Image-guided high-dose-rate brachytherapy as the method of choice in medically inoperable early-stage endometrial cancer patients.

PURPOSE: About 3-9% of patients with endometrial cancer are unable to undergo surgery due to medical comorbidities, including morbid obesity, or age-related frailty syndrome. An alternative curative option is irradiation. The aim of this prospective study was to evaluate clinical outcomes of high-dose-rate intracavitary brachytherapy (HDR-ICBT) treatment in such patients. MATERIALS AND METHODS: Seventy-eight patients with FIGO stage I-II endometrial cancer disqualified from surgery were treated with HDR-ICBT with 45-52,5 Gy prescribed to high-risk clinical target volume (HR-CTV) in 5-9 fractions given once a week. All fractions were planned using computed tomography (CT) scans. RESULTS: The median follow-up time was 67 months. Median age was 79 years (range: 42-93 years). Median body mass index (BMI) was 39,1 kg/m2 (range: 24,2-68 kg/m2). We observed no statistically significant impact of BMI ≥ 40 on overall survival (OS) or prgression free survival (PFS). The 3- and 5-year OS for the whole population were 69% and 55%, respectively. The impact of high risk features (FIGO II, grade 3 or type 2 cancer) on OS was significant (p = 0,049). The 5-year cumulative incidence of local failure, distant metastases and non-cancer death were 12,9% [95% CI: 5,4%-20,5%], 6,4% [95% CI: 0,9%-11,9%], 33,1% [95% CI: 22,3%-43,9%], respectively. The 5-year risk of cancer and non-cancer death were 9% (95% CI: 3%-16%) and 36% (95% CI: 25%-47%), respectively. We observed G1 vaginal apex stenosis only. CONCLUSIONS: CT-guided HDR-ICBT is a feasible and safe management of FIGO stage I endometrial cancer in obese and elderly patients. The survival outcome of the treated group is influenced more by associated comorbidities than by the progression of endometrial cancer.

Patterns of care and outcomes of radiotherapy or hormone therapy in patients with medically inoperable endometrial adenocarcinoma.

OBJECTIVE: The optimal treatment for medically inoperable endometrioid endometrial adenocarcinoma is unknown. The goal of this study was to evaluate the patterns of care and efficacy of radiotherapy (RT) or hormone therapy (HT) in the treatment of these patients. METHODS: We performed a query of the National Cancer Database (NCDB) of patients with medically inoperable endometrioid adenocarcinoma of the endometrium diagnosed between 2004 and 2016 and treated with either RT or HT. A multivariate Cox regression model and propensity weighted analyses were used to evaluate overall survival after controlling for confounding variables. A multinomial logistic regression model was used to assess predictors of RT or HT use. RESULTS: A total of 1036 patients were included in this cohort, and 73% (n = 759) were treated with RT alone. Patients who received definitive HT compared to RT were more likely to be older, diagnosed in the earlier years of this analysis, treated at lower-case volume centers, diagnosed with high-grade disease, or located outside of metropolitan areas. On multivariate analysis, treatment with HT alone versus RT alone was associated with significantly worse overall survival in the multivariate Cox model but not on propensity score weighted analysis. Interaction effect testing revealed that older patients and those treated at lower-volume centers had improved survival with RT compared to HT. CONCLUSIONS: We identified factors associated with the receipt of RT or HT in medically inoperable endometrial cancer patients. Treatment with RT correlated with improved survival compared to HT in older patients and those treated at lower-volume centers.

National Cancer Database analysis of radiation therapy consolidation modality and dose for inoperable endometrial cancer.

OBJECTIVE: We utilized the National Cancer Database (NCDB) to evaluate trends and assess outcomes in radiation therapy (RT) boost modality and total dose among medically inoperable endometrial cancer (EC) patients with locoregional disease. METHODS: Patients with International Federation of Gynecology and Obstetrics (FIGO) stage I - IIIC2 inoperable EC treated with RT ± chemotherapy were analyzed. Practice patterns compared external beam RT (EBRT) versus high-dose-rate brachytherapy (BT) boost and total RT dose (palliative: ≤3000 cGy, definitive low dose [DLD]: 4500 - 6249 cGy, definitive high dose [DHD]: ≥6250 cGy) over time. Kaplan-Meier method evaluated overall survival (OS) and Cox proportional hazard modeling assessed variables associated with OS. RESULTS: NCDB included 1755 total cases, of which 1209 received a radiotherapy boost. From 2004 to 2019, boost modality rates differed with increasing utilization of BT consolidation and a decreasing rate of palliation. Predictors of a palliative dose were stage III disease, Black race, N2 disease, and poorly or undifferentiated grade. Multivariable analysis found BT boost was associated with lower mortality compared to EBRT (HR: 0.81, CI: 0.68-0.97; p = 0.019). Mortality rates were higher for palliation versus DHD. Additional factors associated with inferior survival were increasing age, worse Charlson-Deyo score, higher T stage, higher N stage, and moderately, poorly, or undifferentiated grade. CONCLUSIONS: Utilization of BT boost for locoregionally confined, medically inoperable EC has increased since 2004. Brachytherapy consolidation remains an effective RT modality for medically inoperable EC, associated with lower mortality compared to EBRT consolidation.

What is appropriate target delineation for MRI-based brachytherapy for medically inoperable endometrial cancer?

PURPOSE: For medically inoperable endometrial cancer (MIEC), the volumetric target of image-guided brachytherapy (IGBT) techniques is not well established. We propose a high-risk CTV (HRCTV) concept and report associated rates of local control and toxicity. METHODS AND MATERIALS: For all MIEC patients receiving definitive external beam radiotherapy (EBRT) followed by MRI-based IGBT at a single institution, BT dose was prescribed to HRCTV defined as GTV plus endometrial cavity with a planning goal of a summed EQD2 D90 of ≥85 Gy. Freedom from local progression (FFLP) and overall survival (OS) were estimated via Kaplan Meier method. RESULTS: Thirty two MIEC patients received EBRT followed by MRI-based IGBT between December 2015 and August 2020. Median follow up was 19.8 months. A total of 75% of patients had FIGO stage I/II disease, 56% endometrioid histology, and 50% grade 3 disease. OS was 73.6% (95% CI 57.8%-89.3%) at 12 months and 65.8% (95% CI 48.4%-83.2%) at 24 months. FFLP was 93.8% (95% CI 85.3%-100%) at 12 months and 88.8% (95% CI 86.6%-91.0%) at 24 months. 23 (72%) patients experienced no RT-related toxicity, while 2 of 32 patients (6%) experienced late grade 3+ toxicities (grade 3 refractory vomiting; grade 5 GI bleed secondary to RT-induced proctitis). CONCLUSIONS: Patients with MIEC receiving definitive EBRT followed by MRI-based IGBT prescribed to the MRI-defined HRCTV demonstrated favorable long-term local control with an acceptable toxicity profile.

Exclusive 3D-brachytherapy as a good option for stage-I inoperable endometrial cancer: a retrospective analysis in the gynaecological cancer GEC-ESTRO Working Group.

PURPOSE: Analyse outcomes of stage-I inoperable endometrial cancer (EC) patients from seven European centres treated with 3D-image-guided brachytherapy (IGBT) alone. MATERIALS AND METHODS: From 2004 to 2018, 62 patients (41 stage-IA and 21 IB) were retrospectively studied, analysing anaesthetic procedure, applicator type, BT-planning imaging, clinical target volume (CTV), BT schedule, overall daily-dose equivalent to 2 Gy (EQD2(α/ß=4.5 or 3)) to the CTV(α/ß=4.5) and D2 cm3(α/ß=3) for organs at risk. Complications were evaluated using CTCAEv4 scores. The 2 and 5 year survival was calculated [cancer-specific survival (CSS), disease-free survival (DFS), local relapse-free survival (LRFS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS)]. Descriptive analysis and the Kaplan-Meier method were used for survival analysis. RESULTS: Mean follow-up: 32.8 months (SD 33.7). Spinal anaesthesia (38/62) followed by none (16/62) were the most common. Y-shaped Rotte applicators were used in 74% of patients. High-dose rate brachytherapy was administered in 89%. Median D90 to the CTV was 58.9 Gy (8.66-144 Gy). Eight patients presented relapse: four uterine, four nodal and four distant. The 2 and 5 year CSS was 93.3 and 80.5%, DFS 84.8 and 80.5%, LRFS was 93.1 and 88.7%, LRRFS was 91 and 91% and DMFS was 90.2 and 90.2%, respectively, CSS was better in stage-IA vs. IB (p = 0.043). Late vaginal and bladder G3-complication rates were 2.1%, respectively. CONCLUSION: Inoperable EC patients can be safely treated by BT with 2 and 5 year CSS of 93 and 80.5%, respectively, with even better results for IA cases. Prospective studies on 3D-IGBT are necessary to better analyse EC patient outcomes based on dose and treated volumes.

The clinical management of inoperable endometrial carcinoma.

Unresectable endometrial cancer, while rare, has a very poor prognosis, with a survival rate of 2 to 8 months. Although endometrial cancer is generally regarded as a survivable disease, the less common advanced and aggressive forms account for a large portion of endometrial cancer related deaths. Given the paucity of inoperable disease, randomized clinical data is lacking in this specific patient population. Management decisions regarding radiation therapy or systemic therapy are largely guided by the existing data in the setting of recurrence or second-line treatment, adjuvant therapy following optimal debulking, or in patients who are considered inoperable due to medical comorbidities rather than the extent of their disease.