I-125 eye-plaque seed economics: To re-use or to not re-use? A single institutional cost savings analysis of re-using I-125 radioactive seeds for eye-Plaque brachytherapy.

INTRODUCTION: Iodine-125 (I-125) seeds, commonly used in low-dose rate brachytherapy for ocular malignancies, are often discarded after a single use. This study examines the potential cost savings at an institution with high ocular melanoma referrals, by re-using I-125 seeds for eye-plaque brachytherapy. METHODS: In this single-institutional retrospective analysis, data was collected from I-125 seed orders from 8/2019 through 10/2022. Information including number of seeds ordered per lot, number of plaques built per lot, and number of seeds used per lot were collected. Cost per lot of seed was assumed to be the current cost from the most recent lot of 35 seeds. RESULTS: During the study, 72 I-125 seed lots were ordered bi-weekly, with a median of 35 seeds per lot (Range: 15-35). Each seed was used on average 2.26 times prior to being discarded. The average duration of each seed lot used was 62.2 days (Range: 21-126). Each seed lot contributed to the construction of an average of 8.4 eye plaques (Range: 2-20). With seed recycling, 2,475 seeds were used to construct 608 eye-plaques. Without re-using practice this would require 5,694 seeds. This resulted in a percentage cost savings of 56.5%, with a total seed cost reduction of $344,884, or $559 per eye-plaque on average. CONCLUSION: This is the first study to evaluate cost savings relative to re-using I-125 seeds for eye plaques. The data demonstrates how an institution can decrease costs associated with I-125 radiation seeds used for eye-plaque brachytherapy by re-using them.

Low energy contact X-ray brachytherapy for treatment of rectal cancer: a health technology appraisal by Health Technology Wales.

AIM: Health Technology Wales sought to evaluate the clinical and cost-effectiveness of contact X-ray brachytherapy (CXB) for early-stage rectal cancer. METHODS: Relevant studies were identified through systematic searches of MEDLINE, Embase, Cochrane Library and Scopus. A cost-utility model was developed to estimate the cost-effectiveness of CXB in National Health Service Wales, using results of the Organ Preservation in Early Rectal Adenocarcinoma (OPERA) trial. Patient perspectives were obtained through the Papillon Patient Support group and All-Wales Cancer Network. RESULTS: The OPERA randomized controlled trial showed that CXB improved complete response and organ preservation rates compared with external-beam boost for people with T2-3b, N0-1, M0 rectal cancer who are fit for surgery. Managing more of this population non-operatively after CXB was estimated to provide 0.2 quality-adjusted life years at an additional cost of £887 per person. CXB was cost effective compared with external-beam boost at a cost of £4463 per quality-adjusted life year gained. This conclusion did not change in scenario analysis and CXB was cost effective in 91% of probabilistic sensitivity analyses. Patients valued receiving clear information on all available options to support their individual treatment choices. The detrimental impact of a stoma on quality of life led some patients to reject the idea that surgery was their only option. CONCLUSION: This evidence review and cost-utility analysis indicates that CXB is likely to be clinically and cost effective, as part of a watch and wait strategy for adults fit for surgery. Wider access to CXB is supported by patient testimonies.

Health Services Research in Brachytherapy: Current Understanding and Future Challenges.

Brachytherapy is an integral component of cancer care. Widespread concerns have been expressed though about the need for greater brachytherapy availability across many jurisdictions. Yet, health services research in brachytherapy has lagged behind that in external beam radiotherapy. Optimal brachytherapy utilisation, to help inform expected demand, have not been defined beyond the New South Wales region in Australia, with few studies having reported observed brachytherapy utilisation. There is also a relative lack of robust cost and cost-effectiveness studies, making investment decisions in brachytherapy even more uncertain and challenging to justify, despite its key role in cancer control. As the range of indications for brachytherapy expands, providing organ/function preservation for a wider range of diagnoses, there is an urgent need to redress this balance. By outlining the work undertaken in this area to date, we highlight its importance and explore where further study is required.

Association between Site-of-Care and the Cost and Modality of Radiotherapy for Prostate Cancer: Analysis of Medicare Beneficiaries from 2015 to 2017.

Among 84,447 radiotherapy (RT) courses for Medicare beneficiaries age ≥ 65 with prostate cancer treated with external beam RT (EBRT), brachytherapy, or both, 42,608 (51%) were delivered in hospital-affiliated and 41,695 (49%) in freestanding facilities. Freestanding centers were less likely to use EBRT + brachytherapy than EBRT (OR 0.84 [95%CI 0.84-0.84]; p < .001). Treatment was more costly in freestanding centers (mean difference $2,597 [95%CI $2,475-2,719]; p < .001). Adjusting for modality and fractionation, RT in hospital-affiliated centers was more costly (mean difference $773 [95%CI $693-853]; p < .001). Freestanding centers utilized more expensive RT delivery, but factors unrelated to RT modality or fractionation rendered RT more costly at hospital-affiliated centers.

Cost-utility analysis of selective internal radiation therapy with Y-90 resin microspheres in hepatocellular carcinoma.

Background: The study assessed the cost-utility of selective internal radiation therapy (SIRT) with Y-90 resin microspheres versus sorafenib in UK patients with unresectable hepatocellular carcinoma ineligible for transarterial chemoembolization. Materials & methods: A lifetime partitioned survival model was developed for patients with low tumor burden (≤25%) and good liver function (albumin-bilirubin grade 1). Efficacy, safety and quality of life data were from a European Phase III randomized controlled trial and published studies. Resource use was from registries and clinical surveys. Results: Discounted quality-adjusted life-years were 1.982 and 1.381, and discounted total costs were £29,143 and 30,927, for SIRT and sorafenib, respectively. Conclusion: SIRT has the potential to be a dominant (more efficacious/less costly) or cost-effective alternative to sorafenib in patients with unresectable hepatocellular carcinoma.

Evaluating reimbursement of skin radiation therapy: Technique and fractionation.

PURPOSE: Multiple skin radiation therapy techniques exist including electron beam therapy, high-dose-rate (HDR) brachytherapy, superficial/orthovoltage, and electronic brachytherapy (EB). The purpose of this analysis was to compare reimbursement between these modalities by fractionation regimen. METHODS AND MATERIALS: Reimbursement was derived from the 2020 Medicare Physician Fee Schedule by fractionation schedule or from the 2020 Hospital Outpatient Prospective Payment national benchmarks. A secondary analysis evaluating incorporation of daily simulation codes was also performed to factor in coding heterogeneity. RESULTS: Superficial/orthovoltage was the least costly and EB the next least costly technique regardless of fractionation. When incorporating variations in coding of simulations, reimbursement with superficial/orthovoltage was still least costly, with a reduction in cost of $1,755, $2,715, $5,076, and $7,436 compared with HDR brachytherapy for 6, 10, 20, and 30 fractions, respectively, and a reduction in cost of $1,325, $2,170, $4,281, and $6,392 compared with EB. HDR brachytherapy and EB costs can increase by 63-110% based on nonrecommended variation in daily simulation billing, with superficial/orthovoltage experiencing the highest relative increase. Reimbursement per course can vary by a factor of 4.5-9.3x depending on the modality and fractionation scheme utilized. CONCLUSIONS: Superficial/orthovoltage followed by EB were the least costly modalities with regard to reimbursement; however, costs can vary with frequency of simulation code billing. Consistency and standardization in skin radiation therapy reimbursement is needed, and case rates within a radiation oncology alternative payment model may help to minimize reimbursement heterogeneity among treatment options.

Comparative Healthcare Research Outcomes of Novel Surgery in prostate cancer (IP4-CHRONOS): A prospective, multi-centre therapeutic phase II parallel Randomised Control Trial.

INTRODUCTION: Focal therapy (FT) targets individual areas of cancer within the prostate, providing oncological control with minimal side-effects. Early evidence demonstrates encouraging short-medium-term outcomes. With no randomized controlled trials (RCT) comparing FT to radical therapies, Comparative Healthcare Research Outcomes of Novel Surgery in prostate cancer (CHRONOS) will compare the cancer control of these two strategies. PATIENTS AND METHODS: CHRONOS is a parallel phase II RCT for patients with clinically significant non-metastatic prostate cancer, dependent upon clinician/patient decision, patients will enrol into either CHRONOS-A or CHRONOS-B. CHRONOS-A will randomize patients to either radical treatment or FT. CHRONOS-B is a multi-arm, multistage RCT comparing focal therapy alone to FT with neoadjuvant agents that might improve the current focal therapy outcomes. An internal pilot will determine the feasibility of, and compliance to, randomization. The proposed definitive study plans to recruit and randomize 1190 patients into CHRONOS-A and 1260 patients into CHRONOS-B. RESULTS: Primary outcome in CHRONOS-A is progression-free survival (transition to salvage local or systemic therapy, development of metastases or prostate-cancer-related mortality) and in CHRONOS-B is failure-free survival (includes the above definition and recurrence of clinically significant prostate cancer after initial FT). Secondary outcomes include adverse events, health economics and functional outcomes measured using validated questionnaires. CHRONOS is powered to assess non-inferiority of FT compared to radical therapy in CHRONOS-A, and superiority of neoadjuvant agents with FT in CHRONOS-B. CONCLUSION: CHRONOS will assess the oncological outcomes after FT compared to radical therapy and whether neoadjuvant treatments improve cancer control following one FT session.

Clinical utility and value contribution of an MRI-positive line marker for image-guided brachytherapy in gynecologic malignancies.

PURPOSE: The purpose of this study was to investigate the utility of a novel MRI-positive line marker, composed of C4:S (cobalt chloride-based contrast agent) encapsulated in high-density polyethylene tubing, in permitting dosimetry and treatment planning directly on MRI. METHODS AND MATERIALS: We evaluated the clinical feasibility of the C4:S line markers in nine sequential brachytherapy procedures for gynecologic malignancies, including six tandem-and-ovoid and three interstitial cases. We then quantified the internal resource utilization of an intraoperative MRI-guided procedural episode via time-driven activity-based costing, identifying opportunities for cost-containment with use of the C4:S line markers. RESULTS: The C4:S line markers demonstrated the strongest positive signal visibility on 3D constructive interference in steady state (CISS)/FIESTA-C followed by T1-weighted sequences, permitting accurate delineation of the applicator lumen and thus the source path. These images may be fused along with traditional T2-weighted sequences for optimal tumor and anatomy contouring, followed by treatment planning directly on MRI. By eliminating postoperative CT for fusion and applicator registration from the procedural episode, use of the C4:S line markers could decrease workflow time and lower total delivery costs per procedure. CONCLUSIONS: This analysis supports the clinical utility and value contribution of the C4:S line markers, which permit accurate MRI-based dosimetry and treatment planning, thereby eliminating the need for postoperative CT for fusion and applicator registration.

Time-driven activity-based costing of a novel form of CT-guided high-dose-rate brachytherapy intraoperative radiation therapy compared with conventional breast intraoperative radiation therapy for early stage breast cancer.

INTRODUCTION: Intraoperative radiation therapy is an emerging option for adjuvant therapy for early stage breast cancer, although it is not currently considered standard of care in the United States. We applied time-driven activity-based costing to compare two alternative methods of breast intraoperative radiation therapy, including treatment similar to the techniques employed in the TARGIT-A clinical trial and a novel version with CT-guidance and high-dose-rate (HRD) brachytherapy. METHODS AND MATERIALS: Process maps were created to describe the steps required to deliver intraoperative radiation therapy for early stage breast cancer at each institution. The components of intraoperative radiation therapy included personnel, equipment, and consumable supplies. The capacity cost rate was determined for each resource. Based on this, the delivery costs were calculated for each regimen. For comparison across centers, we did not account for indirect facilities costs and interinstitutional differences in personnel salaries. RESULTS: The CT-guided, HRD form of intraoperative radiation therapy costs more to deliver ($4,126.21) than the conventional method studied in the TARGIT-A trial ($1,070.45). The cost of the brachytherapy balloon applicator ($2,750) was the primary driver of the estimated differences in costs. Consumable supplies were the largest contributor to the brachytherapy-based approach, whereas personnel costs were the largest contributor to costs of the standard form of intraoperative radiation therapy. CONCLUSIONS: When compared with the more established method of intraoperative radiation therapy using a portable superficial photon unit, the delivery of treatment with CT guidance and HDR brachytherapy is associated with substantially higher costs. The excess costs are driven primarily by the cost of the disposable brachytherapy balloon applicator and, to a lesser extent, additional personnel costs. Future work should include evaluation of a less expensive brachytherapy applicator to increase the anticipated value of brachytherapy-based intraoperative radiation therapy.

A cost analysis of SIR-Spheres yttrium-90 resin microspheres versus tyrosine kinase inhibitors in the treatment of unresectable hepatocellular carcinoma in France, Italy, Spain and the UK.

Background and aims: A wide range of treatment options are available for hepatocellular carcinoma (HCC), including systemic treatment with tyrosine kinase inhibitors (TKIs) such as sorafenib and lenvatinib, immunotherapies, locoregional therapies such as selective internal radiation therapy (SIRT) and treatments with curative intent such as resection, radiofrequency ablation and liver transplantation. Given the substantial economic burden associated with HCC treatment, the aim of the present analysis was to establish the cost of using SIRT with SIR-Spheres yttrium-90 (Y-90) resin microspheres versus TKIs from healthcare payer perspectives in France, Italy, Spain and the United Kingdom (UK).Methods: A cost model was developed to capture the costs of initial systemic treatment with sorafenib (95%) or lenvatinib (5%) versus SIRT in patients with HCC in Barcelona Clinic Liver Cancer (BCLC) stages B and C. A nested Markov model was utilized to model transitions between progression-free survival (PFS), progression and death, in addition to transitions between subsequent treatment lines. Cost and resource use data were identified from published sources in each of the four countries.Results: Relative to TKIs, SIRT with SIR-Spheres Y-90 resin microspheres were found to be cost saving in all four country settings, with the additional costs of the microspheres and the SIRT procedure being more than offset by reductions in drug and drug administration costs, and treatment of adverse events. Across the four country settings, total cost savings with SIR-Spheres Y-90 resin microspheres fell within the range 5.4-24.9% and SIRT resulted in more patients ultimately receiving treatments with curative intent (4.6 vs. 1.4% of eligible patients).Conclusion: SIR-Spheres Y-90 resin microspheres resulted in cost savings relative to TKIs in the treatment of unresectable HCC in all four country settings, while increasing the proportion of patients who become eligible for treatments with curative intent.

Declining brachytherapy utilization for cervical cancer patients - Have we reversed the trend?

OBJECTIVE: Studies examining temporal trends in cervical brachytherapy use are conflicting and examined different health insurance populations. This study examined brachytherapy utilization over time by health insurance type and whether reported declines in brachytherapy have reversed. METHODS: The National Cancer Database (NCDB) was queried for patients with FIGO IIB-IVA cervical cancer treated with definitive chemoradiotherapy between 2004 and 2014, identifying 17,442 patients. Brachytherapy utilization over time and by insurance type and other sociodemographic factors were compared using binary logistic regression. A sensitivity analysis was done in a sub-cohort of patients using the boost modality variable in the NCDB. RESULTS: Brachytherapy utilization declined during 2008-10 (52.6%) compared to 2004-2007 (54.4%; odds ratio [OR] 0.93, 95% confidence interval [CI] 0.86-1.01) and declines were disproportionately larger for patients with government insurance (49.4% vs 52.3%, respectively) than privately-insured patients (57.6% vs 58.9%, respectively). However, rates of brachytherapy use subsequently recovered during 2011-14 in all insurance groups (58.0%, OR 1.24, 95% CI 1.16-1.34) and was especially improved for Medicaid (OR 1.44, 95% CI 1.26-1.65) and uninsured patients (OR 1.28, 95% CI 1.03-1.57). Sensitivity analysis using the boost modality variable confirmed these trends. CONCLUSIONS: In patients with FIGO IIB-IVA cervical cancer treated with definitive chemoradiotherapy from 2004 to 2014, brachytherapy utilization declined during the late 2000s and disproportionately affected patients with government insurance, but subsequently recovered in the early 2010s. Since government insurance covers vulnerable patient populations at-risk for future declines in brachytherapy use, proposed alternative payment models should incentivize cervical brachytherapy to solidify gains in brachytherapy utilization.

Time-driven activity-based costing of adjuvant vaginal cuff brachytherapy for uterine cancer in an integrated brachytherapy suite.

PURPOSE: Adjuvant vaginal cuff brachytherapy is well tolerated and reduces the risk of local recurrence in endometrial cancer. However, there is provider variation in the number of radiation treatments, which ranges from three to six fractions. Using time-driven activity-based costing, we calculated the cost to deliver three vs six fractions to determine the value of each regimen at our brachytherapy suite with CT-on-rails. METHODS AND MATERIALS: Process maps were created to represent each step from initial consult to completion of therapy. Components of care included personnel, equipment, and consumable supplies. The capacity cost rate was determined for each resource and calculated for each regimen. RESULTS: The total direct costs to deliver three- and six-fraction treatment courses were $1,415 and $2,227, respectively. Personnel cost accounted for 63% of overall expenditures. Computed tomography simulation and planning, required for the first fraction, cost $232 for both regimens. Duties of the procedural nurse (scheduling, patient setup, and turnover) consumed the most time at 35% of total personnel minutes. CONCLUSIONS: Time-driven activity-based cost analysis revealed a 57% relative increase, but modest absolute increase, in delivery costs for six vs three fractions of brachytherapy at our institution. This current analysis may influence considerations of the relative value between the two treatment schedules, but this methodology should not be interpreted as informative for reimbursement policy evaluation.

Economic impact of decreasing the fraction number in vaginal cuff brachytherapy: A direct cost analysis.

PURPOSE: The purpose of this study was to analyze the direct economic impact of two vaginal cuff brachytherapy (VBT) schedules in postoperative endometrial carcinoma (PEC) with similar vaginal control and toxicity results. MATERIALS AND METHODS: From 2006 to 2015, 397 PEC patients (p) were treated with VBT: mean 40p/year, 67.5% received external beam radiotherapy (EBRT)+VBT and 32.5% exclusive VBT. Schedule 1: 3 fractions (Fr) after EBRT and 6Fr (4-6 Gy/Fr) in exclusive VBT. Schedule 2: 7Gy × 1Fr + EBRT and 6Gy × 3Fr in exclusive VBT. Differential cost analysis of the two schedules was retrospectively performed. The direct costs in each schedule were (1) Personnel: radiotherapy technicians, nurses, radiation oncologists, medical physicists, administrative personnel, orderlies; time dedicated by each professional during CT planning acquisitions and delineation of vagina/organs at risk, dosimetric study and evaluation, autoradiography, procedure reporting time during/after treatment, removal of bladder/rectal tubes and applicators, material cleaning and transportation for sterilization; (2) Health care material (gels, gauzes, gloves, etc); (3) Equipment (time equipment used). The differential between the two schedules was estimated. Indirect costs and evaluation of quality of life-adjusted costs were not considered. RESULTS: The overall reduction in the number of Fr per year in Schedule 2 was 93. Cost savings included treatment time per year: 4,185 min (70 h); personnel: 221€ ($246)/p in EBRT + VBT and 331€ ($368)/p in exclusive VBT; and health care material and equipment: 40€ ($44.5)/p in EBRT + VBT and 90€ ($100.2)/p in exclusive VBT. The overall savings per patient was 261€ ($295) in combined treatment and 421€ ($475.7) in exclusive VBT. The total savings per year with Schedule 2 in 40p was 12,503€ ($13,915.8). CONCLUSIONS: A 41% reduction in the fractions number in VBT for PEC allowed economic savings of 261€ ($290.5)/p in combined treatment and 421€ ($475.7)/p in exclusive VBT. Other benefits include patient comfort and fewer treatment visits.

Developing an intraoperative 3T MRI-guided brachytherapy program within a diagnostic imaging suite: Methods, process workflow, and value-based analysis.

PURPOSE: We integrated a brachytherapy procedural workflow within an existing diagnostic 3.0-T (3T) MRI suite. This setup facilitates intraoperative MRI guidance for optimal applicator positioning, particularly for interstitial needle placements in gynecologic cases with extensive parametrial involvement. METHODS AND MATERIALS: Here we summarize the multidisciplinary collaboration, equipment, and supplies necessary to implement an intraoperative MRI-guided brachytherapy program; outline the operational workflow via process maps; and address safety precautions. We evaluate internal resource utilization associated with this progressive approach via time-driven activity-based costing methodology, comparing institutional costs to that of a traditional workflow (within a CT suite, followed by separate postprocedure MRI) over a single brachytherapy procedural episode. RESULTS: Resource utilization was only 15% higher for the intraoperative MRI-based workflow, attributable to use of the MRI suite and increased radiologist effort. Personnel expenses were the greatest cost drivers for either workflow, accounting for 76-77% of total resource utilization. However, use of the MRI suite allows for potential cost-shifting opportunities from other resources, such as CT, during the procedural episode. Improvements in process speed can also decrease costs: for each 10% decrease in case duration from baseline procedure time, total costs could decrease by roughly 8%. CONCLUSIONS: This analysis supports the feasibility of an intraoperative MRI-guided brachytherapy program within a diagnostic MRI suite and defines many of the resources required for this procedural workflow. Longer followup will define the full utility of this approach in optimizing the therapeutic ratio for gynecologic cancers, which may translate into lower costs and higher value with time, over a full cycle of care.

The Cost-Effectiveness and Value Proposition of Brachytherapy.

Brachytherapy is an effective treatment modality for a wide range of malignancies. However, brachytherapy utilization for both prostate and gynecologic malignancies has significantly declined over the last 20 years in favor of external beam radiation techniques. The cause of this decline is multifactorial, with logistical challenges, lower reimbursement, and inadequate training contributing to the preference of many radiation oncologists to more frequently recommend external beam radiation therapy. While the authors recognize the application of brachytherapy to a wider range of disease presentations among which include breast, skin, head and neck, and connective tissue cancers, in this review, we will review the analyses supporting brachytherapy as a cost-effective component of the management in patients with prostate, cervix, and endometrial cancer.

How might financial pressures have impacted brachytherapy? A proposed narrative to explain the declines in cervical and prostate brachytherapy utilization.

Rates of brachytherapy administration in the United States have declined for both cervical and prostate cancers, and we argue that the available facts suggest financial considerations are a major contributor to this issue. In this narrative, we discuss financial pressures that have existed for cervical and prostate brachytherapy and how they may have influenced their declining usage, consider other proposed influences, and provide suggestions for future research to understand the scope of the issue.

Impact of different adjuvant radiotherapy modalities on women with early-stage intermediate- to high-risk endometrial cancer.

OBJECTIVE: Vaginal brachytherapy was recommended for patients with intermediate-risk endometrial cancer, however, optimal radiotherapy modalities for intermediate-high- or high-risk patients remains controversial. Previous studies have mainly focused on survival outcomes and have seldom taken cost issues into consideration, especially for high-risk patients. The purpose of this study is to compare the survival outcomes and costs associated with two adjuvant radiotherapy modalities in the management of patients with early-stage, intermediate- to high-risk endometrial cancer. METHODS: According to ESMO-ESCO-ESTRO criteria, 238 patients with stage I/II, intermediate- to high-risk endometrial cancer who underwent radiotherapy from January 2003 to December 2015 at our institution were reviewed. The vaginal brachytherapy group and external beam radiation therapy combined with the vaginal brachytherapy group were propensity score-matched at a 1:1 ratio. The Kaplan-Meier method and Cox proportional hazards regression model were used. RESULTS: A total of 361 patients met our inclusion criteria, the median age of the patients was 58 years (range, 28-85). All were diagnosed with stage I-II endometrial cancer (324 with stage I and 37 with stage II; 350 with endometrioid adenocarcinoma; and 10 with mucinous carcinoma). The median follow-up time was 60.5 months (range, 3-177). Among 119 matched pairs, no significant differences were found in overall (10.9% vs 8.4%, P=0.51), locoregional (4.2% vs 1.7%, P=0.45), or distant recurrence rates (6.7% vs 6.7%, P=1.0) between the two groups. There were also no differences in the 5-year overall (94.8% vs 93.9%, P=0.78) or progression-free survival (90.0% vs 84.4%, P=0.23) between the two groups. The rates of acute and late toxicity were significantly higher in the external beam radiation therapy combined with vaginal brachytherapy vs the vaginal brachytherapy group (all P<0.05), except for the acute hematological toxicity rate (17.6% vs 9.2%, P=0.06). External beam radiation therapy combined with vaginal brachytherapy had a higher median cost ($2759 vs $937, P<0.001) and longer median radiotherapy duration (41 days vs 17 days, P<0.001) than vaginal brachytherapy. CONCLUSION: Vaginal brachytherapy was associated with similar local control and long-term survival outcomes relative to the combination of external beam radiotherapy and vaginal brachytherapy and it also minimizes radiation-related complications, reduces medical costs, and shortens radiotherapy duration. Vaginal brachytherapy may be the optimal radiation modality for patients with early-stage endometrial cancer at intermediate to high risk.