Brachytherapy: An overview for clinicians.

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.

Selective de-implementation of routine in vivo dosimetry.

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.

Radiation oncology management of stage III and IVA cervical carcinoma.

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.

Fully automated segmentation of clinical target volume in cervical cancer from magnetic resonance imaging with convolutional neural network.

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.

MR-Tracked Deflectable Stylet for Gynecologic Brachytherapy.

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.

Vaginal necrosis: A rare late toxicity after radiation therapy.

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.

Optimal overall treatment time for adjuvant therapy for women with completely resected, node-positive vulvar cancer.

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.

Radiation therapy for gynecologic malignancies during the COVID-19 pandemic: International expert consensus recommendations.

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.

Adjuvant therapy for early stage, endometrial cancer with lymphovascular space invasion: Is there a role for chemotherapy?

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.

Technical assessment of a mobile CT scanner for image-guided brachytherapy.

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.

Comparison of treatment planning approaches for spatially fractionated irradiation of deep tumors.

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 (GRID2 cm ) and 3-cm center-to-center spacing (GRID3 cm ), all contained within a larger cylinder (8 and 10 cm in diameter for the GRID2 cm and GRID3 cm , respectively). In a single patient, a GRID3 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 (TOMO2.5 cm ) 2.5 cm and (TOMO5 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 GRID2 cm /GRID3 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, TOMO5 cm , and TOMO2.5 cm plans, respectively. The peak-to-edge ratios for GRID2 cm /GRID3 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, TOMO5 cm , and TOMO2.5 cm plans, respectively. The volume of normal tissue receiving 7.5 Gy was lowest in the TOMO2.5 cm plan (GRID2 cm /GRID3 cm /Patient = 54 cm3 /19 cm3 /10 cm3 ). The VMAT plans had the lowest delivery times (GRID2 cm /GRID3 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.

Adoption of an incident learning system in a regionally expanding academic radiation oncology department.

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.

Cervical cancer: A global health crisis.

Cervical cancer is the fourth most common malignancy diagnosed in women worldwide. Nearly all cases of cervical cancer result from infection with the human papillomavirus, and the prevention of cervical cancer includes screening and vaccination. Primary treatment options for patients with cervical cancer may include surgery or a concurrent chemoradiotherapy regimen consisting of cisplatin-based chemotherapy with external beam radiotherapy and brachytherapy. Cervical cancer causes more than one quarter of a million deaths per year as a result of grossly deficient treatments in many developing countries. This warrants a concerted global effort to counter the shocking loss of life and suffering that largely goes unreported. This article provides a review of the biology, prevention, and treatment of cervical cancer, and discusses the global cervical cancer crisis and efforts to improve the prevention and treatment of the disease in underdeveloped countries. Cancer 2017;123:2404-12. © 2017 American Cancer Society.

Frailty measure is more predictive of outcomes after curative therapy for endometrial cancer than traditional risk factors in women 60 and older.

OBJECTIVES: To determine if readily obtainable markers of frailty predict disease-free survival (DFS) in elderly women with endometrial cancer treated with curative intent. METHODS: 88 consecutive women≥age 60 treated with surgery, chemotherapy and radiation for stage I-IV endometrial cancer were included. We considered the following health deficits as markers of "frailty": albumin <3.5mg/dL, hemoglobin <10mg/dL, BMI<20kg/m,2 unintentional weight loss, ECOG performance status ≥2, history of osteopenia or osteoporosis and Charlson comorbidity score. Kaplan-Meier estimates and Cox proportional hazards models of DFS were calculated. RESULTS: The median age was 68.5 (range 60-88years). The majority of women (65/88) had at least one frailty factor at baseline and 23/88 had two or more. All women received radiation and chemotherapy. Treatment was delayed, modified or truncated in 46% (40/88) of women due to treatment-related toxicity. Age (< 70 vs. ≥70 y) did not independently predict toxicity or recurrence risk. Women with at least one baseline frailty factor had twice the risk of disease recurrence (HR=2.21;95% CI:1.02-4.80) when adjusted for age, stage, grade and Charlson score. The 3-year DFS was 77% in those with no frailty markers and 48% in those with at least one (p=0.02). The presence of a frailty marker also predicted shortened overall survival (HR=2.34;95% CI:1.08-5.03) irrespective of treatment administered and stage of disease. CONCLUSIONS: A combined frailty measure was a more robust predictor of DFS and OS than patient age, tumor characteristics and comorbidities in this cohort of older women with very good functional status.

Comparison of outcomes for MR-guided versus CT-guided high-dose-rate interstitial brachytherapy in women with locally advanced carcinoma of the cervix.

OBJECTIVE: The purpose was to compare local control (LC), overall survival (OS) and dose to the organs at risk (OAR) in women with locally advanced cervical cancer treated with MR-guided versus CT-guided interstitial brachytherapy (BT). METHODS: 56 patients (29 MR, 27 CT) were treated with high-dose-rate (HDR) interstitial BT between 2005-2015. The MR patients had been prospectively enrolled on a Phase II clinical trial. Data were analyzed using Kaplan-Meier (K-M) and Cox proportional hazards statistical modeling in JMP® & R®. RESULTS: Median follow-up time was 19.7months (MR group) and 18.4months (CT group). There were no statistically significant differences in patient age at diagnosis, histology, percent with tumor size >4cm, grade, FIGO stage or lymph node involvement between the groups. Patients in the MR group had more lymphovascular involvement compared to patients in the CT group (p<0.01). When evaluating plans generated, there were no statistically significant differences in median cumulative dose to the high-risk clinical target volume or the OAR. 2-year K-M LC rates for MR-based and CT-based treatments were 96% and 87%, respectively (log-rank p=0.65). At 2years, OS was significantly better in the MR-guided cohort (84% vs. 56%, p=0.036). On multivariate analysis, squamous histology was associated with longer OS (HR 0.23, 95% CI 0.07-0.72) in a model with MR BT (HR 0.35, 95% CI 0.08-1.18). There was no difference in toxicities between CT and MR BT. CONCLUSION: In this population of locally advanced cervical-cancer patients, MR-guided HDR BT resulted in estimated 96% 2-year local control and excellent survival and toxicity rates.

Therapeutic radiation and the potential risk of second malignancies.

Radiation has long been associated with carcinogenesis. Nevertheless, it is an important part of multimodality therapy for many malignancies. It is critical to assess the risk of secondary malignant neoplasms (SMNs) after radiation treatment. The authors reviewed the literature with a focus on radiation and associated SMNs for primary hematologic, breast, gynecologic, and pediatric tumors. Radiation appeared to increase the risk of SMN in all of these; however, this risk was found to be associated with age, hormonal influences, chemotherapy use, environmental influences, genetic predisposition, infection, and immunosuppression. The risk also appears to be altered with modern radiotherapy techniques. Practitioners of all specialties who treat cancer survivors in follow-up should be aware of this potential risk. Cancer 2016;122:1809-21. © 2016 American Cancer Society.

Characterizing gradient echo signal decays in gynecologic cancers at 3T using a Gaussian augmentation of the monoexponential (GAME) model.

PURPOSE: To assess whether R2* mapping with a standard Monoexponential (ME) or a Gaussian Augmentation of the Monoexponential (GAME) decay model better characterizes gradient-echo signal decays in gynecological cancers after external beam radiation therapy at 3T, and evaluate implications of modeling for noninvasive identification of intratumoral hypoxia. MATERIALS AND METHODS: Multi-gradient-echo signals were acquired on 25 consecutive patients with gynecologic cancers and three healthy participants during inhalation of different oxygen concentrations at 3T. Data were fitted with both ME and GAME models. Models were compared using F-tests in tumors and muscles in patients, muscles, cervix, and uterus in healthy participants, and across oxygenation levels. RESULTS: GAME significantly improved fitting over ME (P < 0.05): Improvements with GAME covered 34% of tumor regions-of-interest on average, ranging from 6% (of a vaginal tumor) to 68% (of a cervical tumor) in individual tumors. Improvements with GAME were more prominent in areas that would be assumed hypoxic based on ME alone, reaching 90% as ME R2* approached 100 Hz. Gradient echo decay parameters at different oxygenation levels were not significantly different (P = 0.81). CONCLUSION: R2* may prove sensitive to hypoxia; however, inaccurate representations of underlying data may limit the success of quantitative assessments. Although the degree to which R2 or σ values correlate with hypoxia remains unknown, improved characterization with GAME increases the potential for determining any correlates of fit parameters with biomarkers, such as oxygenation status. J. MAGN. RESON. IMAGING 2016;44:1020-1030.

Pros and cons of vaginal brachytherapy after external beam radiation therapy in endometrial cancer.

A large number of studies have looked at the role of radiation therapy in the treatment of endometrial cancer. One particular radiation strategy in common practice is the use of adjuvant external beam (EB) radiotherapy followed by vaginal brachytherapy (VB). While the addition of VB to EB provides a theoretical benefit of a localized boost with higher focused dose to an area of potentially high recurrence risk, a randomized clinical trial to compare outcomes and toxicities of EB+VB vs. EB alone is lacking. The goal of this review is to present the current data for and against the use of this combined radiation modality and to provide some preliminary evidence regarding which patient populations may be most likely to benefit.

Prognostic importance of human papillomavirus (HPV) and p16 positivity in squamous cell carcinoma of the vulva treated with radiotherapy.

OBJECTIVE: HPV status is an important prognostic factor for patients with oropharyngeal, anal and cervical cancers treated with radiotherapy. This study evaluates the association between HPV and p16 status and outcome in a radiation-treated cohort with vulvar squamous cell carcinoma (SCC). METHODS: Patients with vulvar SCC who received radiotherapy with or without surgical resection between 1985 and 2011 were identified retrospectively. Immunostaining for p16 and multiplex PCR for HPV genotyping were performed using archival tumor tissue from 57 patients. Actuarial estimates of PFS, OS and in-field recurrence were calculated using the Kaplan-Meier method. Cox proportional hazards models were used for multivariable analysis. Median follow-up was 58months among the 57 patients with an available tumor specimen. RESULTS: HPV prevalence was implied in 37% by (diffuse linear) p16 immunostaining and confirmed in 27% by HPV PCR with good agreement (κ=0.7). HPV-16 was identified in 80% of HPV-positive tumors. Women with p16-positive tumors had significantly higher 5-year PFS (65% vs. 16%, p<0.01) and OS (65% vs. 22%, p=0.01) rates, as well as lower in-field relapse rates (19% vs. 75%, p<0.01) compared to those with p16-negative disease. On multivariable analysis adjusted for age and stage, p16 positivity was significantly associated with better PFS (HR 0.4, 95% CI 0.2-0.9) and lower rates of in-field relapse (HR 0.2, 95% CI 0.06-0.6). Results were similar when analyzed by HPV DNA status. CONCLUSION: In this study, the presence of HPV or its surrogate of p16 immunostaining was an independent prognostic factor for in-field relapse and survival in women with vulvar SCC treated with radiotherapy. This finding warrants validation in larger cohorts or the prospective setting.

Outcomes with volume-based dose specification in CT-planned high-dose-rate brachytherapy for stage I-II cervical carcinoma: A 10-year institutional experience.

OBJECTIVE: To determine prognostic factors for progression-free survival (PFS) and overall survival (OS) for stage I-II cervical-cancer patients treated using computed-tomography (CT)-planned high-dose-rate (HDR) intracavitary brachytherapy (BT). METHODS: A total of 150 patients were treated for Stage I-II cervical cancer using CT-planned BT between 4/2004 and 10/2014. Of these, 128 were eligible for inclusion. Kaplan-Meier local control (LC), pelvic control (PC), overall survival (OS), and PFS estimates were calculated. RESULTS: After a median follow-up of 30months, the 2-year LC rate was 96%, PFS was 88%, and OS was 88%. Overall, 18 patients (14%) experienced any recurrence (AR), 8 had distant recurrence only and 10 had a combination of local, pelvic, regional, and distant recurrence. No patients had LR only. A prognostic factor for AR was tumor size >4cm (p=0.01). Patients with tumors >4cm were 3.3 times more likely to have AR than those with tumors ≤4cm (hazard ratio [HR]=3.3; 95% confidence interval [CI] 1.28-9.47). Point A was 85% of prescription for tumors < 4 cm and decreased approximately 3% over 5 fractions compared to 90% of prescription for tumors > 4 cm that decreased approximately 4% over 5 fractions. Two patients (2%) experienced grade≥2 late toxicity. There were no acute or late grade≥3 toxicities. CONCLUSION: CT-planned BT resulted in excellent local control and survival. Large tumor size was associated with an increased risk of recurrence outside the radiation field and worse PFS and OS. A volume-optimized plan treated a smaller area than a point A standard plan for patients with Stage I-II cervical cancer that have received chemoradiation. Given the outstanding LC achieved with modern therapy including chemoradiation, HDR, and image-based BT, further efforts to combat spread outside the radiation field with novel therapies are warranted.