Dosimetric evaluation of high-Z inhomogeneity used for hip prosthesis: A multi-institutional collaborative study.

PURPOSE: A multi-institutional investigation for dosimetric evaluation of high-Z hip prosthetic device in photon beam. METHODS: A bilateral hip prosthetic case was chosen. An in-house phantom was built to replicate the human pelvis with two different prostheses. Dosimetric parameters: dose to the target and organs at risk (OARs) were compared for the clinical case generated by various treatment planning system (TPS) with varied algorithms. Single beam plans with different TPS for phantom using 6 MV and 15 MV photon beams with and without density correction were compared with measurement. RESULTS: Wide variations in target and OAR dosimetry were recorded for different TPS. For clinical case ideal PTV coverage was noted for plans generated with Corvus and Prowess TPS only. However, none of the TPS were able to meet plan objective for the bladder. Good correlation was noticed for the measured and the Pinnacle TPS for corrected dose calculation at the interfaces as well as the dose ratio in elsewhere. On comparing measured and calculated dose, the difference across the TPS varied from -20% to 60% for 6 MV and 3% to 50% for the 15 MV, respectively. CONCLUSION: Most TPS do not provide accurate dosimetry with high-Z prosthesis. It is important to check the TPS under extreme conditions of beams passing through the high-Z region. Metal artifact reduction algorithms may reduce the difference between the measured and calculated dose but still significant differences exist. Further studies are required to validate the calculational accuracy.

Minibeam radiation therapy enhanced tumor delivery of PEGylated liposomal doxorubicin in a triple-negative breast cancer mouse model.

BACKGROUND: Minibeam radiation therapy is an experimental radiation therapy utilizing an array of parallel submillimeter planar X-ray beams. In preclinical studies, minibeam radiation therapy has been shown to eradicate tumors and cause significantly less damage to normal tissue compared to equivalent radiation doses delivered by conventional broadbeam radiation therapy, where radiation dose is uniformly distributed. METHODS: Expanding on prior studies that suggested minibeam radiation therapy increased perfusion in tumors, we compared a single fraction of minibeam radiation therapy (peak dose:valley dose of 28 Gy:2.1 Gy and 100 Gy:7.5 Gy) and broadbeam radiation therapy (7 Gy) in their ability to enhance tumor delivery of PEGylated liposomal doxorubicin and alter the tumor microenvironment in a murine tumor model. Plasma and tumor pharmacokinetic studies of PEGylated liposomal doxorubicin and tumor microenvironment profiling were performed in a genetically engineered mouse model of claudin-low triple-negative breast cancer (T11). RESULTS: Minibeam radiation therapy (28 Gy) and broadbeam radiation therapy (7 Gy) increased PEGylated liposomal doxorubicin tumor delivery by 7.1-fold and 2.7-fold, respectively, compared to PEGylated liposomal doxorubicin alone, without altering the plasma disposition. The enhanced tumor delivery of PEGylated liposomal doxorubicin by minibeam radiation therapy is consistent after repeated dosing, is associated with changes in tumor macrophages but not collagen or angiogenesis, and nontoxic to local tissues. Our study indicated that the minibeam radiation therapy's ability to enhance the drug delivery decreases from 28 to 100 Gy peak dose. DISCUSSION: Our studies suggest that low-dose minibeam radiation therapy is a safe and effective method to significantly enhance the tumor delivery of nanoparticle agents.

Photon GRID Radiation Therapy: A Physics and Dosimetry White Paper from the Radiosurgery Society (RSS) GRID/LATTICE, Microbeam and FLASH Radiotherapy Working Group.

The limits of radiation tolerance, which often deter the use of large doses, have been a major challenge to the treatment of bulky primary and metastatic cancers. A novel technique using spatial modulation of megavoltage therapy beams, commonly referred to as spatially fractionated radiation therapy (SFRT) (e.g., GRID radiation therapy), which purposefully maintains a high degree of dose heterogeneity across the treated tumor volume, has shown promise in clinical studies as a method to improve treatment response of advanced, bulky tumors. Compared to conventional uniform-dose radiotherapy, the complexities of megavoltage GRID therapy include its highly heterogeneous dose distribution, very high prescription doses, and the overall lack of experience among physicists and clinicians. Since only a few centers have used GRID radiation therapy in the clinic, wide and effective use of this technique has been hindered. To date, the mechanisms underlying the observed high tumor response and low toxicity are still not well understood. To advance SFRT technology and planning, the Physics Working Group of the Radiosurgery Society (RSS) GRID/Lattice, Microbeam and Flash Radiotherapy Working Groups, was established after an RSS-NCI Workshop. One of the goals of the Physics Working Group was to develop consensus recommendations to standardize dose prescription, treatment planning approach, response modeling and dose reporting in GRID therapy. The objective of this report is to present the results of the Physics Working Group's consensus that includes recommendations on GRID therapy as an SFRT technology, field dosimetric properties, techniques for generating GRID fields, the GRID therapy planning methods, documentation metrics and clinical practice recommendations. Such understanding is essential for clinical patient care, effective comparisons of outcome results, and for the design of rigorous clinical trials in the area of SFRT. The results of well-conducted GRID radiation therapy studies have the potential to advance the clinical management of bulky and advanced tumors by providing improved treatment response, and to further develop our current radiobiology models and parameters of radiation therapy design.

The Technical and Clinical Implementation of LATTICE Radiation Therapy (LRT).

The concept of spatially fractionated radiation therapy (SFRT) was conceived over 100 years ago, first in the form of GRID, which has been applied to clinical practice since its early inception and continued to the present even with markedly improved instrumentation in radiation therapy. LATTICE radiation therapy (LRT) was introduced in 2010 as a conceptual 3D extension of GRID therapy with several uniquely different features. Since 2014, when the first patient was treated, over 150 patients with bulky tumors worldwide have received LRT. Through a brief review of the basic principles and the analysis of the collective clinical experience, a set of technical recommendations and guidelines are proposed for the clinical implementation of LRT. It is to be recognized that the current clinical practice of SFRT (GRID or LRT) is still largely based on the heuristic principles. With advancements in basic biological research and the anticipated clinical trials to systemically assess the efficacy and risk, progressively robust optimizations of the technical parameters are essential for the broader application of SFRT in clinical practice.

Conventional dose rate spatially-fractionated radiation therapy (SFRT) treatment response and its association with dosimetric parameters-A preclinical study in a Fischer 344 rat model.

PURPOSE: To identify key dosimetric parameters that have close associations with tumor treatment response and body weight change in SFRT treatments with a large range of spatial-fractionation scale at dose rates of several Gy/min. METHODS: Six study arms using uniform tumor radiation, half-tumor radiation, 2mm beam array radiation, 0.3mm minibeam radiation, and an untreated arm were used. All treatments were delivered on a 320kV x-ray irradiator. Forty-two female Fischer 344 rats with fibrosarcoma tumor allografts were used. Dosimetric parameters studied are peak dose and width, valley dose and width, peak-to-valley-dose-ratio (PVDR), volumetric average dose, percentage volume directly irradiated, and tumor- and normal-tissue EUD. Animal survival, tumor volume change, and body weight change (indicative of treatment toxicity) are tested for association with the dosimetric parameters using linear regression and Cox Proportional Hazards models. RESULTS: The dosimetric parameters most closely associated with tumor response are tumor EUD (R2 = 0.7923, F-stat = 15.26*; z-test = -4.07***), valley (minimum) dose (R2 = 0.7636, F-stat = 12.92*; z-test = -4.338***), and percentage tumor directly irradiated (R2 = 0.7153, F-stat = 10.05*; z-test = -3.837***) per the linear regression and Cox Proportional Hazards models, respectively. Tumor response is linearly proportional to valley (minimum) doses and tumor EUD. Average dose (R2 = 0.2745, F-stat = 1.514 (no sig.); z-test = -2.811**) and peak dose (R2 = 0.04472, F-stat = 0.6874 (not sig.); z-test = -0.786 (not sig.)) show the weakest associations to tumor response. Only the uniform radiation arm did not gain body weight post-radiation, indicative of treatment toxicity; however, body weight change in general shows weak association with all dosimetric parameters except for valley (minimum) dose (R2 = 0.3814, F-stat = 13.56**), valley width (R2 = 0.2853, F-stat = 8.783**), and peak width (R2 = 0.2759, F-stat = 8.382**). CONCLUSIONS: For a single-fraction SFRT at conventional dose rates, valley, not peak, dose is closely associated with tumor treatment response and thus should be used for treatment prescription. Tumor EUD, valley (minimum) dose, and percentage tumor directly irradiated are the top three dosimetric parameters that exhibited close associations with tumor response.

Erratum: Early Assessment of Tumor Response to Radiation Therapy using High-Resolution Quantitative Microvascular Ultrasound Imaging: Erratum.

[This corrects the article DOI: 10.7150/thno.19703.].

Early Assessment of Tumor Response to Radiation Therapy using High-Resolution Quantitative Microvascular Ultrasound Imaging.

Measuring changes in tumor volume using anatomical imaging weeks to months post radiation therapy (RT) is currently the clinical standard for indicating treatment response to RT. For patients whose tumors do not respond successfully to treatment, this approach is suboptimal as timely modification of the treatment approach may lead to better clinical outcomes. We propose to use tumor microvasculature as a biomarker for early assessment of tumor response to RT. Acoustic angiography is a novel contrast ultrasound imaging technique that enables high-resolution microvascular imaging and has been shown to detect changes in microvascular structure due to cancer growth. Data suggest that acoustic angiography can detect longitudinal changes in the tumor microvascular environment that correlate with RT response. Methods: Three cohorts of Fisher 344 rats were implanted with rat fibrosarcoma tumors and were treated with a single fraction of RT at three dose levels (15 Gy, 20 Gy, and 25 Gy) at a dose rate of 300 MU/min. A simple treatment condition was chosen for testing the feasibility of our imaging technique. All tumors were longitudinally imaged immediately prior to and after treatment and then every 3 days after treatment for a total of 30 days. Both acoustic angiography (using in-house produced microbubble contrast agents) and standard b-mode imaging was performed at each imaging time point using a pre-clinical Vevo770 scanner and a custom modified dual-frequency transducer. Results: Results show that all treated tumors in each dose group initially responded to treatment between days 3-15 as indicated by decreased tumor growth accompanied with decreased vascular density. Untreated tumors continued to increase in both volume and vascular density until they reached the maximum allowable size of 2 cm in diameter. Tumors that displayed complete control (no tumor recurrence) continued to decrease in size and vascular density, while tumors that progressed after the initial response presented an increase in tumor volume and volumetric vascular density. The increase in tumor volumetric vascular density in recurring tumors can be detected 10.25 ± 1.5 days, 6 ± 0 days, and 4 ± 1.4 days earlier than the measurable increase in tumor volume in the 15, 20, and 25 Gy dose groups, respectively. A dose-dependent growth rate for tumor recurrence was also observed. Conclusions: In this feasibility study we have demonstrated the ability of acoustic angiography to detect longitudinal changes in vascular density, which was shown to be a potential biomarker for tumor response to RT.

Radiation Sensitivity in a Preclinical Mouse Model of Medulloblastoma Relies on the Function of the Intrinsic Apoptotic Pathway.

While treatments that induce DNA damage are commonly used as anticancer therapies, the mechanisms through which DNA damage produces a therapeutic response are incompletely understood. Here we have tested whether medulloblastomas must be competent for apoptosis to be sensitive to radiotherapy. Whether apoptosis is required for radiation sensitivity has been controversial. Medulloblastoma, the most common malignant brain tumor in children, is a biologically heterogeneous set of tumors typically sensitive to radiation and chemotherapy; 80% of medulloblastoma patients survive long-term after treatment. We used functional genetic studies to determine whether the intrinsic apoptotic pathway is required for radiation to produce a therapeutic response in mice with primary, Shh-driven medulloblastoma. We found that cranial radiation extended the survival of medulloblastoma-bearing mice and induced widespread apoptosis. Expression analysis and conditional deletion studies showed that Trp53 (p53) was the predominant transcriptional regulator activated by radiation and was strictly required for treatment response. Deletion of Bax, which blocked apoptosis downstream of p53, was sufficient to render tumors radiation resistant. In apoptosis-incompetent, Bax-deleted tumors, radiation activated p53-dependent transcription without provoking cell death and caused two discrete populations to emerge. Most radiated tumor cells underwent terminal differentiation. Perivascular cells, however, quickly resumed proliferation despite p53 activation, behaved as stem cells, and rapidly drove recurrence. These data show that radiation must induce apoptosis in tumor stem cells to be effective. Mutations that disable the intrinsic apoptotic pathways are sufficient to impart radiation resistance. We suggest that medulloblastomas are typically sensitive to DNA-damaging therapies, because they retain apoptosis competence. Cancer Res; 76(11); 3211-23. ©2016 AACR.

Technical Note: Fabricating Cerrobend grids with 3D printing for spatially modulated radiation therapy: A feasibility study.

PURPOSE: Grid therapy has promising applications in the radiation treatment of large tumors. However, research and applications of grid therapy are limited by the accessibility of the specialized blocks that produce the grid of pencil-like radiation beams. In this study, a Cerrobend grid block was fabricated using the 3D printing technique. METHODS: A grid block mold was designed with flared tubes which follow the divergence of the beam. The mold was 3D printed using a resin with the working temperature below 230 °C. The melted Cerrobend liquid at 120 °C was cast into the resin mold to yield a block with a thickness of 7.4 cm. At the isocenter plane, the grid had a hexagonal pattern, with each pencil beam diameter of 1.4 cm; the distance between the beam centers was 2.1 cm. RESULTS: The dosimetric properties of the grid block were studied using small field dosimeters: a pinpoint ionization chamber and a stereotactic diode. For a 6 MV photon beam, its valley-to-peak ratio was 20% at dmax and 30% at 10 cm depth; the output factor was 84.9% at dmax and 65.1% at 10 cm depth. CONCLUSIONS: This study demonstrates that it is feasible to implement 3D printing technique in applying grid therapy in clinic.

Fiber-optic detector for real time dosimetry of a micro-planar x-ray beam.

PURPOSE: Here, the authors describe a dosimetry measurement technique for microbeam radiation therapy using a nanoparticle-terminated fiber-optic dosimeter (nano-FOD). METHODS: The nano-FOD was placed in the center of a 2 cm diameter mouse phantom to measure the deep tissue dose and lateral beam profile of a planar x-ray microbeam. RESULTS: The continuous dose rate at the x-ray microbeam peak measured with the nano-FOD was 1.91 ± 0.06 cGy s(-1), a value 2.7% higher than that determined via radiochromic film measurements (1.86 ± 0.15 cGy s(-1)). The nano-FOD-determined lateral beam full-width half max value of 420 µm exceeded that measured using radiochromic film (320 µm). Due to the 8° angle of the collimated microbeam and resulting volumetric effects within the scintillator, the profile measurements reported here are estimated to achieve a resolution of ∼0.1 mm; however, for a beam angle of 0°, the theoretical resolution would approach the thickness of the scintillator (∼0.01 mm). CONCLUSIONS: This work provides proof-of-concept data and demonstrates that the novel nano-FOD device can be used to perform real-time dosimetry in microbeam radiation therapy to measure the continuous dose rate at the x-ray microbeam peak as well as the lateral beam shape.

Direct aperture optimization using an inverse form of back-projection.

Direct aperture optimization (DAO) has been used to produce high dosimetric quality intensity-modulated radiotherapy (IMRT) treatment plans with fast treatment delivery by directly modeling the multileaf collimator segment shapes and weights. To improve plan quality and reduce treatment time for our in-house treatment planning system, we implemented a new DAO approach without using a global objective function (GFO). An index concept is introduced as an inverse form of back-projection used in the CT multiplicative algebraic reconstruction technique (MART). The index, introduced for IMRT optimization in this work, is analogous to the multiplicand in MART. The index is defined as the ratio of the optima over the current. It is assigned to each voxel and beamlet to optimize the fluence map. The indices for beamlets and segments are used to optimize multileaf collimator (MLC) segment shapes and segment weights, respectively. Preliminary data show that without sacrificing dosimetric quality, the implementation of the DAO reduced average IMRT treatment time from 13 min to 8 min for the prostate, and from 15 min to 9 min for the head and neck using our in-house treatment planning system PlanUNC. The DAO approach has also shown promise in optimizing rotational IMRT with burst mode in a head and neck test case.

Tonic activation of Bax primes neural progenitors for rapid apoptosis through a mechanism preserved in medulloblastoma.

Commitment to survival or apoptosis within expanding progenitor populations poses distinct risks and benefits to the organism. We investigated whether specialized mechanisms regulate apoptosis in mouse neural progenitors and in the progenitor-derived brain tumor medulloblastoma. Here, we identified constitutive activation of proapoptotic Bax, maintained in check by Bcl-xL, as a mechanism for rapid cell death, common to postnatal neural progenitors and medulloblastoma. We found that tonic activation of Bax in cerebellar progenitors, along with sensitivity to DNA damage, was linked to differentiation state. In cerebellar progenitors, active Bax localized to mitochondria, where it was bound to Bcl-xL. Disruption of Bax:Bcl-xL binding by BH3-mimetic ABT 737 caused rapid apoptosis of cerebellar progenitors and primary murine medulloblastoma cells. Conditional deletion of Mcl-1, in contrast, did not cause death of cerebellar progenitors. Our findings identify a mechanism for the sensitivity of brain progenitors to typical anticancer therapies and reveal that this mechanism persists in medulloblastoma, a malignant brain tumor markedly sensitive to radiation and chemotherapy.

Monte Carlo simulation of a compact microbeam radiotherapy system based on carbon nanotube field emission technology.

PURPOSE: Microbeam radiation therapy (MRT) is an experimental radiotherapy technique that has shown potent antitumor effects with minimal damage to normal tissue in animal studies. This unique form of radiation is currently only produced in a few large synchrotron accelerator research facilities in the world. To promote widespread translational research on this promising treatment technology we have proposed and are in the initial development stages of a compact MRT system that is based on carbon nanotube field emission x-ray technology. We report on a Monte Carlo based feasibility study of the compact MRT system design. METHODS: Monte Carlo calculations were performed using EGSnrc-based codes. The proposed small animal research MRT device design includes carbon nanotube cathodes shaped to match the corresponding MRT collimator apertures, a common reflection anode with filter, and a MRT collimator. Each collimator aperture is sized to deliver a beam width ranging from 30 to 200 µm at 18.6 cm source-to-axis distance. Design parameters studied with Monte Carlo include electron energy, cathode design, anode angle, filtration, and collimator design. Calculations were performed for single and multibeam configurations. RESULTS: Increasing the energy from 100 kVp to 160 kVp increased the photon fluence through the collimator by a factor of 1.7. Both energies produced a largely uniform fluence along the long dimension of the microbeam, with 5% decreases in intensity near the edges. The isocentric dose rate for 160 kVp was calculated to be 700 Gy∕min∕A in the center of a 3 cm diameter target. Scatter contributions resulting from collimator size were found to produce only small (<7%) changes in the dose rate for field widths greater than 50 µm. Dose vs depth was weakly dependent on filtration material. The peak-to-valley ratio varied from 10 to 100 as the separation between adjacent microbeams varies from 150 to 1000 µm. CONCLUSIONS: Monte Carlo simulations demonstrate that the proposed compact MRT system design is capable of delivering a sufficient dose rate and peak-to-valley ratio for small animal MRT studies.

Quantitative assessment of workload and stressors in clinical radiation oncology.

PURPOSE: Workload level and sources of stressors have been implicated as sources of error in multiple settings. We assessed workload levels and sources of stressors among radiation oncology professionals. Furthermore, we explored the potential association between workload and the frequency of reported radiotherapy incidents by the World Health Organization (WHO). METHODS AND MATERIALS: Data collection was aimed at various tasks performed by 21 study participants from different radiation oncology professional subgroups (simulation therapists, radiation therapists, physicists, dosimetrists, and physicians). Workload was assessed using National Aeronautics and Space Administration Task-Load Index (NASA TLX). Sources of stressors were quantified using observational methods and segregated using a standard taxonomy. Comparisons between professional subgroups and tasks were made using analysis of variance ANOVA, multivariate ANOVA, and Duncan test. An association between workload levels (NASA TLX) and the frequency of radiotherapy incidents (WHO incidents) was explored (Pearson correlation test). RESULTS: A total of 173 workload assessments were obtained. Overall, simulation therapists had relatively low workloads (NASA TLX range, 30-36), and physicists had relatively high workloads (NASA TLX range, 51-63). NASA TLX scores for physicians, radiation therapists, and dosimetrists ranged from 40-52. There was marked intertask/professional subgroup variation (P<.0001). Mental demand (P<.001), physical demand (P=.001), and effort (P=.006) significantly differed among professional subgroups. Typically, there were 3-5 stressors per cycle of analyzed tasks with the following distribution: interruptions (41.4%), time factors (17%), technical factors (13.6%), teamwork issues (11.6%), patient factors (9.0%), and environmental factors (7.4%). A positive association between workload and frequency of reported radiotherapy incidents by the WHO was found (r = 0.87, P value=.045). CONCLUSIONS: Workload level and sources of stressors vary among professional subgroups. Understanding the factors that influence these findings can guide adjustments to the workflow procedures, physical layout, and/or communication protocols to enhance safety. Additional evaluations are needed in order to better understand if these findings are systemic.

The challenge of maximizing safety in radiation oncology.

There is a growing interest in the evolving nature of safety challenges in radiation oncology. Understandably, there has been a great deal of focus on the mechanical and computer aspects of new high-technology treatments (eg, intensity-modulated radiation therapy). However, safety concerns are not limited to dose calculations and data transfer associated with advanced technologies. They also stem from fundamental changes in our workflow (eg, multiple hand-offs), the relative loss of some traditional "end of the line" quality assurance tools (port films and light fields), condensed fractionation schedules, and an under-appreciation for the physical limitations of new techniques. Furthermore, changes in our workspace and tools (eg, electronic records, planning systems), and workloads (eg, billing, insurance, regulations) may have unforeseen effects on safety. Safety initiatives need to acknowledge the multiple factors affecting risk. Our current challenges will not be adequately addressed simply by defining new policies and procedures. Rather, we need to understand the frequency and causes of errors better, particularly those that are most likely to cause harm. Then we can incorporate principles into our workspace that minimize these risks (eg, automation, standardization, checklists, redundancy, and consideration of "human factors" in the design of products and workspaces). Opportunities to enhance safety involve providing support through diligent examinations of staffing, schedules, communications, teamwork, and work environments. We need to develop a culture of safety in which all team members are alerted to the possibility of harm, and they all work together to maximize safety. The goal is not to eliminate every error. Rather, we should focus our attention on conditions (eg, rushing) that can cause real patient harm, and/or those conditions that reflect systemic problems that might lead to errors more likely to cause harm. Ongoing changes in clinical practice mandate continued vigilance to minimize the risks of error, combined with new, nontraditional approaches to create a safer patient environment.

Comparison of three concomitant boost techniques for early-stage breast cancer.

PURPOSE: Whole breast radiotherapy (RT) followed by a tumor bed boost typically spans 5-6 weeks of treatment. Interest is growing in RT regimens, such as concomitant boost, that decrease overall treatment time, lessening the time/cost burden to patients and facilities. METHODS AND MATERIALS: Computed tomography (CT) scans from 20 cases were selected for this retrospective, dosimetric study to compare three different techniques of concomitant boost delivery: (1) standard tangents plus an electron boost, (2) intensity-modulated RT (IMRT) tangents using custom compensators plus an electron boost, and (3) IMRT tangents plus a conformal photon boost. The equivalent uniform dose model was used to compare the plans. RESULTS: The average breast equivalent uniform dose value for the three techniques (standard, IMRT plus electrons, and IMRT plus photons) was 48.6, 47.9, and 48.3, respectively. The plans using IMRT more closely approximated the prescribed dose of 46 Gy to the whole breast. The breast volume receiving >110% of the dose was less with the IMRT tangents than with standard RT (p = 0.037), but no significant difference in the maximal dose or other evaluated parameters was noted. CONCLUSION: Although the IMRT techniques delivered the prescribed dose with better dose uniformity, the small improvement seen did not support a goal of improved resource use.

Compensators: an alternative IMRT delivery technique.

Seven years of experience in compensator intensity-modulated radiotherapy (IMRT) clinical implementation are presented. An inverse planning dose optimization algorithm was used to generate intensity modulation maps, which were delivered via either the compensator or segmental multileaf collimator (MLC) IMRT techniques. The in-house developed compensator-IMRT technique is presented with the focus on several design issues. The dosimetry of the delivery techniques was analyzed for several clinical cases. The treatment time for both delivery techniques on Siemens accelerators was retrospectively analyzed based on the electronic treatment record in LANTIS for 95 patients. We found that the compensator technique consistently took noticeably less time for treatment of equal numbers of fields compared to the segmental technique. The typical time needed to fabricate a compensator was 13 min, 3 min of which was manual processing. More than 80% of the approximately 700 compensators evaluated had a maximum deviation of less than 5% from the calculation in intensity profile. Seventy-two percent of the patient treatment dosimetry measurements for 340 patients have an error of no more than 5%. The pros and cons of different IMRT compensator materials are also discussed. Our experience shows that the compensator-IMRT technique offers robustness, excellent intensity modulation resolution, high treatment delivery efficiency, simple fabrication and quality assurance (QA) procedures, and the flexibility to be used in any teletherapy unit.

Dose optimization via index-dose gradient minimization.

This paper presents an iterative optimization algorithm based on gradient minimization of index dose, defined as the product of physical dose and a numerical index. Acting as a template the index distribution is designed to represent the dosimetry that meets the dose volume histogram-based optimization objectives. The treatment dosimetry is optimized when the uniformity of the index-dose distribution is maximized. Prior to optimization the user can select all or only some of the beams to be intensity modulated. The remaining unmodulated beams can be either open or wedged photon beams, electron beams, or beams of previous treatments. The optimization result and treatment delivery efficiency can often be enhanced by including not only the IM photon beams but also all suitable fixed-beams available on the linac in the treatment plan. In addition, the doses from previous treatments can also be considered in the optimization of current treatment. Five clinical examples with different complexities in optimization objective are presented. The effects of two nonoptimization variables, beam setup and initial beam weights, on the quality of the dose optimization are also presented. The results are analyzed in terms of isodose distribution, dose volume histograms, and a dose optimization quality factor. The optimization algorithm, implemented in our in-house TPS PLanUNC, has been used in clinical application since 1996. The primary advantages of our optimization algorithm include computational efficiency, intensity modulation selection choice, and performance reliability for a wide range of clinical beam setups and optimization objectives.

A quality and efficiency analysis of the IMFAST segmentation algorithm in head and neck "step & shoot" IMRT treatments.

The performance of segmentation algorithms used in IMFAST for "step & shoot" IMRT treatment delivery is evaluated for three head and neck clinical treatments of different optimization objectives. The segmentation uses the intensity maps generated by the in-house TPS PLANUNC using the index-dose minimization algorithm. The dose optimization objectives include PTV dose uniformity and dose volume histogram-specified critical structure sparing. The optimized continuous intensity maps were truncated into five and ten intensity levels and exported to IMFAST for MLC segments optimization. The MLC segments were imported back to PLUNC for dose optimization quality calculation. The five basic segmentation algorithms included in IMFAST were evaluated alone and in combination with either tongue and groove/match line correction or fluence correction or both. Two criteria were used in the evaluation: treatment efficiency represented by the total number of MLC segments and optimization quality represented by a clinically relevant optimization quality factor. We found that the treatment efficiency depends first on the number of intensity levels used in the intensity map and second the segmentation technique used. The standard optimal segmentation with fluence correction is a consistent good performer for all treatment plans studied. All segmentation techniques evaluated produced treatments with similar dose optimization quality values, especially when ten-level intensity maps are used.