Visualising a rare and complex case of advanced hilar cholangiocarcinoma.

The Toronto Video Atlas of Liver, Pancreas, Biliary, and Transplant Surgery (TVASurg) is a free online library of three-dimensional (3D) animation-enhanced surgical videos, designed to instruct surgical fellows in hepato-pancreato-biliary (HPB) and transplant procedures. The video 'Klatskin tumours: Extended left hepatectomy with complex portal vein reconstruction and in situ cold perfusion of the liver', which is available to watch at http://TVASurg.ca , is a unique and valuable visual resource for surgeons in training to assist them in learning this rare procedure. This paper describes the methodologies used in producing this 3D animation-enhanced surgical video.

Creating an animation-enhanced video library of hepato-pancreato-biliary and transplantation surgical procedures.

The potential for integrating real-time surgical video and state-of-the art animation techniques has not been widely applied to surgical education. This paper describes the use of new technology for creating videos of liver, pancreas and transplant surgery, annotating them with 3D animations, resulting in a freely-accessible online resource: The Toronto Video Atlas of Liver, Pancreas and Transplant Surgery ( http://tvasurg.ca ). The atlas complements the teaching provided to trainees in the operating room, and the techniques described in this study can be readily adapted by other surgical training programmes.

Efficacy and safety of canagliflozin compared with placebo in older patients with type 2 diabetes mellitus: a pooled analysis of clinical studies.

BACKGROUND: Canagliflozin is a sodium glucose co-transporter 2 inhibitor developed for the treatment of patients with type 2 diabetes mellitus (T2DM). The efficacy and safety of canagliflozin were evaluated in patients with T2DM <65 and ≥65 years of age. METHODS: Pooled data from 4 randomised, placebo-controlled, 26-week, Phase 3 studies (N = 2,313) evaluating canagliflozin 100 and 300 mg were analysed by age: <65 years (n = 1,868; mean age, 52.8 years) or ≥65 years (n = 445; mean age, 69.3 years). Efficacy evaluations included change from baseline in glycaemic parameters and systolic blood pressure (BP), and percent change from baseline in body weight. Assessment of safety/tolerability included adverse event (AE) reports, incidence of documented hypoglycaemia, and percent change from baseline in fasting plasma lipids. RESULTS: Canagliflozin 100 and 300 mg reduced HbA1c and fasting plasma glucose relative to placebo in patients <65 and ≥65 years of age. Both canagliflozin doses reduced body weight and systolic BP relative to placebo in patients <65 and ≥65 years of age. Incidence of overall AEs was similar across all treatment groups in patients <65 and ≥65 years of age. Incidences of serious AEs and AE-related discontinuations were similar across all treatment groups in patients <65 years of age and higher with canagliflozin 100 mg than other groups in patients ≥65 years of age. As in patients <65 years of age, incidences of genital mycotic infections and osmotic diuresis-related AEs were higher with canagliflozin relative to placebo in those ≥65 years of age. Incidences of urinary tract infections (UTIs), renal-related AEs, AEs related to volume depletion, and documented hypoglycaemia episodes were similar across all treatment groups in patients ≥65 years of age; no notable trends were observed with canagliflozin 100 and 300 mg relative to placebo in these AEs among patients <65 years of age. Changes in lipid parameters with canagliflozin were similar in both age subsets. CONCLUSIONS: Canagliflozin improved glycaemic control, body weight, and systolic BP, and was generally well tolerated in older patients with T2DM. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01081834; NCT01106677; NCT01106625; NCT01106690.

Phase 1/2 AAV5-hRKp.RPGR (Botaretigene Sparoparvovec) Gene Therapy: Safety and Efficacy in RPGR-associated X-linked Retinitis Pigmentosa.

PURPOSE: To assess the safety and efficacy of AAV5-hRKp.RPGR in participants with retinitis pigmentosa GTPase regulator (RPGR)-associated X-linked retinitis pigmentosa (XLRP). DESIGN: Open-label, phase 1/2 dose escalation/expansion study (NCT03252847). METHODS: Males (≥5 years old) with XLRP-RPGR were evaluated. In the dose escalation phase, subretinal AAV5-hRKp.RPGR (low: 1.0×1011 vg/ml; intermediate: 2.0×1011 vg/ml; high: 4.0×1011 vg/ml) was administered to the poorer-seeing eye (n = 10). Dose confirmation (intermediate dose) was carried out in 3 pediatric participants. In the dose expansion phase, 36 participants were randomized 1:1:1 to immediate (low or intermediate dose) or deferred (control) treatment. The primary outcome was safety. Secondary efficacy outcomes included static perimetry, microperimetry, vision-guided mobility, best corrected visual acuity, and contrast sensitivity. Safety and efficacy outcomes were assessed for 52 weeks for immediate treatment participants and 26 weeks for control participants. RESULTS: AAV5-hRKp.RPGR was safe and well tolerated, with no reported dose-limiting events. Most adverse events (AEs) were transient and related to the surgical procedure, resolving without intervention. Two serious AEs were reported with immediate treatment (retinal detachment, uveitis). A third serious AE (increased intraocular pressure) was reported outside the reporting period. All ocular inflammation-related AEs responded to corticosteroids. Treatment with AAV5-hRKp.RPGR resulted in improvements in retinal sensitivity and functional vision compared with the deferred group at Week 26; similar trends were observed at Week 52. CONCLUSIONS: AAV5-hRKp.RPGR demonstrated an anticipated and manageable AE profile through 52 weeks. Safety and efficacy findings support investigation in a phase 3 trial.

Off-label medication use in rare pediatric diseases in the United States.

Many pediatric patients with rare diseases use drugs off-label due to limited data in pediatric patients. Off-label treatment remains an important public health issue for neonates, infants, children, and adolescents, especially for pediatric patients with rare diseases. For patients with rare diseases, the majority of medications have no or limited information in labelling for pediatric use. Children present unique considerations in clinical trials due to ethical and clinical concerns, which have limited and even discouraged testing of drugs in the pediatric population. Numerous legislative measures have been enacted to address barriers in pediatric drug testing. This research reviewed off-label medication use in rare pediatric diseases, evaluated recent medication uses in pediatric clinical practice, discussed key regulations for rare pediatric diseases, and summarized recent drug approvals for rare pediatric diseases. This study demonstrates the ongoing medical need for newly approved medications to treat pediatric rare diseases and revealed the positive impact of regulations from the Orphan Drug Act of 1983 to the Research to Accelerate Cures and Equity (RACE) for Children Act on drug development and off-label medication practice in rare pediatric disease management. This article provides informative historical background and current considerations of off-label use of medications in neonates, infants, children, and adolescents with rare diseases.

Response of the inner ear to lipopolysaccharide introduced directly into scala media.

In an attempt to develop an animal model of immune mediated Meniere's disease, we have injected lipopolysaccharide (LPS) directly into scala media of guinea pigs and monitored functional and morphological changes over a period of 6 weeks. Depending on the concentration of LPS, changes ranged from moderate-to-severe hearing loss and endolymphatic hydrops with minimal cellular infiltrate or fibrosis, to dense cellular infiltration that filled the scalae. Interestingly, higher concentrations of LPS not only induced severe cellular infiltration, hydrops, and hearing loss, but also a substantial enlargement of the endolymphatic duct and sac. Moreover, LPS injections into perilymph failed to induce hydrops, yet still resulted in cellular infiltration and fibrosis in the cochlea. This suggests that chronic hydrops resulting from an immune challenge of the cochlea may not be due to blockage of the endolymphatic duct and sac, restricting fluid absorption. Furthermore, injecting antigen into endolymph may produce chronic immune-mediated hydrops, and provide a more promising animal model of Meniere's, although animals did not display signs of vestibular dysfunction, and the hearing loss was relatively severe.

Depicting surgical anatomy of the porta hepatis in living donor liver transplantation.

Visualizing the complex anatomy of vascular and biliary structures of the liver on a case-by-case basis has been challenging. A living donor liver transplant (LDLT) right hepatectomy case, with focus on the porta hepatis, was used to demonstrate an innovative method to visualize anatomy with the purpose of refining preoperative planning and teaching of complex surgical procedures. The production of an animation-enhanced video consisted of many stages including the integration of pre-surgical planning; case-specific footage and 3D models of the liver and associated vasculature, reconstructed from contrast-enhanced CTs. Reconstructions of the biliary system were modeled from intraoperative cholangiograms. The distribution of the donor portal veins, hepatic arteries and bile ducts was defined from the porta hepatis intrahepatically to the point of surgical division. Each step of the surgery was enhanced with 3D animation to provide sequential and seamless visualization from pre-surgical planning to outcome. Use of visualization techniques such as transparency and overlays allows viewers not only to see the operative field, but also the origin and course of segmental branches and their spatial relationships. This novel educational approach enables integrating case-based operative footage with advanced editing techniques for visualizing not only the surgical procedure, but also complex anatomy such as vascular and biliary structures. The surgical team has found this approach to be beneficial for preoperative planning and clinical teaching, especially for complex cases. Each animation-enhanced video case is posted to the open-access Toronto Video Atlas of Surgery (TVASurg), an education resource with a global clinical and patient user base. The novel educational system described in this paper enables integrating operative footage with 3D animation and cinematic editing techniques for seamless sequential organization from pre-surgical planning to outcome.

Coadministration of Canagliflozin and Phentermine for Weight Management in Overweight and Obese Individuals Without Diabetes: A Randomized Clinical Trial.

OBJECTIVE: To assess the efficacy and safety of coadministration of canagliflozin (CANA) and phentermine (PHEN) compared with placebo (PBO) and CANA or PHEN monotherapies in individuals who were overweight and obese without type 2 diabetes. RESEARCH DESIGN AND METHODS: This 26-week, phase 2a, randomized, double-blind, PBO-controlled, multicenter, parallel-group study enrolled individuals who were obese or overweight without type 2 diabetes (N = 335, aged 18-65 years, BMI ≥30 to <50 kg/m2 or BMI ≥27 to <50 kg/m2 with hypertension and/or dyslipidemia). Participants were randomized (1:1:1:1) to receive PBO, CANA 300 mg, PHEN 15 mg, or coadministration of CANA 300 mg and PHEN 15 mg (CANA/PHEN) orally once daily. The primary end point was percent change in body weight from baseline to week 26; key secondary end points were the proportion of participants achieving weight loss ≥5% and change from baseline in systolic blood pressure. RESULTS: CANA/PHEN provided statistically superior weight loss from baseline versus PBO at week 26 (least squares mean difference -6.9% [95% CI -8.6 to -5.2]; P < 0.001). CANA/PHEN also provided statistically superior achievement of weight loss ≥5% and reduction in systolic blood pressure compared with PBO. CANA/PHEN was generally well tolerated, with a safety and tolerability profile consistent with that of the individual components. CONCLUSIONS: CANA/PHEN produced meaningful reductions in body weight and was generally well tolerated in individuals who were overweight or obese without type 2 diabetes. Further studies are warranted to evaluate potential use of this combination for long-term weight management.

Ultrasound-based guidance of intensity-modulated radiation therapy.

In ultrasound-guided intensity-modulated radiation therapy (IMRT) of prostate cancer, ultrasound imaging ascertains the anatomical position of patients during x-ray therapy delivery. The ultrasound transducers are made of piezoelectric ceramics. The same crystal is used for both ultrasound production and reception. Three-dimensional (3D) ultrasound devices capture and correlate series of 2-dimensional (2D) B-mode images. The transducers are often arranged in a convex array for focusing. Lower frequency reaches greater depth, but results in low resolution. For clear image, some gel is usually applied between the probe and the skin contact surface. For prostate positioning, axial and sagittal scans are performed, and the volume contours from computed tomography (CT) planning are superimposed on the ultrasound images obtained before radiation delivery at the linear accelerator. The planning volumes are then overlaid on the ultrasound images and adjusted until they match. The computer automatically deduces the offset necessary to move the patient so that the treatment area is in the correct location. The couch is translated as needed. The currently available commercial equipment can attain a positional accuracy of 1-2 mm. Commercial manufacturer designs differ in the detection of probe coordinates relative to the isocenter. Some use a position-sensing robotic arm, while others have infrared light-emitting diodes or pattern-recognition software with charge-couple-device cameras. Commissioning includes testing of image quality and positional accuracy. Ultrasound is mainly used in prostate positioning. Data for 7825 daily fractions of 234 prostate patients indicated average 3D inter-fractional displacement of about 7.8 mm. There was no perceivable trend of shift over time. Scatter plots showed slight prevalence toward superior-posterior directions. Uncertainties of ultrasound guidance included tissue inhomogeneities, speckle noise, probe pressure, and inter-observer variation. Some published studies detected improvement in treatment based on gastrointestinal toxicity and the reduction of prostate movement.

The effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on mineral metabolism and bone in patients with type 2 diabetes mellitus.

BACKGROUND: Sodium glucose co-transporter 2 (SGLT2) inhibitors lower blood glucose levels in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion. This review provides a comprehensive summary of preclinical and clinical data on the effects of the SGLT2 inhibitor canagliflozin on mineral balance and bone. METHODS: Published articles and internal study reports through November 2015 were included. RESULTS: In clinical studies, canagliflozin was not associated with meaningful changes in serum or urine calcium, parathyroid hormone, or vitamin D. Canagliflozin was associated with increases in serum magnesium and phosphate without changes in their urinary excretion. Increases in serum collagen type-1 beta-carboxy-telopeptide (beta-CTX), a bone resorption marker, and osteocalcin, a bone formation marker, were observed with canagliflozin. Decreases in total hip bone mineral density (BMD) of up to 1.2% were seen with canagliflozin after 2 years; no changes in BMD were seen at other skeletal sites. Changes in total hip BMD and serum beta-CTX with canagliflozin correlated with decreases in body weight. In a clinical program-wide analysis, canagliflozin was associated with increased fracture risk that was driven by a higher incidence in the cardiovascular safety study (CANVAS), with no fracture imbalance seen in pooled data from other Phase 3 studies. The fracture imbalance occurred within 12 weeks after initiating treatment, most frequently in the distal portion of the upper and lower extremities. CONCLUSIONS: Across clinical studies, canagliflozin did not meaningfully affect calcium homeostasis or hormones regulating calcium homeostasis. Increases in bone turnover markers and decreases in BMD at the total hip, but not at other sites, that correlated with weight loss were seen with canagliflozin. Canagliflozin was associated with a higher fracture incidence within 12 weeks, primarily in distal extremities. Data from ongoing canagliflozin studies will provide additional information on fracture risk.

Effects of canagliflozin on body weight and body composition in patients with type 2 diabetes over 104 weeks.

OBJECTIVES: Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, has been associated with weight loss in a broad range of patients with type 2 diabetes mellitus (T2DM). This analysis further evaluated changes in body weight and composition with canagliflozin in two 104-week, Phase 3 studies. METHODS: In Study 1, patients aged 18-80 years (N = 1,450) received canagliflozin 100 or 300 mg or glimepiride as add-on to metformin for a 52-week core treatment period, followed by a 52-week extension period. In Study 2, patients aged 55-80 years (N = 714) received canagliflozin 100 or 300 mg or placebo added to stable background antihyperglycemic agents for a 26-week core treatment period, followed by a 78-week extension period. Percent change from baseline in body weight; proportion of patients with any weight loss, ≥5% weight loss, and ≥10% weight loss; change in body mass index (BMI) and waist circumference; change in body weight across weight-loss quartiles; and changes in body composition were evaluated in both studies. RESULTS: Canagliflozin 100 and 300 mg provided sustained weight loss versus either glimepiride or placebo over 104 weeks. More patients experienced any weight loss and ≥5% weight loss with canagliflozin versus comparator. Across the 3 highest weight-loss quartiles, canagliflozin provided greater weight loss versus glimepiride or placebo. BMI and waist circumference reductions were observed with canagliflozin 100 and 300 mg versus either glimepiride or placebo over 104 weeks; more patients had BMI or waist circumference reductions with canagliflozin versus comparator. Body composition analysis indicated that the majority of weight loss was due to loss of fat mass. Canagliflozin was generally well tolerated, with increased incidence of adverse events related to the SGLT2 inhibition mechanism. CONCLUSIONS: Canagliflozin 100 and 300 mg provided sustained reductions in body weight, BMI, and waist circumference in a greater proportion of patients with T2DM versus glimepiride or placebo over 104 weeks. TRIAL REGISTRATION: ClinicalTrials.gov NCT00968812, NCT01106651.

Evaluation of Bone Mineral Density and Bone Biomarkers in Patients With Type 2 Diabetes Treated With Canagliflozin.

CONTEXT: Canagliflozin is a sodium glucose cotransporter 2 inhibitor developed to treat type 2 diabetes mellitus (T2DM). OBJECTIVE: Our objective is to describe the effects of canagliflozin on bone mineral density (BMD) and bone biomarkers in patients with T2DM. DESIGN: This was a randomized study, consisting of a 26-week, double-blind, placebo-controlled period and a 78-week, double-blind, placebo-controlled extension. SETTING: This study was undertaken in 90 centers in 17 countries. PATIENTS: Patients were aged 55-80 years (N = 716) and whose T2DM was inadequately controlled on a stable antihyperglycemic regimen. INTERVENTIONS: Canagliflozin 100 or 300 mg or placebo were administered once daily. OUTCOME AND MEASURES: BMD was assessed using dual-energy x-ray absorptiometry at weeks 26, 52, and 104. Bone strength was assessed using quantitative computed tomography and finite element analysis at week 52. Serum collagen type 1 ß-carboxy-telopeptide, osteocalcin, and estradiol were assessed at weeks 26 and 52. RESULTS: Canagliflozin doses of 100 and 300 mg were associated with a decrease in total hip BMD over 104 weeks, (placebo-subtracted changes: -0.9% and -1.2%, respectively), but not at other sites measured (femoral neck, lumbar spine, or distal forearm). No meaningful changes in bone strength were observed. At week 52, canagliflozin was associated with an increase in collagen type 1 ß-carboxy-telopeptide that was significantly correlated with a reduction in body weight, an increase in osteocalcin, and, in women, a decrease in estradiol. CONCLUSIONS: In older patients with T2DM, canagliflozin showed small but significant reductions in total hip BMD and increases in bone formation and resorption biomarkers, due at least in part to weight loss.

Prostate motion and isocenter adjustment from ultrasound-based localization during delivery of radiation therapy.

PURPOSE: To study prostate motion from 4,154 ultrasound alignment fractions on 130 prostate patients treated with conformal radiotherapy or intensity-modulated radiation therapy at the University of Nebraska Medical Center. METHODS AND MATERIALS: Each prostate patient was immobilized in a vacuum cradle. Daily treatment was verified by ultrasound scan after laser setup with skin marks and before radiation delivery by the same physician responsible for anatomic delineation during planning. Directional statistics were employed to test the significance of shift directions. RESULTS: Polar histograms showed the prevalence of prostate motion in superior-posterior directions. The average direction was about 27 degrees from the superior axis. The average changes of prostate position in superior to inferior (SI), anterior-posterior (AP), and left to right (LR) directions and in radial distance were 0.25, -0.13, 0.03, and 0.92, cm respectively. Our data indicated that prostate motion was not patient specific, and its average magnitude remained virtually unchanged over time. Recommended planning target volume (PTV) margins for use without ultrasound localization were 0.90 cm in SI, 1.02 cm in AP, and 0.80 cm in LR directions. CONCLUSION: Ultrasound localization revealed a predominance of prostate shift from planning position in the superior-posterior direction, with an average closer to the superior axis. The motion data provides recommended margins for PTV.

Effects of field parameters on IMRT plan quality for gynecological cancer: a case study.

Traditional external beam radiotherapy of gynecological cancer consists of a 3D, four-field-box technique. The radiation treatment area is a large region of normal tissue, with greater inhomogeneity over the treatment volume, which could benefit more with intensity-modulated radiation therapy (IMRT). This is a case report of IMRT planning for a patient with endometrial cancer. The planning target volume (PTV) spanned the intrapelvic and periaortic lymph nodes to a 33-cm length. Planning and treatment were accomplished using double isocenters. The IMRT plan was compared with a 3D plan, and the effects of field parameters were studied. Delineated anatomical contours included the intrapelvic nodes (PTV), bone marrow, small bowel, bladder, rectum, sigmoid colon, periaortic nodes (PTV), spinal cord, left kidney, right kidney, large bowel, liver, and tissue (excluding the PTVs). Comparisons were made between IMRT and 3D plans, 23-MV and 6-MV energies, zero and rotated collimator angles, different numbers of segments, and opposite gantry angle configurations. The plans were evaluated based on dosevolume histograms (DVHs). Compared with the 3D plan, the IMRT plan had superior dose conformity and spared the bladder and sigmoid colon embedded in the intrapelvic nodes. The higher energy (23 MV) reduced the dose to most critical organs and delivered less integral dose. Zero collimator angles resulted in a better plan than "optimized" collimator angles, with lower dose to most of the normal structures. The number of segments did not have much effect on isodose distribution, but a reasonable number of segments was necessary to keep treatment time from being prohibitively long. Gantry angles, when evenly spaced, had no noticeable effect on the plan. The patient tolerated the treatment well, and the initial complete blood count was favorable. Our results indicated that large-volume tumor sites may also benefit from precise conformal delivery of IMRT.

A comparison of two image fusion techniques in ct-on-rails localization of radiation delivery.

A computed tomography (ct) scanner on Rails has been installed in a linear accelerator room at Morristown Memorial Hospital since 2000. The ct-on-Rails has been used for the localization of patient position during radiation delivery for prostate, lung and liver cancer patients. The image management system, the Siemens Syngo system, is the primary software employed in the registration of the planning ct and the treatment ct images. This study compares the two image fusion methods available in the system: Landmark Registration and Visual Alignment. Shifts in 6 ct scans with Rando phantom were deduced from Landmark Registration (automatic algorithm) and from Visual Alignment (manual registration), and compared with the shifts directly measured on the phantom. For Visual Alignment, the isocenter shifts deduced from the fused images generally agreed well with the directly measured shifts on the Rando phantom, with average absolute error of 0.9 mm in anterior-posterior (ap) direction, 1.0 mm in right-left (rl) direction, and 2.0 mm in superior-inferior (si) direction. The image fusion algorithm was confirmed to be accurate. Some scans with Landmark Registration gave erroneous ap shifts when the anterior radio-opaque marker (bb) registration was of in the ap direction. Visual Alignment was more robust than Landmark Registration in these clinical situations.

Towards integrating functional imaging in the treatment of prostate cancer with radiation: the registration of the MR spectroscopy imaging to ultrasound/CT images and its implementation in treatment planning.

PURPOSE: Dose-escalation to intraprostatic tumor deposits detected by magnetic resonance spectroscopy (MRS) is an example of tumor-targeted radiation therapy. Because treatment planning for prostate brachytherapy is performed based on ultrasound (US)/computed tomography (CT) images, a sine qua non of this technique is the ability to map MRS-positive volumes (obtained in a gland deformed by the endorectal balloon coil) to the US/CT images. An empirical algorithm designed to perform this function, and its validation, are described. METHODS AND MATERIALS: Mathematically, the problem of mapping points between the MR and US/CT domains comes to: (a) ascertaining that the position of any point in the interior of the prostate is uniquely determined by the shape of the gland, and (b) finding an algorithm that describes this relationship. The image registration algorithm described here is based on the assumption that points within the gland maintain the same relative position with respect to both the axial contours of the prostate and the center of the prostate along the superior-inferior direction. Relative positions of MRS-positive voxels are calculated with this method in both MR and US/CT space. For a particular voxel in the MR space, one obtains first the z coordinate in the US/CT space, that is, along the superior-inferior direction. This determines the axial slice in the US/CT frame of reference where the other two coordinates (x, y) will be calculated. The validity of this algorithm was examined with the aid of a pelvic phantom built to simulate realistically the prostate and its surrounding bony and tissue structures and with CT scans of implanted patients obtained, at several weeks' intervals, as part of an edema-resolution study. Seventy-five "dummy" seeds were placed in the phantom, within the simulated prostate gland, in a quasi-regular pattern. The coordinates of these seeds were determined and thus served as markers of prostate deformation when an inflated rectal probe was introduced in the phantom. CT images of this phantom were taken for different volumes of the MR rectal probe and in each case the prostate outlines were contoured and seed coordinates calculated. Using these data, the predictions of the mapping algorithm could be directly verified. RESULTS: Absolute values of the 3D-positional errors in this algorithm were 2.2 mm +/- 1.2 mm (average +/- SD). Only 6 of 75 seeds had positional displacement of 4 mm or more. Similar results were obtained in the patient analysis. CONCLUSIONS: In comparison to the MRS voxel size (6.25 x 6.25 x 3.0 mm3), the present algorithm achieves the desired clinical accuracy. As well, with this 3D algorithm seed positions are reconstructed with an uncertainty that, along the z direction, is less than half the thickness of the typical US slice (0.5 cm).

C-Arm imaging for brachytherapy source reconstruction: geometrical accuracy.

We study the accuracy of brachytherapy source reconstruction using C-Arm images. We use a phantom embedded with dummy ribbons in a regular pattern, placed at the rotation center of the C-Arm. With a commercial reconstruction jig, radiographic films are taken without the image intensifier. The average error in reconstructed seed coordinates is 0.1 cm. However, the jig is inconvenient for patient procedures. For C-Arm reconstruction without the jig, the magnifications of the image intensifier along orthogonal directions are different. We "stretch" the image to equalize the magnifications. Afterward, seed reconstruction has an average error of 0.1 cm in all directions.

The syed temporary interstitial iridium gynaecological implant: an inverse planning system.

Patients with advanced gynaecological cancer are often treated with a temporary interstitial implant using the Syed template and Ir- 192 ribbons at the Memorial Sloan-Kettering Cancer Center. Urgency in planning is great. We created a computerized inverse planning system for the Syed temporary gynaecological implant, which optimized the ribbon strengths a few seconds after catheter digitization. Inverse planning was achieved with simulated annealing. We discovered that hand-drawn target volumes had drawbacks; hence instead of producing a grid of points based on target volume, the optimization points were generated directly from the catheter positions without requiring an explicit target volume. Since all seeds in the same ribbon had the same strength, the minimum doses were located at both ends of the implant. Optimization points generated at both ends ensured coverage of the whole implant. Inverse planning took only a few seconds, and generated plans that provide a good starting point for manual improvement.

Automated planning volume definition in soft-tissue sarcoma adjuvant brachytherapy.

In current practice, the planning volume for adjuvant brachytherapy treatment for soft-tissue sarcoma is either not determined a priori (in this case, seed locations are selected based on isodose curves conforming to a visual estimate of the planning volume), or it is derived via a tedious manual process. In either case, the process is subjective and time consuming, and is highly dependent on the human planner. The focus of the work described herein involves the development of an automated contouring algorithm to outline the planning volume. Such an automatic procedure will save time and provide a consistent and objective method for determining planning volumes. In addition, a definitive representation of the planning volume will allow for sophisticated brachytherapy treatment planning approaches to be applied when designing treatment plans, so as to maximize local tumour control and minimize normal tissue complications. An automated tumour volume contouring algorithm is developed utilizing computational geometry and numerical interpolation techniques in conjunction with an artificial intelligence method. The target volume is defined to be the slab of tissue r cm perpendicularly away from the curvilinear plane defined by the mesh of catheters. We assume that if adjacent catheters are over 2r cm apart, the tissue between the two catheters is part of the tumour bed. Input data consist of the digitized coordinates of the catheter positions in each of several cross-sectional slices of the tumour bed, and the estimated distance r from the catheters to the tumour surface. Mathematically, one can view the planning volume as the volume enclosed within a minimal smoothly-connected surface which contains a set of circles, each circle centred at a given catheter position in a given cross-sectional slice. The algorithm performs local interpolation on consecutive triplets of circles. The effectiveness of the algorithm is evaluated based on its performance on a collection of soft-tissue sarcoma tumour beds within various anatomical structures. For each of 15 patient cases considered, the algorithm takes approximately 2 min to generate the planning volume. Although the tumour shapes are rather different, the algorithm consistently generates planning volumes that visually demonstrate smooth curves compactly encapsulating the circles. This general-purpose contouring algorithm works well whether the catheters are all close together, spread far apart in the plane or arranged in a convoluted way. The automatic contouring algorithm significantly reduces labour time and provides a consistent and objective method for determining planning volumes for soft-tissue sarcoma. Further studies are needed to validate the significance of the resulting planning volumes in designing treatment plans and the role that sophisticated brachytherapy treatment planning optimization may have in producing good plans.

Optimized planning for intraoperative planar permanent-seed implant.

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