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Purpose: To evaluate late gastrointestinal (GI) and genitourinary (GU) toxicity of moderately hypofractionated intensity modulated proton therapy (IMPT) targeting the prostate and pelvic lymph nodes., Methods and Materials: A target accrual of 56 patients with high-risk or unfavorable intermediate risk prostate cancer were enrolled into a prospective study (ClinicalTrials.gov: NCT02874014) of moderately hypofractionated IMPT. IMPT with pencil beam scanning was used to deliver 6750 and 4500 cGy relative biological effectiveness in 25 daily fractions simultaneously to the prostate and pelvic lymph nodes, respectively. All received androgen deprivation therapy. Late GI and GU toxicity was prospectively assessed using Common Terminology Criteria for Adverse Events version 4.0, at baseline, weekly during radiation therapy, 3-month postradiation therapy, and then every 6 months. Actuarial rates of late GI and GU toxicity were estimated using Kaplan-Meier method., Results: Median age was 75.5 years. Fifty-four patients were available for late toxicity evaluation. Median follow-up was 43.9 months (range, 16-66). The actuarial rate of late grade ≥2 GI toxicity at both 2 and 3 years was 7.4% (95% confidence interval [CI], 0.2%-14.2%). The actuarial rate of late grade 3 GI toxicity at both 2 and 3 years was 1.9% (95% CI, 0%-5.4%). One patient experienced grade 3 GI toxicity with proctitis. The actuarial rate of late grade ≥2 GU toxicity was 20.5% (95% CI, 8.9%-30.6%) at 2 years, and 29.2 % (95% CI, 15.5%-40.7%) at 3 years. None had grade 3 GU toxicity. The presence of baseline GU symptoms was associated with a higher likelihood of experiencing late grade 2 GU toxicity., Conclusions: A moderately hypofractionated IMPT targeting the prostate and regional pelvic lymph nodes was generally well tolerated. Patients with pre-existing GU symptoms had a higher rate of late grade 2 GU toxicity. A phase 3 study is needed to assess any therapeutic gain of IMPT, in comparison with photon-based radiation therapy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Very-high-risk (VHR) prostate cancer (PC) is an aggressive subgroup with high risk of distant disease progression. Systemic treatment intensification with abiraterone or docetaxel reduces PC-specific mortality (PCSM) and distant metastasis (DM) in men receiving external beam radiation therapy (EBRT) with androgen deprivation therapy (ADT). Whether prostate-directed treatment intensification with the addition of brachytherapy (BT) boost to EBRT with ADT improves outcomes in this group is unclear., Methods and Materials: This cohort study from 16 centers across 4 countries included men with VHR PC treated with either dose-escalated EBRT with ≥24 months of ADT or EBRT + BT boost with ≥12 months of ADT. VHR was defined by National Comprehensive Cancer Network (NCCN) criteria (clinical T3b-4, primary Gleason pattern 5, or ≥2 NCCN high-risk features), and results were corroborated in a subgroup of men who met Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trials inclusion criteria (≥2 of the following: clinical T3-4, Gleason 8-10, or PSA ≥40 ng/mL). PCSM and DM between EBRT and EBRT + BT were compared using inverse probability of treatment weight-adjusted Fine-Gray competing risk regression., Results: Among the entire cohort, 270 underwent EBRT and 101 EBRT + BT. After a median follow-up of 7.8 years, 6.7% and 5.9% of men died of PC and 16.3% and 9.9% had DM after EBRT and EBRT + BT, respectively. There was no significant difference in PCSM (sHR, 1.47 [95% CI, 0.57-3.75]; P = .42) or DM (sHR, 0.72, [95% CI, 0.30-1.71]; P = .45) between EBRT + BT and EBRT. Results were similar within the STAMPEDE-defined VHR subgroup (PCSM: sHR, 1.67 [95% CI, 0.48-5.81]; P = .42; DM: sHR, 0.56 [95% CI, 0.15-2.04]; P = .38)., Conclusions: In this VHR PC cohort, no difference in clinically meaningful outcomes was observed between EBRT alone with ≥24 months of ADT compared with EBRT + BT with ≥12 months of ADT. Comparative analyses in men treated with intensified systemic therapy are warranted., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Data comparing moderately hypofractionated intensity modulated radiation therapy (IMRT) and proton beam therapy (PBT) are lacking. We aim to compare late toxicity profiles of patients with early-stage prostate cancer treated with moderately hypofractionated PBT and IMRT., Methods and Materials: This multi-institutional analysis included patients with low- or intermediate-risk biopsy-proven prostate adenocarcinoma from 7 tertiary referral centers treated from 1998 to 2018. All patients were treated with moderately hypofractionated radiation, defined as 250 to 300 cGy per daily fraction given for 4 to 6 weeks, and stratified by use of IMRT or PBT. Primary outcomes were late genitourinary (GU) and gastrointestinal (GI) toxicity. Adjusted toxicity rates were calculated using inverse probability of treatment weighting, accounting for race, National Comprehensive Cancer Network risk group, age, pretreatment International Prostate Symptom Score (GU only), and anticoagulant use (GI only)., Results: A total of 1850 patients were included: 1282 IMRT (median follow-up 80.0 months) and 568 PBT (median follow-up 43.9 months). Overall toxicity rates were low, with the majority of patients experiencing no late GU (56.6%, n = 1048) or late GI (74.4%, n = 1377) toxicity. No difference was seen in the rates of late toxicity between the groups, with late grade 3+ GU toxicity of 2.0% versus 3.9% (odds ratio [OR] 0.47; 95% confidence interval 0.17-1.28) and late grade 2+ GI toxicity of 14.6% versus 4.7% (OR 2.69; confidence interval 0.80-9.05) for the PBT and IMRT cohorts, respectively. On multivariable analysis, no factors were significantly predictive of GU toxicity, and only anticoagulant use was significantly predictive of GI toxicity (OR 1.90; P = .008)., Conclusions: In this large, multi-institutional analysis of 1850 patients with early-stage prostate cancer, treatment with moderately hypofractionated IMRT and PBT resulted in low rates of toxicity. No difference was seen in late GI and GU toxicity between the modalities during long-term follow-up. Both treatments are safe and well tolerated., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Definitive radiation therapy (RT), with or without concurrent chemotherapy, is an alternative to radical cystectomy for patients with localized, muscle-invasive bladder cancer (MIBC) who are either not surgical candidates or prefer organ preservation. We aim to synthesize an evidence-based guideline regarding the appropriate use of RT., Methods and Materials: We performed a Preferred Reporting Items for Systematic Reviews and Meta-analyses literature review using the PubMed and Embase databases. Based on the literature review, critical management topics were identified and reformulated into consensus questions. An expert panel was assembled to address key areas of both consensus and controversy using the modified Delphi framework., Results: A total of 761 articles were screened, of which 61 were published between 1975 and 2019 and included for full review. There were 7 well-designed studies, 20 good quality studies, 28 quality studies with design limitations, and 6 references not suited as primary evidence. Adjuvant radiation therapy after cystectomy was not included owing to lack of high-quality data or clinical use. An expert panel consisting of 14 radiation oncologists, 1 medical oncologist, and 1 urologist was assembled. We identified 4 clinical variants of MIBC: surgically fit patients who wish to pursue organ preservation, patients surgically unfit for cystectomy, patients medically unfit for cisplatin-based chemotherapy, and borderline cystectomy candidates based on age with unilateral hydronephrosis and normal renal function. We identified key areas of controversy, including use of definitive radiation therapy for patients with negative prognostic factors, appropriate radiation therapy dose, fractionation, fields and technique when used, and chemotherapy sequencing and choice of agent., Conclusions: There is limited level-one evidence to guide appropriate treatment of MIBC. Studies vary significantly with regards to patient selection, chemotherapy use, and radiation therapy technique. A consensus guideline on the appropriateness of RT for MIBC may aid practicing oncologists in bridging the gap between data and clinical practice., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: In 2009, the Radiation Therapy Oncology Group (RTOG) genitourinary members published a consensus atlas for contouring prostate pelvic nodal clinical target volumes (CTVs). Data have emerged further informing nodal recurrence patterns. The objective of this study is to provide an updated prostate pelvic nodal consensus atlas., Methods and Materials: A literature review was performed abstracting data on nodal recurrence patterns. Data were presented to a panel of international experts, including radiation oncologists, radiologists, and urologists. After data review, participants contoured nodal CTVs on 3 cases: postoperative, intact node positive, and intact node negative. Radiation oncologist contours were analyzed qualitatively using count maps, which provided a visual assessment of controversial regions, and quantitatively analyzed using Sorensen-Dice similarity coefficients and Hausdorff distances compared with the 2009 RTOG atlas. Diagnostic radiologists generated a reference table outlining considerations for determining clinical node positivity., Results: Eighteen radiation oncologists' contours (54 CTVs) were included. Two urologists' volumes were examined in a separate analysis. The mean CTV for the postoperative case was 302 cm 3 , intact node positive case was 409 cm 3 , and intact node negative case was 342 cm 3 . Compared with the original RTOG consensus, the mean Sorensen-Dice similarity coefficient for the postoperative case was 0.63 (standard deviation [SD] 0.13), the intact node positive case was 0.68 (SD 0.13), and the intact node negative case was 0.66 (SD 0.18). The mean Hausdorff distance (in cm) for the postoperative case was 0.24 (SD 0.13), the intact node positive case was 0.23 (SD 0.09), and intact node negative case was 0.33 (SD 0.24). Four regions of CTV controversy were identified, and consensus for each of these areas was reached., Conclusions: Discordance with the 2009 RTOG consensus atlas was seen in a group of experienced NRG Oncology and international genitourinary radiation oncologists. To address areas of variability and account for new data, an updated NRG Oncology consensus contour atlas was developed., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: This study examined the effects of metastasis-directed stereotactic body radiation therapy (mdSBRT) on CD8 + T-cell subpopulations and correlated post-mdSBRT immunophenotypic responses with clinical outcomes in patients with oligometastatic prostate cancer (OPCa)., Methods and Materials: Peripheral blood mononuclear cells were prospectively isolated from 37 patients with OPCa (≤3 metastases) who were treated with mdSBRT. Immunophenotyping identified circulating CD8 + T-cell subpopulations, including tumor-reactive (T TR ), effector memory, central memory (T CM ), effector, and naïve T cells from samples collected before and after mdSBRT. Univariate Cox proportional hazards regression was used to assess whether changes in these T-cell subpopulations were potential risk factors for death and/or progression. The Kaplan-Meier method was used for survival. Cumulative incidence for progression and new distant metastasis weas estimated, considering death as a competing risk., Results: Median follow-up was 39 months (interquartile range, 34-43). Overall survival at 3 years was 78.2%. Cumulative incidence for local progression and new distant metastasis at 3 years was 16.5% and 67.6%, respectively. Between baseline and day 14 after mdSBRT, an increase in the T CM cell subpopulation was associated with the risk of death (hazard ratio, 1.22 [95% confidence interval, 1.02-1.47]; P = .033), and an increase in the T TR cell subpopulation was protective against the risk of local progression (hazard ratio, 0.80 [95% confidence interval, 0.65-0.98]; P = .032)., Conclusions: An increase in the T TR cell subpopulation was protective against the risk of disease progression, and an increase in the T CM cell subpopulation was associated with the risk of death in patients with OPCa treated with mdSBRT. Disease control may be further improved by better understanding the CD8 + T-cell subpopulations and by enhancing their antitumor effect., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To evaluate C-11 choline positron emission tomography/computed tomography (CholPET) in staging and determining patterns of recurrence in prostate cancer patients with rising prostate-specific antigen levels after prostatectomy radiation therapy (RT)., Methods and Materials: The study includes patients with biochemical failure after postprostatectomy RT who underwent CholPET between 2008 and 2015. Patient and disease characteristics were examined in relation to sites of recurrence. All RT dosimetry records were reviewed, and recurrences were mapped on a representative computed tomography dataset with their relationship relative to the irradiated fossa field as out of field (OOF), edge of field (EOF; recurrence within <45-Gy isodose lines), or in field (IF; recurrence within ≥45-Gy isodose lines)., Results: Forty-one patients were identified with 121 sites of recurrence (median 2 sites; interquartile range [IQR], 1-4). The median prostate-specific antigen level at CholPET was 3.1 (IQR, 1.9-5.6) ng/mL. Median interval from RT to biochemical failure was 24 (IQR, 10-46) months, with recurrence identified on CholPET at a median of 15 (IQR, 7-28) months from biochemical failure. Histologic confirmation of recurrence was obtained in 20 patients (49%), with the remainder confirmed by treatment response. Five patients (12%) had IF recurrences, 10 patients (24%) had EOF recurrences (median dose 10 Gy; IQR, 5-30 Gy), and 36 patients (88%) had OOF recurrences. Ten patients had combination failures: 6 (15%) EOF/OOF and 4 (10%) IF/OOF. Fifty-seven recurrences (47%) were pelvic nodal sites inferior to the L5-S1 interspace, of which 52 (43%) were within a pelvic RT field. Eighty-one recurrences (67%) were nodal and inferior to the aortic bifurcation., Conclusions: Using CholPET, we found that the majority of patients evaluated for biochemical failure recurred outside of the postprostatectomy RT field. Furthermore, most recurrence sites were nodal and inferior to the aortic bifurcation. These results provide data that may be useful for examining strategies that include elective lymph node irradiation in postprostatectomy patients., Competing Interests: See conflict of interest statements by each author:, (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this guideline was to provide a clinical framework for the use of radiation therapy after radical prostatectomy as adjuvant or salvage therapy., Methods and Materials: A systematic literature review using PubMed, Embase, and Cochrane database was conducted to identify peer-reviewed publications relevant to the use of radiation therapy after prostatectomy. The review yielded 294 articles; these publications were used to create the evidence-based guideline statements. Additional guidance is provided as Clinical Principles when insufficient evidence existed., Results: Guideline statements are provided for patient counseling, use of radiation therapy in the adjuvant and salvage contexts, defining biochemical recurrence, and conducting a restaging evaluation., Conclusions: Physicians should offer adjuvant radiation therapy to patients with adverse pathologic findings at prostatectomy (ie, seminal vesicle invastion, positive surgical margins, extraprostatic extension) and salvage radiation therapy to patients with prostate-specific antigen (PSA) or local recurrence after prostatectomy in whom there is no evidence of distant metastatic disease. The offer of radiation therapy should be made in the context of a thoughtful discussion of possible short- and long-term side effects of radiation therapy as well as the potential benefits of preventing recurrence. The decision to administer radiation therapy should be made by the patient and the multidisciplinary treatment team with full consideration of the patient's history, values, preferences, quality of life, and functional status. The American Society for Radiation Oncology and American Urological Association websites show this guideline in its entirety, including the full literature review., (Copyright © 2013. Published by Elsevier Inc.)

Purpose: To report outcomes of a multimodality therapy combining maximal surgical resection and intraoperative electron radiotherapy (IOERT) for patients with locoregionally (LR) recurrent renal cell carcinoma (RCC) after radical nephrectomy or LR advanced primary RCC., Methods and Materials: From 1989 through 2005, a total of 22 patients with LR recurrent (n = 19) or LR advanced primary (n = 3) RCC were treated with this multimodality approach. The median patient age was 63 years (range 46-78). Twenty-one patients (95%) received perioperative external beam radiotherapy (EBRT) with a median dose of 4,500 cGy (range, 4,140-5,500). Surgical resection was R0 (negative margins) in 5 patients (23%) and R1 (residual microscopic disease) in 17 patients (77%). The median IOERT dose delivered was 1,250 cGy (range, 1,000-2,000). Overall survival (OS) and disease-free survival (DFS) and relapse patterns were estimated using the Kaplan-Meier method., Results: The median follow-up for surviving patients was 9.9 years (range, 3.6-20 years). The OS and DFS at 1, 5, and 10 years were 91%, 40%, and 35% and 64%, 31%, and 31%, respectively. Central recurrence (within the IOERT field), LR relapse (tumor bed or regional lymph nodes), and distant metastases at 5 years were 9%, 27%, and 64%, respectively. Mortality within 30 days of surgery and IOERT was 0%. Five patients (23%) experienced acute or late National Cancer Institute Common Toxicity Criteria (NCI-CTCAE) Version 4 Grade 3 to 5 toxicities., Conclusions: In patients with LR recurrent or LR advanced primary RCC, a multimodality approach of perioperative EBRT, maximal surgical resection, and IOERT yielded encouraging results. This regimen warrants further investigation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To report a multi-institutional outcomes study on permanent prostate brachytherapy (PPB) to 9 years that includes postimplant dosimetry, to develop a postimplant nomogram predicting biochemical freedom from recurrence., Methods and Materials: Cox regression analysis was used to model the clinical information for 5,931 patients who underwent PPB for clinically localized prostate cancer from six centers. The model was validated against the dataset using bootstrapping. Disease progression was determined using the Phoenix definition. The biological equivalent dose was calculated from the minimum dose to 90% of the prostate volume (D90) and external-beam radiotherapy dose using an alpha/beta of 2., Results: The 9-year biochemical freedom from recurrence probability for the modeling set was 77% (95% confidence interval, 73-81%). In the model, prostate-specific antigen, Gleason sum, isotope, external beam radiation, year of treatment, and D90 were associated with recurrence (each p < 0.05), whereas clinical stage was not. The concordance index of the model was 0.710., Conclusion: A predictive model for a postimplant nomogram for prostate cancer recurrence at 9-years after PPB has been developed and validated from a large multi-institutional database. This study also demonstrates the significance of implant dosimetry for predicting outcome. Unique to predictive models, these nomograms may be used a priori to calculate a D90 that likely achieves a desired outcome with further validation. Thus, a personalized dose prescription can potentially be calculated for each patient., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: To investigate the biochemical control rates and survival for Gleason score 7-10 prostate cancer patients undergoing permanent prostate brachytherapy as a function of the biologic effective dose (BED)., Methods and Materials: Six centers provided data on 5,889 permanent prostate brachytherapy patients, of whom 1,078 had Gleason score 7 (n = 845) or Gleason score 8-10 (n = 233) prostate cancer and postimplant dosimetry results available. The median prostate-specific antigen level was 7.5 ng/mL (range, 0.4-300). The median follow-up for censored patients was 46 months (range, 5-130). Short-term hormonal therapy (median duration, 3.9 months) was used in 666 patients (61.8%) and supplemental external beam radiotherapy (EBRT) in 620 (57.5%). The patients were stratified into three BED groups: <200 Gy (n = 645), 200-220 Gy (n = 199), and >220 Gy (n = 234). Biochemical freedom from failure (bFFF) was determined using the Phoenix definition., Results: The 5-year bFFF rate was 80%. The bFFF rate stratified by the three BED groups was 76.4%, 83.5%, and 88.3% (p < 0.001), respectively. Cox regression analysis revealed Gleason score, prostate-specific antigen level, use of hormonal therapy, EBRT, and BED were associated with bFFF (p < 0.001). Freedom from metastasis improved from 92% to 99% with the greatest doses. The overall survival rate at 5 years for the three BED groups for Gleason score 8-10 cancer was 86.6%, 89.4%, and 94.6%, respectively (p = 0.048)., Conclusion: These data suggest that permanent prostate brachytherapy combined with EBRT and hormonal therapy yields excellent bFFF and survival results in Gleason score 7-10 patients when the delivered BEDs are >220 Gy. These doses can be achieved by a combination of 45-Gy EBRT with a minimal dose received by 90% of the target volume of 120 Gy of (103)Pd or 130 Gy of (125)I.

Purpose: To determine planning target volume (PTV) margins for prostate radiotherapy based on the internal margin (IM) (intrafractional motion) and the setup margin (SM) (interfractional motion) for four daily localization methods: skin marks (tattoo), pelvic bony anatomy (bone), intraprostatic gold seeds using a 5-mm action threshold, and using no threshold., Methods and Materials: Forty prostate cancer patients were treated with external radiotherapy according to an online localization protocol using four intraprostatic gold seeds and electronic portal images (EPIs). Daily localization and treatment EPIs were obtained. These data allowed inter- and intrafractional analysis of prostate motion. The SM for the four daily localization methods and the IM were determined., Results: A total of 1532 fractions were analyzed. Tattoo localization requires a SM of 6.8 mm left-right (LR), 7.2 mm inferior-superior (IS), and 9.8 mm anterior-posterior (AP). Bone localization requires 3.1, 8.9, and 10.7 mm, respectively. The 5-mm threshold localization requires 4.0, 3.9, and 3.7 mm. No threshold localization requires 3.4, 3.2, and 3.2 mm. The intrafractional prostate motion requires an IM of 2.4 mm LR, 3.4 mm IS and AP. The PTV margin using the 5-mm threshold, including interobserver uncertainty, IM, and SM, is 4.8 mm LR, 5.4 mm IS, and 5.2 mm AP., Conclusions: Localization based on EPI with implanted gold seeds allows a large PTV margin reduction when compared with tattoo localization. Except for the LR direction, bony anatomy localization does not decrease the margins compared with tattoo localization. Intrafractional prostate motion is a limiting factor on margin reduction.

Purpose: To investigate the biochemical control rate in patients undergoing permanent prostate brachytherapy as a function of the biologically effective dose (BED) and risk group., Methods and Materials: Six centers provided data on 3,928 permanent brachytherapy patients with postimplant dosimetry results. The mean prostate-specific antigen level was 8.9 ng/mL. (125)I was used in 2,293 (58%), (103)Pd in 1,635, and supplemental external beam radiotherapy in 882 (22.5%) patients. The patients were stratified into low- (n = 2,188), intermediate- (n = 1,188), and high- (n = 552) risk groups and into three BED groups of < 140 Gy (n = 524), 140-200 Gy (n = 2284), and >200 Gy (n = 1,115). Freedom from biochemical disease progression (biochemical freedom from failure [bFFF]) was determined using the American Society for Therapeutic Radiology Oncology and Phoenix definitions and calculated using the Kaplan-Meier method, with factors compared using the log-rank test., Results: The 10-year prostate-specific antigen bFFF rate for the American Society for Therapeutic Radiology Oncology and Phoenix definitions was 79.2% and 70%, respectively. The corresponding bFFF rates for the low-, intermediate-, and high-risk groups was 84.1% and 78.1%, 76.8% and 63.6%, and 64.4% and 58.2%, respectively (p < 0.0001). The corresponding bFFF rate for the three BED groups was 56.1% and 41.4%, 80% and 77.9%, and 91.1% and 82.9% (p < 0.0001). The corresponding bFFF rate for the low-risk patients by dose group was 69.8% and 49.8%, 86% and 85.2%, and 88.1% and 88.3% for the low-, intermediate, and high-dose group, respectively (p <0.0001). The corresponding bFFF rate for the intermediate-risk patients by dose group was 52.9% and 23.1%, 74.1% and 77.7%, and 94.3% and 88.8% for the low-, intermediate-, and high-dose group, respectively (p < 0.0001). The corresponding bFFF rate for high-risk patients by dose group was 19.2% and 41.7%, 61.8% and 53.2%, and 90% and 69.6% for the low-, intermediate-, and high-dose group, respectively (p < 0.0001)., Conclusions: These data suggest that permanent brachytherapy dose prescriptions can be customized to risk status. In low-risk patients, achieving a BED of >or=140 Gy might be adequate for prostate-specific antigen control. However, high-risk disease might require a BED dose of >or=200 Gy.

Purpose: Extraprostatic extension (EPE) of tumor conveys an adverse prognosis in early-stage prostate cancer. Previous studies reported on the linear and radial distance of EPE (EPEr) as measured from the prostate edge. In this study, the correlation of the EPEr from a large whole mount prostatectomy series was determined with respect to the needle biopsy and prostatectomy specimen findings., Methods and Materials: In a 24-month period, 404 patients underwent radical prostatectomy and the specimens were whole mounted. The preoperative records, biopsy findings, and EPEr from these specimens were evaluated., Results: The range of the EPEr distance was 0.0-5.7 mm. A three-category model was used that included 283 patients (70%) with no EPE, 59 (15%) with "near EPE" (range, 0.01-0.59 mm), and 62 (15%) with "far EPE" (>or=0.6 mm). Univariate analysis revealed that patient age and prostate volume did not correlate with EPEr, in contrast to all other factors evaluated. Multivariate analysis identified the preoperative serum prostate-specific antigen, the percentage of cancer in the biopsy cores, and clinical tumor stage as significant. However, the Gleason score was not associated with the EPEr. Greater discrimination was possible in estimating the probability of extension in the "near" category than in the "far" category., Conclusion: EPEr is associated with the preoperative prostate-specific antigen level, percentage of cancer in the biopsy cores, and clinical tumor stage. These data might be useful in planning local therapies for prostate cancer, but additional studies identifying factors associated with EPEr beyond 3-5 mm could have relevance regarding the appropriate radiotherapeutic management strategies.

Purpose: To quantify prostate volume (pvol) changes with transrectal ultrasound (TRUS) immediately after permanent prostate brachytherapy (PPB) and to correlate these changes with postimplant computed tomography (CT) volumetrics. To provide data relevant to evaluating the potential of TRUS-based image fusion for intraoperative dosimetry., Methods and Materials: Between July 2000 and January 2003, 177 patients underwent (125)I PPB monotherapy at our institution, and 165 patients provided research authorization. A total of 136 patients (82%) completed 4 imaging studies: planning TRUS, intraoperative pre- and postimplant TRUS, and CT., Results: Mean planning TRUS pvol was 38.7 +/- 11.7 cc standard deviation (SD), 95% confidence interval (CI) (36.7, 40.7). Mean intraoperative TRUS pvol preimplant was 37.1 +/- 11.7 cc SD, 95% CI (35.1, 39.0), and postimplant was 44.5 +/- 15.1 cc SD, 95% CI (42.0, 47.1). The mean ratio of postimplant:preimplant intraoperative TRUS pvols was 1.2 +/- 0.2 SD, 95% CI (1.18, 1.24), and the difference in mean values was 7.5 cc (p < 0.0001). CT performed within 1 day revealed a mean pvol of 47.9 +/- 15.7 cc SD, 95% CI (45.2, 50.5). The mean volumetric ratio of CT to postimplant TRUS pvol was 1.13 +/- 0.36, 95% CI (1.07-1.19)., Conclusions: Whereas mean preimplant step-section TRUS pvol measurements are similar, postimplant TRUS and CT measurements have greater variability that depend on initial pvol. CT-based pvol measurements determined a mean of 10.6 hours after implant were more likely to be identical to those of immediate postimplant TRUS in prostates >33 cc. These data are relevant for establishing accuracy in image-fusion based approaches being investigated for real-time intraoperative PPB dosimetry.

Purpose: To examine the incidence of seed migration detected on chest X-ray and to identify the predictors associated with its occurrence., Methods and Materials: Between May 1998 and April 2000, 102 patients underwent permanent prostate brachytherapy at our institution and 100 were eligible for the study. Chest X-rays obtained at follow-up were examined for the number and location of seeds. The patient and treatment variables potentially associated with the occurrence and number of seed migrations were analyzed., Results: One or more seeds were identified on the chest X-rays of 55 (55%) of 100 patients. The mean number of intrathoracic seeds in patients with migration was 2.2 (range, 1-10), and the proportion of seeds that migrated to the thorax was 0.98%. The rate of extraprostatic seeds planned was 43.9%, and postimplant CT identified 37.9% in such a location. The number of seeds planned for extraprostatic placement and below the apex were statistically significant (alpha = 0.05) predictors in univariate logistic analysis. Multivariate analysis revealed the planned number of extraprostatic seeds as the only statistically significant predictor (p = 0.04)., Conclusion: Extraprostatic placement of loose seeds is associated with an increased likelihood for, and frequency of, seed migration to the thorax. Nonetheless, the small proportion of implanted seeds that migrated (

Purpose: To develop a real-time electronic portal imaging device (EPID) procedure to identify intraprostatic gold markers and correct daily variations in target position during external beam radiotherapy for prostate cancer., Methods and Materials: Pretherapy electronic portal images (EPIs) were acquired with a small portion of the therapeutic 18-MV dose from an orthogonal pair of treatment fields. The position of the intraprostatic gold markers on the EPIs was aligned with that on the simulation digitally reconstructed radiographs. If the initial three-dimensional target displacement (3DI) exceeded 5 mm or rotations exceeded 3 degrees, the beam was realigned before the remainder of the dose was delivered. Field-only EPIs were then acquired for all fields and offline analysis was performed to determine the final 3D target placement (3DF)., Results: Twenty patients completed protocol-specified treatment, and all markers were identified on 99.6% of the pretherapy EPIs. Overall, 53% of treatment fractions were realigned. The mean 3DI was 5.6 mm in all patients (range 3.7-9.3), and the mean 3DF was 2.8 mm (range 1.6-4.0), which was statistically significant (p < 0.001). Rotational corrections were made on 15% of treatments. Mean treatment duration was 1.4 min greater for protocol patients than for similar patients in whom localization was not performed., Conclusions: Frequent field misalignment occurs when external fiducial marks are used for patient alignment. Misalignments can be readily and rapidly identified and corrected with an EPID-based online correction procedure that integrates commercially available equipment and software.

Purpose: To measure the relative ultrasound backscatter of different seed types as a function of seed orientation and to evaluate the corresponding images of these seeds., Methods and Materials: Three seed types were evaluated: OncoSeed (standard), EchoSeed (corrugated), and RAPID Strand(RS). Ultrasound images for angles of incidence varying from 90 degrees (perpendicular) to 20 degrees at 5MHz and 7.5MHz were produced by raster scanning the seeds in a degassed water bath. Seed images were visually inspected and analyzed using the integrated-optical-density (IOD) method., Results: Corrugated seeds appear as contiguous objects over the range of frequencies and orientations examined, whereas standard seeds appear as contiguous objects from 90 degrees to 80 degrees only. The ranges and means of the backscattered IOD ratio of the seeds from 85 degrees to 20 degrees were: (corrugated vs. standard) 1.48 to 3.72 (2.32 +/- 0.62) for 5 MHz and 1.26 to 3.77 (2.19 +/- 0.84) for 7.5 MHz and (corrugated vs. RS) 1.21 to 9.53 (2.98 +/- 2.48) for 5 MHz and 1.008 to 10.86 (2.79 +/- 3.08) for 7.5 MHz. Backscattered signal increase ranged from 1.66 dB to 20.7 dB for the corrugated seed as compared to the other seeds., Conclusions: Corrugated seeds produce greater backscatter signal and a more readily identifiable seed image over a large range of seed orientation as compared with standard brachytherapy seeds.

Purpose: To quantitatively compare a scanning liquid ion chamber electronic portal imaging device (SLIC-EPID) and an amorphous silicon flat panel (aSi) EPID with portal film in clinical applications using measures of landmark visibility and treatment review accuracy., Methods and Materials: Six radiation oncologists viewed 39 electronic portal images (EPIs) from the SLIC-EPID, 36 EPIs from the aSi-EPID, and portal films of each of these treatment fields. The physicians rated the clarity of anatomic landmarks in the portal images, and the scores were compared between EPID and film. Nine hundred portal image reviews were performed. EPID and film portal images were acquired with known setup errors in either phantom or cadaver treatments. Physicians identified the errors visually in portal films and with computerized analysis for EPID., Results: There were no statistically significant (p < 0.05) differences between film and SLIC-EPID in ratings of landmark clarity. Eleven of 12 landmarks were more visible in aSi-EPID than in film. Translational setup errors were identified with an average accuracy of 2.5 mm in film, compared to 1.5 mm with SLIC-EPID and 1.3 mm with aSi-EPID., Conclusions: Both EPIDs are clinically viable replacements for film, but aSi-EPID represents a significant advancement in image quality over film.