BrachyView: development of an algorithm for real-time automatic LDR brachytherapy seed detection.

BrachyView is a novel in-body imaging system developed to provide real-time intraoperative dosimetry for low dose rate prostate brachytherapy treatments. Seed positions can be reconstructed after in-vivo implantation using a high-resolution pinhole gamma camera inserted into the patient rectum. The obtained data is a set of 2D projections of the seeds on the image plane. The 3D reconstruction algorithm requires the identification of the seed's centre of mass. This work presents the development and techniques adopted to build an algorithm that provides the means for fully automatic seed centre of mass identification and 3D position reconstruction for real-time applications. The algorithm presented uses a local feature detector, speeded up robust features, to perform detection of brachytherapy seed 2D projections from images, allowing for robust seed identification. Initial results have been obtained with datasets of 30, 96 and 98 I-125 brachytherapy seeds implanted into a prostate gel phantom. It can detect 97% of seeds and correctly match 97% of seeds. The average overall computation time of 2.75 s per image and improved reconstruction accuracy of 22.87% for the 98 seed dataset was noted. Elimination processes for initial false positive detection removal have shown to be extremely effective, resulting in a 99.9% reduction of false positives, and when paired with automatic frame alignment and subtraction procedures allows for the effective removal of excess counts generated by previously implanted needles. The proposed algorithm will allow the BrachyView system to be used as a real-time intraoperative dosimetry tool for low dose rate prostate brachytherapy treatments.

BrachyView: Reconstruction of seed positions and volume of an LDR prostate brachytherapy patient plan using a baseline subtraction algorithm.

PURPOSE: BrachyView is a novel in-body imaging system developed with the objective to provide real-time intraoperative dosimetry for low dose rate (LDR) prostate brachytherapy treatments. The BrachyView coordinates combined with conventional transrectal ultrasound (TRUS) imaging, provides the possibility to localise the effective position of the implanted seeds inside the prostate volume, providing a unique tool for intra-operative verification of the quality of the implantation. This research presents the first complete LDR brachytherapy plan reconstructed by the BrachyView system and is used to evaluate the effectiveness of an imaging algorithm with baseline subtraction. METHODS: A plan featuring 98 I-125 brachytherapy seeds, with an average activity of 0.248 mCi, were implanted into a prostate gel phantom under TRUS guidance. Images of implanted seeds were obtained by the BrachyView after the implantation of seeds. The baseline subtraction algorithm is applied as a pixel-to-pixel counts subtraction and is applied to every second projection obtained after the implantation of each needle. Seed positions and effectiveness of the baseline reconstruction in the identification of seeds were verified by a high-resolution post-implant CT scan. RESULTS: A complete brachytherapy plan has been reconstructed with a 100% detection rate. This is possible due to the effectiveness of the baseline subtraction, with its application an overall increase of 11.3% in position accuracy and 8.2% increase in detection rate was noted. CONCLUSION: It has been demonstrated that the BrachyView system shows the potential to be a solution to providing clinics with the means for intraoperative dosimetry for LDR prostate brachytherapy treatments.

BrachyView: initial preclinical results for a real-time in-body HDR PBT source tracking system with simultaneous TRUS image fusion.

A prototype in-body gamma camera system with integrated trans-rectal ultrasound (TRUS) and associated real-time image acquisition and analysis software was developed for intraoperative source tracking in high dose rate (HDR) brachytherapy. The accuracy and temporal resolution of the system was validated experimentally using a deformable tissue-equivalent prostate gel phantom and a full clinical HDR treatment plan. The BrachyView system was able to measure 78% of the 200 source positions with an accuracy of better than 1 mm. A minimum acquisition time of 0.28 s/frame was required to achieve this accuracy, restricting dwell times to a minimum of 0.3 s. Additionally, the performance of the BrachyView-TRUS fusion probe for mapping the spatial location of the tracked source within the prostate volume was evaluated. A global coordinate system was defined by scanning the phantom with the probe in situ using a CT scanner, and was subsequently used for co-registration of the BrachyView and TRUS fields of view (FoVs). TRUS imaging was used to segment the prostate volume and reconstruct it into a three-dimensional (3D) image. Fusion of the estimated source locations with the 3D prostate image was performed using integrated 3D visualisation software. HDR BrachyView is demonstrated to be a valuable tool for intraoperative source tracking in HDR brachytherapy, capable of resolving source dwell locations relative to the prostate anatomy when combined with TRUS.

Clinical application of MOSkin dosimeters to rectal wall in vivo dosimetry in gynecological HDR brachytherapy.

PURPOSE: Three MOSkins dosimeters were assembled over a rectal probe and used to perform in vivo dosimetry during HDR brachytherapy treatments of vaginal cancer. The purpose of this study was to verify the applicability of the developed tool to evaluate discrepancies between planned and measured doses to the rectal wall. MATERIALS AND METHODS: MOSkin dosimeters from the Centre for Medical Radiation Physics are particularly suitable for brachytherapy procedures for their ability to be easily incorporated into treatment instrumentation. In this study, 26 treatment sessions of HDR vaginal brachytherapy were monitored using three MOSkin mounted on a rectal probe. A total of 78 measurements were collected and compared to doses determined by the treatment planning system. RESULTS: Mean dose discrepancy was determined as 2.2±6.9%, with 44.6% of the measurements within ±5%, 89.2% within ±10% and 10.8% higher than ±10%. When dose discrepancies were grouped according to the time elapsed between imaging and treatment (i.e., group 1: ≤90min; group 2: >90min), mean discrepancies resulted in 4.7±3.6% and 7.1±5.0% for groups 1 and 2, respectively. Furthermore, the position of the dosimeter on the rectal catheter was found to affect uncertainty, where highest uncertainties were observed for the dosimeter furthest inside the rectum. CONCLUSIONS: This study has verified MOSkin applicability to in-patient dose monitoring in gynecological brachytherapy procedures, demonstrating the dosimetric rectal probe setup as an accurate and convenient IVD instrument for rectal wall dose verification. Furthermore, the study demonstrates that the delivered dose discrepancy may be affected by the duration of treatment planning.

BrachyView: Combining LDR seed positions with transrectal ultrasound imaging in a prostate gel phantom.

PURPOSE: BrachyView is a novel in-body imaging system which aims to provide LDR brachytherapy seeds position reconstruction within the prostate in real-time. The first prototype is presented in this study: the probe consists of a gamma camera featuring three single cone pinhole collimators embedded in a tungsten tube, above three, high resolution pixelated detectors (Timepix). METHODS: The prostate was imaged with a TRUS system using a sagittal crystal with a 2.5mm slice thickness. Eleven needles containing a total of thirty 0.508U125I seeds were implanted under ultrasound guidance. A CT scan was used to localise the seed positions, as well as provide a reference when performing the image co-registration between the BrachyView coordinate system and the TRUS coordinate system. An in-house visualisation software interface was developed to provide a quantitative 3D reconstructed prostate based on the TRUS images and co-registered with the LDR seeds in situ. A rigid body image registration was performed between the BrachyView and TRUS systems, with the BrachyView and CT-derived source locations compared. RESULTS: The reconstructed seed positions determined by the BrachyView probe showed a maximum discrepancy of 1.78mm, with 75% of the seeds reconstructed within 1mm of their nominal location. An accurate co-registration between the BrachyView and TRUS coordinate system was established. CONCLUSIONS: The BrachyView system has shown its ability to reconstruct all implanted LDR seeds within a tissue equivalent prostate gel phantom, providing both anatomical and seed position information in a single interface.

BrachyView, a novel in-body imaging system for HDR prostate brachytherapy: Experimental evaluation.

PURPOSE: This paper presents initial experimental results from a prototype of high dose rate (HDR) BrachyView, a novel in-body source tracking system for HDR brachytherapy based on a multipinhole tungsten collimator and a high resolution pixellated silicon detector array. The probe and its associated position estimation algorithms are validated and a comprehensive evaluation of the accuracy of its position estimation capabilities is presented. METHODS: The HDR brachytherapy source is moved through a sequence of positions in a prostate phantom, for various displacements in x, y, and z. For each position, multiple image acquisitions are performed, and source positions are reconstructed. Error estimates in each dimension are calculated at each source position and combined to calculate overall positioning errors. Gafchromic film is used to validate the accuracy of source placement within the phantom. RESULTS: More than 90% of evaluated source positions were estimated with an error of less than one millimeter, with the worst-case error being 1.3 mm. Experimental results were in close agreement with previously published Monte Carlo simulation results. CONCLUSIONS: The prototype of HDR BrachyView demonstrates a satisfactory level of accuracy in its source position estimation, and additional improvements are achievable with further refinement of HDR BrachyView's image processing algorithms.

The investigation of prostatic calcifications using µ-PIXE analysis and their dosimetric effect in low dose rate brachytherapy treatments using Geant4.

Low dose rate brachytherapy is a widely used modality for the treatment of prostate cancer. Most clinical treatment planning systems currently in use approximate all tissue to water, neglecting the existence of inhomogeneities, such as calcifications. The presence of prostatic calcifications may perturb the dose due to the higher photoelectric effect cross section in comparison to water. This study quantitatively evaluates the effect of prostatic calcifications on the dosimetric outcome of brachytherapy treatments by means of Monte Carlo simulations and its potential clinical consequences.Four pathological calcification samples were characterised with micro-particle induced x-ray emission (µ-PIXE) to determine their heavy elemental composition. Calcium, phosphorus and zinc were found to be the predominant heavy elements in the calcification composition. Four clinical patient brachytherapy treatments were modelled using Geant4 based Monte Carlo simulations, in terms of the distribution of brachytherapy seeds and calcifications in the prostate. Dose reductions were observed to be up to 30% locally to the calcification boundary, calcification size dependent. Single large calcifications and closely placed calculi caused local dose reductions of between 30-60%. Individual calculi smaller than 0.5 mm in diameter showed minimal dosimetric impact, however, the effects of small or diffuse calcifications within the prostatic tissue could not be determined using the methods employed in the study. The simulation study showed a varying reduction on common dosimetric parameters. D90 showed a reduction of 2-5%, regardless of calcification surface area and volume. The parameters V100, V150 and V200 were also reduced by as much as 3% and on average by 1%. These reductions were also found to relate to the surface area and volume of calcifications, which may have a significant dosimetric impact on brachytherapy treatment, however, such impacts depend strongly on specific factors in the patient's individual treatment. These factors include the number, size, composition and spatial distribution of calcifications in the prostate as well as the distribution of brachytherapy seeds.

The evaluation of a 2D diode array in "magic phantom" for use in high dose rate brachytherapy pretreatment quality assurance.

PURPOSE: High dose rate (HDR) brachytherapy is a treatment method that is used increasingly worldwide. The development of a sound quality assurance program for the verification of treatment deliveries can be challenging due to the high source activity utilized and the need for precise measurements of dwell positions and times. This paper describes the application of a novel phantom, based on a 2D 11 × 11 diode array detection system, named "magic phantom" (MPh), to accurately measure plan dwell positions and times, compare them directly to the treatment plan, determine errors in treatment delivery, and calculate absorbed dose. METHODS: The magic phantom system was CT scanned and a 20 catheter plan was generated to simulate a nonspecific treatment scenario. This plan was delivered to the MPh and, using a custom developed software suite, the dwell positions and times were measured and compared to the plan. The original plan was also modified, with changes not disclosed to the primary authors, and measured again using the device and software to determine the modifications. A new metric, the "position­time gamma index," was developed to quantify the quality of a treatment delivery when compared to the treatment plan. The MPh was evaluated to determine the minimum measurable dwell time and step size. The incorporation of the TG-43U1 formalism directly into the software allows for dose calculations to be made based on the measured plan. The estimated dose distributions calculated by the software were compared to the treatment plan and to calibrated EBT3 film, using the 2D gamma analysis method. RESULTS: For the original plan, the magic phantom system was capable of measuring all dwell points and dwell times and the majority were found to be within 0.93 mm and 0.25 s, respectively, from the plan. By measuring the altered plan and comparing it to the unmodified treatment plan, the use of the position­time gamma index showed that all modifications made could be readily detected. The MPh was able to measure dwell times down to 0.067 ± 0.001 s and planned dwell positions separated by 1 mm. The dose calculation carried out by the MPh software was found to be in agreement with values calculated by the treatment planning system within 0.75%. Using the 2D gamma index, the dose map of the MPh plane and measured EBT3 were found to have a pass rate of over 95% when compared to the original plan. CONCLUSIONS: The application of this magic phantom quality assurance system to HDR brachytherapy has demonstrated promising ability to perform the verification of treatment plans, based upon the measured dwell positions and times. The introduction of the quantitative position­time gamma index allows for direct comparison of measured parameters against the plan and could be used prior to patient treatment to ensure accurate delivery.

The evaluation of a 2D diode array in "magic phantom" for use in high dose rate brachytherapy pretreatment quality assurance.

PURPOSE: High dose rate (HDR) brachytherapy is a treatment method that is used increasingly worldwide. The development of a sound quality assurance program for the verification of treatment deliveries can be challenging due to the high source activity utilized and the need for precise measurements of dwell positions and times. This paper describes the application of a novel phantom, based on a 2D 11 × 11 diode array detection system, named "magic phantom" (MPh), to accurately measure plan dwell positions and times, compare them directly to the treatment plan, determine errors in treatment delivery, and calculate absorbed dose. METHODS: The magic phantom system was CT scanned and a 20 catheter plan was generated to simulate a nonspecific treatment scenario. This plan was delivered to the MPh and, using a custom developed software suite, the dwell positions and times were measured and compared to the plan. The original plan was also modified, with changes not disclosed to the primary authors, and measured again using the device and software to determine the modifications. A new metric, the "position-time gamma index," was developed to quantify the quality of a treatment delivery when compared to the treatment plan. The MPh was evaluated to determine the minimum measurable dwell time and step size. The incorporation of the TG-43U1 formalism directly into the software allows for dose calculations to be made based on the measured plan. The estimated dose distributions calculated by the software were compared to the treatment plan and to calibrated EBT3 film, using the 2D gamma analysis method. RESULTS: For the original plan, the magic phantom system was capable of measuring all dwell points and dwell times and the majority were found to be within 0.93 mm and 0.25 s, respectively, from the plan. By measuring the altered plan and comparing it to the unmodified treatment plan, the use of the position-time gamma index showed that all modifications made could be readily detected. The MPh was able to measure dwell times down to 0.067 ± 0.001 s and planned dwell positions separated by 1 mm. The dose calculation carried out by the MPh software was found to be in agreement with values calculated by the treatment planning system within 0.75%. Using the 2D gamma index, the dose map of the MPh plane and measured EBT3 were found to have a pass rate of over 95% when compared to the original plan. CONCLUSIONS: The application of this magic phantom quality assurance system to HDR brachytherapy has demonstrated promising ability to perform the verification of treatment plans, based upon the measured dwell positions and times. The introduction of the quantitative position-time gamma index allows for direct comparison of measured parameters against the plan and could be used prior to patient treatment to ensure accurate delivery.

Radiation dose enhancement at tissue-tungsten interfaces in HDR brachytherapy.

HDR BrachyView is a novel in-body dosimetric imaging system for real-time monitoring and verification of the source position in high dose rate (HDR) prostate brachytherapy treatment. It is based on a high-resolution pixelated detector array with a semi-cylindrical multi-pinhole tungsten collimator and is designed to fit inside a compact rectal probe, and is able to resolve the 3D position of the source with a maximum error of 1.5 mm. This paper presents an evaluation of the additional dose that will be delivered to the patient as a result of backscatter radiation from the collimator. Monte Carlo simulations of planar and cylindrical collimators embedded in a tissue-equivalent phantom were performed using Geant4, with an (192)Ir source placed at two different source-collimator distances. The planar configuration was replicated experimentally to validate the simulations, with a MOSkin dosimetry probe used to measure dose at three distances from the collimator. For the cylindrical collimator simulation, backscatter dose enhancement was calculated as a function of axial and azimuthal displacement, and dose distribution maps were generated at three distances from the collimator surface. Although significant backscatter dose enhancement was observed for both geometries immediately adjacent to the collimator, simulations and experiments indicate that backscatter dose is negligible at distances beyond 1 mm from the collimator. Since HDR BrachyView is enclosed within a 1 mm thick tissue-equivalent plastic shell, all backscatter radiation resulting from its use will therefore be absorbed before reaching the rectal wall or other tissues. dosimetry, brachytherapy, HDR.

PI3K/Akt/mTOR pathway inhibitors enhance radiosensitivity in radioresistant prostate cancer cells through inducing apoptosis, reducing autophagy, suppressing NHEJ and HR repair pathways.

The PI3K/Akt/mTOR pathway has a central role in cancer metastasis and radiotherapy. To develop effective therapeutics to improve radiosensitivity, understanding the possible pathways of radioresistance involved and the effects of a combination of the PI3K/Akt/mTOR inhibitors with radiotherapy on prostate cancer (CaP) radioresistant cells is needed. We found that compared with parent CaP cells, CaP-radioresistant cells demonstrated G0/G1 and S phase arrest, activation of cell cycle check point, autophagy and DNA repair pathway proteins, and inactivation of apoptotic proteins. We also demonstrated that compared with combination of single PI3K or mTOR inhibitors (BKM120 or Rapamycin) and radiation, low-dose of dual PI3K/mTOR inhibitors (BEZ235 or PI103) combined with radiation greatly improved treatment efficacy by repressing colony formation, inducing more apoptosis, leading to the arrest of the G2/M phase, increased double-strand break levels and less inactivation of cell cycle check point, autophagy and non-homologous end joining (NHEJ)/homologous recombination (HR) repair pathway proteins in CaP-radioresistant cells. This study describes the possible pathways associated with CaP radioresistance and demonstrates the putative mechanisms of the radiosensitization effect in CaP-resistant cells in the combination treatment. The findings from this study suggest that the combination of dual PI3K/Akt/mTOR inhibitors (BEZ235 or PI103) with radiotherapy is a promising modality for the treatment of CaP to overcome radioresistance.

Acquisition of epithelial-mesenchymal transition and cancer stem cell phenotypes is associated with activation of the PI3K/Akt/mTOR pathway in prostate cancer radioresistance.

Radioresistance is a major challenge in prostate cancer (CaP) radiotherapy (RT). In this study, we investigated the role and association of epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs) and the PI3K/Akt/mTOR signaling pathway in CaP radioresistance. We developed three novel CaP radioresistant (RR) cell lines (PC-3RR, DU145RR and LNCaPRR) by radiation treatment and confirmed their radioresistance using a clonogenic survival assay. Compared with untreated CaP-control cells, the CaP-RR cells had increased colony formation, invasion ability and spheroid formation capability (P<0.05). In addition, enhanced EMT/CSC phenotypes and activation of the checkpoint proteins (Chk1 and Chk2) and the PI3K/Akt/mTOR signaling pathway proteins were also found in CaP-RR cells using immunofluorescence, western blotting and quantitative real-time PCR (qRT-PCR). Furthermore, combination of a dual PI3K/mTOR inhibitor (BEZ235) with RT effectively increased radiosensitivity and induced more apoptosis in CaP-RR cells, concomitantly correlated with the reduced expression of EMT/CSC markers and the PI3K/Akt/mTOR signaling pathway proteins compared with RT alone. Our findings indicate that CaP radioresistance is associated with EMT and enhanced CSC phenotypes via activation of the PI3K/Akt/mTOR signaling pathway, and that the combination of BEZ235 with RT is a promising modality to overcome radioresistance in the treatment of CaP. This combination approach warrants future in vivo animal study and clinical trials.

BrachyView, a novel inbody imaging system for HDR prostate brachytherapy: design and Monte Carlo feasibility study.

PURPOSE: High dose rate (HDR) brachytherapy is a form of radiation therapy for treating prostate cancer whereby a high activity radiation source is moved between predefined positions inside applicators inserted within the treatment volume. Accurate positioning of the source is essential in delivering the desired dose to the target area while avoiding radiation injury to the surrounding tissue. In this paper, HDR BrachyView, a novel inbody dosimetric imaging system for real time monitoring and verification of the radioactive seed position in HDR prostate brachytherapy treatment is introduced. The current prototype consists of a 15 × 60 mm(2) silicon pixel detector with a multipinhole tungsten collimator placed 6.5 mm above the detector. Seven identical pinholes allow full imaging coverage of the entire treatment volume. The combined pinhole and pixel sensor arrangement is geometrically designed to be able to resolve the three-dimensional location of the source. The probe may be rotated to keep the whole prostate within the transverse plane. The purpose of this paper is to demonstrate the efficacy of the design through computer simulation, and to estimate the accuracy in resolving the source position (in detector plane and in 3D space) as part of the feasibility study for the BrachyView project. METHODS: Monte Carlo simulations were performed using the GEANT4 radiation transport model, with a (192)Ir source placed in different locations within a prostate phantom. A geometrically accurate model of the detector and collimator were constructed. Simulations were conducted with a single pinhole to evaluate the pinhole design and the signal to background ratio obtained. Second, a pair of adjacent pinholes were simulated to evaluate the error in calculated source location. RESULTS: Simulation results show that accurate determination of the true source position is easily obtainable within the typical one second source dwell time. The maximum error in the estimated projection position was found to be 0.95 mm in the imaging (detector) plane, resulting in a maximum source positioning estimation error of 1.48 mm. CONCLUSIONS: HDR BrachyView is a feasible design for real-time source tracking in HDR prostate brachytherapy. It is capable of resolving the source position within a subsecond dwell time. In combination with anatomical information obtained from transrectal ultrasound imaging, HDR BrachyView adds a significant quality assurance capability to HDR brachytherapy treatment systems.

BrachyView: proof-of-principle of a novel in-body gamma camera for low dose-rate prostate brachytherapy.

PURPOSE: The conformity of the achieved dose distribution to the treatment plan strongly correlates with the accuracy of seed implantation in a prostate brachytherapy treatment procedure. Incorrect seed placement leads to both short and long term complications, including urethral and rectal toxicity. The authors present BrachyView, a novel concept of a fast intraoperative treatment planning system, to provide real-time seed placement information based on in-body gamma camera data. BrachyView combines the high spatial resolution of a pixellated silicon detector (Medipix2) with the volumetric information acquired by a transrectal ultrasound (TRUS). The two systems will be embedded in the same probe so as to provide anatomically correct seed positions for intraoperative planning and postimplant dosimetry. Dosimetric calculations are based on the TG-43 method using the real position of the seeds. The purpose of this paper is to demonstrate the feasibility of BrachyView using the Medipix2 pixel detector and a pinhole collimator to reconstruct the real-time 3D position of low dose-rate brachytherapy seeds in a phantom. METHODS: BrachyView incorporates three Medipix2 detectors coupled to a multipinhole collimator. Three-dimensionally triangulated seed positions from multiple planar images are used to determine the seed placement in a PMMA prostate phantom in real time. MATLAB codes were used to test the reconstruction method and to optimize the device geometry. RESULTS: The results presented in this paper show a 3D position reconstruction accuracy of the seed in the range of 0.5-3 mm for a 10-60 mm seed-to-detector distance interval (Z direction), respectively. The BrachyView system also demonstrates a spatial resolution of 0.25 mm in the XY plane for sources at 10 mm distance from Medipix2 detector plane, comparable to the theoretical value calculated for an equivalent gamma camera arrangement. The authors successfully demonstrated the capability of BrachyView for real-time imaging (using a 3 s data acquisition time) of different brachytherapy seed configurations (with an activity of 0.05 U) throughout a 60 × 60 × 60 mm(3) Perspex prostate phantom. CONCLUSIONS: The newly developed miniature gamma camera component of BrachyView, with its high spatial resolution and real time capability, allows accurate 3D localization of seeds in a prostate phantom. Combination of the gamma camera with TRUS in a single probe will complete the BrachyView system.

Randomized comparison of whole brain radiotherapy, 20 Gy in four daily fractions versus 40 Gy in 20 twice-daily fractions, for brain metastases.

PURPOSE: The present study compared the intracranial control rate and quality of life for two radiation fractionation schemes for cerebral metastases. METHODS AND MATERIALS: A total of 113 patients with a Eastern Cooperative Oncology Group performance status <3; and stable (>2 months), absent, or concurrent presentation of extracranial disease were randomized to 40 Gy in 20 twice-daily fractions (Arm A) or 20 Gy in four daily fractions (Arm B), stratified by resection status. The European Organization for Research and Treatment of Cancer Quality of Life 30-item questionnaire was administered monthly during Year 1, bimonthly during Year 2, and then every 6 months to Year 5. RESULTS: The patient age range was 28-83 years (mean 62). Of the 113 patients, 41 had undergone surgical resection, and 74 patients had extracranial disease (31 concurrent and 43 stable). The median survival time was 6.1 months in Arm A and 6.6 months in Arm B, and the overall 5-year survival rate was 3.5%. Intracranial progression occurred in 44% of Arm A and 64% of Arm B patients (p = .03). Salvage surgery or radiotherapy was used in 4% of Arm A patients and 21% of Arm B patients (p = .004). Death was attributed to central nervous system progression in 32% of patients in Arm A and 52% of patients in Arm B (p = .03). The toxicity was minimal, with a minor increase in short-term cutaneous reactions in Arm A. The patients' quality of life was not impaired by the more intense treatment in Arm A. CONCLUSION: Intracranial disease control was improved and the quality of life was maintained with 40 Gy in 20 twice-daily fractions. This schema should be considered for better prognosis subgroups of patients with cerebral metastases.

The effect of rectal heterogeneity on wall dose in high dose rate brachytherapy.

When treating prostate cancer using high dose rate (HDR) brachytherapy, overdosing the rectal wall may lead to post-treatment rectal complications. An area of concern is related to how the rectal wall dose is calculated by treatment planning systems (TPSs). TPSs are used to calculate the dose delivered to the rectal wall, but they assume that the rectum is a water-equivalent homogeneous medium of infinite size and do not consider the effect that an air-filled "empty" rectal cavity would have on the dose absorbed along the rectal wall. The aim of this research is to quantify the effect that an air cavity has on the rectal wall dose, as its presence changes the backscatter conditions in the region. The MO Skin and RADFET dosimeters proved capable of measuring absolute dose with increasing distance from the HDR Ir-192 brachytherapy source. However, the anterior rectal wall doses measured by the MOSkin and RADFET in an empty rectal cavity were 14.7 +/- 0.2% and 13.7 +/- 0.6% lower than the dose measured in a homogeneous rectal phantom. Monte Carlo simulations corroborated the experimentally obtained results, reporting a -13.2 +/- 0.6% difference. The dose measured at the posterior wall of an empty rectal cavity was between 22% and 26% greater than the dose measured in a full rectal cavity. The heterogeneity of the rectal volume appears to have a significant effect on the rectal dose when compared to calculated rectal dose.

A comparison of blue crab and bivalve delta15N tissue enrichment in two North Carolina estuaries.

Stable isotope analyses (delta(15)N) were used to examine invertebrate tissue enrichment in two North Carolina estuaries with differing amounts of nutrient loading. Bivalves collected from a nutrient sensitive estuary yielded a significant difference in mean nitrogen isotopic composition of tissue (10.4 per thousand+/-0.82; N=66) compared to bivalves collected from a less nutrient sensitive estuary (6.4 per thousand+/-0.63; N=45). Similarly, blue crabs from nutrient sensitive sites had a nitrogen isotopic composition of 11.4 per thousand (+/-1.3, N=77), which was significantly different (P<0.001) than the tissue of less nutrient sensitive blue crabs (9.6 per thousand+/-0.6; N=77). The results showed that an inverse relationship exists between invertebrate tissue enrichment and indicators of water quality across estuarine sites. This study suggests that a relationship may exist between nutrient sources and subsequent energy transfer to estuarine consumers in two North Carolina estuaries.

Risk factors for hospitalizations resulting from pulmonary embolism after renal transplantation in the United States.

BACKGROUND: Risk factors for pulmonary embolism (PE) have been identified in the general population but have not been studied in a national population of renal transplant recipients. METHODS: Therefore, 33,479 renal transplant recipients in the United States Renal Data System from 1 July 1994-30 June 1997 were analyzed in a historical cohort study of hospitalized PE (ICD9 Code 415.1x). HCFA form 2728 was used for comorbidities. RESULTS: Renal transplant recipients had an incidence of PE of 2.26 hospitalizations per 1000 patient years at risk. In multivariate analysis, polycystic kidney disease (adjusted odds ratio, 4.44, 95% confidence interval, 2.31-8.53), older recipient age, higher recipient weight, cadaveric donation, history of ischemic heart disease, and decreased serum albumin were associated with increased risk of PE. Body mass index and hemoglobin were not significant. Kidney-pancreas transplantation was also not significant. In Cox Regression analysis PE was associated with increased mortality (hazard ratio 2.06, 95% CI 1.34-3.18). CONCLUSIONS: The most important risk factors for PE in this population were polycystic kidney disease, advanced age and increased weight. The reasons for the increased risk of polycystic kidney disease remain to be determined but were independent of hematocrit level at initiation of end stage renal disease, and may result from venous compression. Prospective studies of anatomical and hemostatic changes after renal transplantation in recipients with polycystic kidney disease are warranted.

Implications of extranodal spread in node positive breast cancer: a review of survival and local recurrence.

An evaluation of extra nodal spread (ENS) in predicting overall survival and locoregional relapse rates in 311 node positive breast cancer patients was undertaken: the study group comprised 71 patients with ENS and the control group comprised 240 patients with no ENS. A review of pathology reports that described ENS was performed and a scoring system to categorize focal involvement, extensive axillary fat involvement, and positive axillary surgical margins was devised. Median follow up time was 3.1 years. Overall survival, disease specific survival and disease-free survival rates were significantly worse in the study group in comparison with the control group. Poorer survival with more extensive pathological invasion of ENS was demonstrated. Multivariate analysis of disease specific survival in those patient with 1-3 involved lymph nodes demonstrated that ENS positivity was prognostically significant (P=0.013). Although locoregional relapse was increased in the presence of ENS, axillary relapses were uncommon and do not warrant axillary radiation.