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71 Post implant dosimetry evaluation for prostate interstitial brachytherapy: A comparison of two commonly used techniques
among different sites. Prescription dose margins around the ultrasound gland edge were measured at base, mid-gland and apex. Base and apex margins varies considerably. Mid-gland posterior margins were fairly uniform, ranging from 1 to 3 mm. Anterior and lateral margins at mid-gland ranged from -1 to 10 m m and 0 to 6 m m respectively. Conclusions: Even among institutions with similar approaches to permanent I-125 prostate brachytherapy, considerable differences were found in the total volume irradiated, the margin of the dose around the gland, and the accepted intensity of dose within the implant. This reflects differing treatment philosophies of the various members of the group, and defines a spectrum of current practice across many active brachytherapy practices. Qualitative analysis of these planning differences will be possible only if outcome data is obtained and linked to the intended planning philosophy. These data are currently being prospectively gathered in a phase 111randomized trial of the Prostate Brachytherapy Research Group. 70 INTRAOPERATIVE CONFORMAL OPTIMIZATION FOR TRANSPERINEAL PROSTATE IMPLANTATIONUSING M R SPECTROSCOPIC IMAGING Michael J. Zelefsky ~, M.D., Gilad Cohen*, M.Sc., Kristen L. Zakian*, Ph.D., Jonathan Dyke*, Ph.D., Jason A. Koutcher*, M.D., Ph.D. Marco Zaider*, Ph.D. Departments of Radiation Oncology, *Medical Physics and Medical Oncology# Memorial Sloan-Kettering Cancer Center, New York, NY, USA Purpose: Recent studies have demonstrated that magnetic resonance spectroscopic imaging (MRSI) of the prostate may effectively distinguish between regions of cancer and normal prostatic epithelium. This diagnostic imaging tool takes advantage of the increased choline versus citrate ratio found in malignant compared normal prostate tissue. A method is described which registers MRSI to intraoperative-obtained ultrasound images and incorporates this information into a treatment planning system to achieve dose escalation to intraprostatic tumor deposits. The purpose of this study is to report our preliminary experience and dosimetric outcome with ten consecutive patients who underwent permanent interstitial implantation using intraoperative computer-based treatment-planning with MRSI optimization. Materials and methods: MRSI was obtained preoperatively for ten patients with clinically localized prostate cancer. The ratios of choline and citrate for the prostate were analyzed, and regions of high risk for malignant cells were identified. The ratios representing peaks on the MR spectrum were calculated on a spatial grid covering the prostate tissue. A procedure for mapping points of interest from the MRSI to the ultrasound images is described. A computer-based treatment planning system was used which relied on a genetic algorithm to determine the optimal seed distribution to achieve maximal target volume reduction and maintain urethra and rectal doses within tolerance ranges. MRSI data was incorporated into the treatment planning system to test the feasibility of dose escalation to positive voxels with relative sparing of surrounding normal tissues. Post-implant CT scans were performed on the same day of the procedure in all cases, and dosimetric guidelines of the American Brachytherapy Society were used to assess implant quality. Results: The intraoperative optimization treatment planning program was able to achieve a minimum dose of 139% - 192% of the 144 Gy prescription to the MRS positive voxels using I- 125 seeds. The percentage of the prostate volume receiving 100% of the prescription dose (V 100) ranged from 92%-97% and the D90 for the target volume ranged from 96%-100%. Despite the dose escalation achieved for the MRSI positive voxels, the urethral and rectal doses were maintained within tolerance ranges. The average and maximal rectal doses ranged from 28-42% and 69115%, respectively. The average and maximal urethral doses ranged from 66-144% and 138-166%, respectively. Conclusions: Using this brachytherapy optimization system, we could demonstrate the feasibility of MRS-optimized dose distributions for I-125 permanent prostate implants. This approach may have an impact on the ability to safely employ dose escalation for patients treated with permanent interstitial implantation and improve outcome for patients with organ confined prostatic cancers. 71 POST IMPLANT DOSIMETRY EVALUATIONFOR PROSTATE INTERSTITIAL BRACHYTHERAPY: A COMPARISON OF TWO COMMONLY USED TECHNIQUES S.K. Saraf, Ph.D., A. Zablow, M.D., R.L. Goodman, M.D., and K.D. Steidley, Ph.D. Department of Radiation Oncology, Saint Barnabas Medical Center, Livingston, NJ 07039 Purpose: Permanent prostate implants using 1-125 and Pd-103 radioactive seeds have been performed for early stage disease. Several techniques for seed implantation have been developed. Two of the most commonly used techniques utilize 1) PREPLAN volume scans, and 2) REAL TIME volume scans. We have compared the two techniques following ABS recommended methodology. Methods and materials: 30 patients were studied, 15 implanted using pre-plan ultrasound scans obtained 2 weeks earlier and the remaining 15 patients using real time scans obtained at the time of seed implantation. A pre-plan scan is usually obtained for all patients, but for patients implanted using real time scans, pre-plan scans were omitted. Three weeks following seed implantation CT Scans along with simulation films were obtained to evaluate the implants. As proposed by ABS, DI00, D90, V100 and V150 indices were calculated for each patient. D100 and D90 are defined as the mPD Dose that covers 100% and 90% of the prostate volume, while V 100 and V 150 are defined as the percentage of the prostate volume that receives 100% and 150% of the prescribed dose. Results: The mPD for Pd-103 and 1-125 implants were 115 Gy and 144 Gy (TG-43) respectively. The pre-plan patients had their implant performed from a plan devised using pre-plan scans. At the time of seed placement, variations in the prostate volume scans were minimized to achieve the dose distribution as close to the pre-planned volume as could be achieved. Such an extra effort is not needed for real time implant technique as the implant is performed on the volume scans obtained at the time of the implant. The following table provides an in-depth comparison of the two techniques used.
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1-125 Pd-103
TRUS Vol. 35.5 32.5
CT Vol. 45.2 41.0
Pre-Plan Technique DI00 D90 Gy Gy 102.0 137.0 85.0 106.0
V100 87% 85%
V150 55% 52%
TRUS Vol. 35.6 32.5
CT Vol. 44.8 41.3
Real Time Technique DI00 D90 Gy Gy 127.0 150.0 106.0 120.0
V100
V150
95% 96%
38% 32%
Data are shown for an average size prostate gland volume of 35cc. % in volume are with reference to CT volume. TRUS -> Trans Rectal Ultra Sound Conclusion: It has been found that although the pre-scans can usually be matched very closely to the scans obtained at the time of implant, a mismatch can result in large dose inhomogeneities (D100) especially for the lower energy isotope Pd-103, as dose gradients are large in value. For the real time implantation technique, the pre-scans derived preliminary dosimetry of the implant can be valuable in ordering the isotope and in seed placement adjustment at the time of implant. Most importantly, we have found that the high dose region (V 150) in the real time implant technique is significantly lower than the high dose region derived from pre-plan scans. 72 L o w DOSE ( L D R ) OR HIGH DOSE ( H D R ) RATE IR-192 CONFORMAL BRACHYTHERAPY WITH TEMPORARY TRANSPERINEAL IMPLANTATION IN COMBINATION WITH EXTERNAL BEAM RADIATION ( E B R ) FOR NON-METASTATIC PROSTATE ADENOCARCINOMA: THE CENTRE FRAN(~OIS BACLESSE EXPERIENCE IN 531 CASES TREATED BETWEEN JULY 1 9 8 7 AND DECEMBER 1997.
D. Brune, J.F. Lesaunier, D. Benabid, M. Henry-Amar, Centre Franqois Baclesse, 14076 Caen Cedex, France Technique: We use transperineal implantation with 4 to 6 20 cm divergent needles, held in place by template. Planned and control dosimetries are carried out using orthogonal X-rays and CT scan, with dummy sources in urethral, bladder and rectal probes. Implantation is made with general anesthesia, the patient being in dorsal decubitus on a radiological table to which an implanter is attached. The positioning of the needles is carried out under scopic X-ray and ultrasound control. Treatment protocol: The first protocol involved 15 Gy LDR brachytherapy and 45 Gy pelvic EBR. The second protocol combined 15 Gy LDR brachytherapy and 45 Gy prostate EBR in well localized tumors (Tlb-c, T2a), tumors of small volume (<4cm in diameter), or for vulnerable patients (ECOG-2). When the implantation was geometrically correct, the 15 Gy LDR brachytherapy was replaced by 2 x 4.7 Gy HDR brachytherapy delivering a maximal dose of 2 x 4.7 Gy to the anterior rectal mucosa and 2 x 9 Gy to the urethral mucosa (mean dose). Finally, for patients with only one risk factor (stage, Gleason, initial PSA, NO or N-) the brachytherapy dose was 25 Gy LDR, equivalent to 4 x 3.9 Gy HDR combined with 35 Gy EBR limited to the prostate. Study population: The characteristics of the 531 patients were: mean age 69 years (45 to 85 years), 30% ECOG-2, 78% with previous cardiovascular and/or metabolic history and 50% with history of abdominal surgery. 462 patients had histologically known Gleason with 66% Gleason II to VI, 25% Gleason VII, 9% Gleason VIII to X. Initial PSA (hybritec technique, normal level < 4 ng/ml) was available for 526 patients. The median PSA was 21 ng/ml (0 to 500). 22% of patients had PSA 0 to 10 nffml; 26% had PSA 11 to 20 ng/ml; and 51% had PSA > 20 ng/ml. There were 15% patients with TI, 51% with T2, 33% with T3, while T4 was observed in only 2 cases and Tx in 3 cases. 21% of patients were Nx, 74% were NO and 5% NI-N2. Results: The overall survival (OS) rate was 91% at 3 years, 82.4% at 5 years, and 44.1% at 10 years. Of the 421 patients treated with exclusive radio-brachytherapy, 77% normalised their PSA (55% with PSA < 1 ng/ml). In patients treated with 25 Gy LDR or 4 x 3.9 Gy HDR and 35 Gy prostate EBR, PSA normalization was obtained in 88% in an average time-scale of 172 days. In patients treated with 15 Gy LDR or 2 x 4.7 Gy HDR and 45 Gy prostate EBR, PSA normalization was obtained in 87% and in 205 days. In patients treated with 15 Gy LDR or 2 x 4.7 Gy HDR and 45 Gy pelvic EBR, PSA normalization was obtained in 73 % of the cases and in 234 days. PSA normalization < I ng/ml was obtained in 66%, 64% and 50% in the three groups, respectively. In the overall population, the cumulative rate of clinical or histologic local recurrence (CRLR) was 4.2% at 3 years, 10.5% at 5 years, and 28.1% at 10 years. The cumulated rate of treatment failure (CRTF, local recurrence or metastasis) was 19.3%, 34.7% and 59.2% at 3, 5 and 10 years, respectively. Two patient groups with known Gleason and initial PSA were selected, i.e. those with well localized tumors (WLT, Tlb-c or T2a, n = 120) and those with locally extended tumors (LET, T2b or T3a-b, n=227). The two groups characteristics were the following: Gleason VII-X, 18% vs 43%; initial PSA > 20 ng/ml, 38% vs. 58%. In these two groups, the CRLR, CRTF and OS rate were respectively: In the WLT group at 3 years 1.9% 10.1% 98.2% at 5 years 3.3% 17.1% 93.1% In the LET group at 3 years 5.7% 25.1% 90.1% at 5 years 13.9% 43.2% 78.6% Complications: according to the Soma-Lent system, the 5-year cumulative rate of grade ll-lll urinary, digestive and sexual complications was of 11.1%, 5.1% and 30.2 %, respectively. Of 148 sexually active patients, 110 (74%) had sexual activity 5 years later. Conclusion: In this high risk population (84% with T2-T3, initial median PSA > 20 ng/ml, 34% with Gleason > VI) the use of combined brachytherapy and EBR provides fairly good results with acceptable complication rate. 73 H D R BRACHYTHERAPY TREATMENT FOR LOCAL RECURRENCE AFTER RADICAL PROSTATECTOMY" FIRST RESULTS AND EXPERIENCES
P. Niehoff, T. koch*, R. Galalae. O. Thiemann*, N. Narnberg*, P. Kohr. G. Kovacs Interdisciplinary Center for Brachytherapy and *Clinic for Urology, Christian-Albrechts-University Hospital, Kiel, Germany Introduction: Increase of prostate specific antigen (PSA) after radical prostatectomy indicates a systemic progress or a local recurrence. In the
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43
1-125 Pd-103
TRUS Vol. 35.5 32.5
CT Vol. 45.2 41.0
Pre-Plan Technique DI00 D90 Gy Gy 102.0 137.0 85.0 106.0
V100 87% 85%
V150 55% 52%
TRUS Vol. 35.6 32.5
CT Vol. 44.8 41.3
Real Time Technique DI00 D90 Gy Gy 127.0 150.0 106.0 120.0
V100
V150
95% 96%
38% 32%
Data are shown for an average size prostate gland volume of 35cc. % in volume are with reference to CT volume. TRUS -> Trans Rectal Ultra Sound Conclusion: It has been found that although the pre-scans can usually be matched very closely to the scans obtained at the time of implant, a mismatch can result in large dose inhomogeneities (D100) especially for the lower energy isotope Pd-103, as dose gradients are large in value. For the real time implantation technique, the pre-scans derived preliminary dosimetry of the implant can be valuable in ordering the isotope and in seed placement adjustment at the time of implant. Most importantly, we have found that the high dose region (V 150) in the real time implant technique is significantly lower than the high dose region derived from pre-plan scans. 72 L o w DOSE ( L D R ) OR HIGH DOSE ( H D R ) RATE IR-192 CONFORMAL BRACHYTHERAPY WITH TEMPORARY TRANSPERINEAL IMPLANTATION IN COMBINATION WITH EXTERNAL BEAM RADIATION ( E B R ) FOR NON-METASTATIC PROSTATE ADENOCARCINOMA: THE CENTRE FRAN(~OIS BACLESSE EXPERIENCE IN 531 CASES TREATED BETWEEN JULY 1 9 8 7 AND DECEMBER 1997.
D. Brune, J.F. Lesaunier, D. Benabid, M. Henry-Amar, Centre Franqois Baclesse, 14076 Caen Cedex, France Technique: We use transperineal implantation with 4 to 6 20 cm divergent needles, held in place by template. Planned and control dosimetries are carried out using orthogonal X-rays and CT scan, with dummy sources in urethral, bladder and rectal probes. Implantation is made with general anesthesia, the patient being in dorsal decubitus on a radiological table to which an implanter is attached. The positioning of the needles is carried out under scopic X-ray and ultrasound control. Treatment protocol: The first protocol involved 15 Gy LDR brachytherapy and 45 Gy pelvic EBR. The second protocol combined 15 Gy LDR brachytherapy and 45 Gy prostate EBR in well localized tumors (Tlb-c, T2a), tumors of small volume (<4cm in diameter), or for vulnerable patients (ECOG-2). When the implantation was geometrically correct, the 15 Gy LDR brachytherapy was replaced by 2 x 4.7 Gy HDR brachytherapy delivering a maximal dose of 2 x 4.7 Gy to the anterior rectal mucosa and 2 x 9 Gy to the urethral mucosa (mean dose). Finally, for patients with only one risk factor (stage, Gleason, initial PSA, NO or N-) the brachytherapy dose was 25 Gy LDR, equivalent to 4 x 3.9 Gy HDR combined with 35 Gy EBR limited to the prostate. Study population: The characteristics of the 531 patients were: mean age 69 years (45 to 85 years), 30% ECOG-2, 78% with previous cardiovascular and/or metabolic history and 50% with history of abdominal surgery. 462 patients had histologically known Gleason with 66% Gleason II to VI, 25% Gleason VII, 9% Gleason VIII to X. Initial PSA (hybritec technique, normal level < 4 ng/ml) was available for 526 patients. The median PSA was 21 ng/ml (0 to 500). 22% of patients had PSA 0 to 10 nffml; 26% had PSA 11 to 20 ng/ml; and 51% had PSA > 20 ng/ml. There were 15% patients with TI, 51% with T2, 33% with T3, while T4 was observed in only 2 cases and Tx in 3 cases. 21% of patients were Nx, 74% were NO and 5% NI-N2. Results: The overall survival (OS) rate was 91% at 3 years, 82.4% at 5 years, and 44.1% at 10 years. Of the 421 patients treated with exclusive radio-brachytherapy, 77% normalised their PSA (55% with PSA < 1 ng/ml). In patients treated with 25 Gy LDR or 4 x 3.9 Gy HDR and 35 Gy prostate EBR, PSA normalization was obtained in 88% in an average time-scale of 172 days. In patients treated with 15 Gy LDR or 2 x 4.7 Gy HDR and 45 Gy prostate EBR, PSA normalization was obtained in 87% and in 205 days. In patients treated with 15 Gy LDR or 2 x 4.7 Gy HDR and 45 Gy pelvic EBR, PSA normalization was obtained in 73 % of the cases and in 234 days. PSA normalization < I ng/ml was obtained in 66%, 64% and 50% in the three groups, respectively. In the overall population, the cumulative rate of clinical or histologic local recurrence (CRLR) was 4.2% at 3 years, 10.5% at 5 years, and 28.1% at 10 years. The cumulated rate of treatment failure (CRTF, local recurrence or metastasis) was 19.3%, 34.7% and 59.2% at 3, 5 and 10 years, respectively. Two patient groups with known Gleason and initial PSA were selected, i.e. those with well localized tumors (WLT, Tlb-c or T2a, n = 120) and those with locally extended tumors (LET, T2b or T3a-b, n=227). The two groups characteristics were the following: Gleason VII-X, 18% vs 43%; initial PSA > 20 ng/ml, 38% vs. 58%. In these two groups, the CRLR, CRTF and OS rate were respectively: In the WLT group at 3 years 1.9% 10.1% 98.2% at 5 years 3.3% 17.1% 93.1% In the LET group at 3 years 5.7% 25.1% 90.1% at 5 years 13.9% 43.2% 78.6% Complications: according to the Soma-Lent system, the 5-year cumulative rate of grade ll-lll urinary, digestive and sexual complications was of 11.1%, 5.1% and 30.2 %, respectively. Of 148 sexually active patients, 110 (74%) had sexual activity 5 years later. Conclusion: In this high risk population (84% with T2-T3, initial median PSA > 20 ng/ml, 34% with Gleason > VI) the use of combined brachytherapy and EBR provides fairly good results with acceptable complication rate. 73 H D R BRACHYTHERAPY TREATMENT FOR LOCAL RECURRENCE AFTER RADICAL PROSTATECTOMY" FIRST RESULTS AND EXPERIENCES
P. Niehoff, T. koch*, R. Galalae. O. Thiemann*, N. Narnberg*, P. Kohr. G. Kovacs Interdisciplinary Center for Brachytherapy and *Clinic for Urology, Christian-Albrechts-University Hospital, Kiel, Germany Introduction: Increase of prostate specific antigen (PSA) after radical prostatectomy indicates a systemic progress or a local recurrence. In the
44