RESUMEN
BACKGROUND: Standard first-line chemotherapy for endometrial cancer is paclitaxel plus carboplatin. The benefit of adding pembrolizumab to chemotherapy remains unclear. METHODS: In this double-blind, placebo-controlled, randomized, phase 3 trial, we assigned 816 patients with measurable disease (stage III or IVA) or stage IVB or recurrent endometrial cancer in a 1:1 ratio to receive pembrolizumab or placebo along with combination therapy with paclitaxel plus carboplatin. The administration of pembrolizumab or placebo was planned in 6 cycles every 3 weeks, followed by up to 14 maintenance cycles every 6 weeks. The patients were stratified into two cohorts according to whether they had mismatch repair-deficient (dMMR) or mismatch repair-proficient (pMMR) disease. Previous adjuvant chemotherapy was permitted if the treatment-free interval was at least 12 months. The primary outcome was progression-free survival in the two cohorts. Interim analyses were scheduled to be triggered after the occurrence of at least 84 events of death or progression in the dMMR cohort and at least 196 events in the pMMR cohort. RESULTS: In the 12-month analysis, Kaplan-Meier estimates of progression-free survival in the dMMR cohort were 74% in the pembrolizumab group and 38% in the placebo group (hazard ratio for progression or death, 0.30; 95% confidence interval [CI], 0.19 to 0.48; P<0.001), a 70% difference in relative risk. In the pMMR cohort, median progression-free survival was 13.1 months with pembrolizumab and 8.7 months with placebo (hazard ratio, 0.54; 95% CI, 0.41 to 0.71; P<0.001). Adverse events were as expected for pembrolizumab and combination chemotherapy. CONCLUSIONS: In patients with advanced or recurrent endometrial cancer, the addition of pembrolizumab to standard chemotherapy resulted in significantly longer progression-free survival than with chemotherapy alone. (Funded by the National Cancer Institute and others; NRG-GY018 ClinicalTrials.gov number, NCT03914612.).
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Endometriales , Femenino , Humanos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Reparación de la Incompatibilidad de ADN , Método Doble Ciego , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/genética , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversosRESUMEN
OBJECTIVE: Due to limited data on homologous recombination deficiency (HRD) in older patients (≥ 70 years) with advanced stage high grade serous ovarian cancer (HGSC), we aimed to determine the rates of HRD at diagnosis in this age group. METHODS: From the Phase 3 trial VELIA the frequency of HRD and BRCA1/2 pathogenic variants (PVs) was compared between younger (< 70 years) and older participants. HRD and somatic(s) BRCA1/2 pathogenic variants (PVs) were determined at diagnosis using Myriad myChoice® CDx and germline(g) BRCA1/2 PVs using Myriad BRACAnalysis CDx®. HRD was defined if a BRCA PV was present, or the genomic instability score (GIS) met threshold (GIS ≥ 33 & ≥ 42 analyzed). RESULTS: Of 1140 participants, 21% were ≥ 70 years. In total, 26% (n = 298) had a BRCA1/2 PV and HRD, 29% (n = 329) were HRD/BRCA wild-type, 33% (n = 372) non-HRD, and 12% HR-status unknown (n = 141). HRD rates were higher in younger participants, 59% (n = 476/802), compared to 40% (n = 78/197) of older participants (GIS ≥ 42) [p < 0.001]; similar rates demonstrated with GIS ≥ 33, 66% vs 48% [p < 0.001]. gBRCA PVs observed in 24% younger vs 8% of older participants (p < 0.001); sBRCA in 8% vs 10% (p = 0.2559), and HRD (GIS ≥ 42) not due to gBRCA was 35% vs 31% (p = 0.36). CONCLUSIONS: HRD frequency was similar in participants aged < 70 and ≥ 70 years (35% vs 31%) when the contribution of gBRCA was excluded; rates of sBRCA PVs were also similar (8% v 10%), thus underscoring the importance of HRD and BRCA testing at diagnosis in older patients with advanced HGSC given the therapeutic implications.
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Proteína BRCA1 , Cistadenocarcinoma Seroso , Neoplasias Ováricas , Humanos , Femenino , Anciano , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Persona de Mediana Edad , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patología , Proteína BRCA1/genética , Proteína BRCA2/genética , Anciano de 80 o más Años , Factores de Edad , Adulto , Recombinación Homóloga , Estadificación de Neoplasias , Clasificación del Tumor , Pruebas Genéticas/métodosRESUMEN
OBJECTIVE: This study investigated the risk of an aggressive endometrial cancer (EC) diagnosis by race, ethnicity, and country of origin to further elucidate histologic disparities in non-Hispanic Black (NHB), Hispanic, Asian/Pacific Islander (API), American Indian/Alaskan Native (AIAN) vs. non-Hispanic White (NHW) patients, particularly in Hispanic or API subgroups. METHODS: Patient diagnosed between 2004 and 2020 with low grade (LG)-endometrioid endometrial cancer (ECC) or an aggressive EC including grade 3 EEC, serous carcinoma, clear cell carcinoma, mixed epithelial carcinoma, or carcinosarcoma in the National Cancer Database were studied. The odds ratio (OR) and 95% confidence interval (CI) for diagnosis of an aggressive EC histology was estimated using logistic modeling. RESULTS: There were 343,868 NHW, 48,897 NHB, 30,013 Hispanic, 15,015 API and 1646 AIAN patients. The OR (95% CI) for an aggressive EC diagnosis was 3.07 (3.01-3.13) for NHB, 1.08 (1.06-1.11) for Hispanic, 1.17 (1.13-1.21) for API and 1.07 (0.96-1.19) for AIAN, relative to NHW patients. Subset analyses by country of origin illustrated the diversity in the OR for an aggressive EC diagnosis among Hispanic (1.18 for Mexican to 1.87 for Dominican), Asian (1.14 Asian Indian-Pakistani to 1.48 Korean) and Pacific Islander (1.00 for Hawaiian to 1.33 for Samoan) descendants. Hispanic, API and AIAN patients were diagnosed 5-years younger that NHW patients, and the risk for an aggressive EC histology were all significantly higher than NHW patients after correcting for age. Insurance status was another independent risk factor for aggressive histology. CONCLUSIONS: Risk of an aggressive EC diagnosis varied by race, ethnicity, and country of origin. NHB patients had the highest risk, followed by Dominican, South/Central American, Cuban, Korean, Thai, Vietnamese, and Filipino descendants.
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Neoplasias Endometriales , Humanos , Femenino , Neoplasias Endometriales/etnología , Neoplasias Endometriales/patología , Persona de Mediana Edad , Anciano , Estados Unidos/epidemiología , Adulto , Población Blanca/estadística & datos numéricos , Hispánicos o Latinos/estadística & datos numéricos , Adenocarcinoma de Células Claras/patología , Adenocarcinoma de Células Claras/etnología , Adenocarcinoma de Células Claras/epidemiología , Carcinosarcoma/patología , Carcinosarcoma/etnología , Nativos de Hawái y Otras Islas del Pacífico/estadística & datos numéricos , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/etnología , Anciano de 80 o más Años , Etnicidad/estadística & datos numéricos , Disparidades en el Estado de Salud , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/etnología , Negro o Afroamericano/estadística & datos numéricosRESUMEN
PURPOSE: We investigated racial disparities in survival by histology in cervical cancer and examined the factors contributing to these disparities. METHODS: Non-Hispanic Black and non-Hispanic White (hereafter known as Black and White) patients with stage I-IV cervical carcinoma diagnosed between 2004 and 2017 in the National Cancer Database were studied. Survival differences were compared using Cox modeling to estimate hazard ratio (HR) or adjusted HR (AHR) and 95% confidence interval (CI). The contribution of demographic, socioeconomic and clinical factors to the Black vs White differences in survival was estimated after applying propensity score weighting in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC). RESULTS: This study included 10,111 Black and 43,252 White patients with cervical cancer. Black patients had worse survival than White cervical cancer patients (HR = 1.40, 95% CI = 1.35-1.45). Survival disparities between Black and White patients varied significantly by histology (HR = 1.20, 95% CI = 1.15-1.24 for SCC; HR = 2.32, 95% CI = 2.12-2.54 for AC, interaction p < 0.0001). After balancing the selected demographic, socioeconomic and clinical factors, survival in Black vs. White patients was no longer different in those with SCC (AHR = 1.01, 95% CI 0.97-1.06) or AC (AHR = 1.09, 95% CI = 0.96-1.24). In SCC, the largest contributors to survival disparities were neighborhood income and insurance. In AC, age was the most significant contributor followed by neighborhood income, insurance, and stage. Diagnosis of AC (but not SCC) at ≥65 years old was more common in Black vs. White patients (26% vs. 13%, respectively). CONCLUSIONS: Histology matters in survival disparities and diagnosis at ≥65 years old between Black and White cervical cancer patients. These disparities were largely explained by modifiable factors.
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Negro o Afroamericano , Carcinoma de Células Escamosas , Neoplasias del Cuello Uterino , Población Blanca , Humanos , Femenino , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/etnología , Neoplasias del Cuello Uterino/mortalidad , Población Blanca/estadística & datos numéricos , Persona de Mediana Edad , Negro o Afroamericano/estadística & datos numéricos , Anciano , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/etnología , Carcinoma de Células Escamosas/mortalidad , Adulto , Adenocarcinoma/patología , Adenocarcinoma/etnología , Adenocarcinoma/mortalidad , Estados Unidos/epidemiología , Disparidades en Atención de Salud/etnología , Disparidades en Atención de Salud/estadística & datos numéricos , Disparidades en el Estado de Salud , Factores Socioeconómicos , Modelos de Riesgos Proporcionales , Estadificación de NeoplasiasRESUMEN
OBJECTIVE: Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC). METHODS: Black and White patients diagnosed with EEC who underwent hysterectomy ± adjuvant treatment in SEER, National Cancer Database (NCDB), the Genomics Evidence Neoplasia Information Exchange (GENIE) project (v.13.0), and eight NCI-sponsored randomized phase III clinical trials (RCTs) were studied. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for cancer-related death (CRD), non-cancer death (NCD), and all-cause death. RESULTS: Black (n = 4397) vs. White (n = 47,959) patients in SEER had a HR (95% CI) of 2.04 (1.87-2.23) for CRD and 1.22 (1.09-1.36) for NCD. In NCDB, the HR (95% CI) for death in Black (n = 13,468) vs. White (n = 155,706) patients was 1.52 (1.46-1.58) dropping to 1.29 (1.23-1.36) after propensity-score matching for age, comorbidity, income, insurance, grade, stage, LVSI, and treatment. In GENIE, Black (n = 109) vs. White (n = 1780) patients had fewer PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K-pathway-related gene mutations. In contrast, TP53 and DNA-repair-related gene mutation frequency as well as tumor mutational burden-high status were similar in Black and White patients. In RCTs, Black (n = 187) vs. White (n = 2877) patients were more likely to have advanced or recurrent disease, higher grade, worse performance status and progressive disease. Risk of death in Black vs. White patients in RCTs was 2.19 (1.77-2.71) persisting to 1.32 (1.09-1.61) after matching for grade, stage, and treatment arm while balancing age and performance status. CONCLUSIONS: Differences exist in clinical presentation, outcomes, and molecular features in Black vs. White patients with EEC in real-world registries and RCTs. Targeted-drug development, strategies to modify social determinants, and diverse inclusion in RCTs are approaches to reduce disparities.
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Negro o Afroamericano , Carcinoma Endometrioide , Progresión de la Enfermedad , Neoplasias Endometriales , Población Blanca , Humanos , Femenino , Población Blanca/estadística & datos numéricos , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/terapia , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/etnología , Carcinoma Endometrioide/mortalidad , Neoplasias Endometriales/genética , Neoplasias Endometriales/terapia , Neoplasias Endometriales/etnología , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Persona de Mediana Edad , Negro o Afroamericano/estadística & datos numéricos , Anciano , Ensayos Clínicos Controlados Aleatorios como Asunto , Estados Unidos/epidemiología , Programa de VERF , Sistema de Registros , Ensayos Clínicos Fase III como Asunto , AdultoRESUMEN
OBJECTIVE: To evaluate the impact of a mobile health patient engagement technology (PET) on postoperative outcomes in gynecologic oncology patients. METHODS: All gynecologic oncology patients undergoing laparotomy on an enhanced recovery program (ERP) were approached from July 2019 to May 2021 to enroll in a PET, which can be accessed by computer, tablet, or smart phone. This platform provides enhanced pre- and postoperative patient education and remote patient monitoring. Patients who elected to participate were provided with targeted education based on their age and comorbidities and were asked to complete daily health checks during the postoperative period. Participants in the PET were compared to patients who opted out as well as to a historical cohort from prior to PET implementation. Patient and procedure-level factors were recorded. The primary outcomes were length of stay (LOS) and 30-day readmission rate. Analysis was performed using SPSS v.26. RESULTS: 682 women met inclusion criteria during the study time; 347 in the PET group and 335 in the control group. Demographic and other factors including race, BMI (kg/m2), Charlson Comorbidity Index (CCI), surgical complexity, and insurance status were not different between the PET and control group; however, patients in the PET cohort were slightly younger (55.0 yo vs. 57.2 yo; p = 0.04). Patients in the PET group had a significantly shorter LOS (2.9 days vs. 3.6 days; p < 0.01) and lower readmission rate (4.3% vs. 8.6%; p < 0.01) when compared with the control group. CONCLUSIONS: Use of a PET in our gynecologic oncology patients decreased LOS by nearly one day despite an absence of differences in other demographic and surgical factors other than age. Furthermore, there was a 50% reduction in readmission rates in the PET group. The use of a PET allows for healthcare professionals to engage, evaluate, and treat patients in a way that improves perioperative care.
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Neoplasias de los Genitales Femeninos , Humanos , Femenino , Neoplasias de los Genitales Femeninos/cirugía , Neoplasias de los Genitales Femeninos/etiología , Estudios Retrospectivos , Participación del Paciente , Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Atención Perioperativa , Tiempo de Internación , Complicaciones Posoperatorias/etiologíaRESUMEN
BACKGROUND: Data are limited regarding the use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors, such as veliparib, in combination with chemotherapy followed by maintenance as initial treatment in patients with high-grade serous ovarian carcinoma. METHODS: In an international, phase 3, placebo-controlled trial, we assessed the efficacy of veliparib added to first-line induction chemotherapy with carboplatin and paclitaxel and continued as maintenance monotherapy in patients with previously untreated stage III or IV high-grade serous ovarian carcinoma. Patients were randomly assigned in a 1:1:1 ratio to receive chemotherapy plus placebo followed by placebo maintenance (control), chemotherapy plus veliparib followed by placebo maintenance (veliparib combination only), or chemotherapy plus veliparib followed by veliparib maintenance (veliparib throughout). Cytoreductive surgery could be performed before initiation or after 3 cycles of trial treatment. Combination chemotherapy was 6 cycles, and maintenance therapy was 30 additional cycles. The primary end point was investigator-assessed progression-free survival in the veliparib-throughout group as compared with the control group, analyzed sequentially in the BRCA-mutation cohort, the cohort with homologous-recombination deficiency (HRD) (which included the BRCA-mutation cohort), and the intention-to-treat population. RESULTS: A total of 1140 patients underwent randomization. In the BRCA-mutation cohort, the median progression-free survival was 34.7 months in the veliparib-throughout group and 22.0 months in the control group (hazard ratio for progression or death, 0.44; 95% confidence interval [CI], 0.28 to 0.68; P<0.001); in the HRD cohort, it was 31.9 months and 20.5 months, respectively (hazard ratio, 0.57; 95 CI, 0.43 to 0.76; P<0.001); and in the intention-to-treat population, it was 23.5 months and 17.3 months (hazard ratio, 0.68; 95% CI, 0.56 to 0.83; P<0.001). Veliparib led to a higher incidence of anemia and thrombocytopenia when combined with chemotherapy as well as of nausea and fatigue overall. CONCLUSIONS: Across all trial populations, a regimen of carboplatin, paclitaxel, and veliparib induction therapy followed by veliparib maintenance therapy led to significantly longer progression-free survival than carboplatin plus paclitaxel induction therapy alone. The independent value of adding veliparib during induction therapy without veliparib maintenance was less clear. (Funded by AbbVie; VELIA/GOG-3005 ClinicalTrials.gov number, NCT02470585.).
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bencimidazoles/uso terapéutico , Cistadenocarcinoma Seroso/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bencimidazoles/efectos adversos , Carboplatino/administración & dosificación , Terapia Combinada , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/cirugía , Método Doble Ciego , Femenino , Genes BRCA1 , Genes BRCA2 , Humanos , Análisis de Intención de Tratar , Quimioterapia de Mantención , Persona de Mediana Edad , Mutación , Neoplasias Ováricas/genética , Neoplasias Ováricas/cirugía , Paclitaxel/administración & dosificación , Inhibidores de Poli(ADP-Ribosa) Polimerasas/efectos adversos , Supervivencia sin Progresión , Calidad de VidaRESUMEN
OBJECTIVE: The Laparoscopic Approach to Cervical Cancer (LACC) trial found that minimally invasive radical hysterectomy compared to open radical hysterectomy compromised oncologic outcomes and was associated with worse progression-free survival (PFS) and overall survival (OS) in early-stage cervical carcinoma. We sought to assess oncologic outcomes at multiple centers between minimally invasive (MIS) radical hysterectomy and OPEN radical hysterectomy. METHODS: This is a multi-institutional, retrospective cohort study of patients with 2009 FIGO stage IA1 (with lymphovascular space invasion) to IB1 cervical carcinoma from 1/2007-12/2016. Patients who underwent preoperative therapy were excluded. Squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinomas were included. Appropriate statistical tests were used. RESULTS: We identified 1093 cases for analysis-715 MIS (558 robotic [78%]) and 378. OPEN procedures. The OPEN cohort had more patients with tumors >2 cm, residual disease in the hysterectomy specimen, and more likely to have had adjuvant therapy. Median follow-up for the MIS and OPEN cohorts were 38.5 months (range, 0.03-149.51) and 54.98 months (range, 0.03-145.20), respectively. Three-year PFS rates were 87.9% (95% CI: 84.9-90.4%) and 89% (95% CI: 84.9-92%), respectively (P = 0.6). On multivariate analysis, the adjusted HR for recurrence/death was 0.70 (95% CI: 0.47-1.03; P = 0.07). Three-year OS rates were 95.8% (95% CI: 93.6-97.2%) and 96.6% (95% CI: 93.8-98.2%), respectively (P = 0.8). On multivariate analysis, the adjusted HR for death was 0.81 (95% CI: 0.43-1.52; P = 0.5). CONCLUSION: This multi-institutional analysis showed that an MIS compared to OPEN radical hysterectomy for cervical cancer did not appear to compromise oncologic outcomes, with similar PFS and OS.
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Laparoscopía , Neoplasias del Cuello Uterino , Supervivencia sin Enfermedad , Femenino , Humanos , Histerectomía/métodos , Laparoscopía/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Estadificación de Neoplasias , Estudios Retrospectivos , Neoplasias del Cuello Uterino/patologíaRESUMEN
Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years following diagnosis. The NCCN Guidelines for Ovarian Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with ovarian, fallopian tube, and primary peritoneal cancers. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised guidance on alternative chemotherapy regimens for patients with advanced age and/or comorbidities, a new algorithm for recurrent low-grade serous carcinoma based on developing research and novel therapeutic agents, and updated language regarding tumor molecular analysis applications in ovarian cancer.
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Cistadenocarcinoma Seroso , Neoplasias Ováricas , Neoplasias Peritoneales , Carcinoma Epitelial de Ovario/diagnóstico , Carcinoma Epitelial de Ovario/terapia , Cistadenocarcinoma Seroso/patología , Femenino , Humanos , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/patología , Neoplasias Ováricas/terapia , Estados UnidosRESUMEN
PURPOSE OF REVIEW: In this review, we discuss modern cytokine delivery systems in oncologic care, focusing on modalities being developed in the clinical trials or currently in use. These include pegylation, immune-cytokine drug conjugates, cytokine-expressing plasmid nanoparticles, nonviral cytokine nanoparticles, viral systems, and AcTakines. RECENT FINDINGS: Cytokine therapy has the potential to contribute to cancer treatment options by modulating the immune system towards an improved antitumor response and has shown promise both independently and in combination with other immunotherapy agents. Despite promising preliminary studies, systemic toxicities and challenges with administration have limited the impact of unmodified cytokine therapy. In the last decade, novel delivery systems have been developed to address these challenges and facilitate cytokine-based oncologic treatments. Novel delivery systems provide potential solutions to decrease dose-limiting side effects, facilitate administration, and increase the therapeutic activity of cytokine treatments in oncology care. The expanding clinical and translational research in these systems provides an opportunity to augment the armamentarium of immune oncology and may represent the next frontier of cytokine-based immuno-oncology.
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Nanopartículas , Neoplasias , Citocinas/uso terapéutico , Humanos , Factores Inmunológicos , Inmunoterapia/efectos adversos , Neoplasias/patologíaRESUMEN
OBJECTIVES: The aim of the study is to evaluate the use of a bipolar electrocautery device for complete salpingectomy at cesarean to improve procedure completion rates, operative time, and surgeon reported satisfaction as compared with standard bilateral tubal ligation (BTL) and suture-cut-tie salpingectomy. STUDY DESIGN: This is a prospective cohort study of women undergoing planned, non-emergent cesarean with desired sterilization with complete salpingectomy utilizing a bipolar electrocautery device. Study patients were compared with historic controls from a randomized controlled trial (RCT) of complete salpingectomy via suture-cut-tie method versus BTL conducted at our institution (SCORE trial, NCT02374827). Outcomes were compared with groups from the original RCT. RESULTS: Thirty-nine women were consecutively enrolled (12/2018-11/2019) into the device arm of the study and compared with the original SCORE cohort (n = 40 BTL, n = 40 salpingectomy without a device). Salpingectomy performance with the bipolar electrocautery device was successfully completed in 100% (39/39) of enrolled women, with one device failure requiring the use of a second device, as compared with 95% (38/40) in the BTL (p = 0.49) and 67.5% (27/40) in salpingectomies without a device (p < 0.001). Mean operative time of sterilization procedure alone demonstrated device use as having the shortest operative time of all (device salpingectomy 5.0 ± 3.6 vs. no device 18.5 ± 8.3 minutes, p < 0.001; and vs. BTL 6.9 ± 5.0, p = 0.032). Mean sterilization procedure endoscopic band ligation (EBL) was demonstrated to be significantly different between each group, least amongst BTL followed by device (6.3 ± 4.8 vs. 8.4 ± 24.8, p < 0.001), and most by suture-cut-tie method (17.7 ± 14.3, p < 0.001 compared with device). Surgeon reported attitudes of complete salpingectomy performance in general practice outside an academic setting was greater with a device than without (79.5 vs. 35.3%; p < 0.001). CONCLUSION: Use of a bipolar electrocautery device improved operative times and surgeon satisfaction for salpingectomy at cesarean over standard suture ligation. Device use improved surgeon reported outcomes and may improve incorporation of complete salpingectomy at cesarean. KEY POINTS: · Electrocautery bipolar device use was safe at the time of salpingectomy during cesarean.. · Greater surgeon satisfaction occurs using a device than without.. · Decreased surgical time with device use is seen making the procedure equal to BTL..
RESUMEN
BACKGROUND: Both incidence and mortality of uterine cancer are on the rise and mortality is higher for African American women. The aim of our study was to evaluate how Next Generation Sequencing (NGS) may facilitate identification of and intervention for treatment disparities when integrated into clinical workflows. RESULTS: Our cohort included 159 uterine cancer patients with recurrent/progressive and newly diagnosed advanced stage and/or high-risk histology. The most common tumor histological subtypes included EEC (n = 67), SEC (n = 34), UCS (n = 20), and mixed (n = 14). Black patients were most likely to present with aggressive histology: (SEC, 34.0%) and carcinosarcoma (UCS, 14.0%). The four most common mutations across all subtypes were TP53, PIK3CA, PTEN, and ARID1A. There was racial disparity between Black versus non-Black patients who were initiated on targeted therapy (28.2% vs. 38.2%, respectively) and clinical trial (15% vs. 22.6%, respectively). Compared to non-Black patients, Black patients had a significantly higher percentage TP53 mutations (p < 0.05) and a significantly lower percentage ARID1A mutations (p < 0.05). CONCLUSIONS: NGS for uterine malignancies provides actionable information for targetable mutations and/or clinical trial enrollment in most patients; further investigation is necessary to identify potentially modifiable factors contributing to current disparities that may improve targeted therapy uptake and clinical trial participation.
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Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Terapia Molecular Dirigida , Mutación , Neoplasias Uterinas/tratamiento farmacológico , Adulto , Negro o Afroamericano , Anciano , Anciano de 80 o más Años , Proteínas de Unión al ADN/genética , Femenino , Genes p53 , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Factores de Transcripción/genética , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/genéticaRESUMEN
Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States and is the country's fifth most common cause of cancer mortality in women. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. These NCCN Guidelines discuss cancers originating in the ovary, fallopian tube, or peritoneum, as these are all managed in a similar manner. Most of the recommendations are based on data from patients with the most common subtypesâhigh-grade serous and grade 2/3 endometrioid. The NCCN Guidelines also include recommendations specifically for patients with less common ovarian cancers, which in the guidelines include the following: carcinosarcoma, clear cell carcinoma, mucinous carcinoma, low-grade serous, grade 1 endometrioid, borderline epithelial, malignant sex cord-stromal, and malignant germ cell tumors. This manuscript focuses on certain aspects of primary treatment, including primary surgery, adjuvant therapy, and maintenance therapy options (including PARP inhibitors) after completion of first-line chemotherapy.
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Carcinoma Epitelial de Ovario , Neoplasias Ováricas , Adenocarcinoma de Células Claras , Carcinoma Epitelial de Ovario/diagnóstico , Carcinoma Epitelial de Ovario/epidemiología , Carcinoma Epitelial de Ovario/terapia , Femenino , Humanos , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/terapiaRESUMEN
STUDY OBJECTIVE: Determine near-optimal dose, safety, and efficacy of nerindocianine in pelvic ureter detection with near-infrared fluorescence imaging in women undergoing minimally invasive pelvic surgery with 3 Food and Drug Administration-cleared imaging systems. DESIGN: Open label, phase 1/2a study. SETTING: University of Alabama at Birmingham. PATIENTS: Forty-one female subjects undergoing minimally invasive gynecologic surgery. INTERVENTIONS: Subjects received a single dose of nerindocianine sodium, starting at 0.06-mg/kg body weight and increased/decreased until the near-optimal dose was determined (part A). Examine the degree of concordance between endoscopic and robotic devices (part B). MEASUREMENTS AND MAIN RESULTS: In part A, composite scores were collected every 10 minutes for 30 minutes and then every 15 minutes through 90 minutes using a scale measuring the anatomy/laterality of ureter visualization. In part B (paired imaging system efficacy), 2 cohorts of 8 subjects each received the near-optimal dose. Composite scores for visualization of the ureter were collected at 10 and 30 minutes postinfusion with the Firefly Imaging System and either the PINPOINT or 1588 AIM endoscope. Composite scores were compared to examine the degree of concordance between devices. Part A comprised 25 total subjects enrolled in dosing groups 1, 2, and 3 (0.06-, 0.12-, and 0.045-mg/kg, respectively). Median time to first ureter visualization was 10 minutes (all groups). The nerindocianine 0.06-mg/kg and 0.12-mg/kg groups had longer length of time of visualization than the 0.045-mg/kg group, resulting in the selection of 0.06 mg/kg as the near-optimal dose. Part B enrolled 16 total subjects in 2 groups dosed at 0.06 mg/kg. Efficacy analysis showed no statistically significant difference in composite scores with Firefly versus PINPOINT or 1588 AIM. CONCLUSION: Nerindocianine was well tolerated with visualization of the ureter demonstrated in 88.9% of the subjects through 90 minutes postdosing. No meaningful visualization differences were observed among the Food and Drug Administration-cleared surgical imaging systems used.
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Procedimientos Quirúrgicos Mínimamente Invasivos , Imagen Óptica , Uréter/diagnóstico por imagen , Uréter/cirugía , Adulto , Anciano , Femenino , Fluorescencia , Colorantes Fluorescentes/farmacología , Humanos , Indoles/farmacología , Laparoscopía/métodos , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Imagen Óptica/métodos , Cirugía Asistida por Computador/métodosRESUMEN
PURPOSE OF REVIEW: Novel therapies are needed for the treatment of recurrent cervical cancer. The best chemotherapy regimen to date has a response rate of 48% with an overall survival of 17 months, with limited options for second-line chemotherapy. Immunotherapy can induce a strong immune response in cervical cancer due to retained viral antigens and is reviewed in this article. RECENT FINDINGS: Current clinical trials include treatment with Listeria that elicits an immune response against the E7 oncoprotein and active vaccines against the E7 oncoprotein. Although the response rates to programmed cell death 1 (PD-1) inhibition alone have been modest, the landmark survival reported in these trials suggests the activity of these agents may not be measured by RECIST criteria. The KEYNOTE-158 trial has led to the approval of pembrolizumab in recurrent programmed cell death ligand 1 (PD-L1) positive cervical cancer. Combinations of programmed cell death 1 and anticytotoxic T-lymphocyte-associated protein 4 inhibitors (CTLA4) inhibitors have shown promising and durable activity. There is active research with new combinations of checkpoint inhibitors, as well as combinations of these drugs with chemotherapy and radiation, and other novel approaches. SUMMARY: Immune therapy has broad activity in cervical cancer. Responses to immunotherapy can be dramatic and durable. Continued work to find the optimal combination and setting for immunotherapy is ongoing.
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Inmunoterapia/métodos , Recurrencia Local de Neoplasia/terapia , Neoplasias del Cuello Uterino/terapia , Animales , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Femenino , Humanos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/inmunología , Vacunas contra Papillomavirus/inmunología , Vacunas contra Papillomavirus/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/inmunologíaRESUMEN
OBJECTIVE: The objective of this study was to evaluate the impact of a post-surgical restrictive opioid prescribing algorithm (ROPA) in gynecologic oncology patients. METHODS: This cohort study included gynecologic oncology patients undergoing any surgical procedure from 08/2018-7/2019 after implementation of a ROPA. Patients were compared to historical controls managed without a ROPA from 10/2016-9/2017. Patients were educated preoperatively about pain management goals, the ROPA, and opioid disposal. A 4-tiered system was developed to standardize prescriptions at discharge based on surgical complexity and inpatient opioid requirements. Patients were surveyed at their postoperative visit to assess home opioid use and satisfaction. Statistical analysis was performed using SPSS Statistics v.24. RESULTS: 2549 patients met inclusion criteria; 1321 in the historical control group and 1228 in the ROPA group. Demographics, including age, BMI, and performance status were similar. Compared with the control group, the average number of opioid pills prescribed was significantly lower in the ROPA group (30.5 vs 11.3; p < 0.001) along with the morphine milligram equivalents (MME) (152.5 MME vs. 83.3 MME; p < 0.001). The percentage of patients requiring opioid refill within 30 days was similar (13.0% vs. 12.6%; p = 0.71). 95.7% of patients surveyed were satisfied with their pain regimen. The total number of pills prescribed annually decreased from 34,130 in the control group to 13,888 in the ROPA group. CONCLUSIONS: A restrictive prescribing practice allows for a significantly lower number of opioids to be prescribed to postoperative patients while maintaining patient satisfaction. There was no increase in opioid refill requests using a ROPA in patients undergoing surgery.
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Analgésicos Opioides/administración & dosificación , Neoplasias de los Genitales Femeninos/cirugía , Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Dolor Postoperatorio/tratamiento farmacológico , Pautas de la Práctica en Medicina/organización & administración , Pautas de la Práctica en Medicina/estadística & datos numéricos , Adulto , Anciano , Analgésicos Opioides/efectos adversos , Prescripciones de Medicamentos/normas , Prescripciones de Medicamentos/estadística & datos numéricos , Registros Electrónicos de Salud/estadística & datos numéricos , Femenino , Ginecología/organización & administración , Ginecología/normas , Ginecología/estadística & datos numéricos , Implementación de Plan de Salud , Humanos , Oncología Médica/organización & administración , Oncología Médica/normas , Oncología Médica/estadística & datos numéricos , Persona de Mediana Edad , Epidemia de Opioides/prevención & control , Trastornos Relacionados con Opioides/epidemiología , Trastornos Relacionados con Opioides/etiología , Trastornos Relacionados con Opioides/prevención & control , Manejo del Dolor/métodos , Manejo del Dolor/normas , Manejo del Dolor/estadística & datos numéricos , Dolor Postoperatorio/etiología , Satisfacción del Paciente/estadística & datos numéricos , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/normas , Evaluación de Programas y Proyectos de Salud , Estudios Prospectivos , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: Women with persistent, recurrent, and/or metastatic cervical cancer have a poor prognosis. Even with the availability of cisplatin plus paclitaxel and bevacizumab, median overall survival (OS) is only 17.0 months, with median post-progression survival of approximately seven months. We studied the therapeutic vaccine, Axalimogene filolisbac (ADXS-HPV), in women who had progressed following at least one prior line of therapy (Gynecologic Oncology Group protocol 265/NCT01266460). METHODS: Volunteers ≥18 years with advanced cervical cancer and GOG performance status score of 0 or 1 were eligible for participation in this 2-stage, phase II trial. In stage 1, women received up to three doses of ADXS-HPV (1 × 109 colony-forming units in 250 mL IV over 15 min every 28 days) and were monitored for tumor progression. In stage 2, women were treated until progression, intolerable adverse events (AEs), or voluntary withdrawal of consent. Co-primary endpoints were safety and proportion of volunteers surviving ≥12 months. An estimated, combined (stages 1 + 2) 12-month OS of 35% was calculated from historical GOG cohorts to declare ADXS-HPV sufficiently active in this platinum-pre-treated population. Secondary endpoints were OS and progression-free survival (PFS). RESULTS: Among 50 evaluable volunteers, the 12-month OS was 38% (n = 19). Median OS was 6.1 months (95% CI: 4.3-12.1) and median PFS was 2.8 months (95% CI: 2.6-3.0). The most common treatment-related AEs were fatigue, chills, fever, nausea, and anemia. The majority of AEs were grade 1 or 2 and resolved spontaneously or with appropriate treatment. CONCLUSION: At the dose and schedule studied, ADXS-HPV immunotherapy was tolerable and met the protocol-specified benchmark for activity required to warrant further investigation in volunteers with cervical carcinoma.
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Vacunas contra el Cáncer/administración & dosificación , Listeria monocytogenes/inmunología , Proteínas E7 de Papillomavirus/inmunología , Neoplasias del Cuello Uterino/terapia , Adulto , Anciano , Vacunas contra el Cáncer/efectos adversos , Vacunas contra el Cáncer/inmunología , Resistencia a Antineoplásicos , Femenino , Humanos , Persona de Mediana Edad , Compuestos Organoplatinos/farmacología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/inmunologíaRESUMEN
Uterine clear cell cancer (UCCC) is a rare but aggressive disease. Due to its rarity, large, prospective studies focused on UCCC are exceedingly difficult therefore available data are generally from small, retrospective studies. There is also pertinent information from subsection analysis of larger studies that include UCCC and other histotypes. In 2009, the clinical practice committee of the Society of Gynecologic Oncology (SGO) published a review on UCCC aimed at guiding management. Since that publication, there have been developments which are relevant to UCCC, these include availability of data from landmark trials regarding adjuvant therapy, increasing utilization of sentinel lymph node approach and availability of immunotherapy as a treatment option. This SGO review is updated with all relevant, published information since 2009 considered clinically important for management of UCCC. In addition, it follows the new SGO's style for this type of publication which includes utilization of the question and answer format.
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Adenocarcinoma de Células Claras/terapia , Neoplasias Uterinas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Braquiterapia/métodos , Quimioradioterapia Adyuvante , Quimioterapia Adyuvante , Terapia Combinada , Femenino , Humanos , Inmunoterapia/métodos , Recurrencia Local de Neoplasia/terapia , Guías de Práctica Clínica como Asunto , Radioterapia Adyuvante , Estudios RetrospectivosRESUMEN
OBJECTIVE: To compare the perioperative morbidity and survival between abdominal radical hysterectomy (ARH) and robotic radical hysterectomy (RRH). METHODS: A retrospective cohort of patients undergoing radical hysterectomy for cervical cancer from 2010 to 2016 was identified. Patients with stage IB1 cervical cancer were included and were grouped by ARH vs. RRH. Tumor characteristics, perioperative complications, recurrence rate, progression-free survival (PFS), and overall survival (OS) were compared between groups. RESULTS: 105 patients were identified; 56 underwent ARH and 49 underwent RRH. Those who had ARH were more likely to have lesions that were ≥2â¯cm (62% vs. 39%, pâ¯=â¯0.02) and that were higher grade (pâ¯=â¯0.048). Other tumor characteristics were similar between groups. There was no difference in perioperative complication rates between groups. Additionally, there were no differences in recurrence risk (RR) (14% vs. 24%, pâ¯=â¯0.22), progression-free survival (PFS) (pâ¯=â¯0.28), or overall survival (OS) (pâ¯=â¯0.16). However, in those with tumors ≥2â¯cm there was a higher risk of recurrence in the overall cohort (30% vs. 8%, pâ¯=â¯0.006), and a shorter PFS in the RRH group (HR 0.31, pâ¯=â¯0.04). On multivariate analysis patients that underwent ARH or had tumorsâ¯<â¯2â¯cm had a lower likelihood of recurrence (HR 0.38, pâ¯=â¯0.04; HR 0.175, pâ¯=â¯0.002) and death (HR 0.21, pâ¯=â¯0.029; HR 0.15, pâ¯=â¯0.02). CONCLUSION: Perioperative morbidity was similar between those undergoing ARH vs. RRH for IB1 cervical cancer. Patients with tumorsâ¯≥â¯2â¯cm undergoing RRH had a shorter PFS compared to ARH. On multivariate analysis, RRH and tumor sizeâ¯≥â¯2â¯cm were independently associated with recurrence and death in this population.
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Histerectomía/métodos , Complicaciones Intraoperatorias/epidemiología , Recurrencia Local de Neoplasia/epidemiología , Complicaciones Posoperatorias/epidemiología , Procedimientos Quirúrgicos Robotizados/métodos , Neoplasias del Cuello Uterino/cirugía , Adulto , Femenino , Humanos , Histerectomía/efectos adversos , Complicaciones Intraoperatorias/etiología , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Estadificación de Neoplasias , Complicaciones Posoperatorias/etiología , Supervivencia sin Progresión , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Tasa de Supervivencia , Factores de Tiempo , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patologíaRESUMEN
OBJECTIVES: Opportunistic salpingectomy is a cost-effective strategy recommended for ovarian cancer (OvCa) risk reduction at the time of gynecologic surgery in women who have completed childbearing. We aimed to evaluate the cost-effectiveness of opportunistic salpingectomy compared to standard tubal ligation (TL) during cesarean delivery. STUDY DESIGN: A cost-effectiveness analysis using decision modeling to compare opportunistic salpingectomy to TL at the time of cesarean using probabilities of procedure completion derived from a trial. Probability and cost inputs were derived from local data and the literature. The primary outcome was the incremental cost-effectiveness ratio (ICER) in 2017â¯U.S. dollars per quality-adjusted life year (QALY) at a cost-effectiveness threshold of $100,000/QALY. One- and two-way sensitivity analyses were performed for all variables. A probabilistic sensitivity analysis determined the proportion of simulations in which each strategy would be cost-effective. RESULTS: Opportunistic salpingectomy was cost-effective compared to TL with an ICER of $26,616 per QALY. In 10,000 women desiring sterilization with cesarean, opportunistic salpingectomy would result in 17 fewer OvCa diagnoses, 13 fewer OvCa deaths, and 25 fewer unintended pregnancies compared to TL - with an associated cost increase of $4.7 million. The model was sensitive only to OvCa risk reduction from salpingectomy and TL. Opportunistic salpingectomy was not cost-effective if its cost was >$3163.74 more than TL, if the risk-reduction of salpingectomy was <41%, or if the risk-reduction of TL was >46%. In probabilistic sensitivity analysis opportunistic salpingectomy was cost effective in 75% of simulations. CONCLUSIONS: In women undergoing cesarean with sterilization, opportunistic salpingectomy is likely cost-effective and may be cost-saving in comparison to TL for OvCa risk reduction.