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Purpose: To evaluate the relationship between delivered radiation (RT) and post-RT inversion-recovery ultrashort-echo-time (IR-UTE) MRI signal-intensity (SI) in gynecologic cancer patients treated with high-dose-rate (HDR) brachytherapy (BT)., Methods: Seven patients underwent whole-pelvis RT (WPRT) followed by BT to the high-risk clinical target volume (HR-CTV). MR images were acquired at three time-points; pre-RT, post-WPRT/pre-BT, and 3-6 months post-BT. Diffuse-fibrosis (F Diffuse ) was imaged with a non-contrast dual-echo IR (inversion time [TI] = 60 ms) UTE research application, with image-subtraction of the later echo, only retaining the ultrashort-echo SI. Dense-fibrosis (F Dense ) imaging utilized single-echo Late-Gadolinium-Enhanced IR-UTE, acquired ∼ 15 min post-Gadavist injection. Resulting F Diffuse and F Dense SI were normalized to the corresponding gluteal-muscle SI. Images were deformably registered between time-points based on normal tissue anatomy. The remnant tumor at both time-points was segmented using multi-parametric MRI. Contours corresponding to the 50%, 100%, 150%, and 200% isodose lines (IDLs) of the prescription BT-dose were created. Mean F Diffuse and F Dense SI within (i) each IDL contour and (ii) the remnant tumor were calculated. Post-BT F Diffuse and F Dense SI were correlated with prescribed BT-dose. To determine the relationship between BT-dose and IR-UTE SI, the differences in the post-BT F Dense across IDLs was determined using paired t-tests with Bonferroni correction., Results: F Dense was higher in regions of higher dose for 6/7 patients, with mean ± SD values of 357 ± 103% and 331 ± 97% (p = .03) in the 100% and 50% IDL, respectively. F Dense was higher in regions of higher dose in the responsive regions with mean ± SD values of 380 ± 122% and 356 ± 135% (p = .03) in the 150% and 50% IDL, respectively. Within the segmented remnant tumor, an increase in prescribed dose correlated with an increase in F Dense post-BT (n = 5, r = .89, p = .04). Post-BT F Diffuse inversely correlated (n = 7, r = -.83, p = .02) with prescribed BT-dose within the 100% IDL., Conclusions: Results suggest that F Dense SI 3-6 months post-BT is a sensitive measure of tissue response to heterogeneous BT radiation-dose. Future studies will validate whether F Diffuse and F Dense are accurate biomarkers of fibrotic radiation response., (© 2024. The Author(s).)

Purpose: The use of stereotactic body radiation therapy (SBRT) for gynecologic malignancies is controversial. We discuss certain circumstances when highly precise SBRT may be a useful tool to consider in the management of selected patients., Methods and Materials: Case selection included the following scenarios, the first 2 with palliative intent, para-aortic nodal oligorecurrence of ovarian cancer, pelvic sidewall oligorecurrence of cervical cancer, and inoperable endometrial cancer boost after intensity modulated radiation to the pelvis treated with curative intent. Patient characteristics, fractionation, prescription dose, treatment technique, and dose constraints were discussed. Relevant literature to these cases was summarized to provide a framework for treatment of similar patients., Results: Treatment of gynecologic malignancies with SBRT requires many considerations, including treatment intent, optimal patient selection, fractionation selection, tumor localization, and plan optimization. Although other treatment paradigms including conventionally fractionated radiation therapy and brachytherapy remain the standard-of-care for definitive treatment of gynecologic malignancies, SBRT may have a role in palliative cases or those where high doses are not required due to the unacceptable toxicity that may occur with SBRT., Conclusions: A case-based practice review was developed by the Radiosurgery Society to provide a practical guide to the common scenarios noted above affecting patients with gynecologic malignancies., Competing Interests: Disclosure Sushil Beriwal reports employment by Varian, membership on the Xoft DSMB, and is a consultant for Elsevier ClinicalPath. Beth Erickson reports serving on the ASTRO Board of Directors as the Chair of the Educational Council. David Gaffney reports grant funding from Elekta and NCI UG1 LAPS and serving as chair of the Merck DSMC. Simon S. Lo reports grant funding from Kuni Foundation, Hutchinson Center, and Elekta, travel support from the Japanese Society for Radiation Oncology (JASTRO) and serves as Member of Board of Directors and National Medical Director of the Distinction in Practice in Stereotactic Radiotherapy Program for the Radiosurgery Society and Alternate Councilor for the American College of Radiology., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Our previous Surveillance, Epidemiology, and End Results (SEER) study revealed a concerning decline in brachytherapy utilization in the United States between 1988 and 2009. This study evaluates recent trends in brachytherapy utilization in cervical cancer and identifies factors and survival benefit associated with the use of brachytherapy treatment., Methods and Materials: Using SEER data, 8500 patients with International Federation of Gynecologists and Obstetricians 2009 stage IB2-IVA cervical cancer treated with external beam radiation therapy (EBRT) between 2000 and 2020 were identified. Logistic regression analysis was performed on potential factors associated with brachytherapy use: age, marital status, race, ethnicity, income, metropolitan status, year of diagnosis, SEER region, histology, grade, and stage. To adjust for differences between patients who received brachytherapy and those who did not, propensity-score matching was used. Multivariable Cox regression analysis assessed the association of brachytherapy use with cervical cancer-specific mortality (CSM) and all-cause mortality (ACM) in the matched cohort., Results: Sixty-four percent of the 8500 women received brachytherapy in combination with EBRT; 36% received EBRT alone. The brachytherapy utilization rate declined sharply in 2003/2004 (lowest rate 44% in 2003) and then gradually improved especially in 2018 to 2020 (76%). Factors associated with higher odds of brachytherapy use included younger age, married (vs single), later years of diagnosis, certain SEER regions, and earlier stage. In the propensity-score matched cohort, brachytherapy treatment was associated with lower 4-year cumulative incidence of cancer death (32.1% vs 43.4%; P < .001) and better overall survival (64.0% vs 51.4%; P < .001). Brachytherapy treatment was independently associated with lower CSM (hazard ratio, 0.70; 95% CI, 0.64-0.76; P < .001) and ACM (hazard ratio, 0.72; 95% CI, 0.67-0.78; P < .001)., Conclusions: Brachytherapy utilization among SEER regions has improved since 2004 in patients with stage IB2-IVA cervical cancer. Brachytherapy use remains independently associated with significantly lower CSM and ACM and is an essential component of treatment for patients with locally advanced cervical cancer., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Lower brachytherapy utilization for cervical cancer patients is associated with decreased survival. This study examines more recent trends in brachytherapy utilization from 2004 to 2020 to assess any trend reversal after awareness increased regarding the importance of brachytherapy., Methods and Materials: This study analyzed data from the National Cancer Database of patients with Federation of Gynecology and Obstetrics (FIGO) IB to IVA cervical cancer treated with radiation therapy between 2004 and 2020. To compare brachytherapy utilization over time, 2- to 3-year categories were created to account for potential variation seen in individual years. A multivariate log binomial regression with robust variance was used to estimate the incidence rate ratio (IRR) of brachytherapy utilization in each year category in reference to the 2004-2006 category. Additionally, risk factors for brachytherapy utilization were identified., Results: Overall brachytherapy utilization for cervical cancer increased from 54.9% in 2004 to 75.7% in 2020. Compared with 2004 to 2006 when rates of utilization totaled 55.2%, brachytherapy utilization significantly increased to 63.4% in 2011 to 2014 (IRR, 1.15; 95% CI, 1.11-1.19), 66.0% in 2015 to 2017 (1.20 [1.16-1.23]), and 76.0% in 2018 to 2020 (1.38 [1.34-1.42]). Sociodemographic factors associated with lower brachytherapy utilization included Black race (0.94 [0.92-0.97]), Hispanic ethnicity (0.92 [0.90-0.95]), and age >59 years (age ≥60-69: 0.96 [0.94-0.98]; age ≥70-79: 0.89 [0.87-0.92]; age ≥80: 0.73 [0.69-0.77]). Positive predictors of brachytherapy utilization included having insurance (IRR, 1.11; 95% CI, 1.07-1.14)., Conclusions: In patients with FIGO IB-IVA cervical cancer treated with radiation therapy from 2004 to 2020, brachytherapy utilization has increased during the past decade. These results are encouraging given the known benefit to cause-specific survival and overall survival provided by brachytherapy treatment and indicate a reversal in the trend of declining brachytherapy noted previously. Concerns related to disparities by race, ethnicity, and insurance status require further interventions., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Radiation therapy (RT) refusal is known to have deleterious effects on survival for multiple cancer types. Factors associated with RT refusal by patients with gynecologic malignancies have not been well described. This study aimed to examine factors associated with and the survival impact of documented RT refusal among patients with gynecologic cancers., Methods and Materials: This study analyzed data from the National Cancer Database (NCDB) of patients with gynecologic cancers diagnosed between 2004 and 2020. Patients were included if they had complete survival data and a documented RT recommendation by their treating physician in the NCDB. Patients coded as received RT were compared with those coded as refused RT in the NCDB using a multivariate log binomial regression with robust variance to yield incidence rate ratios (IRR). Overall survival was analyzed using a multivariate (MV) Cox proportional hazards model to yield hazard ratios., Results: This study identified 209,976 patients. A total of 5.75% (n = 12,081) patients were coded as refusing RT. Multivariable IRR showed that documentation of RT refusal was positively associated with older age (MV IRR, 1.04; 95% CI, 1.041-1.045), Native Hawaiian Pacific Islander race (1.72 [1.27-2.32]), and increased morbidity (score = 1: 1.06 [1.02-1.11]; score = 2: 1.20 [1.12-1.29]; score ≥3: 1.26 [1.14-1.38]). Negative associations were seen with Hispanic ethnicity (0.74 [0.67-0.80]), having insurance (0.58 [0.53-0.63]), and annual income >$74,063 (0.85 [0.81-0.90]). During the 16-year period, a statistically significant test for trend (P = .001) for increasing RT refusal was noted. RT refusal was associated with a significantly higher risk of death (MV hazard ratio, 1.59 [1.55-1.63])., Conclusions: For patients with gynecologic malignancies diagnosed from 2004 to 2020, an increase in documented RT refusal is associated with decreased overall survival in all disease types. Targeted interventions aimed at mitigating potential sociodemographic barriers to receipt of RT are warranted., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: This work describes the first implementation and in vivo study of ultrahigh-dose-rate radiation (>37 Gy/s; FLASH) effects induced by kilovoltage (kV) x-ray from a rotating-anode x-ray source., Methods and Materials: A high-capacity rotating-anode x-ray tube with an 80-kW generator was implemented for preclinical FLASH radiation research. A custom 3-dimensionally printed immobilization and positioning tool was developed for reproducible irradiation of a mouse hind limb. Calibrated Gafchromic (EBT3) film and thermoluminescent dosimeters (LiF:Mg,Ti) were used for in-phantom and in vivo dosimetry. Healthy FVB/N and FVBN/C57BL/6 outbred mice were irradiated on 1 hind leg to doses up to 43 Gy at FLASH (87 Gy/s) and conventional (CONV; <0.05 Gy/s) dose rates. The radiation doses were delivered using a single pulse with the widths up to 500 ms and 15 minutes at FLASH and CONV dose rates. Histologic assessment of radiation-induced skin damage was performed at 8 weeks posttreatment. Tumor growth suppression was assessed using a B16F10 flank tumor model in C57BL6J mice irradiated to 35 Gy at both FLASH and CONV dose rates., Results: FLASH-irradiated mice experienced milder radiation-induced skin injuries than CONV-irradiated mice, visible by 4 weeks posttreatment. At 8 weeks posttreatment, normal tissue injury was significantly reduced in FLASH-irradiated animals compared with CONV-irradiated animals for histologic endpoints including inflammation, ulceration, hyperplasia, and fibrosis. No difference in tumor growth response was observed between FLASH and CONV irradiations at 35 Gy. The normal tissue sparing effects of FLASH irradiations were observed only for high-severity endpoint of ulceration at 43 Gy, which suggests the dependency of biologic endpoints to FLASH radiation dose., Conclusions: Rotating-anode x-ray sources can achieve FLASH dose rates in a single pulse with dosimetric properties suitable for small-animal experiments. We observed FLASH normal tissue sparing of radiation toxicities in mouse skin irradiated at 35 Gy with no sacrifice to tumor growth suppression. This study highlights an accessible new modality for laboratory study of the FLASH effect., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Effective radiation therapy aims to maximize the radiation dose delivered to the tumor while minimizing damage to the surrounding healthy tissues, which can be a challenging task when the tissue-tumor space is small. To eliminate the damage to healthy tissue, it is now possible to inject biocompatible hydrogels between cancerous targets and surrounding tissues to create a spacer pocket. Conventional methods have limitations in poor target visualization and device tracking. In this paper, we leverage our MR-tracking technique to develop a novel injection needle for hydrogel spacer deployment. Herein, we present the working principle and fabrication method, followed by benchtop validation in an agar phantom, and MRI-guided validation in tissue-mimic prostate phantom and sexually mature female swine. Animal trials indicated that the spacer pockets in the rectovaginal septum can be accurately visualized on T2-weighted MRI. The experimental results showed that the vaginal-rectal spacing was successfully increased by 12 ± 2 mm anterior-posterior.

As cone-beam computed tomography (CBCT) has become the localization method for a majority of cases, the indications for diode-based confirmation of accurate patient set-up and treatment are now limited and must be balanced between proper resource allocation and optimizing efficiency without compromising safety. We undertook a de-implementation quality improvement project to discontinue routine diode use in non-intensity modulated radiotherapy (IMRT) cases in favor of tailored selection of scenarios where diodes may be useful. After analysis of safety reports from the last 5 years, literature review, and stakeholder discussions, our safety and quality (SAQ) committee introduced a recommendation to limit diode use to specific scenarios in which in vivo verification may add value to standard quality assurance (QA) processes. To assess changes in patterns of use, we reviewed diode use by clinical indication 4 months prior and after the implementation of the revised policy, which includes use of diodes for: 3D conformal photon fields set up without CBCT; total body irradiation (TBI); electron beams; cardiac devices within 10 cm of the treatment field; and unique scenarios on a case-by-case basis. We identified 4459 prescriptions and 1038 unique instances of diode use across five clinical sites from 5/2021 to 1/2022. After implementation of the revised policy, we observed an overall decrease in diode use from 32% to 13.2%, with a precipitous drop in 3D cases utilizing CBCT (from 23.2% to 4%), while maintaining diode utilization in the 5 selected scenarios including 100% of TBI and electron cases. By identifying specific indications for diode use and creating a user-friendly platform for case selection, we have successfully de-implemented routine diode use in favor of a selective process that identifies cases where the diode is important for patient safety. In doing so, we have streamlined patient care and decreased cost without compromising patient safety., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Purpose: To develop the safest possible environment for treating urgent patients with COVID-19 requiring radiation, we describe the unique construction of negative air pressure computed tomography simulator and linear accelerator treatment vaults in addition to screening, delay, and treatment protocols and their evolution over the course of the COVID-19 pandemic., Methods and Materials: Construction of large high-efficiency particulate air filter air-flow systems into existing ductwork in computed tomography simulator rooms and photon and proton treatment vaults was completed to create negative-pressure rooms. An asymptomatic COVID-19 screening protocol was implemented for all patients before initiation of treatment. Patients could undergo simulation and/or treatment in the biocontainment environments according to a predefined priority scale and protocol. Patients treated under the COVID-19 protocol from June 2020 to January 2022 were retrospectively reviewed., Results: Negative air-flow environments were created across a regional network, including a multi-gantry proton therapy unit. In total, 6525 patients were treated from June 2020 through January 2022 across 5 separate centers. The majority of patients with COVID-19 had radiation treatment deferred when deemed safe. A total of 42 patients with COVID-19, who were at highest risk of an adverse outcome should there be a radiation delay, were treated under the COVID-19 biocontainment protocol in contrast to those who were placed on treatment break. For 61.9% of patients, these safety measures mitigated an extended break during treatment. The majority of patients (64.3%) were treated with curative intent. The median number of biocontainment sessions required by each patient was 6 (range, 1-15) before COVID-19 clearance and resumption of treatment in a normal air-flow environment., Conclusions: Constructing negative-pressure environments and developing a COVID-19 biocontainment treatment protocol allowed for the safe treatment of urgent radiation oncology patients with COVID-19 within our department and strengthens future biopreparedness. These biocontainment units set a high standard of safety in radiation oncology during the current or for any future infectious outbreak., (© 2022 The Author(s).)

Purpose/objectives: There is a clinical need to develop anatomic phantoms for simulation-based learning in gynecological brachytherapy. Here, we provide a step-by-step approach to build a life-sized gynecological training phantom based on magnetic resonance imaging (MRI) of an individual patient. Our hypothesis is that this phantom can generate convincing ultrasound (US) images that are similar to patient scans., Methods: Organs-at-risk were manually segmented using patient scans (MRI). The gynecological phantom was constructed using positive molds from 3D printing and polyvinyl chloride (PVC) plastisol. Tissue texture/acoustic properties were simulated using different plastic softener/hardener ratios and microbead densities. Nine readers (residents) were asked to evaluate 10 cases (1 ultrasound image per case) and categorize each as a "patient" or "phantom" image. To evaluate whether the phantom and patient images were equivalent, we used a multireader, multicase equivalence study design with two composite null hypotheses with proportion (p r ) at H 01 : p r ≤ 0.35 and H 02 : p r ≥ 0.65. Readers were also asked to review US videos and identify the insertion of an interstitial needle into the pelvic phantom. Computed Tomography (CT) and magnetic resonance (MR) images of the phantom were acquired for a feasibility study., Results: Readers correctly classified "patient" and "phantom" scans at p r  = 53.3% ± 6.2% (p values 0.013 for H 01 and 0.054 for H 02 , df = 5.96). Readers reviewed US videos and identified the interstitial needle 100% of the time in transabdominal view, and 78% in transrectal view. The phantom was CT and MR safe., Conclusions: We have outlined a manufacturing process to create a life-sized, gynecological phantom that is compatible with multi-modality imaging and can be used to simulate clinical scenarios in image-guided brachytherapy procedures., (Copyright © 2022 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Traditional peer reviews occur weekly, and can take place up to 1 week after the start of treatment. The American Society for Radiation Oncology peer-review white paper identified stereotactic body radiation therapy (SBRT) as a high priority for contour/plan review before the start of treatment, considering both the rapid-dose falloff and short treatment course. Yet, peer-review goals for SBRT must also balance physician time demands and the desire to avoid routine treatment delays that would occur in the setting of a 100% pretreatment (pre-Tx) review compliance requirement or prolonging the standard treatment planning timeline. Herein, we report on our pilot experience of a pre-Tx peer review of thoracic SBRT cases., Methods and Materials: From March 2020 to August 2021, patients undergoing thoracic SBRT were identified for pre-Tx review, and placed on a quality checklist. We implemented twice-weekly meetings for detailed pre-Tx review of organ-at-risk/target contours and dose constraints in the treatment planning system for SBRT cases. Our quality metric goal was to peer review ≥90% of SBRT cases before exceeding 25% of the dose delivered. We used a statistical process control chart with sigma limits (ie, standard deviations [SDs]) to access compliance rates with pre-Tx review implementation., Results: We identified 252 patients treated with SBRT to 294 lung nodules. When comparing pre-Tx review completion from initial rollout to full implementation, our rates improved from 19% to 79% (ie, from 1 sigma limit [SDs]) below to >2 sigma limits (SDs) above. Additionally, early completion of any form of contour/plan review (defined as any pre-Tx or standard review completed before exceeding 25% of the dose delivered) increased from 67% to 85% (March 2020-November 2020) to 76% to 94% (December 2020-August 2021)., Conclusions: We successfully implemented a sustainable workflow for detailed pre-Tx contour/plan review for thoracic SBRT cases in the context of twice-weekly disease site-specific peer-review meetings. We reached our quality improvement objective to peer review ≥90% of SBRT cases before exceeding 25% of the dose delivered. This process was feasible to conduct in an integrated network of sites across our system., (© 2022 The Authors.)

Purpose: Contouring clinical target volume (CTV) from medical images is an essential step for radiotherapy (RT) planning. Magnetic resonance imaging (MRI) is used as a standard imaging modality for CTV segmentation in cervical cancer due to its superior soft-tissue contrast. However, the delineation of CTV is challenging as CTV contains microscopic extensions that are not clearly visible even in MR images, resulting in significant contour variability among radiation oncologists depending on their knowledge and experience. In this study, we propose a fully automated deep learning-based method to segment CTV from MR images., Methods: Our method begins with the bladder segmentation, from which the CTV position is estimated in the axial view. The superior-inferior CTV span is then detected using an Attention U-Net. A CTV-specific region of interest (ROI) is determined, and three-dimensional (3-D) blocks are extracted from the ROI volume. Finally, a CTV segmentation map is computed using a 3-D U-Net from the extracted 3-D blocks., Results: We developed and evaluated our method using 213 MRI scans obtained from 125 patients (183 for training, 30 for test). Our method achieved (mean ± SD) Dice similarity coefficient of 0.85 ± 0.03 and the 95th percentile Hausdorff distance of 3.70 ± 0.35 mm on test cases, outperforming other state-of-the-art methods significantly (p-value < 0.05). Our method also produces an uncertainty map along with the CTV segmentation by employing the Monte Carlo dropout technique to draw physician's attention to the regions with high uncertainty, where careful review and manual correction may be needed., Conclusions: Experimental results show that the developed method is accurate, fast, and reproducible for contouring CTV from MRI, demonstrating its potential to assist radiation oncologists in alleviating the burden of tedious contouring for RT planning in cervical cancer., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Aim/objectives/background: The American College of Radiology (ACR), the American Brachytherapy Society (ABS), and the American Society for Radiation Oncology (ASTRO) have jointly developed the following practice parameter for the performance of low-dose-rate (LDR) brachytherapy. LDR brachytherapy is the application of radioactive sources in or on tumors in a clinical setting with therapeutic intent. The advantages of LDR brachytherapy include improving therapeutic ratios with lower doses to nontarget organs-at-risk and higher doses to a specific target., Methods: This practice parameter was developed according to the process described under the heading. The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters-Radiation Oncology of the Commission on Radiation Oncology, in collaboration with ABS and ASTRO., Results: This practice parameter was developed to serve as a tool in the appropriate application of this evolving technology in the care of cancer patients or other patients with conditions where radiation therapy is indicated. It addresses clinical implementation of LDR brachytherapy including personnel qualifications, quality assurance standards, indications, and suggested documentation. This includes a contemporary literature search., Conclusions: This practice parameter is a tool to guide the use of LDR brachytherapy and does not assess relative clinical indication for LDR brachytherapy when compared with other forms of brachytherapy or external beam therapy, but to focus on the best practices required to deliver LDR brachytherapy safely and effectively, when clinically indicated. Comparative costs of versus other modalities therapy may also need to be considered., Competing Interests: L.L.L. reports grants from National Cancer Institute, other from Astrazeneca, other from Pfizer, outside the submitted work. P.O. reports personal fees from Palette Life Sciences, outside the submitted work. D.S. reports grants from the National Cancer Institute, outside the submitted work. W.S. reports personal fees from Carl Zeiss Meditech, personal fees from Merck, personal fees from Varian, grants from University of Utah, other from NRG Oncology, outside the submitted work. The remaining authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Worldwide, stage III-IVA carcinomas of the uterine cervix comprise a significant proportion of cases at presentation, and have a higher rate of recurrence and worse overall survival. This review will discuss the epidemiology, prevention strategies, clinical presentation, and treatment recommendations for stage III-IVA cervical cancer. The focus will be on the role of radiation therapy, concurrent chemoradiotherapy, and brachytherapy, including the potential benefits and anticipated toxicities. The unique challenges and considerations of fistula formation and approaches to management will be highlighted, and follow-up care and future directions discussed. As low and middle income countries bear the highest burden of advanced stage carcinoma of the uterine cervix, this review will address the unique needs of global communities., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Brachytherapy is a radiation based treatment that is implemented by precisely placing focused radiation sources into tumors. In advanced interstitial cervical cancer bracytherapy treatment, this is performed by placing a metallic rod ("stylet") inside a hollow cylindrical tube ("catheter") and advancing the pair to the desired target. The stylet is removed once the target is reached, followed by the insertion of radiation sources into the catheter. However, manually advancing an initially straight stylet into the tumor with millimeter spatial accuracy has been a long-standing challenge, which requires multiple insertions and retractions, due to the unforeseen stylet deflection caused by the stiff muscle tissue that is traversed. In this paper, we develop a novel tendon-actuated deflectable stylet equipped with MR active-tracking coils that may enhance brachytherapy treatment outcomes by allowing accurate stylet trajectory control. Herein we present the design concept and fabrication method, followed by the kinematic and mechanics models of the deflectable stylet. The hardware and theoretical models are extensively validated via benchtop and MRI-guided characterization. At insertion depths of 60 mm, benchtop phantom targeting tests provided a targeting error of 1. 23 ± 0. 47 mm, and porcine tissue targeting tests provided a targeting error of 1. 65 ± 0. 64 mm, after only a single insertion. MR-guided experiments indicate that the stylet can be safely and accurately located within the MRI environment.

Purpose: Brachytherapy combined with external beam radiotherapy (EBRT) is the standard treatment for cervical cancer and has been shown to improve overall survival rates compared to EBRT only. Magnetic resonance (MR) imaging is used for radiotherapy (RT) planning and image guidance due to its excellent soft tissue image contrast. Rapid and accurate segmentation of organs at risk (OAR) is a crucial step in MR image-guided RT. In this paper, we propose a fully automated two-step convolutional neural network (CNN) approach to delineate multiple OARs from T2-weighted (T2W) MR images., Methods: We employ a coarse-to-fine segmentation strategy. The coarse segmentation step first identifies the approximate boundary of each organ of interest and crops the MR volume around the centroid of organ-specific region of interest (ROI). The cropped ROI volumes are then fed to organ-specific fine segmentation networks to produce detailed segmentation of each organ. A three-dimensional (3-D) U-Net is trained to perform the coarse segmentation. For the fine segmentation, a 3-D Dense U-Net is employed in which a modified 3-D dense block is incorporated into the 3-D U-Net-like network to acquire inter and intra-slice features and improve information flow while reducing computational complexity. Two sets of T2W MR images (221 cases for MR1 and 62 for MR2) were taken with slightly different imaging parameters and used for our network training and test. The network was first trained on MR1 which was a larger sample set. The trained model was then transferred to the MR2 domain via a fine-tuning approach. Active learning strategy was utilized for selecting the most valuable data from MR2 to be included in the adaptation via transfer learning., Results: The proposed method was tested on 20 MR1 and 32 MR2 test sets. Mean ± SD dice similarity coefficients are 0.93 ± 0.04, 0.87 ± 0.03, and 0.80 ± 0.10 on MR1 and 0.94 ± 0.05, 0.88 ± 0.04, and 0.80 ± 0.05 on MR2 for bladder, rectum, and sigmoid, respectively. Hausdorff distances (95th percentile) are 4.18 ± 0.52, 2.54 ± 0.41, and 5.03 ± 1.31 mm on MR1 and 2.89 ± 0.33, 2.24 ± 0.40, and 3.28 ± 1.08 mm on MR2, respectively. The performance of our method is superior to other state-of-the-art segmentation methods., Conclusions: We proposed a two-step CNN approach for fully automated segmentation of female pelvic MR bladder, rectum, and sigmoid from T2W MR volume. Our experimental results demonstrate that the developed method is accurate, fast, and reproducible, and outperforms alternative state-of-the-art methods for OAR segmentation significantly (p < 0.05)., (© 2021 American Association of Physicists in Medicine.)

Purpose: To develop an endovaginal MRI array that provides signal enhancement forward into the posterior parametrium and sideways into the vaginal wall, accelerating multiple-contrast detection of residual tumors that survive external beam radiation. The array's enclosure should form an obturator for cervical cancer brachytherapy, allowing integration with MRI-guided catheter placement, CT, and interstitial radiation dose delivery., Methods: The endovaginal array consisted of forward-looking and sideways-looking components. The forward-looking element imaged the cervix and posterior endometrium, and the sideways-looking elements imaged the vaginal wall. Electromagnetic simulation was performed to optimize the geometry of a forward-looking coil placed on a conductive-metallic substrate, extending the forward penetration above the coil's tip. Thereafter, an endovaginal array with one forward-looking coil and four sideways-looking elements was constructed and tested at 1.5 Tesla in saline and gel phantoms, and three sexually mature swine. Each coil's tuning, matching, and decoupling were optimized theoretically, implemented with electronic circuits, and validated with network-analyzer measurements. The array enclosure emulates a conventional brachytherapy obturator, allowing use of the internal imaging array together with tandem coils and interstitial catheters, as well as use of the enclosure alone during CT and radiation delivery. To evaluate the receive magnetic field ( B 1 - ) spatial profile, the endovaginal array's specific absorption-rate (SAR) distribution was simulated inside a gel ASTM phantom to determine extreme heating locations in advance of a heating test. Heating tests were then performed during high SAR imaging in a gel phantom at the predetermined locations, testing compliance with MRI safety standards. To assess array imaging performance, signal-to-noise-ratios (SNR) were calculated in a saline phantom and in vivo. Swine images were acquired with the endovaginal array combined with the scanner's body and spine arrays., Results: Simulated B 1 - profiles for the forward-looking lobe pattern, obtained while varying several geometric parameters, disclosed that a forward-looking coil placed on a metal-backed substrate could double the effective forward penetration from approximately 25 to ∼40 mm. An endovaginal array, enclosed in an obturator enclosure was then constructed, with all coils tuned, matched, and decoupled. The ASTM gel-phantom SAR test showed that peak local SAR was 1.2 W/kg in the forward-looking coil and 0.3 W/kg in the sideways-looking elements, well within ASTM/FDA/IEC guidelines. A 15-min 4 W/kg average SAR imaging experiment resulted in less than 2 o C temperature increase, also within ASTM/FDA/IEC heating limits. In a saline phantom, the forward-looking coil and sideways-looking array's SNR was four to eight times, over a 20-30 mm field-of-view (FOV), and five to eight times, over a 15-25 mm FOV, relative to the spine array's SNR, respectively. In three sexually mature swine, the forward-looking coil provided a 5 + 0.2 SNR enhancement factor within the cervix and posterior endometrium, and the sideways-looking array provided a 4 + 0.2 SNR gain factor in the vaginal wall, relative to the Siemens spine array, demonstrating that the array could significantly reduce imaging time., Conclusions: Higher SNR gynecological imaging is supported by forward-looking and sideways-looking coils. A forward-looking endovaginal coil for cervix and parametrium imaging was built with optimized metal backing. Array placement within an obturator enhanced integration with the brachytherapy procedure and accelerated imaging for detecting postexternal-beam residual tumors., (© 2021 American Association of Physicists in Medicine.)

Purpose: The purpose of this study was to evaluate the impact of dose reporting schemes and tissue/applicator heterogeneities for 192 Ir-, 75 Se-, and 169 Yb-based MRI-guided conventional and intensity-modulated brachytherapy., Methods and Materials: Treatment plans using a variety of dose reporting and tissue/applicator segmentation schemes were generated for a cohort (n = 10) of cervical cancer patients treated with 192 Ir-based Venezia brachytherapy. Dose calculations were performed using RapidBrachyMCTPS, a Geant4-based research Monte Carlo treatment planning system. Ultimately, five dose calculation scenarios were evaluated: (a) dose to water in water (D w,w ); (b) D w,w taking the applicator material into consideration (D w,wApp ); (c) dose to water in medium (D w,m ); (d and e) dose to medium in medium with mass densities assigned either nominally per structure (D m,m (Nom) ) or voxel-by-voxel (D m,m )., Results: Ignoring the plastic Venezia applicator (D w,wApp ) overestimates D m,m by up to 1% (average) with high energy source ( 192 Ir and 75 Se) and up to 2% with 169 Yb. Scoring dose to water (D w,wApp or D w,m ) generally overestimates dose and this effect increases with decreasing photon energy. Reporting dose other than D m,m (or D m,m Nom ) for 169 Yb-based conventional and intensity-modulated brachytherapy leads to a simultaneous overestimation (up to 4%) of CTV HR D 90 and underestimation (up to 2%) of bladder D 2cc due to a significant dip in the mass-energy absorption ratios at the depths of nearby targets and OARs. Using a nominal mass-density assignment per structure, rather than a CT-derived voxel-by-voxel assignment for MRI-guided brachytherapy, amounts to a dose error up to 1% for all radionuclides considered., Conclusions: The effects of the considered dose reporting schemes trend correspondingly between conventional and intensity-modulated brachytherapy. In the absence of CT-derived mass densities, MRI-only-based dosimetry can adequately approximate D m,m by assigning nominal mass densities to structures. Tissue and applicator heterogeneities do not significantly impact dosimetry for 192 Ir and 75 Se, but do for 169 Yb; dose reporting must be explicitly defined since D w,m and D w,w may overstate the dosimetric benefits., (© 2021 American Association of Physicists in Medicine.)

Introduction: The optimal overall treatment time (OTT) from radical surgery to the end of adjuvant radiation therapy for some squamous cell carcinomas has been found to impact treatment outcomes. This study aims to identify the impact of OTT on overall survival (OS) for women with completely resected, node-positive squamous cell carcinomas of the vulva., Materials and Methods: The National Cancer Data Base was queried for women with surgically resected, node-positive vulvar squamous cell carcinomas between 2004 and 2016 who were treated with adjuvant radiation therapy. Kaplan-Meier analysis with log-rank test and Cox proportional hazards tests were utilized for OS calculations., Results: A total of 1500 women met inclusion criteria. The median OTT was 104 days. Shorter OTT was associated with age, facility volume, private insurance, and duration of post-operative hospitalization. Median OS with OTT ≤ 104 days was 56.1 months vs 45.4 months if ≥105 days (p = 0.015). On multivariable Cox analysis, OTT was independently associated with an increased risk of death of 0.4% per additional day (95%CI 1.001-1.007, p = 0.003), as were age at diagnosis (HR 1.031 [95%CI 1.024-1.037], p < 0.001), number of nodes positive (HR 1.031 [95%CI 1.024-1.037], p = 0.006), the use of concurrent chemotherapy (HR 0.815 [95%CI 0.693-0.960], p = 0.014) and increasing pT/pN stage. After propensity adjustment for factors predicting a shorter OTT, OTT continued to be associated with an increased risk of death per additional day (HR 1.004 [95%CI 1.001-1.007], p = 0.007)., Conclusion: Overall treatment time is an independent risk factor for death in women being treated with adjuvant radiation therapy following complete resection of node-positive squamous cell carcinoma of the vulva., Competing Interests: Declaration of Competing Interest The authors of this manuscript do not have any conflicts of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Accurate target definition is critical for the appropriate application of radiation therapy. In 2008, the Radiation Therapy Oncology Group (RTOG) published an international collaborative atlas to define the clinical target volume (CTV) for intensity modulated pelvic radiation therapy in the postoperative treatment of endometrial and cervical cancer. The current project is an updated consensus of CTV definitions, with removal of all references to bony landmarks and inclusion of the para-aortic and inferior obturator nodal regions., Methods and Materials: An international consensus guideline working group discussed modifications of the current atlas and areas of controversy. A document was prepared to assist in contouring definitions. A sample case abdominopelvic computed tomographic image was made available, on which experts contoured targets. Targets were analyzed for consistency of delineation using an expectation-maximization algorithm for simultaneous truth and performance level estimation with kappa statistics as a measure of agreement between observers., Results: Sixteen participants provided 13 sets of contours. Participants were asked to provide separate contours of the following areas: vaginal cuff, obturator, internal iliac, external iliac, presacral, common iliac, and para-aortic regions. There was substantial agreement for the common iliac region (sensitivity 0.71, specificity 0.981, kappa 0.64), moderate agreement in the external iliac, para-aortic, internal iliac and vaginal cuff regions (sensitivity 0.66, 0.74, 0.62, 0.59; specificity 0.989, 0.966, 0.986, 0.976; kappa 0.60, 0.58, 0.52, 0.47, respectively), and fair agreement in the presacral and obturator regions (sensitivity 0.55, 0.35; specificity 0.986, 0.988; kappa 0.36, 0.21, respectively). A 95% agreement contour was smoothed and a final contour atlas was produced according to consensus., Conclusions: Agreement among the participants was most consistent in the common iliac region and least in the presacral and obturator nodal regions. The consensus volumes formed the basis of the updated NRG/RTOG Oncology postoperative atlas. Continued patterns of recurrence research are encouraged to refine these volumes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Vaginal necrosis is a late radiation tissue injury with serious morbidity complications. It is rare, and its incidence is not well assessed in prospective trials. Patient comorbidities and radiation dose can significantly increase the risk. As treatment of gynecologic malignancies often involve a multidisciplinary approach, timely diagnosis and appropriate management by physicians of the team are crucial. Untreated vaginal necrosis can lead to infection, hemorrhage, necrosis-related fistulation to the bladder or rectum, perforation, and death. In this review, we describe the pathophysiology of vaginal necrosis, its clinical course, and management options., Competing Interests: Declaration of Competing Interest The authors have no relevant conflicts of interest to disclose. Dr. Viswanathan is the principal investigator for NIH R01 CA237005., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To present a novel, MRI-compatible dynamicshield intensity modulated brachytherapy (IMBT) applicator and delivery system using 192 Ir, 75 Se, and 169 Yb radioisotopes for the treatment of locally advanced cervical cancer. Needle-free IMBT is a promising technique for improving target coverage and organs at risk (OAR) sparing., Methods and Materials: The IMBT delivery system dynamically controls the rotation of a novel tungsten shield placed inside an MRI-compatible, 6-mm wide intrauterine tandem. Using 36 cervical cancer cases, conventional intracavitary brachytherapy (IC-BT) and intracavitary/interstitial brachytherapy (IC/IS-BT) (10Ci 192 Ir) plans were compared to IMBT (10Ci 192 Ir; 11.5Ci 75 Se; 44Ci 169 Yb). All plans were generated using the Geant4-based Monte Carlo dose calculation engine, RapidBrachyMC. Treatment plans were optimized then normalized to the same high-risk clinical target volume (HR-CTV) D 90 and the D 2cc for bladder, rectum, and sigmoid in the research brachytherapy planning system, RapidBrachyMCTPS. Plans were renormalized until either of the three OAR reached dose limits to calculate the maximum achievable HR-CTV D 90 and D 98 ., Results: Compared to IC-BT, IMBT with either of the three radionuclides significantly improves the HR-CTV D 90 and D 98 by up to 5.2% ± 0.3% (P < 0.001) and 6.7% ± 0.5% (P < 0.001), respectively, with the largest dosimetric enhancement when using 169 Yb followed by 75 Se and then 192 Ir. Similarly, D 2cc for all OAR improved with IMBT by up to 7.7% ± 0.6% (P < 0.001). For IC/IS-BT cases, needle-free IMBT achieved clinically acceptable plans with 169 Yb-based IMBT further improving HR-CTV D 98 by 1.5% ± 0.2% (P = 0.034) and decreasing sigmoid D 2cc by 1.9% ± 0.4% (P = 0.048). Delivery times for IMBT are increased by a factor of 1.7, 3.3, and 2.3 for 192 Ir, 75 Se, and 169 Yb, respectively, relative to conventional 192 Ir BT., Conclusions: Dynamic shield IMBT provides a promising alternative to conventional IC- and IC/IS-BT techniques with significant dosimetric enhancements and even greater improvements with intermediate energy radionuclides. The ability to deliver a highly conformal, OAR-sparing dose without IS needles provides a simplified method for improving the therapeutic ratio less invasively and in a less resource intensive manner., (© 2020 American Association of Physicists in Medicine.)

Competing Interests: Declaration of Competing Interest Christina Annunziata (American Society of Clinical Oncology representative): MaxCyte, Medivir, and Precision Biologics (research), Horizon Pharma and Merck (provided drugs for clinical trial); Sushil Beriwal: Eisai, Institute of Education, and Via Oncology (honoraria), Varian (consultant), XOFT (DSMB); Matthew Harkenrider: AstraZeneca (advisory board [ended]), Varian (advisory board [ended]); Christine Holschneider (Society of Gynecologic Oncology representative): UpToDate (honoraria); Mitchell Kamrava: Augmenix (speakers bureau); Lilie Lin: AstraZeneca (research); Jyoti Mayadev: AstraZeneca (consultant), Varian (advisory board); Marc Morcos: Elekta (travel); Daniel Petereit: (American Brachytherapy Society representative and president): BMS Foundation (research and salary support), Irving A Hansen Memorial Foundation (patient funding), Ralph Lauren Pink Pony Foundation (board member); Beth Erickson: Elekta (research and travel); and Junzo Chino, Akila Viswanathan, Emma Fields, Jane Fitch (patient representative), Eric Leung, and Chika Nwachukwu reported no disclosures.

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., (Copyright © 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: In India, where the annual incidence of cancer is projected to reach 1.7 million by 2020, the need for clinical research to establish the most effective, resource-guided, and evidence-based care is paramount. In this study, we sought to better understand the research training needs of radiation oncologists in India., Methods: A 12 item questionnaire was developed to assess research training needs and was distributed at the research methods course jointly organized by Indian College of Radiation Oncology, the American Brachytherapy Society, and Education Committee of the American Society of Therapeutic Radiation Oncology during the Indian Cancer Congress, 2017., Results: Of 100 participants who received the questionnaire, 63% responded. Ninety percent (56/63) were Radiation Oncologists. Forty-two percent (26/63) of respondents had previously conducted research. A longer length of practice (>10 years) was significantly associated with conducting research (odds ratio (OR) 6.99, P = 0.031) and having formal research training trended toward significance (OR 3.03, P = 0.058). The most common reason for not conducting research was "lack of training" (41%, 14/34). The most common types of research conducted were Audits and Retrospective studies (62%, 16/26), followed by a Phase I/II/III Trial (46%, 10/26). Having formal research training was a significant factor associated with writing a protocol (OR 5.53, P = 0.016). Limited training in research methods (54%, 13/24) and lack of mentorship (42%, 10/24) were cited as reasons for not developing a protocol. Ninety-seven percent (57/59) of respondents were interested in a didactic session on research, specifically focusing on biostatistics., Conclusions: With research training and mentorship, there is a greater likelihood that concepts and written protocols will translate into successfully completed studies in radiation therapy., Competing Interests: None

The use of brachytherapy for the treatment of gynecologic malignancies, particularly cervical cancer, has a long and rich history that is nearly as long as the history of radiation oncology itself. From the first gynecologic brachytherapy treatments in the early 20th century to the modern era, significant transformation has occurred driven largely by advancements in technology. The development of high-dose rate sources, remote afterloaders, novel applicators, and 3-dimensional image guidance has led to improved local control, and thus improved survival, solidifying the role of brachytherapy as an integral component in the treatment of locally advanced cervical cancer. Current research efforts examining novel magnetic resonance imaging sequences, active magnetic resonance tracking, and the application of hydrogel aim to further improve local control and reduce treatment toxicity., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To develop expert consensus recommendations regarding radiation therapy for gynecologic malignancies during the COVID-19 pandemic., Methods: An international committee of ten experts in gynecologic radiation oncology convened to provide consensus recommendations for patients with gynecologic malignancies referred for radiation therapy. Treatment priority groups were established. A review of the relevant literature was performed and different clinical scenarios were categorized into three priority groups. For each stage and clinical scenario in cervical, endometrial, vulvar, vaginal and ovarian cancer, specific recommendations regarding dose, technique, and timing were provided by the panel., Results: Expert review and discussion generated consensus recommendations to guide radiation oncologists treating gynecologic malignancies during the COVID-19 pandemic. Priority scales for cervical, endometrial, vulvar, vaginal, and ovarian cancers are presented. Both radical and palliative treatments are discussed. Management of COVID-19 positive patients is considered. Hypofractionated radiation therapy should be used when feasible and recommendations regarding radiation dose, timing, and technique have been provided for external beam and brachytherapy treatments. Concurrent chemotherapy may be limited in some countries, and consideration of radiation alone is recommended., Conclusions: The expert consensus recommendations provide guidance for delivering radiation therapy during the COVID-19 pandemic. Specific recommendations have been provided for common clinical scenarios encountered in gynecologic radiation oncology with a focus on strategies to reduce patient and staff exposure to COVID-19., Competing Interests: Declaration of Competing Interest Christen Elledge, Supriya Chopra, Beth Erikson, David Gaffney, Anuja Jhingran, Ann Klopp, and Catherine Yashar have nothing to disclose. Akila Viswanathan is the principal investigator of NIH R01 CA237005. Sushil Beriwal is a consultant for Varian and Medical Director of Via Oncology, outside the submitted work. Cyrus Chargari receives grant funding from Roche, personal fees from Merck Sharp & Dohme Corp., Elekta, and GlaxoSmithKline, as well as non-financial support from TherAguiX and GlaxoSmithKline, all outside the submitted work. William Small is the co-chair of the NRG Gyn Committee, has served on an advisory board for Merck, and has received honoraria for invited talks from Carl Zeiss Meditech, outside the submitted work., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: This guideline reviews the evidence and provides recommendations for the indications and appropriate techniques of radiation therapy (RT) in the treatment of nonmetastatic cervical cancer., Methods: The American Society for Radiation Oncology convened a task force to address 5 key questions focused on the use of RT in definitive and postoperative management of cervical cancer. These questions included the indications for postoperative and definitive RT, the use of chemotherapy in sequence or concurrent with RT, the use of intensity modulated radiation therapy (IMRT), and the indications and techniques of brachytherapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength., Results: The guideline recommends postoperative RT for those with intermediate risk factors, and chemoradiation for those with high-risk factors. In the definitive setting, chemoradiation is recommended for stages IB3-IVA, and RT or chemoradiation is conditionally recommended for stages IA1-IB2 if medically inoperable. IMRT is recommended for postoperative RT and conditionally recommended for definitive RT, for the purposes of reducing acute and late toxicity. Brachytherapy is strongly recommended for all women receiving definitive RT, and several recommendations are made for target dose and fractionation, the use of intraoperative imaging, volume-based planning, and recommendations for doses limits for organs at risk., Conclusions: There is strong evidence supporting the use of RT with or without chemotherapy in both definitive and postoperative settings. Brachytherapy is an essential part of definitive management and volumetric planning is recommended. IMRT may be used for the reduction of acute and late toxicity. The use of radiation remains an essential component for women with cervical cancer to achieve cure., (Copyright © 2020 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Current treatment options for advanced cervical cancer are limited, especially for patients in poor-resource settings, with a 17% 5-year overall survival rate. Here, we report results in animal models of advanced cervical cancer, showing that anti-CD40 therapy can effectively boost the abscopal effect, whereby radiotherapy of a tumor at one site can engender therapeutically significant responses in tumors at distant untreated sites. In this study, two subcutaneous cervical cancer tumors representing one primary and one metastatic tumor were generated in each animal. Only the primary tumor was treated and the responses of both tumors were monitored. The study was repeated as a function of different treatment parameters, including radiotherapy dose and dosing schedule of immunoadjuvant anti-CD40. The results consistently suggest that one fraction dose of radiotherapy with a single dose of agonistic anti-CD40 can generate highly effective abscopal responses, with a significant increase in animal survival ( p = 0.0004). Overall, 60% of the mice treated with this combination showed long term survival with complete tumor regression, where tumors of mice in other cohorts continued to grow. Moreover, re-challenged responders to the treatment developed vitiligo, suggesting developed immune memory for this cancer. The findings offer a potential new therapy approach, which could be further investigated and developed for the treatment of advanced cervical cancer, with major potential impact, especially in resource-poor settings.

Objectives: Lymphovascular space invasion (LVSI) is an independent risk factor for recurrence and poor survival in early-stage endometrioid endometrial cancer (EEC), but optimal adjuvant treatment is unknown. We aimed to compare the survival of women with early-stage EEC with LVSI treated postoperatively with observation (OBS), radiation (RAD, external beam and/or vaginal brachytherapy), or chemotherapy (CHEMO)+/-RAD., Methods: This was a multi-institutional, retrospective cohort study of women with stage I or II EEC with LVSI who underwent hysterectomy+/-lymphadenectomy from 2005 to 2015 and received OBS, RAD, or CHEMO+/-RAD postoperatively. Progression-free survival and overall survival were evaluated using Kaplan-Meier estimates and Cox proportional hazards models., Results: In total, 478 women were included; median age was 64 years, median follow-up was 50.3 months. After surgery, 143 (30%) underwent OBS, 232 (48.5%) received RAD, and 103(21.5%) received CHEMO+/-RAD (95% of whom received RAD). Demographics were similar among groups, but those undergoing OBS had lower stage and grade. A total of 101 (21%) women recurred. Progression-free survival (PFS) was improved in both CHEMO+/-RAD (HR = 0.18, 95% CI: 0.09-0.39) and RAD (HR = 0.31, 95% CI: 0.18-0.54) groups compared to OBS, though neither adjuvant therapy was superior to the other. However, in grade 3 tumors, the CHEMO+/-RAD group had superior PFS compared to both RAD (HR 0.25; 95% CI: 0.12-0.52) and OBS cohorts (HR = 0.10, 95% CI: 0.03-0.32). Overall survival did not differ by treatment., Conclusions: In early-stage EEC with LVSI, adjuvant therapy improved PFS compared to observation alone. In those with grade 3 EEC, adjuvant chemotherapy with or without radiation improved PFS compared to observation or radiation alone., Competing Interests: Declaration of competing interest All authors reported their potential conflicts of interest, and there were not relevant conflicts of interest disclosed., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Recurrences of previously irradiated gynecological malignancies are uncommon. Standardized management of these cases is not well established. We aim to provide an in-depth literature review and present current practice patterns among an international group of experienced practitioners in the reirradiation setting of gynecologic cancers., Methods and Materials: An extensive literature search was performed and 35 articles were selected based on preset criteria. A 20-question online survey of 10 experts regarding their retreatment practices was also conducted., Results: The reviewed publications include a diverse group of patients, multiple treatment techniques, a range of total doses, local control, overall survival, and toxicity outcomes. Overall, local control ranged from 44% to 88% over 1-5 years with OS in the range of 39.5-82% at 2-5 years. Late G3-4 toxicity varied very broadly from 0% to 42.9%, with most papers reporting serious toxicities greater than 15%. The most common reirradiation technique utilized was brachytherapy. Some low-dose-rate data suggest improved outcomes with doses >50 Gy. The high-dose-rate data are more varied with some studies suggesting improved local control with doses >40 Gy. In general, a longer time interval between the first and second course of radiation as well as recurrences <2-4 cm tend to have improved outcomes., Conclusions: Reirradiation with brachytherapy results in relatively reasonable local control and toxicities for women with recurrent gynecologic cancers. The appropriate dose for each case needs to be individualized given the heterogeneity of cases. Multidisciplinary management is critical to develop individualized plans and to clearly communicate potential side effects and expected treatment outcomes., Take Home Message: Reirradiation with brachytherapy is an acceptable effective organ preserving approach for recurrent gynecologic cancers with a reasonable local control and toxicity profile. Each case requires multidisciplinary management to develop an individualized approach. Monitoring for potential long-term toxicities is essential., (Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

The incorporation of magnetic resonance imaging in brachytherapy has resulted in an increased use of interstitial catheters in order to create a comprehensive treatment plan that covers the visualized tumor. However, the insertion with passive, image-guidance requires estimating the location of the tumor during the insertion process, rather than visualizing and inserting the catheters directly to the desired location under active tracking. In order to treat residual disease, multiparametric MR sequences can enhance the information available to the clinician. The precision availed by MR-guided brachytherapy results in substantial improvements in needle positioning, and resulting treatment plans., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: The imaging performance and dose of a mobile CT scanner (Brainlab Airo®, Munich, Germany) is evaluated, with particular consideration to assessment of technique protocols for image-guided brachytherapy., Method: Dose measurements were performed using a 100-mm-length pencil chamber at the center and periphery of 16- and 32-cm-diameter CTDI phantoms. Hounsfield unit (HU) accuracy and linearity were assessed using materials of specified electron density (Gammex RMI, Madison, WI), and image uniformity, noise, and noise-power spectrum (NPS) were evaluated in a 20-cm-diameter water phantom as well as an American College of Radiology (ACR) CT accreditation phantom (Model 464, Sun Nuclear, Melbourne, FL). Spatial resolution (modulation transfer function, MTF) was assessed with an edge-spread phantom and visually assessed with respect to line-pair patterns in the ACR phantom and in structures of interest in anthropomorphic phantoms. Images were also obtained on a diagnostic CT scanner (Big Bore CT simulator, Philips, Amsterdam, Netherlands) for qualitative and quantitative comparison. The manufacturer's metal artifact reduction (MAR) algorithm was assessed in an anthropomorphic body phantom containing surgical instrumentation. Performance in application to brachytherapy was assessed with a set of anthropomorphic brachytherapy phantoms - for example, a vaginal cylinder and interstitial ring and tandem., Result: Nominal dose for helical and axial modes, respectively, was 56.4 and 78.9 mGy for the head protocol and 17.8 and 24.9 mGy for the body protocol. A high degree of HU accuracy and linearity was observed for both axial and helical scan modes. Image nonuniformity (e.g., cupping artifact) in the transverse (x,y) plane was less than 5 HU, but stitching artifacts (~5 HU) in the longitudinal (z) direction were observed in axial scan mode. Helical and axial modes demonstrated comparable spatial resolution of ~5 lp/cm, with the MTF reduced to 10% at ~0.38 mm -1 . Contrast-to-noise ratio was suitable to soft-tissue visualization (e.g., fat and muscle), but windmill artifacts were observed in helical mode in relation to high-frequency bone and metal. The MAR algorithm provided modest improvement to image quality. Overall, image quality appeared suitable to relevant clinical tasks in intracavitary and interstitial (e.g., gynecological) brachytherapy, including visualization of soft-tissue structures in proximity to the applicators., Conclusion: The technical assessment highlighted key characteristics of dose and imaging performance pertinent to incorporation of the mobile CT scanner in clinical procedures, helping to inform clinical deployment and technique protocol selection in brachytherapy. For this and other possible applications, the work helps to identify protocols that could reduce radiation dose and/or improve image quality. The work also identified areas for future improvement, including reduction of stitching, windmill, and metal artifacts., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Brachytherapy is a specific form of radiotherapy consisting of the precise placement of radioactive sources directly into or next to the tumor. This technique is indicated for patients affected by various types of cancers. It is an optimal tool for delivering very high doses to the tumor focally while minimizing the probability of normal tissue complications. Physicians from a wide range of specialties may be involved in either the referral to or the placement of brachytherapy. Many patients require brachytherapy as either primary treatment or as part of their oncologic care. On the basis of high-level evidence from randomized controlled trials, brachytherapy is mainly indicated: 1) as standard in combination with chemoradiation in patients with locally advanced cervical cancer; 2) in surgically treated patients with uterine endometrial cancer for decreasing the risk of vaginal vault recurrence; 3) in patients with high-risk prostate cancer to perform dose escalation and improve progression-free survival; and 4) in patients with breast cancer as adjuvant, accelerated partial breast irradiation or to boost the tumor bed. In this review, the authors discuss the clinical relevance of brachytherapy with a focus on indications, levels of evidence, and results in the overall context of radiation use for patients with cancer., (© 2019 American Cancer Society.)

Aim and Background: We describe a successful implementation of a departmental incident learning system (ILS) across a regionally expanding academic radiation oncology department, dovetailing with a structured integration of the safety and quality program across clinical sites., Materials and Methods M: Over 6 years between 2011 and 2017, a long-standing departmental ILS was deployed to 4 clinical locations beyond the primary clinical location where it had been established. We queried all events reported to the ILS during this period and analyzed trends in reporting by clinical site. The chi-square test was used to determine whether differences over time in the rate of reporting were statistically significant. We describe a synchronous development of a common safety and quality program over the same period., Results: There was an overall increase in the number of event reports from each location over the time period from 2011 to 2017. The percentage increase in reported events from the first year of implementation to 2017 was 457% in site 1, 166.7% in site 2, 194.3% in site 3, 1025% in site 4, and 633.3% in site 5, with an overall increase of 677.7%. A statistically significant increase in the rate of reporting was seen from the first year of implementation to 2017 ( p  < 0.001 for all sites)., Conclusions: We observed significant increases in event reporting over a 6-year period across 5 regional sites within a large academic radiation oncology department, during which time we expanded and enhanced our safety and quality program, including regional integration. Implementing an ILS and structuring a safety and quality program together result in the successful integration of the ILS into existing departmental infrastructure.

Purpose: We evaluated patterns of event reporting across five clinical locations within an academic radiation oncology department, with the goal of better understanding variability across sites., Methods and Materials: We analyzed 1,351 events reported to a departmental incident learning system over 1 calendar year across the five locations with respect to volume of events, event type, process map location of origin and detection, and event reporter., Results: We found marked variability in reporting patterns, including reporting rate, event type, event severity, event location of origin and detection within the departmental process map, and discipline of event reporters. These differences relate both to variability in process and workflow (reflected by frequency of specific workflow events at each site) and in reporting culture (reflected by volume or rate of event reporting, and discipline of event reporter)., Conclusions: These data highlight the variability in reporting culture even within a single department, and therefore the need to tailor and individualize safety and quality programs to the unique clinical site, with the long-term goal of achieving a common culture of safety while supporting unique processes at individual locations. This work also raises concern about extrapolating single-institution incident learning system results without understanding the unique workflow and culture of clinical sites., (Copyright © 2019. Published by Elsevier Inc.)

Purpose: The purpose of this work was to compare the dosimetry and delivery times of 3D-conformal (3DCRT)-, volumetric modulated arc therapy (VMAT)-, and tomotherapy-based approaches for spatially fractionated radiation therapy for deep tumor targets., Methods: Two virtual GRID phantoms were created consisting of 7 "target" cylinders (1-cm diameter) aligned longitudinally along the tumor in a honey-comb pattern, mimicking a conventional GRID block, with 2-cm center-to-center spacing (GRID 2 cm ) and 3-cm center-to-center spacing (GRID 3 cm ), all contained within a larger cylinder (8 and 10 cm in diameter for the GRID 2 cm and GRID 3 cm , respectively). In a single patient, a GRID 3 cm structure was created within the gross tumor volume (GTV). Tomotherapy, VMAT (6 MV + 6 MV-flattening-filter-free) and multi-leaf collimator segment 3DCRT (6 MV) plans were created using commercially available software. Two tomotherapy plans were created with field widths (TOMO 2.5 cm ) 2.5 cm and (TOMO 5 cm ) 5 cm. Prescriptions for all plans were set to deliver a mean dose of 15 Gy to the GRID targets in one fraction. The mean dose to the GRID target and the heterogeneity of the dose distribution (peak-to-valley and peak-to-edge dose ratios) inside the GRID target were obtained. The volume of normal tissue receiving 7.5 Gy was determined., Results: The peak-to-valley ratios for GRID 2 cm /GRID 3 cm /Patient were 2.1/2.3/2.8, 1.7/1.5/2.8, 1.7/1.9/2.4, and 1.8/2.0/2.8 for the 3DCRT, VMAT, TOMO 5 cm , and TOMO 2.5 cm plans, respectively. The peak-to-edge ratios for GRID 2 cm /GRID 3 cm /Patient were 2.8/3.2/5.4, 2.1/1.8/5.4, 2.0/2.2/3.9, 2.1/2.7/5.2 and for the 3DCRT, VMAT, TOMO 5 cm , and TOMO 2.5 cm plans, respectively. The volume of normal tissue receiving 7.5 Gy was lowest in the TOMO 2.5 cm plan (GRID 2 cm /GRID 3 cm /Patient = 54 cm 3 /19 cm 3 /10 cm 3 ). The VMAT plans had the lowest delivery times (GRID 2 cm /GRID 3 cm /Patient = 17 min/8 min/9 min)., Conclusion: Our results present, for the first time, preliminary evidence comparing IMRT-GRID approaches which result in high-dose "islands" within a target, mimicking what is achieved with a conventional GRID block but without high-dose "tail" regions outside of the target. These approaches differ modestly in their ability to achieve high peak-to-edge ratios and also differ in delivery times., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: To understand the reasons behind current low utilization of brachytherapy for locally advanced cervical cancer in the United States., Methods and Materials: A 17-item survey was e-mailed to the American Brachytherapy Society (ABS) listserv of active members in 2018. Responses of attending physicians in the United States were included in the analysis., Results: Among a total of 135 respondents, 81 completed the survey. Eighty-four percent agree/strongly agree that cervical brachytherapy is underutilized, and 46.9% disagree/strongly disagree that residents are receiving adequate training for brachytherapy; 75.3% agree/strongly agree that inadequate maintenance of brachytherapy skills is a major obstacle to brachytherapy use; and 71.6% agree/strongly agree that increased time requirement constitutes a major obstacle. Over 97% will recommend brachytherapy for most patients with cervical cancer if given access/time; 72.8% always perform their own brachytherapy, whereas 29.6% reported some type of barrier exists in performing brachytherapy themselves, with time required to perform brachytherapy (9.9%) being a leading factor. A quarter (24.7%) routinely refer to other radiation oncologists for brachytherapy. Even among ABS members, 37.0% reported that they would perform an intensity-modulated radiation therapy or stereotactic body radiation therapy boost in specific scenarios in potentially curable patients. The most common scenario is inability to place a uterine tandem (56.7%)., Conclusions: The underutilization of brachytherapy in cervical cancer is widely recognized by ABS members with inadequate training during residency and inadequate maintenance of skills being possible major contributing factors. Even among ABS members, there are identifiable barriers. Continued advocacy and future initiatives in enhancing access to brachytherapy training and efficiency are needed., (Published by Elsevier Inc.)

During the last decade the adoption of image-guided adaptive brachytherapy has dramatically improved local control in patients with locally advanced cervical cancer (LACC) treated with radiotherapy and concomitant chemotherapy; however, nodal failure remains an obstacle. Metastatic lymph nodes can be detected by surgical and imaging approaches with different sensitivities and specificities, that improve the definition of relevant targets for macroscopic and microscopic nodal disease, and that influence our understanding of dose levels of external beam radiotherapy. Systematic use of modern radiotherapy techniques including intensity modulated radiotherapy and simultaneously integrated nodal boosts in combination with daily position verification is emerging as increasingly important for obtaining nodal control in LACC. This review summarizes published and ongoing efforts for optimizing nodal disease treatment in LACC, elaborates the state of the art approach for nodal disease detection, radiotherapy planning and delivery, and discusses future investigational efforts needed for precise optimization., (Copyright © 2018. Published by Elsevier Inc.)

Importance: Despite progress in narrowing gender-based salary gaps, notable disparities persist in the scientific community. The significance of pay difference may be underestimated, with little data evaluating its effect on lifetime wealth after accounting for factors like time to promotion and savings., Objectives: To characterize gender disparities in salary and assess the outcomes associated with a gender equity initiative (GEI)., Design, Setting, and Participants: Quality improvement study with simulations of salary and additional accumulated wealth (AAW) using retrospectively reviewed Johns Hopkins University School of Medicine annual salary and promotion data. All academic faculty were included in the faculty salary analysis from 2005 (n = 1481) and 2016 (n = 1885)., Main Outcomes and Measures: Salary and longitudinal promotion data from 2005 to 2016 were used to estimate gender-based differences in salary and time to promotion. The effect of these differences on total salary and AAW, including retirement and salary-based investments, was simulated for a representative male and female faculty member over a 30-year career in 3 scenarios: (1) pre-GEI, (2) post-GEI, and (3) in real time for GEI, beginning with and progressing through these initiatives., Results: Analyses of salaries of 1481 faculty (432 women) in 2005 and 1885 faculty (742 women) in 2016 revealed that a decade after GEI implementation, the overall mean (SE) salary gap by gender decreased from -2.6% (1.2%) (95% CI, -5.6% to -0.3%) to -1.9% (1.1%) (95% CI, -4.1% to 0.3%). Simulation of pre-GEI disparities correlated with male faculty collecting an average lifetime AAW of $501 416 more than the equivalent woman, with disparities persisting past retirement. The AAW gap decreased to $210 829 in the real-time GEI simulation and to $66 104 using post-GEI conditions, reflecting success of GEI efforts., Conclusions and Relevance: Even small gender-based salary gaps are associated with substantial differences in lifetime wealth, but an institutional commitment to achieving equitable promotion and compensation for women can appreciably reduce these disparities. The findings of this study support broad implementation of similar initiatives without delay, as results may take more than a decade to emerge. A modifiable version of the simulation is provided so that external users may assess the potential disparities present within their own institutions.

Purpose: The optimal approach to managing incident learning system (ILS) reports remains unclear. Here, we describe our experience with prospective coding of events reported to the ILS with comparisons of risk scores on the basis of event type and process map location., Methods and Materials: Reported events were coded by type, origin, and method of discovery. Events were given a risk priority number (RPN) and near-miss risk index (NMRI) score. We compared workflow versus near-miss events with respect to origin and detection in the process map and by risk scores. A χ 2 test was used to compare the differences between workflow and near-miss events. A comparison of RPN scores was done by independent t test., Results: During 2016, 1351 events were reported. Of these events, 1300 (96.2%) were workflow and 51 (3.8%) near-miss events. Workflow events were more likely to both originate (1041 of 1300 events; 81.2%) compared with near-miss events (31 of 51 events; 62.7%; P = .005) and be detected in pre-treatment (997 of 1300 events; 76.7%) compared with near-miss events (24 of 51 events; 47%; P < .001). Average occurrence (scale: 1-10) was 6.14 for workflow versus 3.33 for near-miss events (P < .001), average severity was 2.94 versus 7.35 (P < .001), and average detectability was 1.33 versus 4.67 (P < .001). Mean overall RPN was 22.4 for workflow versus 108.4 for near-miss events (P = .07) and mean NMRI was 1.16 versus 3.19, respectively. Events that originated and were detected in treatment delivery had the greatest mean overall RPN (38.2 and 32.1, respectively) and NMRI scores (1.62 and 1.6, respectively)., Conclusions: Our experience demonstrates that workflow event reports are far more common than near-misses and that near-miss events are more likely to both originate and be discovered in later treatment phases. The frequency of workflow reports highlights the imperative need for safety and operational teams to work collaboratively to maximize the benefit of ILS. We suggest a potential utility of the RPN system to guide mitigation strategies for future near-miss events., (Copyright © 2018 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the survival endpoints in women with International Federation of Gynecology and Obstetrics (FIGO) stage II endometrial cancer who received adjuvant vaginal brachytherapy (VBT) alone using multi-institutional pooled data., Methods and Materials: We performed a multi-institutional analysis of surgically staged patients with FIGO stage II endometrioid-type endometrial cancer treated with VBT alone. Patient, tumor, and treatment characteristics were collected and analyzed. Univariable and multivariable frailty survival models were performed to assess clinicopathologic risk factors for recurrence and death., Results: One hundred six patients were included (92 VBT alone and 14 VBT with chemotherapy) with median follow-up of 39.0 months. Pelvic node dissection was performed in 89.6% of patients. One hundred four patients (98.1%) and 2 patients (1.9%) had microscopic and macroscopic cervical stromal invasion, respectively. Grade 1 or 2 disease occurred in 88.6% of patients. For patients treated with VBT without chemotherapy, the 5-year estimates of vaginal failure, pelvic nodal failure, and distant metastases were 2.6%, 4.2%, and 7.2%, respectively. Five-year progression-free survival and overall survival were 74.0% and 76.2%, respectively. On univariable and multivariable models for progression-free survival, increasing age and lack of pelvic node resection were hazardous (P < .05)., Conclusions: Vaginal and pelvic failure rates were low in this selected population of stage II patients receiving adjuvant VBT without external beam radiation therapy. It is reasonable to consider adjuvant VBT alone in selected patients with grade 1 or 2 disease and microscopic cervical stromal invasion who underwent pelvic lymphadenectomy., (Published by Elsevier Inc.)

Purpose: As a core component of a new gynecologic cancer radiation program, we envisioned, structured, and implemented a novel Interventional Radiation Oncology (IRO) unit and magnetic resonance (MR)-brachytherapy environment in an existing MR simulator., Methods and Materials: We describe the external and internal processes required over a 6-8 month time frame to develop a clinical and research program for gynecologic brachytherapy and to successfully convert an MR simulator into an IRO unit., Results: Support of the institution and department resulted in conversion of an MR simulator to a procedural suite. Development of the MR gynecologic brachytherapy program required novel equipment, staffing, infrastructural development, and cooperative team development with anesthetists, nurses, therapists, physicists, and physicians to ensure a safe and functional environment. Creation of a separate IRO unit permitted a novel billing structure., Conclusions: The creation of an MR-brachytherapy environment in an MR simulator is feasible. Developing infrastructure includes several collaborative elements. Unique to the field of radiation oncology, formalizing the space as an Interventional Radiation Oncology unit permits a sustainable financial structure., (Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To prospectively compare survival between human immunodeficiency virus (HIV)-infected versus HIV-uninfected cervical cancer patients who initiated curative chemoradiation therapy (CRT) in a limited-resource setting., Methods and Materials: Women with locally advanced cervical cancer with or without HIV infection initiating radical CRT in Botswana were enrolled in a prospective, observational, cohort study from July 2013 through January 2015., Results: Of 182 women treated for cervical cancer during the study period, 143 women initiating curative CRT were included in the study. Eighty-five percent of the participants (122 of 143) had stage II/III cervical cancer, and 67% (96 of 143) were HIV-infected. All HIV-infected patients were receiving antiretroviral therapy (ART) at the time of curative cervical cancer treatment initiation. We found no difference in toxicities between HIV-infected and HIV-uninfected women. The 2-year overall survival (OS) rates were 65% for HIV-infected women (95% confidence interval [CI] 54%-74%) and 66% for HIV-uninfected women (95% CI 49%-79%) (P = .70). Factors associated with better 2-year OS on multivariate analyses included baseline hemoglobin >10 g/dL (hazard ratio [HR] 0.37, 95% CI 0.19-0.72, P = .003), total radiation dose ≥75 Gy (HR 0.52, 95% CI 0.27-0.97, P = .04), and age <40 years versus 40-59 years (HR 2.17, 95% CI 1.05-4.47, P = .03)., Conclusions: Human immunodeficiency virus status had no effect on 2-year OS or on acute toxicities in women with well-managed HIV infection who initiated curative CRT in Botswana. In our cohort, we found that baseline hemoglobin levels, total radiation dose, and age were associated with survival, regardless of HIV status., (Copyright © 2018 Elsevier Inc. All rights reserved.)