Development of an adjoint sensitivity field-based treatment-planning technique for the use of newly designed directional LDR sources in brachytherapy.

The development and application of an automated 3D greedy heuristic (GH) optimization algorithm utilizing the adjoint sensitivity fields for treatment planning to assess the advantage of directional interstitial prostate brachytherapy is presented. Directional and isotropic dose kernels generated using Monte Carlo simulations based on Best Industries model 2301 I-125 source are utilized for treatment planning. The newly developed GH algorithm is employed for optimization of the treatment plans for seven interstitial prostate brachytherapy cases using mixed sources (directional brachytherapy) and using only isotropic sources (conventional brachytherapy). All treatment plans resulted in V100 > 98% and D90 > 45 Gy for the target prostate region. For the urethra region, the D10(Ur), D90(Ur) and V150(Ur) and for the rectum region the V100cc, D2cc, D90(Re) and V90(Re) all are reduced significantly when mixed sources brachytherapy is used employing directional sources. The simulations demonstrated that the use of directional sources in the low dose-rate (LDR) brachytherapy of the prostate clearly benefits in sparing the urethra and the rectum sensitive structures from overdose. The time taken for a conventional treatment plan is less than three seconds, while the time taken for a mixed source treatment plan is less than nine seconds, as tested on an Intel Core2 Duo 2.2 GHz processor with 1GB RAM. The new 3D GH algorithm is successful in generating a feasible LDR brachytherapy treatment planning solution with an extra degree of freedom, i.e. directionality in very little time.

18F-labeled resin microspheres as surrogates for 90Y resin microspheres used in the treatment of hepatic tumors: a radiolabeling and PET validation study.

(90)Y-labeled resin microspheres (SIR-Spheres) are currently used to treat patients with primary and metastatic solid liver tumors. This treatment is typically palliative since patients have exhausted all other standard treatment options. Improving the quality of life and extending patient survival are typical benchmarks for tracking patient response. However, the current method for predicting microsphere biodistributions with (99m)Tc-labeled macroaggregated albumin (MAA) does not correlate well with patient response. This work presents the development of a new (18)F-labeled resin microsphere to serve as a surrogate for the treatment microsphere and to employ the superior resolution and sensitivity of positron emission tomography (PET). The (18)F microsphere biodistributions were determined in a rabbit using PET imaging and histological review. The PET-based uptake ratio was shown to agree with the histological findings to better than 3%. In addition, the radiolabeling process was shown to be rapid, efficient and relatively stable in vivo.

Observations on rotating needle insertions using a brachytherapy robot.

A robot designed for prostate brachytherapy implantations has the potential to greatly improve treatment success. Much of the research in robotic surgery focuses on measuring accuracy. However, there exist many factors that must be optimized before an analysis of needle placement accuracy can be determined. Some of these parameters include choice of the needle type, insertion velocity, usefulness of the rotating needle and rotation speed. These parameters may affect the force at which the needle interacts with the tissue. A reduction in force has been shown to decrease the compression of the prostate and potentially increase the accuracy of seed position. Rotating the needle as it is inserted may reduce frictional forces while increasing accuracy. However, needle rotations are considered to increase tissue damage due to the drilling nature of the insertion. We explore many of the factors involved in optimizing a brachytherapy robot, and the potential effects each parameter may have on the procedure. We also investigate the interaction of rotating needles in gel and suggest the rotate-cannula-only method of conical needle insertion to minimize any tissue damage while still maintaining the benefits of reduced force and increased accuracy.

Multi-species prostate implant treatment plans incorporating 192Ir and 125I using a Greedy Heuristic based 3D optimization algorithm.

The goals of interstitial implant brachytherapy include delivery of the target dose in a uniform manner while sparing sensitive structures, and minimizing the number of needles and sources. We investigated the use of a multi-species source arrangement (192Ir with 125I) for treatment in interstitial prostate brachytherapy. The algorithm utilizes an "adjoint ratio," which provides a means of ranking source positions and is the criterion for the Greedy Heuristic optimization. Three cases were compared, each using 0.4 mCi 125I seeds: case I is the base case using 125I alone, case II uses 0.12 mCi 192Ir seeds mixed with 125I, and case III uses 0.25 mCi 192Ir mixed with 125I. Both multi-species cases result in lower exposure of the urethra and central prostate region. Compared with the base case, the exposure to the rectum and normal tissue increases by a significant amount for case III as compared with the increase in case II, signifying the effect of slower dose falloff rate of higher energy gammas of 192Ir in the tissue. The number of seeds and needles decreases in both multi-species cases, with case III requiring fewer seeds and needles than case II. Further, the effect of 192Ir on uniformity was investigated using the 0.12 mCi 192Ir seeds in multi-species implants. An increase in uniformity was observed with an increase in the number of 0.12 mCi 1921r seeds implanted. The effects of prostate size on the evaluation parameters for multi-species implants were investigated using 0.12 mCi 192Ir and 0.4 mCi 125I, and an acceptable treatment plan with increased uniformity was obtained.

A new internal pair production branching ratio of 90Y: the development of a non-destructive assay for 90Y and 90Sr.

(90)Y is utilized as a therapeutic radioisotope in radiolabeled monoclonal antibodies and in microspheres for targeted radiation therapy of the liver. Currently, the widely used dose calibrator assay of (90)Y can have uncertainties exceeding +/-10%. A non-destructive assay using spectroscopy is possible by reducing the currently published uncertainty (+/-12%) in the internal pair production branching ratio for the 0(+)-0(+) transition of (90)Zr. A high-purity germanium detector was used to determine the branching ratio to be (31.86+/-0.47) x 10(-6).

Comparison of two planning systems for HDR brachytherapy gynecological application.

PURPOSE: This report compares the Nucletron NPS and PLATO planning system for patients treated for cervix cancer. MATERIALS AND METHODS: This study compares calculations generated using the older NPS (version 11.43) planning system and the more recent PLATO (version 14.1) system for two cases: 1) a single dwell position and 2) an actual patient application using a tandem and ovoid. RESULTS: For one dwell position: for NPS planning the dose for points along the source axis forward of the cable was 9.85% more than for symmetrically placed points in the cable direction. For PLATO, the same test gave rise to a difference of 10.2%. Comparing the two systems, NPS calculated doses for points in the forward direction 14% greater than those calculated by PLATO. The entry of points using the digitizer accounted for less than 1% of any difference. For the patient case: the dose difference between NPS and PLATO planning for all patient reference points entered from films ranged from 1 to 4%. The difference in dose between optimized and nonoptimized planning was approximately 0.5% for prescription points (points A), while for the bladder and rectum the differences were 6% and 20%, respectively with NPS, and with PLATO, 8% and 22%, respectively. CONCLUSION: This study highlighted the effects of the differences in the calculational algorithm between the older and newer planning systems from Nucletron. While the differences were minimal on the perpendicular bisector of the source, along the axis they become considerable. In a practical gynecological case, these differences mostly affect the dose to the rectum, since that organ receives the greatest proportion of its dose from rays near the same axis. Overall, the PLATO system plan required about 2.5% less integrated reference air kerma than the NPS plan for the same dose to point A. For either planning system, optimization is crucial in decreasing dose to bladder and rectal points.

The water-equivalence of phantom materials for 90Sr-90Y beta particles.

Intravascular brachytherapy requires that the dose be specified within millimeters of the source. High dose gradients near brachytherapy sources require that the source-detector distance be accurately known for dosimetry purposes. Solid phantoms can be designed to accommodate these stringent requirements. This study reports dosimeter readings from 90Sr-90Y sources measured in water, A150, polystyrene and in an epoxy-based water-equivalent plastic. Measurements showed that while A150 and the epoxy-based plastic agreed well with water when the surface of the source contacted the detector housing, the relative response in the phantoms decreased with increasing depth in phantom, falling to approximately 0.55 those of water at a depth of 5 mm. Readings in polystyrene were within 4% of those in water between 1 and 2 mm depth. However, while polystyrene followed water more closely than the other two materials, at greater depths the relative response in polystyrene to water varied from 0.65 to 1.34. When the density of the materials is accounted for, the relative response in A150 is nearly constant with increasing areal density. Furthermore, the response in A150 shows the closest agreement with that in water of any of the solid materials for higher areal densities. For values below 0.3 g/cm2, polystyrene shows the closest agreement with water.

Tissue mimicking materials for a multi-imaging modality prostate phantom.

Materials that simultaneously mimic soft tissue in vivo for magnetic resonance imaging (MRI), ultrasound (US), and computed tomography (CT) for use in a prostate phantom have been developed. Prostate and muscle mimicking materials contain water, agarose, lipid particles, protein, Cu++, EDTA, glass beads, and thimerosal (preservative). Fat was mimicked with safflower oil suffusing a random mesh (network) of polyurethane. Phantom material properties were measured at 22 degrees C. (22 degrees C is a typical room temperature at which phantoms are used.) The values of material properties should match, as well as possible, the values for tissues at body temperature, 37 degrees C. For MRI, the primary properties of interest are T1 and T2 relaxations times, for US they are the attenuation coefficient, propagation speed, and backscatter, and for CT, the x-ray attenuation. Considering the large number of parameters to be mimicked, rather good agreement was found with actual tissue values obtained from the literature. Using published values for prostate parenchyma, T1 and T2 at 37 degrees C and 40 MHz are estimated to be about 1,100 and 98 ms, respectively. The CT number for in vivo prostate is estimated to be 45 HU (Hounsfield units). The prostate mimicking material has a T1 of 937 ms and a T2 of 88 ms at 22 degrees C and 40 MHz; the propagation speed and attenuation coefficient slope are 1,540 m/s and 0.36 dB/cm/MHz, respectively, and the CT number of tissue mimicking prostate is 43 HU. Tissue mimicking (TM) muscle differs from TM prostate in the amount of dry weight agarose, Cu++, EDTA, and the quality and quantity of glass beads. The 18 microm glass beads used in TM muscle increase US backscatter and US attenuation; the presence of the beads also has some effect on T1 but no effect on T2. The composition of tissue-mimicking materials developed is such that different versions can be placed in direct contact with one another in a phantom with no long term change in US, MRI, or CT properties. Thus, anthropomorphic phantoms can be constructed.

An iterative sequential mixed-integer approach to automated prostate brachytherapy treatment plan optimization.

Conventional treatment planning for interstitial prostate brachytherapy is generally a 'trial and error' process in which improved treatment plans are generated by iteratively changing, via expert judgement, the configuration of sources within the target volume in order to achieve a satisfactory dose distribution. We have utilized linear mixed-integer programming (MIP) and the branch-and-bound method, a deterministic search algorithm, to generate treatment plans. The rapidity of dose falloff from an interstitial radioactive source requires fine sampling of the space in which dose is calculated. This leads to a large and complex model that is difficult to solve as a single 3D problem. We have therefore implemented an iterative sequential approach that optimizes pseudo-independent 2D slices to achieve a fine-grid 3D solution. Using our approach, treatment plans can be generated in 20-45 min on a 200 MHz processor. A comparison of our approach with the manual 'trial and error' approach shows that the optimized plans are generally superior. The dose to the urethra and rectum is usually maintained below harmful levels without sacrificing target coverage. In the event that the dose to the urethra is undesirably high, we present a refined optimization approach that lowers urethra dose without significant loss in target coverage. An analysis of the sensitivity of the optimized plans to seed misplacement during the implantation process is also presented that indicates remarkable stability of the dose distribution in comparison with manual treatment plans.

Radiation injury from x-ray exposure during brachytherapy localization.

Two patients developed skin ulcers secondary to high doses of diagnostic-energy x rays received during localization procedures as part of brachytherapy treatments. Both were morbidly obese and diabetic. The obesity led to the delivery of estimated skin doses of 83 Gy in one case and 29 Gy in the other in attempts to produce readable images on localization radiographs. This report discusses the factors leading to the injuries, the progression of the injuries over time, and the variables involved in the localization procedures with the aim of preventing future mishaps. The greatest contribution to the large skin dose was the need, with the equipment available, to use multiple exposures to produce a single film, because of the effect of the resultant reciprocity failure.

Measurements of head-scatter factors with cylindrical build-up caps and columnar miniphantoms.

Head-scatter factors, Sh, also referred to as output factors, are measured in-air with an ion chamber and a semiconductor diode fitted with cylindrical build-up caps and columnar miniphantoms fabricated from materials of different atomic number. Sh increases with field size less rapidly when cylindrical build-up caps are constructed from high atomic number materials. This is a consequence of a net scatter of contamination electrons away from the detector. Ion chambers and diodes give identical results when the same type of build-up caps are used. Contamination electrons can be avoided by the use of columnar miniphantoms that have sufficient wall thickness in the radial direction. This radial wall thickness is characterized in this work for 6, 10, and 18 MV x-ray beams. Sh increases with field size less rapidly when columnar miniphantoms are constructed from high atomic number materials. This is due to the decrease in the average energy of photons at large field sizes. It is concluded that to obtain Sh for dosimetry in water, cylindrical build-up caps and columnar miniphantoms should be constructed from material with an atomic number close to that of water.

A solid water pelvic and prostate phantom for imaging, volume rendering, treatment planning, and dosimetry for an RTOG multi-institutional, 3-D dose escalation study. Radiation Therapy Oncology Group.

PURPOSE: With increased interest in 3-D conformal radiation therapy and dose escalation, it is necessary to provide advanced techniques to assure quality in treatment delivery. Multi-institutional trials for these newer treatment techniques require methods of verifying the consistency of treatments between the participating institutions. For this reason, a phantom was designed to address the quality and consistency of Radiation Therapy Oncology Group (RTOG) 3-D prostate treatment protocol. METHODS AND MATERIALS: A solid water pelvic and prostate phantom for imaging, volume rendering, treatment planning, and dosimetry applications for performing comprehensive quality assurance has been designed and fabricated. Its configuration was based upon CT slices obtained from a patient study. Individual slices were machined with corresponding contours of the prostate, bladder, rectum, and the left and right femurs. Most of the phantom is made of solid water (Gammex/RMI, Middleton, WI), while the femurs are made of bone-equivalent material. The CT numbers from patient images were used to adjust the solid water composition within the organ volumes, providing image contrast from the remainder of the phantom. Cylindrical insertion grooves are machined in the phantom to allow placement of ionization chambers and thermal luminal dosimeters (TLDs) for dosimetry applications. During imaging, the cavities are filled with rods fabricated from solid water material. RESULTS: The phantom is being used to evaluate the consistency of a range of processes in radiation therapy simulation, planning, and delivery of 3-D-based treatments for prostate cancer. CONCLUSION: The ultimate study objective is to use the phantom to evaluate the accuracy and consistency of treatments delivered by institutions participating in national collaborative clinical trials involving 3-D conformal dose escalation.

High dose-rate brachytherapy treatment delivery: report of the AAPM Radiation Therapy Committee Task Group No. 59.

The goals of this task group are to examine the current high dose-rate (HDR) treatment delivery practices and to prepare a document to assure safe delivery of HDR treatments. The document consists of detailed HDR procedures for design of an HDR brachytherapy program, staffing and training, treatment specific quality assurance, and emergency procedures. The document provides an extensive quality assurance (QA) check list. It reviews all aspects of HDR treatment delivery safety, including prescription, treatment plan, treatment delivery, and radiation safety.

An investigation of tomotherapy beam delivery.

Experimental simulations for tomotherapy beam delivery were performed using a computer-controlled phantom positioner, a cylindrical phantom, and a 6 MV x-ray slit beam. Both continuous helical beam and sequential segmented tomotherapy (SST) beam deliveries were evaluated. Beam junctioning problem due to couch indexing error or field width errors presented severe dose uniformity perturbations for SST, while the problem was minimized for helical beam delivery. Longitudinal breathing motions were experimentally simulated for helical and SST beam delivery. While motions reduced the dose uniformity perturbations for SST, small artifacts in dose uniformity can be introduced for helical beam delivery. With typical breath frequency and magnitude, for a slit beam of 2.0 cm width at 4 rpm, the dose uniformity perturbation was not significant. A running start/stop technique was implemented with helical beam delivery to sharpen the 20%-80% longitudinal dose fall-off from 1.5 to 0.5 cm. The latter was comparable to the corresponding dose penumbra of a conventional 6 MV 10 x 10 cm2 field. All together, helical beam delivery showed advantages over SST for tomotherapy beam delivery under similar delivery conditions.

Innovations and advances in brachytherapy.

The treatment of cancer with radioactive sources using topical molds and intracavitary radium showed the efficacy of brachytherapy long before external radiation therapy became common practice. Brachytherapy is progressing in several clinical directions that reflect technological innovation as well as changes in medical care which combine to provide significant advances in the practice of brachytherapy today. A major change in brachytherapy, the development of high intensity sources, promoted clinical and technologic innovations in high dose-rate brachytherapy. Pulse dose-rate brachytherapy is the use of these sources to treat a target by using pulses of radiation for several minutes each hour with the same overall time and total dose as low dose-rate treatment. Recent novel approaches of using radiotherapy for prevention of restenosis in coronary and peripheral vessels has interested laboratory and clinical researchers. Most of the work toward new source material for brachytherapy centers around intravascular applications. Technology to support brachytherapy continues to advance rapidly. The interaction between images from diverse modalities and the various phases of the treatment planning is the basis of enhanced treatment planning procedures. Optimization in brachytherapy entails calculating the source strengths or source dwell times to satisfy a set of dose criteria to achieve the best dose distribution for a brachytherapy implant. Progress in computerization and calculation modeling has promoted this technical advance. Education and training in brachytherapy indications and techniques is mandatory to maintain high standards of brachytherapy practice.

The adverse effect of treatment prolongation in cervical carcinoma.

PURPOSE: Proliferation of surviving tumor clonogens during a course of protracted radiation therapy may be a cause of local failure in cervical carcinoma. The effect of total treatment time was analyzed retrospectively in relation to pelvic control and overall survival for squamous cell carcinomas of the uterine cervix. METHODS AND MATERIALS: Two hundred and nine patients (Stage IB-IIIB) treated with a combination of external beam and low dose rate intracavitary irradiation were evaluable for study. Multivariate analysis and Kaplan-Meier statistical methods were used to determine the effect of treatment time on pelvic control and survival at 5 years. RESULTS: The median treatment duration was 55 days. For all stages combined, the 5-year survival and pelvic control rates were significantly different with treatment times < 55 days vs. > or = 55 days: 65 and 54% (p = 0.03), 87 and 72% (p = 0.006), respectively. By stage, a shorter treatment duration (i.e., < 55 days vs. > or = 55 days) was significant for 5-year overall survival and pelvic control for Stages IB/IIA and III, but not for Stage IIB: Stage IB/IIA (81 and 67%, 96 and 84%), Stage III disease (52 and 42%, 76 and 55%) and Stage IIB (43 and 50%, 74 and 80%, respectively). Survival decreased 0.6%/day and pelvic control decreased 0.7%/day for each additional day of treatment beyond 55 days for all stages of disease. Additionally, significant late complications were not influenced by treatment time. CONCLUSION: These results suggest that prolongation of treatment time is associated with decreased local control and survival in patients with cervical carcinoma. This is consistent with emerging data from other institutions. Therapeutic implications include avoidance of unnecessary treatment breaks, the design of fractionation schemes that decrease treatment duration, and possibly the use of tumor cytostatic drugs during conventional radiation.

Postoperative vaginal cuff irradiation using high dose rate remote afterloading: a phase II clinical protocol.

PURPOSE: In September 1989, a postoperative Phase II high dose rate (HDR) brachytherapy protocol was started for International Federation of Gynecology and Obstetrics (FIGO) Stage I endometrial adenocarcinoma. This review reports the overall survival, local control, and complication rates for the initial 63 patients treated in this Phase II study. METHODS AND MATERIALS: High dose rate brachytherapy was delivered using an Iridium-192 HDR remote afterloader. Sixty-three patients were entered into the Phase II protocol, each receiving two vaginal cuff treatments 1 week apart (range 4-12 days) with vaginal ovoids (diameter 2.0-3.0 cm). No patient received adjuvant external beam radiation. A dose of 32.4 Gy in two fractions was prescribed to the ovoid surface in 63 patients. The first three patients treated at our institution received 15, 16.2, and 29 Gy, respectively, to determine acute effects. RESULTS: At a median follow-up of 1.6 years (range 0.75-4.3 years) no patient has developed a vaginal cuff recurrence. One regional recurrence (1.6%) occurred at 1.2 years at the pelvic side wall. This patient is alive and without evidence of disease 7 months after completion of salvage irradiation, which resulted in the only vaginal stenosis (1.6%). Fourteen patients (22%) experienced vaginal apex fibrosis by physical exam, which was clinically symptomatic in four patients. Two patients reported stress incontinence; however, these symptoms were noted prior to their HDR therapy. One patient died 2.4 years after HDR therapy due to cardiovascular disease without evidence of cancer at autopsy. CONCLUSION: Preliminary results of our phase II HDR vaginal cuff protocol for postoperative FIGO Stage IA, Grade 3 or Stage IB, Grade 1-2 patients demonstrate that 32.4 Gy in two fractions is well tolerated by the vaginal cuff mucosa. Local control appears comparable to our prior experience and others with low dose rate (LDR) brachytherapy. Additional patient accrual and further follow-up will better determine the late morbidity, local control, and overall survival of these patients.

Quality assurance tool for high dose rate brachytherapy.

An insert for a well ionization chamber is described for quality assurance tests for high dose rate remote afterloaders. The use of this insert over time has shown its applicability for efficient QA tests for the high dose rate afterloader. The measurement results are six times greater than the uncertainties involved for the measurements. Checks on position can be made better than 1 mm and dwell times better than 1 s. The overall measurements can be done to better than 1.5%. QA checks can be accomplished in a shorter time period with as great or better accuracy than prior film techniques.

Intercomparison of normalized head-scatter factor measurement techniques.

Normalized head-scatter factors were measured with cylindrical beam coaxial miniphantoms and high purity graphite buildup caps for 4-, 6-, 10-, and 24-MV photon beams at field sizes from 4 x 4 to 40 x 40 cm2. The normalized head-scatter factors determined by the two methods matched well for 4- and 6-MV photon beams. The miniphantom technique produced normalized head-scatter factors 1.5% and 4.8% lower than the buildup caps for the 10- and 24-MV beams for large field sizes, respectively. At small field sizes, the miniphantom technique produced larger normalized head-scatter factors than the buildup caps. Measurements made with an electromagnet indicate that a significant portion of the ionization measured in the buildup cap at 24 MV arises from contamination electrons. Measurements made with the miniphantom and magnet found no contamination electron contribution. The miniphantom technique may exclude such contamination electrons, potentially leading to inaccuracies in tissue-maximum ratios and phantom scatter factors, as well as inaccuracies in monitor unit calculations.

Impact of "optimized" treatment planning for tandem and ring, and tandem and ovoids, using high dose rate brachytherapy for cervical cancer.

PURPOSE: Different treatment techniques are used in high dose rate (HDR) remote afterloading intracavitary brachytherapy for uterine cervical cancer. We have investigated the differences between "optimized" and "nonoptimized" therapy using both a tandem and ring (T/R) applicator, and a tandem and ovoids (T/O), applicator. METHODS AND MATERIALS: HDR afterloading brachytherapy using the Madison System for Stage IB cervical cancer was simulated for 10 different patients using both a T/R applicator and a T/O applicator. A treatment course consists of external beam irradiation and five insertions of HDR afterloading brachytherapy. Full dosimetry calculations were performed at the initial insertion for both applicators and used as a reference for the following four insertions of the appropriate applicator. Forty dosimetry calculations were performed to determine the dose delivered to Point M (similar to Point A), Point E (obturator lymph nodes), vaginal surface, bladder, and rectum. "Optimized" doses were specified to Point M and to the vaginal surface. "Nonoptimized" doses were specified to Point M only. Using the linear-quadratic equation, calculations have been performed to convert the delivered dose using HDR to the biologically equivalent doses at the conventional low dose rate (LDR) at 0.60 Gy/h. RESULTS: Major differences between "optimized" and "nonoptimized" LDR equivalent doses were found at the vaginal surface, bladder, and rectum. Overdoses at the vaginal surface, bladder, and rectum were calculated to be 208%, nil, and 42%, respectively, for the T/R applicator with "nonoptimization." However, for the T/O applicator, the overdoses were smaller, being nil, 32%, and 27%, respectively, with "nonoptimization." CONCLUSION: Doses given in high dose rate intracavitary brachytherapy border on tissue tolerance. "Optimization" of either applicator decreases the risk of a dose that may have potential for complications. Optimization of a tandem and ovoids best ensures that the doses are not diminished at the treatment sites, and that the potential for overdose is reduced.