Prostate V100 Research Articles

Overview of treatment plan quality in a high dose rate prostate brachytherapy workflow

PurposeHigh dose rate brachytherapy (HDR-BT) has been shown to be an effective treatment for prostate cancer, with treatment plan quality dependent on a number of factors. In this work, we report on the overall performance of our Ultrasound (US)-based workflow and the impact of several treatment-specific variables. Methods and MaterialsPatients who underwent HDR-BT (boost, monotherapy, and retreatment) using Varian Bravos/US from 2021-2023 were sampled for this study. Treatment plan quality was analyzed and plans were categorized with regard to a number of metrics, including: prostate volume, treating physician, planning physicist, number of needles included, estimated planning time, rectum-prostate separation, and bladder-prostate separation. The performance of this program was compared to the performance of our program using previously used modality combinations: Varian Varisource/US, Elekta microSelectron/CT. ResultsPlan quality for our Bravos/US workflow was shown to be consistently above acceptability criteria for all personnel involved; on average: prostate V100%: 98.9±0.1%, rectum V75%: 0.04±0.01cc, bladder V75%: 0.06±0.01cc, urethra V125%: 0.00±0.00cc. Prostate coverage was statistically improved with this workflow compared to that using our previous modalities. There was a statistical correlation between organ-at-risk (OAR) sparing/prostate coverage ratio and prostate volume, number of needles/prostate volume, bladder-prostate separation, and rectum-prostate separation. There was no correlation between plan quality and planning time. ConclusionsOur US-based HDR-BT program led to target coverage and OAR sparing that exceeded department thresholds. Results were acceptable regardless of the personnel involved and improved plan quality was obtained using more needles/prostate volume and increased spacing between the prostate and the rectum and bladder.

Prostate size, source configuration, and dosimetry dynamics of stranded 125I seed implants

PURPOSETo quantify changes in prostate size and seed movement over time after transperineal implantation of stranded 125I seeds, and to determine their impact on prostate dosimetry. METHODSCT and MR (T2, balanced steady-state free precession) image triplets were acquired on days 0, 3, 10, and 30 for a cohort of 20 patients and registered automatically. Prostate contours were drawn on MR-T2 images; seeds were found and matched in successive CT images. Prostate volume and dimensions, seed movements, and prostate dose metrics V200, V150, V100 and D90 were calculated, and their dynamic behaviors quantified in an operationally defined prostate coordinate system. RESULTSCohort-averaged reductions in prostate A-P dimension (∼8%) and L-R dimension (∼5%) inferred from seed movements agreed with those obtained from contour measurements, whereas prostate volume and S-I dimension (implant direction) reductions inferred from seed movements were overestimated by about 30%. Average overall seed movement was 4.8 ± 3.0 mm, of which the only identifiable systematic component was resolution of prostate edema. Cohort-averaged ratios of prostate V200, V150, V100, and D90 on day 30 relative to day 0 were 1.67, 1.33, 1.02, and 1.08, respectively. CONCLUSIONSPostimplant prostate size reduction in the SI (implant) direction cannot reliably be inferred from stranded seed movements. Apart from large-scale migration, residual seed movements relative to the prostate after accounting for edema resolution appear to be random. Prostate V100 and D90 changes 30 days post implant are modest, whereas those for V150 and V200 are substantial.

Dosimetric benefits and preclinical performance of steerable needles in HDR prostate brachytherapy

Prostate cancer patients with an enlarged prostate and/or excessive pubic arch interference (PAI) are generally considered non-eligible for high-dose-rate (HDR) brachytherapy (BT). Steerable needles have been developed to make these patients eligible again. This study aims to validate the dosimetric impact and performance of steerable needles within the conventional clinical setting.HDR BT treatment plans were generated, needle implantations were performed in a prostate phantom, with prostate volume > 55 cm3 and excessive PAI of 10 mm, and pre- and post-implant dosimetry were compared considering the dosimetric constraints: prostate V100 > 95 % (13.50 Gy), urethra D0.1cm3 < 115 % (15.53 Gy) and rectum D1cm3 < 75 % (10.13 Gy).The inclusion of steerable needles resulted in a notable enhancement of the dose distribution and prostate V100 compared to treatment plans exclusively employing rigid needles to address PAI. Furthermore, the steerable needle plan demonstrated better agreement between pre- and post-implant dosimetry (prostate V100: 96.24 % vs. 93.74 %) compared to the rigid needle plans (79.13 % vs. 72.86 % and 87.70 % vs. 81.76 %), with no major changes in the clinical workflow and no changes in the clinical set-up.The steerable needle approach allows for more flexibility in needle positioning, ensuring a highly conformal dose distribution, and hence, HDR BT is a feasible treatment option again for prostate cancer patients with an enlarged prostate and/or excessive PAI.

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

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

Efficacy of Curvilinear Needle Implantation for Prostate HDR Brachytherapy

High-dose-rate (HDR) brachytherapy is gaining popularity due to better dose distribution, good clinical outcomes, and convenience of the procedure. Conventionally, Rectilinear (straight needle) Method (RLM) is utilized for HDR procedure. However, the efficacy of a newly developed technique, the Curvilinear (curved needle conforming the prostate shape) Method (CLM), for HDR brachytherapy has not yet been explored. In this study, efficacy of the CLM is evaluated. The CLM technique is expected to significantly improve the radiation dose distribution with small number of needles that will potentially improve the clinical outcomes. Randomly 16 prostate cancer patients were selected (median age: 68.3 yrs, Stage: T1-T2a) from an IRB approved pool of patients. Prostate and OARs (urethra, rectum and bladder) were contoured on T2-weigthed MRI for all the patients. Thirty-two HDR plans, 16 for RLM and 16 for CLM, were prepared using Oncentra treatment planning software with Ir-192 isotope and were optimized using Hybrid Inverse treatment Planning Optimization (HIPO) tool. Prescription dose was 15 Gy in single fraction. Data for relevant parameters (V100, V200, D90, D10, Dmax, etc.) for prostate and OARs were collected using the dose-volume histogram. P-value less than equal to 0.05 was considered statistically significant. Average prostate volume was 33.1cc (range 17.7-51.3cc, median 30.6cc). In CLM technique the target coverage and dose constraints for OARs were improved by 0.3%-6.4% and 1.6%-34.2%, respectively (see Table below). Certain dose constraints were difficult to meet for some cases with RLM (prostate V100 (4 pts) and V200 (5 pts); rectum Dmax (5 pts) and D12 Gy (10 pts). On average, over 44.6% (average 17.5 vs 9.7 needles) reduction of needles was achieved with CLM (p-value < 0.001). The CLM technique generated significantly improved dosimetric plans using less number of needles. Reduction in number of needles would be associated with potential decrease in toxicity and improved clinical outcomes. Future plan includes clinical implementation of the CLM technique.

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.

A dosimetric analysis of rectal hydrogel spacer use in patients with recurrent prostate cancer undergoing salvage high-dose-rate brachytherapy

We hypothesize rectal hydrogel spacer (RHS) improves rectal dosimetry in patients undergoing salvage high-dose-rate brachytherapy (HDR-BT) for intact, recurrent prostate cancer (PC). A prospectively collected institutional database was queried for recurrent PC patients treated with salvage HDR-BT from September 2015 to November 2021. Patients were offered RHS beginning June 2019. Dosimetric variables were compared between RHS and no-RHS groups for the average of two fractions using Wilcoxon rank-sum tests. Primary outcomes were rectal volume receiving 75% of prescription dose (V75%) and prostate volume receiving 100% of prescription dose (V100%). Generalized estimating equation (GEE) model was used to evaluate the association between other planning variables and rectal V75%. Forty-one PC patients received salvage HDR-BT, of whom 20 had RHS. All patients received 2400cGy in 2 fractions. Median RHS volume was 6.2cm3 (Standard deviation [SD]: ± 3.5cm3). Median follow-up was 4 months and 17 months in the RHS and no-RHS groups, respectively. Median rectal V75% with and without RHS were 0.0cm3 (IQR: 0.0-0.0cm3) and 0.06cm3 (IQR: 0.0-0.14cm3), respectively (p<0.001). Median prostate V100% with and without RHS were 98.55% (IQR: 97.86-99.22%) and 97.78% (IQR: 97.50-98.18%), respectively (p = 0.007). RHS, rectum, and prostate volumes did not significantly affect rectal V75% per GEE modeling. There was 10% G1-2 and 5% G3 rectal toxicity in RHS group. There was 9.5% G1-2 and no G3+ rectal toxicities in the no-RHS group. Absolute improvement in rectal V75% and prostate V100% was significant with RHS in PC patients undergoing salvage HDR-BT, but clinical benefit is marginal.

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.

PP09 Presentation Time: 10:50 AM: Interobserver Variability of Prostate MRI-Assisted Radiosurgery Postimplant Dosimetry: Comparison with Automatic Postimplant Dosimetry

<h3>Purpose</h3> To quantify the 2 sources of human interobserver variability (IoV) introduced during prostate MRI-assisted radiosurgery postimplant dosimetry, and compare this human variability to automatically generated postimplant dosimetry. <h3>Materials and Methods</h3> Twenty-five patients underwent LDR prostate brachytherapy (LDRPBT) and were imaged with fully balanced SSFP for postimplant dosimetry. Four certified medical dosimetrists (CMDs) identified the radioactive seeds in each of the 25 postimplant MRIs. Seven additional clinical observers, including 3 radiation oncologists (ROs), contoured the prostate and 4 organs at risk (OARs) on the MRIs. Consensus segmentation masks from the 3 ROs' contours were computed for each patient using the simultaneous truth and performance level estimation (STAPLE) algorithm. Thirty unique postimplant dosimetry plans were computed for each patient. Twenty-eight of the dosimetry plans were computed from each unique pair of the CMDs' seed plans and observer contours (4 CMDs × 7 contourers). One dosimetry plan was performed automatically for each patient using custom autosegmentation and automatic seed identification software developed previously. A reference dosimetry plan for each patient was computed using the consensus STAPLE segmentations and the seeds identified by the most experienced CMD. IoV of 5 dosimetry parameters was quantified separately for each IoV source: IoV introduced by seed localization, and IoV introduced by anatomy contouring. The coefficient of variation (CoV) of each dosimetry parameter was quantified for each patient across CMDs using the consensus STAPLE segmentations. Similarly, the CoV of each dosimetry parameter was quantified for each patient across contouring observers using the seed locations determined by the most experienced CMD. Additionally, the differences in dosimetry parameters between the reference and automatic dosimetry plans were quantified. <h3>Results/Discussion</h3> CoVs due to variability of anatomy contouring (CoV_contours) were significantly higher than those due to variability of seed localization (CoV_seeds) for all dosimetry parameters (median CoV_contours vs. median CoV_seeds: prostate D90 - 15.116% vs. 0.651%, p<0.001; prostate V100 - 5.359% vs. 0.365%, p<0.001; prostate V150 - 7.017% vs. 1.252%, p<0.001; rectum V100 - 79.230% vs. 8.688%, p<0.001; EUS V200 - 107.740% vs. 21.176%, p<0.001). CoV_contours were lower when the contouring observers were restricted to only the 3 ROs, but they were still significantly higher than CoV_seeds for all dosimetry parameters. Median differences in prostate D90, prostate V100, prostate V150, rectum V100, and EUS V200 between automatically computed and reference dosimetry parameters were 3.156%, 1.630%, -1.071%, -0.001%, and -0.002%, respectively. Most automatically computed dosimetry parameters were within the expected variability of those produced by human observers (Figure 1). <h3>Conclusion</h3> IoV of contouring constitutes the largest source of IoV in postimplant dosimetry plans performed by clinical observers. When using automatic contouring and seed localization tools, review and refinement of computer predictions will be necessary for some patients. However, automatic dosimetry tools can estimate postimplant dosimetry that is close to, or within, the expected variability of dosimetry plans produced by clinical observers.

Sunday, June 19, 202210:00 AM - 10:15 AMPO47 Presentation Time: 10:00 AM: Dose Distribution of Permanent Interstitial Brachytherapy (Iodine-125) in Comparison to Temporary Interstitial Brachytherapy (Iridium-192) with a Hydrogel Spacer for Prostate Cancer

<h3>Purpose</h3> Brachytherapy (BT) for prostate cancer can be applied as permanent interstitial brachytherapy BT (LDR, low dose rate) and temporary interstitial brachytherapy BT (HDR, high dose rate), applied also alternatively in many centers. The aim of the study was to analyze the dose distribution in- and outside the prostate. <h3>Methods</h3> The intraoperative dose distribution of 102 LDR-BT patients was compared with the dose distribution of 109 HDR-BT patients (232 HDR-BT fractions). A hydrogel spacer (HS) (10ml) was only applied before HDR-BT. For the analysis of the dose coverage outside the prostate, a 5mm margin was added to prostate volume (PV+). Prostate V100 and V150 denote the PV covered by 100% and 150% of the prescription dose, while prostate D90 and urethra D30 denote the minimum dose in 90% of the PV and 30% of the urethral volume. <h3>Results</h3> The comparison of volume and dose values is shown in the table. HDR-BT patients had on average a slightly larger PV, but considerably larger PV+. The only not significantly different value comparing both methods was prostate V100. LDR-BT was characterized by a considerably more inhomogeneous dose distribution and higher doses to the urethra. However, the minimum dose in 90% of PV+ was lower. As a consequence of the HA in HDR-BT patients, the dose to the rectum was considerably lower. <h3>Conclusion</h3> In comparison to HDR-BT, LDR-BT is characterized by a more inhomogeneous dose inside the prostate, a higher dose to the urethra and a slightly less steep dose drop-off around the prostate. The dose to the rectal wall can be considerably reduced applying the HS.

PP05 Presentation Time: 9:40 AM: 21 Gy Single Fraction Prostate HDR Brachytherapy: Mature Results of a Single Institution Prospective Study.

<h3>Purpose</h3> To present the outcome and toxicity results of a prospective trial of 21 Gy single fraction high-dose-rate (HDR) brachytherapy for men with low- or intermediate-risk prostate cancer. <h3>Materials and Methods</h3> Patients were treated according to an IRB-approved prospective study of single fraction HDR brachytherapy. All patients had low- or intermediate-risk prostate cancer with tumor stage ≤ T2b, PSA ≤ 15, and Gleason score ≤ 7. Patients with prostate volumes > 50 cc or <12 cc, taking alpha-blockers for urinary symptoms, or with baseline American Urologic Association (AUA) symptom scores > 12 were ineligible. Patients underwent trans-rectal ultrasound (TRUS)-guided trans-perineal implant of the prostate followed by single fraction HDR brachytherapy. Treatment was delivered via Ir-192 to a dose of 21 Gy, prescribed to the prostate with no additional margin applied. Treatment planning was TRUS-based with constraints as follows: prostate V100 > 95%; urethral V115 < 1%; rectal V72 ≤ 1% prescription dose. <h3>Results</h3> A total of 26 patients were enrolled. Median follow up was 4.0 years (range 0.6-5.7 years). Median age was 64 years. Median gland volume at the time of treatment was 41 cc. 88.5% of patients had T1 disease, 15.4% had Gleason score 6, 84.6% Gleason score 7, and median pre-treatment PSA was 5.0 (range 2.7-12.2) ng/mL. Acute and chronic grade 2 GU toxicity rates were 26.9% and 38.5%, respectively. Acute grade 3 GU toxicity rate was 11.5%. There were no chronic grade 3 GU toxicities. There were no grade 2+ acute or chronic GI toxicities. The 5-year biochemical failure rate was 35.1%. The 5-year radiographic local failure rate was 32.4%. Biopsy-proven local failure at 5-years was 15.3%. Two patients underwent salvage treatment after experiencing radiographic local failure, without an attempted biopsy of the prostate. No patients developed biopsy proven or radiographic regional lymph node recurrence or distant metastasis. 5-year overall survival was 96.2%. The single patient death was a result of a myocardial infarction approximately 7 months after protocol treatment. Cause-specific survival at 5 years was 100%. <h3>Conclusions</h3> Despite being well-tolerated, 21 Gy single fraction HDR brachytherapy is associated with high biochemical and local failure rates. The results from this prospective pilot study do not support continued investigation of this dosing regimen in subsequent investigation.

Sunday, June 19, 202211:30 AM - 12:30 PMPSOR1 Presentation Time: 11:30 AM: MRI-Guided Neurovascular Bundle Avoidance in HDR Prostate Brachytherapy

<h3>Purpose</h3> Ultrasound or computed tomography (CT) are typically used for treatment planning in HDR prostate brachytherapy. However, the neurovascular bundles (NVB), which are hypothesized to have a role in erectile function, are not well visualized in these studies. Our group has shown that magnetic resonance imaging (MRI) can be used to segment the NVB as an avoidance structure for external beam radiation. In this study we hypothesize that treatment planning MRI will allow avoidance of the NVB during HDR prostate brachytherapy. <h3>Materials and Methods</h3> A retrospective chart review of all individuals with prostate cancer treated with radiation therapy at a single institution was used to identify patients who had HDR brachytherapy as monotherapy. All patients underwent TRUS-guided HDR catheter placement followed by CT and MRI for treatment planning. Patients were treated with two 13.5 Gy fractions utilizing standard clinical plans that optimized prostate coverage and minimized irradiation of the standard organs at risk (OARs) - bladder, rectum, and urethra. When applicable, MRI-defined GTVs were targeted for dose escalation to 150%. Experimental NVB-sparing plans were generated to maintain target coverage and OAR constraints but also to add avoidance of the NVBs. The left and right NVB were contoured on the treatment planning MRI and used as avoidance structures with 0 margin. Differences between target and OAR doses in the original and NVB-sparing plans were assessed pairwise using a two-tailed t-test. <h3>Results</h3> 15 prostate cancer patients at a single institution were treated with HDR monotherapy were included. Segmentation of the left and right NVB was feasible for all patients and 13 MRI-defined GTVs were targeted for dose escalation in 11 patients. Compared to their paired original plans, NVB-sparing plans reduced NVB D0.01cc (18.2 vs 14.6 Gy, p<0.01) and V100 (0.1 cc vs 0.0 cc, p<0.01). There was no difference in prostate D90 (108% vs 108%, p=0.19) and V100 (96.7 vs 95.9%, p=0.17) between plans; prostate V150% (36.5% vs. 34.3%, p<0.01) and V200% (14.4% vs 13.5%, p<0.01) slightly decreased in the NVB-sparing plans. Bladder V75 (0.3 cc vs 0.3 cc, p=1.0), rectum V75 (0.2 cc vs. 0.2 cc, p=0.75), and urethra V125 (0.03 cc vs. 0.03 cc, p=0.33) were similar between plans. In the subset of patients with GTVs, the mean GTV V150 decreased from 80.9% to 74.8% (p = 0.04) in the NVB-sparing plans; in one case NVB-sparing led to GTV min dose less than 100%. <h3>Conclusions</h3> NVB-sparing prostate HDR brachytherapy is feasible. Treatment planning MRI should be considered for NVB delineation. NVB-sparing should be approached with caution if GTVs are in close proximity. Evaluation of the clinical impact of MRI-delineated NVB irradiation is underway.

PSOR11 Presentation Time: 12:20 PM: Long-Term Experience with Pd-103 Prostate Brachytherapy

<h3>Purpose</h3> Although long-term control rates after low dose-rate brachytherapy are available, the majority of such series report patients treated with I-125 or Cs-131, whereas relatively fewer series have reported long-term results with Pd-103. We herein report our long-term experience using Pd-103. <h3>Materials and Methods</h3> Patients were treated with Pd-103 brachytherapy, either monotherapy or as boost with external beam. bRFS was defined as interval from implant date to biochemical failure using Phoenix criteria, while MFS was defined as the interval from implant to development of radiographic evidence of extraprostatic disease or death from any cause. Cox proportional hazards models were constructed with NCCN risk stratification. We also performed a preliminary dosimetric analysis of prostate D90 and V100 (Day 1) to assess implant quality as a predictive factor for bRFS and MFS. <h3>Results</h3> 495 patients treated between 2004-2019 consisted of 53 very-low, 218 low, 177 intermediate (119 favorable, 58 unfavorable), 32 high, and 15 very high-risk patients; the majority of patients with high-risk disease were treated in the period following ASCENDE-RT. One hundred twenty (24.2%) patients received external beam radiation (EBRT); 197 (39.8%) patients received androgen deprivation therapy. Median follow-up was 4.75 years, (0.1- 16.6 years); 168 (34%) of patients had ≥7 years of follow-up. Overall, biochemical relapse occurred in 32 (6.4%) of patients. At 5, 7, and 10 years post-implant, biochemical control rates (95% confidence) were 93.9% [91.5-96.3%], 93% [90.3-95.7%], and 90% [85.9-94.3%], respectively. Similarly, at 5, 7, and 10- years post-implant, 96.4% [94.3-98.5%], 94% [91.1-96.9%], and 88.7% [84.1-93.6%] of patients were free of metastatic disease or death. Among 9 patients with clinical relapse, 5 patients (1.0%) had pelvic nodal involvement and 4 (0.8%) had distant metastatic disease. With regard to metastases and death, high-risk prostate cancer was significantly associated with worse MFS, HR = 5.69 [1.58-20.5] (multivariate) and bRFS, HR = 3.43 [1.10-10.7]. Median MFS in the high-risk group was 13.7 years post-implant; median bRFS was 8.45 years. Low- and intermediate-risk patients had >80% freedom from metastases and all-cause death at 10 years, p = 0.03. Both low- and intermediate-risk patients had similarly excellent survival after brachytherapy, p = 0.3 (bRFS) and p = 0.11 (MFS). Overall, prostate D90 or V100 were not significantly associated with bRFS or MFS, p > 0.3. However, overall implant quality was high, with a median D90 of 112.7% [102.9-124.4]. <h3>Conclusions</h3> Brachytherapy with Pd¹⁰³ results in excellent long-term biochemical and local control at 5, 7, and 10 years. Dosimetry indicators were not significant predictors in this cohort, presumably because implant quality was consistently high.

Feasibility of online adaptive HDR prostate brachytherapy: A novel treatment concept

PurposeThe purpose of this study was to determine the feasibility of online adaptive transrectal ultrasound (TRUS)-based high-dose-rate prostate brachytherapy (HDRPBT) through retrospective simulation of source positioning and catheter swap errors on patient treatment plans. MethodSource positioning errors (catheter shifts in 1 mm increments in the cranial/caudal, anterior/posterior, and medial/lateral directions up to ±6 mm) and catheter swap errors (between the most and least heavily weighted) were introduced retrospectively into DICOM treatment plans of 20 patients that previously received TRUS HDRPBT. Dose volume histogram (DVH) indices were monitored as errors were introduced sequentially into individual catheters, simulating potential errors throughout treatment. Whenever DVH indices were outside institution thresholds: prostate V100% <95%, urethra D0.1cc >118% and rectum Dmax >80%, the plan was adapted using remaining catheters (i.e., simulating previous catheters as previously delivered). The final DVH indices were recorded. ResultsProstate coverage (V100% >95%) could be maintained for source position errors up to 6 mm through online plan adaptation. The source position error at which the urethra D0.1cc and rectum Dmax was able to return to clinically acceptable levels using online adaptation varied between 6 mm to 1 mm, depending on the direction of the source position error and patient anatomy. After introduction of catheter swap errors to patient plans, prostate V100% was recoverable using online adaptation to near original plan characteristics. Urethra D0.1cc and rectum Dmax showed less recoverability. ConclusionOnline adaptive HDRPBT maintains the prostate V100% to clinically acceptable values for majority of directional shifts. However, the current online adaptive method may not correct for source position errors near organs at risk.

HDR prostate brachytherapy plan robustness and its effect on in-vivo source tracking error thresholds: A multi-institutional study.

PurposeThe purpose of this study was to examine the effect of departmental planning techniques on appropriate in‐vivo source tracking error thresholds for high dose rate (HDR) prostate brachytherapy (BT) treatments, and to determine if a single in‐vivo source tracking error threshold would be appropriate for the same patient anatomy.MethodsThe prostate, rectum, and urethra were contoured on a single patient transrectal ultrasound (TRUS) dataset. Anonymized DICOM files were disseminated to 16 departments who created an HDR prostate BT treatment plan on the dataset with a prescription dose of 15 Gy in a single fraction. Departments were asked to follow their own local treatment planning guidelines. Source positioning errors were then simulated in the 16 treatment plans and the effect on dose–volume histogram (DVH) indices calculated. Change in DVH indices were used to determine appropriate in‐vivo source tracking error thresholds. Plans were considered to require intervention if the following DVH conditions occurred: prostate V100% < 90%, urethra D0.1cc > 118%, and rectumtt Dmax > 80%.ResultsThere was wide variation in appropriate in‐vivo source tracking error thresholds among the 16 participating departments, ranging from 1 to 6 mm. Appropriate in‐vivo source tracking error thresholds were also found to depend on the direction of the source positioning error and the endpoint. A robustness parameter was derived, and found to correlate with the sensitivity of plans to source positioning errors.ConclusionsA single HDR prostate BT in‐vivo source tracking error threshold cannot be applied across multiple departments, even for the same patient anatomy. The burden on in‐vivo source tracking devices may be eased through improving HDR prostate BT plan robustness during the plan optimisation phase.

Correlations between intraplan and postplan parameters in I-125 permanent prostate brachytherapy using loose seeds or linked seeds.

ABSTRACTThe purpose of this study was to determine the most appropriate seed arrangement by comparing two different methods (linked seeds and loose seeds). A total of sixty-one patients (28 linked seed brachytherapy cases and 33 loose seed brachytherapy cases) with clinically localized prostate cancer were treated with I-125 permanent prostate brachytherapy. Modified peripheral loading was the method used for seed placement. The parameters evaluated were as follows: prostate D90, V100, and V150; urethral D90, D10, and D5; and rectal V100 (RV100) and D2 (RD2). Coefficient parameters (r and r2) were assessed by regression analysis. Prostate V150, urethral D90, urethral D10, urethral D5, and RD2 showed significant correlations between both methods in all patients. Urethral D90, urethral D10, urethral D5, and RD2 showed significant correlations in patients who received linked seed brachytherapy. Prostate V150, urethral D90, urethral D10, urethral D5, RV100, and RD2 showed significant correlations in patients who received loose seed brachytherapy. Urethral D90, urethral D10, urethral D5, and RD2 showed significant correlations in the linked seed and loose seed brachytherapy analyses. In contrast, prostate D90 and prostate V100 showed no correlation. Parameters of normal organ damage showed good correlations between intraplan and postplan parameters. These parameters may be useful to determine normal organ damage during guided brachytherapy with two different methods (linked seeds and loose seeds).

Dose differentiated high-dose-rate prostate brachytherapy: a feasibility assessment of MRI-guided dose escalation to dominant intra-prostatic lesions.

Prostate brachytherapy is routinely performed with trans-rectal ultrasound (TRUS)- or computed tomography (CT)-based planning that cannot delineate dominant intra-prostatic lesions (DILs). In contrast, magnetic resonance imaging (MRI)-based planning allows for more accurate DIL delineation and dose escalation. This study assessed the maximum achievable dose escalation to DILs. We retrospectively identified 24 patients treated with high-dose-rate (HDR) prostate brachytherapy boost (15 Gy in 1 fraction). All patients had a pre-treatment prostate MRI with 1-3 DILs. MRIs were used to delineate DILs and were co-registered to TRUS intra-procedure. Treatment plans were experimentally re-optimized to escalate DIL dose. Dosimetric indices from the original and re-optimized plans were compared using two-tailed paired t-test. Re-optimized plans were deemed acceptable if they achieved all of the following criteria: prostate D90 > 100%, prostate V100 > 90%, urethra D10 < 118%, rectum V80 < 0.5 cc, bladder D1cc < 75%, or if they did not exceed organs at risk (OARs) doses of the original plan. The mean DIL D90 was significantly increased from 134% of the prescription dose on the original plans to 154% on the re-optimized plans. The mean urethra D10 and mean bladder D1cc were significantly reduced from 123% to 117% and from 72% to 65%, respectively. Prostate D90 was reduced from 106% to 102%, and prostate V100 was reduced from 93% to 91%. We re-optimized HDR brachytherapy plans to escalate DILs dose to a mean D90 of > 150% while maintaining favorable prostate coverage and OARs doses. We propose DIL D90 dose of > 150% (22.5 Gy) as an achievable goal.

Control charts for evaluation of quality of low-dose-rate brachytherapy for prostate cancer.

PurposeVariations in dosimetric outcomes among patients treated with low-dose-rate brachytherapy for prostate cancer exist, even when implants are within dose constraints. Here, we used control charts to investigate reasons for intra-patient dosimetric variability.Material and methodsUnivariate and multivariate control charts for prostate V100 (percentage of prostate volume that received 100% of prescribed radiation dose), D90 (radiation dose to 90% of prostate volume), and RV100 (rectal wall volume that received 100% of prescribed radiation dose) were generated for 212 consecutive prostate cancer patients implanted with iodine-125 (125I) radioactive seeds at the Princess Margaret Cancer Centre. Control limits were calculated based on the first fifty implants. Data points that were out of control were identified, and their pre-treatment and post-treatment dosimetric and clinical parameters were compared to data points that were in-control, using Student’s t-test.ResultsAll implants were clinically acceptable. Twelve data points exceeded multivariate control limits. Ten of those points fell below the lower control limit of V100 control chart. Average prostate edema in the 10 out-of-control patients on both multivariate and V100 charts was 8.3%, as compared to 0.4% for in-control patients (p < 0.04). Two patients were observed to be out-of-control on multivariate control chart, but not on V100 control chart, and were found to have a reduction in prostate volume of 19.1% and 20.1% at one month after seed implant, compared to prostate volumes of pre-implantation evaluations.ConclusionsControl charts helped in identifying cases with out-of-control variability in post-plan prostate dosimetry. Post-treatment prostatic edema and contraction are important factors predicting variability in patients treated with 125I permanent seed brachytherapy.

Dosimetric Predictors of Toxicity and Quality of Life Following Single Fraction High Dose-Rate Prostate Brachytherapy

<h3>Purpose/Objective(s)</h3> Little is known about optimal dose constraints when high dose rate (HDR) brachytherapy is used as monotherapy for prostate cancer. Most dose constraints for HDR monotherapy were extrapolated from predictors of toxicity when HDR brachytherapy was combined with external beam radiotherapy as a boost. We sought to determine clinical and dosimetric predictors of toxicity and health related quality of life (HRQOL) in men treated with HDR brachytherapy as monotherapy. <h3>Materials/Methods</h3> Eligible patients were treated with single fraction HDR brachytherapy as monotherapy on two prospective clinical trials at a single institution. Patients in the first trial (HDR-mono) received a single fraction of 19 Gy without a dominant intraprostatic lesion (DIL) boost, and patients from the second trial (MARS) received 19 Gy in a single fraction with an MRI-guided DIL boost to ≥ 23 Gy. ADT was not used. Univariable and multivariable logistic regression was used to evaluate clinical (age, IPSS score, prostate volume, alpha blocker use at baseline, and receipt of a DIL boost) and dosimetric (prostate V100, V150, V200, D90, Urethral Dmax and D10, and Rectal Dmax and V80) predictors of CTCAE v4 acute/late toxicity and HRQOL changes measured with expanded prostate index composite (EPIC). Three classifications of late minimally clinically important changes (MCICs) were evaluated: small (> 0.5 standard deviation [SD]), moderate (> 1.0 SD) and severe (> 2.0 SD) declines compared to baseline. <h3>Results</h3> 147 patients were included (87 from HDR-mono, 60 from MARS). Median follow-up was 62.8 months. Only increasing prostate size predicted acute GU toxicity ≥ grade 2 (OR 1.05, 95% CI 1.01–1.09, <i>P</i> = 0.021). On multivariable regression, predictors of late GU toxicity ≥ grade 2 were not receiving a DIL boost (OR 3.78, 95% CI 1.88–7.83, <i>P</i> < 0.001) and higher baseline IPSS score (OR 1.89, 95% CI 1.89–3.18, <i>P</i> = 0.015). Rectal and urethral dose constraints were not associated with late GU/GI toxicity ≥ grade 2. Contrary to our hypothesis, small (OR 0.91, 95% CI 0.81–0.98, <i>P</i> = 0.032) and moderate (OR 0.91, 95% CI 0.80–0.98, <i>P</i> = 0.037) urinary MCICs were less frequent in those with higher urethral Dmax. No impact of urethra D10 on urinary MCICs was seen. Rectal Dmax and V80 did not predict bowel MCIC changes at any threshold. <h3>Conclusion</h3> We were unable to identify dose constraints that were predictive of late toxicity or relevant HRQOL changes in single fraction HDR brachytherapy. This suggests dose parameters used in these trials were safe, and that minor variability in plan dosimetry likely has little clinical significance. While increasing urethral Dmax paradoxically predicted for less frequent urinary MCICs, we do not believe this finding is clinically relevant. Further research exploring optimal dose constraints to be used in HDR brachytherapy as monotherapy for prostate cancer is warranted.

Learning-Based Prostate Needle Position Prediction for HDR Brachytherapy

During prostate high-dose-rate (HDR) brachytherapy, physicians select needle positions in a peripheral loading technique based on experience but without knowledge of the achievable dose distribution. Sub-optimal needle placement may lead to unfavorable dose distributions even after plan optimization. We propose a new deep learning-based method to predict HDR needle position for prostate HDR brachytherapy.The proposed framework consists of three major steps: (1) deformable registration via registration network (Reg-Net), (2) multi-atlas ranking and (3) needle regression. To model the global spatial relationship among multiple organs, binary masks of the target and organs at risk are transformed into distance maps which describe the distance of each local voxel to the organ surfaces. Reg-Net is utilized to deformably register the distance maps from multi-atlas set to match a patient's distance map and then bring needle maps from multi-atlas to this patient via spatial transformation. Several criteria are used for multi-atlas ranking including prostate volume similarity, multi-organ semantic image similarity and needle position criteria. Finally, needle regression is used to refine the final needle positions. A retrospective study of consecutively treated patients was used to evaluate the feasibility of the proposed method. We performed a five-fold cross validation to evaluate the proposed method. We generated a new dose plan for each patient based on predicted needle location. Target and organ dose volume histogram (DVH) metrics were used to quantify the difference between the clinical and predicted needle plans. All plans were normalized to prostate V100 of 95%.Ninety predicted needle plans were compared to clinical plans. In each case, the needle prediction algorithm completed within 1 minute. See table for comparison of target and organ DVH metrics (mean and standard deviation). Predicted needle plans had slightly greater target dose heterogeneity. The RTOG constraints of bladder V75% < 1 cc, rectum V75% < 1cc, and urethra V125% < 1 cc were met in all predicted plans.It is feasible to use this novel deep-learning-based method to predict needle locations for HDR prostate brachytherapy a priori. This strategy merits further study to improve utilization and quality of prostate brachytherapy.