Biochemical failure-rate and preservation of erectile function after prostate seed brachytherapy in early-onset prostate cancer.

INTRODUCTION: To analyze biochemical failure-free survival and erectile dysfunction (ED) in younger men treated with prostate seed brachytherapy (PB). MATERIALS AND METHODS: Included were patients ≤ 55 years treated with PB. Erectile function at baseline and after treatment were assessed using the physician-reported CTCAE version 4.0. Biochemical failure (BF) was defined according to the Phoenix Consensus definition (PSA nadir + 2 ng/mL). The log-rank test (Kaplan-Meier method) and cox-regression analysis was used to calculate BF-free survival. RESULTS: Between July 2005 and November 2020, a total of 137 patients ≤ 55 years (range 44-55 years old) were treated with PB. Median follow up was 72 months. Twenty percent had Gleason 3+4 disease and 6% a PSA >10 ng/mL. Median prostate volume was 34 cc. Actuarial biochemical failure free survival at 5, 7, and 10 years, were 98%, 95% and 89%, respectively. Five patients received local salvage treatment. On multivariate analysis, CAPRA-score (HR 4.46, 95%CI 1.76-11.33, p = 0.002) and the dosimetric measure D90 > 130 Gy (p = 0.03) were predictive of BF. Five deaths occurred in our cohort, two due to cardiovascular reasons and three due to another malignancy. At baseline, all patients were able to have erections with or without medication. At 5 years and 7 years after PB, 80% and 64% of patients had little or no ED (erections without the need for medication) respectively. CONCLUSION: In young-onset patients treated with PB, failure rates are similar to their older counterparts. Sexual function decreases with time, even in patients with good sexual function.

Recovery of serum testosterone following neoadjuvant androgen deprivation therapy in Japanese prostate cancer patients treated with low-dose rate brachytherapy.

OBJECTIVE: To investigate the time course of total testosterone (TT) recovery after cessation of androgen deprivation therapy (ADT) in Japanese patients treated with brachytherapy. METHODS: In total, 125 patients with prostate cancer received 6 months of neoadjuvant ADT (nADT) followed by low-dose rate (LDR) brachytherapy. TT was measured every 3 months after cessation of nADT, and some predictive factors affecting TT recovery were analyzed. RESULTS: The cumulative incidence rates of TT recovery to normal levels (TT ≥ 3.0 ng/mL) after 12 and 24 months cessation were 49.6% and 81.6%, respectively. The median interval to recover to normal TT was 15 months. In multivariate analysis, the use of a gonadotropin-releasing hormone (GnRH) antagonist as nADT significantly earlier improved to recovery to normal TT level (p = 0.046). Conversely, higher body mass index (BMI) and hypertension significantly prolonged TT recovery to normal (p = 0.026 and p = 0.026, respectively). CONCLUSIONS: Approximately one-fifth of patients still had low TT levels 2 years after the cessation of 6 months nADT before LDR brachytherapy. Use of a GnRH agonist, higher BMI, and hypertension were the predictive factors for slower TT recovery to normal TT levels after the cessation of nADT.

Relationship between radiation doses and erectile function deterioration in patients with localized prostate cancer treated with permanent prostate brachytherapy.

OBJECTIVES: To investigate the relationship between radiation doses in prostate brachytherapy and deterioration of erectile function in patients with localized prostate cancer. METHODS: A longitudinal survey study was carried out among 261 prostate cancer patients who received prostate brachytherapy. A total of 48 patients were potent at baseline and they did not receive any supplemental therapy preoperatively. Dosimetry parameters of the whole prostate gland, prostate apex, urethra and rectum were collected using the VariSeed 8.0 treatment planning system (Varian Medical Systems, Palo Alto, CA, USA). We carried out a logistic regression analysis to clarify the relationship between radiation doses and erectile function deterioration, which was assessed using the International Index of Erectile Function-15 questionnaire. RESULTS: The median patient age was 66 years (range 53-70 years) with a median follow-up time of 44 months (36-71 months). The mean total International Index of Erectile Function-15 score decreased from 49.9 at baseline to 34.7 after 12 months (P < 0.001), but gradually plateaued within 36 months. Erectile function deterioration was noted in 32 (66.7%) patients 36 months after prostate brachytherapy. In an analysis of risk factors for erectile function deterioration after prostate brachytherapy, age ≥70 years (P = 0.029), prostate V100 ≥95% (P = 0.024), apex V100 ≥95% (P = 0.024), apex V150 ≥70% (P = 0.009) and apex D90 ≥150 Gy (P = 0.011) correlated with erectile function deterioration. A multivariate analysis identified an age of ≥70 years (odds ratio 7.91, P = 0.024) and apex V150 ≥70% (odds ratio 7.75, P = 0.007) as independent risk factors for erectile function deterioration after prostate brachytherapy. CONCLUSIONS: An excessive radiation dose, particularly to the prostate apex area, and an advanced age might have a negative impact on the preservation of potency after prostate brachytherapy.

Development and clinical implementation of SeedNet: A sliding-window convolutional neural network for radioactive seed identification in MRI-assisted radiosurgery (MARS).

PURPOSE: To develop and evaluate a sliding-window convolutional neural network (CNN) for radioactive seed identification in MRI of the prostate after permanent implant brachytherapy. METHODS: Sixty-eight patients underwent prostate cancer low-dose-rate (LDR) brachytherapy using radioactive seeds stranded with positive contrast MR-signal seed markers and were scanned using a balanced steady-state free precession pulse sequence with and without an endorectal coil (ERC). A sliding-window CNN algorithm (SeedNet) was developed to scan the prostate images using 3D sub-windows and to identify the implanted radioactive seeds. The algorithm was trained on sub-windows extracted from 18 patient images. Seed detection performance was evaluated by computing precision, recall, F1 -score, false discovery rate, and false-negative rate. Seed localization performance was evaluated by computing the RMS error (RMSE) between the manually identified and algorithm-inferred seed locations. SeedNet was implemented into a clinical software package and evaluated on sub-windows extracted from 40 test patients. RESULTS: SeedNet achieved 97.6 ± 2.2% recall and 97.2 ± 1.9% precision for radioactive seed detection and 0.19 ± 0.04 mm RMSE for seed localization in the images acquired with an ERC. Without the ERC, the recall remained high, but the false-positive rate increased; the RMSE of the seed locations increased marginally. The clinical integration of SeedNet slightly increased the run-time, but the overall run-time was still low. CONCLUSION: SeedNet can be used to perform automated radioactive seed identification in prostate MRI after LDR brachytherapy. Image quality improvement through pulse sequence optimization is expected to improve SeedNet's performance when imaging without an ERC.

Dosimetric comparison of inverse optimisation methods versus forward optimisation in HDR brachytherapy of breast, cervical and prostate cancer.

OBJECTIVE: Dosimetric comparison of HIPO (hybrid inverse planning optimisation) and IPSA (inverse planning simulated annealing) inverse and forward optimisation (FO) methods in brachytherapy (BT) of breast, cervical and prostate cancer. METHODS: At our institute 38 breast, 47 cervical and 50 prostate cancer patients treated with image-guided interstitial high-dose-rate BT were selected. Treatment plans were created using HIPO and IPSA inverse optimisation methods as well as FO. The dose-volume parameters of different treatment plans were compared with Friedman ANOVA and the LSD post-hoc test. RESULTS: IPSA creates less dose coverage to the target volume than HIPO or FO: V100 was 91.7%, 91% and 91.9% for HIPO, IPSA and FO plans (p = 0.1784) in breast BT; 90.4%, 89.2% and 91% (p = 0.0045) in cervical BT; and 97.1%, 96.2% and 97.7% (p = 0.0005) in prostate BT, respectively. HIPO results in more conformal plans: COIN was 0.72, 0.71 and 0.69 (p = 0.0306) in breast BT; 0.6, 0.47 and 0.58 (p < 0.001) in cervical BT; and 0.8, 0.7 and 0.7 (p < 0.001) in prostate BT, respectively. In breast BT, dose to the skin and lung was smaller with HIPO and FO than with IPSA. In cervical BT, dose to the rectum, sigmoid and bowel was larger using IPSA than with HIPO or FO. In prostate BT, dose to the urethra was higher and the rectal dose was smaller using FO than with inverse methods. CONCLUSION: In interstitial breast and prostate BT, HIPO results in comparable dose-volume parameters to FO, but HIPO plans are more conformal. In cervical BT, HIPO produces dosimetrically acceptable plans only when more needles are used. The dosimetric quality of IPSA plans is suboptimal and results in unnecessary larger active lengths.

Patient-reported outcomes after open radical prostatectomy, laparoscopic radical prostatectomy and permanent prostate brachytherapy.

OBJECTIVE: To assess patient-reported outcomes after open radical prostatectomy, laparoscopic radical prostatectomy and permanent prostate brachytherapy. METHODS: patient-reported outcomes were evaluated using Expanded Prostate Cancer Index Composite scores at baseline and 1, 3, 6, 12 and 36 months after treatment, respectively, using differences from baseline scores. RESULTS: Urinary function was the same in the three groups at baseline, but worse after surgery than after permanent prostate brachytherapy until 12 months, and similar after open radical prostatectomy and permanent prostate brachytherapy and better than after laparoscopic radical prostatectomy at 36 months. Urinary bother was significantly worse at 1 month after surgery, but better after open radical prostatectomy than after permanent prostate brachytherapy and laparoscopic radical prostatectomy at 3 months, after which symptoms improved gradually in all groups. Obstructive/irritative symptoms were worse after permanent prostate brachytherapy than after open radical prostatectomy at 36 months, and worse after laparoscopic radical prostatectomy until 6 months. Urinary incontinence was worse after surgery, particularly after 1 month. This symptom returned to the baseline level at 12 months after open radical prostatectomy, but recovery after laparoscopic radical prostatectomy was slower. Bowel function after permanent prostate brachytherapy was significantly worse than after surgery at 1 month and this continued until 6 months. Bowel bother was slightly worse at 3 and 6 months after permanent prostate brachytherapy compared to these time points after surgery. CONCLUSION: Urinary function and bother were worst after laparoscopic radical prostatectomy, especially in the early postoperative phase, whereas urinary obstructive/irritative symptom, bowel function and bother were worse after permanent prostate brachytherapy. These findings are useful and informative for the treatment of patients with prostate cancer.

Does combination therapy with tamsulosin and trospium chloride improve lower urinary tract symptoms after SEEDS brachytherapy for prostate cancer compared with tamsulosin alone? : A prospective, randomized, controlled trial.

OBJECTIVE: To compare the efficacy of combination therapy with an alpha-blocker and an anticholinergic to monotherapy with an alpha blocker on lower urinary tract symptoms (LUTS) following brachytherapy in prostate cancer patients. MATERIAL AND METHODS: A total of 124 patients that had been clinically diagnosed with localized prostate cancer and underwent prostate brachytherapy were enrolled in the present study. Patients were randomized and allocated to two groups, including 60 to the combination group (tamsulosin 0.2 mg/day and trospium chloride 20 mg twice daily) and 64 to the monotherapy group (tamsulosin 0.2 mg/day). Treatment began 1 day after brachytherapy and continued for 6 months. LUTS were compared between the two groups using the total International Prostate Symptom Score (IPSS), storage and voiding IPSS subscores, quality of life (QoL) scores, maximum flow rate (Qmax), and postvoid residual (PVR) urine volume at 1, 3, 6, and 12 months after implantation. RESULTS: In all, 111 patients were ultimately analyzed in the study. Compared with pretreatment scores, a significant increase in total IPSS was found at 1, 3, and 6 months in both groups, but no statistically significant differences were observed between the two groups. The combination therapy group showed a greater decrease in the IPSS storage score compared with the monotherapy group at 1, 3, and 6 months (p = 0.031, 0.030 and 0.042, respectively). Patients receiving tamsulosin plus trospium chloride also showed significant improvements in QoL at 1 and 3 months compared with tamsulosin alone (P = 0.039, P = 0.047). Between the two groups, there was no significant difference in IPSS voiding score, Qmax, and PVR from baseline to each point of the study period. CONCLUSIONS: Combination therapy with tamsulosin and trospium chloride helped to improve IPSS storage symptoms and Qol scores in prostate brachytherapy patients with LUTS compared with tamsulosin monotherapy.

Results of central pathology review of prostatic biopsies in a contemporary series from a phase III, multicenter, randomized controlled trial (SHIP0804).

To investigate contemporary rates of variation in the biopsy Gleason grading in prostate cancer, between local and central pathologists, based on central review of the pathological slides from Seed and Hormone for Intermediate-risk Prostate Cancer (SHIP) 0804, a phase III, multicenter, randomized, controlled study. From April 2008 to May 2011, 18 Japanese institutions participated. All H&E slides were reviewed independently, without clinical information, and a tumor grade was assigned according to the modified Gleason grading system proposed by the International Society of Urological Pathology (ISUP). Prostate biopsy specimens of 642 cases were available for evaluation. An exact concordance rate of Gleason score (GS) between local and central pathologists was determined to be 65.3%; with the under-grading and over-grading of grades to be 14.6% and 20.1%, respectively. The central review resulted in numbers of tumor-bearing cores reassigned in 99 of 616 cases in which such information by the local pathologists was available (16.1%). Discordance in biopsy Gleason grading was still found in one third of the cases in the SHIP0804 study. This information is valuable in extrapolating the diagnostic error range in contemporary clinical studies conducted without central pathological review.

Development of patient and catheter specific error thresholds for high dose rate prostate brachytherapy.

BACKGROUND: In-vivo source tracking has been an active topic of research in the field of high-dose rate brachytherapy in recent years to verify accuracy in treatment delivery. Although detection systems for source tracking are being developed, the allowable threshold of treatment error is still unknown and is likely patient-specific due to anatomy and planning variation. PURPOSE: The purpose of this study was to determine patient and catheter-specific shift error thresholds for in-vivo source tracking during high-dose-rate prostate brachytherapy (HDRPBT). METHODS: A module was developed in the previously described graphical processor unit multi-criteria optimization (gMCO) algorithm. The module generates systematic catheter shift errors retrospectively into HDRPBT treatment plans, performed on 50 patients. The catheter shift model iterates through the number of catheters shifted in the plan (from 1 to all catheters), the direction of shift (superior, inferior, medial, lateral, cranial, and caudal), and the magnitude of catheter shift (1-6 mm). For each combination of these parameters, 200 error plans were generated, randomly selecting the catheters in the plan to shift. After shifts were applied, dose volume histogram (DVH) parameters were re-calculated. Catheter shift thresholds were then derived based on plans where DVH parameters were clinically unacceptable (prostate V100 < 95%, urethra D0.1cc > 118%, and rectum Dmax > 80%). Catheter thresholds were also Pearson correlated to catheter robustness values. RESULTS: Patient-specific thresholds varied between 1 to 6 mm for all organs, in all shift directions. Overall, patient-specific thresholds typically decrease with an increasing number of catheters shifted. Anterior and inferior directions were less sensitive than other directions. Pearson's correlation test showed a strong correlation between catheter robustness and catheter thresholds for the rectum and urethra, with correlation values of -0.81 and -0.74, respectively (p < 0.01), but no correlation was found for the prostate. CONCLUSIONS: It was possible to determine thresholds for each patient, with thresholds showing dependence on shift direction, and number of catheters shifted. Not every catheter combination is explorable, however, this study shows the feasibility to determine patient-specific thresholds for clinical application. The correlation of patient-specific thresholds with the equivalent robustness value indicated the need for robustness consideration during plan optimization and treatment planning.

Rectal perforation following SpaceOAR placement combined with permanent prostate brachytherapy.

Introduction: We report a case of rectal perforation following SpaceOAR placement utilized with iodine-125 low-dose-rate brachytherapy for prostate cancer. Case presentation: A 65-year-old patient with localized prostate cancer underwent SpaceOAR placement following LDR-BT. No significant issues occurred with the SpaceOAR procedure, and no abnormalities were found on the next day's T2-weighted magnetic resonance imaging. Two weeks later, a colonoscopy was performed due to mucus stools revealing rectal perforation attributed to SpaceOAR. By maintaining Macrogol 4000 and a low residue diet, the perforation healed within 6 months. Conclusion: Rectal ulcers and perforations are the most common severe adverse events from SpaceOAR placement. Effective management strategies are crucial since complications can't be entirely avoided, even with skilled surgeons.

Deep learning-based ultrasound auto-segmentation of the prostate with brachytherapy implanted needles.

BACKGROUND: Accurate segmentation of the clinical target volume (CTV) corresponding to the prostate with or without proximal seminal vesicles is required on transrectal ultrasound (TRUS) images during prostate brachytherapy procedures. Implanted needles cause artifacts that may make this task difficult and time-consuming. Thus, previous studies have focused on the simpler problem of segmentation in the absence of needles at the cost of reduced clinical utility. PURPOSE: To use a convolutional neural network (CNN) algorithm for segmentation of the prostatic CTV in TRUS images post-needle insertion obtained from prostate brachytherapy procedures to better meet the demands of the clinical procedure. METHODS: A dataset consisting of 144 3-dimensional (3D) TRUS images with implanted metal brachytherapy needles and associated manual CTV segmentations was used for training a 2-dimensional (2D) U-Net CNN using a Dice Similarity Coefficient (DSC) loss function. These were split by patient, with 119 used for training and 25 reserved for testing. The 3D TRUS training images were resliced at radial (around the axis normal to the coronal plane) and oblique angles through the center of the 3D image, as well as axial, coronal, and sagittal planes to obtain 3689 2D TRUS images and masks for training. The network generated boundary predictions on 300 2D TRUS images obtained from reslicing each of the 25 3D TRUS images used for testing into 12 radial slices (15° apart), which were then reconstructed into 3D surfaces. Performance metrics included DSC, recall, precision, unsigned and signed volume percentage differences (VPD/sVPD), mean surface distance (MSD), and Hausdorff distance (HD). In addition, we studied whether providing algorithm-predicted boundaries to the physicians and allowing modifications increased the agreement between physicians. This was performed by providing a subset of 3D TRUS images of five patients to five physicians who segmented the CTV using clinical software and repeated this at least 1 week apart. The five physicians were given the algorithm boundary predictions and allowed to modify them, and the resulting inter- and intra-physician variability was evaluated. RESULTS: Median DSC, recall, precision, VPD, sVPD, MSD, and HD of the 3D-reconstructed algorithm segmentations were 87.2 [84.1, 88.8]%, 89.0 [86.3, 92.4]%, 86.6 [78.5, 90.8]%, 10.3 [4.5, 18.4]%, 2.0 [-4.5, 18.4]%, 1.6 [1.2, 2.0] mm, and 6.0 [5.3, 8.0] mm, respectively. Segmentation time for a set of 12 2D radial images was 2.46 [2.44, 2.48] s. With and without U-Net starting points, the intra-physician median DSCs were 97.0 [96.3, 97.8]%, and 94.4 [92.5, 95.4]% (p < 0.0001), respectively, while the inter-physician median DSCs were 94.8 [93.3, 96.8]% and 90.2 [88.7, 92.1]%, respectively (p < 0.0001). The median segmentation time for physicians, with and without U-Net-generated CTV boundaries, were 257.5 [211.8, 300.0] s and 288.0 [232.0, 333.5] s, respectively (p = 0.1034). CONCLUSIONS: Our algorithm performed at a level similar to physicians in a fraction of the time. The use of algorithm-generated boundaries as a starting point and allowing modifications reduced physician variability, although it did not significantly reduce the time compared to manual segmentations.

Feasibility of using micro silica bead TLDs for in-Vivo dosimetry of CT-based HDR prostate brachytherapy: An experimental and simulation study.

PURPOSE: Feasibility of silica-based dosimeters for IVD of HDR prostate brachytherapy. MATERIAL AND METHODS: Plastic dosimeter holders and a water-fillable prostate phantom were built in-house. Interstitial prostate brachytherapy and Monte Carlo simulations were performed. The treatment planning, Monte-Carlo simulation, and dosimetry results were compared. RESULTS: The relative differences between TLD-TPS, TLD-MCNP, and TPS-MCNP were 0.2-6.9 %, 0.5-6.5 %, and 0.6-6.3 %, respectively. CONCLUSION: Micro-silica bead dosimeters can perform offline in situ quality assurance in HDR prostate brachytherapy.

Inter-observer effects in needle reconstruction for temporary prostate brachytherapy: Dosimetric implications and adaptive CBCT-TRUS registration solutions.

PURPOSE: To investigate geometric and dosimetric inter-observer variability in needle reconstruction for temporary prostate brachytherapy. To assess the potential of registrations between transrectal ultrasound (TRUS) and cone-beam computed tomography (CBCT) to support implant reconstructions. METHODS AND MATERIALS: The needles implanted in 28 patients were reconstructed on TRUS by three physicists. Corresponding geometric deviations and associated dosimetric variations to prostate and organs at risk (urethra, bladder, rectum) were analyzed. To account for the found inter-observer variability, various approaches (template-based, probe-based, marker-based) for registrations of CBCT to TRUS were investigated regarding the respective needle transfer accuracy in a phantom study. Three patient cases were examined to assess registration accuracy in-vivo. RESULTS: Geometric inter-observer deviations >1 mm and >3 mm were found for 34.9% and 3.5% of all needles, respectively. Prostate dose coverage (changes up to 7.2%) and urethra dose (partly exceeding given dose constraints) were most affected by associated dosimetric changes. Marker-based and probe-based registrations resulted in the phantom study in high mean needle transfer accuracies of 0.73 mm and 0.12 mm, respectively. In the patient cases, the marker-based approach was the superior technique for CBCT-TRUS fusions. CONCLUSION: Inter-observer variability in needle reconstruction can substantially affect dosimetry for individual patients. Especially marker-based CBCT-TRUS registrations can help to ensure accurate reconstructions for improved treatment planning.

Real-time definition of single seed placement sensitivity in low-dose-rate prostate brachytherapy.

PURPOSE: In low-dose-rate brachytherapy, iodine-125 seeds are implanted based on a treatment plan, generated with respect to different dose constraints. The quality of the dose distribution depends on a precise seed placement, however, during treatment planning the impact on the dose parameters when certain seeds fail to be placed precisely is not clear. METHODS AND MATERIALS: We developed a method using automatic differentiation to calculate gradients of dose parameters with regard to the seeds' positions. Thus, we understand their sensitivity with respect to the seed placement. A statistical analysis is performed on a data set with 35 prostate brachytherapy patients. RESULTS: The most sensitive seeds regarding the dosimetric parameters of both rectum and urethra are close to the corresponding organ. Their gradient directions are mainly orthogonal to their surfaces. However, not all seeds close to the surface are equally sensitive with regard to the dose parameter. The most sensitive seeds regarding the prostate's dose parameters are distributed throughout the prostate and the direction of the gradients are mainly parallel to its surface. A linear regression with respect to different patient parameters shows that dose constraints which are barely fulfilled have large gradients and thus are additionally sensitive to misplacement. CONCLUSION: Automatic differentiation can be used to analyze dose parameter sensitivity with respect to seed placement. Integrating this into treatment planning systems is valuable as it speeds up the planning procedure, making it more robust and less dependent on user experience while showing the operating physician which needle placements require greater accuracy than others.

Optimisation and validation of a co-manipulated robot for brachytherapy procedure.

BACKGROUND: Low-dose rate brachytherapy is the referent treatment for early-stage prostate cancer and consists in manually inserting radioactive seeds within the organ to destroy tumorous cells. This treatment is inaccurate leading to side effects. Researchers developed robots to improve this technique. Despite ameliorating accuracy, they cannot be clinically used because of size and acceptability. Therefore, a 6-DOF parallel and co-manipulated robot is proposed to meet these requirements. METHODS: To fulfil the application requirements, a compact design was modelled. The robot's optimal dimensions were defined by establishing kinematics and implementing genetic algorithm. The robot's relevance was evaluated by measuring workspace and needle placement errors. RESULTS: The robot fits into a cube of 300 × 300 × 300 mm3 and provides a free-singularity workspace of 55 × 55 × 150 mm3 with a possible end-effector rotation of 15° and a needle placement error <3 mm. CONCLUSION: The results are promising and prove that our robot fulfils the application requirements and presents a beneficial alternative to the manual procedure.

A new way to visualize prostate brachytherapy needles using ultrasound color Doppler and needle surface modifications.

PURPOSE: Suboptimal ultrasound conspicuity of the brachytherapy applicator can lead to inaccurate image reconstructions of the applicator resulting in decreased tumor control or increased normal tissue dose. This feasibility study aims to improve ultrasound conspicuity of high-dose rate (HDR) brachytherapy needles by modifying the surface of the needles to produce a color Doppler twinkling signature. MATERIALS AND METHODS: Surface modifications of standard 17-gauge titanium HDR brachytherapy needles included laser-scribing, application of polymethyl methacrylate (PMMA), and coating with a commercially available echogenic coating. Laser-scribing was performed with variable widths (0.1-1 mm) and depths (10-100 µm). The echogenic coating was applied with 3 different thicknesses (27, 40, and 64 µm). Unmodified and modified needles were imaged under B-mode and color Doppler ultrasound in phantom and cadaver, and the signal strength was recorded. RESULTS: Laser-scribed, PMMA-coated, and echogenic-coated brachytherapy needles produced a twinkling signature along the needle shaft on color Doppler ultrasound. Twinkling was observed with laser-scribe depths >20 µm and widths >0.1 mm and from echogenic coatings 40 µm and 64 µm thick. Twinkling was not observed with unmodified needles. The twinkling signature had a spectral composition with a uniform magnitude between the velocities of 2 to 16 cm/s. CONCLUSIONS: Color Doppler ultrasound of surface-modified brachytherapy applicators may improve applicator conspicuity aiding applicator placement and digitization. HDR brachytherapy needles may be modified to produce the twinkling signature via laser-scribing, PMMA rings, or applying an echogenic coating.

Improving ultrasound-based brachytherapy needle conspicuity by applying an echogenic coating.

BACKGROUND: Applicator conspicuity in ultrasound-guided brachytherapy procedures is commonly impaired by imaging artifacts or non-ideal imaging geometry, which can slow down applicator position digitization and increase the geometric uncertainty of the delivered dose distribution. PURPOSE: The purpose of this study was to improve the conspicuity of high-dose rate (HDR) brachytherapy needles under B-mode ultrasound imaging by applying an echogenic surface coating. Our hypothesis was that an echogenic coating would reduce artifacts and improve needle visualization within regions of signal degradation. METHODS: In this study, 17-gauge, 25-cm long titanium HDR brachytherapy needles were coated with acoustically reflective microspheres over a 2.5 cm region starting from the needle tip. Three coating thicknesses (27 µm, 40 µm, 64 µm) were compared against an uncoated control needle. The coated and uncoated needles were imaged using B-mode ultrasound in a tissue-equivalent prostate phantom and in a cadaverous male pelvis using a transrectal probe. Needle conspicuity was assessed under multiple conditions: a single needle implant, an implant with multiple needles between the probe and the needle of interest, and an angled needle implant. All images were assessed qualitatively for needle conspicuity and the presence of artifacts and quantitatively using grey-scale image intensity values. RESULTS: The 64 µm echogenic coating reduced the magnitude of reverberation artifacts by 31 ± 14% and comet tail artifacts by 40%-70%. The echogenic coating also improved needle contrast, measured by the relative differences in signal intensity compared with the adjacent environment, when needles were angled up to 30° with respect to the transducer probe in the cadaver. The improvements in conspicuity and artifact reduction increased with increasing coating thickness. The performance of the needles coated with the 64 µm thickness was qualitatively superior and yielded high-contrast, well-circumscribed signals in the cadaverous male pelvis, even under situations where a needle was acoustically shadowed by multiple other needles. CONCLUSIONS: An echogenic surface coating reduced imaging artifacts and improved needle conspicuity under realistic clinical conditions for ultrasound-based prostate or gynecological brachytherapy. The improved conspicuity has the potential to improve the efficiency of needle placement and the accuracy of needle position digitization during brachytherapy procedures.

Prostate segmentation accuracy using synthetic MRI for high-dose-rate prostate brachytherapy treatment planning.

Objective. Both computed tomography (CT) and magnetic resonance imaging (MRI) images are acquired for high-dose-rate (HDR) prostate brachytherapy patients at our institution. CT is used to identify catheters and MRI is used to segment the prostate. To address scenarios of limited MRI access, we developed a novel generative adversarial network (GAN) to generate synthetic MRI (sMRI) from CT with sufficient soft-tissue contrast to provide accurate prostate segmentation without MRI (rMRI).Approach. Our hybrid GAN, PxCGAN, was trained utilizing 58 paired CT-MRI datasets from our HDR prostate patients. Using 20 independent CT-MRI datasets, the image quality of sMRI was tested using mean absolute error (MAE), mean squared error (MSE), peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM). These metrics were compared with the metrics of sMRI generated using Pix2Pix and CycleGAN. The accuracy of prostate segmentation on sMRI was evaluated using the Dice similarity coefficient (DSC), Hausdorff distance (HD) and mean surface distance (MSD) on the prostate delineated by three radiation oncologists (ROs) on sMRI versus rMRI. To estimate inter-observer variability (IOV), these metrics between prostate contours delineated by each RO on rMRI and the prostate delineated by treating RO on rMRI (gold standard) were calculated.Main results. Qualitatively, sMRI images show enhanced soft-tissue contrast at the prostate boundary compared with CT scans. For MAE and MSE, PxCGAN and CycleGAN have similar results, while the MAE of PxCGAN is smaller than that of Pix2Pix. PSNR and SSIM of PxCGAN are significantly higher than Pix2Pix and CycleGAN (p < 0.01). The DSC for sMRI versus rMRI is within the range of the IOV, while the HD for sMRI versus rMRI is smaller than the HD for the IOV for all ROs (p ≤ 0.03).Significance. PxCGAN generates sMRI images from treatment-planning CT scans that depict enhanced soft-tissue contrast at the prostate boundary. The accuracy of prostate segmentation on sMRI compared to rMRI is within the segmentation variation on rMRI between different ROs.

Salvage prostate brachytherapy in radiorecurrent prostate cancer: An international Delphi consensus study.

BACKGROUND AND PURPOSE: Local recurrences after previous radiotherapy (RT) are increasingly being identified in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option. We sought to generate international consensus statements on the use and preferred technical considerations for salvage prostate BT. MATERIALS AND METHODS: International experts in salvage prostate BT were invited (n = 34) to participate. A three-round modified Delphi technique was utilized, with questions focused on patient- and cancer-specific criteria, type and technique of BT, and follow-up. An a priori threshold for consensus of ≥ 75% was set, with a majority opinion being ≥ 50%. RESULTS: Thirty international experts agreed to participate. Consensus was achieved for 56% (18/32) of statements. Consensus was achieved in several areas of patient selection: 1) A minimum of 2-3 years from initial RT to salvage BT; 2) MRI and PSMA PET should be obtained; and 3) Both targeted and systematic biopsies should be performed. Several areas did not reach consensus: 1) Maximum T stage/PSA at time of salvage; 2) Utilization/duration of ADT; 3) Appropriateness of combining local salvage with SABR for oligometastatic disease and 4) Repeating a second course of salvage BT. A majority opinion preferred High Dose-Rate salvage BT, and indicated that both focal and whole gland techniques could be appropriate. There was no single preferred dose/fractionation. CONCLUSION: Areas of consensus within our Delphi study may serve as practical advice for salvage prostate BT. Future research in salvage BT should address areas of controversy identified in our study.

Validation of automated post-adjustments of HDR prostate brachytherapy treatment plans by quantitative measures and oncologist observer study.

PURPOSE: The aim was to evaluate a postprocessing optimization algorithm's ability to improve the spatial properties of a clinical treatment plan while preserving the target coverage and the dose to the organs at risk. The goal was to obtain a more homogenous treatment plan, minimizing the need for manual adjustments after inverse treatment planning. MATERIALS AND METHODS: The study included 25 previously treated prostate cancer patients. The treatment plans were evaluated on dose-volume histogram parameters established clinical and quantitative measures of the high dose volumes. The volumes of the four largest hot spots were compared and complemented with a human observer study with visual grading by eight oncologists. Statistical analysis was done using ordinal logistic regression. Weighted kappa and Fleiss' kappa were used to evaluate intra- and interobserver reliability. RESULTS: The quantitative analysis showed that there was no change in planning target volume (PTV) coverage and dose to the rectum. There were significant improvements for the adjusted treatment plan in: V150% and V200% for PTV, dose to urethra, conformal index, and dose nonhomogeneity ratio. The three largest hot spots for the adjusted treatment plan were significantly smaller compared to the clinical treatment plan. The observers preferred the adjusted treatment plan in 132 cases and the clinical in 83 cases. The observers preferred the adjusted treatment plan on homogeneity and organs at risk but preferred the clinical plan on PTV coverage. CONCLUSIONS: Quantitative analysis showed that the postadjustment optimization tool could improve the spatial properties of the treatment plans while maintaining the target coverage.