Recurrence characteristics after focal salvage HDR brachytherapy in prostate cancer.

BACKGROUND AND PURPOSE: Radiorecurrent prostate cancer is often confined to the prostate, predominantly near the index lesion. The purpose of this study was to look at recurrence characteristics in patients treated with focal salvage high dose-rate (HDR) brachytherapy. MATERIALS AND METHODS: Patients treated with MRI-guided HDR brachytherapy, with a single fraction of 19 Gy from July 2013 to October 2021 as focal salvage treatment, were prospectively included in the current study. Imaging data were collected regarding the occurrence of local, regional and distant recurrences, including location of local recurrences (LR) in relation to the HDR radiotherapy field. RESULTS: One hundred seventy-five patients were included after focal salvage HDR brachytherapy (median follow-up 36 months (IQR 23-50)). Three-years biochemical recurrence-free survival, LR-free survival, in-field LR-free survival, out-of-field LR-free survival, any-recurrence-free survival and ADT-free survival were 43% (95%CI 34%-52%), 51% (41%-61%), 70% (61%-80%), 92% (88%-97%), 42% (32%-52%) and 86% (80%-92%), respectively. Larger GTV-size and shorter PSA doubling time were associated with in-field LR in multivariable analysis. CONCLUSION: After focal salvage HDR brachytherapy with a dose of 1x19 Gy for local prostate cancer recurrence, subsequent recurrences are mostly local and in-field.

Single shot MR tagging to quantify local tissue deformation during MRI-guided needle interventions: a feasibility study.

PURPOSE: In MRI-guided needle interventions, such as biopsies and brachytherapy, tissue deformation caused by needle movement may result in localization errors and thus hamper the outcome of the procedure. Monitoring the local tissue deformation provides the ability to compensate for it, e.g., by increasing the needle insertion depth. Fast MR scans are useful to track the needle, but cannot be used to quantify local tissue deformation, in case anatomical landmarks are missing. Artificial landmarks can be created by MR tagging. This method provides a spatial saturation pattern (tag) in the tissue. Deformation of this pattern reflects the tissue motion between tag creation and tag imaging. As the needle movement is nonperiodic, k-space cannot be acquired with a multishot approach, like is usually done for cardiac imaging. Hence, a single shot MR tagging sequence is needed, which entails tag creation, needle movement and tag acquisition. In this study, the feasibility of single shot MR tagging for MRI-guided needle interventions in phantom and volunteer experiments is shown. METHODS: Four different experiments were performed on a 1.5 T MR scanner: the first to quantify translations, the second to quantify rotations, the third to mimic a needle intervention, and the fourth to investigate the tag persistence in a volunteer. The tag pattern is created by a 1331 composite pulse. A balanced steady state free precession sequence is used for imaging. To minimize undesired changes in contrast or sharpness of the tag pattern, we chose a relatively small flip angle and a short imaging time in all experiments. In the volunteer experiments, we modified the sequence to also be able to inspect the influence of the used k-space sampling profile and the flip angle on the temporal persistence of image contrast and tag pattern. In all scans, head or surface coils were used for signal reception. RESULTS: In all experiments, the tag pattern was clearly visible and could be used to quantify the local tissue deformation caused by (needle) movement. Strong correlations between the actual and measured (angular) phantom motions were obtained. In the needle intervention experiment, the tag lines were perfectly horizontal when there was no needle movement. With needle movement, local tissue displacements up to 5 mm were observed. Volunteer's anatomy could be discriminated, despite the tag pattern. The tag pattern in the prostate, for example, could still be read in all tagging images acquired 2 s after creating the tag pattern. With optimized scan parameters the tag persistence was even longer. The best image tag contrast was obtained using a large flip angle and the profile order low-high, although the image was slightly blurred. CONCLUSIONS: This study demonstrates that single shot MR tagging can be used to quantify tissue deformation caused by needle movement. The in-vivo tag persistence is sufficient to enable the application of the tagging sequence during MRI-guided needle interventions in patients.

Development and internal validation of multivariable prediction models for biochemical failure after MRI-guided focal salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer.

BACKGROUND AND PURPOSE: Magnetic resonance-guided focal salvage high-dose-rate brachytherapy (FS-HDR-BT) for radiorecurrent prostate cancer (PCa) shows low toxicity rates. However, biochemical failure (BF) after treatment occurs frequently. We developed two prediction models for BF (Phoenix definition) with the aim of enhancing patient counselling before FS-HDR-BT and during follow-up. MATERIALS AND METHODS: A prospective cohort of 150 radiorecurrent PCa patients treated with FS-HDR-BT between 2013 and 2020 was used for model development and internal validation. Multivariable Cox Proportional Hazards regression was applied. For model 1, only pre-salvage variables were included as candidate predictors. For model 2, additional (post-)salvage characteristics were tested. After calibration, nomograms and webtools were constructed. Finally, three risk groups were identified. RESULTS: Sixty-one patients (41%) experienced BF. At baseline (model 1), age, gross tumour volume, pre-salvage PSA, and pre-salvage PSA doubling time (PSADT) were predictive of BF. During follow-up (model 2), age, pre-salvage PSA and PSADT, seminal vesicle involvement, post-salvage time to PSA nadir, and percentage PSA reduction were predictive of BF. The adjusted C-statistics were 0.73 (95% CI: 0.66-0.81) and 0.84 (95% CI: 0.78-0.90), respectively, with acceptable calibration. Estimated 2-year biochemical disease-free survival for the low-, intermediate-, and high-risk groups were 84%, 70%, and 31% (model 1), and 100%, 71%, and 5% (model 2). CONCLUSION: Two models are provided for prediction of BF in patients with radiorecurrent PCa treated with FS-HDR-BT. Based on pre- and post-salvage characteristics, we are able to identify patients with a high risk of BF. These findings can aid patient counselling for FS-HDR-BT.

New method to monitor RF safety in MRI-guided interventions based on RF induced image artefacts.

PURPOSE: Serious tissue heating may occur at the tips of elongated metallic structures used in MRI-guided interventions, such as vascular guidewires, catheters, biopsy needles, and brachytherapy needles. This heating is due to resonating electromagnetic radiofrequency (RF) waves along the structure. Since it is hard to predict the exact length at which resonance occurs under in vivo conditions, there is a need for methods to monitor this resonance behavior. In this study, the authors propose a method based on the RF induced image artefacts and demonstrate its applicability in two phantom experiments. METHODS: The authors developed an analytical model that describes the RF induced image artefacts as a function of the induced current in an elongated metallic structure placed parallel to the static magnetic field. It describes the total RF field as a sum of the RF fields produced by the transmit coil of the MR scanner and by the elongated metallic structure. Several spoiled gradient echo images with different nominal flip angle settings were acquired to map the B1+ field, which is a quantitative measure for the RF distortion around the structure. From this map, the current was extracted by fitting the analytical model. To investigate the sensitivity of our method we performed two phantom experiments with different setup parameters: One that mimics a brachytherapy needle insertion and one that resembles a guidewire intervention. In the first experiment, a short needle was placed centrally in the MR bore to ensure that the induced currents would be small. In the second experiment, a longer wire was placed in an off-center position to mimic a worst case scenario for the patient. In both experiments, a Luxtron (Santa Clara, CA) fiberoptic temperature sensor was positioned at the structure tip to record the temperature. RESULTS: In the first experiment, no significant temperature increases were measured, while the RF image artefacts and the induced currents in the needle increased with the applied insertion depth. The maximum induced current in the needle was 44 mA. Furthermore, a standing wave pattern became clearly visible for larger insertion depths. In the second experiment, significant temperature increases up to 2.4 degrees C in 1 min were recorded during the image acquisitions. The maximum current value was 1.4 A. In both experiments, a proper estimation of the current in the metallic structure could be made using our analytical model. CONCLUSIONS: The authors have developed a method to quantitatively determine the induced current in an elongated metallic structure from its RF distortion. This creates a powerful and sensitive method to investigate the resonant behavior of RF waves along elongated metallic structures used for MRI-guided interventions, for example, to monitor the RF safety or to inspect the influence of coating on the resonance length. Principally, it can be applied under in vivo conditions and for noncylindrical metallic structures such as hip implants by taking their geometry into account.

Focal salvage treatment for radiorecurrent prostate cancer: A magnetic resonance-guided stereotactic body radiotherapy versus high-dose-rate brachytherapy planning study.

BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI)-guided focal salvage high-dose-rate brachytherapy (FS-HDR-BT) is one of the treatment options for radiorecurrent localized prostate cancer. However, due to the invasive nature of the treatment, not all patients are eligible. Magnetic resonance linear accelerator (MR-Linac) systems open up new treatment possibilities and could potentially replace FS-HDR-BT treatment. We conducted a planning study to investigate the feasibility of delivering a single 19 Gy dose to the recurrent lesion using a 1.5 Tesla MR-Linac system. MATERIALS AND METHODS: Thirty patients who underwent FS-HDR-BT were included. The clinical target volume (CTV) encompassed the visible lesion plus a 5 mm margin. Treatment plans were created for a 1.5 Tesla MR-Linac system using a 1 mm planning target volume (PTV) margin. A dose of 19 Gy was prescribed to ≥ 95% of the PTV. In case this target could not be reached, i.e. when organs-at-risk (OAR) constraints were violated, a dose of ≥ 17 Gy to ≥ 90% of the PTV was accepted. MR-Linac plans were compared to clinical FS-HDR-BT plans. RESULTS: Target dose coverage was achieved in 14/30 (47%) FS-HDR-BT plans and 17/30 (57%) MR-Linac plans, with comparable median D95% and D90%. In FS-HDR-BT plans, a larger volume reached ≥ 150% of the prescribed dose. Urethra D10%, rectum D1cm3, and rectum D2cm3 were lower in the FS-HDR-BT plans, while bladder dose was comparable for both modalities. CONCLUSION: Single fraction treatment of recurrent prostate cancer lesions may be feasible using stereotactic body radiotherapy (SBRT) on a MR-Linac system.

MRI-Guided Ultrafocal Salvage High-Dose-Rate Brachytherapy for Localized Radiorecurrent Prostate Cancer: Updated Results of 50 Patients.

PURPOSE: Most patients with local prostate cancer recurrence after radiation therapy undergo palliative androgen deprivation therapy because whole-gland salvage treatments have a high risk of severe toxicity. Focal treatment reduces this risk while offering a second opportunity for cure. We report updated outcomes of ultrafocal salvage high-dose-rate brachytherapy (HDR-BT). METHODS AND MATERIALS: Prospectively collected data from the first 50 treated patients were analyzed. Disease status was assessed by 3T multiparametric magnetic resonance imaging (MRI), 18F-Choline or 68Ga-prostate-specific membrane antigen positron emission tomography/computed tomography, and systematic or tumor-targeted biopsies. Ultrafocal salvage HDR-BT (1 × 19 Gy) was performed by implanting the clinical target volume (CTV: gross tumor volume + 5 mm margin) under fused transrectal ultrasound/MRI guidance. Follow-up included toxicity grading (using Common Terminology Criteria for Adverse Events 4.0), quality of life assessment, and prostate-specific antigen (PSA) testing. RESULTS: Median follow-up was 31 months. Median CTV D95% was 18.8 Gy. We observed 2% grade 3 genitourinary toxicity, no grade 3 gastrointestinal toxicity, and 22% newly developed grade 3 erectile dysfunction. Five of 13 patients (38%) with self-reported pretreatment potency (International Index of Erectile Function >17) remained potent. Clinically relevant quality of life deterioration was reported for only 6 of 31 items and was not statistically significant. Biochemical failure (nadir + 2) occurred in 26 patients. Among intraprostatic recurrences, 73% were in field. After 2.5 years, biochemical disease-free survival was 51% (95% confidence interval, 37%-69%), metastases-free survival was 75% (64%-89%), androgen deprivation therapy-free survival was 90% (82%-99%), and overall survival was 98% (94%-100%). Presalvage PSA, CTV size, and stage ≥T3 were significantly associated with biochemical failure. Higher-risk patients (stage ≥T3, PSA ≥10, or PSA double time ≤9 months) had 25% biochemical disease-free survival at 2.5 years versus 71% for lower-risk patients. CONCLUSIONS: At this early stage, MRI-guided ultrafocal HDR-BT seems to be a safe salvage treatment option, with acceptable biochemical control in a well-selected group of patients and potential for effectively postponing androgen deprivation therapy.

MRI artifact simulation for clinically relevant MRI sequences for guidance of prostate HDR brachytherapy.

For the purpose of magnetic resonance imaging (MRI) guidance of prostate high-dose-rate (HDR) brachytherapy, this paper presents a study on the potential of clinically relevant MRI sequences to facilitate tracking or localization of brachytherapy devices (HDR source/titanium needle), and which could simultaneously be used to visualize the anatomy. The tracking or localization involves simulation of the MRI artifact in combination with a template matching algorithm. Simulations of the MRI artifacts induced by an HDR brachytherapy source and a titanium needle were implemented for four types of sequences: spoiled gradient echo, spin echo, balanced steady-state free precession (bSSFP) and bSSFP with spectral attenuated inversion recovery (SPAIR) fat suppression. A phantom study was conducted in which mentioned sequences (in 2D) as well as the volumetric MRI sequences of the current clinical scan protocol were applied to obtain the induced MRI artifacts for an HDR source and a titanium needle. Localization of the objects was performed by a phase correlation based template matching algorithm. The simulated images demonstrated high correspondences with the acquired MR images, and allowed localization of the objects. A comparison between the object positions obtained for all applied MRI sequences showed deviations (from the average position) of 0.2-0.3 mm, proving that all MRI sequences were suitable for localization of the objects, irrespective of their 2D or volumetric nature. This study demonstrated that the MRI artifact induced by an HDR source or a titanium needle could be simulated for the four investigated types of MRI sequences (spoiled gradient echo, spin echo, bSSFP and bSSFP-SPAIR), valuable for real-time object localization in clinical practice. This leads to more flexibility in the choice of MRI sequences for guidance of HDR brachytherapy, as they are suitable for both object localization and anatomy visualization.

MRI-Guided Ultrafocal HDR Brachytherapy for Localized Prostate Cancer: Median 4-Year Results of a feasibility study.

PURPOSE: For the treatment of localized prostate cancer, focal therapy has the potential to cure with fewer side effects than traditional whole-gland treatments. We report an update on toxicity, quality of life (QoL), and tumor control in our magnetic resonance imaging (MRI)-guided ultrafocal high-dose-rate brachytherapy cohort. METHODS AND MATERIALS: Disease status was evaluated by systematic biopsies and 3T multiparametric MRI. The brachytherapy implant procedure under fused transrectal ultrasound/MRI guidance was followed by a 1.5 T MRI for contour adjustments and catheter position verification. A single dose of 19 Gy was delivered to the tumor with a margin of 5 mm. Genitourinary (GU) toxicity, gastrointestinal (GI) toxicity, and erectile dysfunction (ED) were graded with the Common Terminology Criteria for Adverse Events version 4.0. QoL was measured with RAND-36, European Organisation for Research and Treatment of Cancer QLQ-C30 and PR25. International Prostate Symptom Scores and International Index of Erectile Function scores were obtained. Prostate-specific antigen level was monitored, with biochemical recurrence defined as nadir + 2 ng/mL (Phoenix). RESULTS: Thirty patients with National Comprehensive Cancer Network low- (13%) to intermediate-risk (87%) prostate cancer were treated between May 2013 and April 2016. Median follow-up was 4 years. Median age was 71 years (interquartile range, 68-73) and median initial prostate-specific antigen level was 7.3 ng/mL (5.2-8.1). Maximum Gleason score was 4 + 3 = 7 (in 2 patients). All tumors were radiologic (MRI) stage T2. No grade >2 GU or >1 GI toxicity occurred. International Prostate Symptom Scores only deteriorated temporarily. Mild pretreatment ED deteriorated to moderate/severe ED in 50% of patients. Long-term clinically relevant QoL deterioration was seen in sexual activity and tiredness, whereas emotional and cognitive functioning improved. At 4 years, biochemical disease-free survival was 70% (95% confidence interval, 52%-93%), metastases-free survival was 93% (85%-100%), and overall survival was 100%. Of intraprostatic recurrences, 7 of 9 were out of field. CONCLUSIONS: Ultrafocal high-dose-rate brachytherapy conveys minimal GU or GI toxicity and has a marginal effect on QoL. An early decline in erectile function was seen. Tumor control outcomes are poor (biochemical disease-free survival of 70% [52%-93%] at 4 years), most likely as a result of poor patient selection.

Feasibility of adequate dose coverage in permanent prostate brachytherapy using divergent needle insertion methods.

BACKGROUND AND PURPOSE: The purpose of this study is to investigate the feasibility of adequate dose coverage in permanent prostate brachytherapy using divergent needle insertion methods. These methods can be useful in magnetic resonance imaging (MRI) guided needle insertion techniques to avoid pubic arch interference. METHODS AND MATERIALS: MRI data were collected from 10 patients with T1-T2 prostate cancer. An inverse planning algorithm based on simulated annealing was used to optimize the dose distribution for three needle insertion methods: divergent needles with a single rotation point, divergent needles with a double rotation point, and current parallel needle insertion method. The dose constraints were based on our clinical criteria and the recent ESTRO/EAU/EORTC recommendations. RESULTS: If the planning target volume (PTV) surrounded the prostate and only intraprostatic seeds were allowed, the mean PTV volume that received 100% of the prescribed dose (V(100)) was 99% for all needle insertion methods. If the PTV was increased to the prostate with a 3mm margin, the mean PTV V(100) equalled 94%, 95%, and 94% for the single rotation point, double rotation point and current parallel needle insertion method, respectively. If in the latter case the tips of the seeds were placed 3mm outside the apex and base of the prostate, the mean PTV V(100) was 96% for all needle insertion methods. CONCLUSION: This planning study shows that it is feasible to generate an adequate dose coverage using divergent needle insertion methods.

Development and Testing of a Magnetic Resonance (MR) Conditional Afterloader for Source Tracking in Magnetic Resonance Imaging-Guided High-Dose-Rate (HDR) Brachytherapy.

PURPOSE: For the purpose of magnetic resonance imaging (MRI)-guided high-dose-rate (HDR) brachytherapy, a prototype magnetic resonance (MR) conditional afterloader was developed. This study demonstrates the development and testing of the prototype, while operating simultaneously with MRI. In combination with an MR-based method for HDR source localization, this development enables treatment verification of HDR brachytherapy. Additionally, this allows a direct reconstruction of the source dwell positions after catheter insertion (when using a dummy source) and introduction of a clinical workflow where the patient remains in the same position during dwell position reconstruction, treatment planning and irradiation. METHODS AND MATERIALS: A prototype MR conditional afterloader was developed by providing radiofrequency (RF) shielding and a plastic source cable containing a dummy source. Simultaneous functioning of the afterloader and MRI acquisition was tested in an experimental setting where the afterloader was placed next to the scanner and programmed to send the source to predefined positions within a phantom, while acquiring MR images. The HDR source positions were determined using MR artifact simulation and matching of the MR images to the simulated artifact. Additionally, the impact of the presence and use of the afterloader on the MRI performance was investigated by assessment of RF interference, signal-to-noise ratio (SNR), and B0 field homogeneity. RESULTS: The experiments demonstrated that the prototype MR conditional afterloader and the MRI scanner fully functioned while operating simultaneously, without influencing the other system. The step sizes between the source positions obtained from the MR images corresponded with the afterloader settings. Besides, the MRI performance tests demonstrated no deterioration due to the presence or functioning of the afterloader next to the scanner. CONCLUSIONS: This research has demonstrated the feasibility of simultaneous MR acquisition and employment of an MR conditional afterloader. This development enables real-time HDR source localization for treatment verification of MRI-guided HDR brachytherapy using an MR conditional afterloader.

The effect of catheter displacement and anatomical variations on the dose distribution in MRI-guided focal HDR brachytherapy for prostate cancer.

PURPOSE: The aim of this study was to analyze the effect of catheter displacement and anatomical variations of prostate and organs at risk on dose distribution in MRI-guided 19 Gy single fraction focal high-dose-rate brachytherapy (HDR-BT) of the prostate. METHODS AND MATERIALS: Seventeen patients with localized prostate cancer were enrolled in a prospective trial investigating focal HDR-BT in a 1.5 T MRI-HDR-BT facility. The diagnostic MRI delineations were registered with intraoperative MR scan, and a single fraction of 19 Gy was applied to the visible tumor. Self-anchoring umbrella catheters were used for HDR-BT delivery. A 1.5 T MRI was performed directly after ultrasound (US)-guided catheter placement for treatment planning. After treatment and before removal of catheters, a posttreatment 1.5 T MRI was performed. Regions of interest were also delineated on the posttreatment MR images and the catheters of 17 patients were reconstructed. The dose plan was constructed for the posttreatment MRI scan to assess the influence of catheter migration and anatomical variation on the dose delivered to the target and the organs at risk. Also on the posttreatment MRI, the complete catheter reconstruction was reassessed, to correct for, for example, bending of the catheters. The displacement of catheters between the MRI scans was determined by comparing the catheter tip positions on the treatment planning and posttreatment 1.5 T MRI scans. RESULTS: The displacements of 241 catheters were investigated. Average (range) displacements of the umbrella catheters are 0.6 (0-2.9) mm in the x-direction, 0.5 (0-2.1) mm in the y-direction, and 0.9 (0-5.5) mm in the z-direction. In 3 patients, the displacement was >4 mm and up to 5.5 mm. This occurred in respectively 1/13, 1/16, and 1/18 catheters in these patients. The dosimetric differences between the intraoperative treatment and the posttreatment plans were in most patients less than 1.5 Gy. In 4 patients, a dose difference in clinical target volume D95 of >2 Gy up to 5.8 Gy was reported. No discrimination can be made between dose differences due to catheter displacement and/or organ movement/anatomy changes. CONCLUSIONS: In general, catheter displacements were in the order of a mm and differences in dose to the clinical target volume and the organs at risk between the treatment and posttreatment plans smaller than 1.5 Gy. In some patients, dose differences up to 5.8 Gy were determined, due to either individual larger catheter displacement and/or anatomy changes. A longer followup is necessary to assess the clinical implications of individual large dose differences.

Re-salvage MRI-guided Focal High-dose-rate Brachytherapy for Locally Recurrent Prostate Cancer.

Prostate cancer recurrences are common, even with twenty-first-century primary prostate cancer treatment modalities. The most common salvage treatment is (delayed) hormonal therapy, which is often associated with serious side-effects. Due to the risk of significant toxicity, whole-gland targeted salvage treatments remain unpopular. Consequently, developments in focal therapies have arisen. Magnetic resonance imaging (MRI)-guided focal salvage high-dose-rate brachytherapy (HDR-BT) is a novel treatment aiming for minimal toxicity in recurrent prostate cancer patients. Repeating focal treatment could, therefore, be possible in case of post-salvage recurrence. We report the case of a 77-year-old man who underwent repeat focal HDR-BT.

Development and internal validation of prediction models for biochemical failure and composite failure after focal salvage high intensity focused ultrasound for local radiorecurrent prostate cancer: Presentation of risk scores for individual patient prognoses.

PURPOSE: Patient selection for focal salvage remains difficult. Therefore, we developed and internally validated prediction models for biochemical failure (BF) and a composite endpoint (CE) following focal salvage high intensity focused ultrasound (HIFU) for radiorecurrent prostate cancer. MATERIALS AND METHODS: A prospective HIFU registry identified 150 cases (November 2006-August 2015). Recurrence was assessed with multiparametric magnetic resonance imaging (MRI) combined with template prostate mapping biopsies, targeted biopsies, or systematic transrectal ultrasound-guided biopsies. Metastatic disease was ruled out with a positron emission tomography-computed tomography and a bone scan. Focal salvage HIFU consisted of quadrant-ablation, hemi-ablation, or index-lesion ablation. Cox-regression was used for BF (Phoenix-definition) and CE (BF/MRI+/biopsies+/local or systemic treatment/metastases+/prostate cancer specific mortality+). Internal validation was performed using bootstrap resampling (500 datasets) after which C-statistic and hazard ratios were adjusted. Models were calibrated and risk scores created. RESULTS: Median follow-up was 35 months (interquartile range: 22-52). Median biochemical disease-free survival (DFS) was 33 months (95% CI: 23-45). Median CE-free survival was 24 months (95% CI: 21-35). After multivariable analysis, DFS interval after primary radiotherapy, presalvage prostate-specific antigen (PSA), PSA-doubling time, prostatic volume, and T-stage (both MRI based) predicted BF. For the CE, PSA-doubling time was not predictive but additionally, primary Gleason score was. The adjusted C-statistics were 0.68 and 0.64 for BF and CE, respectively. Calibration was accurate until 48 months. The risk scores showed 3 groups, with biochemical DFS of 60%, 35%, and 7% and CE-free survival of 40%, 24%, and 0% at 4 years. CONCLUSION: Our model, once externally validated, could allow for better selection of patients for focal salvage HIFU.

MRI guided focal HDR brachytherapy for localized prostate cancer: Toxicity, biochemical outcome and quality of life.

PURPOSE: To describe toxicity, biochemical outcome and quality of life after MRI guided focal high dose rate brachytherapy (HDR-BT) in a single fraction of 19 Gy for localized prostate cancer. MATERIALS AND METHODS: Between May 2013 and April 2016, 30 patients were treated by MRI-guided focal HDR-BT. Patients with visible tumour on MRI were included. All patients were ≥65 years, T-stage

Challenges in MR-only seed localization for postimplant dosimetry in permanent prostate brachytherapy.

PURPOSE: An MR-only postimplant dosimetry workflow for low dose rate (LDR) brachytherapy could reduce patient burden, improve accuracy, and improve cost efficiency. However, localization of brachytherapy seeds on MRI scans remains a major challenge for this type of workflow. In this study, we propose and validate an MR-only seed localization method and identify remaining challenges. METHODS AND MATERIALS: The localization method was based on template matching of simulations of complex-valued imaging artifacts around metal brachytherapy seeds. The method was applied to MRI scans of 25 prostate cancer patients who underwent LDR brachytherapy and for whom postimplant dosimetry was performed after 4 weeks. The seed locations found with the MR-only method were validated against the seed locations found on CT. The circumstances in which detection errors were made were classified to gain an insight in the nature of the errors. RESULTS: A total of 1490 of 1557 (96%) seeds were correctly detected, while 67 false-positive errors were made. The correctly detected seed locations had a high spatial accuracy with an average error of 0.8 mm compared with CT. A majority of the false positives occurred near other seeds. Most false negatives were found in either stranded configurations without spacers or near other seeds. CONCLUSIONS: The low detection error rate and high localization accuracy obtained by the complex-valued template matching approach are promising for future clinical application of MR-only dosimetry. The most important remaining challenge is robustness with regard to configurations of multiple seeds in close vicinity, such as in strands of seeds without spacers. This issue could potentially be resolved by simulating specific configurations of multiple seeds or by constraining the treatment planning to avoid these configurations, which could make the proposed method competitive with CT-based seed localization.

Pulse sequence considerations for simulation and postimplant dosimetry of prostate brachytherapy.

PURPOSE: The purpose of this work is to present a brief review of MRI physics principles pertinent to prostate brachytherapy, and a summary of our experience in optimizing protocols for prostate brachytherapy applications. METHODS AND MATERIALS: We summarized essential MR imaging characteristics and their interplays that need to be considered for prostate brachytherapy applications. These include spatial resolution, signal-to-noise ratio, image contrast, artifacts, geometric distortion, specific absorption rate, and total scan time. We further described the optimization of the protocols for three pulse sequences: three-dimensional (3D) fast-spoiled gradient echo sequence for T1-weighted imaging, 3D fast-spin echo sequence for T2-weighted imaging, and 3D fast imaging in steady-state precession sequence for combined T1 and T2-weighed imaging. The utilization of an endorectal coil was also described. RESULTS: Using the optimized protocols, we acquired high-quality images of the entire prostate within 3-5 minutes for each sequence. These images display the desired image contrasts and a spatial resolution that is equal to or better than 0.59 mm × 0.73 mm × 1.2 mm. While 3D fast-spoiled gradient echo sequence and 3D fast-spin echo sequence depict radioactive seed markers and anatomic structures separately, 3D fast imaging in steady-state precession sequence demonstrates great promise for imaging both seed markers and prostate anatomy simultaneously in a single acquisition. CONCLUSIONS: We have optimized current MRI protocols and demonstrated that the anatomic structures and positive contrast radioactive seed markers for prostate post-implant dosimetry can be adequately imaged either separately or simultaneously using different pulse sequences within a total scan time of 3-5 minutes each.

Dosimetric impact of contouring and image registration variability on dynamic 125I prostate brachytherapy.

PURPOSE: The quality of permanent prostate brachytherapy can be increased by addition of imaging modalities in the intraoperative procedure. This addition involves image registration, which inherently has inter- and intraobserver variabilities. We sought to quantify the inter- and intraobserver variabilities in geometry and dosimetry for contouring and image registration and analyze the results for our dynamic 125I brachytherapy procedure. METHODS AND MATERIALS: Five observers contoured 11 transrectal ultrasound (TRUS) data sets three times and 11 CT data sets one time. The observers registered 11 TRUS and MRI data sets to cone beam CT (CBCT) using fiducial gold markers. Geometrical and dosimetrical inter- and intraobserver variabilities were assessed. For the contouring study, structures were subdivided into three parts along the craniocaudal axis. RESULTS: We analyzed 165 observations. Interobserver geometrical variability for prostate was 1.1 mm, resulting in a dosimetric variability of 1.6% for V100 and 9.3% for D90. The geometric intraobserver variability was 0.6 mm with a V100 of 0.7% and D90 of 1.1%. TRUS-CBCT registration showed an interobserver variability in V100 of 2.0% and D90 of 3.1%. Intraobserver variabilities were 0.9% and 1.6%, respectively. For MRI-CBCT registration, V100 and D90 were 1.3% and 2.1%. Intraobserver variabilities were 0.7% and 1.1% for the same. CONCLUSIONS: Prostate dosimetry is affected by interobserver contouring and registration variability. The observed variability is smaller than underdosages that are adapted during our dynamic brachytherapy procedure.

Cone-beam CT-based adaptive planning improves permanent prostate brachytherapy dosimetry: An analysis of 1266 patients.

PURPOSE: To evaluate adaptive planning for permanent prostate brachytherapy and to identify the prostate regions that needed adaptation. METHODS AND MATERIALS: After the implantation of stranded seeds, using real-time intraoperative planning, a transrectal ultrasound (TRUS)-scan was obtained and contoured. The positions of seeds were determined on a C-arm cone-beam computed tomography (CBCT)-scan. The CBCT-scan was registered to the TRUS-scan using fiducial gold markers. If dose coverage on the combined image-dataset was inadequate, an intraoperative adaptation was performed by placing remedial seeds. CBCT-based intraoperative dosimetry was analyzed for the prostate (D90, V100, and V150) and the urethra (D30). The effects of the adaptive dosimetry procedure for Day 30 were separately assessed. RESULTS: We analyzed 1266 patients. In 17.4% of the procedures, an adaptation was performed. Without the dose contribution of the adaptation Day 30 V100 would be < 95% for half of this group. On Day 0, the increase due to the adaptation was 11.8 ± 7.2% (1SD) for D90 and 9.0 ± 6.4% for V100. On Day 30, we observed an increase in D90 of 12.3 ± 6.0% and in V100 of 4.2 ± 4.3%. For the total group, a D90 of 119.6 ± 9.1% and V100 of 97.7 ± 2.5% was achieved. Most remedial seeds were placed anteriorly near the base of the prostate. CONCLUSION: CBCT-based adaptive planning enables identification of implants needing adaptation and improves prostate dose coverage. Adaptations were predominantly performed near the anterior base of the prostate.

Focal MRI-Guided Salvage High-Dose-Rate Brachytherapy in Patients With Radiorecurrent Prostate Cancer.

INTRODUCTION: Whole-gland salvage treatment of radiorecurrent prostate cancer has a high rate of severe toxicity. The standard of care in case of a biochemical recurrence is androgen deprivation treatment, which is associated with morbidity and negative effects on quality of life. A salvage treatment with acceptable toxicity might postpone the start of androgen deprivation treatment, might have a positive influence on the patients' quality of life, and might even be curative. Here, toxicity and biochemical outcome are described after magnetic resonance imaging-guided focal salvage high-dose-rate brachytherapy in patients with radiorecurrent prostate cancer. MATERIALS AND METHODS: Seventeen patients with pathologically proven locally recurrent prostate cancer were treated with focal high-dose-rate brachytherapy in a single 19-Gy fraction using magnetic resonance imaging for treatment guidance. Primary radiotherapy consisted of external beam radiotherapy or low-dose-rate brachytherapy. Tumors were delineated with Ga-68-prostate-specific membrane antigen or F18-choline positron emission tomography in combination with multiparametric magnetic resonance imaging. All patients had a prostate-specific antigen level of less than 10 ng/mL at the time of recurrence and a prostate-specific antigen doubling time of ≥12 months. Toxicity was measured by using the Common Terminology Criteria for Adverse Events version 4. RESULTS: Eight of 17 patients had follow-up interval of at least 1 year. At a median follow-up interval of 10 months (range 3-40 months), 1 patient experienced a biochemical recurrence according to the Phoenix criteria, and prostate-specific membrane antigen testing revealed that this was due to a distant nodal metastasis. One patient had a grade 3 urethral stricture at 2 years after treatment. CONCLUSION: Focal salvage high-dose-rate brachytherapy in patients with radiorecurrent prostate cancer showed grade 3 toxicity in 1 of 17 patients and a distant nodal metastasis in another patient. Whether this treatment option leads to cure in a subset of patients or whether it can successfully postpone androgen deprivation treatment needs further investigation.

A new robotic needle insertion method to minimise attendant prostate motion.

BACKGROUND AND PURPOSE: The purpose of this study is to investigate the efficacy of a new needle insertion method (tapping instead of pushing) in reducing attendant tissue motion. This can be useful in applications where tissue motion due to needle insertion is problematic such as e.g. MRI-guided prostate brachytherapy and breast biopsies. In this study we will focus on prostate motion due to needle insertion. MATERIAL AND METHODS: Prostate motion due to needle insertion was measured in 30 patients, who were transperineally implanted with fiducial gold markers for position verification in prostate intensity modulated radiotherapy. In total 32 needles were manually pushed into the prostate and 29 were tapped with a prototype robotic system. The prostate motion in the cranio-caudal direction was measured on the video record of the ultrasound images. Differences in prostate motion between the two needle insertion methods were analysed making use of SPSS. RESULTS: The mean prostate motion was 5.6mm (range 0.3-21.6) when the needle was pushed and 0.9 mm (range 0-2.0) when the needle was tapped into the prostate (p<0.001). CONCLUSION: Prostate motion was significantly less when the needle was tapped into the prostate compared to when the needle was pushed. This result is important for the development of a tapping, MRI-guided, prostate implant robotic system.