Brachytherapy Monotherapy Research Articles

High-dose-rate Brachytherapy Monotherapy in Patients With Localised Prostate Cancer: Dose Modelling and Optimisation Using Computer Algorithms

AimsInterstitial high-dose-rate brachytherapy (HDR-BT) is an effective therapy modality for patients with localized prostate carcinoma. The objectives of the study were to optimise the therapy regime variables using two models: response surface methodology (RSM) and artificial neural network (ANN). Materials and methodsThirty-one studies with 5651 patients were included (2078 patients presented as low-risk, 3077 patients with intermediate-risk, and 496 patients with high-risk). A comparison of these therapy schedules was carried out using an effective biologically effective dose (BEDef) that was calculated assuming the number of treatment days and dose (D) per day. The modelling and optimization of therapy parameters (BEDef and risk level) in order to obtain the maximum biochemical free survival (BFS) were carried out by the RSM and ANN models. ResultsAn optimal treatment schedule (BFS = 97%) for patients presented with low-risk biochemical recurrence would be D = 26 Gy applied in one application, 2 fractions at least 6 h apart, within an overall treatment time of 1 day (BEDef = 251 Gy) by the RSM and ANN model. For patients presented with intermediate- or high-risk an optimal treatment regime (BFS = 94% and 90%, respectively) would be D = 38 Gy applied in one application, 4 fractions at least 6 h apart, with an overall treatment time of 2 days (BEDef = 279 Gy) by the RSM and ANN models. ConclusionsThe RSM and ANN models determine almost the same optimal values for the set of predicted therapy parameters that make a feasible selection of an optimal treatment regime.

Comparison of the efficacy of Cf-252 neutron intracavitary brachytherapy monotherapy with neutron intracavitary brachytherapy plus external beam radiotherapy in stage IB1 cervical cancer

ObjectiveWe aimed to compare the efficacy of californium (Cf)-252 neutron intracavitary brachytherapy (NIBT) monotherapy with NIBT plus external beam radiotherapy (ERBT) in the treatment of stage IB1 cervical cancer. MethodsFrom May 2006 to March 2014, 38 patients with stage IB1 cervical cancer with negative pelvic lymph node metastasis (NPLNM) who were treated at our hospital were enrolled in this retrospective study. A matched-pair design based on age, hemoglobin level, and tumor histology was used for the analysis. The status of all patients was assessed by the positron emission tomography - computer tomography (PET-CT) scan or the contrast enhancement pelvic CT scan. Cf-252 NIBT was administered for four times, and the total dose at point A was 42–44 Gy. ResultsThe local tumor control rate, overall survival rate, tumor-free survival rate, and late complication incidence rate in the NIBT group were 94.7%, 100%, 94.7% and 0%, respectively, which in the EBRT + NIBT group were 94.7%, 89.5%, 89.5% and 5.26%, respectively. The return of menstruation incidence rate was 36.8% in the NIBT group and 0% in the EBRT + NIBT group. ConclusionThe treatment outcomes in the NIBT group were similar to those in the EBRT + NIBT group for patients with stage IB1 cervical cancer with NPLNM, regular menstruation and at least 3 years of follow-up data. The additional advantage of NIBT monotherapy is the potential preservation of ovarian and endometrial function and hence fertility.

Population-based patient-reported quality of life outcomes following low-dose-rate versus high-dose-rate brachytherapy monotherapy for low-intermediate risk prostate cancer.

To evaluate patient reported quality of life outcomes (QoL) following low-dose-rate brachytherapy (LDR-BT) and high-dose-rate brachytherapy (HDR-BT) monotherapy for prostate cancer at a population-based setting. The study comprised men with low-intermediate risk prostate cancer in the Prostate Cancer Outcomes Registry Victoria (PCOR-Vic), who were treated with LDR-BT or HDR-BT monotherapy between 2015 and 2020 and completed the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire 12-month post-treatment. Men who had ADT were excluded (n = 12). Differences in substantial symptoms (i.e. 'moderate' or 'big' problem on a 5-point Likert scale) between LDR-BT and HDR-BT arms were evaluated using Pearson's chi-squared test. Multivariable linear regressions were used to estimate differences in EPIC-26 urinary, bowel and sexual functional domain scores between LDR-BT and HDR-BT arms. Overall, 198 men were included in this study, of which 167 (84%) had LDR-BT and 31 (16%) had HDR-BT. 9 (4.6%), 10 (5.1%) and 56 (28%) reported substantial symptoms for overall urinary, bowel and sexual function at 12-month post-treatment, with no significant difference between LDR-BT and HDR-BT arms. The adjusted mean differences in urinary incontinence, urinary obstructive, bowel and sexual function domain scores between LDR-BT and HDT-BT were: -3.53 (-8.21 to 1.14), -1.27 (-6.88 to 4.35), -0.01 (-5.63 to 5.63) and -8.68 (-21.44 to 4.07) respectively - these were not statistically significant and did not meet the minimal clinically important difference. This is the first Australian population-based study comparing QoL in men who had LDR-BT and HDR-BT, with no statistically or clinically significant differences in QoL observed at 12-month post-treatment.

Long-Term Outcomes Associated with Different High-Dose-Rate Brachytherapy Dose Regimens for Favorable and Unfavorable Intermediate Risk Prostate Cancer.

To present long-term efficacy outcomes of prostate high-dose-rate (HDR) brachytherapy monotherapy using 38 Gy in 4 fractions, 24 Gy in 2 fractions, and 27 Gy in 2 fractions for men with favorable and unfavorable intermediate risk prostate cancer. Patients treated with HDR brachytherapy monotherapy for NCCN favorable (FIR) or unfavorable (UIR) intermediate risk prostate cancer from 1999-2020 were identified in a prospectively maintained, single institution database. Patients with less than two years of follow-up and those treated with single fraction HDR brachytherapy were excluded. Biochemical failure was determined using Phoenix criteria. 10-year biochemical control (BC), local control (LC), and distant metastasis (DM) rates were estimated using the Kaplan-Meier method. Two hundred sixty-seven patients were included. One hundred eighty-nine had FIR and 78 had UIR prostate cancer, with median follow-up of 9.6 years and 7.2 years, respectively. Of the 189 patients with FIR prostate cancer, 59 (31.2%) received 38 Gy in 4 fractions, 26 (13.7%) received 24 Gy in 2 fractions, and 104 (55.0%) received 27 Gy in 2 fractions. Of the 78 patients with UIR prostate cancer, 20 (25.6%) received 38 Gy in 4 fractions, 11 (14.1%) received 24 Gy in 2 fractions, and 47 (60.2%) received 27 Gy in 2 fractions. Date ranges of treatment for the respective fractionation schedules were 1999-2010, 2007-2016, and 2009-2020. Upfront androgen deprivation therapy (ADT) was given to 12 (6.3%) patients with FIR and 10 (12.8%) patients with UIR. 10-year rates of BC for FIR and UIR patients were 90.1% and 78.8% (p = 0.004), respectively. 10-year rates of LC were 92.4% and 85.0% (p = 0.06), respectively. 10-year rates of DM were 1.9% and 4.7% (p = 0.12), respectively. For FIR patients, 10-year BC rates were 96.2% for patients receiving 38 Gy in 4 fractions vs. 86.3% (p = 0.07) for those treated with the 2-fraction regimens, while 10-year LC rates were 97.9% and 89.0% (p = 0.049), respectively. Within the UIR subset, the 10-year BC rates for patients receiving 38 Gy in 4 fractions and patients receiving treatment in 2 fractions were 95.0% and 70.6% (p = 0.038). 10-year LC rates were 100% and 77.8% (p = 0.045), respectively. 10-year BC rates by treatment schedule are shown in the table below. HDR brachytherapy monotherapy results in excellent long-term local control for intermediate risk prostate cancer. Improvements in biochemical and local disease control for patients treated with 38 Gy in 4 fractions warrants consideration of prospective study of optimal treatment dosing regimens.

46 Patterns of Relapse and Biochemical Control in Intermediate Risk Prostate Cancer Treated with High Dose Rate Brachytherapy (HDRB) Monotherapy

46 Patterns of Relapse and Biochemical Control in Intermediate Risk Prostate Cancer Treated with High Dose Rate Brachytherapy (HDRB) Monotherapy

PP04 Presentation Time: 11:27 AM: Mature Toxicity and Effectiveness Outcomes Associated with Three Treatment Schedules of High-Dose-Rate Brachytherapy Monotherapy for Favorable-Risk Prostate Cancer

PP04 Presentation Time: 11:27 AM: Mature Toxicity and Effectiveness Outcomes Associated with Three Treatment Schedules of High-Dose-Rate Brachytherapy Monotherapy for Favorable-Risk Prostate Cancer

Long-term outcomes of ultra-hypofractionated 2 fractions single day HDR brachytherapy in localized prostate cancer

Introduction and objectivesWe previously published the toxicity and initial results of a prospective cohort of patients treated with 2 fractions HDR-BRT administered in a single day. In the present analysis we report the long-term cancer control results of our prospective trial and investigate the relationship between PSA nadir and biochemical control. Material and methodsA total of 120 patients were treated with HDR Brachytherapy monotherapy administered in two fractions in a single day. Between November 2010 and February 2016, 84 patients with low-risk and 36 patients with intermediate-risk prostate cancer in accordance with the NCCN practice guidelines. ResultsMedian age was 66 years (range 45–84) and median PSA was 7.5 ng/ml (range 0.01–16 ng/ml). Overall, 84.2% had Gleason score 6 and 15.8% Gleason 7. Thirty-one percent of patients received ADT.After a median follow-up of the cohort was 123 months. Actuarial rates of no biochemical evidence of disease (bNED), overall survival, local control and metastasis-free survival for all patients were 93.3%, 86.7%, 95.2% and 96.1%, respectively.The median time to achieve PSA nadir was 80.5 months. Patients who attained a PSA Nadir ≤ 0.20 ng/mL exhibited a 10-year bNED survival rate of 96.9%, whereas thosewho failed to reach this PSA level had a survival rate of only 40%. ConclusionsIn patients with favorable localized prostate cancer, 2 fractions HDR-BT monotherapy is a highly curative radiation technique that attains PSA nadir levels < 0.2 ng/mL in 95% of cases.

Low-dose-rate brachytherapy in low-risk prostate cancer- treatment results, radiation toxicity and quality of life-dissertation project with literature review

Low-dose-rate brachytherapy (LDR-BT) is a an internal radiation therapy method for the treatment of localized prostate cancer The treatment modality has been known for several decades. The choice of the treatment modality for prostate cancer patients depends mainly on the stage of the disease and the prognostic factors. Brachytherapy monotherapy is a well-tolerated procedure compared to alternative treatments. Based on a literature review, we have considered a prospective study on the treatment efficiency after LDR-BT with a permanent iodine-125 (I-125) implant, compared to that of hypo-fractionated external beam radiotherapy (EBRT) alone. The working thesis is to present the advantages and disadvantages of LDR-BT for low-risk prostate carcinoma, compared to a similar group of patients treated with definitive intensity-modulated hypo-fractionated radiotherapy (IMHRT)

External beam radiotherapy combination is a risk factor for bladder cancer in patients with prostate cancer treated with brachytherapy

To investigate the risk of bladder cancer (BCa) in patients treated with brachytherapy for prostate cancer (PCa). We retrospectively analyzed 583 patients with PCa who underwent brachytherapy with or without external beam radiotherapy (EBRT). We analyzed the disease-free survival (DFS) of BCa in patients with PCa who underwent brachytherapy with or without EBRT. We performed multivariate Cox regression analyses of DFS using age, EBRT, and Brinkman index (BI) score (number of cigarettes smoked per day × number of years smoking) ≥ 200 as variables for BCa after brachytherapy. Fourteen patients (2.4%) developed BCa after brachytherapy with or without EBRT. The percentage of high-grade urothelial carcinoma (UC) was 63.6%. A total of 85.7% of patients had non-muscle invasive BCa, and 14.3% of patients had muscle invasive BCa. DFS was longer in brachytherapy monotherapy than in combination therapy (brachytherapy + EBRT). Multivariate Cox regression analysis showed that a BI score ≥ 200 (Hazard Ratio (HR 8.61; 95% Confidence Interval (CI) 1.12-65.98) and EBRT combination (HR 3.29; 95% CI 1.03-10.52) were significantly associated with BCa development in patients with PCa treated with brachytherapy. Furthermore, patients with BI score ≥ 200 and EBRT combination had a significantly higher risk of BCa compared with patients with BI score < 200 (HR Log-rank test P = 0.010). Most cases of BCa after brachytherapy with or without EBRT are high grade and invasive. We hypothesized that the EBRT combination might be a risk factor for BCa in patients with PCa who underwent brachytherapy.

Seed Density as a New Predictive Index of Seed Migration in Brachytherapy for Prostate Cancer Using Iodine-125 Loose Seed

This study aimed to examine the usefulness of seed density as a predictor of seed migration in patients with prostate cancer who received brachytherapy using Iodine-125 loose seed. From May 2006 to April 2016, 320 patients with localized prostate cancer underwent transperineal brachytherapy using iodine-125 loose seeds. Among them, 202 (63.1%) patients received brachytherapy monotherapy and 118 (36.9%) received combined brachytherapy and external beam radiotherapy. Seed density was calculated using the following formula: seed density = implanted seed number/prostate volume. All patients underwent radiography of the chest, abdomen and pelvis, and computed tomography at 1 day, 1 month, and 1 year after brachytherapy to evaluate the presence of seed migration. In total, the number of implanted seeds was 21,876. Seed migration was detected in 92 (28.8%) patients. Of a total of 21,876 seeds, 144 (0.66%) showed migration. The number of needles, number of seeds, and seed density were significantly higher in the group with migration than in the group without migration (p = 0.05). The ROC cutoff values for prostate volume, number of needles, number of seeds, and seed density were 20.9 cc, 21, 65, and 3.0, respectively. In the univariate analysis, prostate volume, number of needles, number of seeds, seed density, and treatment modality were all significant factors in predicting migration (p = 0.05). In the multivariate analysis, seed density and treatment modality were significant factors in predicting migration (p = 0.05). Seed density is useful for predicting seed migration. In cases with seed density > 3.0, it is necessary to take measures such as considering the use of stranded seeds.

Outcomes after PD-103 versus I-125 for low dose rate prostate brachytherapy monotherapy: An international, multi-institutional study

Background and PurposePd-103 and I-125 are commonly used in low dose rate (LDR) brachytherapy for prostate cancer. Comparisons of outcomes by isotope type are limited, but Pd-103 has distinct radiobiologic advantages over I-125 despite its lesser availability outside the United States. We evaluated oncologic outcomes after Pd-103 vs I-125 LDR monotherapy for prostate cancer. Materials and MethodsWe retrospectively analyzed databases at 8 institutions for men who received definitive LDR monotherapy with Pd-103 (n = 1,597) or I-125 (n = 7,504) for prostate cancer. Freedom from clinical failure (FFCF) and freedom from biochemical failure (FFBF) stratified by isotope were analyzed by Kaplan-Meier univariate and Cox multivariate analyses. Biochemical cure rates (prostate-specific antigen level ≤ 0.2 ng/mL between 3.5 and 4.5 years of follow-up) by isotype were calculated for men with at least 3.5 years of follow-up and compared by univariate and multivariate logistic regression. ResultsCompared with I-125, Pd-103 led to higher 7-year rates of FFBF (96.2% vs 87.6%, P < 0.001) and FFCF (96.5% vs 94.3%, P < 0.001). This difference held after multivariate adjustment for baseline factors (FFBF hazard ratio [HR] = 0.31, FFCF HR = 0.49, both P < 0.001). Pd-103 was also associated with higher cure rates on univariate (odds ratio [OR] = 5.9, P < 0.001) and multivariate (OR = 6.0, P < 0.001) analyses. Results retained significance in sensitivity analyses of data from the 4 institutions that used both isotopes (n = 2,971). ConclusionsPd-103 monotherapy was associated with higher FFBF, FFCF, and biochemical cure rates, and suggests that Pd-103 LDR may lead to improved oncologic outcomes compared with I-125.

Validation of the bladder neck as an important organ at risk in prostate seed brachytherapy based on D2cc: A single-institution, retrospective review.

International guidelines recommend urethral dose volume constraints to minimize the risk of urinary toxicity after prostate brachytherapy. An association between dose to the bladder neck (BN) and toxicity has previously been reported, and we sought to evaluate the impact of this organ at risk on urinary toxicity, based on intra-operative contouring. Rates of acute and late urinary toxicity (AUT and LUT, respectively) were graded according to CTCAE version 5.0 for 209 consecutive patients who underwent low-dose-rate (LDR) brachytherapy monotherapy, with approximately equal numbers treated before and after we began routinely contouring the BN. AUT and LUT were compared in patients treated before and after we began contouring the OAR, and also for those treated after we began contouring who had a D2cc of greater than or less than 50% prescription dose. AUT and LUT fell after intra-operative BN contouring was instituted. Rates of grade ≥ 2 AUT fell from 15/101 (15%) to 9/104 (8.6%), p = 0.245. Grade ≥ 2 LUT decreased from 32/100 (32%) to 18/100 (18%), p = 0.034. Grade ≥ 2 AUT was observed in 4/63 (6.3%) and 5/34 (15%) of those with a BN D2cc >/≤ 50%, respectively, of prescription dose. Corresponding rates for LUT were 11/62 (18%) and 5/32 (16%). There were lower urinary toxicity rates for patients treated after we commenced routine intra-operative contouring of the BN. No clear relationship was observed between dosimetry and toxicity in our population.

Sunday, June 19, 2022 10:30 AM - 11:30 AMPP07 Presentation Time: 10:30 AM: Trend of LDR and HDR Brachytherapy Utilization for Prostate Cancer Treatment: Analysis of a Large Hospital Based Registry

<h3>Purpose</h3> Although brachytherapy (BT) is one of the most effective modalities in radiotherapy for the treatment of prostate cancer (PCa), popularity of BT is perceived as on the decline. In this study we have investigated the trend of utilization of low-dose-rate (LDR) and high-dose-rate (HDR) BT over the past 15 years (2004-2018), as well as the application of BT as boost versus BT as monotherapy using a large hospital-based database. <h3>Materials and Methods</h3> We analyzed an extensive data set using National Cancer Database (NCDB) of N0, M0, non-surgical PCa patients diagnosed between 2004 and 2018. Of 247,426 patients who met the criteria, 78,868 had BT monotherapy and 23,453 has BT boost following the external beam radiotherapy (EBRT). Patients were stratified according to the National Comprehensive Cancer Network (NCCN) guidelines: low-risk (clinical stage T1-T2a, Gleason Score (GS) ≤ 6, Prostate-Specific Antigen (PSA) < 10), intermediate-risk (clinical stage T2b or T2c, GS of 7, PSA of 10-20), and high-risk (clinical stage T3-T4, GS of 8-10, PSA > 20). Patients were grouped into two categories based on BT monotherapy modality (LDR, n=52,293 and HDR, n=26,575) for evaluating the utilization as well as assessing the overall survival (OS) probability that was determined using a Kaplan-Meier estimator. Propensity-score matched analysis was performed for each risk group for the two treatments (LDR, and HDR). IBM SPSS software (version 26.0) was used for statistical analysis; p-value <0.05 was considered statistically significant. <h3>Results</h3> During this time span (2004-2018), 70.3% BT was utilized as monotherapy compared to 29.7% as boost with EBRT. LDR monotherapy increased by about 8.8% while HDR increased by 24.7% between 2004 and 2007. However, after 2007 until 2014, BT was decreased by 54.7% and 65.7%, for LDR and HDR, respectively. Since 2014, BT utilization did not change over the years. Maximum decreased utilization was observed in low-risk group, whereas a slight increase in high-risk group was observed since 2013. Median OS was higher in low-risk and intermediate-risk patients treated with HDR (83.7/72.1 months), compared to treated with LDR (77.7/65.7 months). However, for high-risk PCa both the LDR and HDR performed equally well (median OS 69.2 vs. 69.6 months). PSM analysis using the matched dataset for both the risk groups confirmed the results obtained. All figures were found as statistically significant (p<0.001). <h3>Conclusions</h3> This study revealed that despite initial increase (during 2004-2006), there was a steady decline in BT utilization between 2007 and 2014. However, it remained almost unchanged after 2014. Reduction in BT application for low-risk PCa was most prominent, whereas, there was an increased trend of utilization both the LDR and HDR in high-risk group since 2013.

PP06 Presentation Time: 9:50 AM: Biochemical Failure-Free Survival Rates After Brachytherapy with I-125, Pd-103, or Cs-131 for Intermediate-Risk Prostate Cancer: Phase II Trial

<h3>Background</h3> Iodine (I)-125 is traditionally used for low-dose-rate (LDR) brachytherapy for prostate cancer, but emerging data support the use of cesium (Cs)-131 or palladium (Pd)-103 as well. Although the safety and effectiveness of these three isotopes for intermediate risk prostate cancer have been established, the relative efficacy of each is unknown. <h3>Purpose</h3> To compare biochemical outcomes after I-125, Pd-103, or Cs-131 brachytherapy as definitive treatment for intermediate-risk prostate cancer. <h3>Materials and Methods</h3> This prospective phase II trial evaluated ultrasound-guided LDR brachytherapy monotherapy as definitive treatment for intermediate-risk prostate cancer at a single institution in 2006-2013. The choice of isotope and corresponding prescribed dose was made sequentially (starting with I-125, D=144 Gy; followed by Pd-103, D=125 Gy; then Cs-131, D=115 Gy. Patients had intermediate-risk disease (Gleason score [GS] 6 or 7 [3+4 or 4+3]), no evidence of nodal or metastatic disease, and no prior hormonal or radiation therapy. Follow-up visits were every 4 months for the first year after the implant, every 6 months for the next 5 years, and yearly thereafter, with prostate-specific antigen (PSA) levels measured at each visit. Biochemical failure (BCF) was defined per the Phoenix criteria as an increase in PSA value to nadir +2 ng/dL or radiologic or histologic evidence of recurrence with increasing PSA value. Patients were considered to have no evidence of disease (NED) if the PSA was <0.2 ng/dL at the specified time. Treatment efficacy was defined as time to BCF and the presence or absence of NED at a given time. Kaplan-Meier analysis was used to estimate BCF-free survival rates by isotope, with between-group differences assessed with log-rank tests. One-way analysis of variance was used to compare time to BCF between groups. Simple linear regression was used to determine the influence of isotope on achieving NED. <h3>Results</h3> Of the 300 patients in this trial (median age 64.9 years), 100 were treated with Cs-131, 98 with I-125, and 102 with Pd-103. Eleven patients (3.7%) had GS 6 disease, 236 (78.7%) had GS 7 (3+4) disease, and 53 (17.7%) had GS 7 (4+3) disease; 195 (65.0%) had favorable intermediate-risk, and 105 (35.0%) had unfavorable intermediate-risk disease. The median follow-up time was 8.7 years. During follow-up, 27 patients (9.0%) experienced BCF, 7 (7%) in the Cs-131 group, 13 (13.3%) in the I-125 group, and 7 (7.1%) in the Pd-103 group. Among those 27 patients with BCF, 10 (37.0%) received salvage therapy with surgery, brachytherapy, radiation therapy, or cryotherapy. The BCF-free survival rates were 93% for those treated with Cs-131, 86.7% for I-125, and 93.1% for Pd-103 (p=0.86) (Figure); the median time was not reached because of the short follow-up and the limited number of events. Follow-up data were available for 101 patients at 8.7 years; 100 patients (99%) had NED. Although 36 patients (12%) died during the study, only 1 death (0.3%) was related to prostate cancer. <h3>Conclusions</h3> No significant differences in efficacy were found among Cs-131, Pd-103, and I-125 for LDR brachytherapy monotherapy for intermediate-risk prostate cancer. The choice of isotope should be based on dosimetric advantages, estimated risk of toxicity, and quality-of-life profile. A larger randomized trial is needed to assess potential differences in efficacy among isotopes.

PSOR6 Presentation Time: 11:55 AM: A Scoping Review of Immune Changes After Prostate Brachytherapy

<h3>Purpose</h3> Prostate brachytherapy (BT), with either low-dose-rate (LDR) or high-dose-rate (HDR), delivers a highly conformal and heterogeneous dose, allowing for dose escalation beyond external beam radiotherapy (EBRT). Whether this different dose deposition results in opportunistic biological changes that could be harnessed to improve outcomes is not well studied. Given the increasing interest in incorporating immunotherapy into prostate cancer treatment, we sought to investigate the impact of prostate BT on the immune system. <h3>Materials Methods</h3> A scoping review was performed using PubMed and Scopus for papers published between 2011-2021. Search terms used were "brachytherapy" AND "immune" AND "prostate". A total of 62 records were identified. After review, 6 studies were identified for review that included information an immune assessment on patient samples (tissue and/or blood) after prostate BT. <h3>Results</h3> 2 LDR studies (N=68) evaluated changes in the peripheral blood following I-125 BT monotherapy. Both studies demonstrated significant increases in peripheral CD3+ T cells and CD4+ T cells post-BT. However, increased circulating CD8+ T cells were observed in only one study. One study also demonstrated significant increases in Treg subsets up to 150 days post-treatment, which may be compensatory to increased cytotoxic T cell titers. 4 HDR studies (N=37) were identified (HDR fraction sizes 10-15 Gy), and all were done in combination with EBRT. Androgen deprivation therapy was included, for select patients, and one study included nivolumab. Three looked at changes in tissue immune infiltrates seen in post-BT biopsies and 1 looked at changes in both tissue and blood. The largest study (N=24) showed a single 10 Gy fraction of HDR converted 80% of "cold" tumors into an "intermediate" or "hot" state, based on a tumor inflammation signature, when comparing a pre-BT biopsy to a biopsy done prior to HDR fraction 2. In another study (N=6) a significant correlation between increased pathologic response (no tumor in ≥ 4/6 cores) and increased CD4+ and CD8+ T cells in prostate tissue as well as CD4+ T cells in the blood was seen (p values not reported). Tumor infiltrating lymphocyte recruitment may be context dependent given a case report demonstrated decreased T cell infiltration post BT+EBRT. Finally, in a separate study (N=6), peripheral blood analysis demonstrated increased CD8+ T cells with an activated phenotype, decreased CD4+/CD8+ T ratio, decreased CD4+ helper T cells, and increased CD4+PD1+ cells at 3 months post-treatment when compared to baseline levels EBRT. Patients with PSA<0.02 at 3 months were also more likely to have increased CD4+ PD1+ T cells. <h3>Conclusion</h3> Both LDR and HDR BT can invoke an immune activating phenotype in prostate cancer; however, changes in immunosuppressive cells are also seen. Additional data is needed to understand how to better promote synergy between these changes and improving clinical outcomes.

Disparities in Specialized Radiation Treatment Modalities for Grade Group 2, Intermediate-Risk Prostate Cancer

<h3>Purpose/Objective(s)</h3> Men with Grade Group 2 (GG2) intermediate risk (IR) prostate cancer (PCa) have multiple curative radiation (RT) options. Compared to conventional external beam photon RT (XRT), including 3D-conformal RT (3DCRT) and IMRT, highly conformal RT techniques may provide less integral RT dose to normal tissue, including brachytherapy (BT), SBRT, and proton beam radiation therapy (PBT). These treatments require either advanced equipment and/or specialized training. Here we analyzed national trends in utilization of XRT, BT monotherapy, SBRT, and PBT, and assessed potential factors associated with receiving each technique. We hypothesize that socioeconomic and/or racial disparities are associated with differences in utilization of these specialized techniques. <h3>Materials/Methods</h3> Men diagnosed with favorable IR PCa cancer, defined as Gleason 3+4 disease, PSA < 20 and clinical stage T1-T2 N0 M0, between 2004-2017 were identified in the National Cancer Database. Cohorts were defined as: XRT (3DCRT+IMRT, hypofractionated (HF) or standard fractionation (SF)), BT monotherapy (HDR, LDR), SBRT (5 fx) and PBT (HF or SF). Trends in utilization were examined. Associations between technique and patient, clinical disease, and sociodemographic characteristics were assessed by multivariable logistic regression, with <i>P</i><0.05 considered significant. <h3>Results</h3> 71,140 patients met inclusion criteria of which 72.4% received standard XRT and 27.6 % received specialized radiation modalities (18.5% brachytherapy, 6.0% SBRT, & 3.1% PBT). Utilization of XRT and BT declined from 71.0% (XRT) and 27.5% (BT) in 2004 to 69.7% (XRT) and 17.2% (BT) in 2017. Receipt of SBRT and PBT increased from 0% (SBRT) and 1.45% (PBT) in 2004 to 9.9% (SBRT) and 3.3% (PBT) in 2017, respectively. On multivariable logistic regression, Black patients were less likely to receive BT (adjusted OR 0.79; 95%CI 0.74-0.83), SBRT (adjusted OR 0.77; 95%CI 0.70-0.85), or PBT (adjusted OR 0.39; 95%CI 0.33-0.47) compared to XRT (all <i>P</i><0.0001). Socially disadvantaged seniors (SDS; age >65 years with Medicaid insurance) were less likely to receive specialized RT (adjusted OR 0.45; 95%CI 0.31-0.60; P<0.0001). Factors associated with increased likelihood of receiving BT, SBRT, or PBT included: treatment at Academic/Research center, treatment at a metropolitan facility, younger age, lower Charlson-Deyo Comorbidity Score, and lower PSA at presentation (all P < 0.01). <h3>Conclusion</h3> Trends in utilization of RT modalities have dramatically changed in recent years with a sharp decline in BT, a doubling of PBT, and rapid adoption of SBRT, as coded in the NCDB. Compared to White patients with GG2 IR PCa, there are disparities in utilization of BT, SBRT, and PBT for Black patients and for SDS. It is unclear whether similar disparities exist for other prostate cancer grade groups for which BT and SBRT are being utilized. Future efforts should address access-to-care challenges for the use of these specialized techniques as they are expanded into higher GG.

Prostate Brachytherapy Utilization in the COVID-19 Era: A Cross-Sectional Study of Radiation Oncologists in the United States

Purpose/Objective(s)Brachytherapy (BT) is indicated as monotherapy for lower risk prostate cancer (PC) or to boost external beam radiation therapy (EBRT) for higher risk disease. Despite its advantages, such as decreased treatment time and cost, BT utilization in the United States (US) is declining. We surveyed US radiation oncologists (ROs) to determine the proportion of providers who offer BT for PC, by risk group, and whether the COVID-19 pandemic influenced practice patterns. We hypothesized that rates of utilization would continue to lag EBRT.Materials/MethodsFrom July-October 2021, an anonymized survey was distributed to currently practicing US ROs. Demographic and practice characteristics were collected. Questions assessing utilization of BT and EBRT for patients of varying risk group and the effect of the pandemic on practice patterns were administered. The primary endpoint was the rate of BT utilization by risk group. Descriptive statistics were performed. The bivariate relationships between provider characteristics and likelihood of offering BT were assessed using 2-sided chi-squared tests (α=0.05).ResultsOf 203 respondents (72% male, 72% white, 53% non-academic, 69% >10 years in practice), 156 (77%) treated PC. For low (41% total; 25% low dose rate [LDR], 10% high dose rate [HDR], 6% both) and favorable intermediate (FI) (37% total; 21% LDR, 10% HDR, 6% both) PC, BT was less commonly offered then stereotactic body (SBRT – 54% and 48%), moderately hypofractionated (MHFRT – 83% and 87%), and conventionally fractionated (CFEBRT – 37 and 38%) radiation therapy. For unfavorable intermediate PC, BT alone (7%) and BT+EBRT (37%) were less offered then moderately HFRT (82%) and CFEBRT (46%). For high and very high-risk PC, BT boost was not routinely offered (44% and 37%, respectively). For every risk group, academic ROs were more likely to offer BT (50-60% vs. 29-46%, all p < 0.05) (Table 1). For FI only, ROs treating both urban and rural patients were less likely to offer BT than those in an urban or rural setting (p=0.045). No other characteristics were associated with offering BT. <1% of respondents reported increased BT usage due to the pandemic.ConclusionDespite its advantages for patients, BT remains underutilized, particularly in non-academic settings, with <1/2 of surveyed ROs offering BT monotherapy for low to FI risk PC or to boost higher risk disease. Practice patterns were unaffected by COVID-19 likely due to barriers to starting a BT program. Provider retraining may be critical to increasing utilization rates.

Prostate brachytherapy utilization in the COVID-19 era: A cross-sectional study of radiation oncologists in the United States

PURPOSEDespite advantages such as abbreviated treatment course, brachytherapy (BT) utilization rates for prostate cancer (PC) in the United States (US) are declining. We surveyed practicing US radiation oncologists (ROs) to determine the proportion who offer BT for PC and whether the COVID-19 pandemic influenced practice patterns. MATERIALS AND METHODSFrom July-October 2021, we surveyed practicing US ROs. Provider demographic and practice characteristics were collected. Questions assessing utilization of BT and external beam (EBRT) for patients of varying risk groups and the effect of the pandemic on practice patterns were administered. Descriptive statistics were reported. The bivariate relationships between provider characteristics and likelihood of offering BT were assessed using the Chi-square test (α < 0.05). RESULTSSix percent of surveyed ROs responded, with 203 meeting inclusion criteria (72% male, 72% white, 53% non-academic, 69% >10 years in practice) and 156 (77%) treating PC. For low-risk, fewer providers offered BT (41% total; 25% low dose rate [LDR], 10% high dose rate [HDR], 6% both) than stereotactic body (SBRT) (54%) and moderately hypofractionated radiation therapy (MHFRT) (83%). For favorable intermediate risk, fewer offered BT (37% total; 21% LDR, 10% HDR, 6% both) than SBRT (48%), MHFRT (87%), and conventionally fractionated EBRT (38%). For high (44%) and very-high (37%) risk, fewer offered EBRT+BT than EBRT alone. For every risk group, academic ROs were significantly more likely to offer BT (all p-values<0.05). <1% of respondents reported increased pandemic-related BT usage. CONCLUSIONSUS ROs, particularly in non-academic settings, do not routinely offer BT monotherapy or boost (<50%). Practice patterns were unaffected by COVID-19. Retraining may be critical to increasing utilization.

Oncological and urinary outcomes following low-dose-rate brachytherapy with a median follow-up of 11.8 years.

To examine the long-term oncological outcomes and urological morbidity of low-dose-rate prostate brachytherapy (LDRBT) monotherapy using live intraoperative dosimetry planning and an automated needle navigation delivery system for the treatment of men with low and intermediate-risk prostate cancer. A prospective database of 400 consecutive patients who underwent LDRBT between July 2003 and June 2015 was retrospectively reviewed to assess urinary side-effects and biochemical progression, based on the Phoenix definition and also a definition of a prostate-specific antigen (PSA) level of ≥0.2 μg/L. Minimum patient follow-up was 5.5 years. The median follow-up of the entire cohort was 11.8 years. The median (range) PSA level was 6.1 (0.9-17) μg/L and the median Gleason score was 3 + 4. The biochemical relapse-free survival (RFS; freedom from biochemical recurrence) based on the Phoenix definition was 85.8% (343/400). The RFS using a 'surgical' definition of a PSA level of <0.2 μg/L was 71% (284/400). Of the 297 men followed for ≥10 years, prostate cancer-specific survival (PCSS) was 98% (291/297). Post-LDRBT urethral stricture developed in 11 men (2.8%, 11/400). For men with ≥10 years of follow-up, 22 men (7.4%, 22/297) required a pad for either stress or urge urinary incontinence (UI). UI was identified in only 2.2% (one of 46) of men who had a bladder neck incision (BNI) before LDRBT. LDRBT is associated with excellent PCSS, with a median follow-up of 11.8 years. The risk of post-implantation urethral stricture and UI is low and a pre-implantation BNI for management of bladder outflow obstruction does not increase the risk of UI or urethral stricture.

Long term impact of LDR brachytherapy for prostate cancer on erectile function: Single centre tertiary referral outcomes with 8-year follow up

ABSTRACT Introduction Low dose rate (LDR) brachytherapy is an established treatment for localised low and intermediate risk prostate cancer, whereby multiple radioactive seeds are permanently implanted into the prostate. Brachytherapy is considered to be a less invasive option with a more favourable side effect profile compared to radical prostatectomy. Erectile dysfunction (ED) is still common after brachytherapy further understanding of this relationship would enable enhanced patient counselling. Objective To assess rate and severity of ED following LDR Brachytherapy monotherapy for low and intermediate risk prostate cancer in a tertiary referral centre. Methods We conducted a retrospective observational cohort study of patients who underwent LDR Brachytherapy as monotherapy in our institution between 2002 -2019. We extracted and analysed data from a prospective database obtaining baseline demographic data and simplified International Index of Erectile Function (IIEF-5) scores at regular intervals during follow up. The proportion of patients in each IIEF-5 category: severe ED (&amp;lt;12), moderate ED (12-16), mild ED (17-21) and no ED (22-25) were recorded at baseline, at regular intervals for up to 8 years. The degree of ED was assessed by calculating the mean differences between baseline (n=1017) and values at various timepoints; 6 weeks (1-3 months, n=905), 6 months (3-9 months, n=884), 1 year (9-18months, n=838), 2 years (18-30 months, n=705), 3 years, (30-48 months, n=561), 5 years (48-72 months, n= 489) and 8 years (72-120 months, n=262). Results A total of 1491 suitable patients were identified. Baseline IIEF scores were available for 1017 patients. The median age was 63 (40-84), with 98% of patients being between 50 and 80. The proportion of patients with severe ED doubles at 6 weeks, and remains similar throughout the duration of follow up, as can be seen in Figure 1. The distribution of IIEF-5 scores overtime are seen in figure 2. Compared to baseline, at 6 weeks the mean difference in IIEF score is -6.37 (p&amp;lt;0.001), which is also similar to the remainder of the follow up period, with a mean difference of -7.45 at 8 years (p&amp;lt;0.001). These results are seen in Table 1. Conclusion Patients who underwent LDR brachytherapy experienced a mild, early decline in sexual function, which may be explained by the implantation procedure. Sexual function then remained relatively stable with no significant further late deterioration over the subsequent 5-10 years, aside from a slight decrease which would be expected with aging. The majority of patients with no dysfunction at baseline experienced at least mild early and long-term ED over time. We plan to build on this study by conducting multi-variate analysis for predictors of ED post brachytherapy.