30% or more. The same constraint parameters applied to different PTV-NT separations yielded different dose distributions. For most geometries, a range of constraints could be identified that would lead to acceptable plans. The optimization results were fairly independent of beam energy and radius of curvature, but improved as the number of beams increased, particularly for small PTV-NT separations or strict dose constraints., Conclusion: Optimized dose distributions are strongly affected by both the constraint parameters and target-normal tissue geometry. Standard site-specific constraint templates can serve as a starting point for optimization, but the final constraints must be determined iteratively for individual patients. A strategy whereby NT constraints and penalties are modified until the highest acceptable PTV uniformity index is achieved is discussed. This strategy can be used, in simple patient geometries, to ensure the lowest possible normal tissue dose. Strategies for setting the optimum dose constraints and penalties may vary for different optimization algorithms and objective functions. Increasing the number of beams can significantly improve normal tissue dose and target uniformity in situations where the PTV-NT separation is small or the normal tissue dose limits are severe. Setting unrealistically severe constraints in such situations often results in dose distributions that are inferior to plans achieved with more lenient constraints.

Purpose: To compare intensity-modulated radiotherapy (IMRT) and conventional three-dimensional conformal radiotherapy (3D-CRT) for the boost treatment of new-onset nasopharyngeal carcinoma (NPC) or the salvage treatment of locally recurrent NPC., Methods and Materials: Between January 14 and February 23, 2000, 5-field 3D-CRT treatment plans were generated for 14 consecutive NPC patients using the ADAC Pinnacle planning system in Chang Gung Memorial Hospital, Kaohsiung, Taiwan. The planning data of these patients were later transferred to Memorial Sloan-Kettering Cancer Center, where new IMRT plans, also using 5-7 radiation fields were created for each patient using an inverse treatment planning system. The IMRT and 3D-CRT plans were compared for all 14 patients. The relationship between the anatomic shapes and locations of targets and the results of different plans were studied., Results: Target doses were more homogeneous in IMRT plans. The average maximal brainstem dose (D(05), the dose received by 5% of the brainstem volume) decreased from 30.9% of the prescription dose with 3D-CRT to 15.3% and 14.7% with 5- and 7-field IMRT, respectively (p = 0.004 and 0.003, respectively, compared with 3D-CRT, paired Student's t test). Five anatomic factors were found that predicted greater benefits with IMRT. These factors were (1) vertical length of target >7 cm, (2) minimal distance between target and brainstem <0.1 cm, (3) maximal AP overlap of target and brainstem >0.6 cm, (4) maximal AP overlap of target and spinal cord >1 cm, and (5) vertical overlap of target and eyes >0 cm. For the 7 patients with at least 1 of these 5 anatomic factors, the benefits achieved by IMRT planning would have been greater than the benefits for the other 7 patients (p = 0.005, Fisher's exact test)., Conclusion: For boost or salvage treatment of NPC, lower normal tissue doses and more homogeneous target doses were achieved with IMRT plans. For NPC patients with at least 1 of the 5 anatomic factors, IMRT is highly recommended.

In brachytherapy implants, the accuracy of dose calculation depends on the ability to localize radioactive sources correctly. If performed manually using planar images, this is a time-consuming and often error-prone process-primarily because each seed must be identified on (at least) two films. In principle, three films should allow automatic seed identification and position reconstruction; however, practical implementation of the numerous algorithms proposed so far appears to have only limited reliability. The motivation behind this work is to create a fast and reliable system for real-time implant evaluation using digital planar images obtained from radiotherapy simulators, or mobile x-ray/fluoroscopy systems. We have developed algorithms and code for 3D seed coordinate reconstruction. The input consists of projections of seed positions in each of three isocentric images taken at arbitrary angles. The method proposed here consists of a set of heuristic rules (in a sense, a learning algorithm) that attempts to minimize seed misclassifications. In the clinic, this means that the system must be impervious to errors resulting from patient motion as well as from finite tolerances accepted in equipment settings. The software program was tested with simulated data, a pelvic phantom and patient data. One hundred and twenty permanent prostate implants were examined (105 125I and 15 103Pd) with the number of seeds ranging from 35 to 138 (average 79). The mean distance between actual and reconstructed seed positions is in the range 0.03-0.11 cm. On a Pentium III computer at 600 MHz the reconstruction process takes 10-30 s. The total number of seeds is independently validated. The process is robust and able to account for errors introduced in the clinic.

Purpose: The objective of this report is to re-evaluate the role of the Anderson nomograms in treatment planning for permanent prostate implants. The incentive for revisiting this topic concerns three issues: (1) Although nomograms continue to be used in many centers for ordering seeds, few centers use them during treatment planning; (2) Whereas nomograms were designed to deliver a minimum peripheral dose for a uniform distribution of seeds in the gland, many practitioners use peripheral seed loading patterns to reduce urethral toxicity; and (3) As preoperative and intraoperative treatment planning is becoming standard, the apparent role of nomograms is diminished. The nomogram method is reviewed in terms of: (1) total activity predicted, (2) target coverage (as planned in the operating room and as calculated from postimplant computed tomography studies), and (3) reproducibility (i.e., patient-to-patient and planner-to-planner variability). In each case, the computer-optimization system for intraoperative planning currently in use at our institution was taken as the "gold standard.", Methods and Materials: We compared for the same patient the results of nomogram planning to those yielded by genetic algorithm (GA) optimization in terms of total activity predicted (n = 20 cases) and percent target coverage (n = 5 cases). Furthermore, we examined retrospectively the dosimetry of 61 prostate implants planned with the GA (n = 27) and the current implementation of Anderson nomograms (n = 34)., Results: Nomogram predictions of the total activity required are in good agreement (within 10%) with the GA-planned activity. However, computer-optimized plans consistently yield superior plans, as reflected in both pre- and postimplant analyses. We find also that user (specifically, treatment planner) implementation of the nomograms may be a major source of variability in nomogram planning-a difficulty to which robust computer optimization is less prone., Conclusions: Nomograms continue to be useful tools for predicting the total required activity for volume implants, and thus for performing an independent check of this quantity. Not unexpectedly, computer optimization remains the preferred planning method. Generally, nomogram-guided implants do not incorporate structures other than the treatment volume into the planning process. Further yet, they deliver a lower dose than that prescribed and result in greater variability among plans than computer-optimized treatments. In summary, nomograms (1) remain an efficient quality assurance tool for computer-generated plans, (2) serve as a good predictor of the number of seeds required for ordering purposes, and (3) provide a simple and dependable backup planning method in case the intraoperative planning system fails.

We describe a fast, PC-based optimization planning system for a planar permanent-seed implant. Sites where this system is applicable include brain, lung, and head and neck. The system described here allows placing ribbons of different strengths and of different lengths along and across the implant plane. The program takes full advantage of the availability of different source strengths in inventory, and attempts to find configurations of ribbons that result in optimal dose uniformity over the prescription plane. Dosimetry is based on the AAPM TG 43 Report [R. Nath et al., Med. Phys. 22, 209-234 (1995)]. Compared with TG 43 parameters, the classical tables underestimate the I-125 source strengths needed by 40%. The use of several source strengths improves the plan. Typical optimization yields dose uniformity of 10%, and computing times are within 2-3 min. No further enhancement is obtained if ribbons are placed in a grid pattern as opposed to the (simpler) arrangement along parallel lines. Nor is it valuable to have variable ribbon lengths. For an I-125 implant the optimization system described here is a practical alternative to the (strictly speaking inapplicable) classical systems. It calculates correctly the total source strengths, and--most notably--generates plans with optimal dose uniformity. The fast computing time is well suited for planning during surgery in the operating room.

Intensity-modulated radiotherapy represents a recent advancement in conformal radiotherapy. It employs specialized computer-driven technology to generate dose distributions that conform to tumor targets with extremely high precision. Treatment planning is based on inverse planning algorithms and iterative computer-driven optimization to generate treatment fields with varying intensities across the beam section. Combinations of intensity-modulated fields produce custom-tailored conformal dose distributions around the tumor, with steep dose gradients at the transition to adjacent normal tissues. Thus far, data have demonstrated improved precision of tumor targeting in carcinomas of the prostate, head and neck, thyroid, breast, and lung, as well as in gynecologic, brain, and paraspinal tumors and soft tissue sarcomas. In prostate cancer, intensity-modulated radiotherapy has resulted in reduced rectal toxicity and has permitted tumor dose escalation to previously unattainable levels. This experience indicates that intensity-modulated radiotherapy represents a significant advancement in the ability to deliver the high radiation doses that appear to be required to improve the local cure of several types of tumors. The integration of new methods of biologically based imaging into treatment planning is being explored to identify tumor foci with phenotypic expressions of radiation resistance, which would likely require high-dose treatments. Intensity-modulated radiotherapy provides an approach for differential dose painting to selectively increase the dose to specific tumor-bearing regions. The implementation of biologic evaluation of tumor sensitivity, in addition to methods that improve target delineation and dose delivery, represents a new dimension in intensity-modulated radiotherapy research.

Purpose: We describe computer software that performs, quickly and accurately, secondary dose calculations for high-dose-rate (HDR) treatment plans, including those employed for prostate treatments., Methods: The program takes as primary input the data file used by the HDR remote afterloader console for treatment. Dosimetric calculations are performed using the Meisberger polynomial and the anisotropy table for the HDR Iridium-192 source. For standard applicators, treatment geometry is automatically reconstructed and the dose is calculated at relevant reference point(s). Template-based treatment plans (e.g., prostate) require additional user input; the dose calculation is then performed at user-selected reference points. A total dwell time calculation for volume and planar implants using the Manchester tables was also implemented., Results: For fixed-geometry HDR procedures, secondary dose calculations are within 2% of the treatment plan, and results are available for review instantly. For more general applications, the calculated and planned doses are typically within 3% at the prescription isodose line. The Manchester-based dwell time calculation is within 10% of the planned time.

Purpose: Recent studies have demonstrated that magnetic-resonance spectroscopic imaging (MRSI) of the prostate may effectively distinguish between regions of cancer and normal prostatic epithelium. This diagnostic imaging tool takes advantage of the increased choline plus creatine versus citrate ratio found in malignant compared to normal prostate tissue. The purpose of this study is to describe a novel brachytherapy treatment-planning optimization module using an integer programming technique that will utilize biologic-based optimization. A method is described that registers MRSI to intraoperative-obtained ultrasound images and incorporates this information into a treatment-planning system to achieve dose escalation to intraprostatic tumor deposits., Methods: MRSI was obtained for a patient with Gleason 7 clinically localized prostate cancer. The ratios of choline plus creatine to citrate for the prostate were analyzed, and regions of high risk for malignant cells were identified. The ratios representing peaks on the MR spectrum were calculated on a spatial grid covering the prostate tissue. A procedure for mapping points of interest from the MRSI to the ultrasound images is described. An integer-programming technique is described as an optimization module to determine optimal seed distribution for permanent interstitial implantation. MRSI data are incorporated into the treatment-planning system to test the feasibility of dose escalation to positive voxels with relative sparing of surrounding normal tissues. The resultant tumor control probability (TCP) is estimated and compared to TCP for standard brachytherapy-planned implantation., Results: The proposed brachytherapy treatment-planning system is able to achieve a minimum dose of 120% of the 144 Gy prescription to the MRS positive voxels using (125)I seeds. The preset dose bounds of 100-150% to the prostate and 100-120% to the urethra were maintained. When compared to a standard plan without MRS-guided optimization, the estimated TCP for the MRS-optimized plan is superior. The enhanced TCP was more pronounced for smaller volumes of intraprostatic tumor deposits compared to estimated TCP values for larger lesions., Conclusions: Using this brachytherapy-optimization system, we could demonstrate the feasibility of MRS-optimized dose distributions for (125)I permanent prostate implants. Based on probability estimates of anticipated improved TCP, this approach may have an impact on the ability to safely escalate dose and potentially improve outcome for patients with organ-confined but aggressive prostatic cancers. The magnitude of the TCP enhancement, and therefore the risks of ignoring the MR data, appear to be more substantial when the tumor is well localized; however, the gain achievable in TCP may depend quite considerably on the MRS tumor-detection efficiency.

A computer language is presented that can be used to generate image files, as if the images are created with a CT or a MR scanner. The language defines objects in the "scanner's" coordinate system, as sets of quadratic inequalities. Each of these objects, e.g., an ellipsoid or a half-plane or a cylinder, has its own density. Objects can be superimposed and collections of objects are allowed to translate and rotate. The language allows for a concise way of describing complex objects with precisely defined geometries and densities. An implementation of the language can be used for testing, developing, and analyzing diagnostic software, treatment planning systems, etc. A software module that is based on the language can be made available. The utility of the module for acceptance testing of radiation therapy treatment planning systems is described.

Intravascular brachytherapy (IVBT) has rapidly gained acceptance as a new treatment modality for reducing restenosis and improving the success rate of percutaneous transluminal coronary angioplasty (PTCA). Recent clinical results on patients treated with beta-emitting 32P stents suggest that radiation reduces in-stent restenosis but may exacerbate neointimal growth at the edges of the stents. This has been referred to as the "candy wrapper effect." It is well known that radioactive stents yield extremely inhomogeneous dose distributions, with low doses delivered to tissues in between stent struts, at the ends of the stent, and also at depth. Some animal model studies suggest that low doses of radiation may stimulate rather than inhibit neointimal growth in an injured vessel, and it is hypothesized that dose inhomogeneity at the ends of a stent may contribute to the candy wrapper effect. We present here a theoretical study comparing dose distributions for beta stents vs. gamma stents; "dumbbell" radioactive loaded stents vs. uniformly loaded stents; and stents with alternate strut design. Calculations demonstrate that dose inhomogenieties between stent struts, at the ends of stents, and at depth can be reduced by better stent design and isotope selection. Prior to the introduction of radioactive stents, criteria for stent design included factors such as trackability, flexibility, strength, etc. We show here that if stent design also includes criteria for strut shape and spacing that improved dose distributions are possible, which in turn could reduce the candy wrapper effect.

Purpose: Healthy and neoplastic tissues are generally exposed nonuniformly to ionizing radiation. It is thus useful to develop algorithms that predict the probability of tumor control or normal tissue complication probability (NTCP) for any given spatial pattern of dose delivery. The questions addressed here concern: (a) the sensitivity of the NTCP predictions to the actual model used for extrapolation from uniform irradiation (where some clinical data exist) to nonuniform exposures, (b) its dependence on tissue type, and (c) consequences for treatment-plan optimization., Methods and Materials: Two (of several possible) NTCP formulations are used here: the Lyman model and a binomial equation. The effective volume-reduction scheme of Kutcher and Burman is used to obtain the NTCP for an arbitrary distribution of dose. NTCP was calculated for seven organs by postulating a dose distribution of maximum nonuniformity., Results: Both models fit available NTCP data well, but have very different extrapolations for exposures of small tissue volumes and very low values of NTCP (e.g., < 5%) where no data exist. Organs with pronounced volume effects (lung, kidneys) show substantial NTCP differences between the two models. Even in organs where the volume effect is small (e.g., spinal cord, brain), differences in NTCP due to the model selected may still have serious clinical consequences, as an actual example (for the spinal cord) indicates., Conclusions: NTCP calculations based on extrapolations to volume fractions and/or NTCP levels for which reliable data do not exist depend on the model used to fit the data and the degree of dose nonuniformity. If NTCP is to be used in treatment-plan optimization, the prudent approach is to design plans that reproduce the conditions under which available dose-volume data were taken (e. g., uniform dose distributions).

Intraluminal irradiation of coronary and peripheral arteries has been shown to reduce neointimal hyperplasia following balloon angioplasty, thereby inhibiting restenosis. Several irradiation techniques are being investigated, including temporary intravascular insertion of high activity gamma- or beta-emitting seeds and wires; inflation of dilatation balloon catheter with radioactive liquid or gas; insertion of miniature x-ray tubes via coronary catheters; permanent implantation of radioactive stents; and postangioplasty fractionated external beam irradiation. Unlike conventional brachytherapy, intravascular treatment of restenosis requires accurate knowledge of dose at distances of 0.5-5 mm from the radioactive source. This requirement presents special problems with regard to source calibration and dose specification, because dose gradients at such close distances from a radioactive source are extremely large. This makes it virtually impossible to define the characteristics of an ideal radiation source without some knowledge of the location and radiosensitivity of the target tissues, plus the radiotolerance of normal tissues. Hence, the current debate over whether beta or gamma sources are to be preferred. Imprecise knowledge of dose-volume effects for coronary arteries, plus uncertainties in the biological time sequencing of restenosis fuel a second debate on whether external beam treatments may be efficacious, and whether or not permanent radioactive stents may prove superior to high dose, single fraction brachytherapy. We review here the dosimetric properties of the various irradiation techniques and isotopes that have been proposed, including aspects of radiation safety, dose homogeneity, and practical aspects of source delivery.

Background: Intravascular irradiation with beta-emitters has been proposed for inhibition of restenosis in coronary arteries after balloon angioplasty or stent implantation. Previous studies have shown the effectiveness of gamma-radiation to prevent recurrent restenosis, even in the presence of an implanted stent. The limited range of beta-particles compared with gamma-radiation, however, opens the question of whether absorption and scattering of beta-particles by stent struts will cause significant perturbations in the uniformity and magnitude of the radiation dose, which may in turn compromise treatment., Methods and Results: Nine different stents were deployed with a balloon filled with a beta-emitting radioactive liquid. Dose distributions were measured with Gafchromic film. Stents varied significantly in their absorption of beta-particles. Some stents, constructed of fine meshed wires, produced minimal dose perturbations. Others, with thicker, high-atomic-number struts, induced cold spots in the dose distribution adjacent to the wires of

Purpose: We address the question of whether or not, for the same average (or integral) dose, a smaller uniform dose to an entire normal tissue structure always results in a lower normal tissue complication probability (NTCP) than does a proportionally larger dose to a partial volume of the same structure., Methods and Materials: A recent compilation of NTCP data and two theoretical formulations of the dependence of NTCP on dose and partial volume irradiated-the Lyman probit equation and the binomial model-are used to examine this question. Both models fit equally well available NTCP data., Results: Empirical data indicate that for lung, kidney, and possibly liver (but not for esophagus, brain, or heart), given a fixed tumor dose and fixed integral dose, NTCP can be minimized by irradiating a partial volume fraction rather than the entire normal organ. The binomial model supports this interpretation, whereas the probit model predicts that for all organs uniform irradiation of the whole organ always results in the lowest possible NTCP., Conclusions: In contrast to what is commonly believed, this study suggests that for at least two normal tissues, namely lung and kidney, there may be situations where "a lot to a little" (i.e., fewer treatment ports) will result in higher tumor control probability and better treatment plan than "a little to a lot" (i.e., multifield treatment). This finding, which is independent of the binomial or probit models used here, depends only on the accuracy of the empirical NTCP data. It is also interesting to note that: a) lung and kidney are commonly classified as parallel tissues, while the others have more of a serial architecture; and b) the choice of the NTCP model can have a profound impact on treatment planning decisions.

Various forms of GAFChromic (GC) film have been used for several years as radiographic media for measuring dose distributions of brachytherapy sources and small radiation fields. In order to optimize the measurement sensitivity and thus improve precision, we describe a method to calculate the dose response curves (net optical density at a give wavelength or spectrum versus absorbed dose) for different densitometer light sources using measured GC film absorption spectra. Comparison with measurements on the latest version of GC film (model MD-55-2) using four types of densitometers [He-Ne laser, broadband (white light) densitometer, and two LED (red-light) filtered densitometers] confirm the accuracy of this predictive model. The linearity and sensitivity of the dose response curves are found to be highly dependent on the light source spectrum. Initial slope is a function of the average weighted absorbance. Early saturation and decreased linearity of the dose response curves are ascribed to the nonuniform transmission of the light source through the GC film. We found that an LED (red-light) source with a narrow bandpass filter centered at 671 nm near the major absorption peak achieves nearly the maximum possible sensitivity (almost four times more sensitive than He-Ne laser, 632.8 nm) and may be suitable for in vivo dosimetry.

Purpose: Treatment plan optimization in radiation oncology entails designing multiple x-ray beams to irradiate a tumor to a dose that will achieve locoregional control while minimizing normal tissue complications. For some anatomical sites, it is possible to estimate tumor control probabilities (TCP) and normal tissue complication probabilities (NTCP) as a function of radiation dose. Thus, treatment plan optimization can be based on biologic end points rather than on dose calculations alone. Given multiple plans with different NTCPs and TCPs, a tradeoff must be made between maximizing TCP and maintaining an acceptable NTCP. How do physicians reach these decisions? Can the process be quantified? Should patients participate in the process?, Methods and Materials: Physicians and patients were asked to rank a series of treatment plans having different combinations of TCP and NTCP. Responses were parametrized into a figure of merit (FM) equation which quantifies predilections of TCP and NTCP., Results: Physician-based FM equations are site- and patient-specific. Variations exist among physicians, but treatment plan selection is often conservative in accordance with the primum non nocere dictum. FM equations generated from the responses of patients suggest that some patients may be willing to accept higher treatment toxicity in exchange for increased TCP., Conclusion: The term "optimized treatment plan" contains inherently subjective criteria which reflect one's willingness to accept treatment morbidity in exchange for probability of cure. These criteria may differ among patients and/or physicians. A quantifiable FM may permit the design of custom-made treatment plans that include physician and patient input.

Purpose: Recent data indicate that intraluminal irradiation of coronary arteries following balloon angioplasty reduces proliferation of smooth muscle cells, neointima formation, and restenosis. We present calculations for various isotopes and geometries in an attempt to identify suitable source designs for such treatments., Methods and Materials: Analytical calculations of dose distributions and dose rates are presented for 192Ir, 125I, 103Pd, 32P, and 90Sr for use in intracoronary irradiation. The effects of source geometry and positioning accuracy are studied., Results: Accurate source centering, high dose rate, well-defined treatment volume, and radiation safety are all of concern; 15-20 Gy are required to a length of 2-3 cm of vessel wall (2-4 mm diameter). Dose must be confined to the region of the angioplasty, with reduced doses to normal tissues. Beta emitters have radiation safety advantages, but may not have suitable ranges for treating large diameter vessels. Gamma emitters deliver larger doses to normal tissues and to staff. Low energy x-ray emitters such as 125I and 103Pd reduce these risks but are not available at high enough activities. The feasibility of injecting a radioactive liquid directly into the angioplasty balloon is also explored., Conclusions: Accurate source centering is found to be of great importance. If this can be accomplished, then high energy beta emitters such as 90Sr would be ideal sources. Otherwise, gamma emitters such as 192Ir may be optimal. A liquid beta source would have optimal geometry and dose distribution, but available sources, such as 32P are unsafe for use with available balloon catheters.

Purpose: To determine the microdosimetric-derived relative biological effectiveness (RBE) of 103Pd, 125I, 241Am, and 192Ir brachytherapy sources at low doses and/or low dose rates., Methods and Materials: The Theory of Dual Radiation Action can be used to predict expected RBE values based on the spatial distribution of energy deposition at microscopic levels from these sources. Single-event lineal energy spectra for these isotopes have been obtained both experimentally and theoretically. A grid-defined wall-less proportional counter was used to measure the lineal energy distributions. Unlike conventional Rossi proportional counters, the counter used in these measurements has a conducting nylon fiber as the central collecting anode and has no metal parts. Thus, the Z-dependence of the photoelectric effect is eliminated as a source of measurement error. Single-event spectra for these brachytherapy sources have been also calculated by: (a) the Monte Carlo code MCNP to generate the electron slowing down spectrum, (b) transport of monoenergetic electron tracks, event by event, with our Monte Carlo code DELTA, (c) using the concept of associated volume to obtain the lineal energy distribution f(y) for each monoenergetic electron, and (d) obtaining the composite lineal energy spectrum for a given brachytherapy source based on the electron spectrum calculated at step (a)., Results: Relative to 60Co, the RBE values obtained from this study are: 2.3 for 103Pd, 2.1 for 125I, 2.1 for 241Am, and 1.3 for 192Ir., Conclusions: These values are consistent with available data from in vitro cell survival experiments. We suggest that, at least for these brachytherapy sources, microdosimetry may be used as a credible alternative to time-consuming (and often uncertain) radiobiological experiments to obtain information on radiation quality and make reliable predictions of RBE in low dose rate brachytherapy.

Recent reports suggest that intraluminal irradiation of coronary arteries in conjunction with balloon angioplasty reduces proliferation of smooth muscle cells and neointima formation, thereby inhibiting restenosis. One possible irradiation technique is to inflate the balloon dilitation catheter with a radioactive solution. This has advantages over other proposed irradiation procedures, in that accurate source positioning and uniform dose to the vessel wall are assured. Several high-energy beta-minus emitters may be suitable for this application. We present experimental measurements and analytical calculations of the dose distribution around a 3-mm-diam by 20-mm-long balloon filled with 90Y-chloride solution. The dose rate at the surface of the balloon is approximately 0.14 cGy/s per mCi/ml (3.78 x 10(-11) Gy/s per Bq/ml), with the dose decreasing to 53% at 0.5 mm, and < 5% at 3.5-mm radial distance. 90Y and other possible isotopes are currently available at specific concentrations > or = 50 mCi/ml (1.85 x 10(9) Bq/ml), which enables the delivery of 20 Gy in less than 5 min. The dosimetric and radiation safety advantages of this system warrant further feasibility studies. Issues of concern include incorporating the beta-emitter into a suitable chemical form, and assessing organ and whole body doses in the (< 1 in 10(3)) event of balloon failure.

Purpose: Relative biological effectiveness (RBE) values for the high linear-energy-transfer particles produced during boron neutron capture therapy have generally been based on theoretical considerations or in vitro experiments. The purpose of this study was to independently determine RBE values for all of the boron neutron capture therapy dose components., Methods and Materials: Clonogenic cell survival data were obtained for 9L rat gliosarcoma cells irradiated in the Brookhaven Medical Research Reactor thermal neutron beam both in vitro and as an intracerebral tumor. These data were analyzed using the linear quadratic model for cell survival to derive measured RBE values for all beam components and for a number of different boron compounds., Results: In the absence of boron, the combined effects of the protons from the nitrogen capture, 14N(n,p)14C, and the fast neutron scatter, 1H(n,n')p, reactions generated RBEs of 3.7 in vitro and 3.2 in an in vivo/in vitro excision assay, compared to 250 kVp X rays using an end point of 1% cell survival. Apparent RBEs for the 10B(n,alpha)7Li reaction products were calculated from cell survival data following reactor irradiations in the presence of the amino acid p-boronophenylalanine, the sulfhydryl dodecaborate monomer or dimer, or boric acid. Apparent RBEs for the 10B(n,alpha)7Li reaction ranged from 1.2 to 9.8 depending on which boron compound was used. RBEs from the in vitro studies were consistently higher than from the in vivo/in vitro studies. Under any conditions, the apparent RBE for the 10B(n,alpha)7Li reaction with p-boronophenylalanine was higher than that with any other boron compound tested., Conclusions: Generally accepted RBE values for the fast neutron and 14N(n,p)14C reaction components of the total dose are too low. The apparent RBEs calculated for the 10B(n,alpha)7Li reaction were compound-dependent and consistent with differences in the distribution of 10B relative to glioma cell nuclei.