Prostate V100 Research Articles

US-Planned HDR Prostate Brachytherapy Boost: Acute and Late Toxicity

HDR prostate brachytherapy has been combined with external beam (EBRT) for over 2 decades, using a wide range of dose and fractionation schedules. Complications such as urethral strictures are reported from 2-30%. We evaluate acute and long term urinary and bowel toxicity in our first 5 years’ experience. From 06/2011 to 05/2016, 123 patients with upper tier intermediate and high risk prostate cancer were treated by 192-Ir HDR brachytherapy combined with EBRT in 3 consecutive IRB-approved clinical trials with data collected prospectively. EBRT with fiducials for image-guidance followed US-planned HDR BT within 7 days (46Gy/ 23: 81% 3DcRT, 19% IMRT/VMAT). Initially 20Gy/2 in 2 separate implants was prescribed (42%), but later 15Gy/ 1 (58%). HDR planning constraints were prostate V100 ≥98% and V125: 55-62%, urethra Dmax <115% and rectal D1cc ≤70%. Tumor stage was T1c: 16%, T2: 77% and T3: 7%. Gleason score was 7 in 68%; 8-10 in 32%. Median PSA was 10.1 (range: 1.7-35.8). 65% were upper tier intermediate risk; 35% high risk. 54% had androgen ablation (< 6 mos: 7.5%, 6 mos: 21.5%, 9-12 mos: 60%). Median prostate volume at HDR was 35cc (range: 14-82) Toxicities were graded using CTCAE, V3.0. Median follow-up is 24.3 mos (range: 7– 69) but differed between the 2 cohorts, being 43 mos for 20 Gy/2 (range: 23-69) and 17 mos for 15 Gy/1 (range: 7-43).Catheterization was required post implant in 3.3% and in all cases consisted of clean intermittent self-catheterization for 1-5 weeks during the EBRT that immediately followed the HDR, the majority in the 15 Gy/1 cohort (3 of 4). The average prostate volume for these patients was 48cc vs 37cc for all patients. Acute Grade 1 GU toxicity occurred in 52%, G2 in 13%, and G3 in 3.3%. Acute Grade 1 GI toxicity occurred in 43%, G2 in 5.7%, with no G3 or G4 toxicity. Late GU toxicity was Grade 1: 40%, G2: 7.3%, and G3: 4.0 %. Of these, late Grade 1 hematuria was reported by 5.7% and Grade 2 in 1.6%. Urethral strictures occurred in 3.2% (n=4) after an average of 2.8 years (range: 2.2- 3.5 years), equally divided between the two fractionation schemes. All 4 have been effectively managed, 3 with a single visual internal urethrotomy and one with dilatation. Late GI toxicity was Grade 1: 14.6%, G2: 7.3%, and G3: 3.2%. One patient had a colostomy for a sigmoid stricture outside the HDR radiation volume. Rectal bleeding occurred in 11 patients (8.9%), Grade 1 in 7 patients, and G3 in 4, after an average of 17.5 mos (range 3-35). For G3 bleeding, 75% received 15Gy/ 1. The average rectal D1cc for all patients was 61.5% (range 51%-71%) and was not different for those with rectal bleeding (p=0.43). US-planned HDR brachytherapy as 2 fractions of 10 Gy or a single 15 Gy combined with EBRT is well tolerated with low risk of late toxicities. Urethral strictures were seen in 3.2% and grade 3 rectal bleeding in 3.2%. A single 15 Gy is convenient and cost-effective but observed toxicity may increase with longer follow up as only 50% have reached the median time for toxicity development.

A novel urethral sparing technique for high-dose-rate prostate brachytherapy after transurethral resection of the prostate

PurposeThe purpose of this study was to assess retrospectively the variability of the urethral dose optimized using a Foley catheter versus urethral contrast injected using a new modified triple-lumen catheter, in CT-based high-dose-rate (HDR) prostate brachytherapy of posttransurethral resection of prostate (TURP) patients. Methods and MaterialsAt our institution, there were six post-TURP patients with prostate carcinoma between July 2014 and April 2016 who underwent transperineal interstitial HDR brachytherapy (16 needles). A custom modified triple-lumen catheter was placed to inject contrast into the TURP defect. Three-dimensional optimal plans using inverse planning simulated annealing algorithm was generated according to radiation therapy oncology group dose requirements. Alternative plans were retroactively generated for comparison using standard technique based on a Foley catheter as a urethral constraint volume for each patient with the same weighting factors. We compared the dosimetry parameters in each planning using Wilcoxon's ranked sum nonparametric test. ResultsThe median followup of all patients was 17.5 months. No significant genitourinary or gastrointestinal toxicity was noted using this technique. In the dosimetric analysis, the prostate V100 values and TURP urethral V100 were significantly different between plans with and without the contrast (V100 [mean]: 92.4 [%] vs. 94.4 [%], p = 0.046; TURP UV100 [mean]: 1.4 cc vs. 2.2 cc, p = 0.028). There were no statistical differences in the mean values of planning target volume V150%, V200%, and D90, and each bladder V75 and rectum V75. ConclusionsPost-TURP HDR brachytherapy with urethral contrast showed significantly more volume effect of the TURP defect than that with a Foley catheter alone. Better visualization of the TURP defect should lead to more accurate urethral sparing administration of HDR brachytherapy which is necessary to prevent urethral complication.

Risk prediction-modeling approach to identify best predictive parameters for urethral strictures after prostate brachytherapy.

87 Background: Urethral strictures (US) are a rare complication of prostate brachytherapy (BXT), with prior studies showing radiation dose to the bulbomembranous urethra is associated with stricture formation. This retrospective case-control study explored clinical and dosimetric parameters associated with the development of BXT-related urethral strictures. Methods: A cohort of 34 patients developed urethral strictures after BXT at our institution for the period of 2008-2014. Each case was matched with two controls (68 controls) that had not developed a US according to similar baseline International Prostate Symptom Score (IPSS), planned prostate volume, post-implant prostate V150, and post-implant prostate D90 dosimetry parameters. US development was compared with clinical (i.e. age, IPSS, etc) and dosimetric (i.e. prostate, urethra, urethra segments) variables. Statistical modeling for risk prediction was applied, which included adjusted R2, Mallows’ C Selection (Cp), Schwartz’s information criterion (BIC), forward selection (FS), and backward selection (BS) to identify the parameters with prediction ability of toxicity. CV analysis was performed to select the best subset selection on the full data set in order to obtain the most predictive parameter selection. Results: The results show that the R2statistic increases from 6% (only one) to 33 %, (all of the parameters included). The table demonstrates minimum best-fit parameters in the different models. (See table.) CV with minimum standard error (MSE) identified a model with 5 parameters that included age, baseline IPSS, UD30, UD5, and U5mm V200Apex shows best prediction ability for US. Conclusions: This modeling approach, which is novel in BXT, helped to identify a combination of parameters with some predictive ability of radiation toxicity. Further evaluation is required to validation. [Table: see text]

Dosimetry advantages of intraoperatively built custom-linked seeds compared with loose seeds in permanent prostate brachytherapy.

PurposeThe aim of this study was to compare the implant quality between intraoperatively built custom-linked seeds (IBCL) and loose seeds (LS) retrospectively.Material and methodsThis study included 74 prostate cancer patients who were treated with permanent prostate brachytherapy (PPB) using IBCL (n = 37) or LS (n = 37) between July 2014 and June 2016. Dose-volume histogram (DVH) parameters, seed migration, and operation time were compared between the IBCL and LS groups. In addition to the standard target volume of the whole prostate gland, DVH parameters for prostate plus a 3 mm margin (CTV) were evaluated.ResultsIn intraoperative planning, prostate V150 was lower (54.8% vs. 59.6%, p = 0.027), and CTV V100 (88.1% vs. 85.6%, p = 0.019) and D90 (98.5% vs. 92.6%, p = 0.0033) were higher in the IBCL group compared with in the LS group. In post-implant dosimetry, prostate V100 (96.9% vs. 95.2%, p = 0.020), CTV V100 (85.6% vs. 81.7%, p = 0.046), and CTV D90 (94.2% vs. 86.5%, p < 0.001) were higher, and prostate V150 (57.1% vs. 64.5%, p = 0.0051) and CTV V150 (31.5% vs. 35.7%, p = 0.046) were lower in the IBCL group compared with in the LS group. Regarding DVH changes between intraoperative planning and post-implant dosimetry, the decrease in prostate D90 was significantly lower in the IBCL group than in the LS group (–1.16% vs. –4.17%, p < 0.001). For the IBCL group, the operation time was slightly but significantly longer than that for the LS group (50.5 minutes vs. 43.7 minutes, p = 0.011). However, the seed migration rate was significantly lower in the IBCL group than in the LS group (5% vs. 41%, p < 0.001).ConclusionsIntraoperatively built custom-linked is more advantageous than LS in terms of dosimetric parameters and migration.

Evaluation of intraoperative magnetic resonance imaging/ultrasound fusion optimization for low-dose-rate prostate brachytherapy.

PurposeIntraoperative planning with transrectal ultrasound (US) is used for accurate seed placement and optimal dosimetry in prostate brachytherapy. However, prostate magnetic resonance imaging (MRI) has shown superiority in delineation of prostate anatomy. Accordingly, MRI/US fusion may be useful for accurate intraoperative planning. We analyzed planning with MRI/US fusion to compare differences in dosimetry and volume to that derived from the postoperative computed tomography (CT).Material and methodsTwenty patients underwent preoperative prostate MRI, which was fused intraoperatively with US during prostate brachytherapy. Intraoperative 125I or 103Pd seed placement was modified by the use of MRI fusion when indicated. Following implantation, dose comparisons were made between data derived from MRI/US and that from post-operative CT scans. Plan parameters analyzed included the D90 (dose to 90% of the prostate), rectal D30, V30 (volume of the rectum receiving 30 percent of dose), and prostate V100.ResultsThe median number of seeds implanted per patient was seventy-six. The MRI measured prostate volume, which was on average 4.47 cc larger than the CT measured prostate volume. In 9 patients, the apex of the prostate was better identified under MRI with the fusion protocol, and an average of 4 fewer seeds were required to be placed in the apex/urinary sphincter region. Both MRI and US individually showed a reduced intraoperative prostate D90 in comparison to the postoperative CT, with a larger mean difference for MRI in comparison with US (9.71 vs. 4.31 Gy, p = 0.007). This was also true for the prostate V100 (5.18 vs. 2.73 cc, p = 0.009). Post-operative CT underestimated rectal D30 and V30 in comparison to both MRI and US with MRI showing a larger mean difference than US for D30 (40.64 vs. 35.92 Gy, p = 0.04) and V30 (50.20 vs. 44.38 cc, p = 0.009).ConclusionsThe MRI/US fusion demonstrated greater prostate volume compared to standard CT/US based planning likely due to the better resolution of the prostate apex. Furthermore, rectal dose was underestimated with CT vs. MRI based planning. Additional study is required to assess long-term clinical implications of disease control and effects on long-term toxicity, especially as related to the rectum and urinary sphincter. MRI/US intraoperative fusion may improve prostate dosimetry while sparing the rectum and urethra, potentially impacting disease control and late toxicity.

Evaluation of a Machine-Learning Algorithm for Treatment Planning in Prostate Low-Dose-Rate Brachytherapy

This work presents the application of a machine learning (ML) algorithm to automatically generate high-quality, prostate low-dose-rate (LDR) brachytherapy treatment plans. The ML algorithm can mimic characteristics of preoperative treatment plans deemed clinically acceptable by brachytherapists. The planning efficiency, dosimetry, and quality (as assessed by experts) of preoperative plans generated with an ML planning approach was retrospectively evaluated in this study. Preimplantation and postimplantation treatment plans were extracted from 100 high-quality LDR treatments and stored within a training database. The ML training algorithm matches similar features from a new LDR case to those within the training database to rapidly obtain an initial seed distribution; plans were then further fine-tuned using stochastic optimization. Preimplantation treatment plansgenerated by the ML algorithm were compared with brachytherapist (BT) treatment plans in terms of planning time (Wilcoxon rank sum, α=0.05) and dosimetry (1-way analysis of variance, α=0.05). Qualitative preimplantation plan quality was evaluated by expert LDR radiation oncologists using a Likert scale questionnaire. The average planning time for the ML approach was 0.84±0.57minutes, compared with 17.88±8.76minutes for the expert planner (P=.020). Preimplantation plans were dosimetrically equivalent to the BT plans; the average prostate V150% was 4% lower for ML plans (P=.002), although the difference was not clinically significant. Respondents ranked the ML-generated plans as equivalent to expert BT treatment plans in terms of target coverage, normal tissue avoidance, implant confidence, and the need for plan modifications. Respondents had difficulty differentiating between plans generated by a human or those generated by the ML algorithm. Prostate LDR preimplantation treatment plans that have equivalent quality to plans created by brachytherapists can be rapidly generated using ML. The adoption of ML in the brachytherapy workflow is expected to improve LDR treatment plan uniformity while reducing planning time and resources.

Sensitivity of clinically relevant dosimetric parameters to contouring uncertainty in postimplant dosimetry of low-dose-rate prostate permanent seed brachytherapy

PurposeThere is strong evidence relating postimplant dosimetry for low-dose-rate prostate seed brachytherapy to local control rates. The delineation of the prostate on CT images, however, represents a challenge due to the lack of soft-tissue contrast to identify the prostate borders. This study aims at quantifying the sensitivity of prostate V100 and D90 to contouring uncertainty as clinically relevant parameters for evaluation of target coverage in postimplant dosimetry. Methods and MaterialsCT images, postoperative plans, and contours of a cohort of patients (n = 43; low risk = 55.8%, intermediate risk = 39.5%, high risk = 4.7%), who had received prostate seed brachytherapy, were imported into MIM Symphony treatment planning system. The prostate contours in postimplant CT images were expanded or contracted uniformly in extents of ±1.00 mm, ±2.00 mm, ±3.00 mm, ±4.00 mm, and ±5.00 mm. The values for V100 and D90 were extracted from dose-volume histograms for each contour and compared. ResultsSignificant changes were observed in the values of D90 and V100 as well as the number of inacceptable plans for expansion or contraction of only few millimeters. Evaluation of a plan coverage based on D90 was found to be less sensitive to systematic contouring errors compared with V100. Number of plans incorrectly identified for lack or adequacy of coverage is lower using D90 compared with V100 for the same margin of error. ConclusionsEvaluation of a plan coverage based on V100 is too sensitive to systematic contouring errors of prostate. D90 increases the accuracy of CT-based postimplant quality assurance in identifying plans with insufficient coverage compared with V100.

Reductions in Prostatic and Urethral Doses Are Associated With Less Acute Morbidity in Patients Undergoing Pd-103 Brachytherapy: Substantiation of the Rationale for Focal Therapy

Interest in prostate brachytherapy dose reduction or focal treatment exists due to expected reductions in treatment morbidity, but analyses in the modern era have not generally corroborated relationships between prostate or urethral dose and urinary toxicity. However, such analyses have been performed on cohorts receiving uniform prescribed doses. We analyzed patients treated to differing prescription doses to assess for effects of dose reduction on acute urinary morbidity, and to estimate the magnitude of such effects. An IRB-approved database was utilized. Patients treated with Pd-103 to either 125Gy or 90-100Gy were assessed using patient-reported International Prostate Symptom Score (IPSS) at 1-month post-implant, based on published evidence showing urinary morbidity after Pd-103 peaks at 1-month. Patients in 90-100Gy cohort received supplemental EBRT 45Gy after their 1-month assessment, thus toxicities were measured prior to any contribution from EBRT. Baseline patient characteristics were compared to verify subgroup homogeneity. Univariate and multivariate stepwise logistic regression analyses were performed to determine predictors of developing >10 point increase from baseline IPSS at 1 month. Post-implant catheterization rates were compared between groups. One hundred ninety-one patients and forty patients were treated with 125Gy vs 90-100Gy Pd-103, respectively. Treatment groups were similar with respect to pre-and post-implant prostate volumes, number of seeds used, and initial IPSS. Prostate and urethra doses were uniformly higher for the 125Gy group compared to the 90-100Gy group. Prescription dose, Initial IPSS, Prostate V150, V175 and V200Gy (absolute doses), Urethral V100Gy, D5, D10, D20, D30, and D50 (absolute doses) were all significantly associated with or trended toward significance vs IPSS >10 from baseline. The multivariate model demonstrated that Prescription dose, Initial IPSS, Urethral D30, and Prostate V150, V175 and V200Gy were independent predictors of developing >10 point increase from baseline IPSS scores at 1-month follow up. Patients in the 90-100 Gy cohort had median IPSS increase from baseline of 9.7 and 60% freedom from 10-point IPSS increase at 1-month, compared to 14.1 and 29% in the 125Gy cohort (P = 0.004 and <0.001, respectively). Post-implant catheterization occurred in 7.3% of the patients treated to 125Gy versus 0% in the 90-100Gy cohort. Reduced prescription dose, urethral doses and volumes of high dose regions to the prostate correlated with reduced acute urinary morbidity after Pd-103 brachytherapy. This study suggests that focal treatment approaches with modest dose reductions to subregions of the prostate may reduce acute morbidity and potentially expand the number of patients eligible for brachytherapy. Further investigation is warranted to confirm these effects and the feasibility of focal approaches from a cancer control perspective.

Single-Fraction High-Dose-Rate Brachytherapy Using Real-Time Transrectal Ultrasound–Based Planning in Combination With External Beam Radiation Therapy for Prostate Cancer: Dosimetrics and Early Clinical Results

To validate the feasibility of a single-fraction High Dose Rate Brachytherapy (HDRBT) Boost for prostate cancer using real-time Transrectal Ultrasound (TRUS) based planning From August 2012 to September 2015, 126 patients underwent a single-fraction HDRBT boost of 15 Gy using real-time TRUS based planning. External beam radiation therapy (EBRT) (37.5 Gy/15f or 44Gy/22f or 45Gy/25f) was performed before (31%) or after (69%) HDRBT boost. Genito-Urinary (GU) and Gastro-Intestinal (GI) toxicity were assessed 4 and 12 months after the end of combined treatment using the International Prostate Symptom Score Scale (IPSS) and the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. All dose-planning objectives were achieved in 90% of patients. Prostate D90 ≥105% and ≤ 115% was achieved in 99% of patients, prostate V150 ≤ 40% in 99%, prostate V200 < 11% in 96%, urethra D10 <120% for 99%, urethra V125 = 0% in 100% and rectal V75<1cc in 93% of patients. Median IPSS score was 4 at baseline and did not change at 4 and 12 months after combined treatment. No patients developed ≥ grade 2 GI toxicity. With a median follow-up of 10 months, only two patients experienced biochemical failure. Among patients who didn’t receive ADT, cumulative percentage of patients with PSA ≤ 1 ng/mL at 4 and 18 months was respectively 23% and 66%. Single-fraction HDRBT boost of 15 Gy using real-time TRUS based planning achieves consistently high dosimetry quality. In combination with EBRT, toxicity outcomes appear promising. A longer follow-up is needed to assess long-term outcome and toxicities.

Single-fraction high-dose-rate brachytherapy using real-time transrectal ultrasound based planning in combination with external beam radiotherapy for prostate cancer: Dosimetrics and early clinical results

Purpose To validate the feasibility of a single-fraction high-dose-rate brachytherapy (HDRBT) boost for prostate cancer using real-time transrectal ultrasound (TRUS) based planning. Material and methods From August 2012 to September 2015, 126 patients underwent a single-fraction HDRBT boost of 15 Gy using real-time TRUS based planning. External beam radiation therapy (EBRT) (37.5 Gy/15 fractions, 44 Gy/22 fractions, or 45 Gy/25 fractions) was performed before (31%) or after (69%) HDRBT boost. Genito-urinary (GU) and gastro-intestinal (GI) toxicity were assessed 4 and 12 months after the end of combined treatment using the international prostate symptom score scale (IPSS) and the common terminology criteria for adverse events (CTCAE) v3.0. Results All dose-planning objectives were achieved in 90% of patients. Prostate D90 ≥ 105% and ≤ 115% was achieved in 99% of patients, prostate V150 ≤ 40% in 99%, prostate V200 Conclusion Single-fraction HDRBT boost of 15 Gy using real-time TRUS based planning achieves consistently high dosimetry quality.

SU‐F‐T‐46: The Effect of Inter‐Seed Attenuation and Tissue Composition in Prostate 125I Brachytherapy Dose Calculations

Purpose:To investigate the difference of dose distributions with/without the effect of inter‐seed attenuation and tissue compositions in prostate 125I brachytherapy dose calculations, using Monte Carlo simulations of Particle and Heavy Ion Transport code System (PHITS).Methods:The dose distributions in 125I prostate brachytherapy were calculated using PHITS for non‐simultaneous and simultaneous alignments of STM1251 sources in water or prostate phantom for six patients. The PHITS input file was created from DICOM‐RT file which includes source coordinates and structures for clinical target volume (CTV) and organs at risk (OARs) of urethra and rectum, using in‐house Matlab software. Photon and electron cutoff energies were set to 1 keV and 100 MeV, respectively. The dose distributions were calculated with the kerma approximation and the voxel size of 1 × 1 × 1 mm3. The number of incident photon was set to be the statistical uncertainty (1σ) of less than 1%. The effect of inter‐seed attenuation and prostate tissue compositions was evaluated from dose volume histograms (DVHs) for each structure, by comparing to results of the AAPM TG‐43 dose calculation (without the effect of inter‐seed attenuation and prostate tissue compositions).Results:The dose reduction due to the inter‐seed attenuation by source capsules was approximately 2% for CTV and OARs compared to those of TG‐43. In additions, by considering prostate tissue composition, the D90 and V100 of CTV reduced by 6% and 1%, respectively.Conclusion:It needs to consider the dose reduction due to the inter‐seed attenuation and tissue composition in prostate 125I brachytherapy dose calculations.

Intraoperative ultrasound-based planning can effectively replace postoperative CT-based planning for high-dose-rate brachytherapy for prostate cancer

PurposeUltrasound (US)–based planning for high-dose-rate brachytherapy allows prostate patients to be implanted, imaged, planned, and treated without changing position. This is advantageous with respect to accuracy and efficiency of treatment but is only valuable if plan quality relative to CT is maintained. This study evaluates any dosimetric impact of changing from CT- to US-based planning. Methods and MaterialsThirty patients each were randomly selected from CT-planned and US-planned cohorts. All received single fraction high-dose-rate brachytherapy (15 Gy) followed by 37.5 Gy in 15 fractions external beam radiation therapy. Prostate V90, V100, V150, V200, D90, and the dose homogeneity index were compared. For the rectum, Dmax, D0.5cc, D1cc, V10, V50, and V80 were examined. For the urethra, only Dmax and D10 were considered. ResultsUS plans had smaller 200% hot spots, although the dose homogeneity index for both was 0.7 ± 0.1. On average, plans using either modality satisfied planning goals. Although several parameters were significantly different between the two modalities (p < 0.05), the absolute differences were small. Of greatest, clinical relevance was the difference in frequency with which upper dose goals were exceeded. The prostate V200 goal was exceeded in 53% of CT-planned cases, but only 20% of those planned with US. The urethral D10 goal was never exceeded using US but was exceeded in 13% of CT cases. ConclusionsUS planning results in plans that, clinically, are dosimetrically equivalent to CT-based planning. Upper dosimetric goals are, however, exceeded less often with US than with CT.

Focal or Whole-Gland Salvage Prostate Brachytherapy with Iodine Seeds with or without a Rectal Spacer for Post-Radiotherapy Local Failure: How Best to Spare the Rectum?

Salvage Prostate Permanent Implant (sPPI) for post-radiation local failure provides high rates of biochemical control. The cumulative dose delivered to the prostate and the rectum when the dose from the primary irradiation is taken into account is still unknown. We reviewed the post-implant CT-based dosimetry of 18 selected patients who underwent sPPI with 125I seeds for isolated biopsy-proven local failure several years after External Beam Radiation Therapy (EBRT). Ten patients had whole-prostate sPPI and 8 patients had multi-parametric MRI-based focal sPPI. In eight patients, hyaluronic acid (HA) gel was injected into the prostate-rectum space. The Biologically Effective Dose (BED) of the primary EBRT and the BED of the sPPI were calculated using several α/β ratios and t1/2. The median D90 was 65.0 Gy [12.0 - 107.2] and the median prostate V100 was 45.3% [14.4 - 98.3]. The median D90 and the median V100 for the index lesion were 162.0 Gy [139.4 - 199.1] and 96.1% [88.4 - 100.0], respectively. The median cumulative BED after EBRT+sPPI for the prostate and the rectum were higher in patients treated with whole-gland sPPI than in patients treated with focal sPPI (313.5 Gy2 vs 174.4 Gy2, p = 0.06 and 258.1 Gy3 vs 172.6 Gy3, p < 0.01, respectively). The median D0.1 cc for the rectum was significantly lower in patients who had HA gel: 63.3 Gy [29.0 - 78.3] than in patients with no gel: 83.9 Gy [34.9 - 180.0] (p= 0.04). When we combined BED from primary prostate EBRT and BED from sPPI, we found that cumulative prostate and rectum BEDs were lower with focal sPPI than with whole-gland plans. D0.1cc delivered to the rectum was significantly lower after sPPI with HA gel, while there was no difference between focal or whole-gland plans.

Three-dimensional transrectal ultrasound guided high-dose-rate prostate brachytherapy: A comparison of needle segmentation accuracy with two-dimensional image guidance

PurposeConventional transrectal ultrasound guided high-dose-rate prostate brachytherapy (HDR-BT) uses an axially acquired image set for organ segmentation and 2D sagittal images for needle segmentation. Sagittally reconstructed 3D (SR3D) transrectal ultrasound enables both organ and needle segmentation and has the potential to reduce organ-needle alignment uncertainty. This study compares the accuracy of needle tip localization between the conventional 2D sagittally assisted axially reconstructed (SAAR) and SR3D approaches. Methods and MaterialsTwelve patients underwent SAAR-guided HDR-BT, during which SR3D images were acquired for subsequent segmentation and analysis. A total of 183 needles were investigated. Needle end-length measurements were taken, providing a gold standard for insertion depths. Dosimetric impact of insertion depth errors (IDEs) on clinical treatment plans was assessed. ResultsSR3D guidance provided statistically significantly smaller IDEs than SAAR guidance with a mean ± SD of −0.6 ± 3.2 mm and 2.8 ± 3.2 mm, respectively (p < 0.001). Shadow artifacts were found to obstruct the view of some needle tips in SR3D images either partially (12%) or fully (10%); however, SR3D IDEs had a statistically significantly smaller impact on prostate V100% than SAAR IDEs with mean ± SD decreases of −1.2 ± 1.3% and −6.5 ± 6.7%, respectively (p < 0.05). ConclusionsSR3D-guided HDR-BT eliminates a source of systematic uncertainty from the SAAR-guided approach, providing decreased IDEs for most needles, leading to a significant decrease in dosimetric uncertainty. Although imaging artifacts can limit the accuracy of tip localization in a subset of needles, we identified a method to mitigate these artifacts for clinical implementation.

Single-fraction high-dose-rate brachytherapy using real-time transrectal ultrasound based planning in combination with external beam radiotherapy for prostate cancer: dosimetrics and early clinical results.

PurposeTo validate the feasibility of a single-fraction high-dose-rate brachytherapy (HDRBT) boost for prostate cancer using real-time transrectal ultrasound (TRUS) based planning.Material and methodsFrom August 2012 to September 2015, 126 patients underwent a single-fraction HDRBT boost of 15 Gy using real-time TRUS based planning. External beam radiation therapy (EBRT) (37.5 Gy/15 fractions, 44 Gy/22 fractions, or 45 Gy/25 fractions) was performed before (31%) or after (69%) HDRBT boost. Genito-urinary (GU) and gastro-intestinal (GI) toxicity were assessed 4 and 12 months after the end of combined treatment using the international prostate symptom score scale (IPSS) and the common terminology criteria for adverse events (CTCAE) v3.0.ResultsAll dose-planning objectives were achieved in 90% of patients. Prostate D90 ≥ 105% and ≤ 115% was achieved in 99% of patients, prostate V150 ≤ 40% in 99%, prostate V200 < 11% in 96%, urethra D10 < 120% for 99%, urethra V125 = 0% in 100%, and rectal V75 < 1 cc in 93% of patients. Median IPSS score was 4 at baseline and did not change at 4 and 12 months after combined treatment. No patients developed ≥ grade 2 GI toxicity. With a median follow-up of 10 months, only two patients experienced biochemical failure. Among patients who didn't receive ADT, cumulative percentage of patients with PSA ≤ 1 ng/ml at 4 and 18 months was respectively 23% and 66%.ConclusionsSingle-fraction HDRBT boost of 15 Gy using real-time TRUS based planning achieves consistently high dosimetry quality. In combination with EBRT, toxicity outcomes appear promising. A longer follow-up is needed to assess long-term outcome and toxicities.

Assessment of the feasibility of using transrectal ultrasound for postimplant dosimetry in low-dose-rate prostate brachytherapy

A study was performed to establish whether transrectal ultrasound (TRUS)-based postimplant dosimetry (PID) is both practically feasible and comparable to computed tomography (CT)-based PID, recommended in current published guidelines. In total, 22 patients treated consecutively at a single cancer center with low-dose-rate (LDR) brachytherapy for early-stage prostate cancer had a transrectal ultrasound performed immediately after implant (d0-TRUS) and computed tomography scan 30 days after implant (d30-CT). Postimplant dosimetry planning was performed on both image sets and the results were compared. The interobserver reproducibility of the transrectal ultrasound postimplant dosimetry planning technique was also assessed. It was noticed that there was no significant difference in mean prostate D90 (136.5Gy and 144.4Gy, p = 0.2197), V100 (86.4% and 89.1%, p = 0.1480) and V150 (52.0% and 47.8%, p = 0.1657) for d30-CT and d0-TRUS, respectively. Rectal doses were significantly higher for d0-TRUS than d30-CT. Urethral doses were available with d0-TRUS only. We have shown that d0-TRUS PID is a useful tool for assessing the quality of an implant after low-dose-rate prostate brachytherapy and is comparable to d30-CT PID. There are clear advantages to its use in terms of resource and time efficiency both for the clinical team and the patient.

Influence of source batch S dispersion on dosimetry for prostate cancer treatment with permanent implants.

In clinical practice, specific air kerma strength (SK) value is used in treatment planning system (TPS) permanent brachytherapy implant calculations with (125)I and (103)Pd sources; in fact, commercial TPS provide only one SK input value for all implanted sources and the certified shipment average is typically used. However, the value for SK is dispersed: this dispersion is not only due to the manufacturing process and variation between different source batches but also due to the classification of sources into different classes according to their SK values. The purpose of this work is to examine the impact of SK dispersion on typical implant parameters that are used to evaluate the dose volume histogram (DVH) for both planning target volume (PTV) and organs at risk (OARs). The authors have developed a new algorithm to compute dose distributions with different SK values for each source. Three different prostate volumes (20, 30, and 40 cm(3)) were considered and two typical commercial sources of different radionuclides were used. Using a conventional TPS, clinically accepted calculations were made for (125)I sources; for the palladium, typical implants were simulated. To assess the many different possible SK values for each source belonging to a class, the authors assigned an SK value to each source in a randomized process 1000 times for each source and volume. All the dose distributions generated for each set of simulations were assessed through the DVH distributions comparing with dose distributions obtained using a uniform SK value for all the implanted sources. The authors analyzed several dose coverage (V100 and D90) and overdosage parameters for prostate and PTV and also the limiting and overdosage parameters for OARs, urethra and rectum. The parameters analyzed followed a Gaussian distribution for the entire set of computed dosimetries. PTV and prostate V100 and D90 variations ranged between 0.2% and 1.78% for both sources. Variations for the overdosage parameters V150 and V200 compared to dose coverage parameters were observed and, in general, variations were larger for parameters related to (125)I sources than (103)Pd sources. For OAR dosimetry, variations with respect to the reference D0.1cm(3) were observed for rectum values, ranging from 2% to 3%, compared with urethra values, which ranged from 1% to 2%. Dose coverage for prostate and PTV was practically unaffected by SK dispersion, as was the maximum dose deposited in the urethra due to the implant technique geometry. However, the authors observed larger variations for the PTV V150, rectum V100, and rectum D0.1cm(3) values. The variations in rectum parameters were caused by the specific location of sources with SK value that differed from the average in the vicinity. Finally, on comparing the two sources, variations were larger for (125)I than for (103)Pd. This is because for (103)Pd, a greater number of sources were used to obtain a valid dose distribution than for (125)I, resulting in a lower variation for each SK value for each source (because the variations become averaged out statistically speaking).

Reduced dose to urethra and rectum with the use of variable needle spacing in prostate brachytherapy: a potential role for robotic technology.

PurposeSeveral robotic delivery systems for prostate brachytherapy are under development or in pre-clinical testing. One of the features of robotic brachytherapy is the ability to vary spacing of needles at non-fixed intervals. This feature may play an important role in prostate brachytherapy, which is traditionally template-based with fixed needle spacing of 0.5 cm. We sought to quantify potential reductions in the dose to urethra and rectum by utilizing variable needle spacing, as compared to fixed needle spacing.Material and methodsTransrectal ultrasound images from 10 patients were used by 3 experienced planners to create 120 treatment plans. Each planner created 4 plan variations per patient with respect to needle positions: 125I fixed spacing, 125I variable spacing, 103Pd fixed spacing, and 103Pd variable spacing. The primary planning objective was to achieve a prostate V100 of 100% while minimizing dose to urethra and rectum.ResultsAll plans met the objective of achieving prostate V100 of 100%. Combined results for all plans show statistically significant improvements in all assessed dosimetric variables for urethra (Umax, Umean, D30, D5) and rectum (Rmax, Rmean, RV100) when using variable spacing. The dose reductions for mean and maximum urethra dose using variable spacing had p values of 0.011 and 0.024 with 103Pd, and 0.007 and 0.029 with 125I plans. Similarly dose reductions for mean and maximum rectal dose using variable spacing had p values of 0.007 and 0.052 with 103Pd, and 0.012 and 0.037 with 125I plans.ConclusionsThe variable needle spacing achievable by the use of robotics in prostate brachytherapy allows for reductions in both urethral and rectal planned doses while maintaining prostate dose coverage. Such dosimetric advantages have the potential in translating to significant clinical benefits with the use of robotic brachytherapy.

Tissue composition and density impact on the clinical parameters for 125I prostate implants dosimetry

The MCNPX code was used to calculate the TG-43U1 recommended parameters in water and prostate tissue in order to quantify the dosimetric impact in 30 patients treated with 125I prostate implants when replacing the TG-43U1 formalism parameters calculated in water by a prostate-like medium in the planning system (PS) and to evaluate the uncertainties associated with Monte Carlo (MC) calculations. The prostate density was obtained from the CT of 100 patients with prostate cancer. The deviations between our results for water and the TG-43U1 consensus dataset values were −2.6% for prostate V100, −13.0% for V150, and −5.8% for D90; −2.0% for rectum V100, and −5.1% for D0.1; −5.0% for urethra D10, and −5.1% for D30. The same differences between our water and prostate results were all under 0.3%. Uncertainties estimations were up to 2.9% for the gL(r) function, 13.4% for the F(r,θ) function and 7.0% for Λ, mainly due to seed geometry uncertainties. Uncertainties in extracting the TG-43U1 parameters in the MC simulations as well as in the literature comparison are of the same order of magnitude as the differences between dose distributions computed for water and prostate-like medium. The selection of the parameters for the PS should be done carefully, as it may considerably affect the dose distributions. The seeds internal geometry uncertainties are a major limiting factor in the MC parameters deduction.

Dose to the Bladder Neck Is the Most Important Predictor for Acute and Late Toxicity After Low-Dose-Rate Prostate Brachytherapy: Implications for Establishing New Dose Constraints for Treatment Planning

To identify an anatomic structure predictive for acute (AUT) and late (LUT) urinary toxicity in patients with prostate cancer treated with low-dose-rate brachytherapy (LDR) with or without external beam radiation therapy (EBRT). From July 2002 to January 2013, 927 patients with prostate cancer (median age, 66 years) underwent LDR brachytherapy with Iodine 125 (n=753) or Palladium 103 (n=174) as definitive treatment (n=478) and as a boost (n=449) followed by supplemental EBRT (median dose, 50.4 Gy). Structures contoured on the computed tomographic (CT) scan on day 0 after implantation included prostate, urethra, bladder, and the bladder neck, defined as 5 mm around the urethra between the catheter balloon and the prostatic urethra. AUT and LUT were assessed with the Common Terminology Criteria for Adverse Events, version4. Clinical and dosimetric factors associated with AUT and LUT were analyzed with Cox regression and receiver operating characteristic analysis to calculate area under the receiver operator curve (ROC) (AUC). Grade ≥2 AUT and grade ≥2 LUT occurred in 520 patients (56%) and 154 patients (20%), respectively. No grade 4 toxicities were observed. Bladder neck D2cc retained a significant association with AUT (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.03-1.04; P<.0001) and LUT (HR, 1.01; 95% CI, 1.00-1.03; P=.014) on multivariable analysis. In a comparison of bladder neck with the standard dosimetric variables by use of ROC analysis (prostate V100 >90%, D90 >100%, V150 >60%, urethra D20 >130%), bladder neck D2cc >50% was shown to have the strongest prognostic power for AUT (AUC, 0.697; P<.0001) and LUT (AUC, 0.620; P<.001). Bladder neck D2cc >50% was the strongest predictor for grade ≥2 AUT and LUT in patients treated with LDR brachytherapy. These data support inclusion of bladder neck constraints into brachytherapy planning to decrease urinary toxicity.