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• Salvage brachytherapy is safe and effective for radiorecurrent prostate cancer. • Thirty international experts completed a Delphi consensus study. • Consensus was achieved in 18 of 30 statements. • No single preferred dose, fractionation, or technique was found. Local recurrences after previous radiotherapy (RT) are increasingly being identified in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option. We sought to generate international consensus statements on the use and preferred technical considerations for salvage prostate BT. International experts in salvage prostate BT were invited (n = 34) to participate. A three-round modified Delphi technique was utilized, with questions focused on patient- and cancer-specific criteria, type and technique of BT, and follow-up. An a priori threshold for consensus of ≥ 75% was set, with a majority opinion being ≥ 50%. Thirty international experts agreed to participate. Consensus was achieved for 56% (18/32) of statements. Consensus was achieved in several areas of patient selection: 1) A minimum of 2–3 years from initial RT to salvage BT; 2) MRI and PSMA PET should be obtained; and 3) Both targeted and systematic biopsies should be performed. Several areas did not reach consensus: 1) Maximum T stage/PSA at time of salvage; 2) Utilization/duration of ADT; 3) Appropriateness of combining local salvage with SABR for oligometastatic disease and 4) Repeating a second course of salvage BT. A majority opinion preferred High Dose-Rate salvage BT, and indicated that both focal and whole gland techniques could be appropriate. There was no single preferred dose/fractionation. Areas of consensus within our Delphi study may serve as practical advice for salvage prostate BT. Future research in salvage BT should address areas of controversy identified in our study. [ABSTRACT FROM AUTHOR]

Purpose To report the long-term control and toxicity outcomes of patients with clinically localized prostate cancer, who underwent low-dose-rate prostate brachytherapy with magnetic resonance spectroscopic image (MRSI)–directed dose escalation to intraprostatic regions. Methods and Materials Forty-seven consecutive patients between May 2000 and December 2003 were analyzed retrospectively. Each patient underwent a preprocedural MRSI, and MRS-positive voxels suspicious for malignancy were identified. Intraoperative planning was used to determine the optimal seed distribution to deliver a standard prescription dose to the entire prostate, while escalating the dose to MRS-positive voxels to 150% of prescription. Each patient underwent transperineal implantation of radioactive seeds followed by same-day CT for postimplant dosimetry. Results The median prostate D 90 (minimum dose received by 90% of the prostate) was 125.7% (interquartile range [IQR], 110.3–136.5%) of prescription. The median value for the MRS-positive mean dose was 229.9% (IQR, 200.0–251.9%). Median urethra D 30 and rectal D 30 values were 142.2% (137.5–168.2%) and 56.1% (40.1–63.4%), respectively. Median followup was 86.4 months (IQR, 49.8–117.6). The 10-year actuarial prostate-specific antigen relapse–free survival was 98% (95% confidence interval, 93–100%). Five patients (11%) experienced late Grade 3 urinary toxicity (e.g., urethral stricture), which improved after operative intervention. Four of these patients had dose-escalated voxels less than 1.0 cm from the urethra. Conclusions Low-dose-rate brachytherapy with MRSI-directed dose escalation to suspicious intraprostatic regions exhibits excellent long-term biochemical control. Patients with dose-escalated voxels close to the urethra were at higher risk of late urinary stricture. [ABSTRACT FROM AUTHOR]

To estimate the time investment and planning benefit of acquiring treatment planning MRI scans for each insertion for tandem and ring (T&R) cases. Fourteen (14) consecutive cervical cancer patients who underwent intracavitary HDR brachytherapy with T&R applicator were retrospectively analyzed. All patients received 28Gy in 4 fractions delivered in 2 insertions (Ins1 and Ins2), with 2 fractions per insertion, after completion of EBRT. All insertions were performed under general anesthesia with intraoperative CT and MRI guidance. Target (Cx) and normal tissues were contoured on each MRI scan at the time of the procedure. Four patients who did not have both insertions using MRI planning were excluded. Image registration of Ins2 to Ins1 was retrospectively performed in Eclipse (Varian Medical Systems, Palo Alto, CA) based on applicator position. Target contour from Ins2 (Cx2) was copied to the Ins1 structure set (Cx2reg) using this registration. The following metrics were recorded: volume of Cx1, Cx2, and dice similarity coefficient of the two [DSC = 2*(volCx1+volCx2)/(overlap between Cx1 and Cx2reg)] (0 indicates no overlap between the contours; 1 indicates perfect overlap). Target D90 using MRI for each insertion (D90 Cx1 on plan of Ins1 + D90 Cx2 on plan of Ins2) and using only Ins1 MRI (D90 Cx1 on plan of Ins1 + D90 Cx2reg on plan of Ins1). One patient had a replan for the second fraction of the first insertion was therefore excluded from the D90 analysis. Additional time required for MRI-based planning was calculated using the timestamps of the last in-room CT and of the T2 MRI. Cx1 and Cx2 volumes [median, interquartile range (IQR)] were 26.0 cm3 (IQR 11.3 cm3) and 22.9 cm3(IQR 16.7 cm3). DSC was 0.73 (IQR 0.05). Target D90 (as % of prescription dose) using MRI for each insertion vs. using only Ins1 MRI information for Ins2 was 109.6% (IQR 4.8%) vs. 110.1% (IQR 7.5%). Additional time for MRI-based planning was 38.8 minutes (IQR 6.3 minutes). The addition of an MRI for Ins2 added only modest alterations in the target volume and D90, however, did add approximately 40 minutes of added time under anesthesia. The projected target coverage if Cx1 was used in insertion 2 instead of Cx2 would be sufficient and could be more efficient in terms of scan and, potentially, contouring time. This study supports the hypothesis that the time commitment required for MRI acquisition for Ins2 may not be justified by a planning advantage. Limiting factors of this study: contouring and fusion uncertainties; our methods did not consider changes in organs-at-risk between insertions; limited number of patients. [ABSTRACT FROM AUTHOR]

To develop ABCD, an HDR brachytherapy prostate optimizer with mixed bound and unbound functionalities and evaluate its performance. ABCD utilized linear optimization with iterative constraint refinement. ABCD aims to maximize (unbounded) dose to voxels within the prostate while achieving bounded constraints on organs-at-risk (urethra and rectum D max). 20 HDR prostate plans were retrospectively optimized using ABCD and with a commercial optimizer (VEGO, Varian Medical Systems) with constraints of rectum D max < 17.1Gy and urethra D max < 22.8Gy. These constraints were chosen to mimic potential dose constraints for monotherapy prostate HDR patients. For VEGO, a prostate D 90 objective iteratively increased by the user until rectum and urethra limits were reached was used. Prostate V 19Gy , D 90 , D 98 and D min were reported. Statistical comparison was performed using a paired T-test (p < 0.05 for significance). ABCD vs VEGO prostate metrics were (median with range): V 19Gy = 98.3 (85.8 - 100) % vs 95.9 (87.5 - 99.6, p = 0.008 < 0.05) %; D 90 = 20.8 (18.3 - 22.3) Gy vs 21.0 (18.2 - 23.2, p = 0.1 > 0.05) Gy; D 98 = 19.1 (16.6 - 21.1) Gy vs 17.7 (14.1 - 20.0, p = 8 × 10−5 < 0.05) Gy; D min = 16.5 (15.2 - 18.7) Gy vs 12.5 (10.5 - 16.4, p = 4 × 10−10 < 0.05) Gy. ABCD respected rectum and urethral constraints; commercial optimizer plans had to be rescaled to meet the constraints. Dose escalation to the prostate was possible with ABCD without iterative optimization by the user. While ABCD did not specifically aim to escalate D 90 dose, it achieved similar results compared to specific D 90 escalation strategies with a commercial optimizer while at the same time permitting statistically significant dose escalation of all other metrics investigated. Further work is ongoing to investigate the utility in DIL boosts, as well as integrating needle suggestions within the optimization step to provide superior dose coverage. [ABSTRACT FROM AUTHOR]

External beam radiotherapy (EBRT) followed by brachytherapy is standard of care in the management of cervical cancer. Whether early imaging response can predict longer term outcome is unclear. In this study, we investigated the role of interim pelvic magnetic resonance imaging (MRI), done prior to brachytherapy (BT) in predicting local tumor control. We identified 87 consecutive patients who underwent definitive EBRT followed by BT for FIGO IIB-IVA cervical cancer at our institution between 2012 and 2020. The median age was 54 years (range, 23-81 years). Most patients had squamous cell carcinoma (77%), advanced stage disease (57.5% stage IIIA and higher, 51.7% nodal disease) and received concurrent cisplatin (98.8%). All patients had an MRI at baseline (MRb) and prior to brachytherapy boost (MRpb). The median time from completion of EBRT to MRpb was 3 days (IQR: -14d to +1d). EBRT included the regional LNs and primary site (median dose 45Gy, range 45-54Gy). Node positive patients also received a boost (median 5.4Gy, range 5.4-14.4Gy) Fifty-seven patients (65.5%) had intracavitary brachytherapy (median dose 28Gy, range 2-28Gy) and 30 (34.5%) had an interstitial BT (median dose 24Gy, range 20-28Gy). Adjuvant chemotherapy was delivered in 24 cases (27.6%). Patients were followed post-treatment with pelvic exams/cytology every 3 months for years 1-2 and every 6 months thereafter. PET/CT and a pelvic MRI were done 3 months posttreatment and as clinically indicated thereafter. Median follow up time was 35.5 months (range 3.8-114.2 months). Response to EBRT on MRpb was defined as residual disease > 2 cm, residual disease ≤ 2 cm and no measurable disease (complete response, CR). Local failure was defined as recurrent or persistent tumor in the cervix following all treatment and confirmed pathologically. Chi square test was used to compare categorical data. Overall, 19.5% of patients had a CR, 22.9% had residual disease ≤2cm and 57.5% had residual disease >2cm noted on MRpb. No patients who achieved a CR on MRpb had local recurrence. Of patients with residual disease ≤2 cm on MRpb, 19/20 patients (95%) ultimately achieved CR on subsequent imaging (median time to CR 3.1 months; range, 2.7-8.6 months), none of whom had a local failure. Of patients with residual disease >2 cm on MRpb, 40/50 (80%) ultimately achieved CR on subsequent imaging (median time to CR, 3.6 months; range, 2.1 - 18.6 months). Of the 10 patients with residual disease >2 cm on MRpb who did not achieve a CR, 4 had local failure, 1 had local and distant failure and 5 had regional or distant failure only. Overall, 6/50 (15%) patients with persistent disease >2 cm had local failure, compared with none of the patients who had more profound responses. Local disease response on MRpb did not predict regional or distant failure (p=0.35). Interim pre-BT MRI seems promising in predicting local tumor control in the definitive management of cervical cancer and could be instrumental in dose intensification/de-escalation efforts. Further investigation of various MRI sequences in predicting response and long-term control is ongoing. [ABSTRACT FROM AUTHOR]

Purpose To investigate the association between statin use and prostate cancer outcomes in intermediate- and high-risk patients treated with brachytherapy for prostate cancer. Methods and Materials Between 1998 and 2010, 754 men with National Comprehensive Cancer Network intermediate- ( n = 627) and high-risk ( n = 127) prostate cancer were treated with prostate brachytherapy at our institution. Patients received either low-dose-rate or high-dose-rate brachytherapy as monotherapy or in combination with supplemental external beam radiotherapy. Two hundred eighty-five patients (37.8%) also received androgen-deprivation therapy. Two hundred seventy-three men (36.2%) were identified as taking statin medication before initiating radiation therapy. Prostate-specific antigen relapse–free survival (PSA-RFS), distant metastasis–free survival (DMFS), and overall survival were compared using log-rank tests. Associations of patient and treatment characteristics with outcomes were analyzed with univariate and multivariate regression. The median followup was 48 months. Results The 8-year PSA-RFS for intermediate-risk, high-risk, and all patients was 92.2%, 64.1%, and 87.7%, respectively. The 8-year DMFS was 97.1%, 82.9%, and 94.9%, respectively. The 8-year overall survival for the entire cohort was 86.6%. There were no significant differences between statin users and nonusers when stratified by risk group, nor when analyzed as a full cohort. On multivariate analysis, Gleason score 4 + 3 = 7 and >7 were significantly associated with worse PSA-RFS ( p ≤ 0.003 and <0.001, respectively). Gleason score > 7 ( p = 0.008) and the use of neoadjuvant androgen-deprivation therapy ( p = 0.03) was associated with worse DMFS. Statin use did not significantly impact PSA-RFS or DMFS. Conclusions Pretreatment statin use is not associated with improved outcomes in intermediate- and high-risk patients undergoing prostate brachytherapy-based regimens for prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose To compare the potential benefits of continuous monitoring of prostate position and intervention (CMI) using 2-mm displacement thresholds during stereotactic body radiation therapy (SBRT) treatment to those of a conventional image-guided procedure involving single localization prior to treatment. Methods and Materials Eighty-nine patients accrued to a prostate SBRT dose escalation protocol were implanted with radiofrequency transponder beacons. The planning target volume (PTV) margin was 5 mm in all directions, except for 3 mm in the posterior direction. The prostate was kept within 2 mm of its planned position by the therapists halting dose delivery and, if necessary, correcting the couch position. We computed the number, type, and time required for interventions and where the prostate would have been during dose delivery had there been, instead, a single image-guided setup procedure prior to each treatment. Distributions of prostate displacements were computed as a function of time. Results After the initial setup, 1.7 interventions per fraction were required, with a concomitant increase in time for dose delivery of approximately 65 seconds. Small systematic drifts in prostate position in the posterior and inferior directions were observed in the study patients. Without CMI, intrafractional motion would have resulted in approximately 10% of patients having a delivered dose that did not meet our clinical coverage requirement, that is, a PTV D95 of >90%. The posterior PTV margin required for 95% of the dose to be delivered with the target positioned within the PTV was computed as a function of time. The margin necessary was found to increase by 2 mm every 5 minutes, starting from the time of the imaging procedure. Conclusions CMI using a tight 2-mm displacement threshold was not only feasible but was found to deliver superior PTV coverage compared with the conventional image-guided procedure in the SBRT setting. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine the associations of quantitative parameters derived from multiphase contrast-enhanced magnetic resonance imaging (CE-MRI), diffusion-weighted (DW) MRI and 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT) with clinico-histopathological prognostic factors, disease-free survival (DFS) and overall survival (OS) in patients with cervical cancer. Methods and materials: Our institutional review board approved this retrospective study of 49 patients (median age, 45 years) with histopathologically proven IB-IVB International Federation of Gynecology and Obstetrics (FIGO) cervical cancer who underwent pre-treatment pelvic MRI and whole-body 18F-FDG PET/CT between February 2009 and May 2012. Maximum diameter (maxTD), percentage enhancement (PE) and mean apparent diffusion coefficient (ADCmean) of the primary tumor were measured on MRI. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG) were measured on 18F-FDG PET/CT. Correlations between imaging metrics and clinico-histopathological parameters including revised 2009 FIGO stage, tumor histology, grade and lymph node (LN) metastasis at diagnosis were evaluated using the Wilcoxon rank sum test. Cox modeling was used to determine associations with DFS and OS. Results: Median follow-up was 17 months. 41 patients (83.6%) were alive. 8 patients (16.3%) died of disease. Progression/recurrence occurred in 17 patients (34.6%). Significant differences were observed in ADCmean, SUVmax, MTV and TLG according to FIGO stage (p <0.001–0.025). There were significant correlations between ADCmean, MTV, TLG and LN metastasis (p =0.017–0.032). SUVmax was not associated with LN metastasis. FIGO stage (p =0.017/0.033), LN metastases (p =0.001/0.020), ADCmean (p =0.007/0.020) and MTV (p =0.014/0.026) were adverse predictors of both DFS/OS. maxTD (p =0.005) and TLG (p =0.024) were adverse predictors of DFS. PE and SUVmax did not correlate with DFS or OS (p =0.18–0.72). Conclusions: Quantitative parameters derived from pre-treatment DW-MRI (ADCmean) and from 18F-FDG PET/CT (MTV and TLG) were associated with high-risk features and may serve as prognostic biomarkers of survival in patients with cervical cancer. [Copyright &y& Elsevier]

Purpose: To determine the potential association between genitourinary (GU) toxicity and planning dose–volume parameters for GU pelvic structures after high-dose intensity modulated radiation therapy in localized prostate cancer patients. Methods and Materials: A total of 268 patients who underwent intensity modulated radiation therapy to a prescribed dose of 86.4 Gy in 48 fractions during June 2004-December 2008 were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Dose–volume histograms of the whole bladder, bladder wall, urethra, and bladder trigone were analyzed. The primary endpoint for GU toxicity was an IPSS sum increase ≥10 points over baseline. Univariate and multivariate analyses were done by the Kaplan-Meier method and Cox proportional hazard models, respectively. Results: Median follow-up was 5 years (range, 3-7.7 years). Thirty-nine patients experienced an IPSS sum increase ≥10 during follow-up; 84% remained event free at 5 years. After univariate analysis, lower baseline IPSS sum (P=.006), the V90 of the trigone (P=.006), and the maximal dose to the trigone (P=.003) were significantly associated with an IPSS sum increase ≥10. After multivariate analysis, lower baseline IPSS sum (P=.009) and increased maximal dose to the trigone (P=.005) remained significantly associated. Seventy-two patients had both a lower baseline IPSS sum and a higher maximal dose to the trigone and were defined as high risk, and 68 patients had both a higher baseline IPSS sum and a lower maximal dose to the trigone and were defined as low risk for development of an IPSS sum increase ≥10. Twenty-one of 72 high-risk patients (29%) and 5 of 68 low-risk patients (7%) experienced an IPSS sum increase ≥10 (P=.001; odds ratio 5.19). Conclusions: The application of hot spots to the bladder trigone was significantly associated with relevant changes in IPSS during follow-up. Reduction of radiation dose to the lower bladder and specifically the bladder trigone seems to be associated with a reduction in late GU toxicity. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Stereotactic body radiotherapy (SBRT) is being used with increasing frequency as definitive treatment of early stage prostate cancer. Much of the justification for its adoption was derived from earlier clinical results using high-dose-rate (HDR) brachytherapy. We determine whether HDR's dosimetry can be achieved by virtual SBRT. Methods and Materials: Patients with intermediate-risk prostate cancer on a prospective trial evaluating the efficacy of HDR monotherapy treated to dose of 9.5Gy×4 fractions were used for this study. A total of 5 patients were used in this analysis. Virtual SBRT plans were developed to reproduce the planning target volume (PTV) HDR dose distributions. Both normal tissue– and PTV-prioritized plans were generated. Results: From the normal tissue–prioritized plan, HDR and virtual SBRT achieved similar PTV V 100 (93.8% vs. 93.1%, p =0.20) and V 150 (40.3% vs. 42.9%, p =0.69) coverage. However, the PTV V 200 was not attainable with SBRT (15.2% vs. 0.0%, p <0.001). The rectal D max was significantly lower with HDR (94.2% vs. 99.42%, p =0.05). The rectal D 2 cc was also lower (60.8% vs. 71.1%, p =0.07). Difference in D 1 cc urethral dose was not significantly different (87.7% vs. 75.2%, p =0.33). Comparing the PTV-prioritized plans, the rectal D max (94.2% vs. 111.1%, p =0.05) and mean dose (27.1% vs. 33.3%, p =0.03) were significantly higher using SBRT, and the rectal D 2 cc was higher using SBRT (60.8% vs. 81.8%, p =0.07). Conclusions: HDR achieves significantly higher intraprostatic doses while achieving a lower maximum rectal dose compared with our virtual SBRT treatment planning. Future studies should compare clinical outcomes and toxicity between these modalities. [Copyright &y& Elsevier]

Purpose: To determine whether the response to neoadjuvant androgen deprivation therapy (ADT) defined by a decline in prostate-specific antigen (PSA) to nadir values is associated with improved survival outcomes after external beam radiation therapy (EBRT) for prostate cancer. Methods and Materials: One thousand forty-five patients with localized prostate cancer were treated with definitive EBRT in conjunction with neoadjuvant and concurrent ADT. A 6-month course of ADT was used (3 months during the neoadjuvant phase and 2 to 3 months concurrently with EBRT). The median EBRT prescription dose was 81 Gy using a conformal-based technique. The median follow-up time was 8.5 years. Results: The 10-year PSA relapse-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 74.3%, compared with 57.7% for patients with higher PSA nadir values (P<.001). The 10-year distant metastases-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 86.1%, compared with 78.6% for patients with higher PSA nadir values (P=.004). In a competing-risk analysis, prostate cancer-related deaths were also significantly reduced among patients with pre-radiation therapy PSA nadirs of <0.3 ng/mL compared with higher values (7.8% compared with 13.7%; P=.009). Multivariable analysis demonstrated that the pre-EBRT PSA nadir value was a significant predictor of long-term biochemical tumor control, distant metastases-free survival, and cause-specific survival outcomes. Conclusions: Pre-radiation therapy nadir PSA values of ≤0.3 ng/mL after neoadjuvant ADT were associated with improved long-term biochemical tumor control, reduction in distant metastases, and prostate cancer-related death. Patients with higher nadir values may require alternative adjuvant therapies to improve outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the effect of primary Gleason (pG) grade among a large cohort of Gleason 7 prostate cancer patients treated with external beam radiation therapy (EBRT). Methods and Materials: From May 1989 to January 2011, 1190 Gleason 7 patients with localized prostate cancer were treated with EBRT at a single institution. Of these patients, 613 had a Gleason 7 with a minimum of a sextant biopsy with nonfragmented cores and full biopsy core details available, including number of cores of cancer involved, percentage individual core involvement, location of disease, bilaterality, and presence of perineural invasion. Median follow-up was 6 years (range, 1-16 years). The prognostic implication for the following outcomes was analyzed: biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific mortality (PCSM). Results: The 8-year bRFS rate for pG3 versus pG4 was 77.6% versus 61.3% (P<.0001), DMFS was 96.8% versus 84.3% (P<.0001), and PCSM was 3.7% versus 8.1% (P=.002). On multivariate analysis, pG4 predicted for significantly worse outcome in all parameters. Location of disease (apex, base, mid-gland), perineural involvement, maximum individual core involvement, and the number of Gleason 3+3, 3+4, or 4+3 cores did not predict for distant metastases. Conclusions: Primary Gleason grade 4 independently predicts for worse bRFS, DMFS, and PCSM among Gleason 7 patients. Using complete core information can allow clinicians to utilize pG grade as a prognostic factor, despite not having the full pathologic details from a prostatectomy specimen. Future staging and risk grouping should investigate the incorporation of primary Gleason grade when complete biopsy core information is used. [Copyright &y& Elsevier]

Abstract: Objective: According to national surveys, the use of intensity-modulated radiation therapy (IMRT) in gynecologic cancers is on the rise, yet there is still some reluctance to adopt adjuvant IMRT as standard practice. The purpose of this study is to report a single-institution experience using postoperative pelvic IMRT with or without chemotherapy in high-risk endometrial cancer. Methods: From 11/2004 to 12/2009, 46 patients underwent hysterectomy/bilateral salpingo-oophorectomy for stage I-III (22% stage I/II and 78% stage III) endometrial cancer. Median IMRT dose was 50.4Gy. Adjuvant chemotherapy was given to 30 (65%) patients. Results: With a median follow-up of 52months, 4 patients recurred: 1 vaginal plus lung metastasis, 2 isolated para-aortic recurrences, and 1 lungs and liver metastasis. Five-year relapse rate was 9% (95% CI, 0–13.6%). Five-year disease-free survival (DFS) was 88% (95% CI, 77–98%) and overall survival (OS) was 97% (95% CI, 90–100%). There were 2 patients with non-hematological grade 3 toxicity: 1 (2%) acute and 1 (2%) chronic gastrointestinal toxicity. In patients treated with IMRT and chemotherapy (n =30), 5 had grade 3 leukopenia, 8 grade 2 anemia, and 2 grade 2 thrombocytopenia. Conclusions: Oncologic outcomes with postoperative IMRT were very good, with DFS and OS rates of >88% at median follow-up of 52months, despite a preponderance (78%) of stage III disease. Toxicity was minimal even in the setting of an aggressive trimodality (65% of patients) approach. Data from this study and emerging data from RTOG trial 0418 demonstrate the advantages of IMRT in high-risk endometrial cancer. [Copyright &y& Elsevier]

Purpose: To report long-term survival and toxicity outcomes with the use of high-dose intensity modulated radiation therapy (IMRT) to 86.4 Gy for patients with localized prostate cancer. Methods and Materials: Between August 1997 and December 2008, 1002 patients were treated to a dose of 86.4 Gy using a 5-7 field IMRT technique. Patients were stratified by prognostic risk group based on National Comprehensive Cancer Network risk classification criteria. A total of 587 patients (59%) were treated with neoadjuvant and concurrent androgen deprivation therapy. The median follow-up for the entire cohort was 5.5 years (range, 1-14 years). Results: For low-, intermediate-, and high-risk groups, 7-year biochemical relapse-free survival outcomes were 98.8%, 85.6%, and 67.9%, respectively (P<.001), and distant metastasis-free survival rates were 99.4%, 94.1%, and 82.0% (P<.001), respectively. On multivariate analysis, T stage (P<.001), Gleason score (P<.001), and >50% of initial biopsy positive core (P=.001) were predictive for distant mestastases. No prostate cancer-related deaths were observed in the low-risk group. The 7-year prostate cancer-specific mortality (PCSM) rates, using competing risk analysis for intermediate- and high-risk groups, were 3.3% and 8.1%, respectively (P=.008). On multivariate analysis, Gleason score (P=.004), percentage of biopsy core positivity (P=.003), and T-stage (P=.033) were predictive for PCSM. Actuarial 7-year grade 2 or higher late gastrointestinal and genitourinary toxicities were 4.4% and 21.1%, respectively. Late grade 3 gastrointestinal and genitourinary toxicity was experienced by 7 patients (0.7%) and 22 patients (2.2%), respectively. Of the 427 men with full potency at baseline, 317 men (74%) retained sexual function at time of last follow-up. Conclusions: This study represents the largest cohort of patients treated with high-dose radiation to 86.4 Gy, using IMRT for localized prostate cancer, with the longest follow-up to date. Our findings indicate that this treatment results in excellent clinical outcomes with acceptable toxicity. [Copyright &y& Elsevier]

Abstract: Objective: According to national surveys, the use of intensity-modulated radiation therapy (IMRT) in gynecologic cancers is on the rise, yet there is still some reluctance to adopt adjuvant IMRT as standard practice. The purpose of this study is to report a single-institution experience using postoperative pelvic IMRT with concurrent chemotherapy in intermediate- and high-risk early stage cervical cancer. Methods: From 1/2004 to 12/2009, 34 patients underwent radical hysterectomy and pelvic lymph node dissection (28 median nodes were removed) for early stage cervical cancer. Median dose of postoperative pelvic IMRT was 50.4Gy (range, 45–50.4). All patients received concurrent cisplatin. Results: With a median follow-up of 44months, 3 patients have recurred; 1 vaginal recurrence, 1 regional and distant, and 1 distant. The 3- and 5-year disease-free survival (DFS) was 91.2% (95% CI, 81.4–100%) and overall survival (OS) was 91.1% (95% CI, 81.3–100%). All failures and all deaths were in the high-risk group (n=3/26). There was 32.3% G3–4 hematologic toxicity, 2.9% acute G3 gastrointestinal toxicity, and no acute G3 or higher genitourinary toxicity. There were no chronic G3 or higher toxicities. Conclusions: Oncologic outcomes with postoperative IMRT were very good, with DFS and OS rates of >90% at median follow-up of 44months, despite a preponderance (76.5%) of high-risk features. Toxicity was minimal even in the setting of an aggressive trimodality approach. Data from this study and emerging data from the Phase II RTOG study (0418) demonstrate the advantages of postoperative IMRT in early stage cervical cancer. [Copyright &y& Elsevier]

Abstract: Purpose: To report prostate-specific antigen (PSA) relapse-free survival and treatment-related toxicity outcomes after combining high-dose-rate (HDR) brachytherapy with external beam radiotherapy (EBRT) for patients with clinically localized prostate cancer. Methods and Materials: Between 1998 and 2009, 229 patients were treated with HDR brachytherapy followed 3 weeks later by supplemental EBRT. The HDR brachytherapy boost consisted of three fractions of 192Ir (5.5–7.5Gy per fraction), and EBRT consisted of intensity-modulated radiotherapy delivering an additional 45.0–50.4Gy directed to the prostate gland and seminal vesicles. Median follow-up was 61 months. Results: Seven-year PSA relapse-free survival for low-, intermediate-, and high-risk patients were 95%, 90%, and 57%, respectively (p <0.001). Among high-risk patients treated with biological equivalent doses in excess of 190Gy, 7-year PSA relapse-free survival was 81%. In multivariate analysis, Gleason scores of ≥8 predicted for increased risk of biochemical failure, whereas the use of short-term neoadjuvant androgen deprivation therapy did not influence tumor-control outcomes even among intermediate- or high-risk patients. Seven-year incidence of distant metastases for low-, intermediate-, and high-risk patients were 5%, 3%, and 17%, respectively. Seven-year incidence of late Grade 2 and 3 genitourinary toxicities were 22.1% and 4.9%, respectively and the 7-year incidence of Grade 2 and 3 gastrointestinal toxicities were 1% and 0.4%, respectively. Conclusion: HDR prostate brachytherapy in conjunction with supplemental EBRT results in excellent biochemical relapse-free survival rates with a low incidence of severe late genitourinary or gastrointestinal toxicities. The use of short-term neoadjuvant androgen deprivation did not influence long-term biochemical tumor control in this cohort. [Copyright &y& Elsevier]

Abstract: Objective: The purpose of this study is to report our single-institution experience with concurrent adjuvant intravaginal radiation (IVRT) and carboplatin/paclitaxel chemotherapy for early stage uterine papillary serous carcinoma (UPSC). Methods: From 10/2000 to 12/2009, 41 women with stage I–II UPSC underwent surgery followed by IVRT (median dose of 21Gy in 3 fractions) and concurrent carboplatin (AUC=5–6) and paclitaxel (175mg/m2) for six planned cycles. IVRT was administered on non-chemotherapy weeks. The Kaplan–Meier method was used to estimate survival, and the log-rank test was used for comparisons. Results: Median patient age was 67years (51–80years). Surgery included hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, omental biopsy, and pelvic and paraaortic lymph node sampling. FIGO 2009 stage was IA in 73%, IB in 10%, and II in 17%. Histology was pure serous in 71% of cases. Thirty-five patients (85%) completed all planned treatment. With a median follow-up time of 58months, the 5-year disease-free (DFS) and overall survival (OS) rates were 85% (95%CI, 73–96%) and 90% (95%CI, 80–100%). The 5-year pelvic, para-aortic, and distant recurrence rates were 9%, 5%, and 10%, respectively. There were no vaginal recurrences. Of the 4 pelvic recurrences, 2 were isolated and were successfully salvaged. Patients with stage II disease had lower DFS (71% vs. 88%; p=0.017) and OS (71% vs. 93%; p=0.001) than patients with stage I disease. Conclusions: Concurrent adjuvant carboplatin/paclitaxel chemotherapy and IVRT provide excellent outcomes for early stage UPSC. Whether this regimen is superior to pelvic radiation will require confirmation from the ongoing randomized trial. [Copyright &y& Elsevier]

Purpose: To investigate the utility of endorectal coil magenetic resonance imaging (eMRI) in predicting biochemical relapse in prostate cancer patients treated with combination brachytherapy and external-beam radiotherapy. Methods and Materials: Between 2000 and 2008, 279 men with intermediate- or high-risk prostate cancer underwent eMRI of their prostate before receiving brachytherapy and supplemental intensity-modulated radiotherapy. Endorectal coil MRI was performed before treatment and retrospectively reviewed by two radiologists experienced in genitourinary MRI. Image-based variables, including tumor diameter, location, number of sextants involved, and the presence of extracapsular extension (ECE), were incorporated with other established clinical variables to predict biochemical control outcomes. The median follow-up was 49 months (range, 1–13 years). Results: The 5-year biochemical relapse-free survival for the cohort was 92%. Clinical findings predicting recurrence on univariate analysis included Gleason score (hazard ratio [HR] 3.6, p = 0.001), PSA (HR 1.04, p = 0.005), and National Comprehensive Cancer Network risk group (HR 4.1, p = 0.002). Clinical T stage and the use of androgen deprivation therapy were not correlated with biochemical failure. Imaging findings on univariate analysis associated with relapse included ECE on MRI (HR 3.79, p = 0.003), tumor size (HR 2.58, p = 0.04), and T stage (HR 1.71, p = 0.004). On multivariate analysis incorporating both clinical and imaging findings, only ECE on MRI and Gleason score were independent predictors of recurrence. Conclusions: Pretreatment eMRI findings predict for biochemical recurrence in intermediate- and high-risk prostate cancer patients treated with combination brachytherapy and external-beam radiotherapy. Gleason score and the presence of ECE on MRI were the only significant predictors of biochemical relapse in this group of patients. [Copyright &y& Elsevier]

Purpose: To review the impact of high–dose radiotherapy (RT) in the postprostatectomy salvage setting on long-term biochemical control and distant metastases–free survival, and to identify clinical and pathologic predictors of outcomes. Methods and Materials: During 1988–2007, 285 consecutive patients were treated with salvage RT (SRT) after radical prostatectomy. All patients were treated with either three-dimensional conformal RT or intensity-modulated RT. Two hundred seventy patients (95%) were treated to a dose ≥66 Gy, of whom 205 (72%) received doses ≥70 Gy. Eighty-seven patients (31%) received androgen-deprivation therapy as a component of their salvage treatment. All clinical and pathologic records were reviewed to identify treatment risk factors and response. Results: The median follow-up time after SRT was 60 months. Seven-year actuarial prostate-specific antigen (PSA) relapse-free survival and distant metastases–free survival were 37% and 77%, respectively. Independent predictors of biochemical recurrence were vascular invasion (p < 0.01), negative surgical margins (p < 0.01), presalvage PSA level >0.4 ng/mL (p < 0.01), androgen-deprivation therapy (p = 0.03), Gleason score ≥7 (p = 0.02), and seminal vesicle involvement (p = 0.05). Salvage RT dose ≥70 Gy was not associated with improvement in biochemical control. A doubling time <3 months was the only independent predictor of metastatic disease (p < 0.01). There was a trend suggesting benefit of SRT dose ≥70 Gy in preventing clinical local failure in patients with radiographically visible local disease at time of SRT (7 years: 90% vs. 79.1%, p = 0.07). Conclusion: Salvage RT provides effective long-term biochemical control and freedom from metastasis in selected patients presenting with detectable PSA after prostatectomy. Androgen-deprivation therapy was associated with improvement in biochemical progression-free survival. Clinical local failures were rare but occurred most commonly in patients with greater burden of disease at time of SRT as reflected by either radiographic imaging or a greater PSA level. Salvage radiation doses ≥70 Gy may ultimately be most beneficial in these patients, but this needs to be further studied. [Copyright &y& Elsevier]

Background: Ultrahypofractionated stereotactic body radiation therapy (SBRT) has become a standard treatment intervention for localized prostate cancer., Objective: To report final long-term tumor control outcomes and late gastrointestinal (GI) and genitourinary (GU) toxicities from a single-center phase 1 dose escalation study using SBRT for patients with low- or intermediate-risk prostate cancer., Design, Setting and Participants: Between 2009 and 2012, 136 patients were enrolled and treated. The initial dose level was 32.5 Gy in five fractions. Doses were then sequentially escalated to 35 Gy, 37.5 Gy, and 40 Gy in five fractions delivered every other day., Outcome Measurements and Statistical Analysis: The primary endpoint was late treatment-related toxicity. Secondary endpoints included prostate-specific antigen (PSA) failure., Results and Limitations: The median follow-up was 10.5 yr for the 32.5-Gy group, 9.9 yr for the 35-Gy group, 8.2 yr for the 37.5-Gy group, and 7.3 yr for the 40-Gy group. The 8-yr cumulative incidence of PSA failure was 26% for 32.5 Gy, 15% for 35 Gy, 3.4% for 37.5 Gy, and 6.6% for 40 Gy. Higher radiation dose (37.5-40 Gy) and favorable intermediate risk (vs unfavorable intermediate risk) were associated with better PSA recurrence rates (p = 0.011 and 0.002, respectively). The 8-yr actuarial probability rates for survival free from late grade ≥2 toxicity were 94% for GI toxicity and 86% for GU toxicity. No grade 4 events were recorded. Higher dose levels were not associated with higher rates of late grade ≥2 GI (p = 0.2) or GU (p > 0.9) toxicity., Conclusions: SBRT doses ranging from 32.5 to 40 Gy were associated with low incidence of moderate or severe toxicities. Higher doses resulted in superior disease control outcomes 8 yr after treatment., Patient Summary: We investigated the association between the radiotherapy dose used and the rate of control of prostate cancer. We found that higher doses resulted in more favorable outcomes without excess toxicity. This trial is registered on ClinicalTrials.gov as NCT00911118., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Importance: Patients of Memorial Sloan Kettering Cancer Center in New York, New York, are now offered a choice of either in-person or remote telehealth visits for radiation oncology care. However, safety and satisfaction among patients receiving treatment with fully remote physician management is unclear., Objective: To analyze patient safety and satisfaction, financial implications, and environmental consequences associated with fully remote management among a cohort of patients treated with radiotherapy., Design, Setting, and Participants: This single-institution retrospective cohort study was performed at Memorial Sloan Kettering Cancer Center, with patients treated with radiation who opted for fully remote management between October 1, 2020, and October 31, 2022. Data on patient safety events were prospectively collected with an in-house quality improvement reporting system. Patient satisfaction surveys were distributed electronically before, during, and after treatment. Patient transportation costs and environmental consequences were estimated based on differences in travel distance. Data analysis was performed from March 14 through September 19, 2023., Exposure: Radiotherapy with fully remote physician management., Main Outcomes and Measures: Satisfaction rates among patients opting for fully remote management were analyzed via surveys administered electronically after visits with clinicians. Patient safety events, defined as staff-reported actual events and near misses that had the potential to affect patient care, were reviewed. Rates and types of safety events were analyzed and compared with patients treated by onsite clinicians. Distances between patient home zip codes and treatment site locations were compared with estimated cost savings and decreased emissions., Results: This study included 2817 patients who received radiation oncology care with fully remote physician management. The median age of patients was 65 (range, 9-99) years, and more than half were men (1467 [52.1%]). Of the 764 safety events reported, 763 (99.9%) did not reach patients or caused no harm to patients. Nearly all survey respondents (451 [97.6%]) rated patient satisfaction as good to very good across all domains. For treatment with fully remote physician management, out-of-pocket cost savings totaled $612 912.71 ($466.45 per patient) and decreased carbon dioxide emissions by 174 metric tons., Conclusions and Relevance: In this study, radiation oncology care provided by fully remote clinicians was safe and feasible, with no serious patient events. High patient satisfaction, substantial cost savings, and decreased environmental consequences were observed. These findings support the continuation of a fully remote management option for select patients in the post-COVID-19 era.

Background: Various radiotherapeutic regimens are used in the treatment of bladder cancer., Objective: We aimed to evaluate early toxicity and outcomes associated with hypofractionated radiation therapy (Hypo-RT), 55Gy in 20 fractions., Material and Methods: We identified 40 patients who received definitive Hypo-RT for localized bladder cancer. Most patients were men (62.5%), elderly (median age 82), had high Charlson Comorbidity Index score (median 7, range 4-9) and were nonsurgical candidates (80%). Sixty-eight percent had a macroscopically complete transurethral resection of bladder tumor (TURBT) and 33 patients (82.5%) received concurrent chemotherapy. Acute (< =3mo) and late (>3mo) toxicities were assessed according to CTCAE v4.0. Survival outcomes were estimated using the Kaplan-Meier method. Median follow up after Hypo-RT was 32 months (95% CI: 28-49 months)., Results: Overall rates of acute grade 2 genitourinary (GU) and gastrointestinal (GI) toxicities were 40% each, most commonly urinary frequency and diarrhea. Two cases of acute grade 3 GU/GI toxicity occurred. Late grade 2+ toxicity occurred in 3 patients (7.5%): 2 grade 2 GU and 1 grade 3 GI. Seventy-seven percent achieved a complete response (CR). Six patients (20%) developed disease recurrence at a median time of 9.1 months. The estimated 2-year DFS and 2-year DSS rate were 59% (95% CI, 45-78%) and 78% (95% CI, 65-93%), respectively. Receipt of concurrent chemotherapy ( p  = 0.003) and achieving a CR ( p  = 0.018) were univariably associated with improved DSS. Tis component was associated with worse DSS ( p  = 0.015)., Conclusion: Hypo-RT had a favorable toxicity profile and encouraging cancer control outcomes in this mostly elderly and frail patient cohort., Competing Interests: Jonathan E. Rosenberg and Bernard Bochner are Editorial Board Members of this journal, but were not involved in the peer-review process nor had access to any information regarding its peer-review. Assaf Moore, Stephanie M. Lobaugh, Zhigang Zhang, Gopa Iyer, Min Yuen Teo, Timothy Donahue, David Aramburu Nunez, Alexandra Dreyfuss, Daniel Gorovets, Michael J. Zelefsky and Marisa A. Kollmeier report no perceived conflicts of interest relevant to the current work., (© 2023 – The authors. Published by IOS Press.)

Background: A positive post-treatment prostate biopsy following definitive radiotherapy carries significant prognostic implications., Objective: To determine whether local recurrences after prostate stereotactic body radiation therapy (SBRT) are associated with the presence of and occur more commonly within the region of a PI-RADS 4 or 5 dominant intra-prostatic lesion (DIL) identified on pre-treatment multi-parametric magnetic resonance imaging (MRI)., Design, Setting, and Participants: 247 patients with localized prostate cancer treated with SBRT at our institution from 2009-2018 underwent post-treatment biopsies (median time to biopsy: 2.2 years) to evaluate local control., Interventions: Prostate SBRT (median 40 Gy in 5 fractions)., Outcome Measurements and Statistical Analysis: MRIs were read by a single diagnostic radiologist blinded to other patient characteristics and treatment outcomes. The DIL presence, size, location, and extent were then analyzed to determine associations with the post-treatment biopsy outcomes., Results and Limitations: Among patients who underwent post-treatment biopsies, 39/247 (15.8%) were positive for Gleason-gradable prostate adenocarcinoma, of which 35/39 (90%) had a DIL initially present and 29/39 (74.4%) had a positive biopsy within the DIL. Factors independently associated with post-treatment biopsy outcomes included the presence of a DIL (OR 6.95; p = 0.001), radiographic T3 disease (OR 5.23, p < 0.001), SBRT dose ≥40 Gy (OR 0.26, p = 0.003), and use of androgen deprivation therapy (ADT; OR 0.28, p = 0.027). Among patients with a DIL (N = 149), the only factors associated with post-treatment biopsy outcomes included ≥50% percent cores positive (OR 2.4, p = 0.037), radiographic T3 disease (OR 4.04, p = 0.001), SBRT dose ≥40 Gy (OR 0.22, p < 0.001), and use of ADT (OR 0.21, p = 0.014)., Conclusions: Our results suggest that men with PI-RADS 4 or 5 DILs have a higher risk of local recurrence after prostate SBRT and that most recurrences are located within the DIL., Patient Summary: We found the presence of a dominant tumor on pre-treatment MRI was strongly associated with residual cancer within the prostate after SBRT and that most recurrences were within the dominant tumor., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Although hydrogel spacer placement (HSP) minimizes rectal dose during prostate cancer radiation therapy, its potential benefit for modulating rectal toxicity could depend on the achieved prostate-rectal separation. We therefore developed a quality metric associated with rectal dose reduction and late rectal toxicity among patients treated with prostate stereotactic body radiation therapy (SBRT)., Methods and Materials: A quality metric consisting of prostate-rectal interspace measurements from axial T2-weighted magnetic resonance imaging simulation images was applied to 42 men enrolled in a multi-institutional phase 2 study using HSP with prostate SBRT (45 Gy in 5 fractions). A score of 0, 1, or 2 was assigned to a prostate-rectal interspace measurement of <0.3 cm, 0.3 to 0.9 cm, or ≥1 cm, respectively. An overall spacer quality score (SQS) was computed from individual scores at rectal midline and ±1 cm laterally, located at the prostate base, midgland, and apex. Associations of SQS with rectal dosimetry and late toxicity were evaluated., Results: The majority of the analyzed cohort had an SQS of 1 (n = 17; 41%) or 2 (n = 18; 43%). SQS was associated with maximum rectal point dose (rectal Dmax; P  = .002), maximum dose to 1 cc of rectum (D1cc; P  = .004), and volume of rectum receiving ≥100% of prescription dose (V45; P  = .046) and ≥40 Gy (V40; P  = .005). SQS was also associated with a higher incidence of ( P  = .01) and highest-graded late rectal toxicity ( P  = .01). Among the 20 men who developed late grade ≥1 rectal toxicity, 57%, 71%, and 22% had an SQS of 0, 1, and 2, respectively. Men with an SQS of 0 or 1 compared with 2 had 4.67-fold (95% CI, 0.72-30.11) or 8.40-fold (95% CI, 1.83-38.57) greater odds, respectively, of developing late rectal toxicity., Conclusions: We developed a reliable and informative metric for assessing HSP, which appears to be associated with rectal dosimetry and late rectal toxicity after prostate SBRT., (© 2023 The Authors. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.)

Purpose/objective: To compare toxicity profiles of low-dose rate (LDR) and high-dose rate (HDR) brachytherapy boost combined with ultra-hypofractionated external beam radiation therapy (UH-EBRT)., Materials/methods: 99 patients with intermediate-risk prostate cancer underwent an HDR (n = 59) or LDR (n = 40) boost combined with UH-EBRT (5 Gy x 5) . HDR (Ir-192) was delivered a single dose (15 Gy) and LDR (Pd-103) prescription dose was 100 Gy. Median baseline IPSS was 5 for both cohorts. Median follow-up was 29.3mos. Cumulative incidences were calculated for toxicity. Fisher exact tests were used to evaluate associations., Results: Overall incidence of grade 2 genitourinary toxicity for the entire cohort at 12 and 24 months was 21% and 29%, respectively. The incidence of grade 2 genitourinary toxicity at 12 and 24 months was higher for LDR cohort compared with HDR cohort (45% vs 5.1% and 55% vs 11%; p<0.001). On MVA, only treatment regimen (LDR versus HDR) was associated with grade 2+ genitourinary toxicity (p<0.001). Two patients experienced grade 2 rectal toxicity in each cohort. No grade > 3 toxicities were observed., Conclusions: Both LDR and HDR brachytherapy combined with UH-EBRT had favorable toxicity profiles, but significantly less grade 2+ genitourinary toxicity was observed in patients receiving HDR., (Copyright © 2022 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe technical challenges and complications encountered during and after high-dose-rate prostate brachytherapy (HDR-BT) and review management of these complications., Methods and Materials: The authors performed a systematic review of the literature on toxicities encountered after prostate HDR-BT +/- external beam radiotherapy. A total of 397 studies were identified, of which 64 were included. A focused review of literature regarding the management of acute and late toxicities also performed., Results: Most acute toxicities include grade 0-2 genitourinary and gastrointestinal toxicity. Overall, Grade 3+ Common Terminology Criteria for Adverse Events toxicity after HDR-BT was low [genitourinary: 0-1%; gastrointestinal 0-3%]. Rates of fistula formation were <1%, and radiation cystitis/proctitis were <14% and more commonly reported in cohorts treated with HDR-BT boost and external beam radiotherapy., Conclusions: HDR-BT both as monotherapy or combined with external beam radiotherapy for prostate cancer is well tolerated. Serious complications are rare., (Copyright © 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: Studies using stereotactic body radiotherapy (SBRT) dose escalation in in low- and intermediate-risk prostate cancer patients have indicated favorable outcomes., Objective: To evaluate tolerance and tumor control outcomes in low- and intermediate-risk prostate cancer patients treated with high-dose SBRT following our phase 1 trial., Design, Setting, and Participants: A total of 551 patients with low- or intermediate-risk prostate cancer were treated with SBRT., Intervention: Treatment with 37.5-40Gy SBRT in five fractions directed to the prostate and seminal vesicles., Outcome Measurements and Statistical Analysis: Outcome measurements included acute toxicities (<3 mo after radiotherapy [RT]) and late toxicities (>3 mo after RT) and tumor control evaluation (prostate-specific antigen [PSA] levels at 3-6-mo intervals and post-treatment prostate biopsy at 2yr)., Results and Limitations: Acute grade 2 gastrointestinal (GI) toxicities occurred in 1.8% of patients, and late grade 2 and 3 GI toxicities were observed in 3.4% and 0.4% of patients, respectively. Acute grade 2 genitourinary (GU) toxicities occurred in 10% of patients, and grade 3 acute GU toxicities were observed in 0.7% of patients. Late grade 2 and 3 GU toxicities were observed in 21.1% and 2.5% of patients, respectively. The use of a hydrogel rectal spacer was significantly associated with reduced late GI toxicity and lower odds of developing late GU toxicity. The median follow-up was 17 mo, and 53% of those with at least 2yr of follow-up (103/193) had a biopsy performed. The 5-yr cumulative incidence of PSA failure was 2.1%, and the incidence of a positive 2-yr treatment biopsy was 12%. Limitations to this report include its retrospective nature and short follow-up time., Conclusions: Favorable short-term outcomes were achieved with high-dose SBRT for low- and intermediate-risk disease. Severe late toxicities were observed and favorable tumor control was found., Patient Summary: We utilized stereotactic body radiotherapy, a form of external beam radiotherapy that delivers highly targeted high-dose treatment to the prostate, to treat over 500 localized prostate cancer patients in five sessions over 1.5 wk. Treatments were well tolerated without significant urinary or rectal side effects. Nearly 90% of those who underwent biopsies after treatment did not demonstrate residual active disease., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: To report early toxicity and tumor control outcomes of Pd-103 brachytherapy with ultrahypofractionated stereotactic radiation therapy (RT) for intermediate-risk prostate cancer., Methods and Materials: This prospective trial included 40 patients with intermediate-risk prostate cancer who underwent low-dose-rate (Pd-103) brachytherapy (prescription dose, 100 Gy), followed 1 month later with ultrahypofractionated stereotactic RT (25 Gy in 5 fractions) to the prostate and seminal vesicles. The primary endpoint was the rate of grade 2+ genitourinary toxicity at 12 months using Common Terminology Criteria for Adverse Events v 4.0. Secondary endpoints included patient-reported quality-of-life metrics (International Prostate Scoring System [IPSS], International Index of Erectile Function, and Expanded Prostate Cancer Index Composite-bowel). Biochemical failure was defined as prostate-specific antigen nadir +2 ng/mL. Posttreatment biopsies were performed at between 24 and 36 months; median follow-up was 36 months., Results: The rate of grade 2 urinary toxicity at 12 months was 25% with no grade 3 urinary toxicity noted. Mean IPSS at baseline and 12 and 24 months was 5, 10, and 6.2, respectively. Mean change in IPSS from baseline at 12 months was +5.5 (interquartile range, 1-9.75) and +1.05 (interquartile range, -3 to 3.25) at 24 months. Grade 2 bowel toxicity was 5% at 12 months with no grade 3 bowel toxicity noted. Mean Expanded Prostate Cancer Index Composite-bowel domain scores at baseline and 12 months were 92.8 and 90.3, respectively. Of patients who were potent (International Index of Erectile Function ≥21) at baseline, 75% remained potent at 12 months. Of 40 patients, 28 underwent posttreatment prostate biopsy (PPB), which was negative (n = 20) or demonstrated severe treatment effect (n = 8). No patient had a positive PPB or developed biochemical failure during the follow-up period. One patient without a PPB developed osseous metastases at 18 months posttreatment in the absence of biochemical failure., Conclusion: Low-dose-rate brachytherapy in combination with ultrahypofractionated stereotactic RT was safe and effective for intermediate-risk prostate cancer in early results of this trial., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: There are limited data regarding high-dose stereotactic body radiation therapy (SBRT) for prostate cancer in patients with poor baseline urinary function. The purpose of this study was to evaluate genitourinary (GU) toxicity and changes in patient-reported symptom severity scores after prostate SBRT in men with a high pretreatment International Prostate Symptom Score (IPSS)., Methods and Materials: Seven hundred fifty-three patients treated with prostate SBRT at our institution from 2012 to 2019 were identified, of whom 72 consecutive patients with baseline IPSS ≥15 were selected for this study. GU toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and IPSS were prospectively documented at each follow-up visit. Univariable logistic regression was used to evaluate for potential predictors of GU toxicity., Results: Median follow-up in survivors was 26.8 months. The rates of acute grade 2 and 3 GU toxicity were 20.8% and 1.4%, respectively. The rates of late grade 2 and 3 GU toxicity were 37.5% and 5.6%, respectively. The majority of grade 2+ toxicities resolved by last follow-up, and when toxicities were regraded per CTCAE v5.0, there were no longer any grade 3 adverse events. Total IPSS and individual symptom subscores improved over time. Compared with baseline, median total IPSS at 24 ± 6 months was significantly lower (18 vs 12; P < .001) and the proportion of patients with severe scores (IPSS ≥20) decreased from 29.2% to 13.9%. Pretreatment urinary urgency was associated with late grade 2+ GU toxicity (odds ratio, 2.10; 95% confidence interval, 1.33-3.31; P = .001)., Conclusions: In men with baseline IPSS ≥15 managed with prostate SBRT, the rate of severe GU toxicity was low and patient-reported symptoms generally improved over time. Thus, high pretreatment IPSS should not deter clinicians from offering prostate SBRT., (© 2020 The Author(s).)

Background: Bone metastases cause significant morbidity in patients with cancer, and radiation therapy (RT) is an effective treatment approach. Indications for more complex ablative techniques are emerging. We sought to evaluate RT trends at a large multi-site tertiary cancer center., Methods: Patients who received RT for bone metastases at a single institution (including regional outpatient clinics) from 2016 to 2018 were identified. Patients were grouped by RT regimen: single-fraction conventional RT (8 Gy × 1), 30 Gy in 10 fractions, SBRT, and "other". Multinomial logistic regression was performed to assess trends in regimens over time. Binary logistic regression was performed to evaluate factors associated with receipt of SBRT., Results: Between 2016 and 2018, 5,952 RT episodes were received by 2,969 patients with bone metastases. Overall, 76% of episodes were ≤ 5 fractions. The median number of fractions planned for SBRT and non-SBRT episodes was 3 (IQR 3-3) and 5 (IQR 5-10), respectively. Use of SBRT increased from 2016 to 2018 (39% to 53%, p < 0.01) while use of 30 Gy in 10 fractions decreased (26% to 12%, p < 0.01), and 8 Gy × 1 was stable (5.3% to 6.9%, p = 0.28). SBRT was associated with higher performance status (p < 0.01) and non-radiosensitive histology (p < 0.01). Use of SBRT increased in the regional network (19% to 48%, p < 0.01) and at the main center (52% to 59%, p = 0.02), but did not increase within 30 days of death. More patients treated with 8 Gy × 1 than SBRT died within 30 days of treatment (24% vs 3.8%, respectively, p < 0.01)., Conclusions: SBRT is replacing 30 Gy in 10 fractions for bone metastases, especially among patients with high performance status and non-radiosensitive histologies. Better prognostic algorithms could further improve patient-centered treatment selection at the end of life., (© 2020 Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Purpose: This study reports clinical experience using a linear accelerator-based MV-kV imaging system for intrafraction motion management during prostate stereotactic body radiation therapy (SBRT)., Methods and Materials: From June 2016 to August 2018, 193 prostate SBRT patients were treated using MV-kV motion management (median dose 40 Gy in 5 fractions). Patients had 3 fiducials implanted then simulated and treated with a full bladder and empty rectum. Pretreatment orthogonal kVs and cone beam computed tomography were used to position patients and evaluate internal anatomy. Motion was tracked during volumetric modulated arc therapy delivery using simultaneously acquired kV and MV images from standard on-board systems. Treatment was interrupted to reposition patients when motion >1.5-2 mm was detected. Motion traces were analyzed and compared with Calypso traces from a previously treated similar patient cohort. To evaluate "natural motion" (ie, if we had not interrupted treatment and repositioned), intrafraction couch corrections were removed from all traces. Clinical effectiveness of the MV-kV system was explored by evaluating toxicity (Common Terminology Criteria for Adverse Events v3.0) and biochemical recurrence rates (nadir + 2 ng/mL)., Results: Median number of interruptions for patient repositioning was 1 per fraction (range, 0-9). Median overall treatment time was 8.2 minutes (range, 4.2-44.8 minutes). Predominant motion was inferior and posterior, and probability of motion increased with time. Natural motion >3 mm and >5 mm in any direction was observed in 32.3% and 10.2% of fractions, respectively. Calypso monitoring (n = 50) demonstrated similar motion results. In the 151 MV-kV patients with ≥3-month follow-up (median, 9.5 months; range, 3-26.5 months), grade ≥2 acute genitourinary/gastrointestinal and late genitourinary/gastrointestinal toxicity was observed in 9.9%/2.0% and 11.9%/2.7%, respectively. Biochemical control was 99.3% with a single failure in a high-risk patient., Conclusions: The MV-kV system is an effective method to manage intrafraction prostate motion during SBRT, offering the opportunity to correct for prostate clinical target volume displacements that would have otherwise extended beyond typical planning target volume margins., (Copyright © 2020 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: To identify early biochemical predictors of survival in intermediate- and high-risk prostate cancer patients with a pre-treatment PSA <20 ng/mL following definitive radiation therapy (RT) and androgen deprivation therapy (ADT)., Materials and Methods: A single-institution review of 2566 intermediate and high-risk prostate cancer patients treated with definitive RT and neoadjuvant and concurrent ADT from 1990 to 2012 was performed. The first prostate-specific antigen (PSA) value within three months of ADT initiation (post-ADT PSA) and the first PSA within three months after RT completion (post-RT PSA) were recorded. 1275 had baseline PSA <20 ng/mL and either post-ADT or post-RT PSA available. Median follow-up was 7.6 years. The relationship between post-treatment PSA kinetics and biochemical relapse (BR), distant metastasis (DM), prostate cancer specific death (PCSD) and overall survival (OS) was modeled using Cox regression univariate and multivariate analysis (MVA)., Results: MVA demonstrated a strong association between a post-RT PSA ≥0.09 ng/mL and a significantly higher risk of BR (HR: 1.93; 95% CI: 1.45-2.57; p < 0.001), DM (HR: 2.97; 95% CI: 2.01-4.39; p < 0.001), PCSD (HR: 2.99; 95% CI: 1.73-5.15; p < 0.001) and OS (HR: 1.49; 95% CI: 1.18-1.86; p < 0.001). Post-RT PSA reduction of ≥95% relative to the baseline PSA was associated with a significantly lower risk of BR (MVA HR: 0.58; 95% CI: 0.41-0.83; p = 0.003) and DM (MVA HR: 0.47; 95% CI: 0.30-0.76; p = 0.002)., Conclusion: A PSA value ≥0.09 ng/mL early after RT completion is associated with significantly worse prognosis across all clinical outcomes, and an early PSA reduction of ≥95% is associated with reduced risk of BR and DM. These findings may identify patients who require early aggressive systemic management for high-risk disease., (Copyright © 2019. Published by Elsevier B.V.)

Purpose: The use of magnetic resonance imaging (MRI) for radiation therapy simulation is growing because of its ability to provide excellent delineation of target tissue and organs at risk. With the use of hypofractionated schemes in prostate cancer, urethral sparing is essential; however, visualization of the prostatic urethra can be challenging because of the presence of benign prostatic hyperplasia as well as respiratory motion artifacts. The goal of this study was to compare the utility of 2 motion-insensitive, T2-weighted MRI pulse sequences for urethra visualization in the setting of MRI-based simulation., Methods and Materials: Twenty-two patients undergoing MRI simulation without Foley catheters were imaged on a 3 Tesla MRI scanner between October 2018 and January 2019. Sagittal multislice data were acquired using (1) MultiVane XD radial sampling with parallel imaging acceleration (MVXD) and (2) single-shot fast-spin-echo (SSFSE) sequences with acquisition times of 2 to 3 minutes per sequence. For each examination, 2 genitourinary radiologists scored prostatic urethra visibility on a 1-to-5 scale and rated the signal-to-noise ratio and the presence of artifacts in each series., Results: Urethral visibility was scored higher in the MVXD series than in the SSFSE series in 18 of 22 cases (Reader 1) and 17 of 22 cases (Reader 2). The differences in scores between MVXD and SSFSE were statistically significant for both readers (P < .0001 for both, paired Student's t-test) and interobserver agreement was high (Cohen's kappa = 0.67). Both readers found the signal-to-noise ratio of the MVXD sequence to be superior in all cases. The MVXD sequence was found to generate more artifacts than the SSFSE sequence, but these tended to appear in the periphery and did not affect the ability to visualize the urethra., Conclusions: A radial T2-weighted multislice pulse sequence was superior to an SSFSE sequence for visualization of the urethra in the setting of magnetic resonance simulation for prostate cancer., (Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: To report toxicity outcomes, prostate-specific antigen (PSA) relapse, and cumulative incidence posttreatment biopsy results among patients treated on a prospective dose escalation study using ultra-hypofractionated stereotactic body radiation therapy (SBRT) for patients with low- and intermediate-risk prostate cancer., Methods and Materials: A total of 136 patients were enrolled in a phase 1 dose-escalation study to determine the tolerance of escalating radiation dose levels of SBRT for the treatment of localized prostate cancer. The initial dose level was 32.5 Gy in 5 fractions, and doses were then sequentially escalated to 35 Gy, 37.5 Gy, and 40 Gy. Eligibility criteria included only patients with low and intermediate risk, and the maximum prostate volume was 60 cm 3 . Patients treated with neoadjuvant androgen deprivation were excluded. The median follow-up in survivors for the 4 dose levels was 5.9, 5.4, 4.1, and 3.5 years, respectively., Results: The incidence of acute grade 2 rectal toxicities for dose levels 1 to 4 were 0%, 2.9%, 2.8%, and 11.4% respectively. No grade 3 or 4 acute rectal toxicities were observed. The incidence of acute grade 2 urinary toxicities for dose levels 1 to 4 were 16.7%, 22.9%, 8.3%, and 17.1%, respectively. No grade 3 or 4 acute urinary toxicities were observed. No grade 2 or higher rectal toxicities were observed. The incidence of late grade 2 urinary toxicities for dose levels 1 to 4 was 23.3%, 25.7%, 27.8%, and 31.4%, respectively. Only 1 late grade 3 urinary toxicity (urethral stricture) developed in the 40-Gy dose arm; the stricture was corrected with transurethral resection. No grade 4 late urinary toxicity was observed. The 5-year cumulative incidence of prostate-specific antigen failure for dose levels 1 to 4 was 15%, 6%, 0%, and 0%. The incidence of a 2-year positive posttreatment biopsy was 47.6%, 19.2%, 16.7%, and 7.7%, respectively for the 4 dose arms (P = .013)., Conclusions: SBRT doses ranging from 32.5 to 40 Gy in 5 fractions were well tolerated without severe urinary or rectal toxicities. Biopsy outcomes suggest improved rates of tumor clearance observed with higher doses., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To estimate uterine perforations rates during intracavitary brachytherapy for cervical cancer with and without ultrasound (US) image guidance., Materials and Methods: A systematic search of databases (PubMed and EMBASE) was performed. The pooled summary uterine perforation rate (detected by postinsertion CT or MRI) for the un-guided insertion group and the guided insertion group was calculated by using the random-effects model weighted by the inverse variance., Results: A total of 690 articles were initially found, resulting in 12 studies that met the inclusion criteria. A total of 1757 insertions and 766 patients were included in the meta-analysis. The overall uterine perforation rate per insertion was 4.56% (95%CI: 2.35-8.67) and per patient was 7.39% (95%CI: 3.92-13.50). The pooled perforation rate per insertion without image guidance was 10.54% (95%CI: 6.12-17.57) versus 1.06% (95%CI: 0.41-2.67) with image guidance (p < 0.01). The pooled perforation rate per patient without guidance was 16.67% (95%CI: 10.01-26.45) versus 2.54% (95%CI: 1.21-5.24) with image guidance (p < 0.01). The ratio of perforations in the un-guided/guided groups was 9.94 and 6.56, per insertion and per patient, respectively. The most common sites of perforation were the posterior wall (>47 events) and the uterine fundus (24 events). None of the studies reported significant acute clinical consequences. Prophylactic antibiotic after perforation was used in 3 of the 4 studies that described the management., Conclusion: Using postinsertion CT or MRI to detect the perforation, the rate of uterine perforation per insertion in patients who received US-guided intracavitary brachytherapy insertion is 90% lower than with un-guided insertion., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Salvage brachytherapy is a treatment option for patients with locally recurrent prostate cancer after primary radiation therapy. We reviewed our experience using low-dose-rate (LDR) or high-dose-rate (HDR) brachytherapy to compare the outcome and toxicity profiles of each approach in the salvage brachytherapy setting., Methods and Materials: Ninety-eight patients with biopsy-proven locally recurrent prostate cancer who underwent salvage brachytherapy (LDR = 37; HDR = 61) following an initial course of definitive radiotherapy between 4/2003 and 4/2015 were retrospectively reviewed. All patients underwent salvage brachytherapy using LDR or HDR. Androgen deprivation therapy was used in 45% of the patients. Prostate-specific antigen (PSA) failure was determined using the Phoenix (nadir+2) definition. Toxicity was graded using Common Terminology Criteria for Adverse Events version 4 and patient-reported questionnaires., Results: Median followup was 31 months. The 3-year PSA relapse-free survival (RFS) was 60.1% (95% CI, 49.6-72.5%). There was no difference between LDR and HDR brachytherapy in terms of PSA RFS (p = 0.84 by log-rank test). On multivariate analysis, only prostate-specific antigen doubling time (PSADT) <12 months was significantly associated with PSA relapse. The 3-year PSA RFS for patients with a PSADT <12 months was 39% compared with 73% for PSADT ≥12 months (p = 0.002 by long-rank test). There were no statistically significant differences in toxicity between LDR and HDR brachytherapy. There was a higher peak in urinary symptoms in LDR patients; however by 24-36 months, most patients in both groups returned to baseline., Conclusions: Both LDR and HDR salvage brachytherapy are an excellent treatment options for appropriately selected patients with comparable outcome and toxicity. Patients with a PSADT < 12 months seem to have worse outcomes., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Our purpose was to describe the process and outcome of performing postimplantation dosimetric assessment and intraoperative dose correction during prostate brachytherapy using a novel image fusion-based treatment-planning program., Methods and Materials: Twenty-six consecutive patients underwent intraoperative real-time corrections of their dose distributions at the end of their permanent seed interstitial procedures. After intraoperatively planned seeds were implanted and while the patient remained in the lithotomy position, a cone beam computed tomography scan was obtained to assess adequacy of the prescription dose coverage. The implanted seed positions were automatically segmented from the cone-beam images, fused onto a new set of acquired ultrasound images, reimported into the planning system, and recontoured. Dose distributions were recalculated based upon actual implanted seed coordinates and recontoured ultrasound images and were reviewed. If any dose deficiencies within the prostate target were identified, additional needles and seeds were added. Once an implant was deemed acceptable, the procedure was completed, and anesthesia was reversed., Results: When the intraoperative ultrasound-based quality assurance assessment was performed after seed placement, the median volume receiving 100% of the dose (V100) was 93% (range, 74% to 98%). Before seed correction, 23% (6/26) of cases were noted to have V100 <90%. Based on this intraoperative assessment and replanning, additional seeds were placed into dose-deficient regions within the target to improve target dose distributions. Postcorrection, the median V100 was 97% (range, 93% to 99%). Following intraoperative dose corrections, all implants achieved V100 >90%., Conclusions: In these patients, postimplantation evaluation during the actual prostate seed implant procedure was successfully applied to determine the need for additional seeds to correct dose deficiencies before anesthesia reversal. When applied, this approach should significantly reduce intraoperative errors and chances for suboptimal dose delivery during prostate brachytherapy., (Copyright © 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Introduction: Lower urinary tract symptoms and retention are known complications of radiation for prostate cancer and traditionally transurethral resection of the prostate (TURP) has been avoided in these patients because of the risk of incontinence. The purpose of this study was to evaluate the incidence and predictors of post-TURP incontinence in previously radiated patients., Materials and Methods: One-hundred and eleven patients who underwent brachytherapy or external beam radiotherapy for prostate cancer with subsequent TURP performed between 1992 and 2012 at a single institution were identified. We tested for associations between post-TURP continence status and pre-TURP predictors including age, preoperative urinary symptoms and type and timing of radiation therapy., Results: New-onset incontinence developed in 27% (95% CI 17%, 39%) of patients after first post-radiation TURP and 32% (95% CI 23%, 42%) of patients after any TURP, including repeat TURPs. Forty-three percent of patients had resolution of incontinence with first TURP (95% CI 25%, 63%); only 25% (95% CI 7%, 52%) of patients had resolution following repeat TURPs. Age was significantly associated with incontinence (OR per 10 years 2.02, 95% CI 1.10, 3.74, p = 0.024). Post-TURP incontinence was more common in men with pre-TURP urgency., Conclusions: Rates of post-TURP incontinence were higher in men who were older or had pre-TURP urinary urgency. Assessment of preoperative symptoms would allow for better patient selection. Further research should determine whether this results in better outcomes, including decreased incidence of new onset incontinence and increase in resolution of incontinence.

Brachytherapy is an ideal treatment approach for radiorecurrent prostate cancer given the highly conformal treatment. Increasingly, multiparametric magnetic resonance imaging is being utilized to enhance our ability to assess intraprostatic tumor characteristics. This article aims to review the current literature on whole gland salvage brachytherapy for radiorecurrent prostate cancer as well as the methodology and progress towards a focal approach to salvage brachytherapy. Particular emphasis is placed on the potential role of multiparametric MRI in achieving optimal outcomes with focal salvage brachytherapy., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: To evaluate the incidence and predictors of hip toxicity postradiotherapy for localized prostate cancer., Methods and Materials: 4067 prostate cancer patients were treated with external beam radiotherapy (EBRT; n=2569; 63%) or brachytherapy with or without supplemental EBRT (n=1508; 27%). 43% (n=1738) were treated with neo-adjuvant and concurrent ADT and 57% (n=2329) with radiotherapy alone. Hip toxicity was defined as moderate or severe pain upon ambulation with or without the need for hip-revision surgery. Median follow-up was 7years (range, 3-21years)., Results: One hundred twenty-one (2.7%) patients developed moderate-to-severe hip pain after radiotherapy affecting ambulation. Of these, 73 (60%) required hip replacement secondary to persistent hip pain. Among patients with baseline degenerative joint disease (DJD) changes on scans, 10-year incidence of hip-related toxicity was 11% versus 3% for those without such changes (P<.001). The only variables on multivariate analysis associated with hip-related toxicity post-radiotherapy were baseline DJD on imaging (P<.0001) and prolonged ADT for salvage therapy (P<.0001)., Conclusions: Prostate EBRT or brachytherapy is associated with low incidence of long-term hip-related toxicity. The only variables identified associated with hip toxicity posttherapy was the presence of baseline DJD and prolonged salvage ADT posttreatment for patients developing recurrence., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: To assess whether contemporary adjuvant management of early stage uterine carcinosarcoma (CS) produces equal outcomes as in uterine serous carcinoma (USC)., Methods: We reviewed 172 women treated from 2000 to 2011 for stage I-II USC (n=112, 65%) or CS (n=60, 35%). Adjuvant therapy was initiated in 154 (90%) patients, with 111 patients receiving intravaginal radiotherapy (IVRT)/chemotherapy. Median follow up was 4.6 years for surviving patients., Results: Characteristics for USC vs. CS did not differ significantly by age ≥60, pelvic or para-aortic node sampling, stage, lymphovascular invasion, chemotherapy use, RT use or omission of adjuvant therapy. Outcomes were better for USC vs. CS in 5-year actuarial rates of recurrence [17% (C.I. 10-25%) vs. 45% (C.I. 31-59%), p<0.001],disease-related mortality (DRM) [11% (5-17%) vs. 30% (16-44%), p=0.016], and all-cause mortality [12% (C.I. 6-18%) vs. 34% (C.I. 20-48%), p=0.007]. In multivariable analysis, CS histology remained a significant predictor of risk for recurrence [HR 3.1 (C.I. 1.7-5.7), p<0.001], DRM [HR 2.4 (C.I. 1.1-5.1), p=0.024], and all-cause mortality [HR 2.4 (C.I. 1.2-4.8), p=0.012]. On sub-group analysis of 111 patients (77 USC, 34 CS) able to receive IVRT/chemotherapy, CS no longer was associated significantly with increased recurrence (29% vs. 15%, p=0.18), DRM (22% vs. 10%, p=0.39), or all-cause mortality (22% vs. 10%, p=0.45)., Conclusions: CS was associated with worse outcomes than USC. However, that difference was not maintained in patients able to receive IVRT and chemotherapy. While intriguing, this result may be due in part to selection against rapid early relapsing CS patients in this group., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: We studied adjuvant daily sildenafil citrate during and after radiotherapy for prostate cancer for erectile function preservation., Materials and Methods: We performed a randomized, prospective trial of 279 patients with localized prostate cancer treated with radiotherapy who received sildenafil citrate (50 mg daily) or placebo (2:1 randomization). Medication/placebo was initiated 3 days before treatment and continued daily for 6 months. Before therapy and 3, 6, 9, 12, 18 and 24 months after radiotherapy patients completed the IIEF questionnaire, including the erectile function domain, the I-PSS questionnaire and the RAND SF-36®. All IIEF domains were scored., Results: At 12 months erectile function scores were better for sildenafil citrate than placebo (p = 0.018), 73% of patients on sildenafil citrate vs 50% on placebo had mild/no erectile dysfunction (p = 0.024) and the sildenafil citrate arm had superior overall satisfaction (p = 0.027) and IIEF total scores (p = 0.043). At 24 months erectile function and IIEF scores were no longer significantly better for sildenafil citrate (p = 0.172 and 0.09, respectively) and yet overall satisfaction scores were higher (p = 0.033). Sexual desire scores in patients who received sildenafil citrate were higher at 24 months although they had completed drug therapy 18 months previously (p = 0.049). At 24 months 81.6% of patients on sildenafil citrate and 56.0% of those on placebo achieved functional erection with or without erectile dysfunction medication (p = 0.045)., Conclusions: Daily sildenafil citrate during and after radiotherapy for prostate cancer was associated with improved overall sexual function compared with placebo for various sexual function domains. To our knowledge this is the largest randomized, prospective, controlled trial to show the usefulness of a phosphodiesterase-5 inhibitor as a rehabilitation strategy in patients with prostate cancer who received radiation therapy., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: Advanced endometrial cancer patients comprise a heterogeneous group. This study assessed the association of clinicopathological factors with relapse and death from endometrial cancer., Methods: Eligible patients were treated for stage III (FIGO 2009) endometrial adenocarcinoma, had peritoneal cytology performed, and had no gross residual disease post-operatively., Results: Of 192 patients, 59% were ≥60 years old, 48% had ≥50% myometrial invasion, 71% lymphovascular invasion, 25% cervical stromal invasion, 37% adnexal involvement, and 23% positive peritoneal cytology. High-grade histology (serous, clear cell, undifferentiated, or grade 3 endometrioid) was present in 45%. Pelvic lymphadenectomy was performed in 93% and para-aortic lymphadenectomy in 73%. Adjuvant chemotherapy and/or radiation therapy was administered to 93%. At a median follow-up of 42 months, the 5-year rate of relapse was 37% and of death from endometrial cancer was 30%. On multivariate analysis, both outcomes were associated with high-grade histology, positive peritoneal cytology, and deep myometrial invasion (p≤0.04). The cohort was divided into subgroups of patients with 0 (n=46), 1 (n=83), or ≥2 (n=63) of these high-risk characteristics. The 5-year relapse rate for patients with 0 risk factors was 13%, 1 risk factor was 27%, and ≥2 risk factors was 62% (p<0.001). The corresponding 5-year rates of death from endometrial cancer were 11%, 20%, and 56%, respectively (p<0.001)., Conclusions: Stratification of stage III endometrial cancer according to high-grade histology, positive peritoneal cytology, and deep myometrial invasion is useful for prognostication and may grant insight into the optimal treatment for specific subgroups of patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To determine bladder wall position variability during external beam radiation therapy (EBRT) for bladder cancer with intravesical fiducial markers using 2-dimensional (2D) and volumetric (3D) imaging registration., Methods and Materials: Twenty T2-4aN0-1 bladder cancer patients underwent definitive EBRT with concurrent chemotherapy between May 2001 and January 2012, and had intravesical fiducial marker placement before simulation. Computed tomographic (CT)-based treatment planning was used for an initial phase to deliver 45 Gy (1.8 Gy/fraction) to the bladder and pelvic lymphatics followed by a boost to the involved bladder wall for an additional 21.6 Gy (1.8 Gy/fraction). Orthogonal kilovoltage radiograph images (34-37 images/patient) were obtained daily, registered with digitally reconstructed radiographs from the planning scan. Translational corrections were made daily. A kilovoltage cone-beam CT (kVCBCT) was acquired weekly and its registration with the planning scan was compared with that day's 2D registration results., Results: Of 739 treatments, 6% resulted in ≥15 mm displacement in 1 or more directions and 26% resulted in ≥10 mm displacement in 1 or more directions. Based on 2D registrations, the average millimeter difference between bony registration and fiducial marker registration (BR-FMR) in the right-left (RL) (R+), anterior-posterior (AP) (A+), and superior-inferior (SI) (I+) directions were: 0.5 ± 1.0 (range, -2.0 to +3.8), 1.7 ± 4.4 (range, -8.1 to +13.5) and -3.7 ± 5.8 (range, -16.8 to +8.3), respectively. For kVCBCT registrations, the average mm difference in the RL, AP, and SI directions were 0.3 ± 2.1 (range, -2.4 to +5.1), 3.1 ± 5.9 (range, -2.9 to +13.3) and -4.8 ± 8.0 (range, -16.4 to +9.5), respectively., Conclusions: Using intravesical fiducial markers, the largest difference in bladder motion based BR-FMR differences was in the superior-inferior direction. Because fiducial markers are target surrogates, setup using bony anatomy alone can lead to target displacements up to 13.5 mm anteriorly and 16.8 mm superiorly. This confirms a 1.5-1.7 cm minimum in planning target margins. These findings suggest a significant advantage in using intravesical fiducial markers to determine daily translational corrections., (© 2013. Published by Elsevier Inc. All rights reserved.)

Purpose: We report the toxicity and biochemical tumor control outcome of a prospective Phase II study using high-dose-rate brachytherapy (HDR) alone as a salvage therapy for recurrent disease after external beam radiotherapy (EBRT)., Methods: Forty-two patients with biopsy-proven recurrence were enrolled on a Phase II study of salvage HDR monotherapy using iridium-192. Median pretreatment EBRT dose was 8100 cGy (6840-8640 cGy) and the median time from completion of EBRT to salvage HDR was 73 months. The protocol prescription dose of 3200 cGy was delivered in four fractions over 30 hours in a single insertion. Median followup after salvage HDR was 36 months (6-67 months)., Results: The actuarial prostate-specific antigen biochemical relapse-free survival and distant metastases-free survival rates at 5 years were 68.5% and 81.5%, respectively. Cause-specific survival was 90.3%. Late genitourinary Grade 1and 2 toxicities were found in 38% and 48%, respectively, and one patient developed Grade 3 urinary incontinence. Late Grade 1 and 2 gastrointestinal toxicity was noted in 17% and 8% of patients, respectively. Three patients (7%) developed Grade 2 late urinary toxicity (urethral stricture), which were corrected with urethral dilatation, and one patient developed Grade 3 urinary incontinence. No Grade 4 toxicities were observed., Conclusions: Genitourinary toxicity was the most commonly encountered toxicity observed after salvage HDR but severe toxicities were uncommon. Salvage HDR is an effective and well-tolerated modality for locally recurrent prostate cancer and should be considered even for patients who have previously been treated with ultra-high dose levels of EBRT., (Copyright © 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)