A novel MRI-based approach to prostate brachytherapy

Abstracts / Brachytherapy 7 (2008) 91e194 2

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M.D. Edward Messing, M.D. Wan-Sing Ng, Ph.D. Yan Yu, Ph.D. 1 Radiation Oncology, Thomas Jefferson University, Philadelphia, PA; 2 Urology, Radiology, Surgery, University of Rochester, Rochester, NY; 3 Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore, Singapore. Purpose: To evaluate the performance of an ultrasound image-guided fully automated robotic system developed for prostate seed implant. Methods and Materials: A 7 degree-of-freedom (dof) robotic surgical module has been designed and developed not only to provide flexibility in positioning and orientating along with improved consistency and accuracy of needle insertion and seed deposition but also to assist clinician to treat patients with improved accuracy. The surgery module is installed on a 9 dof positioning module which houses all the electronics and computer. The clinician can use a handheld pendent to takeover the robot control at any point in time. Sterilization and decontamination of required components of the robot have been taken into consideration. Various techniques to enhance precision of needle insertion and seed delivery have been implemented into the system, after extensive verification via phantom experiments. Three force-torque sensors were incorporated for tracking the forces on the needle to improve robot control and to detect pubic arch interference. The system’s provisions for position, velocity and force feedbacks are useful to improve needle insertion and seed delivery accuracy, consistency and efficiency. The integrated software is capable of dosimetric planning, 3D visualization, needle tracking and seed detection for dynamic planning. Preliminary seed implant experiments using tissue mimicking soft material phantoms prepared from polyvinylchloride have been performed. Dummy brachytherapy seeds were deposited in the phantoms at 1cm distance (in x, y and z directions). Results: Assessment of the deposited seeds revealed that the accuracy (rms error) of seed placement is 0.67 mm in x direction (SD 5 0.58 mm), 0.13 mm (SD 5 0.12 mm) in y direction, and 0.11 mm (SD 5 0.11mm) in z direction. The 3D (Euclidean) rms error is 0.69 mm, which is small as compared to clinically acceptable limit. Conclusions: This prototype robotic system is quite accurate in needle placement and seed delivery. The preliminary experimental results exhibit relatively large error in x-direction; this issue is under investigation. However, the 3D seed placement error is at sub-millimeter level. Thus, it appears that this robotic system can potentially improve seed placement accuracy while assisting clinicians. This research work is supported by NCI Grant No. R01 CA91763.

OR26 Presentation Time: 5:40 PM Feasibility and preliminary experiences of choline-PET/CT imaging for salvage HDR brachytherapy for local recurrences of previous irradiated prostate cancer Peter Niehoff, M.D.1 Niels Nurnberg, M.D.2 Frank-Andre Siebert, Ph.D.1 Hagen Bertermann, M.D.2 Bernhard N. Kimmig, M.D., Ph.D.1 1 Radiotherapy (Radiooncology), University Hospital S-H, Campus Kiel, Kiel, Germany; 2Urology Practice, Municipal Hospital Kiel, Kiel, Germany. Purpose: Treatment options for patients with primary irradiated prostate cancer and a PSA progression during antiandrogene therapy are limited. In consecutive referred patients with circumscribed recurrence of the prostate, all eligible for interstitial treatment, we investigated the feasibility of fractionated salvage high-dose-rate brachytherapy (HDRBT). Methods and Materials: Between October 2005 and October 2007 ten patients with PSA progression after radiotherapy were seen in our department. All patients received choline-PET/CT and a transrectal ultrasound before treatment. Four patients had previous primary external beam treatment (EBRT). The mean EBRT dose was 67.5 Gy (range 59.4e70.2 Gy). The other six patients had a primary combined EBRT and HDR-BT with 50 Gy EBRT and 2x15 Gy HDR-BT. A mean of 7.5 needles (range 5e10), guided with transrectal ultrasound (TRUS), were implanted transperinally. Fraction doses of 3x 10 Gy were applied for the first three patients to the PET detected tumor lesion. For the other seven

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patients the target volume was the peripheral zone of the prostate, sparing the urethra. Interfraction time was one week. Results: Nine of the ten patients showed a pathological choline uptake in the prostate. Choline-PET/CT was negative in one patient with an antiandrogene deprivation and a PSA of 0.2 ng/mL. After a mean followup of 11 months (range 3 e 20 months) we observed 7 patients with stable local disease stated by TRUS and PSA. In one case we observed local progress. One patient had local and systemic progress detected by choline-PET/CT. One patient had vessel bleeding after the first implantation and treatment was discontinued. This patient suffer from a urinary retention and required a catheter, because of local progress. The remaining nine patients had no RTOG grade III or IV side effects. All three patients with local progress had only an implantation of the tumor lesions detected in choline-PET/CT. Conclusions: If patients are eligible for implantation, TRUS-guided hypofractionated perineal HDR brachytherapy seems to be a feasible salvage treatment for local recurrences after previous radiotherapy. It seems that a circumscribed implantation of the tumor lesion is insufficient. These early results need to be confirmed by longer followup and a higher number of patients.

OR27 Presentation Time: 5:50 PM A novel MRI-based approach to prostate brachytherapy Steven J. Frank, M.D.1 R. Jason Stafford, Ph.D.2 James A. Bankson, Ph.D.2 Chun Li, Ph.D.3 David A. Swanson, M.D.4 Rajat J. Kudchadker, Ph.D.5 Karen Martirosyan, Ph.D.6 1Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX; 2Imaging Physics, The University of Texas M.D. Anderson Cancer Center, Houston, TX; 3 Experimental Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, TX; 4Urology, The University of Texas M.D. Anderson Cancer Center, Houston, TX; 5Radiation Physics, The University of Texas M.D. Anderson Cancer Center, Houston, TX; 6 Chemical and Biomolecular Engineering, The University of Houston, Houston, TX. Purpose: Magnetic resonance imaging (MRI) is the optimal imaging modality for the prostate and surrounding critical organ structures. However, with MRI, the standard titanium radioactive seeds, strands of seeds, and needle tracks appear as black holes (negative contrast) and cannot be accurately localized within the prostate and periprostatic tissue. The purpose of this study was to develop a novel MRI contrast agent marker that would permit the accurate identification of implanted radioactive seeds. Methods and Materials: We investigated agents with paramagnetic, superparamagnetic, and weak ferromagnetic properties. These agents included cobalt (II) chloride complex compounds with different concentrations. Combinations of seeds and Encapsulated Contrast Agent Markers (ECAM) were implanted into an ex-vivo canine prostate. All measurements were made on a 1.5T clinical MR scanner. Samples were placed in a room temperature water bath and imaged using a quadrature knee coil. T1 measurements used an inversion recovery spin-echo technique (TR/TE 5 5000ms/10ms; TI 5 50ms-4000ms). T2 measurements utilized a spin echo sequence (TR 5 5000ms; TE 5 20ms1000ms). T2* measurements utilized a multi-echo fast, gradient echo acquisition (TR 5 600ms; TE 5 2ms-57ms with an echo-spacing of 3.3ms). All imaging data was analyzed using in-house software written in MATLAB (MathWorks, Natick, MA). Results: Acrylic and glass hollow seeds containing 2e5 mL of the cobalt (II) complex aqueous solution (10-1 wt.%) were well visualized with a relative signal intensity ranging from 10751 to 32767 in a phantom under 1.5-T MRI (T1). At 2% concentration the T1, T2, and T2* data was 63.9, 61.6, and 43.7 ms, respectively. The various combinations of [plastic/glass]titanium-[plastic/glass] and titanium-[plastic/glass]-titanium rows of seeds were visualized in a canine prostate, and calculations verified the distance from the ECAM to the center of the titanium seeds. Conclusions: We have developed a novel ECAM that provides high signal intensity on MRI by shortening the spin lattice relaxation time of water protons. The positive identification of implanted radioactive seeds may

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Abstracts / Brachytherapy 7 (2008) 91e194

facilitate MRI-based brachytherapy.

dosimetry

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image-guided

prostate

OR28 Presentation Time: 6:00 PM Registered ultrasound and fluoroscopy for intraoperative dynamic dosimetry in prostate brachytherapy Danny Y. Song, M.D.1 Anton Deguet, Ph.D.2 Iulian Iordachita, Ph.D.2 Elwood Armour, Ph.D.1 Ameet Jain, Ph.D.2 Everette C. Burdette, Ph.D.3 Gabor Fichtinger, Ph.D.4 1Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD; 2 Computer Science, Johns Hopkins University, Baltimore, MD; 3Acoustic Medsystems Inc, Urbana-Champagne, IL; 4Computer Science, Queen’s University, Kingston, ON, Canada. Purpose: Clinical outcomes following permanent prostate brachytherapy are highly dependent upon dosimetric results achieved intraoperatively. Factors such as tissue deformation, prostatic edema, and source migration create dynamically changing intraoperative dosimetry, yet currently available brachytherapy techniques do not allow identification of source positions after they have been deposited into the prostate. We developed and clinically tested a system which spatially coregisters fluoroscopy images with ultrasound in order to provide dynamic dosimetry intraoperatively. Methods and Materials: The registration of ultrasound to flouroscopy system (RUF) utilizes a non-invasive, radio-opaque fiducial mounted onto the needle guidance template, as well as a unique software algorithm which runs on a laptop computer interfaced with the treatment planning system (Interplant, Computerized Medical Systems, St. Louis, MO). Otherwise no additional hardware is required. For seed position reconstruction, a set of 4-5 non-coplanar X-ray images are acquired with a non-isocentric C-arm. The seed coordinates are calculated by formalizing seed matching as a network flow problem. Calculated seed positions are then imported into the treatment planning software, and the treatment plan re-optimized. Results: Six patients were treated on an IRB-approved protocol. C-arm images were obtained and RUF calculation of seed positions was performed 3 times during each case, and subsequent seed placement modified as determined by physician judgment. Seed counts identified by RUF matched the number of seeds actually placed. Based on RUF data, 3e10 seeds were added to the original treatment plan to alter areas of visualized underdosing. Day 0 CT dose-volume histogram data are as follows: prostate D90 of 98e139%, V100 of 88e99%, urethral D30 98e143%, urethral D5 114e154%, rectal R100 of !0.1 cc. One patient (D90 5 98% and V100 5 88%) was identified intraoperatively as having an area not covered by the prescription isodose line, but all available seeds had been utilized. Conclusions: Dynamic intraoperative dosimetry was achieved using our system of registered ultrasound and fluoroscopy. Further work is directed at streamlining the image processing workflow and developing a system which eliminates the need for the entire fiducial to be captured in every image. A Phase II clinical trial is planned to confirm the dosimetric results achieved in this pilot trial.

MISC ORAL PRESENTATION SESSION Monday May 5, 2008 8:00 AMe9:00 AM OR29 Presentation Time: 8:00 AM External beam radiotherapy and interstitial brachytherapy, with or without chemotherapy in the conservative treatment of anal canal carcinoma Shyam Kishore Shrivastava, M.D., Reena Engineer, M.D, Umesh Mahantshetty, M.D., Ritu Bhutani, M.D., Suman Mallick, M.D., Pramod K. Sharma, M.Sc., Ketayun A. Dinshaw, FRCR Tata Memorial Centre, Mumbai, India.

Purpose: Radiotherapy is the standard treatment of anal canal carcinoma. The aim of this retrospective analysis is to study the effect of addition of high-dose-rate (HDR) brachytherapy boost along with course of external beam radiotherapy series (EBRT) with or without chemotherapy. Methods and Materials: This retrospective analysis included 116 patients with anal cancer who underwent interstitial implant between 1985 and 2004. Five patients were stage I, 95 stage II, 2 stage IIIA and 14 stage IIIB. Fiftyseven (49%) patients underwent external radiotherapy followed by an interstitial implant, remaining 59 (51%) patients received chemotherapy (Mitomycin & 5-FU) in addition to EBRT and brachytherapy boost. The mean EBRT dose was 48 Gy and implant dose was 21 Gy. Results: The median followup was 51 months (range: 3e186 months). Disease-free survival (DFS) and overall survival (OAS) at 5 years for the whole group was 71% and 78%, respectively. Recurrence of disease was seen in 34 (30%) patients, 15 (27%) in the CT+ RT group and 19 (33%) in the RT group. Of the 28 (24%) patients with either persistent disease or locoregional recurrence 11 (39%) were salvaged by surgery. The crude rate of anal preservation was 87% while 3 (3.75%) patients who were locoregionally controlled underwent defunctioning colostomy due to anal stricture. Conclusions: The integration of the HDR boost in EBRT regimen with or without chemotherapy resulted in excellent sphincter function without an increase in severe complications and with rates of LRC, DFS, and OS, which can be compared favorably with those reported in the literature. The addition of chemotherapy did not seem to alter the failure.

OR30 Presentation Time: 8:10 AM Long-term results of function preservation by transrectal ultrasound (TRUS)-guided fractionated HDR brachytherapy boost complementary to external beam radiation ± chemotherapy in anal cancer Gyoergy Kovacs, M.D., Ph.D.1,3 Marek J. Doniec, M.D.2 Bodo Schniewind, M.D.2 Matthias Loehnert, M.D., Ph.D.2 Peter Niehoff, M.D.3 Peter Kohr, Ph.D.3 Bernd Kremer, M.D., Ph.D.2 1Interdisciplinary Brachytherapy Unit, UK-SH Campus Luebeck, Luebeck, Germany; 2 General and Thoracic Surgery, UK-SH Campus Kiel, Kiel, Germany; 3 Radiation Therapy (Radiooncology), UK-SH Campus Kiel, Kiel, Germany. Purpose: In this prospective observation we analyzed the long-term results of endosonography (TRUS)-guided target definition and implantation procedure as well as of real-time volume optimized treatment planning and fractionated radiation delivery in the interstitial boost brachytherapy of anal cancer. Interdisciplinary cooperation and the use of the RASHAapplicator aimed resulting in an improvement in long-term outcome at the function preservative treatment of anal cancers. Methods and Materials: Fifty patients with biopsy proven primary cancer of the anal canal (n 5 38) or-margin (n 5 12) without distant metastases were treated between 1993e2001. Before treatment all pts received TRUS and sphincter function measurements. The treatment started with 45 Gy EBRT to the pelvic region with conventional fraction and in case of N+ or T3-T4 in combination with chemotherapy. Within 2e4 weeks after completing EBRT a high-dose-rate intensity modulated interstitial brachytherapy boost (IMBT) was administered to the tumor bed/residual tumor using two fractions of 4e6 Gy and the RASHA applicator. Fraction dose was defined at the surface of the TRUS visible target volume, needle geometry followed the rules of the Paris system. Mean followup was 34 months (6e96). Results: Ninety-two per cent of the patients demonstrated a complete tumor remission after completing the treatment. Local recurrence occurred in one patient 15 months after treatment. Disease-specific 5-year survival rate was 82%. Five patients received abdomino-perineal resection (3 pts with persistent tumor, 1 with a local recurrence and 1 because of suspected recurrence). Four out of these 5 patients died on progressive disease. Because of the observed mild proctitis (2/50) and severe sphincter necrosis (3/50) we reduced the initial 2x6 Gy HDR fraction dose to 2x4 Gy. In the following there were no acute severe side effects due to