Purpose The objective of this study was to examine feasibility of single- or hypo-fraction of high-dose-rate (HDR) electronic brachytherapy (eBT) in uveal melanoma treatment. Material and methods Biologically effective doses (BED) of organs at risk (OARs) were compared to those of iodine-125-based eye plaque low-dose-rate brachytherapy (125I LDR-BT) with vitreous replacement (VR). Single- or hypo-fractionated equivalent physical doses (SFEDs or HFEDs) for tumor were calculated from tumor BED of 125I LDR-BT using linear-quadratic (LQ) and universal survival curve (USC) models. BED OARs doses to retina opposite the implant, macula, optic disc, and lens were calculated and compared among SFED, HFED, and 125I LDR-BT. Electronic BT of 50 kVp was considered assuming dose fall-off as clinically equivalent to 125I LDR-BT. All OARs BEDs were analyzed with and without silicone oil VR. Results For a single-fraction incorporating VR, the median/interquartile range of LQ (USC)-based BED doses of the retina opposite the implant, macula, optic disc, and lens were 16%/1.2% (33%/4%), 35%/19.5% (64%/17.7%), 37%/19% (75%/17.8%), and 27%/7.9% (68%/23.2%) of those for 125I LDR-BT, respectively. SFED tumor values were 29.8/0.2 Gy and 51.7/0.5 Gy when using LQ and USC models, respectively, which could be delivered within 1 hour. SFED can be delivered within 1 hour using a high-dose-rate eBT. Even four-fraction delivery of HFED without VR resulted in higher OARs doses in the macula, optic disc, and lens (135 ~ 159%) than when using 125I LDR-BT technique. A maximum p-value of 0.005 was observed for these distributions. Conclusions The simulation of single-fraction eBT, including vitreous replacement, resulted in significantly reduced OARs doses (16 ~ 75%) of that achieved with 125I LDR-BT.

The purpose of this report is to provide detailed guidance on the dosimetry of the INTRABEAM® (Carl Zeiss Medical AG, Jena, Germany) electronic brachytherapy (eBT) system as it stands at the present time. This report has been developed by the members of American Association of Physicists in Medicine (AAPM) Task Group 292 and endorsed by the AAPM. Members of AAPM Task Group 292 on Electronic-Brachytherapy Dosimetry have reviewed pertinent publications and user manuals regarding the INTRABEAM system dosimetry and manufacturer-supplied dose calculation protocols. Formal written correspondence with Zeiss has also provided further clarification. Dose-rate calculations for the INTRABEAM system are highly dependent on choice of dosimetry protocol. Even with careful protocol selection, large uncertainties remain due to the incomplete characterization of the ionization chambers used for verification with respect to their energy dependence as well as manufacturing variations. There are two distinct sets of dose-rate data provided by Zeiss for the INTRABEAM system. One dataset (Calibration V4.0) is representative of the physical dose surrounding the source and the other dataset (TARGIT) has been adjusted to be consistent with a clinical trial named TARGIT (TARGeted Intraoperative RadioTherapy). The adjusted TARGIT doses are quite dissimilar to the physical doses, with differences ranging from 14% to 30% at the surface of a spherical applicator, depending on its diameter, and up to a factor of two at closer distances with the smaller needle applicators. In addition, ion chamber selection and associated manufacturing tolerances contribute to significant additional uncertainties. With these substantial differences in dose rates and their associated uncertainties, it is important for users to be aware of how each value is calculated and whether it is appropriate to be used for the intended treatment. If users intend to deliver doses that are the same as they were in 1998 at the onset of the TARGIT trial, then the TARGIT dose-rate tables should be used. The Calibration V4.0 dose rates may be more appropriate to use for applications other than TARGIT trial treatments, since they more closely represent the physical doses being delivered. Users should also be aware of the substantial uncertainties associated with the provided dose rates, which are due to beam hardening, chamber geometry, and selection of the point-of-measurement for a given ionization chamber. This report serves to describe the details and implications of the manufacturer-recommended dosimetry formalism for users of the INTRABEAM system.

The US NRC requires annual training for high dose rate (HDR) brachytherapy emergencies for authorized users. Previous training at our institution involved verbal instruction by the afterloader vendor, followed by a brief hands-on skills session. Based on perceived knowledge gaps and uncertainty in how to respond to HDR “stuck source” emergencies by staff, we developed and evaluated a new HDR emergency training protocol (HDR-ETP). Standardized HDR “stuck source” emergency procedures were developed based on recommendations from the afterloader vendor, modified to reflect clinical practicalities. Detailed action lists for three different HDR staff were developed. An HDR-ETP was then created, consisting of an instructional video, demonstrating use of emergency procedures for various scenarios, and a hands-on HDR emergency simulation. Protocol training commenced with HDR staff watching the short instructional video. Then, a hands-on HDR emergency drill was completed in a team setting, consisting of a physician, a physicist and a radiation therapist. Trained observers evaluated staff on their performance during the simulation and gave direct feedback to each participant. Both before and after completing the HDR-ETP, staff completed a survey to evaluate their knowledge of HDR emergency procedures (using multiple choice questions) and assess their comfort level performing these tasks (using a 5 point Likert scale). A total of 18 staff members participated in the new HDR-ETP. Prior to initiation of training, 22% of participants strongly agreed with the statements “I am familiar with the procedures to follow during an HDR emergency” and “I feel confident in performing my role during an HDR emergency”. After training, 93% and 87% of participants strongly agreed with the above statements, respectively. The average score for knowledge-based questions was 83% (range 60-100%) prior to training. After training, the average score improved to 90% (range 80-100%). Despite high pre-test scores, 44% (8/18) participants made one or more errors during the hands-on simulation. Simulation errors included failure to engage source-retract interlocks, failure to perform a survey for radioactivity at the end of the simulation and general process errors. After training completion, all participants either somewhat or strongly agreed to the statements “I found the video training useful” and “I found the hands-on practice useful”. A standardized HDR-ETP was developed that included an instructional video and a hands-on drill for brachytherapy staff. Our HDR-ETP resulted in improved familiarity and confidence with emergency procedures. Despite good pre-test knowledge and the instructional video, multiple participants made errors during the hands-on simulation, highlighting the necessity of simulated emergency events.

To test the radiobiological impact of hypofractionated uveal melanoma brachytherapy (BT), we calculated a hypo-fractionated equivalent dose (HFED) to the tumor that equates to 85 Gy of I125 low dose rate (LDR) BT for cases with and without vitreous replacement (VR). Corresponding organs-at-risk doses (OARs) were estimated.

PURPOSE:The purpose of this study was to provide guidance on quality management for electronic brachytherapy. MATERIALS AND METHODS:The task group used the risk-assessment approach of Task Group 100 of the American Association of Physicists in Medicine. Because the quality management program for a device is intimately tied to the procedure in which it is used, the task group first designed quality interventions for intracavitary brachytherapy for both commercial electronic brachytherapy units in the setting of accelerated partial-breast irradiation. To demonstrate the methodology to extend an existing risk analysis for a different application, the task group modified the analysis for the case of post-hysterectomy, vaginal cuff irradiation for one of the devices. RESULTS:The analysis illustrated how the TG-100 methodology can lead to interventions to reduce risks and improve quality for each unit and procedure addressed. CONCLUSION:This report provides a model to guide facilities establishing a quality management program for electronic brachytherapy.

Chemoradiation has remained the standard of care treatment for many of the most aggressive cancers. However, despite effective toxicity to cancer cells, current chemoradiation regimens are limited in efficacy due to significant normal cell toxicity. Thus, efforts have been made to identify agents demonstrating selective toxicity, whereby treatments simultaneously sensitize cancer cells to protect normal cells from chemoradiation. Pharmacological ascorbate (intravenous infusions of vitamin C resulting in plasma ascorbate concentrations >= 20 mM; P-AscH(-)) has demonstrated selective toxicity in a variety of preclinical tumor models and is currently being assessed as an adjuvant to standard-of-care therapies in several early phase clinical trials. This review summarizes the most current preclinical and clinical data available demonstrating the multidimensional role of P-AscH(-) in cancer therapy including: selective toxicity to cancer cells via a hydrogen peroxide (H2O2)-mediated mechanism; action as a sensitizing agent of cancer cells to chemoradiation; a protectant of normal tissues exposed to chemoradiation; and its safety and tolerability in clinical trials. (C) 2018 Elsevier Inc. All rights reserved.

Intraoperative radiation therapy (IORT) involves delivering high doses of radiation directly to tumors while sparing healthy tissues in a surgical setting. Current IORT systems are limited in their lack of image guidance and variable needs for shielded operating rooms. They also lack the capability to deliver non-uniform therapeutic radiation to irregular shaped clinical targets. We developed a scanning beam IORT system (SBIORT) to overcome these limitations. SBIORT consists of a low energy x-ray source, a custom compact dynamic x-ray collimator system, a robotic arm, and a 3D surface imaging module. Here we describe the design and validation of the compact dynamic x-ray collimator system and the 3D surface imaging module for use in SBIORT. The proposed collimator can achieve a leaf position accuracy of ± 0.25 mm (95% confidence interval). Phantom studies indicated the 3D surface-imaging module has an accuracy of 1.0 ± 0.6 mm with ability to obtain high resolution surface image within 5 seconds. SBIORT is a novel approach to deliver conformal intensity-modulated intraoperative radiation therapy.

Introduction: Radiation exposure is a health hazard and the potential exposure from healthcare and other anthropogenic sources necessitates radioprotective therapy. MMS350, a water soluble oxetanyl sulfoxide, is a radiation mitigator which has protective effects on pulmonary and bone marrow cells following irradiation. We have previously shown that radiation exposure causes cardiac conduction damage including bradyarrhythmia and atrioventricular (AV) block in mice. This study investigates whether MMS350 protects against cardiac conduction damage in C57Bl/6 mice following radiation exposure. Methods: Mice were treated with MMS350 (400 μM) in drinking water ad libitum for 14 days prior to and for 30 days following irradiation, and were injected with MMS350 (20 mg/kg IV) 30 minutes prior to irradiation. Control (n=12) and MMS350-dosed (n=8) mice were total body irradiated (TBI) using a Pantak HF-320 Orthovoltage X-ray machine for a total dose of 6 Gy (1.38 Gy/min). Four-lead ECGs were performed on anesthetized mice at baseline and at day 30; PR, QRS, and QTc (QT normalized to heart rate) intervals were analyzed. Results: TBI control mice had PR (51.2 ± 5.8 vs. 43.4 ± 2.6 ms, P=0.003) and QRS (13.7 ± 0.2 vs. 13.0 ± 0.6 ms, P=0.02) interval prolongation at 30 days compared to baseline, while QTc trended towards a significant lengthening (88.4 ± 6.8 vs. 80.1 ± 10.4 ms, P=0.06). TBI MMS350 mice had no significant PR (46.2 ± 7.8 vs. 42.9 ± 5.1 ms, P=0.41) or QRS (14.0 ± 2.4 vs. 13.7 ± 0.8 ms, P=0.71) interval prolongation at 30 days compared to baseline, while QTc trended towards a significant lengthening (86.1 ± 7.9 vs. 73.0 ± 15.2 ms, P=0.05). New prolonged pauses and/or AV block occurred by day 30 post-irradiation in a third of TBI control mice but not in TBI MMS350 mice. Additionally, compared to baseline, day 6 post- irradiation TBI-only mice lost weight (males: 25.0 ± 1.8 to 24.2 ± 1.6g, P=0.004; females: 21.2 ± 1.0 to 19.2 ± 1.3g, P=0.01) while MMS350-dosed mice did not (males: 25.4 ± 1.7 to 27.8 ± 0.5g, P=0.12); females: 19.3 ± 0.2 to 21.0 ± 1.2g, P=0.08). Conclusion: Our results suggest that MMS350 protects irradiated mice from bradyarrhythmias, cardiac conduction damage, and radiation-associated weight loss. These findings lend further support to MMS350 as a radiation mitigator.

Purpose: To validate the clinical feasibility and efficacy of a real-time applicator position monitoring system (RAPS) through a phantom study and a prospective clinical trial. Methods and materials: The RAPS measures the brachytherapy applicator displacement in real-time by computing the relative displacement between two infrared reflective targets, one attached to the applicator and the other to the patient's skin. A phantom study was performed to compare RAPS measurements with the ground truth. Six cervical cancer patients were enrolled in the clinical trial using MRI-based high-dose-rate brachytherapy with a Tandem-and-Ovoids applicator. The results from the RAPS are compared with the clinical method. Results: In the phantom study, an average difference between RAPS measurements and known displacements was 0.02 +/- 0.01mmin the superior-inferior direction, 0.02 +/- 0.02mmin the lateral direction, and 0.11 +/- 0.06mmin the anterior-posterior direction. In the clinical trial, the absolute difference in applicator displacement between the RAPS and the clinical method was 1.46 +/- 1.13 mm. In all patient cases, a maximum applicator displacement of 6.66mm (2.0 +/- 1.5mm) was observed using the RAPS. Conclusions: This work demonstrates the clinical efficacy of RAPS to measure applicator displacement.

Purpose:To test the radiobiological impact of hypofractionated choroidal melanoma brachytherapy, we calculated single fraction equivalent doses (SFED) of the tumor that equivalent to 85 Gy of I125‐BT for 20 patients. Corresponding organs‐at‐risks (OARs) doses were estimated.Methods:Twenty patients treated with I125‐BT were retrospectively examined. The tumor SFED values were calculated from tumor BED using a conventional linear‐quadratic (L‐Q) model and an universal survival curve (USC). The opposite retina (α/β = 2.58), macula (2.58), optic disc (1.75), and lens (1.2) were examined. The % doses of OARs over tumor doses were assumed to be the same as for a single fraction delivery. The OAR SFED values were converted into BED and equivalent dose in 2 Gy fraction (EQD2) by using both L‐Q and USC models, then compared to I125‐BT.Results:The USC‐based BED and EQD2 doses of the macula, optic disc, and the lens were on average 118 ± 46% (p < 0.0527), 126 ± 43% (p < 0.0354), and 112 ± 32% (p < 0.0265) higher than those of I125‐BT, respectively. The BED and EQD2 doses of the opposite retina were 52 ± 9% lower than I125‐BT. The tumor SFED values were 25.2 ± 3.3 Gy and 29.1 ± 2.5 Gy when using USC and LQ models which can be delivered within 1 hour. All BED and EQD2 values using L‐Q model were significantly larger when compared to the USC model (p < 0.0274) due to its large single fraction size (> 14 Gy).Conclusion:The estimated single fraction doses were feasible to be delivered within 1 hour using a high dose rate source such as electronic brachytherapy (eBT). However, the estimated OAR doses using eBT were 112 ∼ 118% higher than when using the I125‐BT technique. Continued exploration of alternative dose rate or fractionation schedules should be followed.

It is hypothesized that the real-time applicator position monitoring system (RAPS) can detect intracavitary applicator displacement in real-time when utilized for intracavitary brachytherapy. Applicator displacement during brachytherapy can produce suboptimal dosimetric effects, especially in 3D image guided brachytherapy, which requires high-accuracy applicator localization. Two-D, x-ray imaging devices, such as C-arm, are routinely used for measuring applicator displacement; however, they deliver extra radiation dose to patients and lack the capability of continuous applicator monitoring. The RAPS was developed for continuous applicator position monitoring without any radiation dose. The RAPS consists of two custom-designed tracking targets with infrared reflective markers and a calibrated infrared stereo-camera setup. The RAPS can measure the applicator movement in real-time by computing the relative displacement between the two tracking targets, which are attached to the applicator and the patient. Both 3D printed tracking targets were custom designed for optimal tracking performance and to be easily attached to the tandem and ovoids applicator. A phantom study was conducted to compare RAPS' measurements with known displacements from a high-accuracy positioning stage (0.03 mm accuracy) in the range of +/-25 mm. An IRB-approved patient study is underway to compare RAPS' measurements with those based upon C-arm image analysis. A semi-automatic image registration based method was used to compute the applicator displacement from the C-arm images before/after patient was transferred from MRI scans. The RAPS achieved 120 frames per second using a laptop. At a camera-to-marker distance of 50 cm, the mean difference between RAPS' measurements and the positioning stage was 0.068 mm with a standard deviation (STD) of 0.044 mm in superior-inferior direction, 0.013 mm with a STD of 0.015 mm in lateral direction, and 0.061 mm with a STD of 0.024 mm in anterior-posterior direction. In the first patient study, a difference of 0.97 mm was observed between the RAPS' measurement and those from C-arm images. This work demonstrates the feasibility of RAPS to detect applicator motion in real-time. An accuracy of 0.1 mm was achieved in the phantom study and a difference of 0.97 mm was observed in the first patient study.

Five year data from the Targit-A trial suggests that partial breast intraoperative radiation therapy (IORT) using the Intrabeam device in women with early stage breast cancer is safe and efficacious. However, IORT is not yet accepted as standard of care and is not allowed in many clinical trial protocols. Herein, we report our early institutional experiences with IORT using the Intrabeam. From April 2012 through April 2014, we planned to treat 68 early stage breast cancer patients with IORT and treated 64 patients. Eligibility for IORT included post-menopausal women over the age of 50, an estimated tumor size of less than or equal to 3.5cm, no more than focal lymphovascular invasion, positive ER status (positive PR status was added later) and tumor pathology consistent with either invasive ductal carcinoma (IDC) or ductal carcinoma in situ (DCIS). IORT was delivered concurrently with partial mastectomy, and all patients received 20 Gy prescribed to the applicator surface. Depending on surgeon preference, sentinel lymph node dissection (SLND) was performed before or after the delivery of IORT for patients with invasive cancers. Sizers were designed and manufactured to sound the cavity and determine the correct applicator size for delivery of IORT. Criteria for whole breast radiation therapy (WBRT) after IORT included positive or close margins, lymphovascular invasion or invasive lobular carcinoma (ILC) found on final pathology, involvement of axillary lymph nodes and tumors with an extensive intraductal component. IORT was offered to 68 patients. IORT was aborted in four patients due to the inability to maintain a 1cm margin to the skin, for a 94% IORT delivery completion rate. The median age of patients receiving IORT was 65 (range 51-87) and tumor size ranged from 0.3 to 2.2cm (mean 1cm). Final pathology revealed pure DCIS in 11 patients, ILC in two patients and IDC in 55 patients. A DCIS component was found in 26 patients with invasive tumor. Eight patients (11.7%) had either positive (5) or close (3, <1mm) margins. Re-excision was performed in four patients with no residual tumor, one patient refused, and was not recommended for three patients. WBRT was recommended for nine patients (14%). Reasons for WBRT included positive lymph node status (3), positive lymph node status and ILC (1), close margin and ILC (1), extensive DCIS component and positive/close margin (2), negative PR status (1) and close margin (1). Four patients (6.3%) had acute side effects requiring intervention: two patients developed seroma requiring drainage more than three times; one patient developed hematoma with subsequent abscess, and one patient had delayed wound healing with incision dehiscence. No patients had acute skin reactions. The timing of SLND did not affect the development of acute side effects. In the follow-up period (1 to 25 months), one patient had recurrent/persistent DCIS at one year requiring re-excision and WBRT and two patients died of unrelated reasons. Partial breast IORT is well tolerated in our patient population with a low complication rate. Careful patient selection still resulted in 14% of patients needing to undergo WBRT. Given our recent adoption of IORT, long-term follow-up is required to further address outcomes.

Purpose: To develop a real‐time applicator position monitoring system (RAPS) for intracavitary brachytherapy using an infrared camera and reflective markers. Methods: 3D imaging‐guided brachytherapy requires high accuracy of applicator localization; however, applicator displacement can happen during patient transfer for imaging and treatment delivery. No continuous applicator position monitoring system is currently available. The RAPS system was developed for continuous applicator position monitoring without additional radiation dose to patients. The RAPS system includes an infrared camera, reflective markers, an infrared illuminator, and image processing software. After reflective markers are firmly attached to the applicator and patient body, applicator displacement are measured by computing the relative change in distance between the markers. The reflective markers are magnetic resonance imaging (MRI) compatible, suitable for MRI‐guided conformal HDR brachytherapy paradigm. In our prototype, a Microsoft Kinect sensor with a resolution of 640 by 480 was used as an infrared camera. A phantom study was carried out to compare RAPS' measurements with known displacements ranging from −15 mm to +15mm. A reproducibility test was also conducted. Results: The RAPS can achieve 4 frames per second using a laptop with Intel Core 2 dual CPU. When the pixel size was 0.95 mm, the difference between RAPS' measurements and known shifts ranged from 0 to 0.8 mm, with the mean value of 0.1 mm and a standard deviation of 0.44 mm. The system reproducibility was within 0.6 mm after 10 reposition trials. At SAD of 60 cm, 7 cm camera position uncertainty in vertical direction introduced 1.0 mm measurement uncertainty. Conclusion: This work demonstrates the feasibility of a real‐time infrared camera based brachytherapy applicator monitoring system. Less than 1mm accuracy was achieved when using an off‐the‐shelf low resolution infrared camera.

PURPOSE To develop a real-time applicator position monitoring system (RAPS) for intracavitary brachytherapy using an infrared camera and reflective markers. METHODS 3D image-guided brachytherapy requires high accuracy of applicator localization; however, applicator displacement can happen during patient transfer for imaging and treatment delivery. No continuous applicator position monitoring system is currently available. The RAPS system was developed for real-time applicator position monitoring without additional radiation dose to patients. It includes an infrared camera, reflective markers, an infrared illuminator, and image processing software. After reflective markers are firmly attached to the applicator and the patient body, applicator displacement can be measured by computing the relative change in distance between the markers. The reflective markers are magnetic resonance imaging (MRI) compatible, which is suitable for MRI-guided HDR brachytherapy paradigm. In our prototype, a Microsoft Kinect sensor with a resolution of 640 by 480 pixels is used as an infrared camera. A phantom study was carried out to compare RAPS' measurements with known displacements ranging from -15 to +15 mm. A reproducibility test was also conducted. RESULTS The RAPS can achieve 4 frames/s using a laptop with Intel(®) Core™2 Duo processor. When the pixel size is 0.95 mm, the difference between RAPS' measurements and known shift values varied from 0 to 0.8 mm with the mean value of 0.1 mm and a standard deviation of 0.44 mm. The system reproducibility was within 0.6 mm after ten reposition trials. CONCLUSIONS This work demonstrates the feasibility of a real-time infrared camera based gynecologic intracavitary brachytherapy applicator monitoring system. Less than 1 mm accuracy is achieved when using an off-the-shelf infrared camera.

New technologies continue to be developed to improve the practice of radiation therapy. As several of these technologies have been implemented clinically, the Therapy Committee and the Quality Assurance and Outcomes Improvement Subcommittee of the American Association of Physicists in Medicine commissioned Task Group 147 to review the current nonradiographic technologies used for localization and tracking in radiotherapy. The specific charge of this task group was to make recommendations about the use of nonradiographic methods of localization, specifically; radiofrequency, infrared, laser, and video based patient localization and monitoring systems. The charge of this task group was to review the current use of these technologies and to write quality assurance guidelines for the use of these technologies in the clinical setting. Recommendations include testing of equipment for initial installation as well as ongoing quality assurance. As the equipment included in this task group continues to evolve, both in the type and sophistication of technology and in level of integration with treatment devices, some of the details of how one would conduct such testing will also continue to evolve. This task group, therefore, is focused on providing recommendations on the use of this equipment rather than on the equipment itself, and should be adaptable to each user's situation in helping develop a comprehensive quality assurance program.

Purpose: Unlike plastic applicators, direct reconstruction of Titanium applicators on MRI has been challenging. Hence, we developed three MRI marker-catheters and evaluated their feasibility in terms of applicator reconstruction.

Traditional quality assurance checks of a patient's radiation therapy plan involve printing out treatment parameters from the treatment planning system and the "record and verify" (R&V) system and visually checking the information for one-to-one correspondence. In a paperless environment, one can automate this process through independent software that can read the treatment planning data directly and compare it against the parameters in the R&V system's database. In addition to verifying the data integrity, it is necessary to check the logical consistency of the data and the accuracy of various calculations. The results are then imported into the patient's electronic medical record. Appropriate workflows must be developed to ensure that no steps of the QA process are missed. This paper describes our electronic QA system (EQS), consisting of in-house software and workflows. The EQS covers 3D conformal and intensity modulated radiation therapy, electrons, stereotactic radiosurgery, total body irradiation, and clinical set ups with and without virtual simulation. The planning systems handled by our EQS are ADAC Pinnacle and Varian FASTPLAN, while the R&V systems are LANTIS and VARIS. The improvement in our plan check process over the paperless system is described in terms of the types of detected errors. The potential problems with the implementation and use of the EQS, as well as workarounds for data that are not easily accessible through electronic means, are described.

PURPOSE:We describe the experimental demonstration of the delivery of a three-dimensional conformal radiotherapy dose distribution using in-field modulation of nine fixed-gantry fields.METHODS AND MATERIALS:Two-dimensional in-field modulation profiles, varying from field to field, were realized by quasi-dynamic multileaf collimation using the prototype of a commercially available multileaf collimator installed on a medical linear accelerator. The profiles were calculated to deliver an optimal dose distribution for a patient with a prostate carcinoma. The target volume surface was invaginated and bifurcated. The calculated dose distribution was delivered to a homogeneous polystyrene phantom consisting of 1 cm thick slices that were cut to match the patient's outer contour. Seven therapy verification films were placed between the phantom slices.RESULTS:Analysis of the films revealed a degree of conformation of the high-dose region to the target shape that would not be possible with unmodulated conformal therapy. However, small observed spatial displacements of the dose distribution confirm the need for very accurate positioning.CONCLUSIONS:It is feasible to deliver clinically relevant, three-dimensional dose distributions that conform to invaginated and bifurcated target volumes using fields modulated by multileaf collimators.