RESUMEN
PURPOSE: The aim of this work was to report the effect of mismatch repair (MMR) status on outcomes of patients with stage I-II endometrioid endometrial adenocarcinoma (EEC) who receive adjuvant radiation therapy. METHODS AND MATERIALS: This is a multi-institutional retrospective cohort study across 11 institutions in North America. Patients with known MMR status and stage I-II EEC status postsurgical staging were included. Overall survival (OS) and recurrence-free survival (RFS) rates were estimated via the Kaplan-Meier method. Univariable and multivariable analyses were performed via Cox proportional hazard models for RFS and OS. Statistical analyses were conducted using SPSS version 27. RESULTS: In total, 744 patients with a median age at diagnosis of 65 years (IQR, 58-71) were included. Most patients were White (69.4%) and had Federation of Obstetrics and Gynecology 2009 stage I (84%) and Federation of Obstetrics and Gynecology grade 1 to 2 (73%). MMR deficiency was reported in 234 patients (31.5%), whereas 510 patients (68.5%) had preserved MMR. External beam radiation therapy with or without vaginal brachytherapy was delivered to 186 patients (25%), whereas 558 patients (75%) received vaginal brachytherapy alone. At a median follow-up of 43.5 months, the estimated crude OS and RFS rates for the entire cohort were 92.5% and 84%, respectively. MMR status was significantly correlated with RFS. RFS was inferior for MMR deficiency compared with preserved MMR (74.3% vs 88.6%, P < .001). However, no difference in OS was seen (90.8% vs 93.2%, P = .5). On multivariable analysis, MMR deficiency status was associated with worse RFS (hazard ratio, 1.86; P = .001) but not OS. CONCLUSIONS: MMR status was independently associated with RFS but not OS in patients with early-stage EEC who were treated with adjuvant radiation therapy. These findings suggest that differential approaches to surveillance and/or treatment based on MMR status could be warranted.
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Reparación de la Incompatibilidad de ADN , Neoplasias Endometriales , Estadificación de Neoplasias , Humanos , Femenino , Neoplasias Endometriales/radioterapia , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Neoplasias Endometriales/genética , Persona de Mediana Edad , Anciano , Radioterapia Adyuvante , Estudios Retrospectivos , Pronóstico , Supervivencia sin Enfermedad , Estimación de Kaplan-Meier , Modelos de Riesgos Proporcionales , Carcinoma Endometrioide/radioterapia , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/mortalidad , Carcinoma Endometrioide/genética , BraquiterapiaRESUMEN
OBJECTIVE: Adding chemotherapy to radiotherapy in patients with high-risk endometrioid endometrial cancer (EEC) remains controversial, particularly in stages I-II. We aimed to investigate the effect of treatment modalities on survival in high-risk EEC patients. PATIENTS AND METHODS: Patients with high-risk EEC were evaluated retrospectively between 2010 and 2019. Patients who did not receive adjuvant treatment were excluded. We included seventy patients and formed two groups: patients who received radiotherapy (RT) alone and those who received chemotherapy and radiotherapy (CT and RT). RESULTS: The median follow-up time was 60.3 months (8.0-143.5). 38.5% of the patients had relapsed. Recurrence-free survival (RFS) rates were 97. 1%, 68.3% , and 60.8% at 12-, 36-, and 60-month, respectively. Overall survival rates were 97.1%, 80.6%, and 72.6% at 12-, 36-, and 60-month, respectively. Hematological adverse events and neuropathy were more common in the CT and RT group than in the RT group. Multivariate Cox regression analysis for RFS revealed that the FIGO stage and treatment modalities were statistically independent factors (p=0.031 and p=0.040, respectively). Stage stratified log-rank test revealed that adding chemotherapy improved RFS in patients with stage III (p=0.020) but not in stage I-II disease (p=0.725). The number of chemotherapy cycles administered (≤4 vs. >4) did not affect survival in all patients and stage III disease (p=0.497, and p=0.436, respectively). CONCLUSIONS: Adding chemotherapy to radiotherapy may be considered in high-risk stage III EEC. Further studies are needed to determine the optimal duration of chemotherapy.
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Carcinoma Endometrioide , Neoplasias Endometriales , Femenino , Humanos , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/radioterapia , Estudios Retrospectivos , Radioterapia Adyuvante , Estadificación de Neoplasias , Carcinoma Endometrioide/tratamiento farmacológico , Carcinoma Endometrioide/radioterapia , Quimioterapia AdyuvanteRESUMEN
OBJECTIVE: To evaluate recurrence-free survival (RFS) and cause-specific survival (CSS) after observation or vaginal brachytherapy (VB) alone in all subgroups of early-stage high-intermediate (HIR) and high-risk endometrial cancer (EC). METHODS: We identified patients with stage I HIR (GOG-249 criteria) and stage II endometrioid EC, and stage I and II non-endometrioid EC who underwent surgery at Mayo Clinic and Cleveland Clinic between 1999 and 2016. Three-year RFS and CSS after observation or VB only were estimated in 16 subgroups defined by risk factors. RESULTS: Among 4156 ECs, we identified 447 (10.8%) stage I endometrioid HIR, 52 (1.3%) stage II endometrioid, 350 (8.4%) stage I non-endometrioid, and 17 (0.4%) stage II non-endometrioid ECs; observation or VB alone was applied in 349 (78.1%), 24 (46.2%), 187 (53.4%), and 2 (11.8%) patients, respectively. After observation or VB, stage I HIR endometrioid EC subgroups with <2 factors among grade 3, LVSI, or stage IB had a 3-year CSS >95% (lower 95% confidence intervals limit: 89.8%), whereas subgroups with ≥2 factors had poorer outcomes. No EC-related deaths after 3 years were reported in 97 stage IA non-endometrioid ECs without myometrial invasion. Stage II ECs had poor outcomes regardless of histology. CONCLUSIONS: Observation or VB only may be sufficient in stage I endometrioid HIR ECs with <2 factors among grade 3, LVSI, or IB and in stage IA non-endometrioid ECs without myometrial invasion. Stratification of early-stage HIR and high-risk ECs into risk subgroups potentially alleviates the overtreatment and undertreatment risk and should be considered in future research.
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Braquiterapia , Carcinoma Endometrioide , Neoplasias Endometriales , Femenino , Humanos , Estudios Retrospectivos , Estadificación de Neoplasias , Neoplasias Endometriales/radioterapia , Neoplasias Endometriales/cirugía , Carcinoma Endometrioide/radioterapia , Carcinoma Endometrioide/cirugía , Braquiterapia/efectos adversos , Recurrencia Local de Neoplasia/patología , Radioterapia AdyuvanteRESUMEN
Sentinel lymph node biopsy has led to an increase in the detection of isolated tumor cells (ITCs) in up to 10% of early stage endometrioid endometrial cancer patients. In addition, the risk of nonsentinel lymph node involvement is approximately 10% or lower in patients with ITCs. In most studies, approximately 60% to 70% of patients with ITCs either underwent completion lymphadenectomy or received adjuvant therapy. Therefore, although multiple studies have shown that the effect of ITCs on disease outcomes is favorable, the true effect of ITCs without additional treatment is not known. In this report we describe our philosophy of relying on extent of surgical nodal staging and presence or absence of adverse intrauterine pathologic factors at the time of adjuvant therapy decision making for endometrioid endometrial carcinoma patients with ITCs.
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Carcinoma Endometrioide , Neoplasias Endometriales , Carcinoma Endometrioide/radioterapia , Carcinoma Endometrioide/cirugía , Neoplasias Endometriales/patología , Endometrio/patología , Femenino , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Estadificación de Neoplasias , Radioterapia Adyuvante , Biopsia del Ganglio Linfático CentinelaRESUMEN
OBJECTIVE: The present study was designed to evaluate the effects of adjuvant chemotherapy (CT) vs. radiotherapy (RT, alone or combined with CT) on the prognosis of patients with high-risk, early-stage (stage I and stage II) endometrioid endometrial carcinoma. METHODS: This single-center retrospective clinical study was conducted in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between 2010 and 2019. In the present study, endometrioid endometrial carcinoma patients, who underwent total hysterectomy and bilateral salpingo-oophorectomy followed by postoperative adjuvant CT or RT (alone or combined with CT), and were diagnosed with stage IA grade 2/3 with lymph-vascular space invasion (LVSI), and stage IB with two or more uterine risks, including old age, histological grade 2 or 3, LVSI and stage II, were included. According to the postoperative adjuvant therapy, all eligible patients were divided into two groups: CT group and RT (RT±CT) group. The primary objective was to investigate overall survival (OS) and disease-free survival (DFS) between the CT and RT groups. Grade 3 or worse adverse events were also presented in the present study. RESULTS: A total of 145 eligible patients were included. Among these patients, 97 patients underwent adjuvant CT and 48 patients underwent adjuvant RT (RT±CT). The median follow-up was 47.2 months, and the five-year OS rate was 92.7% in the CT group and 88.6 % in the RT group [hazard ratio (HR): 0.81, 95% confidence interval (CI): 0.22-2.99). The 5-year DFS rate for the two groups was 85.7% and 80.2%, respectively (HR: 0.82, 95% CI: 0.33-2.05). The cumulative incidence of local-regional disease recurrence at 60 months of follow-up was 6.2% in the CT group and 6.3% in the RT group (HR=1.11; 95%CI: 0.28-4.35). The cumulative incidence of distant recurrence at 60 months of follow-up was 5.2% in the CT group and 10.4% in the RT group (HR=0.65; 95%CI: 0.19-2.24). Both groups of patients were well-tolerant, and the only grade 3 or worse adverse events were neutropenia and thrombocytopenia. CONCLUSION: There was no difference in efficacy for adjuvant CT or adjuvant RT (RT±CT) in high-risk, early-stage endometrioid endometrial carcinoma. CT exhibited a trend of reducing the distant relapse, although there was no significant difference, when compared with adjuvant RT (RT±CT).
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Carcinoma Endometrioide/tratamiento farmacológico , Carcinoma Endometrioide/radioterapia , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/radioterapia , Estadificación de Neoplasias , Evaluación de Resultado en la Atención de Salud , Adulto , Anciano , Carcinoma Endometrioide/mortalidad , Carcinoma Endometrioide/cirugía , Quimioradioterapia , Quimioterapia Adyuvante , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/cirugía , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , RiesgoRESUMEN
OBJECTIVES: To examine the impact of mismatch repair (MMR) status on prognosis among patients with high- and low-intermediate-risk endometrioid endometrial cancer (EEC) treated with vaginal brachytherapy (VBT). MATERIALS/METHODS: 198 stage I-II EEC patients with known MMR status treated with adjuvant VBT were identified. Both low-intermediate (LIR) and high-intermediate-risk (HIR) patients were included. Clinical characteristics were compared between patients with proficient and deficient mismatch repair (pMMR and dMMR) using Fisher's exact tests for categorical variables and t-tests for continuous variables. Recurrence-free survival (RFS) and overall survival (OS) were analyzed with Kaplan-Meier estimates, the log-rank test, and Cox proportional hazards regression. RESULTS: Patients with dMMR compared to pMMR were more likely to have grade 2-3 tumors (75% vs. 57%, p = 0.006), lympho-vascular invasion (40% vs. 25%, p = 0.034), and HIR classification (65% vs. 49%, p = 0.011). Three-year RFS was inferior for dMMR compared to pMMR patients (75% vs. 96%, p = 0.001). dMMR patients compared to pMMR had similarly reduced 3-year RFS within the LIR (74% vs. 100%, p = 0.026) and HIR (75% vs. 91%, p = 0.038) subgroups. Three-year OS was not different between dMMR/pMMR patients (98% vs. 97%, p = 0.653) or HIR/LIR patients (97% vs. 97%, p = 0.999). On multivariable Cox regression, dMMR status was a significant prognostic variable for RFS (HR 3.774, CI 1.495-9.526, p = 0.005), though it was not significant for OS. CONCLUSION: Following VBT, patients with dMMR have poorer RFS compared to pMMR patients regardless of HIR/LIR risk classification. The prognosis of intermediate-risk EEC patients may lie more on a continuum dependent on molecular features rather than distinct clinicopathologic risk categories.
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Braquiterapia/métodos , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/radioterapia , Reparación de la Incompatibilidad de ADN , Neoplasias Endometriales/genética , Neoplasias Endometriales/radioterapia , Anciano , Carcinoma Endometrioide/patología , Supervivencia sin Enfermedad , Neoplasias Endometriales/patología , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
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.
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Carcinoma Endometrioide/tratamiento farmacológico , Carcinoma Endometrioide/radioterapia , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/radioterapia , Adulto , Factores de Edad , Anciano , Antineoplásicos Hormonales/uso terapéutico , Carcinoma Endometrioide/patología , Estudios de Cohortes , Neoplasias Endometriales/patología , Femenino , Humanos , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: For stage I to II high-risk endometrioid adenocarcinoma patients, the optimal adjuvant radiotherapy modality remains controversial. The present study sought to optimize the treatment of pelvic external beam radiation (EBRT) with/or vaginal brachytherapy (VBT) for high-risk endometrioid adenocarcinoma patients in multiple radiation oncology centers across China. METHODS: This article retrospectively reviewed stage I to II patients with resected endometrioid adenocarcinoma treated at 13 radiation centers from 1999 to 2015. Patients were eligible if they had high-risk features (stage IB Grade 3 disease or stage II Grade 1-3 disease) on the basis of ESMO-ESGO-ESTRO risk group consensus. RESULTS: A total of 218 patients were included. Fifty-one patients received EBRT, 25 patients received VBT, and 142 patients were administered EBRT combined with VBT. The three groups were comparable in baseline characteristics, except the proportion of stage IB and Grade 3 disease in the VBT group was significantly higher and their age was older. Survival analysis showed that OS, DFS, LRFS and DMFS were significantly different among the three groups. Two out of three groups were compared with each other, and results demonstrated that DFS, LRFS and DMFS were worse in the VBT group than in the EBRT or EBRT + VBT group. The 3-year OS rates were 95.2, 85.2 and 95.1% in the EBRT, VBT and EBRT + VBT groups, respectively (p = 0.043). There was no significant difference in survival outcomes between EBRT group and EBRT + VBT group. A propensity matching analysis was performed to eliminate group differences. The results demonstrated that DFS and LRFS were significantly improved in the pelvic radiation group compared to the VBT group. Distant failure accounted for most of the failure patterns. Patients in the VBT group had significantly increased local and regional recurrence rates than patients in the EBRT or EBRT + VBT group. Acute and chronic radiation-induced toxicities were well tolerated for all patients. CONCLUSION: For patients with postoperative stage I to II high-risk endometrioid adenocarcinoma, compared with VBT alone, radiotherapy modalities including EBRT significantly improved DFS, LRFS and DMFS with tolerable adverse effects. Overall survival was not significantly different between EBRT and EBRT + VBT modalities.
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Adenocarcinoma/radioterapia , Braquiterapia/métodos , Carcinoma Endometrioide/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the impact of surgical lymph node assessment for clinically apparent, stage I endometrioid endometrial adenocarcinoma meeting Mayo criteria for lymphadenectomy. METHODS: Patients with endometrioid endometrial adenocarcinoma meeting Mayo criteria for lymphadenectomy who underwent hysterectomy and lymphadenectomy were identified. Algorithms for adjuvant therapy with and without lymphadenectomy were developed utilizing NCCN guidelines, PORTEC 1, and PORTEC 2. Patients served as their own control to determine the frequency of treatment modification. RESULTS: A total of 357 patients were analyzed. Using our algorithms treatment modification would have occurred because of lymphadenectomy in 62.8% of patients if whole pelvic external beam radiation was used for patients meeting inclusion criteria for PORTEC 1. Treatment modification would have occurred in 16.2% of patients if vaginal brachytherapy was used for patients meeting the inclusion criteria for PORTEC 2. Of the total, 53.8% of patients meeting inclusion criteria for PORTEC 1 would have had a reduction in adjuvant therapy from whole pelvic radiotherapy to vaginal brachytherapy alone. Only 9.0% of patients would have adjuvant therapy increased to include external beam radiotherapy and chemotherapy based on the presence of positive lymph nodes. CONCLUSIONS: Applying standard adjuvant treatment algorithms to real patient data, surgical lymph node assessment appears to frequently alter treatment allocation.
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Algoritmos , Carcinoma Endometrioide/patología , Toma de Decisiones , Neoplasias Endometriales/patología , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/patología , Radioterapia Adyuvante/estadística & datos numéricos , Anciano , Carcinoma Endometrioide/radioterapia , Carcinoma Endometrioide/cirugía , Neoplasias Endometriales/radioterapia , Neoplasias Endometriales/cirugía , Femenino , Estudios de Seguimiento , Humanos , Histerectomía/métodos , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
INTRODUCTION: Substantial as opposed to focal or no lymphovascular space invasion (LVSI) is proposed as an independent adverse prognostic factor in patients with early-stage endometrioid endometrial cancer (EEC). We reviewed outcomes of patients treated with adjuvant vaginal brachytherapy (VB) alone in a single institution, stratified by LVSI extent. METHODS AND MATERIALS: Retrospective review identified Stage I-II EEC patients receiving VB alone from 2010 to 2017. Extent of LVSI was reported as none, focal, or substantial. Kaplan-Meier estimates and Log-Rank test were used to determine significance between variables. Cox proportional hazards model was used for multivariate analyses. RESULTS: In total, 325 patients were identified with a median follow-up of 35 (23-48) months. LVSI was found in 112 patients with extent reported in 78, 45 (58%) had focal, and 33 (42%) substantial LVSI. Estimated disease-free survival for those with substantial LVSI was 73 (57-94)%, focal LVSI 89 (79-100)%, and no LVSI 94 (90-98)% at 48 months (p = 0.012). On multivariate analyses substantial LVSI was the only risk factor predictive of pelvic [HR substantial vs no: 7.2 (1.0-51.6); p = 0.048] and distant failure [HR substantial vs no: 4.4 (1.2-16.3); p = 0.027]. Both high-grade disease [HR 3 vs 1: 5.5 (1.2-25.6); p = 0.031] and extent of LVSI [HR substantial vs no: 4.4 (1.7-11.4); p = 0.002] predicted for worse disease-free survival. DISCUSSION: Substantial LVSI was the strongest adverse prognostic factor for pelvic and distant failure in this cohort of EEC patients receiving adjuvant VB alone, suggesting this subset may benefit from additional adjuvant therapy. This study underscores the importance of quantifying LVSI extent in EEC.
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Braquiterapia , Carcinoma Endometrioide , Neoplasias Endometriales , Braquiterapia/métodos , Carcinoma Endometrioide/radioterapia , Neoplasias Endometriales/radioterapia , Femenino , Humanos , Estimación de Kaplan-Meier , Estudios RetrospectivosRESUMEN
BACKGROUND: Vaginal brachytherapy is currently recommended as adjuvant treatment in patients with high-intermediate risk endometrial cancer to maximize local control and has only mild side effects and no or limited impact on quality of life. However, there is still considerable overtreatment and also some undertreatment, which may be reduced by tailoring adjuvant treatment to the patients' risk of recurrence based on molecular tumor characteristics. PRIMARY OBJECTIVES: To compare the rates of vaginal recurrence in women with high-intermediate risk endometrial cancer, treated after surgery with molecular-integrated risk profile-based recommendations for either observation, vaginal brachytherapy or external pelvic beam radiotherapy or with standard adjuvant vaginal brachytherapy STUDY HYPOTHESIS: Adjuvant treatment based on a molecular-integrated risk profile provides similar local control and recurrence-free survival as current standard adjuvant brachytherapy in patients with high-intermediate risk endometrial cancer, while sparing many patients the morbidity of adjuvant treatment and reducing healthcare costs. TRIAL DESIGN: A multicenter, international phase III randomized trial (2:1) of molecular-integrated risk profile-based adjuvant treatment (experimental arm) or adjuvant vaginal brachytherapy (standard arm). MAJOR INCLUSION/EXCLUSION CRITERIA: Women aged 18 years and over with a histological diagnosis of high-intermediate risk endometrioid endometrial cancer after total abdominal or laparoscopic hysterectomy and bilateral salpingo-oophorectomy. High-intermediate risk factors are defined as: (i) International Federation of Gynecology and Obstetrics stage IA (with invasion) and grade 3; (ii) stage IB grade 1 or 2 with age ≥60 and/or lymph-vascular space invasion; (iii) stage IB, grade 3 without lymph-vascular space invasion; or (iv) stage II (microscopic and grade 1). ENDPOINTS: The primary endpoint is vaginal recurrence. Secondary endpoints are recurrence-free and overall survival; pelvic and distant recurrence; 5-year vaginal control (including treatment for relapse); adverse events and patient-reported symptoms and quality of life; and endometrial cancer-related healthcare costs. SAMPLE SIZE: 500 eligible and evaluable patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Estimated date for completing accrual will be late 2021. Estimated date for presentation of (first) results is expected in 2023. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov (NCT03469674) and ISRCTN (11659025).
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Carcinoma Endometrioide/genética , Carcinoma Endometrioide/terapia , Neoplasias Endometriales/genética , Neoplasias Endometriales/terapia , Braquiterapia , Carcinoma Endometrioide/radioterapia , Ensayos Clínicos Fase III como Asunto , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Neoplasias Endometriales/radioterapia , Femenino , Humanos , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/genética , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/metabolismo , Estudios Multicéntricos como Asunto , Homólogo 1 de la Proteína MutL/genética , Homólogo 1 de la Proteína MutL/metabolismo , Proteína 2 Homóloga a MutS/genética , Proteína 2 Homóloga a MutS/metabolismo , Radioterapia Adyuvante , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
PURPOSE: The purpose of this study was to evaluate the use of a semiautomatic algorithm to simultaneously segment multiple high-dose-rate (HDR) gynecologic interstitial brachytherapy (ISBT) needles in three-dimensional (3D) transvaginal ultrasound (TVUS) images, with the aim of providing a clinically useful tool for intraoperative implant assessment. METHODS AND MATERIALS: A needle segmentation algorithm previously developed for HDR prostate brachytherapy was adapted and extended to 3D TVUS images from gynecologic ISBT patients with vaginal tumors. Two patients were used for refining/validating the modified algorithm and five patients (8-12 needles/patient) were reserved as an unseen test data set. The images were filtered to enhance needle edges, using intensity peaks to generate feature points, and leveraged the randomized 3D Hough transform to identify candidate needle trajectories. Algorithmic segmentations were compared against manual segmentations and calculated dwell positions were evaluated. RESULTS: All 50 test data set needles were successfully segmented with 96% of algorithmically segmented needles having angular differences <3° compared with manually segmented needles and the maximum Euclidean distance was <2.1 mm. The median distance between corresponding dwell positions was 0.77 mm with 86% of needles having maximum differences <3 mm. The mean segmentation time using the algorithm was <30 s/patient. CONCLUSIONS: We successfully segmented multiple needles simultaneously in intraoperative 3D TVUS images from gynecologic HDR-ISBT patients with vaginal tumors and demonstrated the robustness of the algorithmic approach to image artifacts. This method provided accurate segmentations within a clinically efficient timeframe, providing the potential to be translated into intraoperative clinical use for implant assessment.
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Adenocarcinoma de Células Claras/radioterapia , Braquiterapia/métodos , Carcinoma Endometrioide/radioterapia , Carcinoma de Células Escamosas/radioterapia , Neoplasias Vaginales/radioterapia , Adenocarcinoma de Células Claras/secundario , Anciano , Anciano de 80 o más Años , Algoritmos , Braquiterapia/instrumentación , Carcinoma Endometrioide/secundario , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/secundario , Neoplasias Endometriales/patología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional/métodos , Masculino , Persona de Mediana Edad , Agujas , Neoplasias Ováricas/patología , Próstata/diagnóstico por imagen , Planificación de la Radioterapia Asistida por Computador , Ultrasonografía/métodos , Neoplasias Vaginales/patología , Neoplasias Vaginales/secundarioRESUMEN
OBJECTIVES: Estimate the association between non-surgical management (NSM) (e.g. hormonal or radiation therapy) and overall survival among women with stage I endometrioid endometrial cancer (EEC) and identify patient and facility characteristics associated with receipt of NSM. METHODS: Women >45â¯years of age with clinical stage I EEC were identified in the National Cancer Database from 2004 to 2016. Women treated with NSM were compared with women treated initially with hysterectomy. Patient and facility characteristics associated with NSM were evaluated using logistic regression models. Association with overall survival was examined using log-rank tests, Kaplan-Meier curves, and Cox proportional hazards regression models with and without propensity score matching (PSM). RESULTS: A total of 112,469 women underwent treatment for stage I EEC between 2004 and 2016. 2776 (3%) received NSM, of whom 1987 (71%) received radiation therapy, 688 (25%) received hormonal therapy, and 101 (4%) received both. Older age, black race, higher Charlson-Deyo scores, Medicaid insurance, and low annual facility hysterectomy volume were associated with receiving NSM. The 5-year survival rate was 40% (95%CI: 37%-42%) for women with NSM compared to 89% (95%CI: 88%-89%) for hysterectomy. Women treated with NSM died at a faster rate than those who underwent primary hysterectomy (HR 7.6, 95%CI: 7.2-8.0; pâ¯<â¯0.001). This statistically significant difference in survival persisted in adjusted Cox proportional hazards models and after PSM. CONCLUSIONS: Women treated with NSM had a significantly higher risk of death compared to those undergoing hysterectomy for stage I EEC. Caution should be used when selecting patients for NSM given its worse outcomes.
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Antineoplásicos Hormonales/uso terapéutico , Carcinoma Endometrioide/tratamiento farmacológico , Carcinoma Endometrioide/radioterapia , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/radioterapia , Factores de Edad , Anciano , Anciano de 80 o más Años , Carcinoma Endometrioide/mortalidad , Quimioradioterapia , Estudios de Cohortes , Bases de Datos Factuales , Neoplasias Endometriales/mortalidad , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Estados Unidos/epidemiologíaRESUMEN
PURPOSE: For many decades, endometrial cancer (EC) has been considered as a homogenous tumor entity with good prognosis. The currently valid risk stratification considers clinical and pathological factors. Treatment recommendations differ considerably from country to country. MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA) Research Network has shown that ECs should be reclassified into four novel molecular prognostic groups, with the potential of changing adjuvant management of EC patients: ultra-mutated, hyper-mutated, copy-number low, and copy-number high. Clinical examples are shown, and the available literature has been highlighted. The European Society of Gynaecological Oncology (ESGO) guideline for endometrial cancer takes the new classification system into consideration for adjuvant treatment decisions and will be published this year. RESULTS: In the near future, we expect new treatment recommendations that may differ considerably from the clinicopathologically driven recommendations on the basis of our deeper insight and better understanding of molecular markers in endometrial cancer. The PORTEC 4a study is the only recruiting study which randomizes patients to adjuvant or no adjuvant treatment on the basis of the aforementioned new classification system. CONCLUSION: The aim of the new classification is a more personalized adjuvant radio(chemo)therapy decision and better oncologic outcomes or avoidance of overtreatment.
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Carcinoma/radioterapia , Neoplasias Endometriales/radioterapia , Radioterapia Adyuvante , Biomarcadores de Tumor , Carcinoma/clasificación , Carcinoma/genética , Carcinoma/patología , Carcinoma Endometrioide/clasificación , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/radioterapia , Toma de Decisiones Clínicas , Neoplasias Endometriales/clasificación , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Estrógenos , Femenino , Predicción , Dosificación de Gen , Genes Relacionados con las Neoplasias , Humanos , Inestabilidad de Microsatélites , Mutación , Neoplasias Hormono-Dependientes/genética , Neoplasias Hormono-Dependientes/radioterapia , Medicina de Precisión/métodos , Progesterona , Pronóstico , Riesgo , Transducción de Señal/genéticaRESUMEN
OBJECTIVE: To evaluate trends in use of radiation therapy and its impact on overall survival in low- and high-grade stage I endometrioid endometrial carcinoma. METHODS: Patients with stage I endometrial cancer who underwent hysterectomy from 2004 to 2013 were identified through the National Cancer Database and classified as: stage IA G1/2, stage IA G3, stage IB G1/2, and stage IB G3. Trends in use of vaginal brachytherapy and external beam radiation therapy were assessed. Overall survival was measured from surgery and estimated using the Kaplan-Meier method. The effect of radiation therapy on overall survival was assessed within each stage/grade group using Cox proportional hazards analysis in propensity-matched treatment groups. RESULTS: A total of 132 393 patients met inclusion criteria, and 81% of patients had stage IA and 19% had stage IB endometrial cancer. Adjuvant therapy was administered in 18% of patients: 52% received vaginal brachytherapy, 30% external beam radiation therapy, and 18% chemotherapy ±radiation therapy. External beam radiation therapy use decreased from 9% in 2004 to 4% in 2012, while vaginal brachytherapy use increased from 8% to 14%. Stage IA G1/2 patients did not benefit from either external beam radiation therapy or vaginal brachytherapy, while administration of vaginal brachytherapy improved overall survival in stage IB G1/2 compared with no treatment (p<0.0001). In stage IB G1/2 and stage IA G3, vaginal brachytherapy was superior to external beam radiation therapy (p=0.0004 and p=0.004, respectively). Stage IB G3 patients had improved overall survival with either vaginal brachytherapy or external beam radiation therapy versus no treatment but no difference in overall survival was seen between vaginal brachytherapy and external beam radiation therapy (p=0.94). CONCLUSIONS: The delivery of adjuvant radiation therapy in patients with stage IA G1/2 endometrial carcinoma is not associated with improvement in overall survival. Patients with stage IB G1/2 and G3 as well as stage IA G3 are shown to benefit from improved overall survival when adjuvant radiation therapy is administered. These findings demonstrate potential opportunities to reduce both overtreatment and undertreatment in stage I endometrial cancer patients.
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Braquiterapia/tendencias , Carcinoma Endometrioide/radioterapia , Neoplasias Endometriales/radioterapia , Anciano , Carcinoma Endometrioide/mortalidad , Neoplasias Endometriales/mortalidad , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: To better delineate optimal management of high-risk, early-stage endometrial cancer, as national guidelines permit substantial practice variations. METHODS: Patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB grade 3 and stage II endometrioid carcinoma who underwent at least total hysterectomy were identified in SEER-Medicare. Adjuvant treatments were brachytherapy (BT), external beam radiation therapy (EBRT), and chemotherapy. Death from endometrial cancer (cancer-specific mortality [CSM]) and local recurrence were analyzed using Gray's test and Fine-Gray regression. RESULTS: In total, 1,095 patients were identified: 52% received BT, 56% received EBRT, 16% received chemotherapy, and 29% received no adjuvant treatment. Survival outcomes were significantly worse for stage IB grade 3 and stage II grade 3 relative to stage II grades 1-2 (5-year CSM: 18% and 23% vs. 10%; p<0.001 and p=0.003, respectively), while there was no difference between stage IB grade 3 and stage II grade 3 (p=0.618). BT had a local control benefit across all patients (p<0.001) that translated into a survival benefit in stage IB grade 3 (adjusted hazard ratio [HR] for CSM=0.47, p=0.003). EBRT had a survival benefit in stage II grade 3 (adjusted HR for CSM=0.36; p=0.031), as did lymph node dissection (p=0.015). Chemotherapy was not significantly correlated with CSM. CONCLUSIONS: High-risk, early-stage endometrioid carcinoma is a heterogeneous population. BT was associated with a survival benefit in stage IB grade 3, whereas regional treatment with EBRT and lymphadenectomy was associated with a survival benefit in stage II grade 3.
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Carcinoma Endometrioide , Neoplasias Endometriales , Anciano , Anciano de 80 o más Años , Braquiterapia , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/radioterapia , Neoplasias Endometriales/patología , Neoplasias Endometriales/radioterapia , Femenino , Humanos , Histerectomía , Medicare , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Radioterapia Adyuvante , Estudios Retrospectivos , Estados UnidosRESUMEN
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.
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Carcinoma Endometrioide/tratamiento farmacológico , Neoplasias Endometriales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/radioterapia , Carcinoma Endometrioide/cirugía , Quimioradioterapia Adyuvante , Quimioterapia Adyuvante , Estudios de Cohortes , Supervivencia sin Enfermedad , Neoplasias Endometriales/patología , Neoplasias Endometriales/radioterapia , Neoplasias Endometriales/cirugía , Femenino , Humanos , Histerectomía , Escisión del Ganglio Linfático , Metástasis Linfática , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
PURPOSE: Our purpose was to evaluate outcomes and sites of failure for women with early stage endometrial adenocarcinoma treated with adjuvant high-dose-rate (HDR) vaginal brachytherapy (VB) with a low dose scheme. METHODS AND MATERIALS: Retrospective review identified 318 patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II endometrioid endometrial cancer who received adjuvant HDR VB to a dose of 24 Gray (Gy) in 6 fractions from 2005 to 2017. Patients with <6 months follow-up were excluded. Dose was prescribed to cylinder surface and computerized tomography (CT) imaging was performed before each fraction to assess cylinder placement. Rates of vaginal relapse (VR), pelvic nodal relapse, distant metastasis, recurrence-free survival, and overall survival were calculated by Kaplan-Meier method. Univariate analysis was performed by log rank test or Cox proportional hazards. Pretreatment CT images were analyzed for patients with VR. RESULTS: Median follow-up was 42 months for 243 patients. The 3-year rates of VR, pelvic nodal relapse, distant metastasis, recurrence-free survival, and overall survival were 1.9%, 1.5%, 4.3%, 94.1%, and 98.9%, respectively. The 3-year VR rates by Gynecologic Oncology (GOG)-99 risk groups were 0%, 1.4%, and 3.2% for low risk, low-intermediate risk, and high-intermediate risk (HIR) disease (P = .5). By Post-operative Radiation Therapy in Endometrial Carcinoma (PORTEC) risk stratification, 3-year VR rate was 1.3% for HIR disease. On review of pretreatment CT images of the 6 patients with VR, 3 patients had relapse at the introitus outside of the treated vaginal length, and 3 had in-field recurrence at the vaginal apex. Higher body mass index (BMI) was associated with VR, with a 14% increase in risk per BMI unit (kg/m2, P = .02). There were no reported grade 2 GI or any grade 3 toxicities. CONCLUSIONS: Adjuvant HDR VB with a low-dose regimen results in excellent clinical outcomes for patients with early stage endometrioid endometrial cancer. Patients with higher BMI may be at increased risk of VR, and additional study is needed to optimize brachytherapy treatment parameters.
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Braquiterapia/métodos , Carcinoma Endometrioide/radioterapia , Neoplasias Endometriales/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Endometrioide/mortalidad , Neoplasias Endometriales/mortalidad , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
OBJECTIVE: Advances in minimally invasive surgery, particularly with robotic surgery, have resulted in improved peri-operative outcomes in patients with endometrial cancer. In addition, randomized trials have shown that addition of adjuvant radiotherapy following surgery improves loco-regional disease control among stage I intermediate-risk endometrial cancer patients. We aimed to investigate the efficacy and safety of combined treatment of robotic surgery and adjuvant radiotherapy in this patient population. METHODS: A single-center retrospective study was conducted on stage I endometrioid-type endometrial cancer patients with intermediate-risk features (<50% myometrial involvement and grade 2-3 histopathology, or >50% myometrial involvement and grade 1-2 histopathology) treated with hysterectomy and adjuvant radiotherapy between January 2010 and December 2015. Data on surgery and radiotherapy were collected and correlated with clinical and surgical outcomes using log-rank. Oncologic outcomes were then compared between robotic surgery and laparotomy. RESULTS: A total of 179 intermediate-risk endometrial cancer patients were identified, of whom 135 (75.4%) received adjuvant radiotherapy and were included in the final analysis. Median age at diagnosis was 63 years (range 40-89) and median follow-up was 4.7 years (range 1.1-8.8). Seventy-seven patients (57%) underwent robotic surgery and 58 patients (43%) underwent laparotomy. Surgical staging with lymph node dissection was performed on 79.3% of the patients. The majority of patients (79.3%) received vaginal brachytherapy as part of adjuvant radiotherapy, while 20.7% received external-beam radiotherapy. Among the entire cohort, eight (5.9%) patients recurred and all eight recurrences occurred in the robotic surgery group; no recurrence was found in the laparotomy group. This translated into 5 year disease-free survival of 100% in the laparotomy group, compared with 91.8% in the robotic surgery group (p=0.005). No difference in overall survival was found between the two groups (p=0.51). CONCLUSION: Oncologic outcomes for stage I intermediate-risk endometrial cancer treated with hysterectomy and adjuvant radiotherapy at our institution are comparable to the previously published literature. The higher recurrence rate observed with robotic surgery at our institution has not been observed previously and requires further investigation.