Response-dependent and reduced treatment in lower risk Hodgkin lymphoma in children and adolescents, results of P9426: a report from the Children's Oncology Group.

BACKGROUND: Hodgkin lymphoma is highly curable but associated with significant late effects. Reduction of total treatment would be anticipated to reduce late effects. This aim of this study was to demonstrate that a reduction in treatment was possible without compromising survival outcomes. METHODS: Protocol P9426, a response-dependent and reduced treatment for low risk Hodgkin lymphoma (stages I, IIA, and IIIA(1) ) was designed in 1994 based on a previous pilot project. Patients were enrolled from October 15, 1996 to September 19, 2000. Patients were randomized to receive or not receive dexrazoxane and received two cycles of chemotherapy consisting of doxorubicin, bleomycin, vincristine, and etoposide. After two cycles, patients were evaluated for response. Those in complete response (CR) received 2,550 cGy of involved field radiation therapy (IFRT). Patient with partial response or stable disease, received two more cycles of chemotherapy and IFRT at 2,550 cGy. RESULTS: There were 294 patients enrolled, with 255 eligible for analysis. The 8-year event free survival (EFS) between the dexrazoxane randomized groups did not differ (EFS 86.8 ± 3.1% with DRZ, and 85.7 ± 3.3% without DRZ (P = 0.70). Forty-five percent of patients demonstrated CR after two cycles of chemotherapy. There was no difference in EFS by histology, rapidity of response, or number of cycles of chemotherapy. Six of the eight secondary malignancies in this study have been previously reported. CONCLUSIONS: Despite reduced therapy and exclusion of most patients with lymphocyte predominant histology, EFS and overall survival are similar to other reported studies. The protocol documents that it is safe and effective to reduce therapy in low-risk Hodgkin lymphoma based on early response to chemotherapy with rapid responding patients having the same outcome as slower-responding patients when given 50% of the chemotherapy.

Does hydronephrosis predict the presence of severe vesicoureteral reflux?

UNLABELLED: We hypothesized that, in patients with vesicoureteral reflux (VUR) grade IV or V, hydronephrosis will likely be found, if the patient has a full bladder during the renal ultrasound examination. Eight hundred thirty-seven patients were included in the study. Patients ranged in age from <1 month to 18.7 years, with a median age of 1.3 years. Five hundred sixty-nine were female and 268 were male. In this retrospective study, each patient underwent a voiding cystourethrogram (VCUG) and a renal ultrasound examination. The presence of hydronephrosis and bladder filling status in 131 renal units with VUR grade IV or V was evaluated. Sensitivity and specificity for hydronephrosis to detect the presence of VUR grades IV and V were 60 and 92 %, respectively. Positive predictive value and negative predictive value were 74 and 87 %, respectively. Odds ratios for the relationship between hydronephrosis and severe VUR was significant (p = 0.046). CONCLUSION: In patients with grade IV or V VUR, hydronephrosis will be observed in the presence of a full bladder. Therefore, a renal ultrasound could be considered a screening test to decide on performing a VCUG.

Hybrid computational phantoms of the 15-year male and female adolescent: applications to CT organ dosimetry for patients of variable morphometry.

Currently, two classes of the computational phantoms have been developed for dosimetry calculation: (1) stylized (or mathematical) and (2) voxel (or tomographic) phantoms describing human anatomy through mathematical surface equations and three-dimensional labeled voxel matrices, respectively. Mathematical surface equations in stylized phantoms provide flexibility in phantom design and alteration, but the resulting anatomical description is, in many cases, not very realistic. Voxel phantoms display far better anatomical realism, but they are limited in terms of their ability to alter organ shape, position, and depth, as well as body posture. A new class of computational phantoms--called hybrid phantoms-takes advantage of the best features of stylized and voxel phantoms-flexibility and anatomical realism, respectively. In the current study, hybrid computational phantoms representing reference 15-year male and female body anatomy and anthropometry are presented. For the male phantom, organ contours were extracted from the University of Florida (UF) 14-year series B male voxel phantom, while for the female phantom, original computed tomography (CT) data from two 14-year female patients were used. Polygon mesh models for the major organs and tissues were reconstructed for nonuniform rational B-spline (NURBS) surface modeling. The resulting NURBS/polygon mesh models representing body contour and internal anatomy were matched to anthropometric data and reference organ mass data provided by the Centers for Disease Control and Prevention (CDC) and the International Commission on Radiation Protection (ICRP), respectively. Finally, two hybrid 15-year male and female phantoms were completed where a total of eight anthropometric data categories were matched to standard values within 4% and organ masses matched to ICRP data within 1% with the exception of total skin. To highlight the flexibility of the hybrid phantoms, 10th and 90th weight percentile 15-year male and female phantoms were further developed from the 50th percentile phantoms through adjustments in the body contour to match the total body masses given in CDC pediatric growth curves. The resulting six NURBS phantoms, male and female phantoms representing their 10th, 50th, and 90th weight percentiles, were used to investigate the influence of body fat distributions on internal organ doses following CT imaging. The phantoms were exposed to multislice chest and abdomen helical CT scans, and in-field organ absorbed doses were calculated. The results demonstrated that the use of traditional stylized phantoms yielded organ dose estimates that deviate from those given by the UF reference hybrid phantoms by up to a factor of 2. The study also showed that use of reference, or 50th percentile, phantoms to assess organ doses in underweight 15-year-old children would not lead to significant organ dose errors (typically less than 10%). However, more significant errors were noted (up to approximately 30%) when reference phantoms are used to represent overweight children in CT imaging dosimetry. These errors are expected to only further increase as one considers CT organ doses in overweight and obese individuals of the adult patient population, thus emphasizing the advantages of patient-sculptable phantom technology.

Anthropometric approaches and their uncertainties to assigning computational phantoms to individual patients in pediatric dosimetry studies.

Current efforts to reconstruct organ doses in children undergoing diagnostic imaging or therapeutic interventions using ionizing radiation typically rely upon the use of reference anthropomorphic computational phantoms coupled to Monte Carlo radiation transport codes. These phantoms are generally matched to individual patients based upon nearest age or sometimes total body mass. In this study, we explore alternative methods of phantom-to-patient matching with the goal of identifying those methods which yield the lowest residual errors in internal organ volumes. Various thoracic and abdominal organs were segmented and organ volumes obtained from chest-abdominal-pelvic (CAP) computed tomography (CT) image sets from 38 pediatric patients ranging in age from 2 months to 15 years. The organs segmented included the skeleton, heart, kidneys, liver, lungs and spleen. For each organ, least-squared regression lines, 95th percentile confidence intervals and 95th percentile prediction intervals were established as a function of patient age, trunk volume, estimated trunk mass, trunk height, and three estimates of the ventral body cavity volume based on trunk height alone, or in combination with circumferential, width and/or breadth measurements in the mid-chest of the patient. When matching phantom to patient based upon age, residual uncertainties in organ volumes ranged from 53% (lungs) to 33% (kidneys), and when trunk mass was used (surrogate for total body mass as we did not have images of patient head, arms or legs), these uncertainties ranged from 56% (spleen) to 32% (liver). When trunk height is used as the matching parameter, residual uncertainties in organ volumes were reduced to between 21 and 29% for all organs except the spleen (40%). In the case of the lungs and skeleton, the two-fold reduction in organ volume uncertainties was seen in moving from patient age to trunk height-a parameter easily measured in the clinic. When ventral body cavity volumes were used, residual uncertainties were lowered even further to a range of between 14 and 20% for all organs except the spleen, which continued to remain at around 40%. The results of this study suggest that a more anthropometric pairing of computational phantom to individual patient based on simple measurements of trunk height and possibly mid-chest circumference or thickness (where influences of subcutaneous fat are minimized) can lead to significant reductions in organ volume uncertainties: ranges of 40-50% (based on patient age) to between 15 and 20% (based on body cavity volumes tied to trunk height). An expanded series of non-uniform rational B-spine (NURBS) pediatric phantoms are being created at the University of Florida to allow the full application of this new approach in pediatric medical imaging studies.

Hybrid computational phantoms of the male and female newborn patient: NURBS-based whole-body models.

Anthropomorphic computational phantoms are computer models of the human body for use in the evaluation of dose distributions resulting from either internal or external radiation sources. Currently, two classes of computational phantoms have been developed and widely utilized for organ dose assessment: (1) stylized phantoms and (2) voxel phantoms which describe the human anatomy via mathematical surface equations or 3D voxel matrices, respectively. Although stylized phantoms based on mathematical equations can be very flexible in regard to making changes in organ position and geometrical shape, they are limited in their ability to fully capture the anatomic complexities of human internal anatomy. In turn, voxel phantoms have been developed through image-based segmentation and correspondingly provide much better anatomical realism in comparison to simpler stylized phantoms. However, they themselves are limited in defining organs presented in low contrast within either magnetic resonance or computed tomography images-the two major sources in voxel phantom construction. By definition, voxel phantoms are typically constructed via segmentation of transaxial images, and thus while fine anatomic features are seen in this viewing plane, slice-to-slice discontinuities become apparent in viewing the anatomy of voxel phantoms in the sagittal or coronal planes. This study introduces the concept of a hybrid computational newborn phantom that takes full advantage of the best features of both its stylized and voxel counterparts: flexibility in phantom alterations and anatomic realism. Non-uniform rational B-spline (NURBS) surfaces, a mathematical modeling tool traditionally applied to graphical animation studies, was adopted to replace the limited mathematical surface equations of stylized phantoms. A previously developed whole-body voxel phantom of the newborn female was utilized as a realistic anatomical framework for hybrid phantom construction. The construction of a hybrid phantom is performed in three steps: polygonization of the voxel phantom, organ modeling via NURBS surfaces and phantom voxelization. Two 3D graphic tools, 3D-DOCTOR and Rhinoceros, were utilized to polygonize the newborn voxel phantom and generate NURBS surfaces, while an in-house MATLAB code was used to voxelize the resulting NURBS model into a final computational phantom ready for use in Monte Carlo radiation transport calculations. A total of 126 anatomical organ and tissue models, including 38 skeletal sites and 31 cartilage sites, were described within the hybrid phantom using either NURBS or polygon surfaces. A male hybrid newborn phantom was constructed following the development of the female phantom through the replacement of female-specific organs with male-specific organs. The outer body contour and internal anatomy of the NURBS-based phantoms were adjusted to match anthropometric and reference newborn data reported by the International Commission on Radiological Protection in their Publication 89. The voxelization process was designed to accurately convert NURBS models to a voxel phantom with minimum volumetric change. A sensitivity study was additionally performed to better understand how the meshing tolerance and voxel resolution would affect volumetric changes between the hybrid-NURBS and hybrid-voxel phantoms. The male and female hybrid-NURBS phantoms were constructed in a manner so that all internal organs approached their ICRP reference masses to within 1%, with the exception of the skin (-6.5% relative error) and brain (-15.4% relative error). Both hybrid-voxel phantoms were constructed with an isotropic voxel resolution of 0.663 mm--equivalent to the ICRP 89 reference thickness of the newborn skin (dermis and epidermis). Hybrid-NURBS phantoms used to create their voxel counterpart retain the non-uniform scalability of stylized phantoms, while maintaining the anatomic realism of segmented voxel phantoms with respect to organ shape, depth and inter-organ positioning.

Whole-body voxel phantoms of paediatric patients--UF Series B.

Following the previous development of the head and torso voxel phantoms of paediatric patients for use in medical radiation protection (UF Series A), a set of whole-body voxel phantoms of paediatric patients (9-month male, 4-year female, 8-year female, 11-year male and 14-year male) has been developed through the attachment of arms and legs from segmented CT images of a healthy Korean adult (UF Series B). Even though partial-body phantoms (head-torso) may be used in a variety of medical dose reconstruction studies where the extremities are out-of-field or receive only very low levels of scatter radiation, whole-body phantoms play important roles in general radiation protection and in nuclear medicine dosimetry. Inclusion of the arms and legs is critical for dosimetry studies of paediatric patients due to the presence of active bone marrow within the extremities of children. While the UF Series A phantoms preserved the body dimensions and organ masses as seen in the original patients who were scanned, comprehensive adjustments were made for the Series B phantoms to better match International Commission on Radiological Protection (ICRP) age-interpolated reference body masses, body heights, sitting heights and internal organ masses. The CT images of arms and legs of a Korean adult were digitally rescaled and attached to each phantom of the UF series. After completion, the resolutions of the phantoms for the 9-month, 4-year, 8-year, 11-year and 14-year were set at 0.86 mm x 0.86 mm x 3.0 mm, 0.90 mm x 0.90 mm x 5.0 mm, 1.16 mm x 1.16 mm x 6.0 mm, 0.94 mm x 0.94 mm x 6.00 mm and 1.18 mm x 1.18 mm x 6.72 mm, respectively.

The UF series of tomographic computational phantoms of pediatric patients.

Two classes of anthropomorphic computational phantoms exist for use in Monte Carlo radiation transport simulations: tomographic voxel phantoms based upon three-dimensional (3D) medical images, and stylized mathematical phantoms based upon 3D surface equations for internal organ definition. Tomographic phantoms have shown distinct advantages over the stylized phantoms regarding their similarity to real human anatomy. However, while a number of adult tomographic phantoms have been developed since the early 1990s, very few pediatric tomographic phantoms are presently available to support dosimetry in pediatric diagnostic and therapy examinations. As part of a larger effort to construct a series of tomographic phantoms of pediatric patients, five phantoms of different ages (9-month male, 4-year female, 8-year female, 11-year male, and 14-year male) have been constructed from computed tomography (CT) image data of live patients using an IDL-based image segmentation tool. Lungs, bones, and adipose tissue were automatically segmented through use of window leveling of the original CT numbers. Additional organs were segmented either semiautomatically or manually with the aid of both anatomical knowledge and available image-processing techniques. Layers of skin were created by adding voxels along the exterior contour of the bodies. The phantoms were created from fused images taken from head and chest-abdomen-pelvis CT exams of the same individuals (9-month and 4-year phantoms) or of two different individuals of the same sex and similar age (8-year, 11-year, and 14-year phantoms). For each model, the resolution and slice positions of the image sets were adjusted based upon their anatomical coverage and then fused to a single head-torso image set. The resolutions of the phantoms for the 9-month, 4-year, 8-year, 11-year, and 14-year are 0.43 x 0.43 x 3.0 mm, 0.45 x 0.45 x 5.0 mm, 0.58 x 0.58 x 6.0 mm, 0.47 X 0.47 x 6.00 mm, and 0.625 x 0.625 x 6.0 mm, respectively. While organ masses can be matched to reference values in both stylized and tomographic phantoms, side-by-side comparisons of organ doses in both phantom classes indicate that organ shape and positioning are equally important parameters to consider in accurate determinations of organ absorbed dose from external photon irradiation. Preliminary studies of external photon irradiation of the 11-year phantom indicate significant departures of organ dose coefficients from that predicted by the existing stylized phantom series. Notable differences between pediatric stylized and tomographic phantoms include anterior-posterior (AP) and right lateral (RLAT) irradiation of the stomach wall, left lateral (LLAT) and right lateral (RLAT) irradiation of the thyroid, and AP and posterior-anterior (PA) irradiation of the urinary bladder.

A video analysis technique for organ dose assessment in pediatric fluoroscopy: applications to voiding cystourethrograms (VCUG).

The time-sequence videotape-analysis methodology, originally developed by Sulieman et al. [Radiol. 178, 653-658 (1991)] for use in tissue dose estimation in adult fluoroscopy exams, has been adapted to the study of the newborn voiding cystourethrogram (VCUG). Individual frames of fluoroscopic and radiographic video were analyzed with respect to unique combinations of field size, field center, projection, tube potential, and mA or mAs, respectively. A modified version of the stylized ORNL newborn model was coupled to the MCNP4C radiation transport code to report organ doses per unit entrance air kerma (free-in-air) for each identified x-ray field. A series of urinary bladder models was additionally developed representing the organ at differing stages of contrast filling. The technique was subsequently applied to two patients, a 3-month male and a 1-month female, examined via a conventional fluoroscopy system used just prior to departmental conversion to digital systems. The effective dose to these patients was estimated as 0.47 mSv and 1.36 mSv, respectively (ratio of 2.9). Corresponding ratios of cumulative fluoroscopy time and entrance air kerma were 2.2 and 1.6, respectively. For the male patient, the mean percent dose contribution from fluoroscopy for all irradiated organs was 71 +/- 12%, while that value for the female patient was 88 +/- 4%.

Mucopolysaccharidosis Type VII presenting with isolated neonatal ascites.

Mucopolysaccharidosis Type VII (MPS VII) is a lysosomal storage disease caused by a deficiency of the enzyme, beta-glucuronidase. MPS VII has a wide variation in phenotypic expression, including presentation in the neonatal period with nonimmune hydrops fetalis. We report a neonate with MPS VII who initially presented with marked isolated ascites not associated with hydrops fetalis. This appears to be a novel finding in patients with MPS VII.

Hybrid computational phantoms representing the reference adult male and adult female: construction and applications for retrospective dosimetry.

Currently, two classes of computational phantoms have been developed for dosimetry calculation: (1) stylized (or mathematical) and (2) voxel (or tomographic) phantoms describing human anatomy through mathematical surface equations and 3D voxel matrices, respectively. Mathematical surface equations in stylized phantoms are flexible, but the resulting anatomy is not as realistic. Voxel phantoms display far better anatomical realism, but they are limited in terms of their ability to alter organ shape, position, and depth, as well as body posture. A new class of computational phantoms called hybrid phantoms takes advantage of the best features of stylized and voxel phantoms-flexibility and anatomical realism, respectively. In the current study, hybrid computational phantoms representing the adult male and female reference anatomy and anthropometry are presented. These phantoms serve as the starting framework for creating patient or worker sculpted whole-body phantoms for retrospective dose reconstruction. Contours of major organs and tissues were converted or segmented from computed tomography images of a 36-y-old Korean volunteer and a 25-y-old U.S. female patient, respectively, with supplemental high-resolution CT images of the cranium. Polygon mesh models for the major organs and tissues were reconstructed and imported into Rhinoceros™ for non-uniform rational B-spline (NURBS) surface modeling. The resulting NURBS/polygon mesh models representing body contour and internal anatomy were matched to anthropometric data and reference organ mass data provided by Centers for Disease Control and Prevention and International Commission on Radiation Protection, respectively. Finally, two hybrid adult male and female phantoms were completed where a total of eight anthropometric data categories were matched to standard values within 4% and organ volumes matched to ICRP data within 1% with the exception of total skin. The hybrid phantoms were voxelized from the NURBS phantoms at resolutions of 0.158 × 0.158 × 0.158 cm and 0.126 × 0.126 × 0.126 cm for the male and female, respectively. To highlight the flexibility of the hybrid phantoms, graphical displays are given of (1) underweight and overweight adult male phantoms, (2) a sitting position for the adult female phantom, and (3) extraction and higher-resolution voxelization of the small intestine for localized dosimetry of mucosal and stem cell layers. These phantoms are used to model radioactively contaminated individuals and to then assess time-dependent detector count rate thresholds corresponding to 50, 250, and 500 mSv effective dose, as might be needed during in-field radiological triage by first responders or first receivers.

A newborn liver mass that never existed: a somber reminder of embryonic ties between umbilical vein and portal venous system.

A 6-day-old, known to have transposition of the great vessels, received care in the neonatal intensive care unit at a tertiary care center. A computed tomography scan was performed for abdominal distention and upper gastrointestinal bleeding, which revealed a "mass lesion" in the left liver lobe. Analysis of antecedent events and the clinical and laboratory course uncovered an iatrogenic etiology and pathogenesis of the lesion. As the nature of the lesion was clarified, no specific therapy was required. This case is presented to show a serious yet preventable complication of a commonly performed procedure.

The UF family of reference hybrid phantoms for computational radiation dosimetry.

Computational human phantoms are computer models used to obtain dose distributions within the human body exposed to internal or external radiation sources. In addition, they are increasingly used to develop detector efficiencies for in vivo whole-body counters. Two classes of computational human phantoms have been widely utilized for dosimetry calculation: stylized and voxel phantoms that describe human anatomy through mathematical surface equations and 3D voxel matrices, respectively. Stylized phantoms are flexible in that changes to organ position and shape are possible given avoidance of region overlap, while voxel phantoms are typically fixed to a given patient anatomy, yet can be proportionally scaled to match individuals of larger or smaller stature, but of equivalent organ anatomy. Voxel phantoms provide much better anatomical realism as compared to stylized phantoms which are intrinsically limited by mathematical surface equations. To address the drawbacks of these phantoms, hybrid phantoms based on non-uniform rational B-spline (NURBS) surfaces have been introduced wherein anthropomorphic flexibility and anatomic realism are both preserved. Researchers at the University of Florida have introduced a series of hybrid phantoms representing the ICRP Publication 89 reference newborn, 15 year, and adult male and female. In this study, six additional phantoms are added to the UF family of hybrid phantoms-those of the reference 1 year, 5 year and 10 year child. Head and torso CT images of patients whose ages were close to the targeted ages were obtained under approved protocols. Major organs and tissues were segmented from these images using an image processing software, 3D-DOCTOR. NURBS and polygon mesh surfaces were then used to model individual organs and tissues after importing the segmented organ models to the 3D NURBS modeling software, Rhinoceros. The phantoms were matched to four reference datasets: (1) standard anthropometric data, (2) reference organ masses from ICRP Publication 89, (3) reference elemental compositions provided in ICRP 89 as well as ICRU Report 46, and (4) reference data on the alimentary tract organs given in ICRP Publications 89 and 100. Various adjustments and refinements to the organ systems of the previously described newborn, 15 year and adult phantoms are also presented. The UF series of hybrid phantoms retain the non-uniform scalability of stylized phantoms while maintaining the anatomical realism of patient-specific voxel phantoms with respect to organ shape, depth and inter-organ distance. While the final versions of these phantoms are in a voxelized format for radiation transport simulation, their primary format is given as NURBS and polygon mesh surfaces, thus permitting one to sculpt non-reference phantoms using the reference phantoms as an anatomic template.

A survey of radiation dose associated with pediatric plain-film chest X-ray examinations.

BACKGROUND: The effective doses delivered to pediatric patients are not well characterized for many plain-film X-ray examination techniques. The few data available on clinical doses in pediatric radiology are generally outdated because of the changes in X-ray generators and hardware that have taken place over the past decade. OBJECTIVE: This survey characterizes X-ray examination techniques and measures effective doses delivered to a phantom representing a 1 year old in order to identify specific examination features that may result in greater than necessary doses to pediatric patients. MATERIALS AND METHODS: An anthropomorphic phantom representing a 1 year old was developed for use as a survey tool. The phantom incorporates direct reading metal oxide semiconductor field effect transistor (MOSFET) dosimeters that permit the effective dose to be measured for clinical examinations. Seventeen commonly performed examinations were characterized at ten facilities with doses determined for a chest series of exams at each facility. RESULTS: The survey demonstrates that the effective dose for a given examination can vary by an order of magnitude between institutions. Distributions of examination parameters identified those that are most significant for minimizing patient dose. CONCLUSION: Efforts spent to determine pediatric specific radiographic techniques contribute more to effective imaging with low patient doses than utilizing AEC controls or high-frequency generators.