Effect of Brachytherapy With External Beam Radiation Therapy Versus Brachytherapy Alone for Intermediate-Risk Prostate Cancer: NRG Oncology RTOG 0232 Randomized Clinical Trial.

PURPOSE: To determine whether addition of external beam radiation therapy (EBRT) to brachytherapy (BT) (COMBO) compared with BT alone would improve 5-year freedom from progression (FFP) in intermediate-risk prostate cancer. METHODS: Men with prostate cancer stage cT1c-T2bN0M0, Gleason Score (GS) 2-6 and prostate-specific antigen (PSA) 10-20 or GS 7, and PSA < 10 were eligible. The COMBO arm was EBRT (45 Gy in 25 fractions) to prostate and seminal vesicles followed by BT prostate boost (110 Gy if 125-Iodine, 100 Gy if 103-Pd). BT arm was delivered to prostate only (145 Gy if 125-Iodine, 125 Gy if 103-Pd). The primary end point was FFP: PSA failure (American Society for Therapeutic Radiology and Oncology [ASTRO] or Phoenix definitions), local failure, distant failure, or death. RESULTS: Five hundred eighty-eight men were randomly assigned; 579 were eligible: 287 and 292 in COMBO and BT arms, respectively. The median age was 67 years; 89.1% had PSA < 10 ng/mL, 89.1% had GS 7, and 66.7% had T1 disease. There were no differences in FFP. The 5-year FFP-ASTRO was 85.6% (95% CI, 81.4 to 89.7) with COMBO compared with 82.7% (95% CI, 78.3 to 87.1) with BT (odds ratio [OR], 0.80; 95% CI, 0.51 to 1.26; Greenwood T P = .18). The 5-year FFP-Phoenix was 88.0% (95% CI, 84.2 to 91.9) with COMBO compared with 85.5% (95% CI, 81.3 to 89.6) with BT (OR, 0.80; 95% CI, 0.49 to 1.30; Greenwood T P = .19). There were no differences in the rates of genitourinary (GU) or GI acute toxicities. The 5-year cumulative incidence for late GU/GI grade 2+ toxicity is 42.8% (95% CI, 37.0 to 48.6) for COMBO compared with 25.8% (95% CI, 20.9 to 31.0) for BT (P < .0001). The 5-year cumulative incidence for late GU/GI grade 3+ toxicity is 8.2% (95% CI, 5.4 to 11.8) compared with 3.8% (95% CI, 2.0 to 6.5; P = .006). CONCLUSION: Compared with BT, COMBO did not improve FFP for prostate cancer but caused greater toxicity. BT alone can be considered as a standard treatment for men with intermediate-risk prostate cancer.

The impact of COVID-19 on service delivery systems: evidence from a survey of United States refugee resettlement agencies.

BACKGROUND: Key to the US refugee resettlement effort is the role of non-governmental organizations (NGOs) who receive, place, and provide transitional programs and referrals to new and recently resettled refugees. Yet only one rapid assessment study thus far examined the impact of COVID-19 on service delivery systems of US refugee resettlement agencies. This exploratory study describes the capability and preparedness of US refugee resettlement agencies to provide services and care to clients during the COVID-19 pandemic. METHODS: Using both telephone interviews and an internet survey, we assessed the impact of COVID-19 on service delivery, agency capacity, and preparedness of 101 US refugee resettlement agencies. Descriptive statistics were used to describe the dataset, while chi-square (χ2) tests were used to examine relationships by resettlement agency size (number of employees in each agency). RESULTS: Despite a temporary pause on refugee admissions, restrictive stay-at-home orders, and refugee travel restrictions, the majority of responding US refugee resettlement agencies continued to provide specialized services and care to resettled refugees and other immigrants. Among the more important findings was that agencies that continued to provide refugee services and care onsite in their existing facilities or office rather than moving such services offsite differed by agency size [χ2 (9.494, n = 101), p < 0.05]. Almost all agencies (93.1%) strongly agreed or agreed that staff have timely access to COVID-19 information. Most of the refugee services were provided offsite (n = 72 agencies, some with multiple offices across the US). CONCLUSIONS: US refugee resettlement agencies continued to perform admirably despite a lack of funding. Future research is underway to obtain a more balanced understanding of the impact of COVID-19 on practice or operations.

Salvage Low-Dose-Rate Prostate Brachytherapy: Clinical Outcomes of a Phase 2 Trial for Local Recurrence after External Beam Radiation Therapy (NRG Oncology/RTOG 0526).

PURPOSE: We report efficacy of a prospective phase 2 trial (NCT00450411) of salvage low-dose-rate (LDR) prostate brachytherapy (BT) for local failure (LF) after prior external beam radiation therapy (EBRT) with minimum 5-years' follow-up. METHODS AND MATERIALS: Eligible patients had low/intermediate risk prostate cancer (PCa) before EBRT and biopsy-proven LF >30 months after EBRT, with prostate-specific antigen <10 ng/mL and no regional/distant disease. The primary endpoint, late gastrointestinal and genitourinary adverse events (Common Terminology Criteria for Adverse Events v3.0) grade ≥3 were 14%. With minimum 5-year follow-up after salvage BT, secondary clinical outcomes including disease-free survival (DFS; includes death from any cause), disease-specific survival, and overall survival (OS) were estimated using the Kaplan-Meier method and modelled using Cox proportional hazards regression. Local tumor progression (ie, LF), distant failure (DF), and biochemical failure (BF) were estimated using cumulative incidence. Time to LF, DF, and BF were modeled by cause-specific Cox proportional hazards regression. RESULTS: From May 2007 to January 2014, 20 centers registered 100 patients (92 analyzable). Median follow-up is 6.7 years (range, 0.3-11.2); median age 70 years (range, 55-82); median prior EBRT dose 74 Gy [interquartile range (IQR):70 - 76] at a median of 85 months prior (IQR 60-119 months). Androgen deprivation was combined with salvage BT in 16%. Ten-year OS is 70% [95% confidence interval (CI) 58% - 83%]. Nineteen patients died (5 PCa, 10 other, 4 unknown). Ten-year failure rates are local 5% (95% CI, 1-11), distant 19% (95% CI, 10-29), and biochemical 46% (95% CI, 34-57). DFS is 61% at 5 years and 33% at 10 years. No baseline characteristic was significantly associated with any clinical outcome. CONCLUSIONS: This is the first prospective multicenter trial reporting outcomes of salvage LDR BT for LF after EBRT. Five-year freedom from BF is 68%, comparable to other salvage modalities. Although further LF is rare (5%), BF climbs to 46% by 10 years.

The ABS brachytherapy schools.

The American Brachytherapy Society brachytherapy schools have been pivotal in teaching and evolving the art of brachytherapy over the past decades. Founded in 1995, the schools have consistently provided content for the major disease sites including gynecologic, prostate, and breast with ocular, vascular, head and neck, pediatric, intraluminal, systemic, and intraoperative approaches more selectively addressed. In addition, Physics schools, either coupled with clinical schools or as stand-alone venues, have provided an essential educational component for practicing physicists, a pivotal part of the brachytherapy team. Celebrating 25 years in existence, this historical overview of the American Brachytherapy Society brachytherapy schools is a tribute to the many teachers who have shared their expertise, to the many students who have been enthusiastic and interactive participants, and the staff who have made it all possible, with the reward of perpetuating the important and timely art of brachytherapy.

A Prospective Phase 2 Trial of Transperineal Ultrasound-Guided Brachytherapy for Locally Recurrent Prostate Cancer After External Beam Radiation Therapy (NRG Oncology/RTOG-0526).

PURPOSE: Only retrospective data are available for low-dose-rate (LDR) salvage prostate brachytherapy for local recurrence after external beam radiation therapy (EBRT). The primary objective of this prospective phase 2 trial (NCT00450411) was to evaluate late gastrointestinal and genitourinary adverse events (AEs) after salvage LDR brachytherapy. METHODS AND MATERIALS: Eligible patients had low- or intermediate-risk prostate cancer before EBRT and biopsy-proven recurrence >30 months after EBRT, with prostate-specific antigen levels <10 ng/mL and no regional/distant disease. The primary endpoint was grade 3 or higher late treatment-related gastrointestinal or genitourinary AEs occurring 9 to 24 months after brachytherapy. These AEs were projected to be ≤10%, with ≥20% considered unacceptable. All events were graded with National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Multivariate analyses investigated associations of pretreatment or treatment variables with AEs. RESULTS: One hundred patients from 20 centers were registered from May 2007 to January 2014. The 92 analyzable patients had a median follow-up of 54 months (range, 4-97) and a median age of 70 years (interquartile range [IQR], 65-74). The initial Gleason score was 7 in 48% of patients. The median dose of EBRT was 74 Gy (IQR, 70-76) at a median interval of 85 months previously (IQR, 60-119). Only 16% had androgen deprivation at study entry. Twelve patients (14%) had late grade 3 gastrointestinal/genitourinary AEs, with no treatment-related grade 4 or 5 AEs. No pretreatment variable predicted late AEs, including prior EBRT dose and elapsed interval. Higher V100 (percentage of prostate enclosed by prescription isodose) predicted both occurrence of late AEs (odds ratio, 1.24; 95% confidence interval, 1.02-1.52; P = .03) and earlier time to first occurrence (hazard ratio, 1.18; 95% CI, 1.03-1.34; P = .02). CONCLUSIONS: This prospective multicenter trial reports outcomes of salvage LDR brachytherapy for post-EBRT recurrence. The rate of late grade 3 AEs did not exceed the unacceptable threshold. The only factor predictive of late AEs was implant dosimetry reflected by V100. Efficacy outcomes will be reported at a minimum of 5-year follow-up.

Real-time Doppler ultrasound to identify vessels and guide needle placement for gynecologic interstitial brachytherapy.

PURPOSE: Doppler ultrasound (US) gives real-time information regarding anatomy and blood vessel location to guide needle placement for gynecologic interstitial (IS) brachytherapy (BT). We retrospectively assessed Doppler US images for vessel quantity, size, and distribution in cervical cancer patients undergoing high-dose-rate BT at our institution. METHODS AND MATERIALS: Eleven consecutive patients undergoing IS high-dose-rate BT implants for cervical cancer between 2015 and 2017 were included. Transrectal Doppler US was used for real-time image guidance. US images were retrospectively evaluated. Vessel quantity, size, and distribution at superior and inferior levels of the cervix were recorded. Correlation of vessel quantity with tumor size and International Federation of Gynecology and Obstetrics stage was evaluated. RESULTS: Average vessel quantity was 4.2 in the inferior cervix and 3.8 in the superior cervix (range 1-11). Median vessel diameter was 2 mm in the inferior cervix and 2 mm in the superior cervix (range 1-6 mm). The most common location was posterolateral (3:00-5:00 and 7:00-9:00), outer third (78% of vessels inferiorly, 64% of vessels superiorly). Vessel quantity was correlated to initial tumor size superiorly (p = 0.04, paired t-test) but not inferiorly (p = 0.31, paired t-test). There was no correlation between vessel quantity and International Federation of Gynecology and Obstetrics stage (p > 0.05, analysis of variance). Doppler US was successfully used to guide needle placement away from visualized blood vessels with no incidents of hemorrhage in these patients. CONCLUSIONS: Doppler US is a useful tool to guide needle placement for IS BT for cervical cancer. Vessel quantity varied with increased vessel quantity seen higher in the cervix for larger tumors. Vessels were most commonly distributed in the outer third of the posterolateral cervix.

AAPM recommendations on dose prescription and reporting methods for permanent interstitial brachytherapy for prostate cancer: report of Task Group 137.

During the past decade, permanent radioactive source implantation of the prostate has become the standard of care for selected prostate cancer patients, and the techniques for implantation have evolved in many different forms. Although most implants use 125I or 103Pd sources, clinical use of 131Cs sources has also recently been introduced. These sources produce different dose distributions and irradiate the tumors at different dose rates. Ultrasound was used originally to guide the planning and implantation of sources in the tumor. More recently, CT and/or MR are used routinely in many clinics for dose evaluation and planning. Several investigators reported that the tumor volumes and target volumes delineated from ultrasound, CT, and MR can vary substantially because of the inherent differences in these imaging modalities. It has also been reported that these volumes depend critically on the time of imaging after the implant. Many clinics, in particular those using intraoperative implantation, perform imaging only on the day of the implant. Because the effects of edema caused by surgical trauma can vary from one patient to another and resolve at different rates, the timing of imaging for dosimetry evaluation can have a profound effect on the dose reported (to have been delivered), i.e., for the same implant (same dose delivered), CT at different timing can yield different doses reported. Also, many different loading patterns and margins around the tumor volumes have been used, and these may lead to variations in the dose delivered. In this report, the current literature on these issues is reviewed, and the impact of these issues on the radiobiological response is estimated. The radiobiological models for the biological equivalent dose (BED) are reviewed. Starting with the BED model for acute single doses, the models for fractionated doses, continuous low-dose-rate irradiation, and both homogeneous and inhomogeneous dose distributions, as well as tumor cure probability models, are reviewed. Based on these developments in literature, the AAPM recommends guidelines for dose prescription from a physics perspective for routine patient treatment, clinical trials, and for treatment planning software developers. The authors continue to follow the current recommendations on using D90 and V100 as the primary quantitles, with more specific guidelines on the use of the imaging modalities and the timing of the imaging. The AAPM recommends that the postimplant evaluation should be performed at the optimum time for specific radionuclides. In addition, they encourage the use of a radiobiological model with a specific set of parameters to facilitate relative comparisons of treatment plans reported by different institutions using different loading patterns or radionuclides.

Third-party brachytherapy source calibrations and physicist responsibilities: report of the AAPM Low Energy Brachytherapy Source Calibration Working Group.

The AAPM Low Energy Brachytherapy Source Calibration Working Group was formed to investigate and recommend quality control and quality assurance procedures for brachytherapy sources prior to clinical use. Compiling and clarifying recommendations established by previous AAPM Task Groups 40, 56, and 64 were among the working group's charges, which also included the role of third-party handlers to perform loading and assay of sources. This document presents the findings of the working group on the responsibilities of the institutional medical physicist and a clarification of the existing AAPM recommendations in the assay of brachytherapy sources. Responsibility for the performance and attestation of source assays rests with the institutional medical physicist, who must use calibration equipment appropriate for each source type used at the institution. Such equipment and calibration procedures shall ensure secondary traceability to a national standard. For each multi-source implant, 10% of the sources or ten sources, whichever is greater, are to be assayed. Procedures for presterilized source packaging are outlined. The mean source strength of the assayed sources must agree with the manufacturer's stated strength to within 3%, or action must be taken to resolve the difference. Third party assays do not absolve the institutional physicist from the responsibility to perform the institutional measurement and attest to the strength of the implanted sources. The AAPM leaves it to the discretion of the institutional medical physicist whether the manufacturer's or institutional physicist's measured value should be used in performing dosimetry calculations.

Recommendations for permanent prostate brachytherapy with (131)Cs: a consensus report from the Cesium Advisory Group.

PURPOSE: Published clinical information on the safety and efficacy of (131)Cs implants is limited. We provide consensus recommendations for (131)Cs prostate brachytherapy based on experience to date. METHODS AND MATERIALS: The Cesium Advisory Group (CAG) consists of experienced (131)Cs users. Recommendations are based on three clinical trials, one of which has completed accrual and has been published in the peer reviewed literature, and combined CAG experience of more than 1200 (131)Cs implants. RESULTS: We recommend using 1.059cGyh(-1)U(-1) as the dose rate constant for the IsoRay source. The prescription for monotherapy implants is 115Gy and when combined with 45-50Gy external beam it is 85Gy. Suggested individual source strength ranges from 1.6 to 2.2U. The release criterion for (131)Cs implants is 6mRh(-1) at 1m. (131)Cs brachytherapy should be performed differently from (125)I and (103)Pd brachytherapy: source placement is further from the urethra and rectum; the prostate V(150) should be < or =45%; sufficient margins may be obtained while limiting source placement to the capsule or close to the capsule. The increased dose rate may cause degradation of postimplant quantifiers due to edema. However, large variability in the magnitude and rate of resolution of edema make determination of the most representative postoperative imaging time impossible. The CAG recommends postimplant imaging on the day of the implant. Recommended postimplant evaluation goals include prostate D(90) greater than the prescription dose; maintaining D(u)(,30)<140% of the prescription dose and keeping V(r)(,100)<0.5cm(3). CONCLUSION: It was the consensus of the CAG that optimal (131)Cs implants should be performed differently from those performed with (125)I or (103)Pd. Guidelines have been established to allow for safe and effective delivery of (131)Cs prostate brachytherapy.

Characterization of an in vivo diode dosimetry system for clinical use.

An in vivo dosimetry system that uses p-type semiconductor diodes with buildup caps was characterized for clinical use on accelerators ranging in energy from 4 to 18 MV. The dose per pulse dependence was investigated. This was done by altering the source-surface distance, field size, and wedge for photons. The off-axis correction and effect of changing repetition rate were also investigated. A model was developed to fit the measured two-dimensional diode correction factors.