PURPOSE:Ultra-hypofractionation (UHF) has emerged as a safe and effective strategy; however, its role in prostate cancer (PCa) pelvic nodal irradiation combined with high-dose-rate brachytherapy (HDR-BT) and androgen deprivation therapy (ADT) remains insufficiently defined. PCS-XI (NCT05820633) is a multicentre, phase III randomized trial evaluating pelvic UHF versus conventionally fractionated (CF) radiotherapy. We report a prespecified interim analysis focusing on toxicity and patient-reported outcomes (PROs). METHODS:Men with unfavorable-intermediate to very-high-risk prostate adenocarcinoma were enrolled. Patients were randomized 1:1 to CF (43 Gy/20 fractions, 44 Gy/22 fractions, or 46 Gy/23 fractions) or UHF (25 Gy in 5 fractions delivered every other day) whole pelvis radiotherapy, combined with single-fraction 15 Gy HDR-BT to the prostate with concomitant ADT. Genitourinary and gastrointestinal toxicities (CTCAE v5.0) and PROs (IPSS, SHIM, EPIC-26) were collected longitudinally. RESULTS:At interim analysis, 142 patients were randomized (CF = 73; UHF = 69), with a median follow-up of 17.6 months. Baseline clinicopathologic characteristics, ADT exposure, and treatment volumes were well balanced between arms. Grade 2-3 GU and GI toxicity rates were low and comparable between arms. No grade 4-5 toxicities were observed. Longitudinal PRO analyses demonstrated parallel trajectories. Clinically meaningful differences favoring UHF were observed for urinary incontinence at 12 months and bowel function at 18 months. Conversely, the CF arm demonstrated superior early hormonal function at 3 and 9 months. CONCLUSIONS:Pelvic UHF combined with HDR-BT and ADT was well tolerated compared to CF. These findings support its short-term safety and tolerability. Longer follow-up is required to prove non-inferiority and assess oncologic outcomes.

Purpose gMCO generated plans for HDR prostate brachytherapy have been shown to be superior to standard reference clinical plans in a blinded pairwise comparison[1]. The purpose of this work, a first-in-man trial, was to compare gMCO and reference plans in terms of planning time and plan quality for prostate HDR brachytherapy 15Gy boosts in a randomized clinical trial. Materials and Methods The brachytherapy procedure was as follows: 1) Patient walk-in/installation/anaesthesia 2) Positioning/Catheter implantation under transrectal ultrasound (US) guidance 3) 3D US scan 4) Contouring/catheter reconstruction on Oncentra Prostate (Elekta, Veenendaal, Netherlands) 5) Planning 6) Treatment. Planning (step 5) was performed, after randomization, using either IPSA (Oncentra Prostate, Veenendaal, Netherlands) or gMCO (in-house platform). For gMCO planning, the contours and reconstructed catheters were exported to gMCO at step 4) and the resulting plan was imported on OCP at step 6). The planning times on IPSA or gMCO were recorded. Patients previously had a planning MR in order to identify the gross tumor volume (GTV, PIRADS 3 and above)and, if present, received a boost of 125% of the prescription dose. At the time of writing, 55 (of 60) patients have been accrued and treated on this trial. Of those, only 10 patients had no GTV. Dosimetric parameters (Prostate V100, V150, V200, GTV D90, Urethra D10, Rectum and Bladder V75 and D1cc) of gMCO and IPSA plans were compared (Student's T test) to determine if plan quality and planning times were statistically different. Results Figure 1 shows a) a boxplot of the the planning times (minutes), b) a boxplot of the GTV D90 coverage (Gy) and c) a histogram of the proportion of GTVs with more than 19, 19.5 and 20 Gy D90 coverage for gMCO and IPSA for the 55 accrued patients (29 gMCO and 26 IPSA). Figure 1 a) shows that the median planning time for clinical cases is roughly halved (p=0.0002) for gMCO (5.0 min) compared to IPSA (10.0 min) and b) shows a trend towards higher GTV D90s for gMCO planning compared to IPSA (p=0.26). The median GTV volume and standard deviation was 3.5 cc (4.2 cc std) for gMCO and 2.8 cc (2.3 cc std) for IPSA patients (p=0.21). Additionally, we found no learning curve effect in the planning using gMCO. No statistically significant differences were found between dosimetric parameters for the prostate V100, V150, D90, Bladder V75, Rectum V75 and Urethra D10. The prostate V200 was statistically higher for gMCO (p=0.048), possibly because of higher GTV D90 to the (19.8 Gy) compared to IPSA (19.3 Gy). Figure 1c) shows that a superior GTV D90 coverage can be obtained more consistently for gMCO as compared to IPSA at 19, 19.5 and 20 Gy. Conclusion This work presents a first-in-man trial of GPU based multicriteria optimization in prostate HDR brachytherapy. The planning time was halved when using gMCO as compared to IPSA. Better GTV D90s were achieved without compromising the OARs. No learning curve effect was present in gMCO planning. [1] C. Bélanger et al., “Inter-observer evaluation of a GPU-based multicriteria optimization algorithm combined with plan navigation tools for HDR brachytherapy”, Brachytherapy 21 (2022), 551-560.

PURPOSE:ACR and AAPM task group's guidelines addressing commissioning for dedicated MR simulators were recently published. The goal of the current paper is to present the authors' 2-year experience regarding the commissioning and introduction of a QA program based on these guidelines and an associated automated workflow. METHODS:All mandatory commissioning tests suggested by AAPM report 284 were performed and results are reported for two MRI scanners (MAGNETOM Sola and Aera). Visual inspection, vendor clinical or service platform, third-party software, or in-house python-based code were used. Automated QA and data analysis was performed via vendor, in-house or third-party software. QATrack+ was used for QA data logging and storage. 3D geometric distortion, B0 inhomogeneity, EPI, and parallel imaging performance were evaluated. RESULTS:Contrasting with AAPM report 284 recommendations, homogeneity and RF tests were performed monthly. The QA program allowed us to detect major failures over time (shimming, gradient calibration and RF interference). Automated QA, data analysis, and logging allowed fast ACR analysis daily and monthly QA to be performed in 3 h. On the Sola, the average distortion is 1 mm for imaging radii of 250 mm or less. For radii of up to 200 mm, the maximum, average (standard deviation) distortion is 1.2  and 0.4 mm (0.3 mm). Aera values are roughly double the Sola for radii up to 200 mm. EPI geometric distortion, ghosting ratio, and long-term stability were found to be under the maximum recommended values. Parallel imaging SNR ratio was stable and close to the theoretical value (ideal g-factor). No major failures were detected during commissioning. CONCLUSION:An automated workflow and enhanced QA program allowed to automatically track machine and environmental changes over time and to detect periodic failures and errors that might otherwise have gone unnoticed. The Sola is more geometrically accurate, with a more homogenous B0 field than the Aera.

Purpose To evaluate the biochemical cure rate at 4 or more years (defined by PSA<0.2ng/ml) after ultra hypofractionated radiotherapy (UHF) combined with high dose rate (HDR) brachytherapy boost (BB) in comparison to a moderate hypofractionated (MHF) regimen, in patients treated for intermediate risk prostate cancer(according to NCCN guidelines). Materials and Methods In this prospective single institution study, 28 patients with intermediate risk prostate cancer were recruited to the experimental treatment of 25 Gy in 5 fractions using image guided radiation therapy (IGRT) plus a 15 Gy HDR BB. They were compared to two historical control groups, treated with either 36 Gy in 12 fractions or 37.5 Gy in 15 fractions with an identical HDR BB. The control groups included 151 and 311 patients respectively. Patients in the experimental cohort for UHF treatment regimen were enrolled between July 2015 and November 2016. Follow up visits and PSA testing were scheduled six weeks after the implant and every 4 months for the first year, then every 6 months for years 2 to 5 and yearly thereafter. The biochemical cure after brachytherapy (PSA <0.2ng/ml) > 4 years was defined according to the criteria defined by Crook et al [1], based on biochemical failure after radical prostatectomy. Results Of the 28 patients recruited, 3 died free of prostate cancer. At the time of analysis, median follow up was 81 months for the 25 Gy group, 47 months for the 36 Gy group and 60 months for the 37.5 Gy group. 85.7%, 78.8% and 67.8% of patients had a PSA <= 0.2ng/ml at more than 4 years in the UHF and both MHF groups, respectively. This difference was statistically significant (Chi-Square p-value = 0.012). The ISUP grade was not different between the three groups p= 0.64. However, in the 36 Gy group more patients with a PSA > 0.2ng/ml at 4 years had received short term androgen deprivation therapy (STADT) (p=0.0056). After logistic regression, no factor analyzed (total dose of radiotherapy, ISUP or STADT) were identified as related to a PSA level > 0.2ng/ml at 4 years (p= 0.74, p=0.65 and p=0.12 respectively). Estimated biochemical recurrence free survival at 4 years was 100% (standard error 0.00) for the UHF group, 95 % (0.02) for the 36 Gy arm and 91% (0.02) for the 37.5 Gy arm. Conclusion UHF treatment combined with HDR BB seems better than MHF in term of biochemical cure. Larger cohorts in prospective trial with longer follow up are currently ongoing and needed to confirm our findings. Keywords: Prostate cancer, Brachytherapy, Ultra hypofractionation, Biochemical cure. [1] Crook JM, Tang C, Thames H, Blanchard P, Sanders J, Ciezki J, et al. A biochemical definition of cure after brachytherapy for prostate cancer. Radiother Oncol 2020;149:64-9. https://doi.org/10.1016/j.radonc.2020.04.038. To evaluate the biochemical cure rate at 4 or more years (defined by PSA<0.2ng/ml) after ultra hypofractionated radiotherapy (UHF) combined with high dose rate (HDR) brachytherapy boost (BB) in comparison to a moderate hypofractionated (MHF) regimen, in patients treated for intermediate risk prostate cancer(according to NCCN guidelines). In this prospective single institution study, 28 patients with intermediate risk prostate cancer were recruited to the experimental treatment of 25 Gy in 5 fractions using image guided radiation therapy (IGRT) plus a 15 Gy HDR BB. They were compared to two historical control groups, treated with either 36 Gy in 12 fractions or 37.5 Gy in 15 fractions with an identical HDR BB. The control groups included 151 and 311 patients respectively. Patients in the experimental cohort for UHF treatment regimen were enrolled between July 2015 and November 2016. Follow up visits and PSA testing were scheduled six weeks after the implant and every 4 months for the first year, then every 6 months for years 2 to 5 and yearly thereafter. The biochemical cure after brachytherapy (PSA <0.2ng/ml) > 4 years was defined according to the criteria defined by Crook et al [1], based on biochemical failure after radical prostatectomy. Of the 28 patients recruited, 3 died free of prostate cancer. At the time of analysis, median follow up was 81 months for the 25 Gy group, 47 months for the 36 Gy group and 60 months for the 37.5 Gy group. 85.7%, 78.8% and 67.8% of patients had a PSA <= 0.2ng/ml at more than 4 years in the UHF and both MHF groups, respectively. This difference was statistically significant (Chi-Square p-value = 0.012). The ISUP grade was not different between the three groups p= 0.64. However, in the 36 Gy group more patients with a PSA > 0.2ng/ml at 4 years had received short term androgen deprivation therapy (STADT) (p=0.0056). After logistic regression, no factor analyzed (total dose of radiotherapy, ISUP or STADT) were identified as related to a PSA level > 0.2ng/ml at 4 years (p= 0.74, p=0.65 and p=0.12 respectively). Estimated biochemical recurrence free survival at 4 years was 100% (standard error 0.00) for the UHF group, 95 % (0.02) for the 36 Gy arm and 91% (0.02) for the 37.5 Gy arm. UHF treatment combined with HDR BB seems better than MHF in term of biochemical cure. Larger cohorts in prospective trial with longer follow up are currently ongoing and needed to confirm our findings. Keywords: Prostate cancer, Brachytherapy, Ultra hypofractionation, Biochemical cure. [1] Crook JM, Tang C, Thames H, Blanchard P, Sanders J, Ciezki J, et al. A biochemical definition of cure after brachytherapy for prostate cancer. Radiother Oncol 2020;149:64-9. https://doi.org/10.1016/j.radonc.2020.04.038.

Purpose We report our initial experience with the Getinge Pilot System, initially designed for neurosurgery, after it was modified to be used in a brachytherapy suite. The objective was to develop a workflow integrating Magnetic Resonance Imaging (MRI) and standard Computed Tomography (CT) for each GYN brachytherapy fraction without compromising patient access and minimizing motion. Materials and Methods The first 100 GYN brachytherapy fractions treated in the new facility were included in this analysis. The duration of each step of the procedure was acquired for every patient. Based on the available information, modifications were incorporated into the workflow to optimize the procedure and gain efficiency. Our analysis is focused on 2 specific steps of the procedure: preparation and transfer to the MRI (once the insertion of the applicators is completed and the patient is moved to the MRI) and the time between the end of the MRI and the completion of CT planning (transfer to a different room and completion of CT Scan). In order to evaluate the impact of the learning curve with this new technology, we analysed the average time of the first three fractions separately and compared it with the following 97 fractions. Results Fig.1 We observed a 56% reduction in the average time to complete the preparation and transfer to the MRI portion of the procedure over time, going from an average of 27 minutes for the first three fractions to an average of 12 min for the next 97 fractions (3-25 minutes). A similar reduction of 42% was observed for the time interval between the end of the MRI and the completion of CT, going from an average of 24 minutes for the first three fractions to 14 minutes (7-40 minutes) for the subsequent 97 fractions. Conclusions The time associated with the addition of MRI for every fraction and patient transfer from one room to the other was significantly reduced after adjustments were made to optimize the workflow. This new, time efficient workflow using the Getinge Pilot system allowed us to incorporate daily MR Imaging to standard CT treatment planning in GYN brachytherapy without a reduction in the number of cases treated on a daily basis compared to MR imaging only for the first fraction. The Getinge system, although it was designed for neurosurgery, is very well suited to the reality of brachytherapy interventions with multiple imaging. We report our initial experience with the Getinge Pilot System, initially designed for neurosurgery, after it was modified to be used in a brachytherapy suite. The objective was to develop a workflow integrating Magnetic Resonance Imaging (MRI) and standard Computed Tomography (CT) for each GYN brachytherapy fraction without compromising patient access and minimizing motion. The first 100 GYN brachytherapy fractions treated in the new facility were included in this analysis. The duration of each step of the procedure was acquired for every patient. Based on the available information, modifications were incorporated into the workflow to optimize the procedure and gain efficiency. Our analysis is focused on 2 specific steps of the procedure: preparation and transfer to the MRI (once the insertion of the applicators is completed and the patient is moved to the MRI) and the time between the end of the MRI and the completion of CT planning (transfer to a different room and completion of CT Scan). In order to evaluate the impact of the learning curve with this new technology, we analysed the average time of the first three fractions separately and compared it with the following 97 fractions. Fig.1 We observed a 56% reduction in the average time to complete the preparation and transfer to the MRI portion of the procedure over time, going from an average of 27 minutes for the first three fractions to an average of 12 min for the next 97 fractions (3-25 minutes). A similar reduction of 42% was observed for the time interval between the end of the MRI and the completion of CT, going from an average of 24 minutes for the first three fractions to 14 minutes (7-40 minutes) for the subsequent 97 fractions. The time associated with the addition of MRI for every fraction and patient transfer from one room to the other was significantly reduced after adjustments were made to optimize the workflow. This new, time efficient workflow using the Getinge Pilot system allowed us to incorporate daily MR Imaging to standard CT treatment planning in GYN brachytherapy without a reduction in the number of cases treated on a daily basis compared to MR imaging only for the first fraction. The Getinge system, although it was designed for neurosurgery, is very well suited to the reality of brachytherapy interventions with multiple imaging.

Purpose The study aimed to report clinical outcomes of high-risk prostate cancer (PCa) patients treated with external beam radiation therapy (EBRT) and high dose-rate boost (HDRB) according to CAPRA score. Material and Methods The study sample consisted of 361 high-risk PCa patients stratified according to D'Amico classification and treated with EBRT and HDRB and antiandrogen therapy (ADT) between 1999 and 2016. We conducted retrospective competing-risk survival analyses to compare individuals with a CAPRA score lesser than or equal to five and greater than five on biochemical recurrence (BCR) and metastasis incidence. Kaplan-Meier analysis was performed to assess overall survival (OS). Subsequently, we used ROC curves to compare the performance of the CAPRA model to the MSKCC stratification tool on BCR and metastasis incidence. Results The mean age of the patients at treatment time was 69.6±7.3 years. The median follow-up was 55.5 months. Of the 361 individuals, 52,4 % (n=189) had a CAPRA score above five. In comparison to individuals with a CAPRA score lesser than or equal to five, individuals with a CAPRA score above five were deemed at higher risk of BCR (sHR = 2.74, 95% CI: 1.12-6.66, p=0.027) and demonstrated a tendency towards significance in their metastasis incidence trend (sHR 2.33 95% CI: 0.89-6.12, p = 0.085). For 10-year OS, there was a HR for mortality of 1.89 (95% CI: 1.04-3.43, p=0.036) for individuals with a CAPRA score above five. There was no significant difference between either risk stratification strategy in ROC curves analysis. Conclusions The data suggest that patients' tumours classified as high-risk using the CAPRA score correlated with a higher risk of BCR, metastasis, and mortality when compared to lower-risk tumours. Further studies are needed to validate the use of the CAPRA score to predict cancer-specific mortality (CSM) as an initial risk stratification tool.

Purpose To evaluate the variability of prostate contours delineated on computed tomography (CT) and transrectal ultrasound (TRUS). Material and methods A TRUS-based high-dose-rate (HDR) brachytherapy procedure was introduced in 2016 in our center. The first thirty patients were additionally imaged with CT immediately after the treatment. In 2018, four different radiation oncologists (ROs: 1, 2, 3, 4) contoured the prostate on both modalities. A volume comparison was performed between CT and TRUS imaging. Using prostate gold fiducial makers, a rigid registration between CT and TRUS was done in 20 of the 30 patients studied. Jaccard index (JI) was computed to evaluate the inter-observer volume delineation agreement. Results The ratio of TRUS/CT volumes was 0.82 (95% CI: 0.79-0.87%). The mean JI was 87% for CT and 92% for TRUS, when comparing all four ROs; CT and TRUS JIs were significantly different (p < 0.001). The mean JI for the prostate on CT was significantly more consistent (p < 0.001) when comparing RO1, 2, and 3 together (RO1-2, RO1-3, and RO2-3; mean = 89%) than when comparing RO4 (newest to clinical practice) to others (RO1-4, RO2-4, and RO3-4; mean = 85%). For TRUS planning, the mean JI was not significantly different (p > 0.05) when comparing all ROs. Conclusions The inter-observer and intra-observer variability were statistically significantly smaller on TRUS compared to CT-based planning, despite varying ROs clinical experiences. The superior soft tissue contrast offered by TRUS obviates the effect of the ROs experience on prostate contour volumes and enables more reproducible prostate delineation.

PURPOSE: To evaluate the PSA outcomes and the late patient's reported health related quality of life (HRQOL) and toxicity after single-fraction High-Dose-Rate brachytherapy (HDRB) and Low-Dose-Rate brachytherapy (LDRB) for prostate cancer. METHODS: Men with low and favorable intermediate-risk prostate cancer across 3 centres were randomized between monotherapy brachytherapy with either Iodine-125 LDRB or 19 Gy single-fraction HDRB. Biochemical outcomes were evaluated using the Phoenix definition, PSA nadir and absolute PSA value < 0.4 ng/mL. Toxicities and HRQOL were recorded at 24 and 36 months. RESULTS: A total of 31 patients were randomized, 15 in the LDRB arm and 16 patients in the HDRB arm. After a median follow-up of 45(36-53) months, 3 patients in the HDRB arm experienced biochemical failure (p = 0.092). Nineteen Gy single-fraction HDRB was associated with significantly higher PSA nadir compared to LDRB (1.02 +/- 0.66 vs 0.25 +/- 0.39, p < 0.0001). Moreover, a significantly larger proportion of patients in the LDRB group had a PSA < 0.4 ng/mL (13/15 vs 2/16, p < 0.0001). For late Genito-Urinary, Gastro-Intestinal, and sexual toxicities at 24 and 36 months, no significant differences were found between the 2 arms. As for HRQOL, the IPSS and EPIC-26 urinary irritative score were significantly better for patients treated with HDRB over the first 36 months post-treatment (p=0.001 and p = 0.01, respectively), reflecting superior HRQOL. CONCLUSION: HDRB resulted in superior HRQOL in the irritative urinary domain compared to LDRB. PSA nadir was significantly lower in the LDRB group and a higher proportion of patients in the LDRB group reached PSA < 0.4 ng/mL. (C) 2021 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

The UHF treatment scheme with HDR BB seems equivalent to standard treatment arms in terms of long-term toxicities and local control. The adoption of the UHF regimen would not only reduce the socioeconomic burden, it would also offer the shortest treatment time for intermediate risk prostate cancer known to date, of interest in the actual pandemic situation. Randomized control trials with larger cohorts are needed to further confirm our findings.

PURPOSE: The purpose of this study was to evaluate whether the dose to bladder neck (BN) is a predictor of acute and late urinary toxicity after high-dose-rate brachytherapy (HDRB) boost for prostate cancer. METHODS AND MATERIALS: Between 2014 and 2016, patients with prostate cancer treated at our institution with external beam radiation therapy and 15 Gy single-fraction HDRB boost for intermediate- and high-risk disease according to D'Amico definition were reviewed. Intraoperative CT scan-based inverse planning and ultrasound-based inverse planning were performed in 173 and 136 patients, respectively. The following structures were prospectively contoured: prostate, urethra, rectum, bladder, and the BN defined as 5 mm around the urethra between the catheter balloon and the prostatic urethra. Dose to the BN was reported only, no constraint was applied. Acute and late urinary toxicity were assessed using the International Prostate Symptom Score (IPSS) and the Common Terminology Criteria for Adverse Events v.4.0. Clinical and dosimetry factors associated with urinary toxicity were analyzed using generalized linear models. RESULTS: A total of 309 patients with median age of 71 years (range 50-89) were included. Median followup was 25 months (range 0-39 months). Using D'Amico definition, 71% of the patients had intermediate-risk disease, whereas 29% had high-risk disease. The mean pretreatment prostate-specific antigen value was 9.65 ng/mL. The mean pretreatment, after 6 weeks and over 6 months IPSSs were 8.34, 12.14, and 10.02, respectively. Urinary obstruction was reported in 14 cases (4.5%). Pretreatment IPSS (p = 0.003) and prostate volume (p = 0.024) were significantly associated with acute and late urinary toxicity. The dose for the most exposed 2 cc (D-2cc) of BN was not correlated with acute (p = 0.798) or late urinary toxicity (p = 0.859). BN D-2cc was not correlated with urinary obstruction (p = 0.272), but bladder V-75 was (p = 0.021). CONCLUSIONS: High pretreatment IPSS, large prostate volume and bladder V-75 were the only predictors of acute and late urinary toxicity after HDRB boost in our study. Although BN D-2cc was associated with acute and late urinary toxicity after low-dose-rate brachytherapy, no correlation was found after HDRB. A prospective study comparing dose to the BN in HDRB monotherapy would validate the impact of BN dose on acute and late urinary toxicity. (C) 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

To evaluate whether the dose to Bladder Neck is a predictor of urinary toxicity after High Dose-Rate Brachytherapy (HDRB) for prostate cancer.