Evelyn Sebastian

PHASE II PROSPECTIVE STUDY OF THE USE OF CONFORMAL HIGH- DOSE-RATE BRACHYTHERAPY AS MONOTHERAPY FOR THE TREATMENT OF FAVORABLE STAGE PROSTATE CANCER: A FEASIBILITY REPORT

PURPOSE To evaluate the technical feasibility and tolerance of image-guided transperineal conformal high-dose-rate (C-HDR) brachytherapy as the sole treatment modality for favorable, localized cancer of the prostate, and to analyze possible intrafraction and interfraction volume changes in the prostate gland which may affect dosimetric quality. METHODS AND MATERIALS Patients were eligible for this prospective Phase II trial if they had biopsy proven adenocarcinoma of the prostate with favorable prognostic factors (Gleason score < or =7, PSA < or =10 ng/ml and Stage < or =T2a). The technique consisted of a transperineal implant procedure using a template with transrectal ultrasound (TRUS) guidance. An interactive on-line real-time planning system was utilized with geometric optimization. This allowed dosimetry to be generated and modified as required intraoperatively. Prescription was to the minimum dose point in the implanted volume, assuring conformal coverage of the prostate at its widest dimension with no margin. Total dose was 3800 cGy in 4 fractions of 950 cGy each, delivered twice a day over 2 days. The dose to any segment of rectum and urethra was limited to < or =75% and < or =125% of the prescription dose, respectively. Before each fraction, needle positions were verified under fluoroscopy and adjusted as required. For the last 10 patients, the adjustments required were measured in a prospective fashion in representative extrema of the gland. TRUS images were recorded for all patients before any needle manipulation, again just before delivering the first fraction and immediately after the last fraction. This typically meant approximately 36 h to pass between the first and last measurements. Implant quality was assessed via dose-volume histograms (DVH). RESULTS Between 3/99 and 6/00, 41 patients received C-HDR interstitial brachytherapy as their only treatment for prostate cancer at our institution. Median age was 64 years (range 51-79). Stage distribution was 27 T1c patients and 14 T2a patients. Three patients had Gleason score (GS) of 5; 34 had GS of 6; 4 patients had GS of 7. Median pretreatment PSA was 4.7 ng/ml (range 0.8-13.3). All patients tolerated the treatment well with minimal discomfort. For 23 patients, data on volume changes in the gland during the implant were tabulated. They demonstrated a mean prostate volume of 30.7 cc before any manipulation with needles, 37.0 cc at the end of fraction 1, and 38.2 cc at the end of fraction 4. In addition, for those 10 patients prospectively evaluated for required adjustments, the overall mean adjustment between fraction 1 and fraction 2 was 2.0 cm, between fraction 2 and 3 was 0.4 cm, and between fractions 3 and 4 was 0.4 cm. For 10 consecutive patients, the average prescriptions dose -D90 for fractions 1 and 4 were 104% and 100%, respectively. The corresponding average urethral D10 for fractions 1 and 4 were 122% and 132%. CONCLUSION Our protocol using C-HDR interstitial brachytherapy as monotherapy for early cancer of the prostate was feasible and well tolerated by 41 patients treated. Changes in interfraction prostate volume do not appear to be significant enough to warrant modification of dosimetry for each fraction. Both excellent dose coverage of the prostate gland and low urethral dose are achieved as measured by DVH. However, paramount attention should be given to needle displacement before each fraction. Needle movement is most significant between fractions 1 and 2. Acute toxicity (RTOG) has been modest. Late toxicity and tumor control rates will be reported as longer follow-up allows.

High-Dose-Rate Brachytherapy as Monotherapy Delivered in Two Fractions Within One Day for Favorable/Intermediate-Risk Prostate Cancer: Preliminary Toxicity Data

PURPOSE To report the toxicity profile of high-dose-rate (HDR)-brachytherapy (BT) as monotherapy in a Human Investigation Committee-approved study consisting of a single implant and two fractions (12 Gy × 2) for a total dose of 24 Gy, delivered within 1 day. The dose was subsequently increased to 27 Gy (13.5 Gy × 2) delivered in 1 day. We report the acute and early chronic genitourinary and gastrointestinal toxicity. METHODS AND MATERIALS A total of 173 patients were treated between December 2005 and July 2010. However, only the first 100 were part of the IRB-approved study and out of these, only 94 had a minimal follow-up of 6 months, representing the study population for this preliminary report. All patients had clinical Stage T2b or less (American Joint Committee on Cancer, 5th edition), Gleason score 6-7 (3+4), and prostate-specific antigen level of ≤12 ng/mL. Ultrasound-guided HDR-BT with real-time dosimetry was used. The prescription dose was 24 Gy for the first 50 patients and 27 Gy thereafter. The dosimetric goals and constraints were the same for the two dose groups. Toxicity was scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. The highest toxicity scores encountered at any point during follow-up are reported. RESULTS The median follow-up was 17 months (range, 6-40.5). Most patients had Grade 0-1 acute toxicity. The Grade 2 acute genitourinary toxicity was mainly frequency/urgency (13%), dysuria (5%), hematuria, and dribbling/hesitancy (2%). None of the patients required a Foley catheter at any time; however, 8% of the patients experienced transient Grade 1 diarrhea. No other acute gastrointestinal toxicities were found. The most common chronic toxicity was Grade 2 urinary frequency/urgency in 16% of patients followed by dysuria in 4% of patients; 2 patients had Grade 2 rectal bleeding and 1 had Grade 4, requiring laser treatment. CONCLUSIONS Favorable-risk prostate cancer patients treated with a single implant HDR-BT to 24-27 Gy in two fractions within 1 day have excellent tolerance with minimal acute and chronic toxicity. Longer follow-up is needed to confirm these encouraging early results.

Real‐time catheter tracking for high‐dose‐rate prostate brachytherapy using an electromagnetic 3D‐guidance device: A preliminary performance study

PURPOSE In order to increase the accuracy and speed of catheter reconstruction in a high-dose-rate (HDR) prostate implant procedure, an automatic tracking system has been developed using an electromagnetic (EM) device (trakSTAR, Ascension Technology, VT). The performance of the system, including the accuracy and noise level with various tracking parameters and conditions, were investigated. METHODS A direct current (dc) EM transmitter (midrange model) and a sensor with diameter of 1.3 mm (Model 130) were used in the trakSTAR system for tracking catheter position during HDR prostate brachytherapy. Localization accuracy was assessed under both static and dynamic analyses conditions. For the static analysis, a calibration phantom was used to investigate error dependency on operating room (OR) table height (bottom vs midposition vs top), sensor position (distal tip of catheter vs connector end of catheter), direction [left-right (LR) vs anterior-posterior (AP) vs superior-inferior (SI)], sampling frequency (40 vs 80 vs 120 Hz), and interference from OR equipment (present vs absent). The mean and standard deviation of the localization offset in each direction and the corresponding error vectors were calculated. For dynamic analysis, the paths of five straight catheters were tracked to study the effects of directions, sampling frequency, and interference of EM field. Statistical analysis was conducted to compare the results in different configurations. RESULTS When interference was present in the static analysis, the error vectors were significantly higher at the top table position (3.3 ± 1.3 vs 1.8 ± 0.9 mm at bottom and 1.7 ± 1.0 mm at middle, p < 0.001), at catheter end position (3.1 ± 1.1 vs 1.4 ± 0.7 mm at the tip position, p < 0.001), and at 40 Hz sampling frequency (2.6 ± 1.1 vs 2.4 ± 1.5 mm at 80 Hz and 1.8 ± 1.1 at 160 Hz, p < 0.001). So did the mean offset errors in the LR direction (-1.7 ± 1.4 vs 0.4 ± 0.5 mm in AP and 0.8 ± 0.8 mm in SI directions, p < 0.001). The error vectors were significantly higher with surrounding interference (2.2 ± 1.3 mm) vs without interference (1.0 ± 0.7 mm, p < 0.001). An accuracy of 1.6 ± 0.2 mm can be reached when using optimum configuration (160 Hz at middle table position). When interference was present in the dynamic tracking, the mean tracking errors in LR direction (1.4 ± 0.5 mm) was significantly higher than that in AP direction (0.3 ± 0.2 mm, p < 0.001). So did the mean vector errors at 40 Hz (2.1 ± 0.2 mm vs 1.3 ± 0.2 mm at 80 Hz and 0.9 ± 0.2 mm at 160 Hz, p < 0.05). However, when interference was absent, they were comparable in the both directions and at all sampling frequencies. An accuracy of 0.9 ± 0.2 mm was obtained for the dynamic tracking when using optimum configuration. CONCLUSIONS The performance of an EM tracking system depends highly on the system configuration and surrounding environment. The accuracy of EM tracking for catheter reconstruction in a prostate HDR brachytherapy procedure can be improved by reducing interference from surrounding equipment, decreasing distance from transmitter to tracking area, and choosing appropriated sampling frequency. A calibration scheme is needed to further reduce the tracking error when the interference is high.

The clinical advantages of I-125 seeds as a substitute for IR-192 seeds in temporary plastic tube implants☆

In August of 1986 at William Beaumont Hospital, Iodine-125 (I-125) seeds were introduced in the clinical practice as a substitute for Iridium-192 (Ir-192) seeds in patients undergoing temporary plastic tube interstitial implants. Through February 1988, 108 I-125 implants were performed in 105 patients. Acute and chronic toxicity was indistinguishable from Ir-192. However, improved radiation safety and a dynamic dosimetric program have resulted from this endeavor. Because of the multiple clinical advantages of I-125, we feel that this should be considered the isotope of choice in temporary interstitial plastic tube implants.

SU‐D‐213AB‐01: Dosimetry Improvement and Needle Number Reduction in Prostate Brachytherapy Using Electromagnetically Guided Needle Placement

PURPOSE To investigate dosimetry improvement in prostate brachytherapy by conforming needles to urethral and prostate shape using an electromagnetic tracking device. METHODS We have reported a needle tracking system using an electromagnetic sensor embedded inside the tip of the needle to improve needle reconstruction accuracy and efficiency in conventional prostate HDR brachytherapy. Utilizing the same system, we propose to guide needle insertion following pre-optimized tracks based onthe target shape. In this study, we investigate possible dosimetry improvement and needle number reduction by comparing plans using the conventional implant method and the proposed method. Twelve prostate brachytherapy patients were selected and studied retrospectively. New virtual plans were created using the proposed method and conforming needle tracks to the urethral and prostate shapes. Same optimization constraints were applied to both the conventional and the new plans. DVH parameters and total needles used have been analyzed to quantify dosimetry improvement and potential toxicity sparing due to reduction in implant needles. RESULTS Prostate volumes are 41.16±13.27 cc. Number of needles used for the conventional plan is 16.6±1.2, vs. 13 for all the new plans. The prostate volume receiving 100% (V100), 125% (V125), and 150% (V150) of the prescription dose in conventional plans vs. those in the new plans are 99.48%±0.21% vs. 99.53%±0.20%, 53.90%±5.61% vs. 50.30%±5.23%, and 25.37%±4.91% vs. 20.96%±3.41%, respectively. The corresponding urethra V100 and V110 are 90.96%±3.10% vs. 85.78%±7.76% and 2.06%±1.23 vs. 0.46%±0.28%. CONCLUSIONS The needle numbers and the urethral V110 in the new plans are significantly lower than those in conventional plans(p<0.001 and p=0.004, respectively), with no significant changes in doses tothe prostate. Conformai needle implant following pre-optimized tracks with electromagnetic guidance may significantly reduce acute and late toxicities in prostate brachytherapy by reducing the number of needles and theurethral doses.

WE‐A‐BRB‐04: Real‐Time Catheter Tracking for HDR Prostate Implant Using an Electromagnetic 3D Guidance Device

Purpose: In order to increase the accuracy and speed of catheter reconstruction in an HDR prostate implant procedure, an automatic tracking system has been developed using an electromagnetic device. The performance of the system was investigated. Methods: A transmitter with detection range of 36 cm and a sensor with diameter of 0.9 mm were used for needle position tracking during a HDR prostate implant. Due to substantial interference in the electromagnetic field from the surgical table, implant stepper/stabilizer etc, a calibration algorithm using a scattered data interpolation scheme was implemented to correct tracking location error. Reproducibility of the calibration algorithm was determined under various equipment arrangements. A QA phantom with straight catheters was constructed for deriving calibration profiles, and for investigating the accuracy of the system. Tracking of catheter positions was conducted at distances between 140 mm and 280 mm from the transmitter. In addition, the QA phantom was inserted 17 needles with curved trajectories to simulate a typical prostate implant. Needle reconstruction time was recorded and compared to general ultrasound reconstruction times while reconstruction positions were compared to CT reconstructions of the phantom to validate the system. Results: Average tracking accuracies after calibration were 0.4 ± 0.3 mm and 2.4 ±1.7 mm without calibration. The max standard deviation was 0.9 mm in the test range for the reproducibility test. The total tracking time for the 17 catheters was less than 4 minutes and the reconstruction result matches CT data within 2.0 mm. Conclusions: Compared to conventional ultrasound based real‐time catheter reconstruction method in the HDR prostate implant, the system can reduce the error from > 3 mm to < 1.5 mm, shorten the time from 15–60 minutes to < 4 minutes. Furthermore, this technique can also be used for other HDR implants.

WE‐B‐BRA‐02: Deformable Registration Based Tool to Obtain Cumulative Doses from External Beam IMRT and HDR Interstitial Brachytherapy

Purpose: To obtain cumulative doses from external beam (EB) IMRT and HDR interstitial brachytherapy (BT) for prostate cancer. Methods and Materials: A tool was developed for multimodality image manipulation and registration within our current treatment planning framework to obtain cumulative doses from BT and EB‐IMRT. The HDR BT boost performed under transrectal ultrasound guidance is planned using Nucletron Oncentra prostate TPS. A total implant dose of 21 Gy is administered in two 10.5 Gy fractions. The daily external beam dose to the PTV was 2 Gy given in 23 fractions and planned with IMRT using Pinnacle TPS. US DICOM images, structures and 3‐D dose matrix were pre‐processed for import with in Pinnacle TPS. US and CTimages were rigidly registered as a preliminiary step inside Pinnacle based on prostate contours on two imagesets and implanted visicoils markers. A linear‐quadratic model is applied to calculate the total equivalent dose in 2Gy fractions (EQD2) with αβ=4 for prostate. Tools were developed to perform deformable registration based on biomechanical model of human organs and the finite element analysis methods. Result: A biomechanical model of US and CT prostate volume was generated on a clinical case using 5544 nodes (5240 subvolumes). The deformation vector field generated after deforming prostate contours was used to deform 3D USdose matrix on to CT grid. Using EQD2 of 50.4 Gy from brachytherapy and 46 Gy from IMRT, the cumulative D99 and D95 to CT prostate volume was 98.2 Gy and 100.4Gy. Conclusion: There is a lack of availability of commercial TPS in which EBRT and BT plans can be fully integrated. The tool provides a robust and accurate means of obtaining cumulative doses from brachytherapy and EB‐ IMRT. It also has the potential to incorporate doses from brachytherapy during inverse planning adaptive optimization of external beam IMRT.