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1.
Gynecol Oncol ; 160(3): 835-843, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33388156

RESUMO

As interventional oncology services within radiology mature, image-guided ablation techniques are increasingly applied to recurrent gynecologic malignancies. Ablation may be performed using thermal techniques like cryoablation, microwave ablation, or radiofrequency ablation, as well as non-thermal ones, such as focused ultrasound or irreversible electroporation. Feasibility and approach depend on tumor type, size, number, anatomic location, proximity of critical structures, and goals of therapy. Current indications include local control of limited metastatic disease or palliation of painful bone metastases refractory or unsuitable to conventional therapies. Technical aspects of these procedures, including methods to protect nearby critical structures are presented through illustrative examples. Cases amenable to image-guided ablation include, but are not limited to, hepatic or pulmonary metastases, musculoskeletal metastases, retroperitoneal nodal metastases, pelvic side wall disease, abdominal wall disease, and vaginal or vulvar tumors. Protective maneuvers, such as hydro-displacement of bowel, neuromonitoring, and retrograde pyeloperfusion through ureteral stents, permit safe ablation despite close proximity to vulnerable nerves or organs. Image-guided ablation offers an alternative modality to achieve local tumor control without the risks associated with surgery or systemic treatment in appropriately selected patients. A multidisciplinary approach to use of image-guided ablation includes collaboration between gynecologic oncology, interventional radiology, anesthesia, urology and radiation oncology teams allowing for appropriate patient-centered case selection. Long-term follow up and additional studies are needed to determine the oncologic benefits of such techniques.

2.
PLoS One ; 16(1): e0245664, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33503056

RESUMO

During the past decade, the age-adjusted mortality rate for endometrial cancer (EC) increased 1.9% annually with TP53 mutant (TP53-mu) EC disproportionally represented in advanced disease and deaths. Therefore, we aimed to assess pivotal molecular parameters that differentiate clinical outcomes in high- and low-risk EC. Using the Cancer Genome Atlas, we analyzed EC specimens with available DNA sequences and quantitative gene-specific RNA expression data. After polymerase ɛ (POLE)-mutant specimens were excluded, differential gene-specific mutations and mRNA expressions were annotated and integrated. Consequent to TP53-mu failure to induce p21, derepression of multiple oncogenes harboring promoter p21 repressive sites was observed, including CCNA2 and FOXM1 (P < .001 compared with TP53 wild type [TP53-wt]). TP53-wt EC with high CCNA2 expression (CCNA2-H) had a targeted transcriptomic profile similar to that of TP53-mu EC, suggesting CCNA2 is a seminal determinant for both TP53-wt and TP53-mu EC. CCNA2 enhances E2F1 function, upregulating FOXM1 and CIP2A, as observed in TP53-mu and CCNA2-H TP53-wt EC (P < .001). CIP2A inhibits protein phosphatase 2A, leading to AKT inactivation of GSK3ß and restricted oncoprotein degradation; PPP2R1A and FBXW7 mutations yield similar results. Upregulation of FOXM1 and failed degradation of FOXM1 is evidenced by marked upregulation of multiple homologous recombination genes (P < .001). Integrating these molecular aberrations generated a molecular biomarker panel with significant prognostic discrimination (P = 5.8×10-7); adjusting for age, histology, grade, myometrial invasion, TP53 status, and stage, only CCNA2-H/E2F1-H (P = .0003), FBXW7-mu/PPP2R1A-mu (P = .0002), and stage (P = .017) were significant. The generated prognostic molecular classification system identifies dissimilar signaling aberrations potentially amenable to targetable therapeutic options.

3.
Int J Cancer ; 148(2): 307-319, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32851660

RESUMO

Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two-sample Mendelian randomization analysis to investigate the relationship between levels of three blood lipids (low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol, and triglycerides) and endometrial cancer risk. Genetic variants associated with each of these blood lipid levels (P < 5 × 10-8 ) were identified as instrumental variables, and assessed using genome-wide association study data from the Endometrial Cancer Association Consortium (12 906 cases and 108 979 controls) and the Global Lipids Genetic Consortium (n = 188 578). Mendelian randomization analyses found genetically raised LDL cholesterol levels to be associated with lower risks of endometrial cancer of all histologies combined, and of endometrioid and non-endometrioid subtypes. Conversely, higher genetically predicted HDL cholesterol levels were associated with increased risk of non-endometrioid endometrial cancer. After accounting for the potential confounding role of obesity (as measured by genetic variants associated with body mass index), the association between genetically predicted increased LDL cholesterol levels and lower endometrial cancer risk remained significant, especially for non-endometrioid endometrial cancer. There was no evidence to support a role for triglycerides in endometrial cancer development. Our study supports a role for LDL and HDL cholesterol in the development of non-endometrioid endometrial cancer. Further studies are required to understand the mechanisms underlying these findings.

7.
Int J Gynecol Cancer ; 30(11): 1738-1747, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32771986

RESUMO

BACKGROUND: Adjuvant therapy in early-stage endometrial cancer has not shown a clear overall survival benefit, and hence, patient selection remains crucial. OBJECTIVE: To determine whether women with high-intermediate risk, early-stage endometrial cancer with lymphovascular space invasion particularly benefit from adjuvant treatment in improving oncologic outcomes. METHODS: A multi-center retrospective study was conducted in women with stage IA, IB, and II endometrial cancer with lymphovascular space invasion who met criteria for high-intermediate risk by Gynecologic Oncology Group (GOG) 99. Patients were stratified by the type of adjuvant treatment received. Clinical and pathologic features were abstracted. Progression-free and overall survival were evaluated using multivariable analysis. RESULTS: 405 patients were included with the median age of 67 years (range 27-92, IQR 59-73). 75.0% of the patients had full staging with lymphadenectomy, and 8.6% had sentinel lymph node biopsy (total 83.6%). After surgery, 24.9% of the patients underwent observation and 75.1% received adjuvant therapy, which included external beam radiation therapy (15.1%), vaginal brachytherapy (45.4%), and combined brachytherapy + chemotherapy (19.1%). Overall, adjuvant treatment resulted in improved oncologic outcomes for both 5-year progression-free survival (77.2% vs 69.6%, HR 0.55, p=0.01) and overall survival (81.5% vs 60.2%, HR 0.42, p<0.001). After adjusting for stage, grade 2/3, and age, improved progression-free survival and overall survival were observed for the following adjuvant subgroups compared with observation: external beam radiation (overall survival HR 0.47, p=0.047, progression-free survival not significant), vaginal brachytherapy (overall survival HR 0.35, p<0.001; progression-free survival HR 0.42, p=0.003), and brachytherapy + chemotherapy (overall survival HR 0.30 p=0.002; progression-free survival HR 0.35, p=0.006). Compared with vaginal brachytherapy alone, external beam radiation or the addition of chemotherapy did not further improve progression-free survival (p=0.80, p=0.65, respectively) or overall survival (p=0.47, p=0.74, respectively). CONCLUSION: Adjuvant therapy improves both progression-free survival and overall survival in women with early-stage endometrial cancer meeting high-intermediate risk criteria with lymphovascular space invasion. External beam radiation or adding chemotherapy did not confer additional survival advantage compared with vaginal brachytherapy alone.

10.
JAMA Netw Open ; 3(7): e2010383, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32662845

RESUMO

Importance: The Centers for Medicare and Medicaid Services's (CMS's) 30-day risk-standardized mortality rate (RSMR) and risk-standardized readmission rate (RSRR) models do not adjust for do-not-resuscitate (DNR) status of hospitalized patients and may bias Hospital Readmissions Reduction Program (HRRP) financial penalties and Overall Hospital Quality Star Ratings. Objective: To identify the association between hospital-level DNR prevalence and condition-specific 30-day RSMR and RSRR and the implications of this association for HRRP financial penalty. Design, Setting, and Participants: This cross-sectional study obtained patient-level data from the Medicare Limited Data Set Inpatient Standard Analytical File and hospital-level data from the CMS Hospital Compare website for all consecutive Medicare inpatient encounters from July 1, 2015, to June 30, 2018, in 4484 US hospitals. Hospitalized patients had a principal diagnosis of acute myocardial infarction (AMI), heart failure (HF), stroke, pneumonia, or chronic obstructive pulmonary disease (COPD). Incoming acute care transfers, discharges against medical advice, and patients coming from or discharged to hospice were among those excluded from the analysis. Exposures: Present-on-admission (POA) DNR status was defined as an International Classification of Diseases, Ninth Revision diagnosis code of V49.86 (before October 1, 2015) or as an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis code of Z66 (beginning October 1, 2015). Hospital-level prevalence of POA DNR status was calculated for each of the 5 conditions. Main Outcomes and Measures: Hospital-level 30-day RSMRs and RSRRs for 5 condition-specific cohorts (mortality cohorts: AMI, HF, stroke, pneumonia, and COPD; readmission cohorts: AMI, HF, pneumonia, and COPD) and HRRP financial penalty status (yes or no). Results: Included in the study were 4 884 237 inpatient encounters across condition-specific 30-day mortality cohorts (patient mean [SD] age, 78.8 [8.5] years; 2 608 182 women [53.4%]) and 4 450 378 inpatient encounters across condition-specific 30-day readmission cohorts (patient mean [SD] age, 78.6 [8.5] years; 2 349 799 women [52.8%]). Hospital-level median (interquartile range [IQR]) prevalence of POA DNR status in the mortality cohorts varied: 11% (7%-16%) for AMI, 13% (7%-23%) for HF, 14% (9%-22%) for stroke, 17% (9%-26%) for pneumonia, and 10% (5%-18%) for COPD. For the readmission cohorts, the hospital-level median (IQR) POA DNR prevalence was 9% (6%-15%) for AMI, 12% (6%-22%) for HF, 16% (8%-24%) for pneumonia, and 9% (4%-17%) for COPD. The 30-day RSMRs were significantly higher for hospitals in the highest quintiles vs the lowest quintiles of DNR prevalence (eg, AMI: 12.9 [95% CI, 12.8-13.1] vs 12.5 [95% CI, 12.4-12.7]; P < .001). The inverse was true among the readmission cohorts, with the highest quintiles of DNR prevalence exhibiting the lowest RSRRs (eg, AMI: 15.3 [95% CI, 15.1-15.5] vs 15.9 [95% CI, 15.7-16.0]; P < .001). A 1% absolute increase in risk-adjusted hospital-level DNR prevalence was associated with greater odds of avoiding HRRP financial penalty (odds ratio, 1.06; 95% CI, 1.04-1.08; P < .001). Conclusions and Relevance: This cross-sectional study found that the lack of adjustment in CMS 30-day RSMR and RSRR models for POA DNR status of hospitalized patients may be associated with biased readmission penalization and hospital-level performance.

11.
Am J Obstet Gynecol ; 223(4): 475-485, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32717257

RESUMO

This is the first collaborative Enhanced Recovery After Surgery Society guideline for optimal perioperative care for vulvar and vaginal surgeries. An Embase and PubMed database search of publications was performed. Studies on each topic within the Enhanced Recovery After Surgery vulvar and vaginal outline were selected, with emphasis on meta-analyses, randomized controlled trials, and prospective cohort studies. All studies were reviewed and graded according to the Grading of Recommendations, Assessment, Development and Evaluation system. All recommendations on the Enhanced Recovery After Surgery topics are based on the best available evidence. The level of evidence for each item is presented.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Procedimentos Cirúrgicos em Ginecologia/métodos , Vagina/cirurgia , Vulva/cirurgia , Antibioticoprofilaxia/métodos , Bandagens , Feminino , Hidratação/métodos , Humanos , Dor Pós-Operatória/tratamento farmacológico , Educação de Pacientes como Assunto/métodos , Assistência Perioperatória , Tromboembolia/prevenção & controle , Cateterismo Urinário/métodos
12.
Gynecol Oncol ; 158(2): 236-243, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32532460

RESUMO

The COVID-19 pandemic has challenged our ability to provide timely surgical care for our patients. In response, the U.S. Surgeon General, the American College of Srugeons, and other surgical professional societies recommended postponing elective surgical procedures and proceeding cautiously with cancer procedures that may require significant hospital resources and expose vulnerable patients to the virus. These challenges have particularly distressing for women with a gynecologic cancer diagnosis and their providers. Currently, circumstances vary greatly by region and by hospital, depending on COVID-19 prevalence, case mix, hospital type, and available resources. Therefore, COVID-19-related modifications to surgical practice guidelines must be individualized. Special consideration is necessary to evaluate the appropriateness of procedural interventions, recognizing the significant resources and personnel they require. Additionally, the pandemic may occur in waves, with patient demand for surgery ebbing and flowing accordingly. Hospitals, cancer centers and providers must prepare themselves to meet this demand. The purpose of this white paper is to highlight all phases of gynecologic cancer surgical care during the COVID-19 pandemic and to illustrate when it is best to operate, to hestitate, and reintegrate surgery. Triage and prioritization of surgical cases, preoperative COVID-19 testing, peri-operative safety principles, and preparations for the post-COVID-19 peak and surgical reintegration are reviewed.


Assuntos
Infecções por Coronavirus/prevenção & controle , Neoplasias dos Genitais Femininos/cirurgia , Neoplasias dos Genitais Femininos/virologia , Procedimentos Cirúrgicos em Ginecologia/métodos , Controle de Infecções/métodos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Oncologia Cirúrgica/métodos , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Técnicas de Laboratório Clínico/normas , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/transmissão , Tomada de Decisões , Feminino , Procedimentos Cirúrgicos em Ginecologia/normas , Humanos , Controle de Infecções/normas , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/transmissão , Oncologia Cirúrgica/normas
15.
Am J Obstet Gynecol ; 223(2): 231.e1-231.e12, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32112733

RESUMO

BACKGROUND: Literature on the use of bowel preparation in gynecologic surgery is scarce and limited to minimally invasive gynecologic surgery. The decision on the use of bowel preparation before benign or malignant hysterectomies is mostly driven by extrapolating data from the colorectal literature. OBJECTIVE: Bowel preparation is a controversial element within enhanced recovery protocols, and literature investigating its efficacy in gynecologic surgery is scarce. Our aim was to determine if mechanical bowel preparation alone, oral antibiotics alone, or a combination are associated with decreased rates of surgical site infections or anastomotic leaks compared to no bowel preparation following benign or malignant hysterectomy. STUDY DESIGN: We identified women who underwent hysterectomy between January 2006 and July 2017 using OptumLabs, a large US commercial health plan database. Inverse propensity score weighting was used separately for benign and malignant groups to balance baseline characteristics. Primary outcomes of 30-day surgical site infection, anastomotic leaks, and major morbidity were assessed using multivariate logistic regression that adjusted for race, census region, household income, diabetes, and other unbalanced variables following propensity score weighting. RESULTS: A total of 224,687 hysterectomies (benign, 186,148; malignant, 38,539) were identified. Median age was 45 years for the benign and 54 years for the malignant cohort. Surgical approach was as follows: benign: laparoscopic/robotic, 27.2%; laparotomy, 32.6%; vaginal, 40.2%; malignant: laparoscopic/robotic, 28.8%; laparotomy, 47.7%; vaginal, 23.5%. Bowel resection was performed in 0.4% of the benign and 2.8% of the malignant cohort. Type of bowel preparation was as follows: benign: none, 93.8%; mechanical bowel preparation only, 4.6%; oral antibiotics only, 1.1%; mechanical bowel preparation with oral antibiotics, 0.5%; malignant: none, 87.2%; mechanical bowel preparation only, 9.6%; oral antibiotics only, 1.8%; mechanical bowel preparation with oral antibiotics, 1.4%. Use of bowel preparation did not decrease rates of surgical site infections, anastomotic leaks, or major morbidity following benign or malignant hysterectomy. Among malignant abdominal hysterectomies, there was no difference in the rates of infectious morbidity between mechanical bowel preparation alone, oral antibiotics alone, or mechanical bowel preparation with oral antibiotics, compared to no preparation. CONCLUSION: Bowel preparation does not protect against surgical site infections or major morbidity following benign or malignant hysterectomy, regardless of surgical approach, and may be safely omitted.


Assuntos
Antibacterianos/uso terapêutico , Catárticos/uso terapêutico , Histerectomia/métodos , Cuidados Pré-Operatórios/métodos , Infecção da Ferida Cirúrgica/epidemiologia , Doenças Uterinas/cirurgia , Neoplasias Uterinas/cirurgia , Administração Oral , Adulto , Fístula Anastomótica/epidemiologia , Feminino , Humanos , Histerectomia Vaginal/métodos , Íleus/epidemiologia , Laparoscopia/métodos , Laparotomia , Modelos Logísticos , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos
16.
Obstet Gynecol ; 135(4): 761-769, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32168206

RESUMO

OBJECTIVE: To evaluate the rate of vaginal hysterectomy and outcomes after initiation of a prospective decision-tree algorithm to determine the optimal surgical route of hysterectomy. METHODS: A prospective algorithm to determine optimal route of hysterectomy was developed, which uses the following factors: history of laparotomy, uterine size, and vaginal access. The algorithm was implemented at our institution from November 24, 2015, to December 31, 2017, for patients requiring hysterectomy for benign indications. Expected route of hysterectomy was assigned by the algorithm and was compared with the actual route performed to identify compliance compared with deviation. Surgical outcomes were analyzed. RESULTS: Of 365 patients who met inclusion criteria, 202 (55.3%) were expected to have a total vaginal hysterectomy, 57 (15.6%) were expected to have an examination under anesthesia followed by total vaginal hysterectomy, 52 (14.2%) were expected to have an examination under anesthesia followed by robotic-assisted total laparoscopic hysterectomy, and 54 (14.8%) were expected to have an abdominal or robotic-laparoscopic route of hysterectomy. Forty-six procedures (12.6%) deviated from the algorithm to a more invasive route (44 robotic, two abdominal). Seven patients had total vaginal hysterectomy when robotic-assisted total laparoscopic hysterectomy or abdominal hysterectomy was expected by the algorithm. Overall, 71% of patients were expected to have a vaginal route of hysterectomy per the algorithm, of whom 81.5% had a total vaginal hysterectomy performed; more than 99% of the total vaginal hysterectomies attempted were successfully completed. CONCLUSION: Vaginal surgery is feasible, carries a low complication rate with excellent outcomes, and should have a place in gynecologic surgery. National use of this prospective algorithm may increase the rate of total vaginal hysterectomy and decrease health care costs.


Assuntos
Algoritmos , Histerectomia , Adulto , Técnicas de Apoio para a Decisão , Árvores de Decisões , Feminino , Ginecologia , Humanos , Valor Preditivo dos Testes , Estudos Prospectivos
17.
Gynecol Oncol ; 157(2): 476-481, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32107048

RESUMO

OBJECTIVES: To report the impact of implementing standardized guidelines for opioid prescriptions after gynecologic surgery and describe patient perspectives before and after implementation for those undergoing laparotomy for ovarian cancer. METHODS: Patients undergoing gynecologic surgery between October 2017 and May 2018 were prescribed opioids at discharge using tiered guidelines; prescriptions were compared to consecutive historical controls (March 2017-October 2017). A subset of ovarian cancer laparotomy patients were surveyed regarding postoperative opioid consumption and patient experience. RESULTS: A total of 620 women in the tiered guideline cohort were compared with 599 historical controls. Following implementation, 95.8% of prescriptions met guidelines. Median milligram morphine equivalents (MME) prescribed decreased from 150 to 75 (p ≤ 0.001) with no change in opioid refills (7.7 vs 6.9%, p = 0.62). In surveyed ovarian cancer patients, 100% of tiered guideline patients and 92% of historical controls felt satisfied with pain control (p = 0.24), despite a 50% reduction in prescribed MME and 14.6% receiving no opioids at discharge (p = 0.002). The median (IQR) MME consumed after discharge was 15 (0, 75) in tiered guideline patients vs. 24 (0, 135) in historical controls, and 38.2% and 42.4% consumed no opioids, respectively. Mean time between surgery and opioid use cessation was <1 week in both groups; patients' perceptions of opioid prescription appropriateness did not change (p = 0.49). More than 75% of patients kept their remaining opioids rather than dispose of them. CONCLUSIONS: Reducing prescribed opioids after gynecologic surgery using tiered guidelines did not increase opioid refills or worsen patients' perceptions of postoperative pain. Even after laparotomy, very little opioids were required over a short duration after dismissal. Infrequent disposal of leftover opioids highlights the need to avoid over-prescribing.


Assuntos
Analgésicos Opioides/administração & dosagem , Neoplasias Ovarianas/cirurgia , Manejo da Dor/normas , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Satisfação do Paciente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Pessoa de Meia-Idade , Manejo da Dor/métodos , Guias de Prática Clínica como Assunto , Prescrições/normas , Estudos Retrospectivos , Adulto Jovem
18.
Gynecol Oncol ; 156(3): 568-574, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31948730

RESUMO

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.


Assuntos
Carcinoma Endometrioide/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/radioterapia , Carcinoma Endometrioide/cirurgia , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Estudos de Coortes , Intervalo Livre de Doença , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/radioterapia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia , Excisão de Linfonodo , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida
19.
Clin Cancer Res ; 26(1): 213-219, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31527166

RESUMO

PURPOSE: Predicting surgical outcome could improve individualizing treatment strategies for patients with advanced ovarian cancer. It has been suggested earlier that gene expression signatures (GES) might harbor the potential to predict surgical outcome. EXPERIMENTAL DESIGN: Data derived from high-grade serous tumor tissue of FIGO stage IIIC/IV patients of AGO-OVAR11 trial were used to generate a transcriptome profiling. Previously identified molecular signatures were tested. A theoretical model was implemented to evaluate the impact of medically associated factors for residual disease (RD) on the performance of GES that predicts RD status. RESULTS: A total of 266 patients met inclusion criteria, of those, 39.1% underwent complete resection. Previously reported GES did not predict RD in this cohort. Similarly, The Cancer Genome Atlas molecular subtypes, an independent de novo signature and the total gene expression dataset using all 21,000 genes were not able to predict RD status. Medical reasons for RD were identified as potential limiting factors that impact the ability to use GES to predict RD. In a center with high complete resection rates, a GES which would perfectly predict tumor biological RD would have a performance of only AUC 0.83, due to reasons other than tumor biology. CONCLUSIONS: Previously identified GES cannot be generalized. Medically associated factors for RD may be the main obstacle to predict surgical outcome in an all-comer population of patients with advanced ovarian cancer. If biomarkers derived from tumor tissue are used to predict outcome of patients with cancer, selection bias should be focused on to prevent overestimation of the power of such a biomarker.See related commentary by Handley and Sood, p. 9.


Assuntos
Carcinoma Epitelial do Ovário , Neoplasias Ovarianas , Biomarcadores , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Estadiamento de Neoplasias
20.
Gynecol Oncol ; 156(1): 62-69, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31776037

RESUMO

OBJECTIVES: To compare survival after nodal assessment using a sentinel lymph node (SLN) algorithm versus comprehensive pelvic and paraaortic lymphadenectomy (LND) in serous or clear cell endometrial carcinoma, and to compare survival in node-negative cases. METHODS: Three-year recurrence-free survival (RFS) and overall survival were compared between one institution that used comprehensive LND to the renal veins and a second institution that used an SLN algorithm with ultra-staging with inverse-probability of treatment weighting (IPTW) derived from propensity scores to adjust for covariate imbalance between cohorts. RESULTS: 214 patients were identified (118 SLN cohort, 96 LND cohort). Adjuvant therapy differed between the cohorts; 84% and 40% in the SLN and LND cohorts, respectively, received chemotherapy ± radiation therapy. The IPTW-adjusted 3-year RFS rates were 69% and 80%, respectively. The IPTW-adjusted 3-year OS rates were 88% and 77%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of surgical approach (SLN vs LND) with progression and death was 1.46 (95% CI: 0.70-3.04) and 0.44 (95% CI: 0.19-1.02), respectively. In the 168 node-negative cases, the IPTW-adjusted 3-year RFS rates were 73% and 91%, respectively. The IPTW-adjusted 3-year OS rates were 88% and 86%, respectively. In this subgroup, IPTW-adjusted HR for the association of surgical approach (SLN vs LND) with progression and death was 3.12 (95% CI: 1.02-9.57) and 0.69 (95% CI: 0.24-1.95), respectively. CONCLUSION: OS was not compromised with the SLN algorithm. SLN may be associated with a decreased RFS but similar OS in node-negative cases despite the majority receiving chemotherapy. This may be due to differences in surveillance.


Assuntos
Adenocarcinoma de Células Claras/cirurgia , Algoritmos , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/cirurgia , Linfonodos/patologia , Linfonodos/cirurgia , Adenocarcinoma de Células Claras/patologia , Idoso , Estudos de Coortes , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Excisão de Linfonodo/métodos , Metástase Linfática , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/métodos , Resultado do Tratamento
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