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1.
N Engl J Med ; 388(23): 2159-2170, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-36972022

RESUMO

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.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Endométrio , Feminino , Humanos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Reparo de Erro de Pareamento de DNA , Método Duplo-Cego , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos
3.
Gynecol Oncol ; 175: 121-127, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37356312

RESUMO

BACKGROUND: The dependent coverage mandate in the 2010 Affordable Care Act (ACA) allows young adults to stay on a parent's private insurance through age 26. While this mandate is associated with gains in insurance and early-stage cancer diagnosis, its long-term impact on survival is unknown. OBJECTIVE: To compare insurance coverage, stage at diagnosis, and overall survival in patients with gynecologic cancer before and after the ACA's dependent coverage mandate. METHODS: Using difference-in-differences (DiD) analysis, we conducted a retrospective cohort study comparing outcomes before and after the implementation of the ACA's dependent coverage mandate in young patients with gynecologic cancer, ages 18-26 years (exposure group) to patients ages 27-35 (control group). We analyzed insurance coverage, stage at diagnosis, and 1, 2, and 3-year overall survival, adjusted for age and comorbidities, utilizing the 2004-2017 National Cancer Database. IRB exemption was obtained. RESULTS: A total of 3553 cases pre-reform and 4535 cases post-reform were identified for patients 18-26 years compared to 14,420 pre-reform and 19,821 post-reform for patients age 27-35. The ACA's dependent coverage mandate was associated with significant gains in insurance (DiD 2%, 95% CI 0.6-3.5) and early-stage diagnosis (3.1%, 95% CI 0.6-5.7). The ACA's dependent coverage mandate was associated with significant gains in 3-year survival (2.4%, 95% CI 0.4-4.3) and non-significant gains in 1 and 2-year survival. CONCLUSION: The ACA's dependent coverage mandate is associated with improvements in early-stage diagnosis and survival for young patients with gynecologic cancer. Maintaining insurance gains-and expanding to the remaining uninsured-are critical for the health of young patients with gynecologic cancer.


Assuntos
Neoplasias dos Genitais Femininos , Patient Protection and Affordable Care Act , Adulto Jovem , Estados Unidos , Humanos , Feminino , Adulto , Estudos Retrospectivos , Cobertura do Seguro , Pessoas sem Cobertura de Seguro de Saúde , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/terapia , Seguro Saúde
4.
Gynecol Oncol ; 174: 98-105, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37172411

RESUMO

OBJECTIVE: To estimate the prevalence of, and identify risk factors associated with, endometrial hyperplasia and/or cancer (EH/EC) in patients ≤45 years old undergoing endometrial sampling for abnormal uterine bleeding (AUB). METHODS: We performed a retrospective cohort study of patients 18-45 years old with AUB who underwent endometrial sampling between 2016 and 2019 within a US-based multi-hospital system using billing code queries. We used multivariable Poisson regression to identify factors associated with EH/EC and calculated prevalence stratified by these factors. We estimated predicted probabilities within combinations of characteristics in order to examine the range of risk in this population. RESULTS: Among 3175 patients, median age was 39 years (interquartile range [IQR]:35-43) and BMI was 29.7 kg/m2 (IQR: 24.2-36.9). Thirty-nine percent were non-Hispanic White, 41% non-Hispanic Black, 9% Hispanic, and 11% Asian/Other/Unknown. BMI and polycystic ovarian syndrome (PCOS) were associated with higher EH/EC risk; non-Hispanic Black race was associated with lower risk. EH/EC prevalence ranged from 2% in BMI <25 to 16% in BMI ≥50 kg/m2 (p-trend <0.001). These prevalence estimates differed by race/ethnicity with the lowest estimates in non-Hispanic Black patients (0.5% BMI <25 vs. 9% BMI ≥50) and highest in Hispanic patients (1.5% BMI <25 vs. 33% BMI ≥50). Accounting for combinations of risk factors, predicted probabilities were highest - 34-36% - among patients with PCOS, diabetes, BMI ≥50, and Hispanic or Asian/Other/Unknown race/ethnicity. CONCLUSIONS: When accounting for combinations of key risk factors, risk of EH/EC in patients ≤45 years old with AUB ranges widely; the more nuanced estimates of risk presented here could help inform clinical decision-making about endometrial sampling in this population.


Assuntos
Hiperplasia Endometrial , Neoplasias do Endométrio , Doenças Uterinas , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Hiperplasia Endometrial/epidemiologia , Hiperplasia Endometrial/complicações , Estudos Retrospectivos , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/complicações , Endométrio , Fatores de Risco
5.
Gynecol Oncol ; 177: 86-94, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37657193

RESUMO

OBJECTIVE: To investigate the incidence of MAPK/ERK pathway genomic alterations among patients with gynecologic malignancies. METHODS: We accessed the American Association of Cancer Research Genomics Evidence of Neoplasia Information Exchange publicly available dataset (v13.0). Patients with malignant tumors of the ovary, uterus, and cervix were identified. Following stratification by tumor site and histology, we examined the prevalence of MAPK/ERK pathway gene alterations (somatic mutation, and/or structural chromosome alterations). We included the following RAS-MAPK pathway genes known to be implicated in the dysregulation of the pathway; KRAS, NRAS, BRAF, HRAS, MAP2K1, RAF1, PTPN11, NF1, and ARAF. Data from the OncoKB database, as provided by cBioPortal, were utilized to determine pathogenic gene alterations. RESULTS: We identified a total of 10,233 patients with gynecologic malignancies; 48.2% (n = 4937) with ovarian, 45.2% (n = 4621) with uterine and 6.6% (n = 675) with cervical cancer respectively. The overall incidence of MAPK pathway gene alterations was 21%; the most commonly altered gene was KRAS (13%), followed by NF1 (7%), NRAS (1.3%), and BRAF (1.2%). The highest incidence was observed among patients with mucinous ovarian (71%), low-grade serous ovarian (48%), endometrioid ovarian (37%), and endometrioid endometrial carcinoma (34%). CONCLUSIONS: Approximately 1 in 5 patients with a gynecologic tumor harbor a MAPK/ERK pathway genomic alteration. Novel treatment strategies capitalizing on these alterations are warranted.

6.
Int J Gynecol Cancer ; 33(9): 1331-1344, 2023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37591609

RESUMO

Compared with high-grade serous carcinoma, low-grade serous carcinoma of the ovary or peritoneum is a less frequent epithelial ovarian cancer type that is poorly sensitive to chemotherapy and affects younger women, many of whom endure years of ineffective treatments and poor quality of life. The pathogenesis of this disease and its management remain incompletely understood. However, recent advances in the molecular characterization of the disease and identification of novel targeted therapies with activity in low-grade serous carcinoma offer the promise of improved outcomes. To update clinicians regarding recent scientific and clinical trial advancements and discuss unanswered questions related to low-grade serous carcinoma diagnosis and treatment, a panel of experts convened for a workshop in October 2022 to develop a consensus document addressing pathology, translational research, epidemiology and risk, clinical management, and ongoing research. In addition, the patient perspective was discussed. The recommendations developed by this expert panel-presented in this consensus document-will guide practitioners in all settings regarding the clinical management of women with low-grade serous carcinoma and discuss future opportunities to improve research and patient care.


Assuntos
Cistadenocarcinoma Papilar , Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Neoplasias Peritoneais , Humanos , Feminino , Consenso , Qualidade de Vida , Carcinoma Epitelial do Ovário/terapia , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/terapia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapia
7.
Int Urogynecol J ; 34(11): 2751-2758, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37449987

RESUMO

INTRODUCTION AND HYPOTHESIS: The objective was to study the effect of immediate pre-operative warm-up using virtual reality simulation on intraoperative robot-assisted laparoscopic hysterectomy (RALH) performance by gynecology trainees (residents and fellows). METHODS: We randomized the first, non-emergent RALH of the day that involved trainees warming up or not warming up. For cases assigned to warm-up, trainees performed a set of exercises on the da Vinci Skills Simulator immediately before the procedure. The supervising attending surgeon, who was not informed whether or not the trainee was assigned to warm-up, assessed the trainee's performance using the Objective Structured Assessment for Technical Skill (OSATS) and the Global Evaluative Assessment of Robotic Skills (GEARS) immediately after each surgery. RESULTS: We randomized 66 cases and analyzed 58 cases (30 warm-up, 28 no warm-up), which involved 21 trainees. Attending surgeons rated trainees similarly irrespective of warm-up randomization with mean (SD) OSATS composite scores of 22.6 (4.3; warm-up) vs 21.8 (3.4; no warm-up) and mean GEARS composite scores of 19.2 (3.8; warm-up) vs 18.8 (3.1; no warm-up). The difference in composite scores between warm-up and no warm-up was 0.34 (95% CI: -1.44, 2.13), and 0.34 (95% CI: -1.22, 1.90) for OSATS and GEARS respectively. Also, we did not observe any significant differences in each of the component/subscale scores within OSATS and GEARS between cases assigned to warm-up and no warm-up. CONCLUSION: Performing a brief virtual reality-based warm-up before RALH did not significantly improve the intraoperative performance of the trainees.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Feminino , Humanos , Simulação por Computador , Histerectomia , Competência Clínica
8.
Gynecol Oncol ; 167(2): 146-151, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36154761

RESUMO

OBJECTIVES: Patients with gynecologic malignancies may have varied responses to COVID-19 infection. We aimed to describe clinical courses, treatment changes, and short-term clinical outcomes for gynecologic oncology patients with concurrent COVID-19 in the United States. METHODS: The Society of Gynecologic Oncology COVID-19 and Gynecologic Cancer Registry was created to capture clinical courses of gynecologic oncology patients with COVID-19. Logistic regression models were employed to evaluate factors for an association with hospitalization and death, respectively, within 30 days of COVID-19 diagnosis. RESULTS: Data were available for 348 patients across 7 institutions. At COVID-19 diagnosis, 125 patients (36%) had active malignancy. Delay (n = 88) or discontinuation (n = 10) of treatment due to COVID-19 infection occurred in 28% with those on chemotherapy (53/88) or recently receiving surgery (32/88) most frequently delayed. In addition to age, performance status, diabetes, and specific COVID symptoms, both non-White race (adjusted odds ratio (aOR) = 3.93, 95% CI 2.06-7.50) and active malignancy (aOR = 2.34, 95% CI 1.30-4.20) were associated with an increased odds of hospitalization. Eight percent of hospitalized patients (8/101) died of COVID-19 complications and 5% (17/348) of the entire cohort died within 30 days after diagnosis. CONCLUSIONS: Gynecologic oncology patients diagnosed with COVID-19 are at risk for hospitalization, delay of anti-cancer treatments, and death. One in 20 gynecologic oncology patients with COVID-19 died within 30 days after diagnosis. Racial disparities exist in patient hospitalizations for COVID-19, a surrogate of disease severity. Additional studies are needed to determine long-term outcomes and the impact of race.


Assuntos
COVID-19 , Neoplasias dos Genitais Femininos , Humanos , Feminino , Estados Unidos/epidemiologia , COVID-19/terapia , Neoplasias dos Genitais Femininos/terapia , Teste para COVID-19 , Hospitalização , Sistema de Registros , Estudos Retrospectivos
9.
J Pathol ; 253(1): 119-128, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33016334

RESUMO

Clinicopathological evidence supports endometrial atypical hyperplasia (AH) or endometrial intraepithelial neoplasia as the precursor of uterine endometrioid carcinoma (EC), the most common gynecologic malignancy. However, the pathogenic progression from AH to EC remains unclear. Here, we employed whole-exome sequencing to identify somatic mutations and copy number changes in micro-dissected lesions from 30 pairs of newly diagnosed AH and EC. We found that all but one pair of AHs shared the same DNA mismatch repair status as their corresponding ECs. The percentage of common mutations between AH lesions and corresponding ECs varied significantly, ranging from 0.1% to 82%. Microsatellite stable AHs had fewer cancer driver mutations than ECs (5 versus 7, p = 0.017), but among microsatellite unstable AHs and ECs there was no difference in mutational numbers (36 versus 38, p = 0.65). As compared to AH specimens, 19 (79%) of 24 microsatellite stable EC tumors gained new cancer driver mutations, most of which involved PTEN, ARID1A, PIK3CA, CTNNB1, or CHD4. Our results suggest that some AH lesions are the immediate precursor of ECs, and progression depends on acquisition of additional cancer driver mutations. However, a complex clonal relationship between AH and EC can also be appreciated, as in some cases both lesions diverge very early or arise independently, thus co-developing with distinct genetic trajectories. Our genome-wide profile of mutations in AH and EC shines new light on the molecular landscape of tumor progression. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Endometrioide/genética , Transformação Celular Neoplásica/genética , Neoplasias do Endométrio/genética , Sequenciamento do Exoma , Mutação , Lesões Pré-Cancerosas/genética , Adulto , Idoso , Baltimore , Pequim , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/cirurgia , Transformação Celular Neoplásica/patologia , Variações do Número de Cópias de DNA , Análise Mutacional de DNA , Progressão da Doença , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Dosagem de Genes , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Fenótipo , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/cirurgia
10.
Int J Gynecol Cancer ; 32(6): 769-780, 2022 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-35459709

RESUMO

OBJECTIVE: To identify patient, clinical and hospital factors associated with long-term survival (≥10 years) in women with serous ovarian cancer. METHODS: This National Cancer Database cohort study included women with stage II-IV serous ovarian cancer. Multivariate logistic regression models were used to examine the association of long-term survival with patient (race, insurance, location, household income, education, distance traveled), clinical (age, comorbidities, stage, grade, primary treatment) and hospital factors (region, institution, hospital volume ≥20). RESULTS: Of the 4640 women identified, 12% (n=561) experienced long-term survival. Median overall survival was 41 months (95% CI 39 to 42). The odds of long-term survival were lower for women with public or no insurance (adjusted OR 0.71, 95% CI 0.55 to 0.92), age ≥75 years (0.33, 0.22 to 0.50), any comorbidities (0.70, 0.54 to 0.92), higher stage (stage III: 0.31, 0.25 to 0.41; stage IV: 0.16, 0.12 to 0.22), and moderately/poorly differentiated, undifferentiated, or tumors of unknown grade (moderately/poorly differentiated: 0.30, 0.20 to 0.47; undifferentiated: 0.28, 0.17 to 0.47; unknown: 0.30, 0.18 to 0.50). The odds of long-term survival among women who were publicly insured were lower with neoadjuvant chemotherapy (0.13, 0.04 to 0.044) and higher with optimal cytoreduction (2.24, 1.49 to 3.36). Among women who were privately insured, the odds of long-term survival were higher with optimal cytoreduction (1.99, 1.46 to 2.70) and unaffected by neoadjuvant chemotherapy. CONCLUSIONS: While immutable clinical factors such as age, stage, and grade are associated with long-term survival in women with serous ovarian cancer, modifiable factors, such as insurance type, optimal cytoreductive status, and neoadjuvant chemotherapy provide an opportunity for targeted improvement in care with potential to affect long-term patient outcomes.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Idoso , Carcinoma Epitelial do Ovário/patologia , Quimioterapia Adjuvante , Estudos de Coortes , Cistadenocarcinoma Seroso/tratamento farmacológico , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco
11.
Gynecol Oncol ; 160(1): 322-332, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33160694

RESUMO

Uterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer. Multimodality treatment with surgery, radiotherapy, and chemotherapy is commonly used, given its propensity for extrauterine spread, distant recurrences, and poor prognosis. However, the use of molecularly-based therapy is expanding. Here, we review key molecular features of USC, discuss current management, and assess the landscape of novel therapies and combinations.


Assuntos
Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/genética , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/genética , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cistadenocarcinoma Seroso/metabolismo , Feminino , Humanos , Terapia de Alvo Molecular , Mutação , Compostos de Fenilureia/administração & dosagem , Quinolinas/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Trastuzumab/administração & dosagem , Proteína Supressora de Tumor p53/genética , Neoplasias Uterinas/metabolismo
12.
Gynecol Oncol ; 163(1): 93-99, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34372971

RESUMO

OBJECTIVE: Due to previously reported trastuzumab safety concerns and the scant data available in endometrial cancer patients, we sought to assess the safety, tolerability and toxicity profile of trastuzumab in patients with advanced/recurrent uterine serous carcinoma (USC) that overexpress HER2/neu in our multicenter randomized phase II trial. METHODS: Patients were randomized 1:1 to receive carboplatin/paclitaxel (C/P) for 6 cycles ± trastuzumab (T) with the experimental arm continuing to receive single agent trastuzumab maintenance treatment until disease progression/toxicity. Progression-free-survival was the primary endpoint; overall-survival and toxicity were secondary endpoints. Adverse events (AEs) were compared between treatment arms. RESULTS: There were 28 patients in the C/P arm and 32 patients in the experimental (C/P + T) arm. Fifty-eight patients (97%) experienced 977 treatment-related AEs of which 875 (89.6%) were low-grade (grade 1-2) and 102 (10.4%) were high-grade (grade 3-5). The mean ± standard deviation of AEs per patient was 15.5 ± 16.3 in the C/P arm and 17.0 ± 16.0 in the C/P + T arm. Gastrointestinal AEs were the most common in both arms (n = 155, 15.7%) of which 94.2% were low-grade (n = 146). Importantly, no significant difference between treatment arms was detected in any system-organ class of AE including cardiac AE. Five (17%) of 29 patients who received prolonged trastuzumab maintenance therapy had no sign of cumulative toxicity after an average (range) of 5.1 (4.2-6.3) years. CONCLUSIONS: Trastuzumab appears to be safe and has a manageable toxicity profile both when used in combination with chemotherapy and when used for single agent maintenance in patients with HER2/neu positive USC. This safety profile is reassuring given the proven efficacy of trastuzumab in advanced/recurrent HER2/neu positive USC.


Assuntos
Cistadenocarcinoma Seroso/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Receptor ErbB-2/análise , Trastuzumab/efeitos adversos , Neoplasias Uterinas/tratamento farmacológico , Idoso , Cistadenocarcinoma Seroso/química , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/química , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Uterinas/química , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/patologia
13.
Gynecol Oncol ; 162(3): 532-538, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34217544

RESUMO

PURPOSE: The Sedlis criteria define risk factors for recurrence warranting post-hysterectomy radiation for early-stage cervical cancer; however, these factors were defined for squamous cell carcinoma (SCC) at an estimated recurrence risk of ≥30%. Our study evaluates and compares risk factors for recurrence for cervical SCC compared with adenocarcinoma (AC) and develops histology-specific nomograms to estimate risk of recurrence and guide adjuvant treatment. METHODS: We performed an ancillary analysis of GOG 49, 92, and 141, and included stage I patients who were surgically managed and received no neoadjuvant/adjuvant therapy. Multivariable Cox proportional hazards models were used to evaluate independent risk factors for recurrence by histology and to generate prognostic histology-specific nomograms for 3-year recurrence risk. RESULTS: We identified 715 patients with SCC and 105 with AC; 20% with SCC and 17% with AC recurred. For SCC, lymphvascular space invasion (LVSI: HR 1.58, CI 1.12-2.22), tumor size (TS ≥4 cm: HR 2.67, CI 1.67-4.29), and depth of invasion (DOI; middle 1/3, HR 4.31, CI 1.81-10.26; deep 1/3, HR 7.05, CI 2.99-16.64) were associated with recurrence. For AC, only TS ≥4 cm, was associated with recurrence (HR 4.69, CI 1.25-17.63). For both histologies, there was an interaction effect between TS and LVSI. For those with SCC, DOI was most associated with recurrence (16% risk); for AC, TS conferred a 15% risk with negative LVSI versus a 25% risk with positive LVSI. CONCLUSIONS: Current treatment standards are based on the Sedlis criteria, specifically derived from data on SCC. However, risk factors for recurrence differ for squamous cell and adenocarcinoma of the cervix. Histology-specific nomograms accurately and linearly represent risk of recurrence for both SCC and AC tumors and may provide a more contemporary and tailored tool for clinicians to base adjuvant treatment recommendations to their patients with cervical cancer.


Assuntos
Recidiva Local de Neoplasia/patologia , Nomogramas , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Neoplasias do Colo do Útero/cirurgia
14.
Int J Gynecol Cancer ; 31(8): 1165-1174, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34210768

RESUMO

The incidence and mortality rates from endometrial cancer continue to increase worldwide, while rates in most other cancers have either plateaued or declined considerably. Uterine serous carcinoma represents a fraction of all endometrial malignancies each year, yet this histology is responsible for nearly 40% of all endometrial cancer-related deaths. These deaths disproportionately affect black women, who have higher rates of advanced disease at diagnosis. Molecular genetic analyses reveal major alterations including TP53 mutation, PIK3CA mutation/amplification, ERBB2 amplification, CCNE1 amplification, FBXW7 mutation/deletion, PPP2R1A mutation, and somatic mutations involving homologous recombination genes. Clinical risk factors for uterine serous carcinoma include advancing age, a history of breast cancer, tamoxifen usage, and the hereditary breast-ovarian cancer syndrome. Surgery remains the cornerstone of treatment. Recent advances in our understanding of uterine serous carcinoma molecular drivers have led to development of targeted therapeutics that promise improved outcomes for patients. Overexpression or amplification of HER2 in uterine serous carcinoma carries a poor prognosis; yet this actionable target has led to the incorporation of several anti-HER2 therapies, including trastuzumab which, when added to conventional chemotherapy, is associated with improved survival for women with advanced and recurrent HER2-positive disease. The combination of pembrolizumab and lenvatinib is also a promising targeted treatment strategy for women with uterine serous carcinoma, with a recent phase II study suggesting a 50% response rate in women with recurrent disease. Several trials examining additional targeted agents are ongoing. Despite years of stalled progress, meaningful, tailored treatment options are emerging for patients with this uncommon and biologically aggressive endometrial cancer subtype.


Assuntos
Cistadenocarcinoma Seroso/terapia , Neoplasias Uterinas/terapia , Feminino , Humanos , Incidência , Prognóstico , Estudos Retrospectivos , Fatores de Risco
15.
J Minim Invasive Gynecol ; 28(2): 179-203, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32827721

RESUMO

This is the first Enhanced Recovery After Surgery (ERAS) guideline dedicated to standardizing and optimizing perioperative care for women undergoing minimally invasive gynecologic surgery. The guideline was rigorously formulated by an American Association of Gynecologic Laparoscopists Task Force of US and Canadian gynecologic surgeons with special interest and experience in adapting ERAS practices for patients requiring minimally invasive gynecologic surgery. It builds on the 2016 ERAS Society recommendations for perioperative care in gynecologic/oncologic surgery by serving as a more comprehensive reference for minimally invasive endoscopic and vaginal surgery for both benign and malignant gynecologic conditions. For example, the section on preoperative optimization provides more specific recommendations derived from the ambulatory surgery and anesthesia literature for the management of anemia, hyperglycemia, and obstructive sleep apnea. Recommendations pertaining to multimodal analgesia account for the recent Food and Drug Administration warnings about respiratory depression from gabapentinoids. The guideline focuses on workflows important to high-value care in minimally invasive surgery, such as same-day discharge, and tackles controversial issues in minimally invasive surgery, such as thromboprophylaxis. In these ways, the guideline supports the American Association of Gynecologic Laparoscopists and our collective mission to elevate the quality and safety of healthcare for women through excellence in clinical practice.


Assuntos
Recuperação Pós-Cirúrgica Melhorada/normas , Doenças dos Genitais Femininos/cirurgia , Procedimentos Cirúrgicos em Ginecologia/reabilitação , Procedimentos Cirúrgicos em Ginecologia/normas , Procedimentos Cirúrgicos Minimamente Invasivos/reabilitação , Procedimentos Cirúrgicos Ambulatórios/métodos , Procedimentos Cirúrgicos Ambulatórios/reabilitação , Procedimentos Cirúrgicos Ambulatórios/normas , Anestesia/métodos , Anestesia/normas , Anticoagulantes/uso terapêutico , Consenso , Aconselhamento Diretivo/métodos , Aconselhamento Diretivo/normas , Feminino , Doenças dos Genitais Femininos/reabilitação , Procedimentos Cirúrgicos em Ginecologia/métodos , Ginecologia/organização & administração , Ginecologia/normas , Humanos , Laparoscopia/métodos , Laparoscopia/reabilitação , Laparoscopia/normas , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/normas , Alta do Paciente/normas , Educação de Pacientes como Assunto/métodos , Educação de Pacientes como Assunto/normas , Assistência Perioperatória/métodos , Assistência Perioperatória/normas , Período Pré-Operatório , Sociedades Médicas/organização & administração , Sociedades Médicas/normas , Infecção da Ferida Cirúrgica/prevenção & controle , Tromboembolia Venosa/prevenção & controle
16.
Histopathology ; 76(3): 354-365, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31564060

RESUMO

AIMS: Hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome is caused by germline mutations in the Fumarate hydratase (FH) gene. In young women, the syndrome often presents with symptomatic uterine leiomyomas, leading to myomectomy or hysterectomy. In this study, we aimed to investigate the incidence and mutational profiles of FH-negative leiomyomas from young patients, thus allowing for early identification and triage of syndromic patients for surveillance. METHODS AND RESULTS: We evaluated 153 cases of uterine leiomyomas from women aged up to 30 years for loss of FH expression by tissue microarray (TMA)-based immunohistochemical staining. Mutational analysis of tumours with loss of FH was carried out by polymerase chain reaction (PCR) amplification of 10 exons within the FH gene and subsequent Sanger sequencing. The status of promoter methylation was assessed by bisulphite sequencing. Loss of FH protein expression was detected in seven (4.6%) of 153 tested uterine leiomyomas from young patients. All FH-negative leiomyomas displayed staghorn vasculature and fibrillary/neurophil-like cytoplasm. We found that six (86%) of seven FH-negative tumours detected by immunohistochemistry harboured FH mutations, 50% of which contained germline mutations. In particular, the germline mutational rate in FH gene was 2.0% (three of 153 cases). Bisulphite sequencing analysis failed to detect promoter methylation in any of the seven tumours. CONCLUSION: Our study showed a relatively high rate of FH germline mutation in FH-negative uterine leiomyomas from patients aged up to 30 years. While genetic mutations confer protein expression loss, epigenetic regulation of the FH gene appears to be unrelated to this phenotype.


Assuntos
Fumarato Hidratase/genética , Leiomioma/genética , Leiomiomatose/genética , Síndromes Neoplásicas Hereditárias/genética , Neoplasias Cutâneas/genética , Neoplasias Uterinas/genética , Adolescente , Adulto , Análise Mutacional de DNA , Feminino , Fumarato Hidratase/metabolismo , Mutação em Linhagem Germinativa , Humanos , Imuno-Histoquímica , Leiomioma/enzimologia , Leiomioma/patologia , Leiomiomatose/enzimologia , Leiomiomatose/patologia , Mutação , Síndromes Neoplásicas Hereditárias/enzimologia , Síndromes Neoplásicas Hereditárias/patologia , Prevalência , Estudos Retrospectivos , Neoplasias Cutâneas/enzimologia , Neoplasias Cutâneas/patologia , Análise Serial de Tecidos , Neoplasias Uterinas/enzimologia , Neoplasias Uterinas/patologia , Adulto Jovem
17.
Gynecol Oncol ; 156(3): 744-745, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31955860

RESUMO

OBJECTIVE/BACKGROUND: Laparoscopic splenectomy is a potential surgical option for the treatment of isolated gynecologic cancer recurrence to the spleen [1-7]. The purpose of this video is to demonstrate a step-by-step approach for laparoscopic splenectomy in the setting of recurrent, oligometastatic ovarian cancer. METHODS: We present the case of a 47-year-old female with recurrent, platinum-sensitive high-grade serous ovarian cancer. A computer tomographic scan demonstrated an isolated 1.5 × 1.0 cm recurrence in the splenic hilum. A laparoscopic secondary cytoreduction with splenectomy was planned. The surgical procedure was recorded via the video camera tower, and the key steps for a laparoscopic splenectomy were identified and highlighted. RESULTS: The indications for secondary cytoreductive surgery, the appropriate candidates for minimally invasive surgery, patient positioning principles to set the surgeon up for success, and left upper quadrant anatomy are reviewed. In the surgical case and in the setting of hilar disease, the technique and rationale for ligating the major splenic ligaments in a particular order are reviewed. The procedure for isolating and ligating the dominant vascular structures - the splenic artery and vein - are reviewed. Finally, perioperative and oncologic outcomes, including an estimated blood loss of 100 cc, operative time of 3 h, a disease-free interval and "no evidence of disease" status after chemotherapy at 14 months, are emphasized. CONCLUSIONS: In this video, both anatomical references and the surgical technique for a laparoscopic splenectomy in the setting of recurrent ovarian cancer are illustrated. We demonstrate that laparoscopic splenectomy is feasible and safe with proper patient selection and positioning as well as meticulous surgical technique.


Assuntos
Cistadenocarcinoma Seroso/cirurgia , Procedimentos Cirúrgicos de Citorredução/métodos , Procedimentos Cirúrgicos em Ginecologia/métodos , Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/cirurgia , Esplenectomia/métodos , Feminino , Humanos , Pessoa de Meia-Idade
18.
Gynecol Oncol ; 158(1): 16-24, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32386911

RESUMO

OBJECTIVES: The COVID-19 pandemic has consumed considerable resources and has impacted the delivery of cancer care. Patients with cancer may have factors which place them at high risk for COVID 19 morbidity or mortality. Highly immunosuppressive chemotherapy regimens and possible exposure to COVID-19 during treatment may put patients at additional risk. The Society of Gynecologic Oncology convened an expert panel to address recommendations for best practices during this crisis to minimize risk to patients from deviations in cancer care and from COVID-19 morbidity. METHODS: An expert panel convened to develop initial consensus guidelines regarding anti-neoplastic therapy during the COVID-19 pandemic with respect to gynecologic cancer care and clinical trials. RESULTS: COVID-19 poses special risks to patients who are older, have medical co-morbidities, and cancer. In addition, this pandemic will likely strain resources, making delivery of cancer care or conduct of clinical trials unpredictable. Recommendations are to limit visits and contact with health care facilities by using telemedicine when appropriate, and choosing regimens which require less frequent visits and which are less immunosuppressive. Deviations will occur in clinical trials as a result of limited resources, and it is important to understand regulatory obligations to trial sponsors as well as to the IRB to ensure that clinical trial and patient safety oversight are maintained. CONCLUSIONS: The ongoing crisis will strain resources needed to deliver cancer care. When alterations to the delivery of care are mandated, efforts should be taken to minimize risks and maximize safety while approximating standard practice.


Assuntos
Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/normas , Infecções por Coronavirus/prevenção & controle , Neoplasias dos Genitais Femininos/terapia , Oncologia/métodos , Oncologia/normas , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , COVID-19 , Infecções por Coronavirus/transmissão , Feminino , Neoplasias dos Genitais Femininos/tratamento farmacológico , Neoplasias dos Genitais Femininos/virologia , Humanos , Pneumonia Viral/transmissão , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas
19.
Gynecol Oncol ; 157(2): 348-356, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32085863

RESUMO

OBJECTIVE: Our objectives were 1) to compare the efficacy of progestin therapy combined with metformin (Prog-Met) to Prog alone as primary fertility sparing treatment in women with atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) or early-stage endometrioid carcinoma (EC), and 2) to analyze the proportion of women achieving live birth following treatment. METHODS: A retrospective cohort study of all reproductive-aged women with AH/IN or EC treated with Prog ± Met from 1999-2018 was conducted. Complete response (CR) was assessed and Kaplan-Meier analysis used to calculate time to CR. Comparison of potential response predictors was performed with multivariable Cox regression models. RESULTS: Ninety-two women met criteria; 59% (n = 54) were treated for AH/EIN and 41% (n = 38) for EC. Their median age, body mass index, and follow up time was 35 years, 37.7 kg/m2, and 28.4 months, respectively. Fifty-eight women (63%) received Prog and 34 (37%) received Prog-Met. Overall, 79% (n = 73) of subjects responded to treatment with a CR of 69% (n = 63). There was no difference in CR (p = 0.90) or time to CR (p = 0.31) between the treatment cohorts. Overall, 22% experienced a disease recurrence. On multivariable analysis, EC histology was the only covariate associated with a decreased Prog response (HR 0.48; p = 0.007). Only 17% of the cohort achieved a live-birth pregnancy, the majority of which required assisted reproductive technologies (81%) and occurred in the Prog treatment group. CONCLUSIONS: Our study does not support the use of Prog-Met therapy for treatment of AH/EIN or EC. Additionally, fewer than 20% of women achieved a live-birth pregnancy during the study period, with most requiring ART.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma in Situ/tratamento farmacológico , Hiperplasia Endometrial/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Preservação da Fertilidade/métodos , Nascido Vivo , Adulto , Carcinoma in Situ/patologia , Estudos de Coortes , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Metformina/administração & dosagem , Recidiva Local de Neoplasia/patologia , Gravidez , Resultado da Gravidez , Progestinas/administração & dosagem , Estudos Retrospectivos
20.
Gynecol Oncol ; 159(1): 17-22, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32709539

RESUMO

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) has emerged as an important prognostic and therapeutic target in advanced stage and recurrent uterine serous carcinoma (USC). The significance of tumoral HER2 expression in early-stage disease has not been established. METHODS: This multi-center cohort study included women with stage I USC treated from 2000 to 2019. Demographic, treatment, recurrence, and survival data were collected. Immunohistochemistry (IHC) was performed for HER2 and scored 0-3+. Equivocal IHC results (2+) were further tested with fluorescence in-situ hybridization (FISH). HER2 positivity was defined as 3+ IHC or FISH positive. RESULTS: One hundred sixty-nine patients with stage I USC were tested for HER2; 26% were HER2-positive. There were no significant differences in age, race, stage, adjuvant therapy, or follow-up duration between the HER2-positive and negative cohorts. Presence of lymph-vascular space invasion was correlated with HER2-positive tumors (p = .003). After a median follow-up of 50 months, there were 43 (25.4%) recurrences. There were significantly more recurrences in the HER2-positive cohort (50.0% vs 16.8%, p < .001). HER2 positive tumors were associated with worse progression-free (PFS) and overall survival (OS) (p < .001 and p = .024). On multivariate analysis, HER2 positive tumors were associated with inferior PFS (aHR 3.50, 95%CI 1.84-6.67; p < .001) and OS (aHR 2.00, 95%CI 1.04-3.88; p = .039) compared to HER2-negative tumors. CONCLUSIONS: Given its significant association with worse recurrence and survival outcomes, HER2 positivity appears to be a prognostic biomarker in women with stage I uterine serous carcinoma. These data provide support for clinical trials with anti-HER2-directed therapy in early-stage disease.


Assuntos
Biomarcadores Tumorais/metabolismo , Cistadenocarcinoma Seroso/patologia , Recidiva Local de Neoplasia/epidemiologia , Receptor ErbB-2/metabolismo , Neoplasias Uterinas/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/antagonistas & inibidores , Quimiorradioterapia Adjuvante/métodos , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/terapia , Feminino , Seguimentos , Humanos , Histerectomia , Imuno-Histoquímica , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Intervalo Livre de Progressão , Receptor ErbB-2/análise , Receptor ErbB-2/antagonistas & inibidores , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos , Estados Unidos/epidemiologia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/terapia , Útero/patologia , Útero/cirurgia
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