Optimized, Person-Centered Workflow Design for a High-Throughput Breast MRI Screening Facility-A Simulation Study.

OBJECTIVES: This project aims to model an optimal scanning environment for breast magnetic resonance imaging (MRI) screening based on real-life data to identify to what extent the logistics of breast MRI can be optimized. MATERIALS AND METHODS: A novel concept for a breast MRI screening facility was developed considering layout of the building, workflow steps, used resources, and MRI protocols. The envisioned screening facility is person centered and aims for an efficient workflow-oriented design. Real-life data, collected from existing breast MRI screening workflows, during 62 scans in 3 different hospitals, were imported into a 3D simulation software for designing and testing new concepts. The model provided several realistic, virtual, logistical pathways for MRI screening and their outcome measures: throughput, waiting times, and other relevant variables. RESULTS: The total average appointment time in the baseline scenario was 25:54 minutes, with 19:06 minutes of MRI room occupation. Simulated improvements consisted of optimizing processes and resources, facility layout, and scanning protocol. In the simulation, time spent in the MRI room was reduced by introducing an optimized facility layout, dockable tables, and adoption of an abbreviated MRI scanning protocol. The total average appointment time was reduced to 19:36 minutes, and in this scenario, the MRI room was occupied for 06:21 minutes. In the most promising scenario, screening of about 68 people per day (10 hours) on a single MRI scanner could be feasible, compared with 36 people per day in the baseline scenario. CONCLUSIONS: This study suggests that by optimizing workflow MRI for breast screening total appointment duration and MRI occupation can be reduced. A throughput of up to 6 people per hour may be achieved, compared with 3 people per hour in the current setup.

Deep Learning-Based Segmentation of Locally Advanced Breast Cancer on MRI in Relation to Residual Cancer Burden: A Multi-Institutional Cohort Study.

BACKGROUND: While several methods have been proposed for automated assessment of breast-cancer response to neoadjuvant chemotherapy on breast MRI, limited information is available about their performance across multiple institutions. PURPOSE: To assess the value and robustness of deep learning-derived volumes of locally advanced breast cancer (LABC) on MRI to infer the presence of residual disease after neoadjuvant chemotherapy. STUDY TYPE: Retrospective. SUBJECTS: Training cohort: 102 consecutive female patients with LABC scheduled for neoadjuvant chemotherapy (NAC) from a single institution (age: 25-73 years). Independent testing cohort: 55 consecutive female patients with LABC from four institutions (age: 25-72 years). FIELD STRENGTH/SEQUENCE: Training cohort: single vendor 1.5 T or 3.0 T. Testing cohort: multivendor 3.0 T. Gradient echo dynamic contrast-enhanced sequences. ASSESSMENT: A convolutional neural network (nnU-Net) was trained to segment LABC. Based on resulting tumor volumes, an extremely randomized tree model was trained to assess residual cancer burden (RCB)-0/I vs. RCB-II/III. An independent model was developed using functional tumor volume (FTV). Models were tested on an independent testing cohort and response assessment performance and robustness across multiple institutions were assessed. STATISTICAL TESTS: The receiver operating characteristic (ROC) was used to calculate the area under the ROC curve (AUC). DeLong's method was used to compare AUCs. Correlations were calculated using Pearson's method. P values <0.05 were considered significant. RESULTS: Automated segmentation resulted in a median (interquartile range [IQR]) Dice score of 0.87 (0.62-0.93), with similar volumetric measurements (R = 0.95, P < 0.05). Automated volumetric measurements were significantly correlated with FTV (R = 0.80). Tumor volume-derived from deep learning of DCE-MRI was associated with RCB, yielding an AUC of 0.76 to discriminate between RCB-0/I and RCB-II/III, performing similar to the FTV-based model (AUC = 0.77, P = 0.66). Performance was comparable across institutions (IQR AUC: 0.71-0.84). DATA CONCLUSION: Deep learning-based segmentation estimates changes in tumor load on DCE-MRI that are associated with RCB after NAC and is robust against variations between institutions. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 4.

Dynamic Contrast-enhanced and Diffusion-weighted Magnetic Resonance Imaging for Response Evaluation After Single-Dose Ablative Neoadjuvant Partial Breast Irradiation.

Purpose: We aimed to evaluate changes in dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance imaging (MRI) scans acquired before and after single-dose ablative neoadjuvant partial breast irradiation (NA-PBI), and explore the relation between semiquantitative MRI parameters and radiologic and pathologic responses. Methods and Materials: We analyzed 3.0T DCE and DW-MRI of 36 patients with low-risk breast cancer who were treated with single-dose NA-PBI, followed by breast-conserving surgery 6 or 8 months later. MRI was acquired before NA-PBI and 1 week, 2, 4, and 6 months after NA-PBI. Breast radiologists assessed the radiologic response and breast pathologists scored the pathologic response after surgery. Patients were grouped as either pathologic responders or nonresponders (<10% vs ≥10% residual tumor cells). The semiquantitative MRI parameters evaluated were time to enhancement (TTE), 1-minute relative enhancement (RE1min), percentage of enhancing voxels (%EV), distribution of washout curve types, and apparent diffusion coefficient (ADC). Results: In general, the enhancement increased 1 week after NA-PBI (baseline vs 1 week median - TTE: 15s vs 10s; RE1min: 161% vs 197%; %EV: 47% vs 67%) and decreased from 2 months onward (6 months median - TTE: 25s; RE1min: 86%; %EV: 12%). Median ADC increased from 0.83 × 10-3 mm2/s at baseline to 1.28 × 10-3 mm2/s at 6 months. TTE, RE1min, and %EV showed the most potential to differentiate between radiologic responses, and TTE, RE1min, and ADC between pathologic responses. Conclusions: Semiquantitative analyses of DCE and DW-MRI showed changes in relative enhancement and ADC 1 week after NA-PBI, indicating acute inflammation, followed by changes indicating tumor regression from 2 to 6 months after radiation therapy. A relation between the MRI parameters and radiologic and pathologic responses could not be proven in this exploratory study.

Focal salvage iodine-125 brachytherapy for prostate cancer recurrences after primary radiotherapy: a retrospective study regarding toxicity, biochemical outcome and quality of life.

PURPOSE: Whole-gland salvage for recurrent prostate cancer (PCa) shows high failure and toxicity rates. Early and adequate localization of recurrences enables focal salvage, thereby potentially improving functional outcomes, while maintaining cancer control. MATERIALS AND METHODS: Retrospective analysis yielded 20 focal salvage I125 brachytherapy patients for locally recurrent PCa after primary radiotherapy. Tumor was defined by multiparametric MRI and correspondence with transrectal biopsies. Dose data were obtained intra-operatively. The tumor was prescribed ⩾144 Gy. Toxicity was scored by the Common Terminology Criteria for Adverse Events version 4 (CTCAE-4). Biochemical failure (BF) was defined using the Phoenix criteria (PSA-nadir + 2.0 ng/ml). Quality of life (QoL) was measured by SF-36 Health Survey and European Organization of Research and Treatment of Cancer (EORTC) C30+3 and PR25 questionnaires. RESULTS: With a median follow-up of 36 months (range 10-45), six patients experienced BF, of which three had no initial response. Grade 3 genitourinary (GU) toxicity occurred in one patient (a urethral stricture). The five previously potent patients retained erectile function. QoL remained decreased with regard to urinary symptoms. CONCLUSION: Focal salvage I125 brachytherapy showed one grade 3 GU toxicity in the 20 treated patients. Biochemical response and QoL were acceptable.

Accurate prostate tumour detection with multiparametric magnetic resonance imaging: dependence on histological properties.

BACKGROUND: To benefit most of focal treatment of prostate tumours, detection with high precision of all tumour voxels is needed. Although diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) have good diagnostic performance, perfect tumour detection is challenging. In this study, we investigated the variation in prostate tissue characteristics Gleason score (GS), cell density (CD) and microvessel density (MVD) to explain the limitations in tumour voxel detection with a MRI-based logistic regression model. MATERIAL AND METHODS: Twelve radical prostatectomy patients underwent a pre-operative 3.0T DWI and DCE-MRI exam. The MRI scans were used to calculate voxel-wise tumour probability with a logistic regression model for the peripheral zone (PZ) of the prostate. Tumour probability maps were correlated and validated with whole-mount histology. Additionally, from the whole-mount histological sections CD, MVD and GS were retrieved for every single voxel. GS, CD and MVD of true- and false-positive voxels and of true- and false-negative voxels were compared using Mann-Whitney U-tests. RESULTS: False-negative tumour voxels had significantly lower CD and MVD (p < 0.0001) and were similar to non-tumour PZ. True-positive detected tumour voxels had high CDs and MVDs (p < 0.0001). In addition, tumour voxels with higher GS showed a trend towards more frequent detection (p = 0.06). Tumour voxels with GS ≥ 3 + 4 showed higher CD and MVD compared to tumour voxels with GS 3 + 3 (p < 0.0001). CONCLUSION: Tumour voxels with low CD and MVD resemble healthy tissue and are limiting tumour voxel detection using DWI and DCE-MRI. Nevertheless, the most aggressive tumour voxels, containing high CD, MVD and GS, are more likely to be detected and can therefore be treated with high dose using focal therapy or focal boosting.

Expression of hypoxia-inducible factor-1α and -2α in whole-mount prostate histology: relation with dynamic contrast-enhanced MRI and Gleason score.

The aim of this study was to investigate the association between the immunohistochemical expression of hypoxia-inducible factor (HIF)-1α and HIF-2α and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters Ktrans and kep in prostate cancer. Therefore, 15 patients with biopsy-confirmed prostate cancer underwent a pre-operative 3T DCE-MRI scan. Immunohistochemical analysis of HIF-1α and HIF-2α, and of CD31 for microvessel density (MVD) was performed. Tumor areas were delineated on whole-mount histopathological sections. Nuclear HIF expression was correlated with the quantitative DCE-MRI parameters Ktrans and kep, MVD and Gleason score. HIF expression was highly heterogeneous within tumors and between patients. Pronounced expression of HIF-2α was present, while HIF-1α expression was more limited. Larger tumors showed higher HIF-2α expression (p=0.041). A correlation between HIF-2α and Ktrans p5th was found (r=0.30, p=0.02), but no differences in Ktrans, kep and MVD were observed for different levels of HIF expression. HIF expression was not associated with Gleason score. In conclusion, in this whole-mount prostate cancer study, larger prostate tumors showed frequently high HIF-2α expression, suggesting that larger tumors are clinically most relevant. However, HIF-1α and HIF-2α were not correlated with DCE-MRI parameters. Given the pronounced expression of HIF-2α and independence of Gleason score, HIF expression may function as a biomarker to guide boost dose prescription.

Why prostate tumour delineation based on apparent diffusion coefficient is challenging: an exploration of the tissue microanatomy.

BACKGROUND: Focal boosting of prostate tumours to improve outcome, requires accurate tumour delineation. For this, the apparent diffusion coefficient (ADC) derived from diffusion-weighted MR imaging (DWI) seems a useful tool. On voxel level, the relationship between ADC and histological presence of tumour is, however, ambiguous. Therefore, in this study the relationship between ADC and histological variables was investigated on voxel level to understand the strengths and limitations of DWI for prostate tumour delineation. MATERIAL AND METHODS: Twelve radical prostatectomy patients underwent a pre-operative 3.0T DWI exam and the ADC was calculated. From whole-mount histological sections cell density and glandular area were retrieved for every voxel. The distribution of all variables was described for tumour, peripheral zone (PZ) and central gland (CG) on regional and voxel level. Correlations between variables and differences between regions were calculated. RESULTS: Large heterogeneity of ADC on voxel level was observed within tumours, between tumours and between patients. This heterogeneity was reflected by the distribution of cell density and glandular area. On regional level, tumour was different from PZ having higher cell density (p = 0.007), less glandular area (p = 0.017) and lower ADCs (p = 0.017). ADC was correlated with glandular area (r = 0.402) and tumour volume (r = -0.608), but not with Gleason score. ADC tended to decrease with increasing cell density (r = -0.327, p = 0.073). On voxel level, correlations between ADC and histological variables varied among patients, for cell density ranging from r = -0.439 to r = 0.261 and for glandular area from r = 0.593 to r = 0.207. CONCLUSIONS: The variation in ADC can to a certain extent be explained by the variation in cell density and glandular area. The ADC is highly heterogeneous, which reflects the heterogeneity of malignant and benign prostate tissue. This heterogeneity might however obscure small tumours or parts of tumours. Therefore, DWI has to be used in the context of multiparametric MRI.

Patterns of outcome and toxicity after salvage prostatectomy, salvage cryosurgery and salvage brachytherapy for prostate cancer recurrences after radiation therapy: a multi-center experience and literature review.

PURPOSE: Current salvage treatments for recurrent prostate cancer after primary radiation therapy include radical prostatectomy, cryosurgery and brachytherapy. Because toxicity and failure rates are considerable, salvage treatments are not commonly performed. As most centers perform only one preferred salvage technique, the literature only describes single-center outcomes from a single salvage technique with a limited number of patients. In this overview, five high-volume Dutch centers describe their toxicity and outcome data using different salvage techniques. This provides a view on how salvage is performed in clinical practice in The Netherlands. METHODS: A total of 129 patients from five different centers in the Netherlands were retrospectively analyzed. Biochemical failure (BF) was defined as PSA >0.1 ng/ml for the salvage prostatectomy group (n = 44) and PSA nadir + 2.0 ng/ml (Phoenix definition) for the salvage cryosurgery (n = 54) and salvage brachytherapy group (n = 31). Toxicity was scored according to the Common Toxicity Criteria for Adverse events (CTCAE v3.0). RESULTS: BF occurred in 25 (81%) patients in the brachytherapy group (mean follow-up 29 ± 24 months), 29 (66%) patients in the prostatectomy group (mean follow-up 22 ± 25 months) and 33 (61%) patients in the cryosurgery group (mean follow-up 14 ± 11 months). Severe (grade >3) genitourinary and gastrointestinal toxicity was observed in up to 30% of patients in all three groups. CONCLUSION: This overview shows clinical practice of prostate cancer salvage. Significant failure and toxicity rates are observed, regardless of salvage technique. Patients should be selected with great care before offering these salvage treatment strategies.

Pathologic validation of a model based on diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging for tumor delineation in the prostate peripheral zone.

PURPOSE: For focal boost strategies in the prostate, the robustness of magnetic resonance imaging-based tumor delineations needs to be improved. To this end we developed a statistical model that predicts tumor presence on a voxel level (2.5×2.5×2.5 mm3) inside the peripheral zone. Furthermore, we show how this model can be used to derive a valuable input for radiotherapy treatment planning. METHODS AND MATERIALS: The model was created on 87 radiotherapy patients. For the validation of the voxelwise performance of the model, an independent group of 12 prostatectomy patients was used. After model validation, the model was stratified to create three different risk levels for tumor presence: gross tumor volume (GTV), high-risk clinical target volume (CTV), and low-risk CTV. RESULTS: The model gave an area under the receiver operating characteristic curve of 0.70 for the prediction of tumor presence in the prostatectomy group. When the registration error between magnetic resonance images and pathologic delineation was taken into account, the area under the curve further improved to 0.89. We propose that model outcome values with a high positive predictive value can be used to define the GTV. Model outcome values with a high negative predictive value can be used to define low-risk CTV regions. The intermediate outcome values can be used to define a high-risk CTV. CONCLUSIONS: We developed a logistic regression with a high diagnostic performance for voxelwise prediction of tumor presence. The model output can be used to define different risk levels for tumor presence, which in turn could serve as an input for dose planning. In this way the robustness of tumor delineations for focal boost therapy can be greatly improved.

Dynamic contrast-enhanced CT for prostate cancer: relationship between image noise, voxel size, and repeatability.

PURPOSE: To evaluate the relationship between image noise, voxel size, and voxel-wise repeatability of a dynamic contrast agent-enhanced (DCE) computed tomographic (CT) examination for prostate cancer. MATERIALS AND METHODS: This prospective study was approved by the local research ethics committee, and all patients gave written informed consent. Twenty-nine patients (mean age, 69.1 years; range, 56-80 years) with biopsy-proved prostate cancer underwent two DCE CT examinations within 1 week prior to radiation therapy. Parameter maps of transfer constant (K(trans)), the fraction of blood plasma (v(p)), the fraction of extravascular extracellular space (v(e)), and the flux rate constant between the extravascular extracellular space and plasma (k(ep)) were calculated at 15 different image resolutions, with kernel sizes ranging from 0.002 to 2.57 cm(3). Statistical analysis to quantify the voxel-wise repeatability was performed by using a Bland-Altman analysis on all tracer kinetic model parameter maps of each patient. From this analysis, the within-voxel standard deviation (wSD) was calculated as a function of spatial resolution. RESULTS: A kernel size in the range of 0.1-0.3 cm(3) yields reliable information. At 0.15 cm(3), the median wSDs of K(trans), k(ep), v(p), and v(e) are 0.047 min(-1), 0.144 min(-1), 0.011, and 0.104, respectively. With increasing kernel size, these values reach stable levels of approximately 0.02 min(-1), 0.05 min(-1), 0.005, and 0.05, respectively. CONCLUSION: There is a high voxel-wise repeatability of the DCE CT imaging technique for prostate cancer for kernel sizes as small as 0.1 cm(3). With the relationship between kernel size, image noise and voxel-wise repeatability, it becomes possible to estimate for alternative DCE CT protocols (eg, those with a reduced radiation dose) at what kernel size a sufficient repeatability can be obtained.

Long-term experience with transrectal and transperineal implantations of fiducial gold markers in the prostate for position verification in external beam radiotherapy; feasibility, toxicity and quality of life.

BACKGROUND AND PURPOSE: This study presents an overview of the experience with transrectal and transperineal implantations of fiducial markers for position verification in prostate radiotherapy, regarding the practical feasibility, procedure-related toxicity and influence on quality of life (QoL). MATERIAL AND METHODS: Since 2001, 914 patients scheduled for intensity-modulated radiotherapy (IMRT) have received gold markers in the prostate. The incidence of severe toxicity, defined by the CTCAE v3.0, was evaluated retrospectively. The influence on QoL was measured prospectively in 36 patients using a combination of three validated questionnaires: the Rand-36, the EORTC QLQ-C30(+3) and the prostate cancer-specific EORTC QLQ-PR25. Next, the incidence of marker migration was assessed. RESULTS: From 2001 to 2005, 402 patients received markers via the transrectal route. Two of these patients developed urosepsis (grade 3 toxicity). Since 2005, 512 patients received markers via the transperineal route. No grade 3 or 4 toxicity occurred in this group. No significant and clinically relevant differences were found in QoL between pre- and post-implant measures. In 5 patients marker migration led to discontinuation of the marker-based IMRT. CONCLUSIONS: Clinical use of transperineal-implanted fiducial gold markers for position verification in external beam radiotherapy for prostate cancer is a feasible and safe procedure without influencing patients' QoL.

Validation of functional imaging with pathology for tumor delineation in the prostate.

INTRODUCTION: A study was performed to validate magnetic resonance (MR) based prostate tumor delineations with pathology. MATERIAL AND METHODS: Five patients with biopsy proven prostate cancer underwent a T2 weighted (T2w), diffusion weighted MRI (DW-MRI) and dynamic contrast-enhanced MRI (DCE-MRI) scan before prostatectomy. Suspicious regions were delineated based on all available MR information. After prostatectomy whole-mount hematoxylin-eosin stained (H&E) sections were made. Tumor tissue was delineated on the H&E stained sections and compared with the MR based delineations. The registration accuracy between the MR images and H&E stained sections was estimated. RESULTS: A tumor coverage of 44-89% was reached by the MR based tumor delineations. The application of a margin of approximately 5mm to the MR based tumor delineations yielded a tumor coverage of 85-100% in all patients. Errors created during the registration procedure were 2-3mm, which cannot completely explain the limited tumor coverage. CONCLUSIONS: An accurate tissue processing and registration method was presented (registration error 2-3mm), which enables the validation of MR based tumor delineations with pathology. Reasonable tumor coverage of about 85% and larger was found when applying a margin of approximately 5 mm to the MR based tumor delineations.

MRI-guided robotic system for transperineal prostate interventions: proof of principle.

In this study, we demonstrate the proof of principle of the University Medical Center Utrecht (UMCU) robot dedicated to magnetic resonance imaging (MRI)-guided interventions in patients. The UMCU robot consists of polymers and non-ferromagnetic materials. For transperineal prostate interventions, it can be placed between the patient's legs inside a closed bore 1.5T MR scanner. The robot can manually be translated and rotated resulting in five degrees of freedom. It contains a pneumatically driven tapping device to automatically insert a needle stepwise into the prostate using a controller unit outside the scanning room. To define the target positions and to verify the needle insertion point and the needle trajectory, a high-resolution 3D balanced steady state free precession (bSSFP) scan that provides a T2/T1-weighted contrast is acquired. During the needle insertion fast 2D bSSFP images are generated to track the needle on-line. When the target position is reached, the radiation oncologist manually places a fiducial gold marker (small seed) at this location. In total two needle trajectories are used to place all markers. Afterwards, a high-resolution 3D bSSFP scan is acquired to visualize the fiducial gold markers. Four fiducial gold markers were placed transperineally into the prostate of a patient with a clinical stage T3 prostate cancer. In the generated scans, it was possible to discriminate the patient's anatomy, the needle and the markers. All markers were delivered inside the prostate. The procedure time was 1.5 h. This study proves that MRI-guided needle placement and seed delivery in the prostate with the UMCU robot are feasible.

The use of probability maps to deal with the uncertainties in prostate cancer delineation.

BACKGROUND AND PURPOSE: The use of dynamic contrast-enhanced (DCE) imaging for delineation of prostate tumors requires that decisions are made on a voxel wise basis about the presence of tumor. While the sensitivity and specificity of this technique is high, we propose a probabilistic approach to deal with the intrinsic imaging uncertainty. MATERIAL AND METHODS: Twenty-nine patients with biopsy-proven prostate cancer underwent a DCE-CT exam prior to radiotherapy. From a logistic regression on K(trans) values from healthy and diseased appearing prostate regions we obtained a probability function for the presence of tumor. K(trans) parameter maps were converted into probability maps and a stratification was applied at the 5% and 95% probability level, to identify low-, intermediate-, and high-risk areas for the presence of tumor. RESULTS: In all patients, regions with high-, intermediate-, and low-risk were identified, with median volume percentages of 7.6%, 40.0%, and 52.1%, respectively. The contiguous areas that resulted from the voxel wise stratification can be interpreted as GTV, high-risk CTV, and CTV. CONCLUSIONS: K(trans) parameter maps from a DCE-CT exam can be converted into probability maps for the presence of tumor. In this way, the intrinsic uncertainty that a voxel contains tumor can be incorporated into the treatment planning process.

Focal salvage guided by T2-weighted and dynamic contrast-enhanced magnetic resonance imaging for prostate cancer recurrences.

PURPOSE: Salvage treatment of the entire prostate for local recurrent cancer after primary radiotherapy is associated with high toxicity rates. Our goal was to show that, using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the visualization of a recurrence, focal salvage treatment can be performed, with, potentially, a reduction in toxicity. METHODS AND MATERIALS: We performed MRI, including a DCE sequence, in 7 patients with biopsy-proven locally recurrent prostate cancer. The specific regions of interest suspect for containing tumor were delineated using DCE and T(2)-weighted MRI scans. Subsequently, focal salvage high-dose-rate brachytherapy plans were created to illustrate the principle of focal salvage. Total salvage treatment plans were also created for comparison. RESULTS: The transfer constant (K(trans)) values from the DCE were 0.33-0.67 min(-1) for areas suspect for tumor and 0.07-0.25 min(-1) for normal tissue. In 4 cases, a focal salvage plan could be generated; 93-100% of the gross tumor volume was covered with the prescribed dose, with relative sparing of the bladder, rectum, and urethra. In the total salvage plans, 24-53% of the gross tumor volume was covered, and the organs at risk received high doses. In 3 cases, a focal salvage plan could not be created because of multifocal tumor, seminal vesicle extension, or capsular extension. CONCLUSION: Focal salvage treatment plans can be created in patients with local recurrent prostate cancer after radiotherapy. DCE-MRI supports the localization of the target area. This could lead to less toxicity in patients with local recurrent prostate cancer.

Treatment outcome and toxicity after salvage 125-I implantation for prostate cancer recurrences after primary 125-I implantation and external beam radiotherapy.

PURPOSE: To evaluate the outcome and toxicity after salvage iodine-125 (125-I) implantation in patients with locally recurrent prostate cancer after primary 125-I implantation and external beam radiotherapy. METHODS AND MATERIALS: Retrospectively, 31 patients were analyzed with pathology-proven local recurrent prostate cancer after primary external beam radiotherapy (n=20) or 125-I implantation (n=11), and who had undergone salvage 125-I implantation between 1994 and 2009. For recording biochemical failure rates, the Phoenix definition and the American Society for Therapeutic Radiology and Oncology definition were applied. Toxicity was scored according to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) (Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Bethesda, MD). RESULTS: The mean (+/-standard deviation [SD]) followup was 9 years (+/-4). The freedom from biochemical failure after 1 and 5 years' followup were 51% and 20%, respectively. Fourteen (45%) patients died of prostate cancer after a mean (+/-SD) followup of 73 (+/-39) months. Grade 1, 2, or 3 toxicity of the genitourinary tract was reported in 29%, 58% and 3% of the patients, respectively, in the acute phase, and in 16%, 39%, and 19%, respectively, in the late phase. Grade 1, 2, or 3 toxicity of the gastrointestinal tract was reported in 45%, 10%, and 0% of the patients, respectively, in the acute phase, and in 48%, 3%, and 6%, respectively, in the late phase. Grade 4 toxicity of any tract occurred in none of the patients in the acute or the late phase. CONCLUSIONS: Freedom from biochemical failure after salvage 125-I implantation for locally recurrent prostate cancer after radiotherapy is limited, and both genitourinary and gastrointestinal toxicity occur frequently.

Difficulties and potential of correlating local recurrences in prostate cancer with the delivered local dose.

In the previous decades the distinction between a local relapse and distant metastases was difficult to accomplish in an early stage. As a consequence, a failure could only be coarsely related to the original radiotherapy treatment. Currently, due to better imaging and position verification techniques, the actual dose within the prostate can be estimated, taking position uncertainties into account. Furthermore, advanced functional MRI techniques, such as MR spectroscopy (MRS) and dynamic contrast-enhanced MRI (DCE-MRI), increase the chance of localizing a local recurrence within the prostate. With this information the correlation between the actual previously delivered dose and a local relapse can be established, using non-rigid registration of the planning CT and the post-recurrence MRI. The current study describes the possibilities and problems in obtaining this correlation. This serves as a framework for investigating a reliable dose effect relationship in the future.

Anosmia after endovascular and open surgical treatment of intracranial aneurysms.

OBJECT: Patients treated for aneurysmal subarachnoid hemorrhage (SAH) often report a loss of smell. To discriminate between the effects of aneurysmal rupture and treatment, the authors assessed the occurrence of anosmia after clipping and coiling of unruptured aneurysms as well as after the coiling of ruptured aneurysms. METHODS: The authors interviewed patients in whom an unruptured aneurysm was treated by clipping (32 cases) or endovascular coiling (26 cases) as well as patients with SAH who underwent coil therapy (32 cases). A geographically defined subset of 20 patients per group was invited to undergo olfactory testing. RESULTS: Nine clip-treated patients (28% [95% CI 14-47%]) in the unruptured group reported having anosmia, and no coil-treated patient in the unruptured group (95% [CI 0-13%]) reported having anosmia; in the SAH group, 7 patients (22% [95% CI 9-40%]) reported having anosmia. Anosmia had improved over time in 3 of the clip-treated patients and in all but 1 of the patients with SAH. Examination revealed olfactory disturbance in 13 (65% [95% CI 41-85%]) of the clip-treated and 8 (42% [95% CI 20-67%]) of the coil-treated patients with unruptured aneurysms, and also in 7 (35% [95% CI 15-59%]) coil-treated patients with SAH. In 20 patients who underwent clip therapy for unruptured aneurysms, 19 (95% [95% CI 75-100%]) had olfactory dysfunction on the side ipsilateral to surgery (anosmia reported by 8 of them). CONCLUSIONS: Both clip treatment and SAH contribute to the occurrence of anosmia, with different chances of improvement. Olfactory dysfunction occurs in almost all patients on the side of surgery and can occur subclinically after coil deployment.