Salvage High-Dose-Rate Brachytherapy for Recurrent Prostate Cancer After Definitive Radiation.

PURPOSE: Salvage high-dose-rate brachytherapy (sHDRBT) for locally recurrent prostate cancer after definitive radiation is associated with biochemical control in approximately half of patients at 3 to 5 years. Given potential toxicity, patient selection is critical. We present our institutional experience with sHDRBT and validate a recursive partitioning machines model for biochemical control. MATERIALS AND METHODS: We performed a retrospective analysis of 129 patients who underwent whole-gland sHDRBT between 1998 and 2016. We evaluated clinical factors associated with biochemical control as well as toxicity. RESULTS: At diagnosis the median prostate-specific antigen (PSA) was 7.77 ng/mL. A majority of patients had T1-2 (73%) and Gleason 6-7 (82%) disease; 71% received external beam radiation therapy (RT) alone, and 22% received permanent prostate implants. The median disease-free interval (DFI) was 56 months, and median presalvage PSA was 4.95 ng/mL. At sHDRBT, 46% had T3 disease and 51% had Gleason 8 to 10 disease. At a median of 68 months after sHDRBT, 3- and 5-year disease-free survival were 85% (95% CI, 79-91) and 71% (95% CI, 62-79), respectively. Median PSA nadir was 0.18 ng/mL, achieved a median of 10 months after sHDRBT. Patients with ≥35%+ cores and a DFI <4.1 years had worse biochemical control (19% vs 50%, P = .02). Local failure (with or without regional/distant failure) was seen in 11% of patients (14/129), and 14 patients (11%) developed acute urinary obstruction requiring Foley placement and 19 patients (15%) developed strictures requiring dilation. CONCLUSIONS: sHDRBT is a reasonable option for patients with locally recurrent prostate cancer after definitive RT. Those with <35%+ cores or an initial DFI of ≥4.1 years may be more likely to achieve long-term disease control after sHDRBT.

Evaluating the impact of real-time multicriteria optimizers integrated with interactive plan navigation tools for HDR brachytherapy.

PURPOSE: Currently in high-dose-rate (HDR) brachytherapy planning, manual fine-tuning of an objective function is a common practice. Furthermore, automated planning approaches such as multicriteria optimization (MCO) are still limited to the automatic generation of a single treatment plan. This study aims to quantify planning efficiency gains when using a graphics processing unit-based MCO (gMCO) algorithm combined with a novel graphical user interface (gMCO-GUI) that integrates efficient automated and interactive plan navigation tools. METHODS AND MATERIALS: The gMCO algorithm was used to generate 1000 Pareto optimal plans per case for 379 prostate cases. gMCO-GUI was developed to allow plan navigation through all plans. gMCO-GUI integrates interactive parameter selection tools directly with the optimization algorithm to allow plan navigation. The quality of each plan was evaluated based on the Radiation Treatment Oncology Group 0924 protocol and a more stringent institutional protocol (INSTp). gMCO-GUI allows real-time time display of the dose-volume histogram indices, the dose-volume histogram curves, and the isodose lines during the plan navigation. RESULTS: Over the 379 cases, the fraction of Radiation Treatment Oncology Group 0924 protocol valid plans with target coverage greater than 95% was 90.8%, compared with 66.0% for clinical plans. The fraction of INSTp valid plans with target coverage greater than 95% was 81.8%, compared with 62.3% for clinical plans. The average time to compute 1000 deliverable plans with gMCO was 12.5 s, including the full computation of the 3D dose distributions. CONCLUSIONS: Combining the gMCO algorithm with automated and interactive plan navigation tools resulted in simultaneous gains in both plan quality and planning efficiency.

Single-fraction brachytherapy as monotherapy for early-stage prostate cancer: The UCSF experience.

PURPOSE: High-dose-rate (HDR) brachytherapy as monotherapy is an effective treatment option for localized prostate cancer, but experience with single-fraction brachytherapy is limited by studies with small sample size. We report a large single-institution experience with single-fraction HDR brachytherapy as monotherapy for early-stage prostate cancer. METHODS AND MATERIALS: Retrospective chart review was performed for men treated with HDR brachytherapy as monotherapy for low- to intermediate-risk prostate cancer. Competing risk analyses were performed to estimate subdistribution hazard ratio and cumulative incidence of biochemical recurrence (BCR) and prostate cancer-specific mortality. RESULTS: We identified 124 men with a median followup of 2.2 years (interquartile range 25th to 75th percentile: 1.8-3). Overall, 21.0% of patients (n = 26) were low risk, 44.4% (n = 55) were favorable intermediate risk, and 34.7% (n = 43) were unfavorable intermediate risk. At 2 years, the cumulative incidence of BCR was 3.5%: 0% for low risk, 4.0% for favorable intermediate risk patients, and 4.5% for unfavorable intermediate risk patients. In total, 12 BCRs were observed (9.7%) and approximately half occurred after median followup of 2.2 years. Compared with low-risk and favorable intermediate-risk disease, unfavorable intermediate-risk disease was significantly associated with BCR (subdistribution hazard ratio: 3.6, 95% CI: 1.1 to 11.1, p = 0.03). Prostate cancer-specific mortality was 0%. No patient experienced Grade 3 or higher acute or late genitourinary toxicity. CONCLUSIONS: Single-fraction brachytherapy for early-stage prostate cancer was safe with promising short-term disease control rates, especially for low-risk patients. Longer term followup is needed as we observed an overall BCR rate of 9.7%.

Real-time electromagnetic tracking-based treatment platform for high-dose-rate prostate brachytherapy: Clinical workflows and end-to-end validation.

PURPOSE: New technologies were integrated into a novel treatment platform combining electromagnetically (EM) tracked catheters, a 3D ultrasound (3DUS) imaging device, and a new treatment planning system to provide a real-time prostate high-dose-rate (HDR) brachytherapy treatment system. This work defines workflows for offline CT and online 3DUS planning scenarios and preclinical end-to-end validation of the platform. METHODS AND MATERIALS: The platform is composed of an EM-tracked stylet, a EM-tracked 3DUS probe, and an EM-tracked template guide, all used with the NDI Aurora field generator (NDI, Ontario, Canada). The treatment planning system performs continuous position and angular readings from all three EM sensors into a streamlined environment that allows for (1) contouring; (2) planning; (3) catheter insertion guidance and reconstruction; (4) QA of catheter path and tip position; and (5) exporting to an afterloader. Data were gathered on the times required for the various key steps of the 3DUS-based workflow. RESULTS: The complete 3DUS-based workflow on 16-catheter implant phantoms took approximately 15 min. This time is expected to increase for actual patients. Plan generation is fast (7.6 ± 2.5s) and the initial catheter reconstruction with updated dose distribution is obtained at no (time) cost as part of the insertion process. Subsequent catheter reconstruction takes on average 10.5 ± 3.1s per catheter, representing less than 3 min for a 16-catheter implant. CONCLUSIONS: This preclinical study suggests that EM technology could help to significantly streamline real-time US-based high-dose-rate prostate brachytherapy.

Improved rectal dosimetry with the use of SpaceOAR during high-dose-rate brachytherapy.

PURPOSE: Hydrogel spacers have been suggested to limit rectal radiation dose with improvements in clinical outcomes in patients undergoing external beam radiation treatment for prostate cancer. No studies to date have assessed the utility and dosimetric effect of SpaceOAR (Augmenix, Inc, Waltham, MA), the only Food and Drug Administration-approved hydrogel rectal spacer, for high-dose-rate (HDR) brachytherapy. METHODS: Eighteen consecutive patients scheduled for HDR brachytherapy in the treatment of prostate cancer underwent transperineal ultrasound-guided placement of 10 cc of SpaceOAR hydrogel following catheter implantation. Treatment plans were generated using an inverse planning simulated annealing algorithm. Rectal dosimetry for these 18 patients was compared with the 36 preceding patients treated with HDR brachytherapy without SpaceOAR. RESULTS: Fifty-four plans were analyzed. There was no difference in age, pretreatment prostate-specific antigen, Gleason score, clinical stage, prostate volume, or contoured rectal volume between those who received SpaceOAR and those who did not. Patients who received SpaceOAR hydrogel had significantly lower dose to the rectum as measured by percent of contoured organ at risk (median, V80 < 0.005% vs. 0.010%, p = 0.003; V75 < 0.005% vs. 0.14%, p < 0.0005; V70 0.09% vs. 0.88%, p < 0.0005; V60 = 1.16% vs. 3.08%, p < 0.0005); similar results were seen for rectal volume in cubic centimeters. One patient who received SpaceOAR developed a perineal abscess 1 month after treatment. CONCLUSIONS: Transperineal insertion of SpaceOAR hydrogel at the time of HDR brachytherapy is feasible and decreases rectal radiation dose. Further investigation is needed to assess the clinical impact of this dosimetric improvement and potential toxicity reduction.

Inverse Planned High-Dose-Rate Brachytherapy for Locoregionally Advanced Cervical Cancer: 4-Year Outcomes.

PURPOSE: Evaluate the efficacy and toxicity of image guided brachytherapy using inverse planning simulated annealing (IPSA) high-dose-rate brachytherapy (HDRB) boost for locoregionally advanced cervical cancer. METHODS AND MATERIALS: From December 2003 through September 2009, 111 patients with primary cervical cancer were treated definitively with IPSA-planned HDRB boost (28 Gy in 4 fractions) after external radiation at our institution. We performed a retrospective review of our experience using image guided brachytherapy. Of the patients, 70% had a tumor size >4 cm, 38% had regional nodal disease, and 15% had clinically evident distant metastasis, including nonregional nodal disease, at the time of diagnosis. Surgical staging involving pelvic lymph node dissection was performed in 15% of patients, and 93% received concurrent cisplatin-based chemotherapy. Toxicities are reported according to the Common Terminology Criteria for Adverse Events version 4.0 guidelines. RESULTS: With a median follow-up time of 42 months (range, 3-84 months), no acute or late toxicities of grade 4 or higher were observed, and grade 3 toxicities (both acute and late) developed in 8 patients (1 constitutional, 1 hematologic, 2 genitourinary, 4 gastrointestinal). The 4-year Kaplan-Meier estimate of late grade 3 toxicity was 8%. Local recurrence developed in 5 patients (4 to 9 months after HDRB), regional recurrence in 3 (6, 16, and 72 months after HDRB), and locoregional recurrence in 1 (4 months after HDR boost). The 4-year estimates of local, locoregional, and distant control of disease were 94.0%, 91.9%, and 69.1%, respectively. The overall and disease-free survival rates at 4 years were 64.3% (95% confidence interval [CI] of 54%-73%) and 61.0% (95% CI, 51%-70%), respectively. CONCLUSIONS: Definitive radiation by use of inverse planned HDRB boost for locoregionally advanced cervical cancer is well tolerated and achieves excellent local control of disease. However, overall survival continues to be limited by the high rates of distant metastasis.

Evaluation of PC-ISO for customized, 3D Printed, gynecologic 192-Ir HDR brachytherapy applicators.

The purpose of this study was to evaluate the radiation attenuation properties of PC-ISO, a commercially available, biocompatible, sterilizable 3D printing material, and its suitability for customized, single-use gynecologic (GYN) brachytherapy applicators that have the potential for accurate guiding of seeds through linear and curved internal channels. A custom radiochromic film dosimetry apparatus was 3D-printed in PC-ISO with a single catheter channel and a slit to hold a film segment. The apparatus was designed specifically to test geometry pertinent for use of this material in a clinical setting. A brachytherapy dose plan was computed to deliver a cylindrical dose distribution to the film. The dose plan used an 192Ir source and was normalized to 1500 cGy at 1 cm from the channel. The material was evaluated by comparing the film exposure to an identical test done in water. The Hounsfield unit (HU) distributions were computed from a CT scan of the apparatus and compared to the HU distribution of water and the HU distribution of a commercial GYN cylinder applicator. The dose depth curve of PC-ISO as measured by the radiochromic film was within 1% of water between 1 cm and 6 cm from the channel. The mean HU was -10 for PC-ISO and -1 for water. As expected, the honeycombed structure of the PC-ISO 3D printing process created a moderate spread of HU values, but the mean was comparable to water. PC-ISO is sufficiently water-equivalent to be compatible with our HDR brachytherapy planning system and clinical workflow and, therefore, it is suitable for creating custom GYN brachytherapy applicators. Our current clinical practice includes the use of custom GYN applicators made of commercially available PC-ISO when doing so can improve the patient's treatment. 

Urethra low-dose tunnels: validation of and class solution for generating urethra-sparing dose plans using inverse planning simulated annealing for prostate high-dose-rate brachytherapy.

PURPOSE: Urethral dose is related to severity of genitourinary toxicity in patients treated with brachytherapy for prostate cancer. This work describes a dose planning method that uses inverse planning to create a low-dose tunnel around the urethra and presents a class solution to achieve this additional dose sparing of the urethra. METHODS: Fifteen patients on the Radiation Therapy Oncology Group (RTOG) 0321 protocol were treated for prostate cancer with a high-dose-rate brachytherapy dose boost to an external beam radiation treatment regimen. All were treated with 9.5Gy for each of the two fractions after 45Gy of the external beam radiation. The inverse-planning algorithm, inverse planning simulated annealing (IPSA), was used to create both the standard RTOG protocol (SRP) plan for treatment and the a posteriori urethra dose sparing (UDS) plan consisting of a dose tunnel along the urethra. Both plans maintained the protocol parameters: prostate V(100) (volume receiving 100% of prescribed dose)>90% and bladder and rectum V(75)<1 cm(3). In the SRP plans, the urethra surface was optimized to receive <125% of the prescription dose and in the UDS plans <100%. Dose-volume histograms for the clinical treatment volume, bladder, rectum, penile bulb, and urethra for both plans are compared using a paired sample t test with significance claimed for probability values<0.05. RESULTS: UDS planning reduced the urethra V(100) from 88% to 58% on average (p<0.01) and the V(125) from 3.3% to 0.2% (p < 0.01). Bladder and rectum V(75) were maintained at <1 cm(3) and not significantly different between plans. Prostate coverage was maintained per protocol at V(100)>90%, with mean for the SRP V(100)=93% versus UDS plan V(100)=90%. Prostate D(90) for SRP was 104% versus UDS plan D(90)=101%. For all patients, the UDS achieved a dose tunnel surrounding the length of the intraprostatic urethra. The class solution for generating UDS is presented. CONCLUSIONS: A urethral sparing-focused planning solution using IPSA reduces mean urethral dose by 34%, as compared with IPSA-generated plans based on the RTOG 0321 protocol. This is done while maintaining prostate coverage and critical structure dose. This technique can be applied to all patients in whom urethra toxicity is of particular concern.

Comparison of high-dose rate prostate brachytherapy dose distributions with iridium-192, ytterbium-169, and thulium-170 sources.

PURPOSE: Recent studies have identified that among different available radionuclides, the dose characteristics and shielding properties of ytterbium-169 ((169)Yb) and thulium-170 ((170)Tm) may suit high-dose rate (HDR) brachytherapy needs. The purpose of this work was to compare clinically optimized dose distributions using proposed (169)Yb and (170)Tm HDR sources with the clinical dose distribution from a standard microSelectron V2 HDR iridium-192 ((192)Ir) brachytherapy source (Nucletron B.V., Veenendaal, The Netherlands). METHODS AND MATERIALS: CT-based treatment plans of 10 patients having prostate volumes ranging from 17 to 92cm(3) were studied retrospectively. Clinical treatment of these patients involved 16 catheters and a microSelectron V2 HDR (192)Ir source. All dose plans were generated with inverse planning simulated annealing optimization algorithm. Dose objectives used for the (192)Ir radionuclide source were used for the other two radionuclides. The dose objective parameters were adjusted to obtain the same clinical target (prostate) volume coverage as the original (192)Ir radionuclide plan. A complete set of dosimetric indices was used to compare the plans from different radionuclides. A pairwise statistical analysis was also performed. RESULTS AND CONCLUSIONS: All the dose distributions optimized with specific (192)Ir, (169)Yb, and (170)Tm sources satisfied the standard clinical criteria for HDR prostate implants, such as those for the Radiation Therapy Oncology Group clinical trial 0321, for combined HDR and external beam treatment for prostate adenocarcinoma. For equivalent clinical target volume dose coverage, the specific (169)Yb and (170)Tm sources resulted in a statistically significant dose reduction to organs at risk compared with microSelectron V2 HDR (192)Ir source. This study indicates that a (170)Tm or (169)Yb radionuclide source may be an alternative to the (192)Ir radionuclide sources in HDR brachytherapy.

Dosimetric impact of interfraction catheter movement in high-dose rate prostate brachytherapy.

PURPOSE: To evaluate the impact of interfraction catheter movement on dosimetry in prostate high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALS: Fifteen patients were treated with fractionated HDR brachytherapy. Implants were performed on day 1 under transrectal ultrasound guidance. A computed tomography (CT) scan was performed. Inverse planning simulated annealing was used for treatment planning. The first fraction was delivered on day 1. A cone beam CT (CBCT) was performed on day 2 before the second fraction was given. A fusion of the CBCT and CT was performed using intraprostatic gold markers as landmarks. Initial prostate and urethra contours were transferred to the CBCT images. Bladder and rectum contours were drawn, and catheters were digitized on the CBCT. The planned treatment was applied to the CBCT dataset, and dosimetry was analyzed and compared to the initial dose distribution. This process was repeated after a reoptimization was performed, using the same constraints used on day 1. RESULTS: Mean interfraction catheter displacement was 5.1 mm. When we used the initial plan on day 2, the mean prostate V100 (volume receiving 100 Gy or more) decreased from 93.8% to 76.2% (p < 0.01). Rectal V75 went from 0.75 cm(3) to 1.49 cm(3) (p < 0.01). A reoptimization resulted in a mean prostate V100 of 88.1%, closer to the initial plan (p = 0.05). Mean rectal V75 was also improved with a value of 0.59 cm(3). There was no significant change in bladder and urethra dose on day 2. CONCLUSIONS: A mean interfraction catheter displacement of 5.1 mm results in a significant decrease in prostate V100 and an increase in rectum dose. A reoptimization before the second treatment improves dose distribution.

Inverse planning optimization for hybrid prostate permanent-seed implant brachytherapy plans using two source strengths.

The purpose is to demonstrate the ability to generate clinically acceptable prostate permanent seed implant plans using two seed types which are identical except for their activity. The IPSA inverse planning algorithms were modified to include multiple dose matrices for the calculation of dose from different sources, and a selection algorithm was implemented to allow for the swapping of source type at any given source position. Five previously treated patients with a range of prostate volumes from 20-48 cm3 were re-optimized under two hybrid scenarios: (1) using 0.32 and 0.51 mGy m2 / h 125I, and (2) using 0.64 and 0.76 mGy m2 / h 125I. Isodose lines were generated and dosimetric indices , V150Prostate, D90Prostate, V150Urethra, V125Urethra, V120Urethra,V100Urethra, and D10Urethra were calculated. The algorithm allows for the generation of single-isotope, multi-activity hybrid brachytherapy plans. By dealing with only one radionuclide, but of different activity, the biology is unchanged from a standard plan. All V100Prostate were within 2.3 percentage points for every plan and always above the clinically desirable 95%. All V150Urethra were identically zero, and V120Urethra is always below the clinically acceptable value of 1.0 cm3. Clinical optimization times for the hybrid plans are still under one minute, for most cases. It is possible to generate clinically advantageous brachytherapy plans (i.e. obtain the same quality dose distribution as a standard single-activity plan) while incorporating leftover seeds from a previous patient treatment. This method will allow a clinic to continue to provide excellent patient care, but at a reduced cost. Multi-activity hybrid plans were equal in quality (as measured by the standard dosimetric indices) to plans with seeds of a single activity. Despite the expanded search space, optimization times for these studies were still under two minutes on a modern day laptop and can be reduced to below one minute in a clinical setting. With the typical cost of a set of PPI seeds on the order of thousands of dollars, it is possible to reduce the cost of brachytherapy treatments by allowing for easier use of seeds left over from a previous patient or unused due to a cancelled treatment.

Planning Fireworks Trajectories for Steerable Medical Needles to Reduce Patient Trauma.

Accurate insertion of needles to targets in 3D anatomy is required for numerous medical procedures. To reduce patient trauma, a "fireworks" needle insertion approach can be used in which multiple needles are inserted from a single small region on the patient's skin to multiple targets in the tissue. In this paper, we explore motion planning for "fireworks" needle insertion in 3D environments by developing an algorithm based on Rapidly-exploring Random Trees (RRTs). Given a set of targets, we propose an algorithm to quickly explore the configuration space by building a forest of RRTs and to find feasible plans for multiple steerable needles from a single entry region. We present two path selection algorithms with different optimality considerations to optimize the final plan among all feasible outputs. Finally, we demonstrate the performance of the proposed algorithm with a simulation based on a prostate cancer treatment environment.