Cervical cancer patient reported gastrointestinal outcomes: intensity/volumetric modulated vs. 3D conformal radiation therapy.

OBJECTIVE: To evaluate gastrointestinal (GI) patient reported outcomes (PROs) in cervical cancer patients treated with definitive radiotherapy (RT), comparing 3D conformal RT (3DCRT) vs. intensity modulated/volumetric modulated arc therapy (IMRT/VMAT). METHODS: An analysis of patients treated with definitive RT between 2015-2018 was performed. GI PROs were prospectively collected at baseline, during RT (acute), ≤12 weeks after RT (subacute), and >12 weeks after RT (late). GI PROs evaluated three symptom domains: bowel problems (BPs), bowel bother (BB), and abdominal problems (APs). Multiple linear regression analysis was performed to investigate associations between mean changes of symptom scores with clinical and dosimetric variables. RESULTS: The cohort included 167 patients. A total of 100 (60%) patients were treated with IMRT/VMAT and 67 (40%) with 3DCRT. In the subacute phase, the mean change of symptom scores from baseline in 3DCRT vs. IMRT/VMAT were +0.9 vs. -1.15 (p=0.004) for BP, +2.18 vs. -0.10 (p=0.019) for BB, and +1.41 vs. -0.38 (p=0.021) for AP. Likewise, in the late phase, mean changes were +0.72 vs. -0.82 (p=0.014) for BP, +1.98 vs. -0.03 (p=0.008) for BB, and +1.29 vs. -0.31 (p<0.001) for AP. On multiple linear regression, use of 3DCRT vs. IMRT/VMAT was associated with greater mean changes in subacute BP (p=0.023) and late phase AP (p=0.019). A higher small bowel V50Gy was associated increased symptom scores in late AP (p=0.012). CONCLUSION: 3DCRT was associated with significantly greater worsening of GI PRO symptom scores in the subacute and late phase. These data support the ongoing use of IMRT/VMAT in routine practice.

After ASCENDE-RT: Biochemical and survival outcomes following combined external beam radiotherapy and low-dose-rate brachytherapy for high-risk and unfavourable intermediate-risk prostate cancer, a population-based analysis.

PURPOSE: To evaluate the outcomes of unfavorable intermediate-risk (UIR) and high-risk (HR) prostate cancer patients treated with combined external beam radiation therapy (EBRT) and low-dose-rate prostate brachytherapy (LDR-PB). METHODS AND MATERIALS: A population-based cohort of 568 prostate cancer patients treated with combined EBRT and LDR-PB from 2010 to 2016 was analyzed. All patients received EBRT followed by LDR-PB boost. Outcomes were compared with the results for the brachytherapy arm of the ASCENDE-RT trial. RESULTS: The median followup was 4.5 years. Sixty-nine percent (N = 391) had HR disease. Ninety-four percent of the HR and 57% of UIR were treated with androgen deprivation therapy (ADT) with a median duration of 12 months. The 5-year K-M biochemical progression-free survival (b-PFS), metastasis-free survival (MFS), and overall survival (OS) were 84 ± 2%, 90 ± 2%, and 88 ± 2%, similar to 89 ± 5%, 94 ± 4%, and 92 ± 4% for the ASCENDE-RT LDR-PB arm. The likelihood of achieving a PSA ≤0.2 ng/mL at 4 years was 88%, similar to 86% in the ASCENDE-RT LDR-PB arm. Thirty-three men (5.8%) would have been ineligible for ASCENDE-RT due to high-risk features. The 5-year K-M b-PFS, MFS and OS estimates were 86 ± 2%, 92 ± 1% and 89 ± 2% for the ASCENDE-RT eligible versus 56 ± 10% (p < 0.001), 73 ± 8% (p < 0.001), and 77 ± 9% (p = 0.098) for the ineligible patients. CONCLUSIONS: In this population-based cohort, combining LDR-PB with pelvic EBRT (+/- ADT) achieves very favorable b-PFS that compares to the LDR-PB arm of the ASCENDE-RT, supporting the generalizability of those results. Men ineligible for ASCENDE-RT, based on prognostic features, have a much higher risk of biochemical recurrence and metastatic relapse.

Centre-specific autonomous treatment plans for prostate brachytherapy using cGANs.

PURPOSE: In low-dose-rate prostate brachytherapy (LDR-PB), treatment planning is the process of determining the arrangement of implantable radioactive sources that radiates the prostate while sparing healthy surrounding tissues. Currently, these plans are prepared manually by experts incorporating the centre's planning style and guidelines. In this article, we develop a novel framework that can learn a centre's planning strategy and automatically reproduce rapid clinically acceptable plans. METHODS: The proposed framework is based on conditional generative adversarial networks that learn our centre's planning style using a pool of 931 historical LDR-PB planning data. Two additional losses that help constrain prohibited needle patterns and produce similar-looking plans are also proposed. Once trained, this model generates an initial distribution of needles which is passed to a planner. The planner then initializes the sources based on the predicted needles and uses a simulated annealing algorithm to optimize their locations further. RESULTS: Quantitative analysis was carried out on 170 cases which showed the generated plans having similar dosimetry to that of the manual plans but with significantly lower planning durations. Indeed, on the test cases, the clinical target volumes achieving [Formula: see text] of the prescribed dose for the generated plans was on average [Formula: see text] ([Formula: see text] for manual plans) with an average planning time of [Formula: see text] min ([Formula: see text] min for manual plans). Further qualitative analysis was conducted by an expert planner who accepted [Formula: see text] of the plans with some changes ([Formula: see text] requiring minor changes & [Formula: see text] requiring major changes). CONCLUSION: The proposed framework demonstrated the ability to rapidly generate quality treatment plans that not only fulfil the dosimetric requirements but also takes into account the centre's planning style. Adoption of such a framework would save significant amount of time and resources spent on every patient; boosting the overall operational efficiency of this treatment.

Prostate brachytherapy intraoperative dosimetry using a combination of radiographic seed localization with a C-arm and deformed ultrasound prostate contours.

PURPOSE: The purpose of the study was to assess the feasibility of performing intraoperative dosimetry for permanent prostate brachytherapy by combining transrectal ultrasound (TRUS) and fluoroscopy/cone beam CT [CBCT] images and accounting for the effect of prostate deformation. METHODS AND MATERIALS: 13 patients underwent TRUS and multiview two-dimensional fluoroscopic imaging partway through the implant, as well as repeat fluoroscopic imaging with the TRUS probe inserted and retracted, and finally three-dimensional CBCT imaging at the end of the implant. The locations of all the implanted seeds were obtained from the fluoroscopy/CBCT images and were registered to prostate contours delineated on the TRUS images based on a common subset of seeds identified on both image sets. Prostate contours were also deformed, using a finite-element model, to take into account the effect of the TRUS probe pressure. Prostate dosimetry parameters were obtained for fluoroscopic and CBCT-dosimetry approaches and compared with the standard-of-care Day-0 postimplant CT dosimetry. RESULTS: High linear correlation (R2 > 0.8) was observed in the measured values of prostate D90%, V100%, and V150%, between the two intraoperative dosimetry approaches. The prostate D90% and V100% obtained from intraoperative dosimetry methods were in agreement with the postimplant CT dosimetry. Only the prostate V150% was on average 4.1% (p-value <0.05) higher in the CBCT-dosimetry approach and 6.7% (p-value <0.05) higher in postimplant CT dosimetry compared with the fluoroscopic dosimetry approach. Deformation of the prostate by the ultrasound probe appeared to have a minimal effect on prostate dosimetry. CONCLUSIONS: The results of this study have shown that both of the proposed dosimetric evaluation approaches have potential for real-time intraoperative dosimetry.

Automatic detection of brachytherapy seeds in 3D ultrasound images using a convolutional neural network.

A novel approach for automatic localization of brachytherapy seeds in 3D transrectal ultrasound (TRUS) images, using machine learning based algorithm, is presented. 3D radiofrequency ultrasound signals were collected from 13 patients using the linear array of the TRUS probe during the brachytherapy procedure in which needles are used for insertion of stranded seeds. Gold standard for the location of seeds on TRUS data were obtained with the guidance of the complete reconstruction of the seed locations from multiple C-arm fluoroscopy views and used in the creation of the training set. We designed and trained a convolutional neural network (CNN) model that worked on 3D cubical sub-regions of the TRUS images, that will be referred to as patches, representing seed, non-seed within a needle track and non-seed elsewhere in the images. The models were trained with these patches to detect the needle track first and then the individual seeds within the needle track. A leave-one-out cross validation approach was used to test the model on the data from eight of the patients, for whom accurate seed locations were available from fluoroscopic imaging. The total inference time was about 7 min for needle track detection in each patient's image and approximately 1 min for seed detection in each needle, leading to a total seed detection time of less than 15 min. Our seed detection algorithm achieved [Formula: see text] precision, [Formula: see text] recall and [Formula: see text] F1_score. The results from our CNN-based method were compared to manual seed localization performed by an expert. The CNN model yielded higher precision (lower false discovery rate) compared to the manual method. The automated approach requires little modification to the current clinical setups and offers the prospect of application in real time intraoperative dosimetric analysis of the implant.

Accurate and robust deep learning-based segmentation of the prostate clinical target volume in ultrasound images.

The goal of this work was to develop a method for accurate and robust automatic segmentation of the prostate clinical target volume in transrectal ultrasound (TRUS) images for brachytherapy. These images can be difficult to segment because of weak or insufficient landmarks or strong artifacts. We devise a method, based on convolutional neural networks (CNNs), that produces accurate segmentations on easy and difficult images alike. We propose two strategies to achieve improved segmentation accuracy on difficult images. First, for CNN training we adopt an adaptive sampling strategy, whereby the training process is encouraged to pay more attention to images that are difficult to segment. Secondly, we train a CNN ensemble and use the disagreement among this ensemble to identify uncertain segmentations and to estimate a segmentation uncertainty map. We improve uncertain segmentations by utilizing the prior shape information in the form of a statistical shape model. Our method achieves Hausdorff distance of 2.7 ±â€¯2.3 mm and Dice score of 93.9 ±â€¯3.5%. Comparisons with several competing methods show that our method achieves significantly better results and reduces the likelihood of committing large segmentation errors. Furthermore, our experiments show that our approach to estimating segmentation uncertainty is better than or on par with recent methods for estimation of prediction uncertainty in deep learning models. Our study demonstrates that estimation of model uncertainty and use of prior shape information can significantly improve the performance of CNN-based medical image segmentation methods, especially on difficult images.

Association of bladder dose with late urinary side effects in cervical cancer high-dose-rate brachytherapy.

PURPOSE: The purpose of this work was to study the association between specific urinary sequelae and locally accumulated dose to the bladder wall and bladder neck in the treatment of cervical cancer with multifraction high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALS: A cohort of 60 cervical cancer patients, treated with both external beam and five HDR brachytherapy insertions between 2008 and 2014 at the BC Cancer Agency, was identified. The accumulated dose received over five brachytherapy sessions was evaluated for the bladder wall and bladder neck of each patient using dosimetric parameters calculated from deformably registered image data sets. These parameters were examined as potential predictors of urinary sequelae including hematuria, frequency, urgency, incontinence, stream, nocturia, and dysuria. Two different dichotomization schemes were evaluated for grouping patients into Case and Control groups. The two-sample Student's t test was used for normally distributed samples and the Mann-Whitney nonparametric U test for non-normal distributions. RESULTS: A strong association between dose to the bladder neck and incontinence was found (p = 0.001). A statistically significant association (p < 0.05) was also observed between urgency and certain bladder-wall parameters. CONCLUSIONS: Localized dose to the bladder neck is a potential predictor of urinary incontinence, whereas weaker associations were observed between urgency and some bladder-wall parameters.

Focal application of low-dose-rate brachytherapy for prostate cancer: a pilot study.

PURPOSE: To evaluate the feasibility and to report the early outcomes of focal treatment of prostate cancer using low-dose-rate brachytherapy (LDR-PB). MATERIAL AND METHODS: Seventeen patients were screened with multi-parametric magnetic resonance imaging (mpMRI), 14 of whom proceeded to receive trans-perineal template mapping biopsy (TTMB). Focal LDR-PB was performed on five eligible patients using dual air kerma strength treatment plans based on planning target volumes derived from cancer locations and determined by TTMB. Patient follow-up includes prostate specific antigen (PSA) measurements, urinary and sexual function questionnaires, repeated imaging and TTMB at specific intervals post-treatment. RESULTS: Feasibility of focal LDR-PB was shown and short-term outcomes are promising. While the detection rate of tumors, a majority of which were low grade GS 3 + 3, was found to be low on mpMRI (sensitivity of 37.5%), our results suggest the potential of mpMRI in detecting the presence of higher grade (GS ≥ 3 + 4), and bilateral disease indicating its usefulness as a screening tool for focal LDR-PB. CONCLUSIONS: Low-dose-rate brachytherapy is a favorable ablation option for focal treatment of prostate cancer, requiring minimal modification to the standard (whole gland) LDR-PB treatment, and appears to have a more favorable side effect profile. Further investigation, in the form of a larger study, is needed to assess the methods used and the long-term outcomes of focal LDR-PB.

Bladder accumulated dose in image-guided high-dose-rate brachytherapy for locally advanced cervical cancer and its relation to urinary toxicity.

The purpose of this study was to estimate locally accumulated dose to the bladder in multi-fraction high-dose-date (HDR) image-guided intracavitary brachytherapy (IG-ICBT) for cervical cancer, and study the locally-accumulated dose parameters as predictors of late urinary toxicity. A retrospective study of 60 cervical cancer patients who received five HDR IG-ICBT sessions was performed. The bladder outer and inner surfaces were segmented for all sessions and a bladder-wall contour point-set was created in MATLAB. The bladder-wall point-sets for each patient were registered using a deformable point-set registration toolbox called coherent point drift (CPD), and the fraction doses were accumulated. Various dosimetric and volumetric parameters were calculated using the registered doses, including [Formula: see text] (minimum dose to the most exposed n-cm3 volume of bladder wall), r V n Gy (wall volume receiving at least m Gy), and [Formula: see text] (minimum equivalent biologically weighted dose to the most exposed n-cm3 of bladder wall), where n = 1/2/5/10 and m = 3/5/10. Minimum dose to contiguous 1 and 2 cm3 hot-spot volumes was also calculated. The unregistered dose volume histogram (DVH)-summed equivalent of [Formula: see text] and [Formula: see text] parameters (i.e. [Formula: see text] and [Formula: see text]) were determined for comparison. Late urinary toxicity was assessed using the LENT-SOMA scale, with toxicity Grade 0-1 categorized as Controls and Grade 2-4 as Cases. A two-sample t-test was used to identify the differences between the means of Control and Case groups for all parameters. A binomial logistic regression was also performed between the registered dose parameters and toxicity grouping. Seventeen patients were in the Case and 43 patients in the Control group. Contiguous values were on average 16 and 18% smaller than parameters for 1 and 2 cm3 volumes, respectively. Contiguous values were on average 26 and 27% smaller than parameters. The only statistically significant finding for Case versus Control based on both methods of analysis was observed for r V3 Gy (p = 0.01). DVH-summed parameters based on unregistered structure volumes overestimated the bladder dose in our patients, particularly when contiguous high dose volumes were considered. The bladder-wall volume receiving at least 3 Gy of accumulated dose may be a parameter of interest in further investigations of Grade 2+ urinary toxicity.

Source strength verification and quality assurance of preloaded brachytherapy needles using a CMOS flat panel detector.

PURPOSE: Current methods of low dose rate brachytherapy source strength verification for sources preloaded into needles consist of either assaying a small number of seeds from a separate sample belonging to the same lot used to load the needles or performing batch assays of a subset of the preloaded seed trains. Both of these methods are cumbersome and have the limitations inherent to sampling. The purpose of this work was to investigate an alternative approach that uses an image-based, autoradiographic system capable of the rapid and complete assay of all sources without compromising sterility. METHODS: The system consists of a flat panel image detector, an autoclavable needle holder, and software to analyze the detected signals. The needle holder was designed to maintain a fixed vertical spacing between the needles and the image detector, and to collimate the emissions from each seed. It also provides a sterile barrier between the needles and the imager. The image detector has a sufficiently large image capture area to allow several needles to be analyzed simultaneously.Several tests were performed to assess the accuracy and reproducibility of source strengths obtained using this system. Three different seed models (Oncura 6711 and 9011 (125)I seeds, and IsoAid Advantage (103)Pd seeds) were used in the evaluations. Seeds were loaded into trains with at least 1 cm spacing. RESULTS: Using our system, it was possible to obtain linear calibration curves with coverage factor k = 1 prediction intervals of less than ±2% near the centre of their range for the three source models. The uncertainty budget calculated from a combination of type A and type B estimates of potential sources of error was somewhat larger, yielding (k = 1) combined uncertainties for individual seed readings of 6.2% for (125)I 6711 seeds, 4.7% for (125)I 9011 seeds, and 11.0% for Advantage (103)Pd seeds. CONCLUSIONS: This study showed that a flat panel detector dosimetry system is a viable option for source strength verification in preloaded needles, as it is capable of measuring all of the sources intended for implantation. Such a system has the potential to directly and efficiently estimate individual source strengths, the overall mean source strength, and the positions within the seed-spacer train.

Robustness to source displacement in dual air kerma strength planning for focal low-dose-rate brachytherapy of prostate cancer.

PURPOSE: To describe the use of dual source strength implants for focal low-dose-rate brachytherapy. METHODS AND MATERIALS: An interneedle dual source strength planning strategy is described for focal low-dose-rate brachytherapy of the prostate. The implanted treatment plans were designed using peripheral (except near the rectum) needles loaded with high strength (0.9 U) sources and central needles loaded with low strength (0.4 U) sources ("interneedle" dual strength planning). This approach has been applied for focally treating 3 patients. In this article, we compare the characteristics and robustness to source motion of interneedle dual strength planning with four alternative planning strategies (single strength high, low, and intermediate, and intraneedle dual strength) on 50 simulated cases. RESULTS: Interneedle dual source strength planning results in greater robustness to source motion and overall lower seed and needle density compared to the standard low source strength planning currently used in our centre. This planning approach is also significantly superior to single strength high, single strength intermediate and intraneedle dual strength planning strategies in terms of high dose to the urethral avoidance structure. CONCLUSIONS: The use of interneedle dual source strength treatment plans for focal low-dose-rate brachytherapy is possibly the practical solution for limiting the density of sources required to deliver the prescribed dose while limiting proximity of high strength sources to organs at risk.

Validation of non-rigid point-set registration methods using a porcine bladder pelvic phantom.

The problem of accurate dose accumulation in fractionated radiotherapy treatment for highly deformable organs, such as bladder, has garnered increasing interest over the past few years. However, more research is required in order to find a robust and efficient solution and to increase the accuracy over the current methods. The purpose of this study was to evaluate the feasibility and accuracy of utilizing non-rigid (affine or deformable) point-set registration in accumulating dose in bladder of different sizes and shapes. A pelvic phantom was built to house an ex vivo porcine bladder with fiducial landmarks adhered onto its surface. Four different volume fillings of the bladder were used (90, 180, 360 and 480 cc). The performance of MATLAB implementations of five different methods were compared, in aligning the bladder contour point-sets. The approaches evaluated were coherent point drift (CPD), gaussian mixture model, shape context, thin-plate spline robust point matching (TPS-RPM) and finite iterative closest point (ICP-finite). The evaluation metrics included registration runtime, target registration error (TRE), root-mean-square error (RMS) and Hausdorff distance (HD). The reference (source) dataset was alternated through all four points-sets, in order to study the effect of reference volume on the registration outcomes. While all deformable algorithms provided reasonable registration results, CPD provided the best TRE values (6.4 mm), and TPS-RPM yielded the best mean RMS and HD values (1.4 and 6.8 mm, respectively). ICP-finite was the fastest technique and TPS-RPM, the slowest.

Learning-Based Multi-Label Segmentation of Transrectal Ultrasound Images for Prostate Brachytherapy.

Low-dose-rate prostate brachytherapy treatment takes place by implantation of small radioactive seeds in and sometimes adjacent to the prostate gland. A patient specific target anatomy for seed placement is usually determined by contouring a set of collected transrectal ultrasound images prior to implantation. Standard-of-care in prostate brachytherapy is to delineate the clinical target anatomy, which closely follows the real prostate boundary. Subsequently, the boundary is dilated with respect to the clinical guidelines to determine a planning target volume. Manual contouring of these two anatomical targets is a tedious task with relatively high observer variability. In this work, we aim to reduce the segmentation variability and planning time by proposing an efficient learning-based multi-label segmentation algorithm. We incorporate a sparse representation approach in our methodology to learn a dictionary of sparse joint elements consisting of images, and clinical and planning target volume segmentation. The generated dictionary inherently captures the relationships among elements, which also incorporates the institutional clinical guidelines. The proposed multi-label segmentation method is evaluated on a dataset of 590 brachytherapy treatment records by 5-fold cross validation. We show clinically acceptable instantaneous segmentation results for both target volumes.

Statistical Biomechanical Surface Registration: Application to MR-TRUS Fusion for Prostate Interventions.

A common challenge when performing surface-based registration of images is ensuring that the surfaces accurately represent consistent anatomical boundaries. Image segmentation may be difficult in some regions due to either poor contrast, low slice resolution, or tissue ambiguities. To address this, we present a novel non-rigid surface registration method designed to register two partial surfaces, capable of ignoring regions where the anatomical boundary is unclear. Our probabilistic approach incorporates prior geometric information in the form of a statistical shape model (SSM), and physical knowledge in the form of a finite element model (FEM). We validate results in the context of prostate interventions by registering pre-operative magnetic resonance imaging (MRI) to 3D transrectal ultrasound (TRUS). We show that both the geometric and physical priors significantly decrease net target registration error (TRE), leading to TREs of 2.35 ± 0.81 mm and 2.81 ± 0.66 mm when applied to full and partial surfaces, respectively. We investigate robustness in response to errors in segmentation, varying levels of missing data, and adjusting the tunable parameters. Results demonstrate that the proposed surface registration method is an efficient, robust, and effective solution for fusing data from multiple modalities.

Regional dose metrics as predictors of biochemical failure and local recurrence after low-dose-rate prostate brachytherapy.

PURPOSE/OBJECTIVES: To assess regional dose metrics as predictors of disease relapse after low-dose-rate prostate brachytherapy. METHODS AND MATERIALS: A cohort of 2000 consecutive patients with prostate cancer treated with iodine-125 low-dose-rate prostate brachytherapy monotherapy was implanted between July 1998 and November 2007. Within this group, 89 patients had disease relapse, 13 of whom had local failure by clinical or histopathologic criteria. Postoperative computed tomography scans were available for 96.3% of cases, resulting in a data set composed of 87 relapses (including all 13 local relapses) and 1839 nonrelapsed controls. Using the VariSeed 8.0.2 software, we divided the original prostate contours into four quadrants: anterior-superior (ASQ), posterior-superior, anterior-inferior (AIQ), and posterior-inferior. DVH-derived dosimetric parameters were calculated for the whole prostate and each quadrant. RESULTS: Gleason score, prostate-specific antigen, and the use of androgen-deprivation therapy were predictive of disease relapse in a multivariate Cox model. Whole prostate dose metrics did not predict biochemical or local relapse. Dosimetric coverage was sparsest in the ASQ. Despite low values, dose to the ASQ was not predictive of relapse, nor were doses to the remaining three quadrants. AIQ coverage was predictive of local relapse in multivariate Cox model (p = 0.042). However, the AIQ dose metrics exhibited a large variance and on bootstrap analysis, a p value of <0.05 was seen in only 51% of 1000 iterations. CONCLUSIONS: Consistent with previous reports, whole-prostate dose metrics were not predictive of disease relapse (any) or local relapse in our patients. Although significant ASQ underdosage relative to other prostate regions was observed, ASQ dose coverage did not correlate with relapse.

Effect of aging and long-term erectile function after iodine-125 prostate brachytherapy.

PURPOSE: To evaluate long-term erectile function (EF) in men treated with iodine-125 prostate brachytherapy (PB) and to determine factors predictive for erectile dysfunction (ED), including natural decline because of aging. METHODS: Two thousand nine hundred twenty-nine patients (implanted July 1989-June 2012) with baseline EF and greater than 10-month followup (FU) are included. About 78.9% had full and 7.9% had partial EF at baseline. EF was assessed on a physician-reported three-point scale. Poisson regression with generalized estimating equations was used to assess predictors of ED and Kaplan-Meier curves time to ED. The effect of aging was calculated from the declining rate of baseline EF seen in sequential 5-year age cohorts and from the Massachusetts Male Aging Study. RESULTS: The median age was 66 years and median FU 3.5 years (maximum 14 years). About 1142 patients had more than 5 years of FU, and 43% had received 6 months of androgen deprivation therapy (ADT). Significant drop in EF was seen at 6 weeks after PB, with gradual decline thereafter. EF preservation at 5 years for age younger than 55, 56-59, 60-64, 65-69, and 70 year and older was 82%, 73%, 58%, 39%, and 23%, respectively. Comparisons of the 5-year age-related and treatment-related EF decline show that 50% of the long-term EF decline is related to aging. On univariate and multivariate analyses, age at implant, length of FU, hypertension, diabetes, and use of ADT (all p < 0.01) were significant predictors of ED. CONCLUSION: More than 80% of young men have EF preserved 5 years after PB. Age, ADT, history of hypertension, and the natural decline in EF have negative impact on long-term EF after PB.

A multi-atlas-based segmentation framework for prostate brachytherapy.

Low-dose-rate brachytherapy is a radiation treatment method for localized prostate cancer. The standard of care for this treatment procedure is to acquire transrectal ultrasound images of the prostate in order to devise a plan to deliver sufficient radiation dose to the cancerous tissue. Brachytherapy planning involves delineation of contours in these images, which closely follow the prostate boundary, i.e., clinical target volume. This process is currently performed either manually or semi-automatically, which requires user interaction for landmark initialization. In this paper, we propose a multi-atlas fusion framework to automatically delineate the clinical target volume in ultrasound images. A dataset of a priori segmented ultrasound images, i.e., atlases, is registered to a target image. We introduce a pairwise atlas agreement factor that combines an image-similarity metric and similarity between a priori segmented contours. This factor is used in an atlas selection algorithm to prune the dataset before combining the atlas contours to produce a consensus segmentation. We evaluate the proposed segmentation approach on a set of 280 transrectal prostate volume studies. The proposed method produces segmentation results that are within the range of observer variability when compared to a semi-automatic segmentation technique that is routinely used in our cancer clinic.

Late urinary side effects 10 years after low-dose-rate prostate brachytherapy: population-based results from a multiphysician practice treating with a standardized protocol and uniform dosimetric goals.

PURPOSE: To determine late urinary toxicity (>12 months) in a large cohort of uniformly treated low-dose-rate prostate brachytherapy patients. METHODS AND MATERIALS: From 1998 to 2009, 2709 patients with National Comprehensive Cancer Network-defined low-risk and low-tier intermediate-risk prostate cancer were treated with Iodine 125 ((125)I) low-dose-rate prostate brachytherapy; 2011 patients with a minimum of 25 months of follow-up were included in the study. Baseline patients, treatment, implant factors, and late urinary toxicity (Radiation Therapy Oncology Group [RTOG] grading system and International Prostate Symptom Score [IPSS]) were recorded prospectively. Time to IPSS resolution, late RTOG genitourinary toxicity was examined with Kaplan-Meier and log-rank tests. Cox proportional hazards regression was done for individual covariates and multivariable models. RESULTS: Median follow-up was 54.5 months (range, 2-13 years). Actuarial toxicity rates reached 27% and 10% (RTOG ≥2 and ≥3, respectively) at 9-13 years. Symptoms resolved quickly in the majority of patients (88% in 6-12 months). The prevalence of RTOG 0, 1, 2, 3, and 4 toxicity with a minimum of 7 years' follow-up was 70%, 21%, 6.4%, 2.3%, and 0.08%, respectively. Patients with a larger prostate volume, higher baseline IPSS, higher D90, acute toxicity, and age >70 years had more late RTOG ≥2 toxicity (all P≤.02). The IPSS resolved slower in patients with lower baseline IPSS and larger ultrasound prostate volume, those not receiving androgen deprivation therapy, and those with higher D90. The crude rate of RTOG 3 toxicity was 6%. Overall the rate of transurethral resection of the prostate was 1.9%; strictures, 2%; incontinence, 1.3%; severe symptoms, 1.8%; late catheterization, 1.3%; and hematuria, 0.8%. The majority (80%) resolved their symptoms in 6-12 months. CONCLUSION: Long-term urinary toxicity after brachytherapy is low. Although actuarial rates increase with longer follow-up (27% RTOG 2 and 10% RTOG 3 at 13 years), symptoms resolve relatively quickly; between 5 and 13 years' follow-up, >90% of patients have minimal urinary toxicity. Refining patient selection criteria, planning, and treatment delivery may further reduce toxicity.

Comparative analysis of rectal dose parameters in image-guided high-dose-rate brachytherapy for cervical cancer with and without a rectal retractor.

PURPOSE: The objective of this study was to determine if use of a rectal retractor (RR) in high-dose-rate intracavitary brachytherapy for cervical cancer reduces rectal dose parameters. METHODS AND MATERIALS: We reviewed data obtained from patients treated with intracavitary brachytherapy for cervical cancer with and without an RR. Treatment plans for each brachytherapy fraction were separated into two groups; R group with use of an RR and P group with use of vaginal packing. Dose-volume parameters for high-risk clinical target volume (HR-CTV), rectum, sigmoid, small bowel, and vaginal surface were collected for each fraction. Rectal D2cc and International Commission on Radiation Units & Measurements (ICRU) rectal point doses were compared between groups using Student's t tests. Predictors of higher rectal D2cc were determined by univariate and multivariate regression analyses. RESULTS: Four hundred sixty-three brachytherapy fractions from 114 patients were used for analysis, 377 fractions with a RR (R group) and 86 with vaginal packing only (P group). Both groups were similar except for slightly higher mean HR-CTV and mean bladder volume in P group. Both mean ICRU rectal point dose (241.1 vs. 269.9 cGy, p = 0.006) and rectal D2cc (240.6 vs. 283.6 cGy, p < 0.001) were significantly higher in P group. Point A dose, HR-CTV, stage, and use of an RR were significant predictors of rectal D2cc on multivariate analysis. CONCLUSIONS: Our data show that use of an RR leads to lower rectal dose parameters compared with vaginal packing. Further study is needed to determine if this will lead to less long-term toxicity.

Pride or prejudice: does Phoenix flatter radiation therapy?

PURPOSE: To compare disease-free survival (DFS) rates using a >0.4 ng/mL biochemical failure definition with the Phoenix (nadir+2 ng/mL) failure definition by analyzing a consecutive cohort of 1006 patients treated with low-dose-rate prostate brachytherapy (LDR-PB) monotherapy. METHODS AND MATERIALS: Data for first 1006 consecutive LDR-PB implants (1998-2003) were extracted from a prospective database. Patients had low- (58%) or intermediate (42%)-risk disease. Three months neoadjuvant and 3 months concomitant androgen deprivation therapy were used in 65% of cases. The Phoenix definition was modified to "unfail" patients who had a benign prostate-specific antigen (PSA) bounce. RESULTS: The median followup is 7.5 years. The median PSA at latest followup for disease-free patients was 0.04 ng/mL. The Phoenix definition yielded 5- and 10-year Kaplan-Meier DFS estimates of 96.5 ± 1.2% and 93.7 ± 2.0%, respectively. Applying the >0.4 ng/mL threshold reduced these estimates to 94.4 ± 1.6% and 88.8 ± 3.0% (log rank, p = 0.015). CONCLUSIONS: Compared with Phoenix, applying a >0.4 ng/mL failure definition increased biochemical failure by ∼2% at 5 years and ∼5% at 10 years. These data show that Phoenix did not greatly exaggerate DFS estimates compared with a surgical-type threshold. However, this observation is a consequence of the exceptionally low residual PSA values characteristic of LDR-PB and cannot be generalized to other forms of radiation therapy.