Low Dose Rate Brachytherapy Research Articles

21: Comparison of Acute Toxicities in Patients with Prostate Cancer Treated with High Dose Rate Versus Low Dose Rate Brachytherapy Boost

21: Comparison of Acute Toxicities in Patients with Prostate Cancer Treated with High Dose Rate Versus Low Dose Rate Brachytherapy Boost

Coverage of the external prostatic region by the hybrid method compared with the conventional method of prostate low-dose-rate brachytherapy: A randomized controlled study.

To compare the dose evaluation parameters between conventional (using loose seed alone) and hybrid (using loose seeds in combination with stranded seeds) low-dose rate brachytherapy for prostate cancer. Between 2014 and July 2016, a total of 219 patients who underwent low-dose rate brachytherapy were enrolled in a randomized controlled trial (trial number: UMIN 000012780). Patients were randomized and allocated to two groups (conventional method vs hybrid method). Post-dosimetric parameters (%D90, minimal percentage of the dose received by 90% of the prostate gland; V100, percentage of the prostate volume receiving 100% of the prescribed minimal peripheral dose; V150, percentage of the prostate volume receiving 150% of the prescribed minimal peripheral dose; %UD30, minimal percentage of the dose received by 30% of the urethra; R100, rectal volume [mL] receiving 100% of the prescribed dose) calculated at 1month after seed implantation by computed tomography scan were compared between the two groups, as well as the post-dosimetric parameters using the planning target volume of the prostate+5-mm margin. Regarding dose evaluation parameters, the prostate dose (%D90, V100, V150) and the urethral dose (%UD30) were not significantly different between the two groups, whereas V100 (+5-mm margin) and %D90 (+5-mm margin) were significantly higher in the hybrid method group compared with the conventional method group (P<0.001). The present randomized study shows that the hybrid method of low-dose rate brachytherapy can achieve a higher coverage of the periprostatic region compared with the conventional method while maintaining an acceptable level of urethral and rectal doses.

Variations in Resources Among Radiation Oncology Residency Programs in the United States

The purpose of this research was to assess the existing variations in the residency training resources among radiation oncology (RO) residency programs in the United States. We queried each residency program website and Fellowship Residency Electronic Interactive Data Access System website (www.freida.ama-assn.org) to obtain information on faculty and available treatment modalities. The data were continuously updated, most recently as of April 30, 2019. A total of 94 RO residency programs were identified during the academic year 2018-2019, and data were collected. The median number of attending physicians was 13 (range, 4 -71). The median number of physicists and biologists were 9 and 3, respectively. The conventional techniques, including 3 dimensional conformal radation therapy, intensity modulated radiation therapy, electron therapy, and stereotactic body radiation therap/stereotactic radiosurgery, were available in all residency programs. In terms of specialized external beam radiation therapy machines, gamma knife, CyberKnife, and magnetic resonance imaging (MRI) linear accelerator were available in 49 (52%), 21(22%), and 7 (8%) programs, respectively. Only 19 programs (20%) had in-house proton therapy availability; however, 37 programs (39%) offered proton therapy training via resident rotation at an affiliated institution. Prostate, gynecologic, and breast brachytherapy were available in 81 (86%), 82 (87%), and 58 (62%) programs, respectively. Eighty-one (86%) programs reported to have high dose rate, and only 20 (21%) programs had low dose rate brachytherapy. Our study found that marked variations exist among RO residency programs in the United States during academic year 2018-2019 and will serve as a baseline for future intervention.

Management options for vaginal intraepithelial neoplasia.

Vaginal intraepithelial neoplasia (VaIN) is a rare disease of the lower genital tract, strongly associated with HPV infection, which may progress to vaginal carcinoma. The aim of this review is to summarise current treatment options, evaluate their efficacy and make provide recommendations on the optimal management of the disease. A comprehensive search of the literature was performed using the PubMed database for articles referring to the treatment of VaIN. We restricted our search only in articles written in English with publication dates within the last 10 years. Surgical approach included local excision, CO2 laser ablation, CO2 laser skinning colpectomy and laparoscopic upper vaginectomy. Medical management was based on intravaginally administered topical agents such as 5% imiquimod cream, 5-fluorouracil cream and topical oestrogens. Intracavitary radiation therapy was reported in two forms: Low-dose rate (LDR) brachytherapy and high-dose rate (HDR) brachytherapy. All treatment options were well tolerated, with satisfactory cure rates and acceptable recurrence rates. The choice of treatment depends upon many factors. Surgical excision is the mainstay of treatment and should be performed if invasion cannot be excluded. Topical agents are useful for persistent, multifocal lesions or for women that cannot undergo surgical treatment. Brachytherapy is associated with high morbidity rates and should be reserved for women who have multifocal disease, are poor surgical candidates and/or have failed other treatments. CO2 laser ablation achieves minimal scarring and sexual dysfunction; however, invasive disease should be ruled out with biopsies before the initiation of the treatment.

Prostate-specific antigen kinetics and biochemical control following stereotactic body radiation therapy, high dose rate brachytherapy, and low dose rate brachytherapy: A multi-institutional analysis of 3502 patients

Background and purposeStereotactic body radiation therapy (SBRT), low dose rate brachytherapy (LDR-BT) and high dose rate brachytherapy (HDR-BT) are ablative-intent radiotherapy options for prostate cancer (PCa). These vary considerably in dose delivery, which may impact post-treatment prostate-specific antigen (PSA) patterns and biochemical control. We compared PSA kinetics between SBRT, HDR-BT, and LDR-BT, and assessed their relationships to biochemical recurrence-free survival (BCRFS). Methods and materialsRetrospective PSA data were analyzed for 3502 men with low-risk (n = 2223; 63.5%), favorable intermediate-risk (n = 869; 24.8%), and unfavorable intermediate-risk (n = 410; 11.7%) PCa treated with SBRT (n = 1716; 49.0%), HDR-BT (n = 512; 14.6%), or LDR-BT (n = 1274; 36.4%) without upfront androgen deprivation therapy at 10 institutions from 1990 to 2017. We compared nadir PSA (nPSA), time to nPSA, achievement of nPSA <0.2 ng/mL and <0.5 ng/mL, rates of nPSA <0.4 ng/mL at 4 years, and BCRFS. ResultsMedian follow-up was 72 months. Median nPSA and nPSA <0.2 ng/mL were stratified by risk group (interaction p ≤ 0.001). Median nPSA and time to nPSA were 0.2 ng/mL at 44 months after SBRT, 0.1–0.2 ng/mL at 37 months after HDR-BT, and 0.01–0.2 ng/mL at 51 months after LDR-BT (mean log nPSA p ≤ 0.009 for LDR-BT vs. SBRT or HDR-BT for low/favorable intermediate-risk). There were no differences in nPSA <0.4 ng/mL at 4 years (p ≥ 0.51). BCRFS was similar for all three modalities (p ≥ 0.27). Continued PSA decay beyond 4 years was predictive of durable biochemical control. ConclusionLDR-BT led to lower nPSAs with longer continued decay compared to SBRT and HDR-BT, but no differences in BCRFS.

Risk of erectile dysfunction after modern radiotherapy for intact prostate cancer.

Erectile dysfunction (ED) is a prevalent side effect of prostate cancer treatment. We hypothesized that the previously reported rates of ED may have improved with the advent of modern technology. The purpose of this project was to evaluate modern external beam radiotherapy and brachytherapy techniques to determine the incidence of radiotherapy (RT) induced ED. A systematic review of the literature published between January 2002 and December 2018 was performed to obtain patient reported rates of ED after definitive external beam radiotherapy, ultrafractionated stereotactic radiotherapy, and brachytherapy (BT) to the prostate in men who were potent prior to RT. Univariate and multivariate analyses of radiation dose, treatment strategy, and length of follow-up were analyzed to ascertain their relationship with RT-induced ED. Of 890 articles reviewed, 24 met inclusion criteria, providing data from 2714 patients. Diminished erectile function status post RT was common and similar across all studies. The median increase in men reporting ED was 17%, 26%, 23%, and 23%, 3DCRT, IMRT, low dose rate BT, and SBRT, respectively, at 2-year median follow-up. ED is a common side effect of RT. Risk of post-RT ED is similar for both LDR brachytherapy and external beam RT with advanced prostate targeting and penile-bulb sparing techniques utilized in modern RT techniques.

Salvage I-125 brachytherapy for locally-recurrent prostate cancer after radiotherapy.

Retrospective, single-institution analysis of clinical outcomes and treatment-related toxicity in patients treated with salvage I-125 low-dose rate (LDR) brachytherapy (BT) for locally-recurrent prostate cancer after radiotherapy. Between 2008 and 2018, 30 patients with biopsy-confirmed prostate cancer recurrence underwent salvage treatment with I-125 LDR-BT. Of these 30 patients, 14 were previously treated with primary external beam radiotherapy (EBRT; median dose, 73 Gy) and 16 with primary I-125 LDR-BT (145 Gy and 160 Gy in 14 and 2 cases, respectively). At seed implantation, the mean age was 75.8 years, with a median Gleason score of 7 and pre-salvage PSA of <10 ng/mL. Six patients received androgen deprivation therapy for six months after relapse diagnosis. The prescribed salvage I-125 BT dose to the gland was 120-130 Gy, with dose restrictions of Dmax <135% (urethra) and <100% (rectum). Toxicity was evaluated according to the CTCAE scale (v4.0). At a median follow-up of 45 months, the biochemical recurrence-free survival rates at 1, 3 and 5 years were 86.7%, 56.7% and 53.3%, respectively. Overall survival at 5 years was 87%. On the multivariate analysis, two variables were significant predictors of recurrence: PSA at relapse and nadir PSA post-salvage. Grade 3 genitourinary toxicity was observed in 5 patients (radiation-induced cystitis in 3 cases and urethral stenosis in 2) and G3 gastrointestinal toxicity in 3 patients (rectal bleeding). Salvage therapy with I-125 brachytherapy is a safe and effective treatment option for locally-recurrent prostate cancer in previously-irradiated patients. High pre-salvage PSA and post-salvage nadir PSA values were significantly associated with a worse disease control after salvage I-125 LDR-BT. In well-selected patients, I-125 LDR-BT is comparable to other salvage therapies in terms of disease control and toxicity. However, more research is needed to determine the optimal management of locally-recurrent prostate cancer.

A prospective study of oral 5-aminolevulinic acid to prevent adverse events in patients with localized prostate cancer undergoing low-dose-rate brachytherapy: Protocol of the AMBER study

BackgroundRadiotherapy is one of the most frequently selected treatment options for patients with prostate cancer. However, adverse effects related to the irradiated surrounding normal organs are significant clinical concerns. Specifically, genitourinary and gastrointestinal toxicities can lead to a dramatically reduced quality of life. The aim of this clinical trial is to determine the efficacy of oral 5-aminolevulinic acid (ALA) phosphate with sodium ferrous citrate (SFC) in patients treated with low-dose-rate brachytherapy (LDR-BT) using an iodine-125 seed source. MethodsThe AMBER study is a prospective, single-center trial in patients with localized prostate cancer undergoing LDR-BT. Patients who undergo supplementary extra-beam radiotherapy are excluded, whereas those who undergo pre-implantation short-term (4–6 months) androgen deprivation therapy to decrease the prostate volume and/or improve oncological outcomes are included. After the screening and registration, the patients will be instructed to take capsules of ALA-SFC twice a day (200 mg and 229.42 mg per day) for 6 months from the day of seed implantation (prescribed radiation dose of 160 Gy). Patient data will be collected before the implantation; during oral ALA-SFC treatment; and 1, 3, 6, 9, and 12 month(s) after seed implantation. The primary endpoint of this trial is the urinary frequency 3 months after seed implantation. At each visit, the 24-h urinary frequency, total voided volume, and mean voided volume on a frequency volume chart and other patient-reported outcomes are recorded. The data of the trial cases will be compared with those of historical controls, who are consecutive patients undergoing LDR-BT without supplementary extra-beam radiotherapy between January 2016 and January 2019. The number of subjects has been set to be 50 for trial cases and 150 for the historical control cases. Pre- and post-treatment clinicopathologic factors are compared between two groups. DiscussionThe goal of this trial is to determine the potential benefit of ALA-SFC in patients who undergo LDR-BT. To the best of our knowledge, this is the first study investigating the potential clinical benefit of oral ALA-SFC after radiotherapy. More evidence from a further randomized controlled trial is needed to change the standard of care and lead to better post-radiotherapy management. Trial registrationThis clinical trial was prospectively registered with the Japan Registry of Clinical Trials on 5 December 2019. The reference number is jRCTs051190077, nara0013 (Certified Review Board of Nara Medical University).

On the stability of well-type ionization chamber source strength calibration coefficients.

To investigate the variability and stability of brachytherapy source strength calibration coefficients for air-communicating and pressurized well-type ionization chambers among high-dose rate (HDR), low-dose rate (LDR), and electronic brachytherapy (EBT) source qualities. These qualities of an ionization chamber are important features to assess given their role in maintaining traceability to a primary national standards laboratory and facilitating efficacious patient care in brachytherapy. The calibration records from the University of Wisconsin Accredited Dosimetry Calibration Laboratory (UWADCL) customer well-type ionization chamber database were retrospectively analyzed for calibrations performed between 1996 and 2019. A statistical analysis was performed and differentiated among calibration type to quantify the distribution of chamber calibration coefficients among several chamber models. Distributions were quantified based on their moments and by quantile analysis. For LDR calibrations, chamber response was further differentiated by seed type to study the variability in seed dependence within and across chamber models. In addition to these metrics, the calibration lineage at the UWADCL was used to assess the stability of these calibration coefficients among chamber model and source type based on the ratio of subsequent calibration coefficients. The distribution of brachytherapy source strength calibration coefficients for a particular chamber model is not necessarily normally distributed and is sensitive to changes in the machining tolerances or design of the chamber model. Calibration source quality also influenced the distributions of calibration coefficients for a chamber model; the air-kerma rate calibration coefficients for EBT sources were the most variable followed by LDR and then HDR source types. The stability of a chamber's source strength calibration coefficient exhibited a similar dependence on the source quality. Air-communicating and pressurized chambers exhibited an average stability between subsequent calibrations of 0.2% and 3.0%, respectively, for HDR calibrations, but could exhibit more than double this variability characteristic of their leptokurtic distributions. For LDR calibrations, the spread and stability in a model's calibration ratio toward another seed type is extensive and notable. For some seed types and chamber models exhibit variations of <0.5% while others exceeded 2.0%. Furthermore, the magnitude of this dependence is outside the variability of the source's source strength due to manufacturing, which was determined from the manufacturer and NIST source strength intercomparison records at the UWADCL. As a result, establishing and disseminating calibration conversion factors among different source and chamber models is not advised as it would substantially increase the uncertainty in a clinical user's determination of source strength. The calibration of a well-type ionization chamber is unique to the chamber, source, and source holder. Attempting to generalize source strength calibration coefficients among chambers of the same model or source type is impractical given the variation in response observed across the calibration history of the UWADCL. Attempting to quantitate and transfer calibration coefficients in such a relative sense may significantly degrade the uncertainty relative to specifically calibrating a chamber for an individual source.

Analysis of outcomes after non-contour-based dose painting of dominant intra-epithelial lesion in intra-operative low-dose rate brachytherapy

PurposeTo compare the outcomes of patients with intermediate risk prostate cancer (IR-PCa) treated with low-dose rate I-125 seed brachytherapy (LDR-BT) and targeted dose painting of a histologic dominant intra-epithelial lesion (DIL) to those without a DIL. Methods455 patients with IR-PCa were treated at a single center with intra-operatively planned LDR-BT, each following the same in-house dose constraints. Patients with a DIL on pathology had hot spots localized to that region but no specific contouring during the procedure. Results396 (87%) patients had a DIL. Baseline tumor characteristics and overall prostate dosimetry were similar between patients with and without DIL except the median number of biopsy cores taken: 10 (10–12) vs 12 (10–12) (p = 0.002).19 (5%) and 18 (5%) of patients with and 1 (2%) and 0 (0%) of those without DIL experienced CTCAE grade 2 and 3 toxicity respectively. Overall, toxicity grade did not significantly correlate with presence of DIL (p = 0.10).Estimated 7-year freedom from biochemical failure (FFBF) was 84% (95% confidence interval: 79–89) and 70% (54–89) in patients with and without a DIL (log-rank p = 0.315). In DIL patients, cox regression revealed location of DIL (“Base” vs “Apex” HR: 1.03; 1.00–1.06; p = 0.03) and older age (70 vs 60 HR: 1.62; 1.06–2.49; p = 0.03) was associated with poor FFBF. ConclusionsTargeting DIL through dose painting during intraoperatively planned LDR-BT provided no statistically significant change in FFBF. Patients with DILs in the prostate base had slightly lower FFBF despite DIL boost.

Incidence of subsequent primary cancers and radiation-induced subsequent primary cancers after low dose-rate brachytherapy monotherapy for prostate cancer in long-term follow-up

BackgroundAs aging is the most significant risk factor for cancer development, long-term prostate cancer (PCa) survivors have an evident risk of developing subsequent primary cancers (SPCs). Radiotherapy itself is an additional risk factor for cancer development and the SPCs appearing beyond 5 years after radiotherapy in the original treatment field can be considered as radiation-induced subsequent primary cancers (RISPCs).MethodsDuring the years 1999-2008, 241 patients with localized PCa who underwent low dose-rate brachytherapy (LDR-BT) with I125 and were followed-up in Kuopio University Hospital, were included in this study. In this study the incidences and types of SPCs and RISPCs with a very long follow-up time after LDR-BT were evaluated.ResultsDuring the median follow-up time of 11.4 years, a total of 34 (14.1%) patients developed a metachronous SPC. The most abundant SPCs were lung and colorectal cancers, each diagnosed in six patients (16.7% out of all SPCs). The crude incidence rate of RISPC was 1.7% (n = 4). Half of the SPC cases (50%) were diagnosed during the latter half of the follow-up time as the risk to develop an SPC continued throughout the whole follow-up time with the actuarial 10-year SPC rate of 7.0%. The crude death rates due to metachronous out-of-field SPCs and RISPCs were 50 and 50%, respectively.ConclusionThe crude rate of SPC was in line with previously published data and the incidence of RISPC was very low. These results support the role of LDR-BT as a safe treatment option for patients with localized PCa.

A biochemical definition of cure after brachytherapy for prostate cancer

Background and purposeTo identify a PSA threshold value at an intermediate follow-up time after low dose rate (LDR) prostate brachytherapy associated with cure, defined as long-term (10–15 year) freedom from prostate cancer. Materials and methodsData from 7 institutions for 14,220 patients with localized prostate cancer treated with LDR brachytherapy, either alone (8552) or with external beam radiotherapy (n = 1175), androgen deprivation (n = 3165), or both (n = 1328), were analyzed. Risk distribution was 42.4% favorable, 49.2% intermediate, and 8.4% high-risk. Patients with clinical failure before 3.5 years were excluded. Kaplan-Meier analysis was used with clinical failure (local, distant, regional or biochemical triggering salvage) as an endpoint for each of four PSA categories: PSA ≤ 0.2, >0.2 to ≤0.5, >0.5 to ≤1.0, and >1.0 ng/mL. PSA levels at 4 years (±6 months) in 8746 patients without clinical failure were correlated with disease status at 10–15 years. ResultsFor the 77.1% of patients with 4-year PSA ≤ 0.2, the freedom-from-recurrence (FFR) rates were 98.7% (95% CI 98.3–99.0) at 10 years and 96.1% (95% CI 94.8–97.2) at 15 years. Three independent validation cohorts confirmed 97–99% 10-year FFR rates with 4-year PSA ≤ 0.2. Successive PSA categories were associated with diminished disease-free rates at 10 and 15 years. PSA category was strongly associated with treatment success (p < 0.0005). ConclusionsSince 98.7% of patients with PSA ≤ 0.2 ng/mL at 4 years after LDR prostate brachytherapy were disease-free beyond 10 years, we suggest adopting this biochemical definition of cure for patients with ≥4 years’ follow-up after LDR brachytherapy.

Acute patient-reported bowel quality of life and rectal bleeding with the combination of prostate external beam radiation, low-dose-rate brachytherapy boost, and SpaceOAR

PurposeThis study evaluates acute patient-reported bowel quality of life (QOL) and rectal bleeding in prostate cancer patients treated with combination external beam radiation (EBRT), low-dose-rate brachytherapy (LDR-BT), and SpaceOAR. Materials and MethodsA retrospective review of prostate cancer patients treated with EBRT (45 Gy), cesium-131 LDR-BT (85 Gy), and SpaceOAR was conducted. Patient-reported acute (≤3 months after LDR-BT) bowel QOL and rectal bleeding was analyzed from Expanded Prostate Cancer Index Composite (EPIC) questionnaires. Five-point changes in mean bowel QOL scores were considered clinically significant. Clinically significant rectal bleeding was bleeding occurring more than “rarely” (“about half the time,” “usually,” or “always”), and clinically significant bleeding bother was considering bleeding a “small, moderate, or big problem.” Outcomes were analyzed using descriptive statistics and paired t-tests. Results69 patients were identified. Bowel summary, function, and bother scores clinically and significantly decreased 2 weeks after LDR-BT (79.9 ± 15.6, 80.5 ± 15.4, and 79.4 ± 18.1, respectively) compared with pre-EBRT scores (92.3 ± 9.1, 93.3 ± 9.0, and 92.6 ± 11.9, respectively) and pre-LDR-BT scores (91.1 ± 11.0, 91.6 ± 9.8, and 90.6 ± 13.3, respectively), but returned to clinical and statistical baseline pre-EBRT values at 3 months (88.7 ± 12.4, 88.8 ± 11.1, and 88.7 ± 14.5, respectively). The 3-month cumulative incidence of clinically significant rectal bleeding and bleeding bother was 4.35% and 2.90%, respectively. ConclusionsWith combination EBRT, LDR-BT, and SpaceOAR, bowel QOL returned to the baseline 3 months after LDR-BT. Clinically significant rectal bleeding was <5%. Further followup will confirm if low acute rectal toxicity translates to reduced late toxicity.

Conventional vs machine learning–based treatment planning in prostate brachytherapy: Results of a Phase I randomized controlled trial

PurposeThe purpose of this study was to evaluate the noninferiority of Day 30 dosimetry between a machine learning–based treatment planning system for prostate low-dose-rate (LDR) brachytherapy and the conventional, manual planning technique. As a secondary objective, the impact of planning technique on clinical workflow efficiency was also evaluated. Materials and Methods41 consecutive patients who underwent I-125 LDR monotherapy for low- and intermediate-risk prostate cancer were accrued into this single-institution study between 2017 and 2018. Patients were 1:1 randomized to receive treatment planning using a machine learning–based prostate implant planning algorithm (PIPA system) or conventional, manual technique. Treatment plan modifications by the radiation oncologist were evaluated by computing the Dice coefficient of the prostate V150% isodose volume between either the PIPA—or conventional—and final approved plans. Additional evaluations between groups evaluated the total planning time and dosimetric outcomes at preimplant and Day 30. Results21 and 20 patients were treated using the PIPA and conventional techniques, respectively. No significant differences were observed in preimplant or Day 30 prostate D90%, V100%, rectum V100, or rectum D1cc between PIPA and conventional techniques. Although the PIPA group had a larger proportion of patients with plans requiring no modifications (Dice = 1.00), there was no significant difference between the magnitude of modifications between each arm. There was a large significant advantage in mean planning time for the PIPA arm (2.38 ± 0.96 min) compared with the conventional (43.13 ± 58.70 min) technique (p >> 0.05). ConclusionsA machine learning–based planning workflow for prostate LDR brachytherapy has the potential to offer significant time savings and operational efficiencies, while producing noninferior postoperative dosimetry to that of expert, conventional treatment planners.

Evaluation of the urethral α/β ratio and tissue repair half-time for iodine-125 prostate brachytherapy with or without supplemental external beam radiotherapy

PurposeTo assess the correlation between postimplant dosimetric quantifiers and the genitourinary (GU) toxicity of low-dose rate brachytherapy for prostate cancer. Methods and MaterialsThe minimum urethral dose (UD10, 30, and 90) and the percent volume of the urethra receiving the prescription dose (V100, V150) were calculated from the postimplant dose-volume histograms of 182 patients. We then calculated various urethral biologically equivalent doses (uBEDs) using different values of the α/β ratio and tissue repair half-time (t1/2) and examined the correlations with GU toxicity. ResultsCommon dosimetric quantifiers, such as UD90 (brachytherapy) + UD50 (external beam radiotherapy), showed no correlation with Grade ≥ 2 GU toxicity. There was a significant correlation between Grade ≥2 GU toxicity and uBED when the α/β value was 0.5 or 1 Gy and t1/2 was 0.5–2.5 h. An uBED (α/β = 1.0, t1/2 = 0.5) had the largest hazard ratio for GU toxicity, and it was also significantly correlated with Grade ≥ 2 GU toxicity according to multivariate analysis. ConclusionsWe observed a significant correlation of uBED with GU toxicity when α/β was 0.5 or 1.0 Gy and t1/2 was 0.5–2.5 h. As the simple formula we used has not been verified in basic experiments, more data are needed to validate our results.

MP70-11 FOCAL BRACHYTHERAPY FOR LOCALIZED PROSTATE CANCER: MID-TERM OUTCOMES

INTRODUCTION AND OBJECTIVE:Low dose rate brachytherapy (LDR-BT) is a radiation curative therapeutic option for localized prostate cancer (PCa). Focal brachytherapy (F-BT) consists in limiting the s...

Radical radiotherapy for prostate cancer: patterns of care in Sweden 1998–2016

Introduction: Radiotherapy is an established treatment option for prostate cancer (PCa), both as primary treatment and secondary treatment after radical prostatectomy (RP). Since 1998, detailed data on radiotherapy delivered to Swedish men with PCa (e.g. treatment modalities, absorbed doses, fractionation) have been collated within PCa data Base Sweden (PCBaSe). This study reports patterns of radical radiotherapy for PCa in Sweden over the past two decades.Materials and methods: All men with non-metastatic PCa (1998–2016) who received external beam radiotherapy (EBRT) or high or low dose-rate brachytherapy (HDR-BT/LDR-BT) were identified in PCBaSe. Analyses included: trends in radiation techniques, fractionation patterns and total doses over time; PCa-specific survival comparing treatment in 2007–2017 with 1998–2006; and regional variation in type of primary radiotherapy.Results: About 20,876 men underwent primary radiotherapy. The main treatment modalities include conventionally fractionated (2.0 Gy/fraction) EBRT (51%), EBRT with HDR-BT boost (27%) and hypofractionated (>2.4 Gy/fraction) EBRT (11%). EBRT with photon or proton boost and HDR-BT and LDR-BT monotherapies were each used minimally. Use of dose-escalated EBRT (>74 Gy) and moderate hypofractionation increased over time, while use of HDR-BT declined. Considerable regional variation in treatment modalities was apparent. Risk of PCa death following primary radiotherapy had declined for intermediate-risk (HR: 0.60; 95%CI 0.47–0.87) and high-risk PCa (HR: 0.72; 95%CI 0.61-0.86).Discussion: Increased use of dose escalation and hypofractionated EBRT has occurred in Sweden over the past two decades, reflecting current evidence and practice guidelines. Disease-specific outcomes have also improved. Data collected in PCBaSe provide an excellent resource for further research into RT use in PCa management.

The Impact of High-Dose-Rate Brachytherapy: Measuring Clinical Outcomes in the Primary Treatment of Cervical Cancer

PurposeRadical concurrent chemoradiotherapy with combined external beam radiotherapy (EBRT) and brachytherapy is used to treat locally advanced cervical cancer. Our institution has transitioned to high-dose-rate (HDR) intracavitary brachytherapy (ICBT) from low-dose-rate (LDR) brachytherapy in 2008, and a review was conducted on the effect of this change on patient outcomes. Methods and MaterialsA single-arm retrospective chart review was performed on locally advanced (Fédération Internationale de Gynécologie et d’Obstétrique stage IB-IVA) patients with cervical cancer treated with combined external beam radiation therapy and HDR-ICBT with curative intent between 2008 and 2014. Clinical outcomes were evaluated, and multivariate analysis was performed to identify prognostic factors. ResultsOf the 76 patients selected, median age was 47.9 years and median follow-up was 5.2 years. Thirteen patients (17.1%) developed locoregional recurrence and 23 patients (30.3%) patients developed distant recurrence. Five-year progression-free survival and overall survival were 63.7% and 69.3%, respectively. A significant survival difference was found between stages (P < .001). Multivariate analysis found nodal involvement was strongly associated with poorer survival (P = .007). ConclusionsOur experience with the transition to HDR-ICBT as part of concurrent chemoradiotherapy in treatment of locally advanced cervical cancer resulted in acceptable long-term outcomes and toxicity to that of LDR brachytherapy. Potential further improvement of treatment outcomes for patients may be possible with image guided brachytherapy and the addition of effective systemic therapy.

Recovery of serum testosterone following neoadjuvant androgen deprivation therapy in Japanese prostate cancer patients treated with low-dose rate brachytherapy

Objective To investigate the time course of total testosterone (TT) recovery after cessation of androgen deprivation therapy (ADT) in Japanese patients treated with brachytherapy. Methods In total, 125 patients with prostate cancer received 6 months of neoadjuvant ADT (nADT) followed by low-dose rate (LDR) brachytherapy. TT was measured every 3 months after cessation of nADT, and some predictive factors affecting TT recovery were analyzed. Results The cumulative incidence rates of TT recovery to normal levels (TT ≥ 3.0 ng/mL) after 12 and 24 months cessation were 49.6% and 81.6%, respectively. The median interval to recover to normal TT was 15 months. In multivariate analysis, the use of a gonadotropin-releasing hormone (GnRH) antagonist as nADT significantly earlier improved to recovery to normal TT level (p = 0.046). Conversely, higher body mass index (BMI) and hypertension significantly prolonged TT recovery to normal (p = 0.026 and p = 0.026, respectively). Conclusions Approximately one-fifth of patients still had low TT levels 2 years after the cessation of 6 months nADT before LDR brachytherapy. Use of a GnRH agonist, higher BMI, and hypertension were the predictive factors for slower TT recovery to normal TT levels after the cessation of nADT.

Rectal spacing, prostate coverage, and periprocedural outcomes after hydrogel spacer injection during low-dose-rate brachytherapy implantation

To analyze the dosimetric impact and periprocedural outcomes with a bioabsorbable hydrogel rectal spacer injected during low-dose-rate (LDR) prostate brachytherapy implants. A consecutive series of 80 patients implanted with stranded I-125 LDR brachytherapy seeds were evaluated, of which 40 underwent a transperineal injection of polyethylene glycol (5cc) in between the prostate and rectum. Same day CT-based dosimetry was compared between patients with and without hydrogel spacer to evaluate for differences in rectal and prostate dosimetry. Physician-reported toxicities were coded with Common Terminology Criteria for Adverse Events (CTCAE) v4. Baseline patient and implant characteristics were similar. There were no acute genitourinary or rectal toxicities attributed to the hydrogel spacer. Comparing patients with and without hydrogel, the mean separation between the prostate and rectum was 13.9±5.2mm vs. 6.5±5.0mm (p < 0.0001), respectively. The adjusted mean dose to 1cc, 2cc, and 5cc of the rectum relative to prescription dose was decreased by 32% (p < 0.01), 26% (p < 0.01), and 17% (p < 0.01), respectively. There were no statistically significant differences in prostate coverage: mean V100 (92% vs. 91%), V150 (45% vs. 48%), and D90 (106% vs. 106%), respectively. At 1month followup, grade 1 rectal toxicity was 12.5% vs. 17.5% (p= 0.35). No patients developed Grade ≥2 rectal toxicity with hydrogel, although one did without. Hydrogel rectal spacers significantly reduced rectal exposure to LDR brachytherapy seeds without an observable impact on prostate coverage or periprocedural side effects. These outcomes reflect only LDR implants that used stranded seeds.