J. Adam M. Cunha

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.

Toward adaptive stereotactic robotic brachytherapy for prostate cancer: demonstration of an adaptive workflow incorporating inverse planning and an MR stealth robot.

Abstract To translate any robot into a clinical environment, it is critical that the robot can seamlessly integrate with all the technology of a modern clinic. MRBot, an MR-stealth brachytherapy delivery device, was used in a closed-bore 3T MRI and a clinical brachytherapy cone beam CT suite. Targets included ceramic dummy seeds, MR-Spectroscopy-sensitive metabolite, and a prostate phantom. Acquired DICOM images were exported to planning software to register the robot coordinates in the imagers frame, contour and verify target locations, create dose plans, and export needle and seed positions to the robot. The coordination of each system element (imaging device, brachytherapy planning system, robot control, robot) was validated with a seed delivery accuracy of within 2 mm in both a phantom and soft tissue. An adaptive workflow was demonstrated by acquiring images after needle insertion and prior to seed deposition. This allows for adjustment if the needle is in the wrong position. Inverse planning (IPSA) was used to generate a seed placement plan and coordinates for ten needles and 29 seeds were transferred to the robot. After every two needles placed, an image was acquired. The placed seeds were identified and validated prior to placing the seeds in the next two needles. The ability to robotically deliver seeds to locations determined by IPSA and the ability of the system to incorporate novel needle patterns were demonstrated. Shown here is the ability to overcome this critical step. An adaptive brachytherapy workflow is demonstrated which integrates a clinical anatomy-based seed location optimization engine and a robotic brachytherapy device. Demonstration of this workflow is a key element of a successful translation to the clinic of the MRI stealth robotic delivery system, MRBot.

Dosimetric equivalence of non-standard high dose rate (HDR) brachytherapy catheter patterns

PURPOSE To determine whether alternative high dose rate prostate brachytherapy catheter patterns can result in similar or improved dose distributions while providing better access and reducing trauma. MATERIALS AND METHODS Standard prostate cancer high dose rate brachytherapy uses a regular grid of parallel needle positions to guide the catheter insertion. This geometry does not easily allow the physician to avoid piercing the critical structures near the penile bulb nor does it provide position flexibility in the case of pubic arch interference. This study used CT datasets with 3 mm slice spacing from ten previously treated patients and digitized new catheters following three hypothetical catheter patterns: conical, bi-conical, and fireworks. The conical patterns were used to accommodate a robotic delivery using a single entry point. The bi-conical and fireworks patterns were specifically designed to avoid the critical structures near the penile bulb. For each catheter distribution, a plan was optimized with the inverse planning algorithm, IPSA, and compared with the plan used for treatment. Irrelevant of catheter geometry, a plan must fulfill the RTOG-0321 dose criteria for target dose coverage (V100(Prostate) > 90%) and organ-at-risk dose sparing (V75(Bladder) < 1 cc, V75(Rectum) < 1 cc, V125(Urethra) << 1cc). RESULTS The three nonstandard catheter patterns used 16 nonparallel, straight divergent catheters, with entry points in the perineum. Thirty plans from ten patients with prostate sizes ranging from 26 to 89 cc were optimized. All nonstandard patterns fulfilled the RTOG criteria when the clinical plan did. In some cases, the dose distribution was improved by better sparing the organs-at-risk. CONCLUSION Alternative catheter patterns can provide the physician with additional ways to treat patients previously considered unsuited for brachytherapy treatment (pubic arch interference) and facilitate robotic guidance of catheter insertion. In addition, alternative catheter patterns may decrease toxicity by avoidance of the critical structures near the penile bulb while still fulfilling the RTOG criteria.

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 patients 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.

An algorithm for computing customized 3D printed implants with curvature constrained channels for enhancing intracavitary brachytherapy radiation delivery

Brachytherapy is a widely-used treatment modality for cancer in many sites in the body. In brachytherapy, small radioactive sources are positioned proximal to cancerous tumors. An ongoing challenge is to accurately place sources on a set of dwell positions to sufficiently irradiate the tumors while limiting radiation damage to healthy organs and tissues. In current practice, standardized applicators with internal channels are inserted into body cavities to guide the sources. These standardized implants are one-size-fits-all and are prone to shifting inside the body, resulting in suboptimal dosages. We propose a new approach that builds on recent results in 3D printing and steerable needle motion planning to create customized implants containing customized curvature-constrained internal channels that fit securely, minimize air gaps, and precisely guide radioactive sources through printed channels. When compared with standardized implants, customized implants also have the potential to provide better coverage: more potential source dwell positions proximal to tumors. We present an algorithm for computing curvature-constrained channels based on rapidly-expanding randomized trees (RRT). We consider a prototypical case of OB/GYN cervical and vaginal cancer with three treatment options: standardized ring implant (current practice), customized implant with linear channels, and customized implant with curved channels. Results with a two-parameter coverage metric suggest that customized implants with curved channels can offer significant improvement over current practice.

Interactive, multi-modality image registrations for combined MRI/MRSI-planned HDR prostate brachytherapy

Purpose This study presents the steps and criteria involved in the series of image registrations used clinically during the planning and dose delivery of focal high dose-rate (HDR) brachytherapy of the prostate. Material and methods Three imaging modalities – Magnetic Resonance Imaging (MRI), Magnetic Resonance Spectroscopic Imaging (MRSI), and Computed Tomography (CT) – were used at different steps during the process. MRSI is used for identification of dominant intraprosatic lesions (DIL). A series of rigid and nonrigid transformations were applied to the data to correct for endorectal-coil-induced deformations and for alignment with the planning CT. Mutual information was calculated as a morphing metric. An inverse planning optimization algorithm was applied to boost dose to the DIL while providing protection to the urethra, penile bulb, rectum, and bladder. Six prostate cancer patients were treated using this protocol. Results The morphing algorithm successfully modeled the probe-induced prostatic distortion. Mutual information calculated between the morphed images and images acquired without the endorectal probe showed a significant (p = 0.0071) increase to that calculated between the unmorphed images and images acquired without the endorectal probe. Both mutual information and visual inspection serve as effective diagnostics of image morphing. The entire procedure adds less than thirty minutes to the treatment planning. Conclusion This work demonstrates the utility of image transformations and registrations to HDR brachytherapy of prostate cancer.

Patient- and treatment-specific predictors of genitourinary function after high-dose-rate monotherapy for favorable prostate cancer

PURPOSE High-dose-rate (HDR) brachytherapy alone is an effective treatment option for patients with early-stage prostate cancer. The purpose of this study was to quantify patient-reported short- and long-term toxicity and quality of life (QOL) after HDR monotherapy. METHODS AND MATERIALS Thirty-nine consecutive men between May 2001 and January 2012 were identified for this analysis. All patients underwent definitive HDR monotherapy for favorable prostate cancer to a total dose of 3150 cGy in three fractions, 3800 cGy in four fractions, or 3850 in five fractions. Patient-reported genitourinary function was assessed before HDR, during an acute period after treatment (within 90 days of HDR), and on long-term followup using the American Urological Association International Prostate Symptom Score, a urinary QOL Likert questionnaire, and the Sexual Health Inventory for Men questionnaire. Regression analyses were performed using the ordinary least squares method. RESULTS With median followup of 57 months, biochemical progression-free survival was 100%. There were no grade ≥3 toxicities. Dose to the urethra and bladder, as well as prostate size and intraprostatic urethra length were predictive for short-term changes in QOL. Advanced patient age was predictive for worse sexual function on both acute and long-term followup. CONCLUSIONS Toxicity after HDR monotherapy for prostate cancer is acceptable. Patients with larger prostates, longer intraprostatic urethras, and greater doses to the bladder and urethra may experience worse acute urinary QOL. Older patients may experience greater impairment in sexual function in the short and long terms.

Robot-Guided Open-Loop Insertion of Skew-Line Needle Arrangements for High Dose Rate Brachytherapy

We present a study in human-centered automation that has potential to reduce patient side effects from high dose rate brachytherapy (HDR-BT). To efficiently deliver radiation to the prostate while minimizing trauma to sensitive structures such as the penile bulb, we modified the Acubot-RND 7-axis robot to guide insertion of diamond-tip needles into desired skew-line geometric arrangements. We extend and integrate two algorithms: Needle Planning with Integer Programming (NPIP) and Inverse Planning with Integer Programming (IPIP) to compute skew-line needle and dose plans. We performed three physical experiments with anatomically correct phantom models to study performance: two with the robot and one control experiment with an expert human physician (coauthor Hsu) without the robot. All were able to achieve needle arrangements that meet the RTOG-0321 clinical dose objectives with zero trauma to the penile bulb. We analyze systematic and random errors in needle placement; total RMS error for the robot system operating without feedback ranged from 2.6 to 4.3 mm, which is comparable to the RMS error of 2.7 mm obtained in an earlier study for PPI-BT treatment using a robot with 3D ultrasound feedback.

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.

Cold spot mapping inferred from MRI at time of failure predicts biopsy-proven local failure after permanent seed brachytherapy in prostate cancer patients: Implications for focal salvage brachytherapy

BACKGROUND AND PURPOSE (1) To establish a method to evaluate dosimetry at the time of primary prostate permanent implant (pPPI) using MRI of the shrunken prostate at the time of failure (tf). (2) To compare cold spot mapping with sextant-biopsy mapping at tf. MATERIAL AND METHODS Twenty-four patients were referred for biopsy-proven local failure (LF) after pPPI. Multiparametric MRI and combined-sextant biopsy with a central review of the pathology at tf were systematically performed. A model of the shrinking pattern was defined as a Volumetric Change Factor (VCF) as a function of time from time of pPPI (t0). An isotropic expansion to both prostate volume (PV) and seed position (SP) coordinates determined at tf was performed using a validated algorithm using the VCF. RESULTS pPPI CT-based evaluation (at 4weeks) vs. MR-based evaluation: Mean D90% was 145.23±19.16Gy [100.0-167.5] vs. 85.28±27.36Gy [39-139] (p=0.001), respectively. Mean V100% was 91.6±7.9% [70-100%] vs. 73.1±13.8% [55-98%] (p=0.0006), respectively. Seventy-seven per cent of the pathologically positive sextants were classified as cold. CONCLUSIONS Patients with biopsy-proven LF had poorer implantation quality when evaluated by MRI several years after implantation. There is a strong relationship between microscopic involvement at tf and cold spots.