I. Hsu

Registration of MR prostate images with biomechanical modeling and nonlinear parameter estimation

Magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI) have been shown to be very useful for identifying prostate cancers. For high sensitivity, the MRI/MRSI examination is often acquired with an endorectal probe that may cause a substantial deformation of the prostate and surrounding soft tissues. Such a probe is removed prior to radiation therapy treatment. To register diagnostic probe-in magnetic resonance (MR) images to therapeutic probe-out MR images for treatment planning, a new deformable image registration method is developed based on biomechanical modeling of soft tissues and estimation of uncertain tissue parameters using nonlinear optimization. Given two-dimensional (2-D) segmented probe-in and probe-out images, a finite element method (FEM) is used to estimate the deformation of the prostate and surrounding tissues due to displacements and forces resulting from the endorectal probe. Since FEM requires tissue stiffness properties and external force values as input, the method estimates uncertain parameters using nonlinear local optimization. The registration method is evaluated using images from five balloon and five rigid endorectal probe patient cases. It requires on average 37 s of computation time on a 1.6 GHz Pentium-M PC. Comparing the prostate outline in deformed probe-out images to corresponding probe-in images, the method obtains a mean Dice Similarity Coefficient (DSC) of 97.5% for the balloon probe cases and 98.1% for the rigid probe cases. The method improves significantly over previous methods (P < 0.05) with greater improvement for balloon probe cases with larger tissue deformations.

Simulating needle insertion and radioactive seed implantation for prostate brachytherapy.

We are developing a simulation of needle insertion and radioactive seed implantation to facilitate surgeon training and planning for brachytherapy for treating prostate cancer. Inserting a needle into soft tissues causes the tissues to displace and deform: ignoring these effects during seed implantation leads to imprecise seed placements. Surgeons should learn to compensate for these effects so seeds are implanted close to their pre-planned locations. We describe a new 2-D dynamic FEM model based on a 7-phase insertion sequence where the mesh is updated to maintain element boundaries along the needle shaft. The locations of seed implants are predicted as the tissue deforms. The simulation, which achieves 24 frames per second using a 1250 triangular element mesh on a 750Mhz Pentium III PC, is available for surgeon testing by contacting ron@ieor.berkeley.edu.

Feasibility of MR Imaging/MR Spectroscopy-Planned Focal Partial Salvage Permanent Prostate Implant (PPI) for Localized Recurrence After Initial PPI for Prostate Cancer

PURPOSE To assess the feasibility of magnetic resonance imaging (MRI)-planned partial salvage permanent prostate implant (psPPI) among patients with biopsy-proven local recurrence after initial PPI without evidence of distant disease. METHODS AND MATERIALS From 2003-2009, 15 patients underwent MRI/magnetic resonance spectroscopy (MRS) planning for salvage brachytherapy (psPPI, I-125 [n=14; 144 Gy]; Pd-103 [n=1; 125 Gy]) without hormone therapy. Full dose was prescribed to areas of recurrence and underdosage, without entire prostate implantation. Limiting urethral and rectal toxicity was prioritized. Follow-up was from salvage date to prostate-specific antigen (PSA) concentration failure (Phoenix criteria = nadir + 2.0; ASTRO = 3 consecutive rises), recurrence, distant metastases, or last follow-up PSA level. Progression-free survival (PFS) was defined as no PSA failure or biopsy-proven recurrence without all-cause mortality. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. RESULTS At salvage, median age was 68 years, and PSA concentration was 3.5 ng/mL (range, 0.9-5.6 ng/mL). Abnormal MRI/MRS findings were evident in 40% of patients. Biopsy-proven recurrences consisted of a single focus (80%) or 2 foci (20%). At recurrence, Gleason score was 6 (67%) or ≥7 (27%). Median interval between initial and salvage implantation was 69 months (range, 28-132 months). psPPI planning characteristics limited doses to the rectum (mean V100 = 0.5% [0.07 cc]) and urethra (V100 = 12% [0.3 cc]). At median follow-up (23.3 months; range, 8-88 months), treatment failure (n=2) resulted only in localized recurrence; both patients underwent second psPPI with follow-up PSA tests at 12 and 26 months, resulting in 0.6 and 0.7 ng/mL, respectively. American Society for Radiation Oncology PFS rates at 1, 2, and 3 years were 86.7%, 78.4%, and 62.7%, respectively, with 5 patients for whom treatment failed (n=3 with negative transrectal ultrasound-guided biopsy results). Phoenix PFS rates at 1, 2, and 3 years were 100%, 100%, and 71.4%. 73%, respectively; achieved PSA nadir of <0.5 ng/mL; and 47% of patients had a nadir of <0.1 ng/mL. Treatment-related toxicity was minimal, with no operative interventions, fistulas, or other grade ≥3 gastrointestinal (GI)/genitourinary (GU) toxicity. Thirteen percent had grade 1 GI and 33% had grade 2 GU toxicities. Postsalvage, 20% of patients had no erectile dysfunction, 67% of patients had medication-responsive erectile dysfunction, and 13% of patients had erectile dysfunction refractory to medication. CONCLUSIONS Focal psPPI with MR-planning in highly selected patients is feasible with short-term control comparable to conventional salvage, with less toxicity. Longer follow-up is needed to confirm its impact on quality of life and treatment.

Optimization of HDR brachytherapy dose distributions using linear programming with penalty costs

Prostate cancer is increasingly treated with high-dose-rate (HDR) brachytherapy, a type of radiotherapy in which a radioactive source is guided through catheters temporarily implanted in the prostate. Clinicians must set dwell times for the source inside the catheters so the resulting dose distribution minimizes deviation from dose prescriptions that conform to patient-specific anatomy. The primary contribution of this paper is to take the well-established dwell times optimization problem defined by Inverse Planning by Simulated Annealing (IPSA) developed at UCSF and exactly formulate it as a linear programming (LP) problem. Because LP problems can be solved exactly and deterministically, this formulation provides strong performance guarantees: one can rapidly find the dwell times solution that globally minimizes IPSAs objective function for any patient case and clinical criteria parameters. For a sample of 20 prostates with volume ranging from 23to103cc, the new LP method optimized dwell times in less than 15s per case on a standard PC. The dwell times solutions currently being obtained clinically using simulated annealing (SA), a probabilistic method, were quantitatively compared to the mathematically optimal solutions obtained using the LP method. The LP method resulted in significantly improved objective function values compared to SA (P=1.54×10-7), but none of the dosimetric indices indicated a statistically significant difference (P<0.01). The results indicate that solutions generated by the current version of IPSA are clinically equivalent to the mathematically optimal solutions.

Dose uncertainty due to computed tomography (CT) slice thickness in CT‐based high dose rate brachytherapy of the prostate cancer

In computed tomography (CT)-based high dose rate (HDR) brachytherapy, the uncertainty in the localization of the longitudinal catheter-tip positions due to the discrete CT slice thickness, results in a delivered dose uncertainty. Catheter coordinates were extracted from five patients treated for prostate cancer, and three simulation scenarios were followed to mimic the longitudinal imprecision of the catheter tips, hence the dwell positions. All catheters were displaced (1) forward, (2) backward, or (3) randomly distributed within the space defined by one CT slice thickness, for thicknesses ranging from 2 to 5 mm. Average and standard deviation values of the relative dose variations are reported for the various catheter displacement scenarios. Also, the dose points were grouped according to their relative position in the prostate, inner, peripheral and outer area of prostate and base, median and apex zones, in order to estimate the spatial sensitivity of the dose errors. For scenarios (1) and (2), the dose uncertainties due to the finite slice thickness increase linearly with the slice spacing, from 3% to 8% for the slice thickness values ranging from 2 to 5 mm, respectively. The more realistic scenario (3) yields average errors ranging from 0.7% to 1.7%. The apex and the base show larger dose errors and variability of dose errors than the median of the prostate. No statistical difference was observed among different transversal sections of the prostate. A CT slice thickness of 3 mm appears to be a good compromise showing an acceptable average dose uncertainty of 1%, without unduly increasing the number of slices.

ACR Appropriateness Criteria high-dose-rate brachytherapy for prostate cancer

PURPOSE High-dose-rate (HDR) brachytherapy plays a potential curative role in the treatment of prostate cancer. An expert panel was convened to review the recent literature and reach a consensus on its appropriate clinical applications. METHODS AND MATERIALS The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. RESULTS A summary of HDR brachytherapys clinical applications and recent literature review was completed. Three clinical variants were developed to address common HDR dose, fractionations, and indications for its use in definitive therapy for primary and local recurrent prostate cancer. The panel reached a consensus on the specific treatment approaches with numerical rating and commentary. CONCLUSIONS In combining available medical literature and expert opinion, this manuscript may serve as an aid for other practitioners in the appropriate application of HDR brachytherapy for prostate cancer.

Endocervical ultrasound applicator for integrated hyperthermia and HDR brachytherapy in the treatment of locally advanced cervical carcinoma

PURPOSE The clinical success of hyperthermia adjunct to radiotherapy depends on adequate temperature elevation in the tumor with minimal temperature rise in organs at risk. Existing technologies for thermal treatment of the cervix have limited spatial control or rapid energy falloff. The objective of this work is to develop an endocervical applicator using a linear array of multisectored tubular ultrasound transducers to provide 3-D conformal, locally targeted hyperthermia concomitant to radiotherapy in the uterine cervix. The catheter-based device is integrated within a HDR brachytherapy applicator to facilitate sequential and potentially simultaneous heat and radiation delivery. METHODS Treatment planning images from 35 patients who underwent HDR brachytherapy for locally advanced cervical cancer were inspected to assess the dimensions of radiation clinical target volumes (CTVs) and gross tumor volumes (GTVs) surrounding the cervix and the proximity of organs at risk. Biothermal simulation was used to identify applicator and catheter material parameters to adequately heat the cervix with minimal thermal dose accumulation in nontargeted structures. A family of ultrasound applicators was fabricated with two to three tubular transducers operating at 6.6-7.4 MHz that are unsectored (360 degrees), bisectored (2 x 180 degrees), or trisectored (3 x 120 degrees) for control of energy deposition in angle and along the device length in order to satisfy anatomical constraints. The device is housed in a 6 mm diameter PET catheter with cooling water flow for endocervical implantation. Devices were characterized by measuring acoustic efficiencies, rotational acoustic intensity distributions, and rotational temperature distributions in phantom. RESULTS The CTV in HDR brachytherapy plans extends 20.5 +/- 5.0 mm from the endocervical tandem with the rectum and bladder typically <8 mm from the target boundary. The GTV extends 19.4 +/- 7.3 mm from the tandem. Simulations indicate that for 60 min treatments the applicator can heat to 41 degrees C and deliver > 5EM(43 degrees C) over 4-5 cm diameter with Tmax < 45 degrees C and 1 kg m(-3) s(-1) blood perfusion. The 41 degrees C contour diameter is reduced to 3-4 cm at 3 kg m(-3) s(-1) perfusion. Differential power control to transducer elements and sectors demonstrates tailoring of heating along the device length and in angle. Sector cuts are associated with a 14-47 degrees acoustic dead zone, depending on cut width, resulting in a approximately 2-4 degrees C temperature reduction within the dead zone below Tmax. Dead zones can be oriented for thermal protection of the rectum and bladder. Fabricated devices have acoustic efficiencies of 33.4%-51.8% with acoustic output that is well collimated in length, reflects the sectoring strategy, and is strongly correlated with temperature distributions. CONCLUSIONS A catheter-based ultrasound applicator was developed for endocervical implantation with locally targeted, 3-D conformal thermal delivery to the uterine cervix. Feasibility of heating clinically relevant target volumes was demonstrated with power control along the device length and in angle to treat the cervix with minimal thermal dose delivery to the rectum and bladder.

ACR Appropriateness Criteria® External-Beam Radiation Therapy Treatment Planning for Clinically Localized Prostate Cancer

Image-based radiation treatment planning and localization have contributed to better targeting of the prostate and sparing of normal tissues. Guidelines are needed to address radiation dose delivery, including patient setup and immobilization, target volume definition, treatment planning, treatment delivery methods, and target localization. Guidelines for external-beam radiation treatment planning have been updated and are presented here. The use of appropriate doses, simulation techniques, and verification of field setup are essential for the accurate delivery of radiation therapy. The ACR Appropriateness Criteria(®) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

WE-F-16A-01: Commissioning and Clinical Use of PC-ISO for Customized, 3D Printed, Gynecological Brachytherapy Applicators

PURPOSE (1) Evaluate the safety and radiation attenuation properties of PCISO, a bio-compatible, sterilizable 3D printing material by Stratasys, (2) establish a method for commissioning customized multi- and single-use 3D printed applicators, (3) report on use of customized vaginal cylinders used to treat a series of serous endometrial cancer patient. METHODS A custom film dosimetry apparatus was designed to hold a Gafchromic radio film segment between two blocks of PC-ISO and 3D-printed using a Fortus 400mc (StrataSys). A dose plan was computed using 13 dwell positions at 2.5 mm spacing and normalized to 1500 cGy at 1 cm. Film exposure was compared to control tests in only air and only water. The average Hounsfield Unit (HU) was computed and used to verify water equivalency. For the clinical use cases, the physician specifies the dimensions and geometry of a custom applicator from which a CAD model is designed and printed. RESULTS The doses measured from the PC-ISO Gafchromic film test were within 1% of the dose measured in only water between 1cm and 6cm from the channel. Doses increased 7-4% measured in only air. HU range was 11-43. The applicators were sterilized using the Sterrad system multiple times without damage. As of submission 3 unique cylinders have been designed, printed, and used in the clinic. A standardizable workflow for commissioning custom 3D printed applicators was codified and will be reported. CONCLUSIONS Quality assurance (QA) evaluation of the PC-ISO 3D-printing material showed that PC-ISO is a suitable material for a gynecological brachytherapy vaginal cylinder in a clinical setting. With the material commissioning completed, if the physician determines that a better treatment would Result, a customized design is fabricated with limited additional QA necessary. Although this study was specific to PC-ISO, the same setup can be used to evaluate other 3D-printing materials.

American College of Radiology Appropriateness Criteria® — Locally Advanced (High-risk) Prostate Cancer

The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. This review focuses on locally advanced prostate cancer and the evidence for treatment outcomes, both toxicity and efficacy, across the three major treatment modalities of external beam radiotherapy, brachytherapy and surgery. Only data that could pass contemporary quality metrics were used to form this report. This body of literature suffers from an absence of trials prospectively comparing therapies for efficacy and a lack of long-term prospective comparisons of toxicity. Upon review of these data, the authors concluded that there are several acceptable methods for the treatment of locally advanced prostate cancer that is highly dependent of the patients clinical (both prostate cancer-specific and comorbidity-specific) parameters at diagnosis.