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Objective: To explore relationships between dose to periprostatic anatomic structures and erectile dysfunction (ED) outcomes in an institutional cohort treated with prostate brachytherapy., Methods: The Sexual Health Inventory for Men (SHIM) instrument was administered for stage cT1-T2 prostate cancer patients treated with Pd-103 brachytherapy over a 10-year interval. Dose volume histograms for regional organs at risk and periprostatic regions were calculated with and without expansions to account for contouring uncertainty. Regression tree analysis clustered patients into ED risk groups., Results: We identified 115 men treated with definitive prostate brachytherapy who had 2 years of complete follow-up. On univariate analysis, the subapical region (SAR) caudal to prostate was the only defined region with dose volume histograms parameters significant for potency outcomes. Regression tree analysis separated patients into low ED risk (mean 2-year SHIM 20.03), medium ED risk (15.02), and high ED risk (5.54) groups. Among patients with good baseline function (SHIM ≥ 17), a dose ≥72.75 Gy to 20% of the SAR with 1 cm expansion was most predictive for 2-year potency outcome. On multivariate analysis, regression tree risk group remained significant for predicting potency outcomes even after adjustment for baseline SHIM and age., Conclusion: Dose to the SAR immediately caudal to prostate was predictive for potency outcomes in patients with good baseline function. Minimization of dose to this region may improve potency outcomes following prostate brachytherapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To assess the performance of a system of intraoperative dosimetry and obtain estimates of dosimetry outcomes achieved when utilizing the system in a Phase II clinical trial., Methods and Materials: Forty-five patients undergoing permanent Pd-103 seed implantation for prostate cancer were prospectively enrolled. Seed implantation was performed and dose was tracked intraoperatively using intraoperative registered ultrasound and fluoroscopy (iRUF). Three-dimensional seed locations were computed from X-rays and registered to ultrasound for intraoperative dosimetry, followed by adaptive plan modification to achieve prostate V100 ≥95% and ≥95% D90. Time required for iRUF was recorded. Postoperative CT/MRI scans were performed 1 day after the implantation and used as reference for dosimetric analysis. Dosimetric parameters for the prostate and urethra were compared between standard ultrasound-based dosimetry (USD), iRUF, and postoperative CT/MRI., Results: Mean total time for iRUF was <30 min. A mean of four seeds (0-12) were added per implant to correct cold spots discovered by iRUF. Day 1 CT/MRI prostate V100 was ≥95% for 44/45 patients; 1 patient had Day 1 V100 93%. No patient had rectal V100 exceeding 1 cc. Compared to CT/MRI, iRUF dosimetry had significantly smaller mean differences and higher correlations for all prostate and urethral dosimetric parameters examined than USD. Both USD and iRUF tended to overestimate dose, but with less bias in iRUF than USD., Conclusions: Intraoperative dosimetry utilizing iRUF was associated with acceptable increase in procedure time and enabled very high rates of achieving excellent prostate dose coverage. iRUF intraoperative dosimetry approximated postoperative CT/MRI dosimetry to a greater degree than USD for the prostate and urethra., (Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

For the treatment of choroidal melanoma, palladium-103 (Pd) and ruthenium-106 (Ru) plaque brachytherapy shows reduced toxicity compared with the historical standard iodine-125. No report has directly compared the clinical outcomes between Pd and Ru, and the reasons for the selection of one over the other remain purely theoretical. Patients with choroidal melanoma with apical tumor height up to 5 mm were included. Patients from Emory University were treated with Pd between 1993 and 2012. Patients from Cleveland Clinic were treated with Ru between 2005 and 2010. Medical records were retrospectively reviewed. We compared post-treatment visual acuity (VA), toxicity, and oncologic outcomes. Pd patients (n=124) and Ru patients (n=42) had a median follow-up of 4.2 and 5.0 years, respectively. Radiation retinopathy-free survival was similar for both radioisotopes, but Ru had lower grades of retinopathy (P=0.006). Pd was associated with worse VA preservation (≥20/40) by year 3 (odds ratio: 3.8; 95% confidence interval: 1.01-14.31, P=0.048). Pd was associated with higher distant metastases-free survival (DMFS) in multivariate analysis (hazard ratio: 0.10; 95% confidence interval: 0.02-0.38; P<0.001). Ru had lower grades of radiation retinopathy and improved long-term VA preservation, but also inferior DMFS, compared with Pd. Because of the inherent limitations of a retrospective analysis, the significance of the inferior DMFS for Ru remains unclear, although the suggestion of a slight inferiority in terms of DMFS for Ru is consistent with the other limited literature. On the basis of this study, we believe that both radioisotopes remain appropriate for the treatment of small choroidal melanomas up to 5 mm in apical height.

Purpose: Examine modifications to seed placement and target margins necessary to accomplish focal brachytherapy with (103)Pd., Methods: Our proposed focal brachytherapy program will be primarily favorable intermediate-risk patients with a unilateral index lesion confirmed by transperineal template-guided mapping biopsies (TTMB). The dimensions and location of the TTMB core with the index lesion were placed within the 3-D ultrasound planning volume. Implants were planned for the prostate and the focal targets with generous margins. Planning goals were to cover the target with the 125Gy prescription dose and keep D90 (minimum dose covering 90% of the target) between 125% and 150% of the prescription while minimizing urethral and rectal hot spots. Radiobiological parameters - biologically effective dose (BED) and tumor control probability - were integrated over fractional sub-volumes and focal plans compared to whole gland brachytherapy., Results: A typical 30.1cm(3) prostate was expanded to create a 50.6cm(3) planning target volume (PTV) and needed 22 needles containing 86 (103)Pd seeds of strength 3.20U to deliver the prescribed dose. The hemi-prostate required 39 seeds in 12 needles, and the focal core expanded to a target volume of 11.6cm(3) required 29 seeds in 8 needles. All cancerous PTVs and sub volumes had a tumoricidal BED while organs at risk (OAR) met the dose constraints minimizing morbidity., Conclusions: For this single case study, both hemi-prostate and focal brachytherapy using (103)Pd seeds met the same target dosimetric goals and OAR constraints as whole prostate plans but with the expected reduction in number of seeds and needles., (Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: In clinical practice, specific air kerma strength (SK) value is used in treatment planning system (TPS) permanent brachytherapy implant calculations with (125)I and (103)Pd sources; in fact, commercial TPS provide only one SK input value for all implanted sources and the certified shipment average is typically used. However, the value for SK is dispersed: this dispersion is not only due to the manufacturing process and variation between different source batches but also due to the classification of sources into different classes according to their SK values. The purpose of this work is to examine the impact of SK dispersion on typical implant parameters that are used to evaluate the dose volume histogram (DVH) for both planning target volume (PTV) and organs at risk (OARs)., Methods: The authors have developed a new algorithm to compute dose distributions with different SK values for each source. Three different prostate volumes (20, 30, and 40 cm(3)) were considered and two typical commercial sources of different radionuclides were used. Using a conventional TPS, clinically accepted calculations were made for (125)I sources; for the palladium, typical implants were simulated. To assess the many different possible SK values for each source belonging to a class, the authors assigned an SK value to each source in a randomized process 1000 times for each source and volume. All the dose distributions generated for each set of simulations were assessed through the DVH distributions comparing with dose distributions obtained using a uniform SK value for all the implanted sources. The authors analyzed several dose coverage (V100 and D90) and overdosage parameters for prostate and PTV and also the limiting and overdosage parameters for OARs, urethra and rectum., Results: The parameters analyzed followed a Gaussian distribution for the entire set of computed dosimetries. PTV and prostate V100 and D90 variations ranged between 0.2% and 1.78% for both sources. Variations for the overdosage parameters V150 and V200 compared to dose coverage parameters were observed and, in general, variations were larger for parameters related to (125)I sources than (103)Pd sources. For OAR dosimetry, variations with respect to the reference D0.1cm(3) were observed for rectum values, ranging from 2% to 3%, compared with urethra values, which ranged from 1% to 2%., Conclusions: Dose coverage for prostate and PTV was practically unaffected by SK dispersion, as was the maximum dose deposited in the urethra due to the implant technique geometry. However, the authors observed larger variations for the PTV V150, rectum V100, and rectum D0.1cm(3) values. The variations in rectum parameters were caused by the specific location of sources with SK value that differed from the average in the vicinity. Finally, on comparing the two sources, variations were larger for (125)I than for (103)Pd. This is because for (103)Pd, a greater number of sources were used to obtain a valid dose distribution than for (125)I, resulting in a lower variation for each SK value for each source (because the variations become averaged out statistically speaking).

Purpose: Postoperative dosimetry is integral to quality assurance for prostate brachytherapy. Images on Day 0 are typically obtained with a contrast-filled urinary catheter in place for urethral dose calculations. However, expansion of the urethra and perhaps the prostate by the catheter may affect target coverage. We assessed the effect of urinary catheterization on target dosimetry after implantation with palladium-103 ((103)Pd) or iodine-125 ((125)I) seeds., Methods and Materials: Patients were 29 consecutive men with postimplant dosimetry calculated with and without a urinary catheter after brachytherapy seed implantation; 19 patients received (103)Pd seeds and 10 patients received (125)I seeds. In each case, 14-French caude tip urinary catheters were placed before implantation, and axial CT slices of the pelvis were obtained before and after catheter removal for postimplant dosimetry. Dosimetric parameters were measured and compared with paired Student's t tests. Trends were assessed by linear regression with the Pearson correlation coefficient., Results: Removal of the urinary catheter significantly improved V(100) and D(90) for (103)Pd implants (mean±standard deviation (SD), 2.7%±4.2%; range, -0.4% to 15%; p=0.011 and mean±SD, 4.0%±3.4%; range, -0.1% to 13.8%; p<0.01, respectively). For (125)I implants, catheter removal improved D(90) (mean±SD, 1.5%±1.8%; range, -1.3% to 4.2%; p=0.027). For the (103)Pd group, the magnitude of change in V(100) correlated with prostate size (R(2)=0.16) and source number (R(2)=0.15)., Conclusions: Urinary catheterization can artificially reduce target coverage after prostate implant brachytherapy. The patients undergoing (103)Pd implantation with smaller (<30cm(3)) prostates and fewer (<90) sources are particularly susceptible to reduced D(90) and V(100) when a urinary catheter is present., (Copyright © 2011 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Brachytherapy dose distributions are calculated for 15 mm ROPES eye plaque loaded with model Theragenics200 and IR06-(103)Pd seeds. The effects of stainless steel backing and Acrylic insert on dose distribution along the central axis of the eye plaque and at critical ocular structure are investigated. Monte Carlo simulation was carried out with the Version 5 of the MCNP. The dose at critical ocular structure by considering the eye composition was calculated. Results are compared with the calculated data for COMS eye plaque loaded with Theragenics200 palladium-103 seeds and model 6711 iodine-125 seed. The air kerma strength of the IR06-(103)Pd seed to deliver 85 Gy in apex of tumor in water medium was calculated to be 4.10 U/seed. Along the central axis of stainless steel plaque loaded with new (103)Pd seeds in Acrylic insert, the dose reduction relative to water is 6.9% at 5 mm (apex). Removal of the Acrylic insert from the plaque (replacing with water) did not make significantly difference in dose reduction results (~0.2%). The presence of the stainless steel backing results in dose enhancement near the plaque relative to water. Doses at points of interest are higher for ROPES eye plaque when compared to COMS eye plaque. The dosimetric parameters calculated in this work for the new palladium seed, showed that in dosimetry point of view, the IR06-(103)Pd seed is suitable for use in brachytherapy. The effect of Acrylic insert on dose distribution is negligible and the main effect on dose reduction is due to the presence of stainless steel plaque backing.

Over the past two decades, brachytherapy has played an ever expanding role in the definitive radiotherapy of prostate cancer. Brachytherapy surpasses external beam radiotherapy in its ability to deliver intense intraprostatic dose escalation. Although initially low dose rate permanent seed brachytherapy was favored for favorable risk prostate cancers, and high dose rate temporary brachytherapy for intermediate and advanced disease, both types of brachytherapy now have a place across all the risk groups of localized prostate cancer. This article will review indications and patient selection, planning and technical aspects, toxicity and efficacy for both low and high dose rate prostate brachytherapy., (Copyright © 2011. Published by Elsevier SAS.)

Purpose: The radiobiology of prostate cancer appears to favor large fractions. Accelerated hypofractionation treatments may therefore be used to improve the therapeutic ratio, particularly when the doses to rectum and bladder are kept below the prostate dose. The 5-year experience at William Beaumont Hospital (WBH) and the California Endocurietherapy Center (CET) with accelerated-hypofractionated high-dose-rate (HDR) monotherapy in favorable prostate cancer is presented., Materials and Methods: Between 1993 and 2004, 454 patients were treated with brachytherapy of which 248 treated with HDR and 206 patients treated with low-dose-rate Palladium (LDR-Pd¹⁰³). The WBH-HDR dose was 38 Gy, in 4 fractions, twice a day. The CET-HDR dose was 42 Gy in 6 fractions in 2 separate implants 1 week apart. The WBH-LDR dose was 120 Gy., Results: Median follow-up was 4.8 years. The 5-year Phoenix biochemical control (BC) was 89%, 91%, and 88% for WBH-LDR, WBH- HDR, and CET-HDR, respectively. The majority of complications were grade 1. HDR was associated with less acute grade 1 to 3 dysuria 60% versus 39%, (P < 0.001), urinary frequency/urgency 90% to58% (P < 0.001), and rectal pain 17% to 6.5% (P < 0.001). Long-term urinary frequency/urgency 54% versus 43%, (P = 0.03) and dysuria 22% versus 15% were less with HDR. The 5-year actuarial impotence rate was 30% for LDR and 20% for HDR (P = 0.23)., Conclusions: Although the same 5-year BC rates were achieved with HDR (248 patients) and LDR (206 patients) monotherapy, HDR brachytherapy was associated with less acute and chronic genitourinary and gastrointestinal toxicities. As another accepted standard of care, accelerated hypofractionated HDR monotherapy is target specific and efficient radiobiologically than EBRT which has many smaller doses per fraction. It could be considered today as the best option in accelerated hypofractionated prostate cancer treatment.

As a well-established single-modality approach for early-stage prostate cancer, transperineal interstitial permanent prostate brachytherapy (TIPPB) has gained increasing popularity due to its favorable clinical results. Currently, three isotopes, namely Cs-131, I-125, and Pd-103, are commercially available for TIPPB. This is the first study to systematically explore the dosimetric difference of these three isotopes for TIPPB. In total, 25 patients with T1-T2c prostate cancer previously implanted with I-125 seeds were randomly selected and replanned with Cs-131, I-125, and Pd-103 seeds to the prescription doses of 115, 145, and 125 Gy, respectively. The planning goals attempted were prostate V(p)100 approximately 95%, D(p)90 >or= 100%, and prostatic urethra D(u)10

Purpose: This study analyzed rectal dosimetry outcomes of Pro-Qura proctored implants to assess the achievability of proposed rectal dose constraints in the setting of standardized pre- and postimplant dosimetry in community-based brachytherapy programs., Methods and Materials: From August 2005 to July 2007, 713 postimplant CT scans were evaluated from 26 brachytherapists actively participating in Pro-Qura. Postimplant dosimetry was performed in a standardized fashion. The entirety of the rectal wall was contoured and evaluated for dose. Rectal dose was defined in terms of the volume of the rectum receiving 100% of the prescription dose (R(100)). Criteria for implant adequacy for both (103)Pd and (125)I included a prostate the percentage of the prostate volume covered by the prescription dose (V(100))>80%, a prostate the maximum dose covering 90% of the prostate volume (D(90)) of 90-140%, and an R(100)<1.0cm(3) for early (Day 0-7) dosimetry and <1.3cm(3) for late (Day 20-45) dosimetry., Results: Mean prostatic volume was 35.1cm(3). The mean time from implant to CT scan was 29.9 days (range, 0-45 days). The respective mean overall prostate V(100) and D(90) were 89% and 101%, respectively, and remained consistent for sequence groups 1 through 6. Overall, the mean R(100) was 0.97+/-1.04cm(3). The R(100) was 1.15cm(3) for sequence Group 1 and with each subsequent sequence group decreased with a nadir of 0.83cm(3) in sequence Group 6 (p=0.22). Rectal dosimetry was deemed inadequate in 39% of Group 1 implants but only 22% in Group 6 (p=0.016). The reduced rectal doses did not impact prostate gland coverage., Conclusions: Using standardized dosimetry, R(100) improved with increasing brachytherapist's experience, reaching a plateau after approximately 20 patients.

Background: Mucosal melanoma of the female genital tract that recurs locally after definitive surgery presents difficult challenges for salvage therapy., Methods and Materials: A 71-year-old female was diagnosed with a 4.5-cm x 4.1-cm x 2.8-cm vaginal recurrence of genital tract mucosal melanoma after definitive vulvectomy, distal vaginectomy, and distal urethrectomy. She refused surgery and underwent combination external beam radiation therapy (46 Gy) and an ultrasound-guided palladium-103 brachytherapy implant (100 Gy)., Results: The patient experienced complete resolution of the gross tumor and was asymptomatic with a sustained response for over a year before developing metastatic disease., Conclusions: Mucosal melanoma of the female genital tract is an aggressive and often fatal disease. Radical surgical excision is an option for some patients but may require pelvic exenteration and is rarely curative. In selected cases, high-dose conformal radiation therapy delivered by a combination of external beam radiation therapy and interstitial brachytherapy may be an excellent alternative, achieving local control without loss of organ function.

Prostate brachytherapy is a radiotherapy technique for early stage prostate cancer that uses imaging guidance to place radioactive sources directly into the prostate gland. Transrectal ultrasound is used to facilitate a template-guided transperineal approach to the prostate and permits a highly conformal method of prostate radiotherapy with doses far higher than can be achieved with other radiation techniques. Maturing data has validated this technique as an acceptable treatment option with favourable and durable biochemical outcomes. The radiologist has a major role to play in the process: patient selection, guiding source delivery and follow-up after treatment all require close collaboration with colleagues in Radiation Oncology and Medical Physics. This review emphasises the specific contribution of imaging in the context of currently reported outcomes data.

Objectives: To report a single-institution experience and analysis of the role of supplemental external beam radiotherapy (EBRT) with brachytherapy. EBRT is often used in addition to low-dose-rate brachytherapy in the treatment of prostate cancer, particularly for disease with adverse features., Methods: A cohort of 189 consecutive patients, who had undergone low-dose-rate brachytherapy at our institution and who had demographic, disease, and treatment information and a minimum of 2 years of follow-up available, constituted the study group. This cohort was divided into two major groups according to the use of supplemental EBRT. Using two successive prostate-specific antigen rises greater than 1 ng/mL as the definition of failure, biochemical failure-free survival curves were constructed for the EBRT and no-EBRT groups and compared using the log-rank test. Additionally, a multivariate analysis of all major disease and treatment factors was performed using the Cox proportional hazards model., Results: Despite the greater proportion of adverse disease factors in the EBRT group, the 5-year biochemical failure-free survival rate in the EBRT versus no-EBRT groups was 80% versus 59%, respectively (P < 0.01). On multivariate analysis, the only factor reaching significance in predicting biochemical control was the use of EBRT (P = 0.043)., Conclusions: In our study, the addition of EBRT conferred a significant biochemical control advantage when added to low-dose-rate brachytherapy. Because our study was not designed to permit detailed subset analyses, more work is needed to determine the precise brachytherapy population that will benefit from this use of supplemental EBRT.

Purpose: To conduct a multi-institutional comparison of prostate brachytherapy pre-implant dosimetry of Pd-103 and I-125., Methods and Materials: Eight experienced brachytherapists submitted Pd-103 and I-125 monotherapeutic and boost pre-implant dosimetry plans for central review. All 32 plans were calculated using the same transrectal ultrasound volumetric study. Seeds of any strength were acceptable, but were restricted to Theraseed Model 200 (Theragenics Inc., Buford, GA) and Oncura Oncoseed Model 6711 (Oncura, Plymouth Meeting, PA). The dosimetric analysis included evaluation of target volume, target to prostate ratio, target length, number of needles, seed activity, number of seeds, total activity, total activity divided by treatment planning volume, the use of extracapsular seeds, and average treatment margins (defined as the perpendicular distance between the prostate capsule and the 100% isodose line). Prostate coverage was defined in terms of V(100)/V(150)/V(200)/V(300) and D(100)/D(90)/D(50), whereas urethral dosimetry consisted of UV(100)/UV(150)/UV(200) and UD(90)/UD(50)., Results: The mean planning target volume to prostate volume ratio varied dramatically (mean 1.29, range 0.99-1.76) with the target length ranging from 3.5 to 4.5 cm. Although the prostate V(100) was >95% in all cases, the V(150) ranged from 29.9% to 92.1% and the V(200) from 6.72% to 52.5%. The urethral V(100) was 100% in all cases with six of the eight brachytherapists limiting the UV(150) to <3%. However, the median urethral dose varied by up to 50%. Treatment margins also varied significantly (average 3.98 mm, range 0.32-7.68 mm). All brachytherapists used extracapsular seeds with five implanting >25% of the seeds in extracapsular locations (range 6.4-58.2%). In addition, significant variability existed in the number of needles, number of seeds, and seed strength., Conclusions: This study highlights the substantial variability that exists regarding target volume, seed strength, dose homogeneity, treatment margins, and extracapsular seed placement, although prostate brachytherapy prescription doses are uniform. The standardization of pre-implant dosimetry is essential for meaningful multi-institutional comparisons of biochemical outcomes and morbidity.

The purpose of this study was to present a theoretical analysis of how the presence of bone in interstitial brachytherapy affects dose rate distributions. This study was carried out using a Monte Carlo simulation of the dose distribution in homogeneous medium for 3 commonly used brachytherapy seeds. The 3 seeds investigated in this study are iridium-192 (192Ir) iodine-125 (125I), and palladium-103 (103Pd). The computer code was validated by comparing the specific dose rate (Lambda), the radial dose function g(r), and anisotropy function F(r,theta;) for all 3 seeds with the AAPM TG-43 dosimetry formalism and current literature. The 192Ir seed resulted in a dose rate of 1.115 +/- 0.001 cGy-hr(-1)-U(-1), the 125I seed resulted in a dose rate of 0.965 +/- 0.006 cGy/h(-1)/U(-1), and the 103Pd seed resulted in a dose rate of 0.671 +/- 0.002 cGy/h(-1)/U(-1). The results for all 3 seeds are in good agreement with the AAPM TG-43 and current literature. The validated computer code was then applied to a simple inhomogeneous model to determine the effect bone has on dose distribution from an interstitial implant. The inhomogeneous model showed a decrease in dose rate of 2% for the 192Ir, an increase in dose rate of 84% for 125I, and an increase in dose rate of 83% for the 103Pd at the surface of the bone nearest to the source.

Purpose: The purpose of this study was to evaluate the clinical outcomes and compare complication rates for patients with prostate cancer treated with iodine 125 ((125)I) and palladium 103 ((103)Pd) prostate brachytherapy at a single institution., Patients and Methods: Between 1992 and 2002, 272 patients with prostate cancer were treated with ultrasound-guided transperineal implantation incorporating (125)I (107 patients) or (103)Pd (165 patients). Three months of hormonal therapy was incorporated into the treatment program in 33% of the patients in both groups. Nineteen percent of those treated with (125)I were treated with a combination of implantation plus external-beam radiation therapy. Only 6% of the group receiving (103)Pd implants were treated with such a combination. For those treated with (125)I implantation alone, the minimum tumor dose was 145 Gy. The minimum tumor dose for those treated with (103)Pd alone was 125 Gy. Those treated with a combination of external-beam radiation therapy and (125)I received 45 Gy via 1.8-Gy fractions followed by implantation with a minimum tumor dose of 110 Gy. For those treated with external-beam radiation therapy and (103)Pd, the doses were 45 Gy via 1.8-Gy fractions followed by implantation with minimum tumor dose of 98 Gy. Outcomes were evaluated based on radionuclide used, T stage, Gleason score, prostate-specific antigen, and prognostic group. Complications were also evaluated for each radionuclide. The mean follow-up for the (125)I group was 55 months, and the range was 12-108 months. The mean follow-up for the (103)Pd group was 44 months, and the range was 12-72 months., Results: The 5-year biochemical disease-free survival rates for those in the favorable group (clinical stage T1c or T2, prostate-specific antigen level <10, Gleason score <7) were 92% for the (125)I group and 92% for the patients treated with (103)Pd. The 5-year disease-free survival rates for those in the intermediate and poor prognostic groups, which were combined, was 72% and 74%, respectively, for (125)I and (103)Pd. There was no statistically significant difference for either modality for any treatment group tested. In those treated with implantation alone, patients treated with (125)I had higher complication rates than those treated with (103)Pd (15% vs 4%). (125)I-treated patients had a grade 2 complication rate of 8% and a grade 3-4 complication rate of 7%, compared with 3% and 1%, respectively, for the (103)Pd-treated patients., Conclusion: Despite the different management recommendations that evolved during the study period, the clinical outcome for patients treated with either radionuclide were similar with respect to biochemical disease-free survival. Although specific dosimetric comparisons are not valid given differences in imaging over the study course, the complication rate appears to be somewhat higher for (125)I, which is consistent with a radiobiologic model.

Purpose: We evaluated the potential for differing acute and chronic toxicities between 2 monotherapy methods of image guided conformal brachytherapy, high dose rate (HDR) brachytherapy alone and low dose rate (LDR) permanent palladium seeds., Materials and Methods: A total of 149 patients with biopsy proven, early stage prostate cancer were consecutively treated with interstitial brachytherapy as the sole method of treatment at William Beaumont Hospital between 1999 and 2001. Of the 149, 65 patients were treated with HDR using 192 iridium (192Ir), and 84 patients were treated with LDR using 103 palladium (103Pd). The majority of patients had clinical stage II, T1c or T2a disease, pretreatment prostate specific antigen less than 10 ng/ml and Gleason score 6 or less. Neoadjuvant hormones were used in 36% of patients for gland volume optimization. All treatments were performed transperineally with trans-rectal ultrasound guidance and fluoroscopy for verification of needle/seed positions. The HDR dose was 38 Gy delivered in 4 fractions, 2 times daily during 2 days. The LDR dose was 120 Gy. Acute and chronic toxicities were scored according to the Common Toxicity Criteria scale, version 2.0., Results: Median followup for all patients was 35 months. The 2 treatment groups were well-balanced with respect to age, clinical stage, prostate specific antigen, Gleason score, use of neoadjuvant hormones, pretreatment genitourinary symptoms, implanted gland volume and length of followup. Biochemical control (American Society for Therapeutic Radiology and Oncology definition) was 97% and 98% for LDR and HDR, respectively. HDR brachytherapy alone was associated with decreased acute rates of grade 1 to 3 dysuria (67% versus 36%, p <0.001), urinary frequency/urgency (92% versus 54%, p <0.001) and rectal pain (20% versus 6%, p = 0.017). These differences remained significant when patients who received prior hormonal therapy were excluded from analysis. Selected chronic toxicities were also decreased with HDR, including long-term urinary frequency and urgency, 32% (HDR) vs 56% (103Pd), p = 0.004. There were no differences in the rates of chronic dysuria, urinary incontinence, retention or hematuria. Urethral stricture rates were 8% in the HDR alone group vs 3% for 103 Pd (p = 0.177). The 3-year actuarial impotence rate was 45% for the LDR group and only 16% for HDR. The majority of complications were grade 1. No grade 4 toxicities were encountered in either group. HDR decreased treatment cost by 19%., Conclusions: While HDR (192 iridium) and LDR (103Pd) monotherapy maintained the same biochemical control, the use of HDR brachytherapy as monotherapy was associated with decreased rates of acute urinary frequency, urgency, dysuria and rectal pain compared to LDR. Chronic urinary frequency, urgency and grade 2 rectal toxicities were also decreased with HDR. A dramatic decrease (66%) was noted in the rate of sexual impotency with HDR. In addition, patients treated with HDR did not remain radioactive after treatment. There was a decrease in cost from not purchasing seeds per patient. HDR monotherapy as prostate cancer treatment resulted in the same biochemical control with much lower toxicity. It is an accepted, convenient, cost-effective method of prostate brachytherapy for patients with favorable risk prostate cancer.

Objectives: To analyze the incidence, time-course, and potential predisposing factors for what was clinically diagnosed as postimplant epididymitis., Methods: Of 517 patients randomized and treated on two treatment protocols, with a planned total accrual of 1200, 5 patients were identified who developed clinically diagnosed epididymitis after iodine-125 or pallidium-103 prostate brachytherapy. Implants were performed by standard techniques, using a modified peripheral loading pattern. Perioperative antibiotics (cefazolin and ciprofloxacin) were given to 258 patients, according to physician preference. Treatment-related morbidity was monitored by mailed questionnaires, using standard American Urological Association (AUA) and Radiation Therapy Oncology Group criteria at 1, 3, 6, 12, and 24 months. Patients who did not respond to the mailed questionnaires were interviewed by telephone. Although the patients were not queried specifically regarding epididymitis, its occurrence was noted when discovered in the course of follow-up examinations., Results: Postimplant epididymitis occurred in 5 (1%) of 517 consecutive brachytherapy patients. None of the 5 patients had had a prior history of orchitis, epididymitis, vasectomy, or preimplant catheterization. The symptoms of epididymitis first appeared at 4, 7, 10, 150, and 300 days after implantation. Patients with epididymitis had prostate volumes, preimplant AUA scores, and ages typical of other implant patients. No association was apparent between postimplant epididymitis and the degree of implant-related prostate swelling or the number of seeds implanted. Only the preimplant AUA score predicted for epididymitis, but 2 of the 5 patients had low scores. Only 1 (0.4%) of the 258 patients who received perioperative antibiotics developed epididymitis, and 4 (1.5%) of the 259 patients with prophylactic antibiotics developed epididymitis., Conclusions: Epididymitis is an uncommon postimplant complication occurring in 1% of a large patient cohort. That epididymitis patients had greater preimplant AUA scores is consistent with a retrograde infection route, at least in some cases.

Purpose: To compare the results of intraoperative dosimetry with those of CT-based postimplant dosimetry in patients undergoing prostate seed implantation., Methods and Materials: Seventy-seven patients with T1-T3 prostate cancer received an ultrasound-guided permanent seed implant (36 received (125)I, 7 (103)Pd, and 34 a partial (103)Pd implant plus external beam radiation therapy). The implantation was augmented with an intraoperative dosimetric planning system. After the peripheral needles were placed, 5-mm axial images were acquired into the treatment planning system. Soft tissue structures (prostate, urethra, and rectum) were contoured, and exact needle positions were registered. Seeds were placed with an applicator, and their positions were entered into the planning system. The dose distributions for the implant were calculated after interior needle and seed placement. Postimplant dosimetry was performed 1 month later on the basis of CT imaging. Prostate and urethral doses were compared, by using paired t tests, for the real-time dosimetry in the operating room (OR) and the postimplant dosimetry., Results: The mean preimplant prostate volume was 39.8 cm(3), the postneedle planning volume was 41.5 cm(3) (p<0.001), and the 1-month CT volume was 43.6 cm(3) (p<0.001). The mean difference between the OR dose received by 90% of the prostate (D(90)) and the CT D(90) was 3.4% (95% confidence interval, 2.5-6.6%; p=0.034). The mean dose to 30% of the urethra was 120% of prescription in the OR and 138% on CT. The mean difference was 18% (95% confidence interval, 13-24%; p<0.001)., Conclusions: Although small differences exist between the OR and CT dosimetry results, these data suggest that this intraoperative implant dosimetric representation system provides a close match to the actual delivered doses. These data support the use of this system to modify the implant during surgery to achieve more consistent dosimetry results.

Recently, 103Pd brachytherapy sources have been increasingly used for interstitial implants as an alternative to 125I sources. The BrachySeedPd-103 Model Pd-1 seed is one of the latest in a series of new brachytherapy sources that have become available commercially. The dosimetric properties of the seed were investigated by Monte Carlo simulation, which was performed using the Integrated Tiger Series CYLTRAN code. Following the AAPM Task Group 43 formalism, the dose rate constant, radial dose function, and anisotropy parameters were determined. The dose rate constant, A, was calculated to be 0.613 +/- 3% cGy h(-1) U(-1). This air kerma strength was derived from Monte Carlo simulation using the point extrapolation method. The radial dose function, g(r), was computed at distances from 0.15 to 10 cm. The anisotropy function, F(r,theta), and anisotropy factor, phi(an)(r), were calculated at distances from 0.5 to 7 cm. The anisotropy constant, phi(an), was determined to be 0.978, which is closer to unity than most other 103Pd seeds, indicating a high degree of uniformity in dose distribution. The dose rate constant and the radial dose function were also investigated by analytical modeling, which served as an independent evaluation of the Monte Carlo data, and found to be in good agreement with the Monte Carlo results.

The effects of edema on urethral dose after interstitial prostate brachytherapy with palladium-103 (103Pd) were studied. Fifty patients underwent a 90-Gy 103Pd implant followed by dosimetric computed tomography (CT). Twenty-one days later, a Foley catheter was reinserted and a dosimetric CT was repeated. The mean reduction in prostate volume between day 0 and day 21 was 16%. Median prostate D90 on day 0 was 89.7 Gy (range 59.5 to 127) and 99.5 Gy (range 62.5 to 130) on day 21. Median prostate V100 was 90% (range 63 to 98%) on day 0 and 96% (range 66 to 99%) on day 21. Median V150 was 61% (range 31 to 85%) on day 0 and 75% (range 39 to 93%) on day 21. Median urethral D50 was 107 Gy (range 57 to 201) on day 0 and 126 Gy (range 64 to 193) on day 21. Regression analysis demonstrated a significant correlation between the decrease in the prostate volume and the increased urethral D50 (r 0.58, p < 0.05). Acute urinary toxicity was 32% grade 0, 38% grade 1, and 30% grade 2. The median urethral D50 increased by a mean of 18% with a correlation coefficient of 0.58 (p < 0.05). Catheterization of the urethra was well tolerated and was of value in better characterizing urethral dose after 103Pd brachytherapy.

Monte Carlo calculations have been performed for the purpose of characterizing the dosimetric properties of three brachytherapy sources. The three sources are manufactured by Syncor Pharmaceuticals Inc. and consist of two 125I seeds (BT-125-1 and BT-125-2) and one 103Pd seed (BT-103-3). The BT-125-1 and BT-125-2 seed consists of a solid palladium and silver core, respectively. A thin layer (0.5 microm) of 125I is adsorbed onto the solid core for each seed and encased within a titanium housing. The BT-103-3 seed consists of a central gold marker and four resin balls encased within a titanium housing. A thin layer of 103Pd is bonded onto each resin ball. The dosimetric properties, including the dose rate constant, radial dose function, and anisotropy were calculated in water according to the TG-43 protocol using the Monte Carlo N-Particle code. The dose rate constant was calculated to be 0.955+/-0.005 and 0.967+/-0.005 cGyh(-1) U(-1) for the BT-125-1 and BT- 125-2 seeds, respectively. A dose rate constant of 0.659+/-0.005 cGy h(-1) U(-1) was calculated for the BT-103-3 seed. Radial dose function, g(r), calculated to a distance of 10 cm, and an isotropy function, F(r, theta), calculated for radii from 0.5 to 7.0 cm, were found to be in close agreement with previously published data.

The incidence of prostate cancer is increasing and, due to the use of PSA, more and more patients are diagnosed with localized disease. These patients may be offered treatment with the intent to cure. Traditionally, this has been either by radical prostatectomy or some form of radiation therapy. This article describes the minimally invasive method with permanent seed implantation. The procedure, indications, contraindications, side effects and results from the literature 28 patients have been treated so far with acceptable proximate side effects and reductions in serum-PSA as expected.

Purpose: A simple, inexpensive method to aid in the accurate placement of permanent seeds for prostate brachytherapy is described. The effect of identifying the prostate base and apex cystoscopically relative to registration seeds placed at the beginning of the implant is discussed., Materials and Methods: At the beginning of each implant procedure a pair of marker seeds are first placed in the prostate, including 1 seed at the base and 1 at the apex. Using a cystoscope, the urologist identifies the prostatic base and apex, and a fluoroscopic record is obtained. The positions of the base and apex relative to the marker seeds are monitored throughout the case via fluoroscopy to aid in needle and seed placement for the implant., Results: Use of this method significantly improved coverage of the prostate apex, reduced overall dose variance in the prostate base and improved overall gland dosimetry by 22% as measured by the D90 quality metric (minimal dose which covers 90% of the prostate volume)., Conclusions: While the clinical efficacy of improved target coverage on local control and survival awaits further clinical investigation, we encourage others to adopt this easy technique to ensure better, more consistent interstitial implants.

Purpose: To derive a rigorous analytic solution to the dosimetric effects of prostate edema so that its impact on the conventional pre-implant and post-implant dosimetry can be studied for any given radioactive isotope and edema characteristics., Methods and Materials: The edema characteristics observed by Waterman et al (Int. J. Rad. Onc. Biol. Phys, 41:1069-1077; 1998) was used to model the time evolution of the prostate and the seed locations. The total dose to any part of prostate tissue from a seed implant was calculated analytically by parameterizing the dose fall-off from a radioactive seed as a single inverse power function of distance, with proper account of the edema-induced time evolution. The dosimetric impact of prostate edema was determined by comparing the dose calculated with full consideration of prostate edema to that calculated with the conventional dosimetry approach where the seed locations and the target volume are assumed to be stationary., Results: A rigorous analytic solution on the relative dosimetric effects of prostate edema was obtained. This solution proved explicitly that the relative dosimetric effects of edema, as found in the previous numerical studies by Yue et. al. (Int. J. Radiat. Oncol. Biol. Phys. 43, 447-454, 1999), are independent of the size and the shape of the implant target volume and are independent of the number and the locations of the seeds implanted. It also showed that the magnitude of relative dosimetric effects is independent of the location of dose evaluation point within the edematous target volume. It implies that the relative dosimetric effects of prostate edema are universal with respect to a given isotope and edema characteristic. A set of master tables for the relative dosimetric effects of edema were obtained for a wide range of edema characteristics for both (125)I and (103)Pd prostate seed implants., Conclusions: A rigorous analytic solution of the relative dosimetric effects of prostate edema has been derived for a class of edema characterized by Waterman et al. The solution proved that the dosimetric effects caused by the edema are universal functions of edema characteristics for a given isotope. It provides an efficient tool to examine the relative dosimetric effects of edema for any given edema characteristics and for any isotopes that may be considered for prostate implants.

Transperineal interstitial permanent prostate brachytherapy (TIPPB) has become an increasingly popular treatment for early-stage/favorable-risk adenocarcinoma of prostate. Within TIPPB, permanent implants often use either (103)Pd (T(1/2) = 17 days) or (125)I (T(1/2) = 60 days). This review compares the radiobiological and treatment planning effectiveness of (103)Pd and (125)I implants by using the linear-quadratic model with recently published data regarding: prostate tumor cell doubling times, T(pot), alpha and alpha/beta, ratio. The tumor potential doubling times (T(pot)) were determined based on recently published proliferation constants (K(p)). The initial slope of the cell radiation dose survival curve, alpha, the terminal slope beta and the alpha/beta ratio were taken from recent published clinical and cellular results. The total dose delivered from each isotope was the dose used clinically, that is, 120 Gy for (103)Pd and 145 Gy for (125)I. Dale's modified linear-quadratic equation was used to estimate the biological effective dose, the cell-surviving fraction, the effective treatment time, and the wasted radiation dose for different values of T(pot). Treatment plans for peripherally loaded implants were compared. The T(pot) reported for organ-confined prostate carcinomas varied from 16 to 67 days. At short T(pot) both isotopes were less effective, but (103)Pd had much less dependence on T(pot) than (125)I. However, at long T(pot) both isotopes produced similar effects. The minimum surviving fraction for exposure to (103)Pd decreased from 1.40 x 10(-4) to 1.31 x 10(-5) as the T(pot) increased from 16 to 67 days. By contrast for exposure to (125)I, the minimum surviving fraction decreased from 3.98 x 10(-3) to 1.98 x 10(-5) over the same range of T(pot). A comparison of treatment plans revealed that (103)Pd plans required more needles and seeds; however, this was a function of seed strength. Both isotopes had similar dose-volume histograms for prostate, urethra, and rectum. The theoretical prediction of effectiveness using the linear quadratic equation for the common clinically prescribed total radiation doses indicated that (103)Pd should be more effective than (125)I because it had less dependence on T(pot). The greatest benefit of (103)Pd was shown to be with tumors with a short T(pot). Although the regrowth delay would be longer with (125)I, the benefit was inconsequential compared with the very slow doubling times of localized prostate cancer. Treatment planning with either isotope revealed no significant differences. These findings may explain why clinically there seemed to be no clear difference in treatment outcome with either isotope. Based on these predictions, we recommend a clinical trial to compare the efficacy of the two isotopes.

This article summarizes recent American Brachytherapy Society (ABS) recommendations for permanent prostate brachytherapy. The ABS recommends treating patients with high probability of organ-confined disease with brachytherapy alone. Brachytherapy candidates with a significant risk of extraprostatic extension should be treated with supplemental external beam radiation therapy (EBRT). The recommended prescription doses for monotherapy are 145 Gy for (125)I and 125 Gy for (103)Pd. The corresponding boost doses (after 40 to 50 Gy EBRT) are 110 Gy and 100 Gy, respectively. The ABS recommends that post-implant dosimetry should be performed on all patients undergoing permanent prostate brachytherapy for optimal patient care. A dose-volume histogram (DVH) of the prostate should be performed and the D(90) (dose to 90% of the prostate gland) reported by all centers. Additionally, the D(80) D(100), the fractional V(80), V(90), V(100), V(150), V(200) (ie, the percentage of prostate volume receiving 80%, 90%, 100%, 150%, and 200% of the prescribed dose, respectively), the rectal and urethral doses should be reported and ultimately correlated with clinical outcome in the research environment. On-line, real-time dosimetry, the effects of dose heterogeneity, and the effects of tissue heterogeneity need further investigation.

Based on suggestions by anecdotal evidence to date, an attempt is made to estimate the occurrence of non-disease-related prostate-specific antigen (PSA) spiking in the serum PSA profiles of a series of men treated by (125)I/(103)Pd brachytherapy with or without external beam irradiation. Five hundred ninety-one patients treated between January 1988 and December 1993 were eligible for study. Patients whose clinical status was described as equivocal (declining PSA > 1.0 ng/mL or rising PSA without documented disease [9.6% of the cohort]) were not considered. Evidence of PSA increases that were followed by decline were identified. Treatment and disease-specific parameters were examined for influence of the occurrence of spiking. In patients judged biochemical successes at last follow-up (serum PSA < or = 1.0 ng/mL), 35.8% exhibited a temporary increase of 0.2 ng/mL or more. Seventy-five percent of these patients exhibited a temporary increase between 0.3 and 3.4 ng/mL. The average time of the temporary increases was 24.8 months after implant. Spiking was not associated with a higher risk of clinical failure in this data set. Conventional risk factors for recurrent disease were not associated with benign PSA spiking. Low-magnitude serum PSA spiking may occur in up to one third of patients following permanent, low-dose rate brachytherapy of the prostate. Most of these observations occur up to 3 years after implant and do not appear to be related to disease recurrence. Caution should be taken before initiating further therapy pursuant to the observation of PSA spiking of less than 2 to 3 ng/mL shortly following brachytherapy. Frequent serum PSA sampling following prostate brachytherapy with early follow-up may overestimate biochemical failure rates.

Interstitial brachytherapy for carcinoma of the prostate is achieved through the use of a configuration of radioactive seeds placed in a manner that delivers a customized, reasonably uniform dose to the target volume. Accurate dose delivery depends on both precise seed placement and reliable seed strength in the implanted configuration. This study assumes the independence of the two issues, and quantifies the reduction in the minimum dose to the surface of the gland due only to variability in individual seed strengths. Current AAPM guidelines pertaining to the acceptable limits on seed-to-seed variability are prudent for small configurations of seeds, yet are likely to be overly stringent for applications such as prostate seed implantation. In this study we determine the reduction in the minimum peripheral dose (mPD) caused by the introduction of source strength variability, and provide statistical insight into this effect. It is concluded that the current guidelines limit the reduction in mPD to < or =0.4% relative to the prescription value, for an average configuration, due to the inclusion of strength variability. The maximum observed reduction in mPD would be < or =1.5%. This value is an order of magnitude lower than the recommendations of the AAPM Task Group 40 for the overall accuracy of brachytherapy procedures, which suggests that seed strength variability is of limited concern and that constraints on this factor should perhaps be reevaluated.

The linear quadratic model predicts that the normal tissue biologically effective dose (BED) will be lower with palladium-103 (Pd-103) vs. iodine-125 (I-125) for the currently prescribed minimum tumor doses (MTD) used for I-125 (160 Gy) and Pd-103 (115 Gy) prostate cancer brachytherapy. The predicted BEDs for I-125 and Pd-103 suggest that the long-term complication rates should be lower with Pd-103 vs. I-125 in clinical practice. A review of 123 early stage T1c and T2 prostate cancer patients implanted at Yale University with I-125 (82 patients) or Pd-103 (41 patients) reveals a significantly lower overall complication rate with Pd-103 (0%) vs. I-125 (13%). Most important, the grade III-IV complication rate for Pd-103 was 0% vs. 6% for I-125. The 3-year actuarial probability of remaining free of a long-term complication was 100% for Pd-103 vs. 82% for I-125 (P<0.01). A review of the literature for 992 patients implanted with I-125 vs. 540 patients implanted with Pd-103 shows a consistently higher complication rate for I-125 vs. Pd-103. Assuming that the MTD for Pd-103 may be increased to produce an equivalent late-reacting normal tissue BED to that for I-125, then the radiobiology model predicts the log10 cell kill for Pd-103 implant will be greater than that of an I-125 implant for all tumor doubling times (high-grade tumors and low-grade tumors). The implications of these findings are discussed in terms of future research directions for prostate implants.

Purpose: Recent data indicate that intraluminal irradiation of coronary arteries following balloon angioplasty reduces proliferation of smooth muscle cells, neointima formation, and restenosis. We present calculations for various isotopes and geometries in an attempt to identify suitable source designs for such treatments., Methods and Materials: Analytical calculations of dose distributions and dose rates are presented for 192Ir, 125I, 103Pd, 32P, and 90Sr for use in intracoronary irradiation. The effects of source geometry and positioning accuracy are studied., Results: Accurate source centering, high dose rate, well-defined treatment volume, and radiation safety are all of concern; 15-20 Gy are required to a length of 2-3 cm of vessel wall (2-4 mm diameter). Dose must be confined to the region of the angioplasty, with reduced doses to normal tissues. Beta emitters have radiation safety advantages, but may not have suitable ranges for treating large diameter vessels. Gamma emitters deliver larger doses to normal tissues and to staff. Low energy x-ray emitters such as 125I and 103Pd reduce these risks but are not available at high enough activities. The feasibility of injecting a radioactive liquid directly into the angioplasty balloon is also explored., Conclusions: Accurate source centering is found to be of great importance. If this can be accomplished, then high energy beta emitters such as 90Sr would be ideal sources. Otherwise, gamma emitters such as 192Ir may be optimal. A liquid beta source would have optimal geometry and dose distribution, but available sources, such as 32P are unsafe for use with available balloon catheters.

Purpose: The purpose of this study was to assess the feasibility of 103Pd brachytherapy in the management of primary unresectable carcinoma of the pancreas., Methods and Materials: Between August 1988 and January 1992, 11 patients with biopsy-proven primary unresectable adenocarcinoma of the pancreas were treated with 103Pd brachytherapy during laparotomy. The median age was 66 (range 57-70). The most common presenting symptoms were weight loss (eight patients), pain (six patients), and nausea/vomiting (four patients). Less common symptoms were jaundice (two patients), early satiety (two patients), and ascites (one patient). All patients underwent laparotomy and surgical staging. Eight patients had T3N0M0 disease, two patients had T3N1M0 disease, and one patient had T3N1M1 disease. The surgical procedure performed was biliary bypass in six patients, biopsy only in four patients, and gastric bypass in one patient. The average tumor dimension was 4.0 cm. The median activity, matched peripheral dose (MPD) and implanted volumes were 95.3 mCi, 124.4 Gy, and 33 cm3, respectively. The median initial dose rate was 0.21 Gy per hour. Five patients received postoperative external beam radiation therapy (median 45 Gy) and seven patients received chemotherapy postoperatively. The median follow-up was 7 months (range 1-19)., Results: The median survival for the entire group of patients was 6.9 months. Ten of 11 patients have died, with 1 patient presently alive and receiving chemotherapy for metastatic disease to the liver, but without local progression radiographically. Five of 11 patients (45%) were locally controlled, defined as either a complete response or freedom from progression at the site of the implant as evaluated by computed tomography scan. In the other six patients, the median time to local progression was 6.9 months. Five patients developed distant metastases (four liver, one subcutaneous nodule). Two patients failed in regional sites (one omentum, one paraaortic lymph node). Four of 11 patients (36%) developed acute postoperative complications that included one gastric outlet obstruction, one duodenal perforation, and two with sepsis. One of 11 patients (9%) developed a late complication of radiation enteritis 5 months after implantation. The median survival for patients experiencing complications was 1.7 months as compared to 8.4 months for the patients who did not develop a complication (p = 0.10). Pain relief was obtained in five out of six (83%) of the patients presenting with pain for a median duration of 24 weeks. Local control did not appear to be related to the MPD, dose rate, implanted volume, treatment with external beam irradiation, or the use of chemotherapy. Patients were more likely to develop a complication if the MPD was greater than 115 Gy (four out of six patients) as compared to those whose MPD was less than 115 Gy (one out of five patients) (p = 0.12)., Conclusions: Because there was no improvement in median survival over conventional modalities, and the complication rate was high; we do not recommend 103Pd brachytherapy as a component of the treatment of unresectable adenocarcinoma of the pancreas.

Palladium-103 (Pd-103) is introduced in brachytherapy procedures because of its favorable physical properties, including its low energy, rapid dose fall-off, short half-life, and total cumulative dose delivery at a higher dose rate than iodine-125 (I-125) isotope. Intraoperative brachytherapy using I-125 pellets was reported to provide significant palliation and meaningful prolongation of life in highly selected patients with unresectable carcinoma of the pancreas. After considering some of the advantages of Pd-103 over I-125, we designed a phase I-II clinical trial to assess the feasibility of intraoperative Pd-103 in unresectable carcinoma of the pancreas to study the related morbidity when combined with chemotherapy and external beam radiation, and to evaluate the impact on palliation and local control rates. Between December 1989 and December 1993, 15 patients with biopsy-proven unresectable adenocarcinoma of the pancreas were treated with interstitial Pd-103 implants during laparotomy. In 13 patients the lesion was located in the head of the pancreas, in one patient in the uncinate process, and in one patient in the body of the pancreas. The stage distribution was as follows: T1 = 2; T2 = 6, and T3 = 7. In addition, all patients underwent biliary and gastric bypass. The mean number of Pd-103 pellets was 45; the mean total activity to obtain a matched peripheral dose (MPD) of 11,000 cGy was 68.9 mCi. The mean tumor volume encompassing the MPD was 16.5 cc. All patients received postoperative external beam radiation (4,500 cGy over 4 1/2 weeks) and chemotherapy (5-fluorouracil and mitomycin C). This combined treatment, consisting of intraoperative brachytherapy using Pd-103 and postoperative external beam radiation with chemotherapy, was well tolerated in all patients. These were no treatment-related mortalities, and no serious complications, such as bleeding or fistula formation. Pain relief was obtained within 3-6 weeks in 10 out of 12 patients presenting with pain. Survival ranged from 6 to 24 months (median 10 months). The study suggests that Pd-103 can be considered an alternative to I-125 for interstitial brachytherapy for unresectable carcinoma of the pancreas. Symptom relief appeared to occur faster and complications are significantly less. However, this study did not show any improvement in the median survival rate over I-125 due to the advanced stage cancer in the majority of patients in the study.

A total of 71 men with clinical T1b-T2c carcinoma of the prostate underwent ultrasound-guided interactive seed implantation of the prostate. Sixty received 125I and II 103Pd implants. A laparoscopic lymph node dissection was performed in 58 patients. The patients have been followed a mean of 2 years (1-4.2 years). With use of a prostate specific antigen (PSA) value of 1 ng/ml, patients (n = 8) who presented with an initial PSA of < or = 4.0 ng/ml were all free from failure. This compared with those who presented with an initial PSA of 4.1-10, 10.1-20, and > or = 20 ng/ml, in whom the freedom from failure rates were 52, 32, and 22%, respectively. Patients (n = 49) who presented with an initial PSA of less than or equal to 15 ng/ml had a median PSA of 0.88 ng/ml at last follow-up compared with 2.25 ng/ml for those with an initial PSA of > 15 ng/ml. Prostate biopsies performed 18-24 months after implantation were negative in 82%. The median PSA for those with a negative biopsy was 0.7 ng/ml vs. 4.9 ng/ml for those with a positive biopsy. There were no long-term persistent urinary complaints. Grade 2 radiation proctitis occurred in three (4.2%). No cases of severe radiation proctitis or cystitis occurred. Urinary retention occurred in four patients (5.6%), one of whom required a transurethral resection of the prostate. No patients developed urinary incontinence. Potency was preserved in 94%. We conclude that the real-time ultrasound-guided transperineal seed implantation technique is an effective and safe method of treating prostate cancer. Longer follow-up is needed to substantiate these early encouraging results.

Anisotropy of dose distributions around 103Pd, 125I, and 192Ir sources for interstitial brachytherapy was examined. Dose rates around 125I models 6702 and 6711 and 192Ir sources were measured using lithium fluoride thermoluminescence dosimeters (LiF TLDs) in a water-equivalent, solid phantom. From these measured data for 125I and 192Ir and the previously published measured data for 103Pd, isodose rate contours were determined using a bivariate interpolation and smooth surface fitting algorithm. The anisotropy functions, F(r,theta), as defined by the Interstitial Collaborative Working Group (ICWG) for each source, were determined. Also, 4 pi-averaged anisotropy factors, phi an(r), for use in point source approximation, have been calculated at radial distances varying from 1-10 cm for 103Pd, 125I, and 192Ir sources. The anisotropy factors had average values of 0.90, 0.93, 0.95, and 0.98 for 103Pd, 125I model 6711, 125I model 6702, and 192Ir, respectively. The anisotropy factors determined from dose measurements in phantom are observed to be closer to unity than from those determined previously from in-air measurements. This can be attributed to the smoothing of two-dimensional dose distributions due to the presence of more scattered photons in the phantom measurements compared to in-air measurements. Because in-phantom measurements simulate more closely the brachytherapy patient, data from these experiments are recommended for a more accurate determination of dose distributions around clinical brachytherapy implants. In this work, we present a complete set of source data for two-dimensional dosimetry following the ICWG formalism.