Chimeric antigen receptor-induced BCL11B suppression propagates NK-like cell development.

The transcription factor B cell CLL/lymphoma 11B (BCL11B) is indispensable for T lineage development of lymphoid progenitors. Here, we show that chimeric antigen receptor (CAR) expression during early phases of ex vivo generation of lymphoid progenitors suppressed BCL11B, leading to suppression of T cell-associated gene expression and acquisition of NK cell-like properties. Upon adoptive transfer into hematopoietic stem cell transplant recipients, CAR-expressing lymphoid progenitors differentiated into CAR-induced killer (CARiK) cells that mediated potent antigen-directed antileukemic activity even across MHC barriers. CD28 and active immunoreceptor tyrosine-based activation motifs were critical for a functional CARiK phenotype. These results give important insights into differentiation of murine and human lymphoid progenitors driven by synthetic CAR transgene expression and encourage further evaluation of ex vivo-generated CARiK cells for targeted immunotherapy.

Two-dimensional speckle tracking echocardiography: standardization efforts based on synthetic ultrasound data.

AIMS: Speckle tracking echocardiography has already demonstrated its clinical potential. However, its use in routine practice is jeopardized by recent reports on high inter-vendor variability of the measurements. As such, the European Association of CardioVascular Imaging (EACVI) and the American Society of Echocardiography (ASE) set up a standardization task force, which was joined by all manufacturers of echocardiographic equipment as well as by companies offering software solutions only, with the ambition to tackle this problem by standardization and quality assurance (QA). METHODS AND RESULTS: In this study, a first step towards QA of all commercially available tracking solutions based on computer-generated ultrasound images is presented. The accuracy of the products was acceptable with relative errors below 10% and intra-vendor reproducibility within 5%. CONCLUSION: Whether these results can be extrapolated to the clinical setting is the topic of an ongoing study of the EACVI/ASE/Industry Task Force to standardize deformation imaging. This study was an important first step in the development of generally accepted tools for QA of speckle tracking echocardiography.

Novel Approach to Three-Dimensional Echocardiographic Quantification of Right Ventricular Volumes and Function from Focused Views.

BACKGROUND: Echocardiographic assessment of the right ventricle is difficult because of its complex shape. Three-dimensional echocardiographic (3DE) imaging allows more accurate and reproducible analysis of the right ventricle than two-dimensional methodology. However, three-dimensional volumetric analysis has been hampered by difficulties obtaining consistently high-quality coronal views, required by the existing software packages. The aim of this study was to test a new approach for volumetric analysis without coronal views by using instead right ventricle-focused three-dimensional acquisition with multiple short-axis views extracted from the same data set. METHODS: Transthoracic 3DE and cardiovascular magnetic resonance (CMR) images were prospectively obtained on the same day in 147 patients with wide ranges of right ventricular (RV) size and function. RV volumes and ejection fraction were measured from 3DE images using the new software and compared with CMR reference values. Comparisons included linear regression and Bland-Altman analyses. Repeated measurements were performed to assess measurement variability. RESULTS: Sixteen patients were excluded because of suboptimal image quality (89% feasibility). RV volumes and ejection fraction obtained with the new 3DE technique were in good agreement with CMR (end-diastolic volume, r = 0.95; end-systolic volume, r = 0.96; ejection fraction, r = 0.83). Biases were, respectively, -6 ± 11%, 0 ± 15%, and -7 ± 17% of the mean measured values. In a subset of patients with suboptimal 3DE images, the new analysis resulted in significantly improved accuracy against CMR and reproducibility, compared with previously used coronal view-based techniques. The time required for the 3DE analysis was approximately 4 min. CONCLUSIONS: The new software is fast, reproducible, and accurate compared with CMR over a wide range of RV size and function. Because right ventricle-focused 3DE acquisition is feasible in most patients, this approach may be applicable to a broader population of patients who can benefit from RV volumetric assessment.

Definitions for a common standard for 2D speckle tracking echocardiography: consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging.

Recognizing the critical need for standardization in strain imaging, in 2010, the European Association of Echocardiography (now the European Association of Cardiovascular Imaging, EACVI) and the American Society of Echocardiography (ASE) invited technical representatives from all interested vendors to participate in a concerted effort to reduce intervendor variability of strain measurement. As an initial product of the work of the EACVI/ASE/Industry initiative to standardize deformation imaging, we prepared this technical document which is intended to provide definitions, names, abbreviations, formulas, and procedures for calculation of physical quantities derived from speckle tracking echocardiography and thus create a common standard.

Definitions for a common standard for 2D speckle tracking echocardiography: consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging.

Recognizing the critical need for standardization in strain imaging, in 2010, the European Association of Echocardiography (now the European Association of Cardiovascular Imaging, EACVI) and the American Society of Echocardiography (ASE) invited technical representatives from all interested vendors to participate in a concerted effort to reduce intervendor variability of strain measurement. As an initial product of the work of the EACVI/ASE/Industry initiative to standardize deformation imaging, we prepared this technical document which is intended to provide definitions, names, abbreviations, formulas, and procedures for calculation of physical quantities derived from speckle tracking echocardiography and thus create a common standard.

Segmental dosimetry, toxicity and long-term outcome in patients with prostate cancer treated with permanent seed implants.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The development of side effects characteristic for the different treatment methods with impact on the patients' quality of life plays a growing role for individual patients with early stage prostate cancer. Using permanent brachytherapy a high dose to the prostate can be applied with a steep dose gradient to the normal tissue. However, small partial volumes of normal tissue may be exposed to high doses inducing special side effects including lower urinary tract symptoms and/or erectile dysfunction. In the literature there are only few publications so far regarding segmental dosimetry and its influence on side effects and the results are conflicting. We could not identify any dosimetric parameter in segmental dosimetry that may have an influence at certain time intervals on the development of side effects such as lower urinary tract symptoms or erectile dysfunction. However, we could state clearly that the preoperative situation is the most important factor for postoperative outcome. OBJECTIVE: To report on the side effects of patients with low to low-intermediate risk prostate cancer treated with permanent interstitial brachytherapy with special emphasis on segmental dosimetry. PATIENTS AND METHODS: A series of 186 consecutive patients treated for early stage prostate cancer receiving definitive I-125 brachytherapy (permanent seed implantation) between November 2001 and April 2005 at our institution were examined for the development of side effects. Morbidity was assessed prospectively using the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function (IIEF-5) in a mean follow-up interval of 30 months. The scores were correlated with segmental dosimetry performed 6 weeks after the implantation. RESULTS: The mean postoperative dose to 90% of the prostate volume (D90) was 180.2 Gy, the mean preoperative IPSS 7.2 and the mean IIEF-5 14.35, with all scores showing a maximum deterioration after 6 weeks with normalization after 24 months. After correlating the segmental dosimetry and the scores at different time intervals, only the baseline scores remained statistically significant in multivariate regression analysis at all time intervals (P < 0.00). CONCLUSIONS: We could not demonstrate a correlation of segmental dosimetry with induction of side effects. There is no relationship between dose exposure of partial volumes and the development of radiation-induced toxicities. The preoperative situation regarding lower urinary tract symptoms and erectile function are the most important factors for postoperative outcome.

Magnetic resonance derived myocardial strain assessment using feature tracking.

PURPOSE: An accurate and practical method to measure parameters like strain in myocardial tissue is of great clinical value, since it has been shown, that strain is a more sensitive and earlier marker for contractile dysfunction than the frequently used parameter EF. Current technologies for CMR are time consuming and difficult to implement in clinical practice. Feature tracking is a technology that can lead to more automatization and robustness of quantitative analysis of medical images with less time consumption than comparable methods. METHODS: An automatic or manual input in a single phase serves as an initialization from which the system starts to track the displacement of individual patterns representing anatomical structures over time. The specialty of this method is that the images do not need to be manipulated in any way beforehand like e.g. tagging of CMR images. RESULTS: The method is very well suited for tracking muscular tissue and with this allowing quantitative elaboration of myocardium and also blood flow. CONCLUSIONS: This new method offers a robust and time saving procedure to quantify myocardial tissue and blood with displacement, velocity and deformation parameters on regular sequences of CMR imaging. It therefore can be implemented in clinical practice.

Modulation of neurogenesis by targeted hippocampal irradiation fails to affect kindling progression.

Changes in the rate of dentate granule cell neurogenesis and in the fate of newborn granule cells have been implicated in the development and progression of epilepsies. Strategies to normalize neurogenesis in chronic epilepsy models are thought to increase our understanding of the functional consequences of aberrant neurogenesis in the epileptic brain. Therefore, we modulated neurogenesis in an amygdala kindling paradigm in rats by targeted irradiation of the hippocampus using a medical linear accelerator device. Selective irradiation normalized the hippocampal cell proliferation rate in kindled animals. Both, in kindled and nonkindled rats the number of BrdU/NeuN-labeled newborn neurons was reduced in response to irradiation. Whereas kindling resulted in a pronounced increase in the number of neuroblasts identified based on doublecortin-labeling, irradiation prevented the expansion of the neuroblast population. Moreover, irradiation counteracted the kindling-associated increase in hilar basal dendrites, and kept the fraction of cells with basal dendrites at control levels. Despite the efficacious modulation of neurogenesis, irradiation did not affect the rate of kindling progression. Both, the number of stimulations as well as the cumulative afterdischarge duration to reach respective seizure stages were comparable in animals with and without irradiation. In addition, pre- and postkindling thresholds as well as seizure parameters recorded at threshold stimulation remained unaffected by irradiation. In conclusion, the fact that the efficacious modulation of neurogenesis by irradiation did not exert any effects on kindling acquisition and kindled seizures suggests that newborn neurons do not critically contribute to the hyperexcitable state in the chronic epilepsy model used.

Multimodality comparison of quantitative volumetric analysis of the right ventricle.

OBJECTIVES: We undertook volumetric analysis of the right ventricle (RV) by real-time 3-dimensional echocardiography (RT3DE), cardiac magnetic resonance (CMR), and cardiac computed tomography (CCT) on images obtained in RV-shaped phantoms and in patients with a wide range of RV geometry. BACKGROUND: Assessment of the RV by 2-dimensional (2D) echocardiography remains challenging due to its unique geometry and limitations of the current analysis techniques. RT3DE, CMR, and CCT, which can quantify RV volumes, promise to overcome the limitations of 2D echocardiography. METHODS: Images were analyzed using RV Analysis software. Volumes measured in vitro were compared with the true volumes. The human protocol included 28 patients who underwent RT3DE, CMR, and CT on the same day. Volumetric analysis of CMR images was used as a reference, against which RT3DE and CCT measurements were compared using linear regression and Bland-Altman analyses. To determine the reproducibility of the volumetric analysis, repeated measurements were performed for all 3 imaging modalities in 11 patients. RESULTS: The in vitro measurements showed that: 1) volumetric analysis of CMR images yielded the most accurate measurements; 2) CCT measurements showed slight (4%) but consistent overestimation; and 3) RT3DE measurements showed small underestimation, but considerably wider margins of error. In humans, both RT3DE and CCT measurements correlated highly with the CMR reference (r=0.79 to 0.89) and showed the same trends of underestimation and overestimation noted in vitro. All interobserver and intraobserver variability values were <14%, with those of CMR being the highest. CONCLUSIONS: Volumetric quantification of RV volume was performed on CMR, CCT, and RT3DE images. Eliminating analysis-related intermodality differences allowed fair comparisons and highlighted the unique limitations of each modality. Understanding these differences promises to aid in the functional assessment of the RV.

Donor T cells primed on leukemia lysate-pulsed recipient APCs mediate strong graft-versus-leukemia effects across MHC barriers in full chimeras.

Antigen-presenting cells (APCs) of host origin drive graft-versus-leukemia (GVL) effects but can also trigger life-threatening graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT) across major histocompatibility complex (MHC) barriers. We show that in vitro priming of donor lymphocytes can circumvent the need of recipient-derived APCs in vivo for mediating robust GVL effects and significantly diminishes the risk of severe GVHD. In vitro, generated and expanded T cells (ETCs) mediate anti-leukemia effects only when primed on recipient-derived APCs. Loading of APCs in vitro with leukemia cell lysate, chimerism status of the recipient, and timing of adoptive transfer after HCT are important factors determining the outcome. Delayed transfer of ETCs resulted in strong GVL effects in leukemia-bearing full chimera (FC) and mixed chimera (MC) recipients, which were comparable with the GVL/GVHD rates observed after the transfer of naive donor lymphocyte infusion (DLI). Upon early transfer, GVL effects were more pronounced with ETCs but at the expense of significant GVHD. The degree of GVHD was most severe in MCs after transfer of ETCs that had been in vitro primed either on nonpulsed recipient-derived APCs or with donor-derived APCs.

Postoperative intravenous infusion of donor-derived transplant acceptance-inducing cells as an adjunct immunosuppressive therapy in a porcine pulmonary allograft model.

There is very limited published information testifying to the safety and possible complications of cell-based therapies. Accurately assessing the potential risks of translating novel, cell-based immunosuppressive protocols into clinical trials is therefore extremely difficult. This report describes the use of a pulmonary allograft model in outbred miniature pigs as a preliminary step in the development of a safe, clinically feasible, cell-based immunosuppressive protocol. Single lung transplants were performed in 22 MHC Class I-mismatched donor-recipient pairs, which were randomized between four treatment groups. For the first 28 days postoperatively, all animals were immunosuppressed with methylprednisilone and tacrolimus, with or without preoperative irradiation; subsequently, pharmacological immunosuppression was stopped in all treatment groups. Animals in two groups also received a central venous infusion of donor-derived 'transplant acceptance-inducing cells' (TAICs) on the seventh and 14th days postoperatively. Allograft survival was monitored by sequential chest X-rays, bronchoscopies and transbronchial biopsy histologies. No acute adverse events were associated with the administration of TAICs and there was no evidence of accelerated graft rejection. The observations presented in this report represent an important first step towards the development of a clinically applicable protocol for the use of TAIC therapy in lung transplantation.

TGFB1 gene polymorphism Leu10Pro (c.29T>C), prostate cancer incidence and quality of life in patients treated with brachytherapy.

OBJECTIVES: Transforming growth factor beta1 gene (TGFB1) variant Leu10Pro (L10P) has previously been implicated in prostate cancer risk and radiation-induced side-effects. We investigated whether prevalence of this polymorphism is increased in prostate cancer patients and whether carriers are at increased risk for treatment-related side effects. METHODS: A series of 445 consecutive patients treated for early-stage prostate cancer receiving definitive I-125 brachytherapy (permanent seed implantation) between 10/2000 and 10/2007 at our institution and a comparison group of 457 healthy male control individuals were screened for TGFB1 L10P (869T>C) polymorphism. Morbidity was assessed prospectively and compared between carriers versus non-carriers using International Prostate Symptom Score (IPSS), disease-specific Quality-of-Life single question added to the IPSS and International Index of Erectile Function with its subgroups. RESULTS: The Leu/Leu genotype was found in 150 patients (34%) versus 180 controls (39%), the Pro/Pro genotype in 75 patients (17%) versus 65 controls (14%) and the Leu/Pro genotype in 220 patients (49%) versus 212 controls (46%) without any statistically significant differences between the two groups. There was a trend towards an increased prevalence of the L10P substitution among patients with a per allele odds ratio of 1.19 (95% CI 0.99-1.44; P = 0.08). After a median follow-up of 18 months (range 1-60 months) there were no statistically significant differences regarding morbidity. CONCLUSIONS: TGFB1 polymorphism L10P is not strongly associated with prostate cancer risk. After 18 months, there was no evidence for increased adverse radiotherapy responses in heterozygote or rare homozygote carriers. Longer follow-up may be necessary to detect a statistically significant difference.

Macrophage Turnover Kinetics in the Lungs of Mice Infected with Streptococcus pneumoniae.

Streptococcus pneumoniae is the most prevalent cause of community-acquired pneumonia and is known to induce apoptosis and necrosis in macrophages in vivo. We analyzed the kinetics of alveolar and lung parenchymal macrophage replacement by newly recruited exudate macrophages in vehicle-treated and S. pneumoniae-challenged bone marrow chimeric CD45.1 mice. After lethal irradiation, CD45.1 alloantigen-expressing recipient mice were transplanted with bone marrow cells from CD45.2 alloantigen-expressing donor mice. After only 24 hours of low-dose S. pneumoniae infection, approximately 60% of CD45.1(pos) recipient-type alveolar macrophages (AM) were replaced by CD45.2(pos) donor-type exudate AM in bronchoalveolar lavage fluid, and this increased to more than 80% on Day 7 of infection. In contrast, lung parenchymal macrophages of S. pneumoniae-infected chimeric CD45.1 mice were replaced by only about 10% by 24 hours, although this increased to over 80% by Days 3 to 7 of infection. This dramatic macrophage turnover was accompanied by early induction of apoptosis/necrosis in donor-type exudate AM peaking at 6 hours after infection, whereas peak apoptosis/necrosis induction in recipient-type AM was delayed until Day 7. Collectively, these data for the first time demonstrate that S. pneumoniae infection of the lung triggers a brisk turnover of both resident and recruited mononuclear phagocyte subsets, and suggest an important role of exudate but not resident macrophages in re-establishing alveolar and lung homeostasis.

Three-dimensional echo for the assessment of valvular heart disease.

Three-dimensional echocardiography (3DE) is a valuable tool to be used in addition to and not instead of two-dimensional echocardiography by providing complementary information and improved quantitative accuracy and reproducibility compared with two-dimensional techniques. 3DE has the potential to become the standard echocardiographic examination procedure for the assessment of valvular disease. This article describes applications of 3DE.

ATM missense variant P1054R predisposes to prostate cancer.

BACKGROUND: Prostate cancer is associated with defective DNA strand break repair after DNA damage leading to genetic instability and prostate cancer progression. The ATM (ataxia-telangiectasia mutated) gene product is known to play an important role in cell cycle regulation and maintenance of genomic integrity. We investigated whether the prevalence of the ATM missense substitution P1054R is increased in a hospital-based series of prostate cancer patients and whether carriers are at increased risk for treatment-related side effects. MATERIALS AND METHODS: A consecutive series of 261 patients treated for early-stage prostate cancer with I-125 brachytherapy (permanent seed implantation) between 10/2000 and 04/2006 at our institution and a comparison group of 460 male control individuals were screened for the presence of the P1054R variant. Outcome of therapy regarding morbidity was assessed prospectively and compared between carriers vs. non-carriers with the International Prostate Symptom Score (IPSS), a Quality-of-Life-index (QoL) and the International Index of Erectile Function (IIEF-15) with its subgroups (IIEF-5 and EF). RESULTS: The proportion of carriers of the P1054R variant was significantly higher among prostate cancer patients than in the general population (25 out of 261 vs. 22 out of 460; OR 2.1; 95% CI 1.2-3.8, p<0.01). A subgroup of the carriers additionally harboured the ATM missense variant F858L that was associated with a similar risk (OR=2.2; 95% CI 1.1-4.6; p=0.03). After a mean follow-up of 18 months there were no statistically significant differences regarding IPSS (p=0.48), QoL (p=0.61), IIEF-15 score (p=0.78), IIEF-5 score (p=0.83), and EF score (p=0.80), respectively. CONCLUSIONS: The ATM missense variant P1054R confers an about twofold increased risk for prostate cancer in our series. The subgroup of patients with the second-site variant F858L is not at significantly higher risk. After 18 months, there was no evidence for an increased adverse radiotherapy response in P1054R carriers.

Use of 3-dimensional color Doppler echocardiography to measure stroke volume in human beings: comparison with thermodilution.

BACKGROUND: The availability of accurate noninvasive measurements of cardiac output (CO) would be useful in assessing disease severity and the effects of therapeutic interventions in many different clinical settings. Current noninvasive methods are limited by their dependence on geometric assumptions. We tested the feasibility of a new technique for CO measurements based on 3-dimensional color Doppler echocardiographic (3D-CD) imaging. OBJECTIVE: We sought to compare the accuracy of CO determination in human beings as measured by 3D-CD and conventional 2-dimensional echocardiography (2DE) using thermodilution as the gold standard for comparison. METHODS: Simultaneous 3D-CD, 2DE, and thermodilution data were acquired in 47 patients postcardiac transplantation with good acoustic windows who required routine hemodynamic evaluation with a pulmonary artery catheter. Data were stored on compact disc and analyzed offline using custom software. Echocardiographic data were compared against thermodilution using linear regression and Bland-Altman analysis. RESULTS: Correlation coefficients for 3D-CD and 2DE of the left ventricular outflow tract were r = 0.94 and r = 0.78, respectively. Correlation coefficients for 3D-CD and 2DE of the mitral valve were r = 0.93 and r = 0.75, respectively. Compared with 2DE, 3D-CD demonstrated a smaller bias and narrower limits of agreement in the left ventricular outflow tract (-1.84 +/- 16.8 vs -8.6 +/- 36.2 mL) and mitral valve inflow (-0.2 +/- 15.6 vs 10.0 +/- 26 mL). CONCLUSION: The 3D-CD determination of CO is feasible and accurate. Compared with previous noninvasive modalities, 3D-CD has the advantages of independence of geometric assumptions and ease of image acquisition and analysis.

Preoperative low-dose irradiation promotes long-term allograft acceptance and induces regulatory T cells in a porcine model of pulmonary transplantation.

BACKGROUND: A simplified conditioning protocol including single-dose preoperative thymic and low-dose whole body irradiation with or without subsequent donor bone marrow transplantation (BMTx) can be applied in porcine lung transplantation. We hypothesized that this protocol would prolong allograft survival. METHODS: Left-sided single lung transplantation from major histocompatibility complex (MHC)-mismatched donors was performed in 27 minipigs. Recipients received whole body (1.5 Gy) and thymic irradiation (7 Gy) before transplantation (IRR group, n=6), intravenous immunosuppression with methylprednisolone, cyclosporine, and azathioprine for 27 postoperative days (IS group, n=5) or both (IRR+IS group, n=10). BMTx group recipients were treated with irradiation, immunosuppression and a donor bone marrow infusion on postoperative day 1. Peripheral blood leukocyte phenotype and donor cell chimerism were monitored by flow cytometry. Purified CD25+ T cells from long-term survivors or rejecting animals were used for in vitro MLR suppression assays. RESULTS: Median graft survival was: IRR 12 days, IS 55 days, IRR+IS 239 days, and BMTx 80 days (P<0.0001). Early peripheral blood macrochimerism was substantial in both the IRR+IS and the BMTX group but was lost in all groups after day 80. The frequency and suppressive function of CD4+CD25+ T cells were enhanced in IRR+IS group long-term survivors. CONCLUSION: Although donor bone marrow infusion was not beneficial in our model, a substantial proportion of the animals treated with irradiation and a 28-day course of immunosuppression accepted their lung allografts long term. The mechanism involved in maintaining allograft tolerance may be based on peripheral T-cell regulation.

Long-term results of interstitial brachytherapy (LDR-Brachytherapy) in the treatment of patients with prostate cancer.

Permanent interstitial brachytherapy represents the most conformal form of radiation therapy of the prostate and the number of patients with prostate cancers treated with permanent radioactive implants is increasing world wide. In the meanwhile long-term data on tumor control and treatment morbidity become available. Biochemical and clinical tumor control appears to be as effective as after radical prostatectomy or external beam radiation therapy in early prostate cancer. The risk of postreatment urinary incontinence and bowel dysfunction is low and erectile function can be preserved in the majority of patients. However, prostate brachytherapy requires a careful selection of patients as pretreatment factors predict for long-term outcome. The need for combined modality approaches in intermediate and high-risk patients remains controversely discussed. The continous refinement of intraoperative planning techniques and the elucidation of the etiology of urinary, sexual, and bowel dysfunction should result in further improvements in biochemical outcomes and decreased morbidity. Improved and standardized postimplantation evaluation will make outcome data more reliable and comparable.

Sonographic guidance for electron boost planning after breast-conserving surgery.

PURPOSE: This study was conducted to determine the feasibility of using sonography for electron boost planning in breast cancer treatment and to define the factors that influence the accuracy and reproducibility of this technique. PATIENTS AND METHODS: Seventy-seven patients underwent 102 sonographic examinations after breast-conserving surgery and before and after radiotherapy. The size of the electron boost field was defined by measuring the postoperative cavity. Reproducibility of the sonographic findings was investigated in 25 of the patients who were examined before and after radiotherapy (at a total dose of 46-50.4 Gy). Depth (distance from the skin surface to the posterior aspect of the postoperative cavity) was measured, and sonographic appearance of the postoperative cavity was evaluated. Type of surgical procedure, time elapsed since surgery, use of systemic therapy, menopausal status, breast size, and radiation dose were investigated for their influence on sonographic appearance and visualization of the postoperative cavity. RESULTS: The postoperative cavity was well visualized in 78% of patients and visualized with some difficulty in 22%. In all but 5 patients, it was hypoechoic and inhomogeneous. The mean depth of the postoperative cavity after radiotherapy was 27 +/- 4 mm. Smaller breast (p < 0.001) and younger age (p < 0.05) were associated with decreased visibility of the postoperative cavity. Sonographic appearance was the same before and after radiotherapy, but the mean difference in postoperative cavity depth between the 2 measurements was 2 mm (range, 0-4 mm). In 43/77 (56%) of the patients, changes in electron energy or in field size were required after sonographic measurement. CONCLUSION: Sonography is a useful and reproducible means of electron boost planning, helping to avoid underdosage of the postoperative cavity and overdosage of normal tissue.