Low Dose Rate Prostate Brachytherapy Research Articles

Aleatoric and epistemic uncertainty extraction of patient-specific deep learning-based dose predictions in LDR prostate brachytherapy.

Objective.In brachytherapy, deep learning (DL) algorithms have shown the capability of predicting 3D dose volumes. The reliability and accuracy of such methodologies remain under scrutiny for prospective clinical applications. This study aims to establish fast DL-based predictive dose algorithms for low-dose rate (LDR) prostate brachytherapy and to evaluate their uncertainty and stability.Approach.Data from 200 prostate patients, treated with125I sources, was collected. The Monte Carlo (MC) ground truth dose volumes were calculated with TOPAS considering the interseed effects and an organ-based material assignment. Two 3D convolutional neural networks, UNet and ResUNet TSE, were trained using the patient geometry and the seed positions as the input data. The dataset was randomly split into training (150), validation (25) and test (25) sets. The aleatoric (associated with the input data) and epistemic (associated with the model) uncertainties of the DL models were assessed.Main results.For the full test set, with respect to the MC reference, the predicted prostateD90metric had mean differences of -0.64% and 0.08% for the UNet and ResUNet TSE models, respectively. In voxel-by-voxel comparisons, the average global dose difference ratio in the [-1%, 1%] range included 91.0% and 93.0% of voxels for the UNet and the ResUNet TSE, respectively. One forward pass or prediction took 4 ms for a 3D dose volume of 2.56 M voxels (128 × 160 × 128). The ResUNet TSE model closely encoded the well-known physics of the problem as seen in a set of uncertainty maps. The ResUNet TSE rectum D2cchad the largest uncertainty metric of 0.0042.Significance.The proposed DL models serve as rapid dose predictors that consider the patient anatomy and interseed attenuation effects. The derived uncertainty is interpretable, highlighting areas where DL models may struggle to provide accurate estimations. The uncertainty analysis offers a comprehensive evaluation tool for dose predictor model assessment.

Comparison of the Efficacy of Low Dose Tadalafil with Tamsulosin against Lower Urinary Tract Symptoms and Sexual Dysfunction after Low Dose Rate Prostate Brachytherapy.

Patients with clinically localized prostate cancer (PCa) can be curatively treated with different modalities, including low dose rate (LDR) prostate brachytherapy (PB). LDR-PB allows the patient a relatively short recovery time compared with other treatment modalities such as prostatectomy. However, PB might exert distinct impact on quality of life, lower urinary tract symptoms (LUTS) and sexual dysfunction (SD) are two major concerns. The aim of present study was to assess prospectively the efficacy of low dose tadalafil treatment on both SD and LUTS compared with tamsulosin treatment in patients treated PB for localized PCa. Patients scheduled for PB with I-125 seeds for low or intermediate-risk localized PCa at our institution were eligible for this study. The prescribed dose was set at 160 gray. Participants were randomized into two groups; those started treating with a daily use of 0.2 mg of tamsulosin hydrochloride or 5 mg of tadalafil just after PB. The duration of the study was 12 months and the patients were assessed for urinary and sexual function status at baseline, and 1, 3, 6, and 12 months after PB. The primary study endpoints were both changes from baseline in urinary and sexual function status. Between July 2015 and August 2020, 120 participants were enrolled in this study. The median age was 68 years with the median PSA of 6.5 ng/ml. A total 15 patients were excluded within 6 months after randomization. All subjective LUTS findings, including International Prostate Symptom Score (IPSS), and Over Active Bladder Symptom Score (OABSS), were significantly deteriorated at 1, 3, and 6 months after PB compared with baseline in both groups, respectively (p<0.05). Among objective LUTS findings, a significant decrease in maximum urinary flow rate (Qmax) was found at 1, 3, 6, and 12 months after PB compared with baseline in both groups, respectively (p<0.05). A significant increase in post void residual urine (PVR) was found at 1, 3, and 6 months after PB compared to baseline in tadalafil group, whereas no significant increase was seen in tamsulosin group. There were no statistically significant differences between the 2 groups in scores of the total International Index of Erectile Function (IIEF)-15 and Erection Hardness Score (EHS) before and at 1 month post PB. The EHS was significantly higher in tadalafil group compared with tamsulosin group at 3, 6 and 12 months (p = 0.001, p = 0.004, and p = 0.019, respectively). The EHS after PB in tadalafil group was not significantly decreased from baseline. After LDR-PB, tamsulosin treatment significantly decreased PVR compared with tadalafil. On the other hand, tadalafil contributed to maintain erection hardness compared with tamsulosin.

Uncertainty in magnetic resonance imaging-based prostate postimplant dosimetry: Results of a 10-person human observer study, and comparisons with automatic postimplant dosimetry

Uncertainties in postimplant quality assessment (QA) for low-dose-rate prostate brachytherapy (LDRPBT) are introduced at two steps: seed localization and contouring. We quantified how interobserver variability (IoV) introduced in both steps impacts dose-volume-histogram (DVH) parameters for MRI-based LDRPBT, and compared it with automatically derived DVH parameters. Twenty-five patients received MRI-based LDRPBT. Seven clinical observers contoured the prostate and four organs at risk, and 4 dosimetrists performed seed localization, on each MRI. Twenty-eight unique manual postimplant QAs were created for each patient from unique observer pairs. Reference QA and automatic QA were also performed for each patient. IoV of prostate, rectum, and external urinary sphincter (EUS) DVH parameters owing to seed localization and contouring was quantified with coefficients of variation. Automatically derived DVH parameters were compared with those of the reference plans. Coefficients of variation (CoVs) owing to contouring variability (CoVcontours) were significantly higher than those due to seed localization variability (CoVseeds) (median CoVcontours vs. median CoVseeds: prostate D90-15.12% vs. 0.65%, p < 0.001; prostate V100-5.36% vs. 0.37%, p < 0.001; rectum V100-79.23% vs. 8.69%, p < 0.001; EUS V200-107.74% vs. 21.18%, p < 0.001). CoVcontours were lower when the contouring observers were restricted to the 3 radiation oncologists, but were still markedly higher than CoVseeds. Median differences in prostate D90, prostate V100, rectum V100, and EUS V200 between automatically computed and reference dosimetry parameters were 3.16%, 1.63%, -0.00 mL, and -0.00 mL, respectively. Seed localization introduces substantially less variability in postimplant QA than does contouring for MRI-based LDRPBT. While automatic seed localization may potentially help improve workflow efficiency, it has limited potential for improving the consistency and quality of postimplant dosimetry.

Reirradiation salvage radiotherapy for recurrent prostate cancer after primary low-dose brachytherapy.

Local recurrence of prostate cancer after low-dose rate brachytherapy is a clinical problem with limited salvage treatment options. This prospective study evaluated the tolerability and outcome of salvage external beam radiation therapy (S-EBRT) for locally recurrent prostate cancer after primary low-dose rate prostate brachytherapy (LDR-BT). Between October 2012 and 2022, 18 patients with biopsy-proven locally recurrent prostate cancer after primary LDR-BT and received S-EBRT. We evaluated biochemical failure (BF), overall survival (OS) and acute/late gastrointestinal and urinary toxicities (CTCAE v5.0 or CTCAE v4, only before 2017). Median follow-up was 32months (range, 5-124). The median age was at S-EBRT 68years (range 59-79). 34% (6/18) were low risk, 44% (8/18) intermediate risk, 5% (1/18) high risk, and 17% (3/18) not specified. All patients were treated with IMRT/VMAT and received 60Gy (2.5Gy/fraction) to the prostate and 40% (7/18) 55.2Gy (2,3Gy/fx) to the seminal vesicles. 56% received ADT The 3-year OS and biochemical relapse-free survival after S-EBRT were 100% and 89%, respectively, with a median PSA nadir 0,035ng/mL (0,01-0,34). Acute cystitis was present in 72% (13/18) of patients (27% of Grade > 2). Urethritis was present in 78% (14/18) patients (16% of cases Grade > 3), and acute rectitis occurred in 22% (4/18) of patients (no cases Grade > 3). Our data suggest that the treatment of locally recurrent prostate cancer with S-EBRT could provide adequate disease control safely and be used as an additional treatment in the natural history of prostate cancer patients. However, the results are still early and the sample is small; larger studies with longer follow-up would be mandatory.

Estimated absolute percentage of biopsied tissue positive for Gleason pattern 4 (eAPP4) in low dose rate prostate brachytherapy: Evaluation of prognostic utility in a large cohort

PurposeTo determine whether a system to estimate Absolute Percentage of Biopsied Tissue Positive for Gleason Pattern 4 (eAPP4) is useful as a prognostication tool for patients with intermediate risk prostate cancer (IR-PCa) undergoing low dose rate prostate brachytherapy. Methods497 patients with IR-PCa and known grade group 2 or 3 disease treated with low dose rate seed brachytherapy (LDR-BT) at a quaternary cancer centre were retrospectively reviewed. Prostate biopsies for each patient included Gleason grading with synoptic reporting that did not include percentage of pattern 4 disease found within the sample. Each core was assigned a grade grouping, however, and that was used with optimized estimates of percentage of pattern four disease to estimate eAPP4. Outcomes including cumulative incidence of recurrence (CIR), treatment of recurrent disease (RRX), and metastasis-free survival (MFS) were then reviewed and the prognostic value of eAPP4 evaluated. Results428 (86%) patients had Gleason grade group 2 and 69 (14%) patients had Gleason grade group 3 disease. 230 (46%) patients had National Comprehensive Cancer Network (NCCN) favourable intermediate at baseline, while 267 (54%) of patients had NCCN unfavourable intermediate at baseline. Median follow-up was 7.3 (5.5–9.6) years. eAPP4 was predictive of CIR (p = 0.003), RRX (p = 0.003), or MFS (p = 0.001) events, while Gleason grade grouping alone was not. eAPP4 was strongest as a predictor for MFS when estimates of 30% (grade group 2) and 80% (grade group 3) were used [HR 1.07 (1.03–1.12); p = 0.001]. ConclusionseAPP4 was strongly predictive of recurrence and metastasis-free survival in a large cohort of patients receiving LDR-BT treatment for IR-PCa. Treatment of future patients with IR-PCa could include the use of eAPP4 prognostication.

Clinical and treatment characteristics of secondary bladder malignancies following low dose rate brachytherapy for prostate cancer.

To characterize the clinical course and prognosis of bladder malignancies associated with prior prostate brachytherapy SUBJECTS/PATIENTS AND METHODS: We queried our institutional database for patients with bladder cancer (BC) diagnosed between January 2005 and April 2019 who had previously undergone low dose rate (LDR) prostate brachytherapy. Patients diagnosed with BC at least 1 year following LDR prostate brachytherapy with or without external beam radiation therapy were included. Clinical and disease-specific characteristics were abstracted from chart review and survival outcomes were estimated using Kaplan-Meier estimates. We compared the pathologic characteristics and prognosis of secondary BCs in our study cohort to those of BCs diagnosed after prostate cancer managed without radiation reported by the Surveillance, Epidemiology, and End Results (SEER) populational database from 2005 to 2018. Three hundred seventy-five patients were identified with combined diagnosis of prostate cancer and BC, 51 of whom met inclusion criteria in the study cohort. Median times from brachytherapy to BC diagnosis for the study and SEER cohort were 9.5 ± 4.5 and 6.3 ± 4.1 years, respectively. Compared to the SEER cohort, significantly greater proportion of BC from the study cohort presented with high-grade (study: 78.4%, SEER: 52.3%, P = 0.0008) and with MIBC (Study BC 35.3%, SEER BC: 17.5%, P = 0.0009). The study and the SEER cohort had similar 5-year overall survival (study: 67.9%, SEER: 58.0%, P = 0.1099), and 5-year cancer-specific survival (study: 81.0%, SEER: 82.8%, P = 0.5559). The 5-year progression-free survival for the study cohort was 43.7% (95% CI: 28.8-57.7). Compared to bladder cancers following prostate cancer managed without radiation, bladder malignancies following prostate LDR brachytherapy present with higher grade and are more likely to be muscle invasive. Despite the aggressive presenting features of postprostate brachytherapy BC, there were no differences in overall and cancer-specific survival between the groups.

Outcomes after PD-103 versus I-125 for low dose rate prostate brachytherapy monotherapy: An international, multi-institutional study

Background and PurposePd-103 and I-125 are commonly used in low dose rate (LDR) brachytherapy for prostate cancer. Comparisons of outcomes by isotope type are limited, but Pd-103 has distinct radiobiologic advantages over I-125 despite its lesser availability outside the United States. We evaluated oncologic outcomes after Pd-103 vs I-125 LDR monotherapy for prostate cancer. Materials and MethodsWe retrospectively analyzed databases at 8 institutions for men who received definitive LDR monotherapy with Pd-103 (n = 1,597) or I-125 (n = 7,504) for prostate cancer. Freedom from clinical failure (FFCF) and freedom from biochemical failure (FFBF) stratified by isotope were analyzed by Kaplan-Meier univariate and Cox multivariate analyses. Biochemical cure rates (prostate-specific antigen level ≤ 0.2 ng/mL between 3.5 and 4.5 years of follow-up) by isotype were calculated for men with at least 3.5 years of follow-up and compared by univariate and multivariate logistic regression. ResultsCompared with I-125, Pd-103 led to higher 7-year rates of FFBF (96.2% vs 87.6%, P < 0.001) and FFCF (96.5% vs 94.3%, P < 0.001). This difference held after multivariate adjustment for baseline factors (FFBF hazard ratio [HR] = 0.31, FFCF HR = 0.49, both P < 0.001). Pd-103 was also associated with higher cure rates on univariate (odds ratio [OR] = 5.9, P < 0.001) and multivariate (OR = 6.0, P < 0.001) analyses. Results retained significance in sensitivity analyses of data from the 4 institutions that used both isotopes (n = 2,971). ConclusionsPd-103 monotherapy was associated with higher FFBF, FFCF, and biochemical cure rates, and suggests that Pd-103 LDR may lead to improved oncologic outcomes compared with I-125.

Dose Distribution of High Dose-Rate and Low Dose-Rate Prostate Brachytherapy at Different Intervals—Impact of a Hydrogel Spacer and Prostate Volume

The study aimed to compare the dose distribution in permanent low-dose-rate brachytherapy (LDR-BT) and high-dose-rate brachytherapy (HDR-BT), specifically focusing on the impact of a spacer and prostate volume. The relative dose distribution of 102 LDR-BT patients (prescription dose 145 Gy) at different intervals was compared with the dose distribution of 105 HDR-BT patients (232 HDR-BT fractions with prescription doses of 9 Gy, n = 151, or 11.5 Gy, n = 81). A hydrogel spacer (10 mL) was only injected before HDR-BT. For the analysis of dose coverage outside the prostate, a 5 mm margin was added to the prostate volume (PV+). Prostate V100 and D90 of HDR-BT and LDR-BT at different intervals were comparable. HDR-BT was characterized by a considerably more homogenous dose distribution and lower doses to the urethra. The minimum dose in 90% of PV+ was higher for larger prostates. As a consequence of the hydrogel spacer in HDR-BT patients, the intraoperative dose at the rectum was considerably lower, especially in smaller prostates. However, prostate volume dose coverage was not improved. The dosimetric results well explain clinical differences between these techniques reported in the literature review, specifically comparable tumor control, higher acute urinary toxicity rates in LDR-BT in comparison to HDR-BT, decreased rectal toxicity after spacer placement, and improved tumor control after HDR-BT in larger prostate volumes.

Single- and dual-source-strength focal boost planning in low-dose-rate prostate brachytherapy: feasibility study

Abstract Introduction: This study investigates the dose escalation to dominant intra-prostatic lesions (DILs) that is achievable using single-source-strength (SSS) and dual-source-strength (DSS) low-dose-rate (LDR) prostate brachytherapy and a sector-based plan approach. Methods: Twenty patients were retrospectively analysed. Image registration and planning were undertaken using VariSeed v9·0. SSS and DSS boost plans were produced and compared to clinical plans. Dosimetric robustness to seed displacement for SSS and DSS plans was compared to clinical plans using Monte Carlo simulations. Results: Fourteen out of 20 patients had DIL identifiable on magnetic resonance imaging. Median increase in sector D90 of 27% (p &lt; 0·0001) and sector V150 of 31% (p &lt; 0·0001) was achieved with SSS planning without exceeding local rectum and urethra dose constraints. DSS plans achieved dose distributions not statistically significantly different from the SSS plans with a median of eight fewer seeds and two fewer needles. SSS and DSS plan sensitivity to random seed displacement was similar to the clinical plans. Conclusions: Treatment planning using VariSeed to produce SSS and DSS focal boost plans is feasible for LDR prostate brachytherapy to achieve a median escalation in sector D90 of 27% without exceeding local urethral and rectal constraints. SSS and DSS plan dosimetric robustness was similar to clinical plan dosimetric robustness.

Determining Combined Modality Dosimetric Constraints by Integration of IMRT and LDR Prostate Brachytherapy Dosimetry and Correlation with Toxicity

Intermediate- and high-risk prostate cancer patients undergoing combination external beam radiation therapy (EBRT) and low dose rate (LDR) brachytherapy have demonstrated increased genitourinary (GU) toxicity. We have previously demonstrated a method to combine EBRT and LDR dosimetry. In this work, we use this technique for a sample of patients with intermediate- and high-risk prostate cancer, correlate with clinical toxicity, and suggest preliminary summed organ-at-risk constraints for future investigation. Intensity modulated EBRT and 103Pd-based LDR treatment plans were combined for 138 patients using biological effective dose (BED) and deformable image registration. GU and gastrointestinal (GI) toxicity were compared with combined dosimetry for the urethra, bladder, and rectum. Differences between doses in each toxicity grade were assessed by analysis of variance (α=0.05). Combined dosimetric constraints are proposed using the mean organ-at-risk dose, subtracting 1 standard deviation for a conservative recommendation. The majority of our 138-patient cohort experienced grade 0 to 2 GU or GI toxicity. Six grade 3 toxicities were noted. Mean prostate BED D90 (± 1 standard deviation) was 165.5±11.1 Gy. Mean urethra BED D10 was 230.3±33.9 Gy. Mean bladder BED was 35.2±11.0 Gy. Mean rectum BED D2cc was 85.6±24.3 Gy. Significant dosimetric differences between toxicity grades were found for mean bladder BED, bladder D15, and rectum D50, but differences between individual means were not statistically significant. Given the low incidence of grade 3 GU and GI toxicity, we propose urethra D10 <200 Gy, rectum D2cc <60 Gy, and bladder D15 <45 Gy as preliminary dose constraints for combined modality therapy. We successfully applied our dose integration technique to a sample of patients with intermediate- and high-risk prostate cancer. Incidence of grade 3 toxicity was low, suggesting that combined doses observed in this study were safe. We suggest preliminary dose constraints as a conservative starting point to investigate and escalate prospectively in a future study.

Detection accuracy of I-125 seeds and needle tips, in MRI prostate tissue mimicking material: Phantom design, fabrication, and testing

• Novel phantom design provides a method of verifying geometric brachytherapy seed and needle tip positions in MRI. • Tests clinically relevant arrangements for seed placements in T1 MRI sequences within prostate tissue mimicking material. • Tests performed with Nitinol needles. • Demonstrates challenges meeting the required accuracy of seed and needle tip detection for brachytherapy in MRI. • Identifies seed placements to be avoided to improve overall accuracy in seed localisation. Accurately identifying needle tip and seed positions for low dose rate prostate brachytherapy on MRI images is challenging. Uncertainties in locating needle tip positions can lead to misplacement of seeds compared to planned coordinates. Furthermore uncertainty in establishing true seed positions on the images, leads to uncertainty in the dose distributions. In this study, a novel phantom has been designed for the analysis of I-125 seed and needle tip detection and tip image distortion. The phantom utilises a gel that mimics prostate tissue in MRI, to evaluate the uncertainty in establishing seed and needle tip positions. Reults are reported for the IsoSeed (Bebig) source, in clinically relevant seed arrangements, and for a novel nitinol needle. The choice of MRI sequence impacts the accuracy of detecting the needle tips and seeds. This is most prevelant when the seeds are in clusters, at the boundary of the prostate and at 90˚ to the long axis of the scanner. Detected needle tip position, when the MRI metal artefact correction algorithm was used, was measured consistently inferior to the actual position (mean tip at -2.3 ± 1.5 mm (k = 2), p = 0.03). We have demonstrated the design of a phantom that can be used to quantitatively assess seed and needle tip positions simultaneously, to establish the accuracy of detection, or presence of artefacts on MRI.

PL04 Presentation Time: 2:45 PM: A Randomized Phase III Trial Comparing Health-Related Quality of Life After Low Dose Rate or High Dose Rate Prostate Brachytherapy Boost Combined with External Beam Pelvic Radiotherapy

<h3>Purpose</h3> This randomized phase III trial compared health related quality of life (HRQOL) in urinary, bowel, and sexual domains in men with intermediate (IR) and high-risk (HR) prostate cancer treated with combined external beam radiation therapy (EBRT) and prostate brachytherapy (BT) using either low dose rate (LDR) or high dose rate (HDR). <h3>Materials and Methods</h3> Eligible men receiving pelvic EBRT (46 Gy/23F) combined with prostate BT were randomized to either an LDR (110 Gy) or HDR (15 Gy) boost. HDRBT preceded EBRT by 1 week while LDRBT followed. Time 0 for QOL evaluations was day 1 of any radiotherapy. The Expanded Prostate Cancer Index Composite (EPIC) questionnaire was used to evaluate HRQOL q3 months for the first year, q6 months to 3 years and then annually. The Mann-Whitney U test was used to compare mean EPIC scores for urinary, bowel and sexual summary domains. <h3>Results</h3> From 01/2014 to 01/2020, 191 men were randomized: 42% IR and 58% HR. Median age was 71 years. T stage was T1c/T2a:34%, T2b:28%, T2c:24% and T3:13%. 57% had Gleason 7, 13% Gleason 8 and 30% Gleason 9. 74% received ADT with at least 3 months neoadjuvant and for a median duration of 12 mo. Median follow-up was 48 mo. HDR patients had higher (better) HRQOL urinary domain scores at 3 mo. (79.0 vs. 69.4; p<.001) and 6 mo. (84.0 vs. 76.9; p<.001), and higher bowel domain scores at 3 mo. (87.0 vs. 82.1; p=.005) and 6 mo. (88.7 vs. 82.8; p=.023). Better bowel domain scores were sustained at 24, 36, and 48 mo. In contrast, HDR patients had worse HRQOL urinary domain scores at 1 mo. (73.6 vs. 80.7; p=.003). There was no statistically significant difference in HRQOL sexual domain scores between the two arms. <h3>Conclusions</h3> The effect of HDRBT on urinary and bowel domains was evident 1 mo. post implant but had recovered at 3 and 6 mo., while LDR patients were still experiencing significant QOL impact of their ongoing LDRBT. Although HDR patients sustained an advantage in long term bowel function compared to LDR, there was no difference in long term urinary QOL between the 2 types of BT after the acute phase subsided. The patient treatment experience of combined EBRT/BT is improved with HDR. Efficacy will be reported at 5 year minimum follow up.

Toxicity Outcomes at 18 Months for Cs-131 Low-Dose-Rate Prostate Brachytherapy Compared to I-125 and Pd-103

<h3>Purpose/Objective(s)</h3> Low dose rate prostate brachytherapy is an established component of definitive radiotherapy options for localized prostate cancer. As the utility of LDR brachytherapy (LDRB) has evolved, the focus has shifted to improving the side effect profile while maintaining oncologic outcomes. Most prior efficacy and toxicity data were gathered using I-125 and Pd-103, but due to the shorter half-life and slightly higher average energy of Cs-131, several institutions have adopted its use in an attempt to improve outcomes and decrease toxicity. To report the toxicity outcomes up to 18 months after Cs-131 LDR brachytherapy at our institution, compared to our experience with I-125 and Pd-103. <h3>Materials/Methods</h3> A retrospective review was performed on the first 50 patients treated with Cs-131 LDRB for localized prostate cancer at our institution. Patients receiving either a full or partial implant were included. Prescription doses of 100Gy and 80Gy were utilized, respectively. Patients receiving partial implants generally received 45Gy external beam radiotherapy starting 6-8 weeks after implant. Data regarding AUA prostate symptom score, sexual health inventory for men (SHIM) score, and RTOG GI toxicity score were assessed pretreatment, at 1 month, and at each subsequent follow up. Demographic and clinical data were also collected. The data was compared to cohorts of the last 50 patients treated I-125 and the last 50 patients treated with Pd-103, to standard doses. Descriptive statistics were used to summarize variables. A linear mixed model was used to compare means and to identify variables as prognostic for toxicity (p≤0.05). <h3>Results</h3> The mean AUA scores prior to brachytherapy were similar for patients in all groups (p=1.00), while at 1-month post-treatment, mean AUA score was significantly higher for patients treated with Cs-131 and Pd-103 compared to I-125 (p<0.001). Mean AUA scores were not significantly different at longer follow-up (p>0.50). The need for a catheter post-brachytherapy occurred in 8% of patients and was not associated with type of isotope on multivariate analysis (MVA). Prostate volume, numbers of seeds, and prostate D90% were significant predictors for the need for a catheter on MVA. The use of ADT and the total activity were significant predictors on MVA for a decrease in SHIM score over time. The type of isotope used did not predict for erectile dysfunction (ED) as measured by SHIM score on MVA. Overall rates of GI toxicity were low with only 3 patients developing RTOG grade 2 toxicity or greater without any obvious difference between isotopes. <h3>Conclusion</h3> In patients treated with Cs-131 or Pd-103 LDRB, acute GU side effects peaked higher at 1 month than with I-125, but rapidly decreased to similar levels with longer follow-up. The type of source used did not predict for need for catheterization, ED, or GI toxicity at any time point.

Is hemi-gland focal LDR brachytherapy as effective as whole-gland treatment for unilateral prostate cancer?

The Hemi-Ablative Prostate Brachytherapy (HAPpy) trial evaluated hemi-gland (HG) low-dose-rate prostate brachytherapy (LDR-PB) as a focal approach to control unilateral localized prostate cancer and reduce treatment-related toxicity at 2-years postimplant. Herewith we present further outcomes with a minimum of 5 years post-implant follow-up. Outcomes of 30 HG implants and 362 whole-gland (WG) brachytherapy controls were monitored with IPSS, urinary Quality-of-Life (QoLU), GI component of EORTC-PR25 (QoLB), and IIEF-5 instruments, and PSA values. The median (range) follow-up for HG and WG cases was 72 (60-96) months and 84 (24-144) months respectively. The IPSS was significantly reduced in HG relative to WG patients and trends indicating improved bowel QoL and erectile function were observed. The mean of change in PSA from baseline to last follow-up was -5.6 and -6.5 in HG and WG respectively (p = 0.1). The mean time to nadir was 4.2 and 4.8 years in HG and WG respectively (p = 0.06). Over time PSA in HG patients mirrored the sustained decline observed in WG cases but levels were higher by an average 0.5 ng/ml over WG controls (p < 0.001). Treatment failure occurred in 2 (6.7%) HG patients and in 20 (5.5%) WG cases. Five-year relapse-free survival was 97% in both groups (p = 0.7). At 5 years postimplant HG LDR-PB was as effective as WG treatment for control of unilateral localized prostate cancer with moderate improvement in treatment-related symptoms. Importantly, PSA is a valuable marker to assess disease control in this form of focal therapy.

Oncological and urinary outcomes following low-dose-rate brachytherapy with a median follow-up of 11.8 years.

To examine the long-term oncological outcomes and urological morbidity of low-dose-rate prostate brachytherapy (LDRBT) monotherapy using live intraoperative dosimetry planning and an automated needle navigation delivery system for the treatment of men with low and intermediate-risk prostate cancer. A prospective database of 400 consecutive patients who underwent LDRBT between July 2003 and June 2015 was retrospectively reviewed to assess urinary side-effects and biochemical progression, based on the Phoenix definition and also a definition of a prostate-specific antigen (PSA) level of ≥0.2 μg/L. Minimum patient follow-up was 5.5 years. The median follow-up of the entire cohort was 11.8 years. The median (range) PSA level was 6.1 (0.9-17) μg/L and the median Gleason score was 3 + 4. The biochemical relapse-free survival (RFS; freedom from biochemical recurrence) based on the Phoenix definition was 85.8% (343/400). The RFS using a 'surgical' definition of a PSA level of <0.2 μg/L was 71% (284/400). Of the 297 men followed for ≥10 years, prostate cancer-specific survival (PCSS) was 98% (291/297). Post-LDRBT urethral stricture developed in 11 men (2.8%, 11/400). For men with ≥10 years of follow-up, 22 men (7.4%, 22/297) required a pad for either stress or urge urinary incontinence (UI). UI was identified in only 2.2% (one of 46) of men who had a bladder neck incision (BNI) before LDRBT. LDRBT is associated with excellent PCSS, with a median follow-up of 11.8 years. The risk of post-implantation urethral stricture and UI is low and a pre-implantation BNI for management of bladder outflow obstruction does not increase the risk of UI or urethral stricture.

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

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

Fast Monte Carlo-Based Inverse Planning for Prostate Brachytherapy by Using Deep Learning

Inverse planning is an essential tool for optimizing the delivered radiation dose on low-dose-rate (LDR) prostate brachytherapy. Clinical inverse planning systems use the TG-43 dose computation formalism in order to perform a fast optimization. However, this method is an approximation that often leads to a dose overestimation, resulting on suboptimal plans. Alternatively, Monte Carlo simulation (MCS) can be used to obtain an accurate dose distribution, but considerably increasing the estimation time. We propose a fast inverse planning method for LDR prostate brachytherapy that uses a deep convolutional neural network (DCNN) trained on a graphics processing unit (GPU)-based MCS generated database to estimate the dose distribution on the prostate and organs at risk. Segmentations of the organs and seeds&#x2019; positions are given as the DCNN input. The mean percent error on the test set was &#x2212;1.19&#x00B1;0.94&#x0025; within the prostate. The DCNN was used to estimate the dosimetric parameters in each organ for every configuration of the optimization loop. The dosimetric parameters of the final DCNN-based brachytherapy plans were in good agreement compared to the same plans recalculated with a full MCS. The proposed inverse planning based on DCNN was capable to reach an equivalent level of accuracy with Monte Carlo with a runtime in less than 1 min using conventional GPU card.

Prospective Evaluation of Prostate and Organs at Risk Segmentation Software for MRI-based Prostate Radiation Therapy.

The segmentation of the prostate and surrounding organs at risk (OARs) is a necessary workflow step for performing dose-volume histogram analyses of prostate radiation therapy procedures. Low-dose-rate prostate brachytherapy (LDRPBT) is a curative prostate radiation therapy treatment that delivers a single fraction of radiation over a period of days. Prior studies have demonstrated the feasibility of fully convolutional networks to segment the prostate and surrounding OARs for LDRPBT dose-volume histogram analyses. However, performance evaluations have been limited to measures of global similarity between algorithm predictions and a reference. To date, the clinical use of automatic segmentation algorithms for LDRPBT has not been evaluated, to the authors' knowledge. The purpose of this work was to assess the performance of fully convolutional networks for prostate and OAR delineation on a prospectively identified cohort of patients who underwent LDRPBT by using clinically relevant metrics. Thirty patients underwent LDRPBT and were imaged with fully balanced steady-state free precession MRI after implantation. Custom automatic segmentation software was used to segment the prostate and four OARs. Dose-volume histogram analyses were performed by using both the original automatically generated contours and the physician-refined contours. Dosimetry parameters of the prostate, external urinary sphincter, and rectum were compared without and with the physician refinements. This study observed that physician refinements to the automatic contours did not significantly affect dosimetry parameters. Keywords: MRI, Neural Networks, Radiation Therapy, Radiation Therapy/Oncology, Genital/Reproductive, Prostate, Segmentation, Dosimetry Supplemental material is available for this article. © RSNA, 2022.

Computer-aided segmentation on MRI for prostate radiotherapy, Part I: Quantifying human interobserver variability of the prostate and organs at risk and its impact on radiation dosimetry

Background and purposeQuantifying the interobserver variability (IoV) of prostate and periprostatic anatomy delineation on prostate MRI is necessary to inform its use for treatment planning, treatment delivery, and treatment quality assessment. Materials and methodsTwenty five prostate cancer patients underwent MRI-based low-dose-rate prostate brachytherapy (LDRPBT). The patients were scanned with a 3D T2-weighted sequence for treatment planning and a 3D T2/T1-weighted sequence for quality assessment. Seven observers involved with the LDRPBT workflow delineated the prostate, external urinary sphincter (EUS), seminal vesicles, rectum, and bladder on all 50 MRIs. IoV was assessed by measuring contour similarity metrics, differences in organ volumes, and differences in dosimetry parameters between unique observer pairs. Measurements from a group of 3 radiation oncologists (G1) were compared against those from a group consisting of the other 4 clinical observers (G2). ResultsIoV of the prostate was lower for G1 than G2 (Matthew’s correlation coefficient [MCC], G1 vs. G2: planning–0.906 vs. 0.870, p < 0.001; postimplant–0.899 vs. 0.861, p < 0.001). IoV of the EUS was highest of all the organs for both groups, but was lower for G1 (MCC, G1 vs. G2: planning–0.659 vs. 0.402, p < 0.001; postimplant–0.684 vs. 0.398, p < 0.001). Large differences in prostate dosimetry parameters were observed (G1 maximum absolute prostate ΔD90: planning–76.223 Gy, postimplant–36.545 Gy; G1 maximum absolute prostate ΔV100: planning–13.927%, postimplant–8.860%). ConclusionsWhile MRI is optimal in the management of prostate cancer with radiation therapy, significant interobserver variability of the prostate and external urinary sphincter still exist.

Defining Biochemical Cure After Low Dose Rate Prostate Brachytherapy: External Validation of 4-year Prostate-specific Antigen Nadir as a Predictor of 10- and 15-year Disease-free Survival

AimsTo externally validate a proposed biochemical definition of cure following low dose rate (LDR) brachytherapy for prostate cancer – 4-year post-implant prostate-specific antigen (PSA) ≤0.2 ng/ml – in a UK population, and report the long-term (10- and 15-year) outcomes for patients stratified by National Comprehensive Cancer Network (NCCN) risk groups, through analysis of a large, prospectively collected, single-centre database. Materials and methodsAll patients treated with LDR brachytherapy for prostate cancer at a single UK centre between 2001 and November 2020 (n = 1142) were eligible; 632 patients met the inclusion criteria for the analysis. The primary end point was disease-free survival (DFS), defined as freedom from clinical, radiological or PSA progression requiring androgen deprivation therapy. Four-year PSA was categorised as ≤0.2, >0.2 to ≤0.5, >0.5 to ≤1.0 and >1.0 ng/ml. Kaplan–Meier analysis to 15 years was undertaken for each group, and sensitivity and specificity of 4-year PSA as a surrogate for long-term cure were calculated. Kaplan–Meier analysis to 15 years was repeated, stratifying patients by NCCN risk groups. ResultsThe median cohort age was 63 years; the median follow-up was 9.1 years (range 3.5–18.7). In total, 248 patients were available for analysis at year 10, 46 at year 15. Sixty-four patients (10.1%) relapsed during the study period. The 10-year DFS for 4-year PSA categories ≤0.2, >0.2 to ≤0.5, >0.5 to ≤1.0 and >1.0 ng/ml (95% confidence intervals) were 97.5% (95.4–99.6), 89.0% (82.4–96.1), 81.5% (70.5–94.2) and 41.8% (29.7–58.9), respectively. The 10-year DFS results for NCCN low, favourable-intermediate and unfavourable-intermediate risk disease were 93.1% (89.6–96.7), 92.1% (87.6–96.9) and 75.9% (67.8–84.9), respectively. ConclusionsPatients with 4-year PSA ≤0.2 ng/ml may be considered cured, and could be discharged to general practitioner follow-up. LDR brachytherapy is an excellent treatment option for patients with low and favourable-intermediate risk prostate cancer, but those with unfavourable-intermediate risk disease should be considered for treatment intensification strategies.